Biology

15 pages, 1797 KB

Open AccessEditor’s ChoiceArticle

First Insights into Bioaccumulation Patterns in Different Tissues of the Greenland Shark Somniosus microcephalus from Kulusuk (Southeastern Greenland)

by Francesca Romana Reinero, Emilio Sperone, Samira Gallo, Donatella Barca, Francesco Luigi Leonetti, Gianni Giglio and Primo Micarelli

Biology 2025, 14(7), 857; https://doi.org/10.3390/biology14070857 - 15 Jul 2025

Viewed by 488

Abstract

Marine environmental pollution has been rapidly increasing in Arctic waters, and the release and bioaccumulation of trace elements in Arctic marine species may pose significant risks to both ecosystem health and human well-being. As a top predator, the Greenland shark is an ideal [...] Read more.

Marine environmental pollution has been rapidly increasing in Arctic waters, and the release and bioaccumulation of trace elements in Arctic marine species may pose significant risks to both ecosystem health and human well-being. As a top predator, the Greenland shark is an ideal sentinel species for ecotoxicological studies in this region. In this study, trace element analyses were conducted on various tissues from two Greenland sharks—a male and a female—collected in Kulusuk (southeastern Greenland). Eleven trace elements (Mn55, Co59, Cu63, Zn64, As75, Se82, Rb85, Mo98, Ag107, Cd112, and Pb208) were measured in different skin samples from both specimens and in the muscle and fat of the female using an Inductively Coupled Plasma Mass Spectrometer (ICP-MS). Principal Component Analyses (PCAs) revealed sex-related differences in skin bioaccumulation patterns, likely due to sampling of different skin regions. Notably, skin tissues from both sharks showed the highest concentration of trace elements, especially for As75 (9.39–41.13 ppm) and Zn64 (24.34–50.99 ppm) and with the exception of Ag107. These findings suggest that environmental exposure may play a more significant role than dietary intake in trace element accumulation in this area. This study represents the first investigation of trace element bioaccumulation in Greenland sharks from Kulusuk. While the results offer important preliminary insights into the species’ ecotoxicology, further research involving more specimens and tissues is needed to confirm these trends. These initial findings contribute to filling key data gaps and have implications for both environmental monitoring and public health within the Greenlandic community. Full article

(This article belongs to the Section Marine Biology)

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20 pages, 5104 KB

Open AccessEditor’s ChoiceArticle

Effects of the Invasive Common Myna (Acridotheres tristis) on Nest Site Competition and Predation in Native Birds: A Before-After-Control-Impact Study

by Iris Fortoune Engel, Ido Izhaki and Motti Charter

Biology 2025, 14(7), 828; https://doi.org/10.3390/biology14070828 - 8 Jul 2025

Viewed by 687

Abstract

Despite concerns about invasive Common Mynas (Acridotheres tristis), few studies have experimentally demonstrated their impact on native birds. Using a Before-After-Control-Impact (BACI) design with 142 nest boxes, we assessed how Myna presence affected House Sparrows (Passer domesticus) and Great [...] Read more.

Despite concerns about invasive Common Mynas (Acridotheres tristis), few studies have experimentally demonstrated their impact on native birds. Using a Before-After-Control-Impact (BACI) design with 142 nest boxes, we assessed how Myna presence affected House Sparrows (Passer domesticus) and Great Tits (Parus major) before (2009–2010) and after (2020–2021) their arrival in 2015. Half the boxes had large entrances accessible to all three species; half had small entrances accessible only to Great Tits. In a 2022 field experiment, we manipulated nest box entrances and used cameras to study Myna predation and nest usurpation. Following the establishment of Myna, House Sparrow breeding declined by 68.1%. Great Tits increased use of small entrance boxes by 59.9% and decreased use of large entrance boxes by 45.4%. Although overall Great Tit breeding increased, fledging success declined in large entrance boxes, but not small entrance ones. In the 2022 experiment, 46% (n = 26) of Great Tit nests were predated; Common Mynas were responsible for 50% of these cases and subsequently bred in the usurped nests. This study experimentally demonstrates that House Sparrow breeding numbers decrease and that Great Tits change their nesting behavior after the appearance of the Common Myna. Additionally, this research found that Common Mynas impact native species by predating and usurping nests. Installing small-entrance boxes can help manage Great Tit populations. Further research should explore nest box designs for House Sparrows and their impacts on other cavity-nesting and non-cavity-nesting bird species. Full article

(This article belongs to the Section Conservation Biology and Biodiversity)

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12 pages, 1116 KB

Open AccessEditor’s ChoiceArticle

Physics-Informed Neural Network-Based Inverse Framework for Time-Fractional Differential Equations for Rheology

by Sukirt Thakur, Harsa Mitra and Arezoo M. Ardekani

Biology 2025, 14(7), 779; https://doi.org/10.3390/biology14070779 - 27 Jun 2025

Viewed by 482

Abstract

Inverse problems involving time-fractional differential equations have become increasingly important for modeling systems with memory-dependent dynamics, particularly in biotransport and viscoelastic materials. Despite their potential, these problems remain challenging due to issues of stability, non-uniqueness, and limited data availability. Recent advancements in Physics-Informed [...] Read more.

Inverse problems involving time-fractional differential equations have become increasingly important for modeling systems with memory-dependent dynamics, particularly in biotransport and viscoelastic materials. Despite their potential, these problems remain challenging due to issues of stability, non-uniqueness, and limited data availability. Recent advancements in Physics-Informed Neural Networks (PINNs) offer a data-efficient framework for solving such inverse problems, yet most implementations are restricted to integer-order derivatives. In this work, we develop a PINN-based framework tailored for inverse problems involving time-fractional derivatives. We consider two representative applications: anomalous diffusion and fractional viscoelasticity. Using both synthetic and experimental datasets, we infer key physical parameters including the generalized diffusion coefficient and the fractional derivative order in the diffusion model and the relaxation parameters in a fractional Maxwell model. Our approach incorporates a customized residual loss function scaled by the standard deviation of observed data to enhance robustness. Even under 25% Gaussian noise, our method recovers model parameters with relative errors below 10%. Additionally, the framework accurately predicts relaxation moduli in porcine tissue experiments, achieving similar error margins. These results demonstrate the framework’s effectiveness in learning fractional dynamics from noisy and sparse data, paving the way for broader applications in complex biological and mechanical systems. Full article

(This article belongs to the Special Issue Computational Modeling of Drug Delivery)

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10 pages, 1875 KB

Open AccessEditor’s ChoiceArticle

Observations on the Frequency of Sightings of White Sharks in the Population of Gansbaai, South Africa, in the Presence of Cage Diving

by Primo Micarelli, Francesca Romana Reinero, Antonio Pacifico, Gianni Giglio, Makenna Mahrer and Emilio Sperone

Biology 2025, 14(7), 762; https://doi.org/10.3390/biology14070762 - 25 Jun 2025

Viewed by 627

Abstract

Shark ecotourism is an ever-expanding reality, with hundreds of thousands of tourists involved annually. Although it represents a fundamental tool for sharing the urgent need to safeguard sharks with the public, the implications for the health and well-being of sharks must be taken [...] Read more.

Shark ecotourism is an ever-expanding reality, with hundreds of thousands of tourists involved annually. Although it represents a fundamental tool for sharing the urgent need to safeguard sharks with the public, the implications for the health and well-being of sharks must be taken into due consideration. In South Africa, cage-diving has been an important form of ecotourism since the 1990s. In Gansbaai, over a 14-year period from 2009 to 2024, excluding the 2020–2021 pandemic years, data was collected from cage diving operators’ boats on the frequency of sightings of white sharks. After approximately 560 h of field observations, averaging about 45 h per year and about 9 h per year between 2023 and 2024, 423 sharks were observed with five re-sightings. We highlighted that the number of sightings did not increase during the presence of cage diving operators and that site fidelity has not been observed by white sharks frequenting this area. Full article

(This article belongs to the Special Issue The Future of Marine Megafauna)

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17 pages, 2046 KB

Open AccessEditor’s ChoiceArticle

Spatial Transcriptomics Reveals Regional and Temporal Dynamics of Gene Expression in the Mouse Brain Across Development and Aging

by Benjamin Conacher, Amanda Moore, Liduo Yin, Yu Lin, Xiguang Xu, Qinwen Mao and Hehuang Xie

Biology 2025, 14(6), 717; https://doi.org/10.3390/biology14060717 - 18 Jun 2025

Viewed by 1176

Abstract

Investigating transcriptomic changes during healthy development and aging provides insights into the molecular mechanisms that regulate the maturation of brain functions and drive age-related decline. Although it has been speculated that aging may represent a reversal of late-stage brain development, direct molecular comparisons [...] Read more.

Investigating transcriptomic changes during healthy development and aging provides insights into the molecular mechanisms that regulate the maturation of brain functions and drive age-related decline. Although it has been speculated that aging may represent a reversal of late-stage brain development, direct molecular comparisons between these two processes have remained limited. This study employs spatial transcriptomics to analyze the mouse brain at three key timepoints: postnatal day 21 (P21), 3 months (adult), and 28 months (aged), to identify region-specific differential gene expression dynamics. We identify widespread transcriptional changes across both brain development and aging, with all brain regions exhibiting distinct, region-specific gene expression dynamics that reflect divergent regulatory trajectories across the lifespan. During development, gene expression patterns were strongly enriched for neurogenesis, synaptic plasticity, and myelination, reflecting active circuit formation and white matter maturation. In contrast, aging was characterized by a decline in myelination-related gene expression and a pronounced increase in inflammatory and glial activation pathways, particularly within the hippocampus. While both development and aging involved changes in myelination-associated genes, the underlying mechanisms appear distinct: developmental upregulation supports circuit establishment and refinement, whereas aging-related downregulation may reflect secondary consequences of neuroinflammation and reactive gliosis. These findings underscore that, despite some overlap in affected pathways, neural maturation and age-related decline are driven by fundamentally different regulatory programs. These findings establish a novel spatial transcriptomic reference for brain development and aging, offering a valuable data resource for investigating neurodevelopmental and neurodegenerative mechanisms. Full article

(This article belongs to the Section Genetics and Genomics)

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44 pages, 65610 KB

Open AccessEditor’s ChoiceArticle

scRL: Utilizing Reinforcement Learning to Evaluate Fate Decisions in Single-Cell Data

by Zeyu Fu, Chunlin Chen, Song Wang, Junping Wang and Shilei Chen

Biology 2025, 14(6), 679; https://doi.org/10.3390/biology14060679 - 11 Jun 2025

Viewed by 1811

Abstract

Single-cell RNA sequencing now profiles whole transcriptomes for hundreds of thousands of cells, yet existing trajectory-inference tools rarely pinpoint where and when fate decisions are made. We present single-cell reinforcement learning (scRL), an actor–critic framework that recasts differentiation as a sequential decision process [...] Read more.

Single-cell RNA sequencing now profiles whole transcriptomes for hundreds of thousands of cells, yet existing trajectory-inference tools rarely pinpoint where and when fate decisions are made. We present single-cell reinforcement learning (scRL), an actor–critic framework that recasts differentiation as a sequential decision process on an interpretable latent manifold derived with Latent Dirichlet Allocation. The critic learns state-value functions that quantify fate intensity for each cell, while the actor traces optimal developmental routes across the manifold. Benchmarks on hematopoiesis, mouse endocrinogenesis, acute myeloid leukemia, and gene-knockout and irradiation datasets show that scRL surpasses fifteen state-of-the-art methods in five independent evaluation dimensions, recovering early decision states that precede overt lineage commitment and revealing regulators such as Dapp1. Beyond fate decisions, the same framework produces competitive measures of lineage-contribution intensity without requiring ground-truth probabilities, providing a unified and extensible approach for decoding developmental logic from single-cell data. Full article

(This article belongs to the Special Issue AI Deep Learning Approach to Study Biological Questions (2nd Edition))

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17 pages, 1105 KB

Open AccessEditor’s ChoiceReview

Heavy Metal Poisoning and Its Impacts on the Conservation of Amazonian Parrots: An Interdisciplinary Review

by Marina Sette Camara Benarrós, Ketelen Ayumi Corrêa Sakata, Brenda Juliane Silva dos Santos and Felipe Masiero Salvarani

Biology 2025, 14(6), 660; https://doi.org/10.3390/biology14060660 - 6 Jun 2025

Viewed by 824

Abstract

Amazonian parrots (Psittacidae) are essential to ecosystem balance. Already vulnerable to habitat fragmentation and weak environmental regulations, they are now increasingly threatened by heavy metal contamination. This review synthesizes evidence on the sources, transgenerational bioaccumulation, and physiological impacts of metals such as mercury [...] Read more.

Amazonian parrots (Psittacidae) are essential to ecosystem balance. Already vulnerable to habitat fragmentation and weak environmental regulations, they are now increasingly threatened by heavy metal contamination. This review synthesizes evidence on the sources, transgenerational bioaccumulation, and physiological impacts of metals such as mercury (Hg), lead (Pb), cadmium (Cd), zinc (Zn), and arsenic (As) in these birds. Anthropogenic activities, including illegal gold mining, agricultural intensification, and urban expansion, release metals that biomagnify along food webs. Parrots, as long-lived, high-trophic consumers, accumulate metals in vital tissues, leading to severe neurotoxic effects, immunosuppression, reproductive failure, and reduced survival. Furthermore, maternal transfer of contaminants to eggs exacerbates genetic erosion and threatens population viability. While biomonitoring tools and habitat restoration have been proposed, current strategies are insufficient against the synergistic pressures of pollution and climate change. Addressing heavy metal exposure is critical to conserving Amazonian biodiversity and safe-guarding ecosystem services. Future efforts should prioritize multidisciplinary predictive models, bioremediation actions, and the strengthening of international environmental governance to ensure the survival of these sentinel species. Full article

(This article belongs to the Special Issue Progress in Wildlife Conservation, Management and Biological Research)

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25 pages, 3966 KB

Open AccessEditor’s ChoiceArticle

BMP-2-Driven Osteogenesis: A Comparative Analysis of Porcine BMSCs and ASCs and the Role of TGF-β and FGF Signaling

by Roman Taday, Pascal Jungbluth, Sebastian Zensen, Thomas Krakau, Joachim Windolf, Michèle J. Hoffmann and Vera Grotheer

Biology 2025, 14(6), 610; https://doi.org/10.3390/biology14060610 - 26 May 2025

Viewed by 570

Abstract

Mesenchymal stromal cells (MSCs), such as bone marrow-derived cells (BMSCs) and adipose-derived cells (ASCs), are key candidates for bone regeneration therapies but have not yet been integrated into standard clinical practice due to heterogeneity in their osteogenic capacities. This study investigated the osteogenic [...] Read more.

Mesenchymal stromal cells (MSCs), such as bone marrow-derived cells (BMSCs) and adipose-derived cells (ASCs), are key candidates for bone regeneration therapies but have not yet been integrated into standard clinical practice due to heterogeneity in their osteogenic capacities. This study investigated the osteogenic differentiation of porcine BMSCs and ASCs by analyzing BMP-2-induced receptor expression and the effects of inhibiting BMP, TGF-β, and FGF signaling pathways. While pBMSCs underwent osteogenesis in standard differentiation medium, pASCs required BMP-2 stimulation to initiate this process. BMP signaling inhibition via dorsomorphin suppressed osteogenic differentiation, but this effect was reversed by co-inhibition of TGF-β or FGF signaling. Notably, simultaneous inhibition of TGF-β and FGF in the presence of BMP-2 optimized osteogenic differentiation in both pMSC types. In pASCs, successful differentiation correlated with early activation of p38 MAPK and Wnt signaling pathways, with BMP-2 serving as a primary driver, while TGF-β and FGF pathways acted as modulators. These findings highlight the importance of signaling context and MSC tissue origin in bone formation and suggest that tailored modulation of BMP, TGF-β, and FGF signaling will be necessary in future in vivo applications to maximize the regenerative potential of MSC-based therapies. Full article

(This article belongs to the Special Issue Bone Cell Biology)

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16 pages, 790 KB

Open AccessEditor’s ChoiceArticle

Fire and Drought Affect Multiple Aspects of Diversity in a Migratory Bird Stopover Community

by Jenna E. Stanek, Chauncey R. Gadek, Sarah E. Milligan, Brent E. Thompson, Keegan A. Tranquillo, Laura L. Trader, Charles D. Hathcock and Stephen M. Fettig

Biology 2025, 14(6), 597; https://doi.org/10.3390/biology14060597 - 24 May 2025

Viewed by 609

Abstract

Drought and high-severity, stand-replacing wildfires can have substantial impacts on the composition of avian communities, including stop-over communities during migration. An inextricable link exists between drought and wildfire, each operating and impacting across different timescales. Many studies have found nonlinear avian abundance trends [...] Read more.

Drought and high-severity, stand-replacing wildfires can have substantial impacts on the composition of avian communities, including stop-over communities during migration. An inextricable link exists between drought and wildfire, each operating and impacting across different timescales. Many studies have found nonlinear avian abundance trends in breeding community time series data that include pre- and post-fire observations, describing an initial decrease in abundance followed by rapid increases that can attenuate over time. Here, we use a fall bird-banding dataset to evaluate shifts in a drought-impacted avian community following wildfire from taxonomic, functional, and phylogenetic perspectives. We looked at the community as a whole and also categorized birds as residents, migrants, and breeders to assess potential varying responses at the study site. We observed post-fire shifts in functional and phylogenetic diversity that corresponded to changes in vegetation. An influx of migratory insectivores post-fire drove much of the variation between pre- and post-fire avian communities and toward a more related, less phylogenetically dispersed community. A concurrent monsoon season drought was also associated with functional and phylogenetic diversity, highlighting the intertwined pulse press effects on avian communities. Overall, our results suggest that, although bird communities are immediately impacted by fire-driven resource changes, they can rebound over time, it is unclear how long-term drought may continue to shape the composition of these avian communities. Full article

(This article belongs to the Special Issue Bird Biology and Conservation)

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40 pages, 3437 KB

Open AccessEditor’s ChoiceReview

Nanobodies: From Discovery to AI-Driven Design

by Haoran Zhu and Yu Ding

Biology 2025, 14(5), 547; https://doi.org/10.3390/biology14050547 - 14 May 2025

Cited by 2 | Viewed by 3036

Abstract

Nanobodies, derived from naturally occurring heavy-chain antibodies in camelids (VHHs) and sharks (V_NARs), are unique single-domain antibodies that have garnered significant attention in therapeutic, diagnostic, and biotechnological applications due to their small size, stability, and high specificity. This review first traces [...] Read more.

Nanobodies, derived from naturally occurring heavy-chain antibodies in camelids (VHHs) and sharks (V_NARs), are unique single-domain antibodies that have garnered significant attention in therapeutic, diagnostic, and biotechnological applications due to their small size, stability, and high specificity. This review first traces the historical discovery of nanobodies, highlighting key milestones in their isolation, characterization, and therapeutic development. We then explore their structure–function relationship, emphasizing features like their single-domain architecture and long CDR3 loop that contribute to their binding versatility. Additionally, we examine the growing interest in multiepitope nanobodies, in which binding to different epitopes on the same antigen not only enhances neutralization and specificity but also allows these nanobodies to be used as controllable modules for precise antigen manipulation. This review also discusses the integration of AI in nanobody design and optimization, showcasing how machine learning and deep learning approaches are revolutionizing rational design, humanization, and affinity maturation processes. With continued advancements in structural biology and computational design, nanobodies are poised to play an increasingly vital role in addressing both existing and emerging biomedical challenges. Full article

(This article belongs to the Special Issue Innovative Biotechnologies for Advancing Protein Function Investigation)

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15 pages, 1656 KB

Open AccessEditor’s ChoiceArticle

Deciphering the Role of Ferroptosis in the Pathogenesis of Peripheral Artery Disease Myopathy

by Trevor Wilkinson, Emma Fletcher, Andrew Ring, Cassandra Bradley, Evlampia Papoutsi, Dimitrios Miserlis, Robert S. Smith, William T. Bohannon, Iraklis I. Pipinos and Panagiotis Koutakis

Biology 2025, 14(5), 537; https://doi.org/10.3390/biology14050537 - 12 May 2025

Viewed by 714

Abstract

This study investigates ferroptosis in the context of peripheral artery disease (PAD), a vascular disease characterized by atherosclerosis of the lower extremities. Muscle atrophy and increased oxidative stress are hallmarks of PAD and correlate with worse clinical outcomes. Given ferroptosis’ association with oxidative [...] Read more.

This study investigates ferroptosis in the context of peripheral artery disease (PAD), a vascular disease characterized by atherosclerosis of the lower extremities. Muscle atrophy and increased oxidative stress are hallmarks of PAD and correlate with worse clinical outcomes. Given ferroptosis’ association with oxidative stress, we explored its role in PAD myopathy by examining gene and protein markers related to metabolic pathways implicated in ferroptosis using both human PAD patients and cultured myotubes. Intermittent claudication (IC) PAD patients, critical limb ischemia (CLI) PAD patients, and non-PAD controls were recruited for this study. Calf muscle biopsies were analyzed for gene expression using qPCR, and protein levels were determined by Western blotting. Cultured myotubes treated with the ferroptosis inducer erastin provided an in vitro comparison. Results demonstrated upregulation of ferroptosis markers such as lipid peroxidation and PTGS2 gene expression in the muscle of CLI PAD patients compared to controls. Increased expression of ferroptosis-related genes HMOX1, ACSL4, ELAVL1, and Beclin-1 was also observed. Protein analysis showed trends consistent with gene expression in some ferroptosis markers. The increase in ferroptosis markers in CLI PAD patients, particularly in iron metabolism and autophagy pathways, suggests ferroptosis contributes to PAD myopathy. Full article

(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)

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21 pages, 9971 KB

Open AccessEditor’s ChoiceArticle

Traces of a Primitive RNA Ring in Current Genomes

by Jacques Demongeot

Biology 2025, 14(5), 538; https://doi.org/10.3390/biology14050538 - 12 May 2025

Viewed by 474

Abstract

(1) Background: Previous theoretical studies have provided arguments for the existence of a circular or hairpin RNA that could have served as a primitive informational and functional molecule at the origin of life. The present article consists of searching in current genomes for [...] Read more.

(1) Background: Previous theoretical studies have provided arguments for the existence of a circular or hairpin RNA that could have served as a primitive informational and functional molecule at the origin of life. The present article consists of searching in current genomes for RNAs closest to this primitive RNA in terms of the occurrence of similar nucleotide motifs. (2) Methods: In searching for the smallest possible RNA capable of interacting with amino acids in the construction of the peptides of the primitive living world, we found a circular docosamer RNA molecule (length 22), which we called AL (for ALpha or Archetypal Loop). Then, we started to systematically track AL relics in current genomes in the form of motifs like pentamers or pairs of consecutive codons in common with AL. (3) Results: The sequence correspondence between AL and RNA sequences of organisms from different kingdoms of life (Archaea, Bacteria, and Eukarya) was found with high statistical significance, with a frequency gradient depending on both the antiquity of the species and the functional necessity of the genes. (4) Conclusions: Considering the suitability of AL as a candidate for being a primitive sequence, and the evolution of the different species considered, we can consider the AL RNA as a possible actor that favored the appearance of life on Earth. Full article

(This article belongs to the Section Theoretical Biology and Biomathematics)

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19 pages, 40636 KB

Open AccessEditor’s ChoiceArticle

Unsupervised Clustering of Cell Populations in Germinal Centers Using Multiplexed Immunofluorescence

by Simon Burgermeister, Michail Orfanakis, Spiros Georgakis, Cloe Brenna, Helen Lindsay, Craig Fenwick, Giuseppe Pantaleo, Raphael Gottardo and Constantinos Petrovas

Biology 2025, 14(5), 530; https://doi.org/10.3390/biology14050530 - 11 May 2025

Viewed by 2630

Abstract

Follicles (Fs)/Germinal Centers (GCs) in tonsils and lymph nodes are dynamic microenvironments where diverse immune cell populations interact for the development of antibody responses against pathogens. The accurate in situ phenotypic analysis of these immune cells is a prerequisite for the comphehensive understanding [...] Read more.

Follicles (Fs)/Germinal Centers (GCs) in tonsils and lymph nodes are dynamic microenvironments where diverse immune cell populations interact for the development of antibody responses against pathogens. The accurate in situ phenotypic analysis of these immune cells is a prerequisite for the comphehensive understanding of GC development. In this study, we explore unsupervised clustering approaches for distinguishing cell populations within F/GCs using marker expression data. We evaluate multiple clustering algorithms and find that k-means clustering provides the most effective separation of distinct cell subsets. Additionally, we investigate the predictive potential of common GC markers (CD3, CD4, CD20 and BCL6) for PD-1 expression, an important immune checkpoint regulator. Our analysis demonstrates that PD-1 expression can be reliably inferred using these markers, suggesting potential applications for automated cell classification in immunological studies. This approach enhances our ability to analyze immune cell heterogeneity and may contribute to improved understanding of GC dynamics in health and disease. Our findings support the use of computational clustering for high-dimensional immune profiling. Full article

(This article belongs to the Section Immunology)

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19 pages, 4585 KB

Open AccessEditor’s ChoiceArticle

Origin of Polyploidy, Phylogenetic Relationships, and Biogeography of Botiid Fishes (Teleostei: Cypriniformes)

by Lei Yang, Richard L. Mayden and Gavin J. P. Naylor

Biology 2025, 14(5), 531; https://doi.org/10.3390/biology14050531 - 11 May 2025

Cited by 1 | Viewed by 793

Abstract

Botiidae is a small family of freshwater fishes distributed across Southeast Asia, South Asia, and East Asia. It comprises two subfamilies: the diploid Leptobotiinae and the tetraploid Botiinae. Whether species in the Botiinae are autotetraploids or allotetraploids and how many polyploidization events occurred [...] Read more.

Botiidae is a small family of freshwater fishes distributed across Southeast Asia, South Asia, and East Asia. It comprises two subfamilies: the diploid Leptobotiinae and the tetraploid Botiinae. Whether species in the Botiinae are autotetraploids or allotetraploids and how many polyploidization events occurred during the evolution of this subfamily remain open questions. The phylogenetic relationships and biogeography of the Botiidae also require further investigation. In the current study, we compared phylogenetic trees constructed using DNA sequences from the mitochondrial genome and five phased nuclear genes. We also performed whole genome sequencing for two tetraploid species: Chromobotia macracanthus and Yasuhikotakia modesta. Genome profiling of five botiine species suggests that they are likely of allotetraploid origin. Nuclear gene tree topologies indicate that the tetraploidization of the Botiinae occurred only once in the common ancestor of this subfamily. Although the possible maternal progenitor and paternal progenitor of the Botiinae cannot be determined, the subfamily Leptobotiinae can be excluded as a progenitor. The gene trees built in this study generally agree on the following sister group relationships: Leptobotiinae/Botiinae, Leptobotia/Parabotia, Chromobotia/Botia, Yasuhikotakia/Syncrossus, and Sinibotia/Ambastaia. Clades formed by the last two generic pairs are also sisters to each other. Timetree analyses and ancestral range reconstruction suggest that the family Botiidae might have originated in East Asia and Mainland Southeast Asia approximately 51 million years ago and later dispersed to South Asia and the islands of Southeast Asia. Full article

(This article belongs to the Special Issue Young Researchers in Conservation Biology and Biodiversity)

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34 pages, 4805 KB

Open AccessEditor’s ChoiceArticle

High-Throughput Analysis of the Flagella FliK-Dependent Surfaceome and Secretome in Bacillus thuringiensis

by Carine Mouawad, Mireille Kallassy Awad, Carine Rodrigues-Machado, Céline Henry, Vincent Sanchis-Borja and Laure El Chamy

Biology 2025, 14(5), 525; https://doi.org/10.3390/biology14050525 - 9 May 2025

Viewed by 559

Abstract

Bacterial pathogens employ multiple strategies to invade and damage host tissues while evading immune defenses. Recent studies highlight flagella as crucial contributors to bacterial virulence, not only by facilitating motility, but also by regulating the secretion of virulence factors. However, the role of [...] Read more.

Bacterial pathogens employ multiple strategies to invade and damage host tissues while evading immune defenses. Recent studies highlight flagella as crucial contributors to bacterial virulence, not only by facilitating motility, but also by regulating the secretion of virulence factors. However, the role of the flagella-dependent secretome remains largely unexplored. We have recently shown that FliK, a key regulator that defines substrate specificity in the flagellar export apparatus, is essential for the resistance of Bacillus thuringiensis (B. thuringiensis) against antimicrobial peptides (AMPs) and its virulence in a Drosophila infection model. In this study, we used liquid chromatography–tandem mass spectrometry to conduct a large-scale comparative analysis of the proteins secreted in culture supernatant or associated with the cell wall of the ΔfliK mutant and its reference strain. Our results reveal significant differences in the secretome and surfaceome of the ΔfliK mutant compared to the reference strain. These findings emphasize the role of FliK in regulating the production and secretion of several proteins, underscoring the importance of flagella in controlling various biological processes. This work provides valuable insights into the functional characterization of potential candidate proteins involved in B. thuringiensis virulence and AMP resistance mechanisms. Overall, these results open new perspectives for understanding the molecular processes that govern bacterial resistance to AMPs. Full article

(This article belongs to the Section Microbiology)

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41 pages, 3386 KB

Open AccessEditor’s ChoiceSystematic Review

Artificial Intelligence in Aquatic Biodiversity Research: A PRISMA-Based Systematic Review

by Tymoteusz Miller, Grzegorz Michoński, Irmina Durlik, Polina Kozlovska and Paweł Biczak

Biology 2025, 14(5), 520; https://doi.org/10.3390/biology14050520 - 8 May 2025

Cited by 3 | Viewed by 2866

Abstract

Freshwater ecosystems are increasingly threatened by climate change and anthropogenic activities, necessitating innovative and scalable monitoring solutions. Artificial intelligence (AI) has emerged as a transformative tool in aquatic biodiversity research, enabling automated species identification, predictive habitat modeling, and conservation planning. This systematic review [...] Read more.

Freshwater ecosystems are increasingly threatened by climate change and anthropogenic activities, necessitating innovative and scalable monitoring solutions. Artificial intelligence (AI) has emerged as a transformative tool in aquatic biodiversity research, enabling automated species identification, predictive habitat modeling, and conservation planning. This systematic review follows the PRISMA framework to analyze AI applications in freshwater biodiversity studies. Using a structured literature search across Scopus, Web of Science, and Google Scholar, we identified 312 relevant studies published between 2010 and 2024. This review categorizes AI applications into species identification, habitat assessment, ecological risk evaluation, and conservation strategies. A risk of bias assessment was conducted using QUADAS-2 and RoB 2 frameworks, highlighting methodological challenges, such as measurement bias and inconsistencies in the model validation. The citation trends demonstrate exponential growth in AI-driven biodiversity research, with leading contributions from China, the United States, and India. Despite the growing use of AI in this field, this review also reveals several persistent challenges, including limited data availability, regional imbalances, and concerns related to model generalizability and transparency. Our findings underscore AI’s potential in revolutionizing biodiversity monitoring but also emphasize the need for standardized methodologies, improved data integration, and interdisciplinary collaboration to enhance ecological insights and conservation efforts. Full article

(This article belongs to the Section Ecology)

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16 pages, 1262 KB

Open AccessEditor’s ChoiceReview

The Extremophiles: Adaptation Mechanisms and Biotechnological Applications

by Gorji Marzban and Donatella Tesei

Biology 2025, 14(4), 412; https://doi.org/10.3390/biology14040412 - 13 Apr 2025

Cited by 4 | Viewed by 4255

Abstract

This review provides an overview of terrestrial extremophiles, highlighting their adaptive strengths and strategies for coping with environmental challenges through the use of specialized proteins. It also explores why their unique lifestyle and ability to adapt to extreme conditions have become a major [...] Read more.

This review provides an overview of terrestrial extremophiles, highlighting their adaptive strengths and strategies for coping with environmental challenges through the use of specialized proteins. It also explores why their unique lifestyle and ability to adapt to extreme conditions have become a major focus of research, as well as the main benefits and advancements in the study of these organisms in recent decades. This review aims to present an objective summary of the knowledge acquired and its translation into applied science and biotechnological applications. Full article

(This article belongs to the Special Issue Multi-Omics of Extremophilic Organisms)

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25 pages, 3032 KB

Open AccessEditor’s ChoiceArticle

Novel Insights and Genomic Characterization of Coral-Associated Microorganisms from Maldives Displaying Antimicrobial, Antioxidant, and UV-Protectant Activities

by Fortunato Palma Esposito, Andrea López-Mobilia, Michael Tangherlini, Vincenza Casella, Alessandro Coppola, Giulia Varola, Laura Vitale, Gerardo Della Sala, Pietro Tedesco, Simone Montano, Davide Seveso, Paolo Galli, Daniela Coppola, Donatella de Pascale and Christian Galasso

Biology 2025, 14(4), 401; https://doi.org/10.3390/biology14040401 - 11 Apr 2025

Viewed by 1176

Abstract

Coral reef survival is crucial for the socio-ecological interest of many countries, particularly for the Republic of Maldives, whose reef integrity influences the country’s livelihoods and economy. These ecosystems are being severely impacted by multiple stressors, leading to declines in biodiversity. In the [...] Read more.

Coral reef survival is crucial for the socio-ecological interest of many countries, particularly for the Republic of Maldives, whose reef integrity influences the country’s livelihoods and economy. These ecosystems are being severely impacted by multiple stressors, leading to declines in biodiversity. In the last few decades, researchers have focused on studying coral-associated microorganisms (CAMs) and their symbiotic role in coral health and resilience. Metabarcoding analysis has been widely utilized to study CAM diversity under various conditions but provides limited information on their functional roles. Therefore, cultivation of bacterial strains remains indispensable for validating ecological and biotechnological hypotheses. In this study, we investigated the microbial community associated with two abundant corals in Maldives, Porites lobata and Acropora gemmifera, and evaluated the antimicrobial, antioxidant, and UV-protectant properties of 10 promising isolated strains. The selected CAMs, Pseudoalteromonas piscicida 39, Streptomyces parvus 79, Microbacterium sp. 92 (a potential novel species), and Micromonospora arenicola 93, exhibited antibiotic activity against a panel of pathogenic strains (MIC from 0.01 to 500 µg/mL), antioxidant (comparable effect to that of Trolox and ascorbic acid), and UV-screen activities (protection of human keratinocytes at 200 µg/mL). Genomes revealed their dual potential in contributing to coral restoration and drug discovery strategies. These findings highlight the biotechnological relevance of CAMs, representing an important step toward the identification of novel and bioactive bacterial species beneficial for coral reef ecosystems and human health. Full article

(This article belongs to the Special Issue Adaptation of Living Species to Environmental Stress)

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19 pages, 3528 KB

Open AccessEditor’s ChoiceArticle

A Frequency Domain Analysis of the Growth Factor-Driven Extra-Cellular-Regulated Kinase (ERK) Pathway

by Nguyen H. N. Tran, Federico Frascoli and Andrew H. A. Clayton

Biology 2025, 14(4), 374; https://doi.org/10.3390/biology14040374 - 5 Apr 2025

Cited by 1 | Viewed by 527

Abstract

The ERK pathway is an important biochemical cascade and acts as a master regulator of myriad cell processes including cell proliferation, differentiation, and survival. Early biochemical work established that the timing of ERK phosphorylation was an important determinant of PC12 cell fate, with [...] Read more.

The ERK pathway is an important biochemical cascade and acts as a master regulator of myriad cell processes including cell proliferation, differentiation, and survival. Early biochemical work established that the timing of ERK phosphorylation was an important determinant of PC12 cell fate, with extended phosphorylation (with nerve growth factor treatment) linked to differentiation but rapid on–off ERK phosphorylation kinetics (with epidermal growth factor treatment) linked to cell proliferation. Recent work from several laboratories has revealed that periodic forcing the phosphorylation of ERK with growth factors, light (optogenetics) or electronically can switch cell fate from proliferative to differentiated depending on type of stimulus (amplitude and frequency). Here, we take an ERK model and analyze it from the frequency domain perspective. The key is the transfer function, which provides a compact description of input (growth factor)–output (ERK activation) behavior over a range of input frequencies, allowing an understanding of system dynamics in terms of amplitude modulations, phase shifts, and signaling bandwidths. Our analysis of transfer functions indicates that, at normal receptor levels, the ERK pathway acts as a negative feedback amplifier to growth factor fluctuations, amplifying them at low receptor occupancy but suppressing them at high receptor occupancy. The frequency dependence is best described as a resonant low pass filter, which selectively filters out high frequency input oscillations. We use the transfer function to predict how different growth factor input dynamics shape ERK activation. Full article

(This article belongs to the Section Biochemistry and Molecular Biology)

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8 pages, 528 KB

Open AccessEditor’s ChoiceCommentary

Preserving Fossilized Soft Tissues: Advancing Proteomics and Unveiling the Evolutionary History of Cancer in Dinosaurs

by Pramodh Chitral Chandrasinghe, Biancastella Cereser, Sergio Bertazzo, Zoltán Csiki-Sava and Justin Stebbing

Biology 2025, 14(4), 370; https://doi.org/10.3390/biology14040370 - 3 Apr 2025

Viewed by 5527

Abstract

Understanding how life-history strategies influence cancer susceptibility in dinosaurs requires a molecular-level analysis of preserved soft tissues. While previous research has largely focused on skeletal remains, the discovery of soft tissue structures in fossils, such as Telmatosaurus transsylvanicus, highlights the need for [...] Read more.

Understanding how life-history strategies influence cancer susceptibility in dinosaurs requires a molecular-level analysis of preserved soft tissues. While previous research has largely focused on skeletal remains, the discovery of soft tissue structures in fossils, such as Telmatosaurus transsylvanicus, highlights the need for a new approach. Paleoproteomics offers a transformative opportunity to analyze ancient proteins, revealing the evolutionary trade-offs between growth, reproduction, and cancer suppression. This study argues that prioritizing fossil collection and soft tissue preservation is crucial, as future advances in molecular techniques will allow deeper insights into disease evolution. By integrating life-history theory with paleopathology, we can better understand the selective pressures that shaped cancer susceptibility in extinct species and identify potential mechanisms of tumor resistance. This commentary highlights the necessity of long-term fossil conservation efforts to support future breakthroughs in evolutionary biology and comparative oncology. Full article

(This article belongs to the Section Evolutionary Biology)

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4 pages, 554 KB

Open AccessEditor’s ChoiceEditorial

Beyond the Surface: The Peculiar World of Benthic Biodiversity, from Microbes to Multicellular Life and Their Ecosystem Roles

by Mayya Gogina and Judith Piontek

Biology 2025, 14(4), 368; https://doi.org/10.3390/biology14040368 - 3 Apr 2025

Viewed by 652

Abstract

Below the water column depths, marine sediments harbor a vibrant tapestry of life that underpins a variety of ecological balances [...] Full article

(This article belongs to the Special Issue Benthic Biodiversity from Microbes to Multicellular Organisms and Its Functional Interplays)

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23 pages, 1932 KB

Open AccessEditor’s ChoiceReview

The Role of IL-23 in the Development of Inflammatory Diseases

by Mario García-Domínguez

Biology 2025, 14(4), 347; https://doi.org/10.3390/biology14040347 - 27 Mar 2025

Cited by 3 | Viewed by 2934

Abstract

Interleukin-23 is crucial in the initiation and progression of certain inflammatory disorders. As a key cytokine, IL-23 is involved in the differentiation and activation of Th17 cells, which play a role in a broad spectrum of inflammatory diseases. This review examines the molecular [...] Read more.

Interleukin-23 is crucial in the initiation and progression of certain inflammatory disorders. As a key cytokine, IL-23 is involved in the differentiation and activation of Th17 cells, which play a role in a broad spectrum of inflammatory diseases. This review examines the molecular mechanisms through which IL-23 contributes to the pathogenesis of conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. By elucidating the significant role of IL-23 in inflammation, this review underscores its importance as a therapeutic target for managing inflammatory conditions, with particular emphasis on current and emerging biologic treatments. Full article

(This article belongs to the Special Issue Innate Immunity and Inflammatory Diseases)

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14 pages, 3580 KB

Open AccessEditor’s ChoiceArticle

Metrics of Genomic Complexity in the Evolution of Bacterial Endosymbiosis

by Pablo Román-Escrivá, Moisès Bernabeu, Eleonora Paganin, Wladimiro Díaz-Villanueva, Miguel Verdú, José L. Oliver, Vicente Arnau and Andrés Moya

Biology 2025, 14(4), 338; https://doi.org/10.3390/biology14040338 - 25 Mar 2025

Viewed by 1070

Abstract

Endosymbiosis can be considered a regressive or degenerative evolutionary process characterized at the genomic level by genome erosion and degeneration due to high mutational pressure toward AT (adenine and thymine) bases. The genomic and biological complexity of endosymbionts must be lower than that [...] Read more.

Endosymbiosis can be considered a regressive or degenerative evolutionary process characterized at the genomic level by genome erosion and degeneration due to high mutational pressure toward AT (adenine and thymine) bases. The genomic and biological complexity of endosymbionts must be lower than that of the free-living bacteria from which they evolved. In the present work, we contrasted whether two proposed metrics for measuring genomic complexity in both types of bacteria, GS and BB, reflect their complexity, expecting higher values in free-living bacteria than in endosymbionts. On the other hand, we endeavored to delve into the factors that contribute to the reduction in metric values in endosymbionts, as well as their eventual relationship with six genomic parameters associated with functionality. This study aimed to test the robustness of these proposed metrics in a well-known biological scenario, such as the endosymbiosis process. Full article

(This article belongs to the Section Evolutionary Biology)

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31 pages, 6261 KB

Open AccessEditor’s ChoiceReview

Huanglongbing as a Persistent Threat to Citriculture in Latin America

by Jael Arely Cervantes-Santos, Hernán Villar-Luna, Ana Marlenne Bojórquez-Orozco, José Ernesto Díaz-Navarro, Ángela Paulina Arce-Leal, María Elena Santos-Cervantes, Manuel Gonzalo Claros, Jesús Méndez-Lozano, Edgar Antonio Rodríguez-Negrete and Norma Elena Leyva-López

Biology 2025, 14(4), 335; https://doi.org/10.3390/biology14040335 - 25 Mar 2025

Viewed by 4283

Abstract

Citrus commercial species are the most important fruit crops in the world; however, their cultivation is seriously threatened by the fast dispersion of emerging diseases, including Huanglongbing (HLB) citrus greening. HLB disease is vectored by psyllid vectors and associated with phloem-limited α-proteobacteria belonging [...] Read more.

Citrus commercial species are the most important fruit crops in the world; however, their cultivation is seriously threatened by the fast dispersion of emerging diseases, including Huanglongbing (HLB) citrus greening. HLB disease is vectored by psyllid vectors and associated with phloem-limited α-proteobacteria belonging to the Candidatus Liberibacter genus. Climatic change and trade globalization have led to the rapid spread of HLB from its origin center in Southeast Asia, causing a great economic impact in the main production areas, including East Asia (China), the Mediterranean basin, North America (the United States), and Latin America (Brazil and Mexico). Despite important advances to understand the HLB epidemiology, Candidatus Liberibacter genetics, psyllid vector control, the molecular citrus–Candidatus Liberibacter interaction, and the development of integral disease management strategies, the study areas have been mostly restricted to high-tech-producing countries. Thus, in this review, we provide an overview of the epidemiology, distribution, genetic diversity, management aspects, and omics analysis of HLB in Latin America, where this information to date is limited. Full article

(This article belongs to the Section Plant Science)

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34 pages, 4139 KB

Open AccessEditor’s ChoiceReview

Mutual Interactions Between Microbiota and the Human Immune System During the First 1000 Days of Life

by Muy Heang Tang, Ishbel Ligthart, Samuel Varga, Sarah Lebeer, Frans J. van Overveld and Ger T. Rijkers

Biology 2025, 14(3), 299; https://doi.org/10.3390/biology14030299 - 16 Mar 2025

Cited by 1 | Viewed by 3332

Abstract

The development of the human immune system starts during the fetal period in a largely, but probably not completely, sterile environment. During and after birth, the immune system is exposed to an increasingly complex microbiota. The first microbiota encountered during passage through the [...] Read more.

The development of the human immune system starts during the fetal period in a largely, but probably not completely, sterile environment. During and after birth, the immune system is exposed to an increasingly complex microbiota. The first microbiota encountered during passage through the birth canal colonize the infant gut and induce the tolerance of the immune system. Transplacentally derived maternal IgG as well as IgA from breast milk protect the infant from infections during the first 100 days, during which the immune system further develops and immunological memory is formed. The Weaning and introduction of solid food expose the immune system to novel (food) antigens and allow for other microbiota to colonize. The cells and molecules involved in the mutual and intricate interactions between microbiota and the developing immune system are now beginning to be recognized. These include bacterial components such as polysaccharide A from Bacteroides fragilis, as well as bacterial metabolites such as the short-chain fatty acid butyrate, indole-3-aldehyde, and indole-3-propionic acid. All these, and probably more, bacterial metabolites have specific immunoregulatory functions which shape the development of the human immune system during the first 1000 days of life. Full article

(This article belongs to the Section Immunology)

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18 pages, 3483 KB

Open AccessEditor’s ChoiceArticle

Enhancing Single-Cell and Bulk Hi-C Data Using a Generative Transformer Model

by Ruoying Gao, Thomas N. Ferraro, Liang Chen, Shaoqiang Zhang and Yong Chen

Biology 2025, 14(3), 288; https://doi.org/10.3390/biology14030288 - 12 Mar 2025

Cited by 1 | Viewed by 1508

Abstract

The 3D organization of chromatin in the nucleus plays a critical role in regulating gene expression and maintaining cellular functions in eukaryotic cells. High-throughput chromosome conformation capture (Hi-C) and its derivative technologies have been developed to map genome-wide chromatin interactions at the population [...] Read more.

The 3D organization of chromatin in the nucleus plays a critical role in regulating gene expression and maintaining cellular functions in eukaryotic cells. High-throughput chromosome conformation capture (Hi-C) and its derivative technologies have been developed to map genome-wide chromatin interactions at the population and single-cell levels. However, insufficient sequencing depth and high noise levels in bulk Hi-C data, particularly in single-cell Hi-C (scHi-C) data, result in low-resolution contact matrices, thereby limiting diverse downstream computational analyses in identifying complex chromosomal organizations. To address these challenges, we developed a transformer-based deep learning model, HiCENT, to impute and enhance both scHi-C and Hi-C contact matrices. Validation experiments on large-scale bulk Hi-C and scHi-C datasets demonstrated that HiCENT achieves superior enhancement effects compared to five popular methods. When applied to real Hi-C data from the GM12878 cell line, HiCENT effectively enhanced 3D structural features at the scales of topologically associated domains and chromosomal loops. Furthermore, when applied to scHi-C data from five human cell lines, it significantly improved clustering performance, outperforming five widely used methods. The adaptability of HiCENT across different datasets and its capacity to improve the quality of chromatin interaction data will facilitate diverse downstream computational analyses in 3D genome research, single-cell studies and other large-scale omics investigations. Full article

(This article belongs to the Special Issue Artificial Intelligence Research for Complex Biological Systems)

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38 pages, 1432 KB

Open AccessEditor’s ChoiceReview

Multi-Omic Advances in Olive Tree (Olea europaea subsp. europaea L.) Under Salinity: Stepping Towards ‘Smart Oliviculture’

by Manuel Gonzalo Claros, Amanda Bullones, Antonio Jesús Castro, Elena Lima-Cabello, María Ángeles Viruel, María Fernanda Suárez, Remedios Romero-Aranda, Noé Fernández-Pozo, Francisco J. Veredas, Andrés Belver and Juan de Dios Alché

Biology 2025, 14(3), 287; https://doi.org/10.3390/biology14030287 - 11 Mar 2025

Cited by 2 | Viewed by 2769

Abstract

Soil salinisation is threatening crop sustainability worldwide, mainly due to anthropogenic climate change. Molecular mechanisms developed to counteract salinity have been intensely studied in model plants. Nevertheless, the economically relevant olive tree (Olea europaea subsp. europaea L.), being highly exposed to soil [...] Read more.

Soil salinisation is threatening crop sustainability worldwide, mainly due to anthropogenic climate change. Molecular mechanisms developed to counteract salinity have been intensely studied in model plants. Nevertheless, the economically relevant olive tree (Olea europaea subsp. europaea L.), being highly exposed to soil salinisation, deserves a specific review to extract the recent genomic advances that support the known morphological and biochemical mechanisms that make it a relative salt-tolerant crop. A comprehensive list of 98 olive cultivars classified by salt tolerance is provided, together with the list of available olive tree genomes and genes known to be involved in salt response. Na⁺ and Cl^– exclusion in leaves and retention in roots seem to be the most prominent adaptations, but cell wall thickening and antioxidant changes are also required for a tolerant response. Several post-translational modifications of proteins are emerging as key factors, together with microbiota amendments, making treatments with biostimulants and chemical compounds a promising approach to enable cultivation in already salinised soils. Low and high-throughput transcriptomics and metagenomics results obtained from salt-sensitive and -tolerant cultivars, and the future advantages of engineering specific metacaspases involved in programmed cell death and autophagy pathways to rapidly raise salt-tolerant cultivars or rootstocks are also discussed. The overview of bioinformatic tools focused on olive tree, combined with machine learning approaches for studying plant stress from a multi-omics perspective, indicates that the development of salt-tolerant cultivars or rootstocks adapted to soil salinisation is progressing. This could pave the way for ‘smart oliviculture’, promoting more productive and sustainable practices under salt stress. Full article

(This article belongs to the Section Genetics and Genomics)

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21 pages, 895 KB

Open AccessEditor’s ChoiceReview

Connecting Bone Remodeling and Regeneration: Unraveling Hormones and Signaling Pathways

by Afshan Mehreen, Muhammad Faisal, Bilal Zulfiqar, Deli Hays, Kavishka Dhananjaya, Faiza Yaseen and Yujun Liang

Biology 2025, 14(3), 274; https://doi.org/10.3390/biology14030274 - 7 Mar 2025

Cited by 4 | Viewed by 2497

Abstract

Recent advancements in tissue engineering and stem cell science have positioned bone disease treatment as a promising frontier in regenerative medicine. This review explores the hormonal and signaling pathways critical to bone regeneration, with a focus on their clinical relevance. Key endocrine factors, [...] Read more.

Recent advancements in tissue engineering and stem cell science have positioned bone disease treatment as a promising frontier in regenerative medicine. This review explores the hormonal and signaling pathways critical to bone regeneration, with a focus on their clinical relevance. Key endocrine factors, including thyroid hormones (T3 and T4), insulin-like growth factor 1 (IGF-1), bone morphogenetic proteins (BMPs), parathyroid hormone (PTH), calcitonin, and fibroblast growth factor 23 (FGF23), play pivotal roles in bone remodeling by regulating osteoblast activity, bone resorption, and mineralization. These factors primarily act through the Wnt/β-catenin, BMP, and FGF signaling pathways, which govern bone repair and regeneration. While animal models, such as axolotls, zebrafish, and Xenopus laevis, provide valuable findings about these mechanisms, translating these findings into human applications presents challenges. This review underscores the therapeutic potential of modulating these hormonal networks to enhance bone regeneration while cautioning against possible adverse effects, such as uncontrolled tissue proliferation or metabolic imbalances. By integrating knowledge from regenerative models, this work provides a foundation for optimizing hormone-based therapies for clinical applications in bone repair and disease treatment. Full article

(This article belongs to the Special Issue Tissue and Organ Regeneration in Fish: Evolutionary Mechanisms)

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15 pages, 1500 KB

Open AccessEditor’s ChoiceReview

The Role of Th17/Treg Axis in Retinal Pathology Associated with Diabetes and Treatment Options

by Michel-Edwar Mickael, Norwin Kubick, Kreshnik Miftari, Jarosław Olav Horbańczuk, Atanas G. Atanasov, Korona Binçe, Piotr Religa, Agnieszka Kamińska, Mariusz Sacharczuk and Michał Ławiński

Biology 2025, 14(3), 275; https://doi.org/10.3390/biology14030275 - 7 Mar 2025

Viewed by 1448

Abstract

Diabetic retinopathy (DR) is a major complication of diabetes, leading to vision impairment and blindness. The pathogenesis of DR involves multiple factors, including hyperglycemia-induced vascular damage, hypertension, obesity, anemia, immune dysregulation, and disruption of the blood–retinal barrier (BRB). Th17 and Treg cells, two [...] Read more.

Diabetic retinopathy (DR) is a major complication of diabetes, leading to vision impairment and blindness. The pathogenesis of DR involves multiple factors, including hyperglycemia-induced vascular damage, hypertension, obesity, anemia, immune dysregulation, and disruption of the blood–retinal barrier (BRB). Th17 and Treg cells, two types of CD4+ T cells, play opposing roles in inflammation. Th17 cells are pro-inflammatory, producing cytokines such as IL-17A, while Treg cells help suppress immune responses and promote anti-inflammatory effects. Recent studies highlight the importance of the Th17/Treg balance in retinal inflammation and disease progression in DR. Our literature review reveals an imbalance in DR, with increased Th17 activity and reduced Treg function. This shift creates a pro-inflammatory environment in the retina, worsening vascular leakage, neovascularization, and vision loss. The limited infiltration of Treg cells suggests that Th17 cells may uniquely infiltrate the retina by overwhelming or outnumbering Tregs or increasing the expression of recruiting chemokines, rather than only taking advantage of a damaged BRB. Therapeutic strategies, such as neutralizing IL-17A and enhancing Treg function with compounds like IL-35 or curcumin, may reduce inflammation and retinal damage. Restoring the balance between Th17 and Treg cells could provide new approaches for treating DR by controlling inflammation and preventing further retinal damage. Full article

(This article belongs to the Section Medical Biology)

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16 pages, 3332 KB

Open AccessEditor’s ChoiceArticle

A Preclinical Model to Assess Intestinal Barrier Integrity Using Canine Enteroids and Colonoids

by Megan P. Corbett, Vojtech Gabriel, Vanessa Livania, David Díaz-Regañón, Abigail Ralston, Christopher Zdyrski, Dongjie Liu, Sarah Minkler, Hannah Wickham, Addison Lincoln, Karel Paukner, Todd Atherly, Maria M. Merodio, Dipak Kumar Sahoo, David K. Meyerholz, Karin Allenspach and Jonathan P. Mochel

Biology 2025, 14(3), 270; https://doi.org/10.3390/biology14030270 - 6 Mar 2025

Viewed by 1671

Abstract

While two-dimensional (2D) cell cultures, such as Caco-2 and Madin–Darby canine kidney (MDCK) cells are widely used in a variety of biological models, these two-dimensional in vitro systems present inherent limitations in replicating the complexities of in vivo biology. Recent progress in three-dimensional [...] Read more.

While two-dimensional (2D) cell cultures, such as Caco-2 and Madin–Darby canine kidney (MDCK) cells are widely used in a variety of biological models, these two-dimensional in vitro systems present inherent limitations in replicating the complexities of in vivo biology. Recent progress in three-dimensional organoid technology has the potential to address these limitations. In this study, the characteristics of conventional 2D cell culture systems were compared to those of canine intestinal organoids (enteroids, ENT, and colonoids, COL). Light microscopy and transmission electron microscopy were employed to evaluate the microanatomy of ENT, COL, Caco-2, and MDCK cell monolayers, while transepithelial electrical resistance (TEER) values were measured to assess monolayer integrity. The TEER values of canine ENT monolayers more closely approximated reported TEER values for human small intestines compared to Caco-2 and MDCK monolayers. Additionally, canine ENT demonstrated greater monolayer stability than Caco-2 and MDCK cells. Notably, while all systems displayed desmosomes, canine ENT and COL exclusively produced mucus. These findings highlight the potential of the canine organoid system as a more biologically relevant model for in vitro studies, addressing the limitations of conventional 2D cell culture systems. Full article

(This article belongs to the Special Issue Animal Models in Toxicology)

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23 pages, 5785 KB

Open AccessEditor’s ChoiceArticle

Uncovering New Biomarkers for Prostate Cancer Through Proteomic and Network Analysis

by Rossana Rossi, Elena Monica Borroni, Ishak Yusuf, Andrea Lomagno, Mohamed A. A. A. Hegazi, Pietro Luigi Mauri, Fabio Grizzi, Gianluigi Taverna and Dario Di Silvestre

Biology 2025, 14(3), 256; https://doi.org/10.3390/biology14030256 - 4 Mar 2025

Cited by 1 | Viewed by 1750

Abstract

Background: Prostate cancer (PCa), is the second most prevalent solid tumor among men worldwide (7.3%), and the leading non-skin cancer in USA where it represents 14.9% of all new cancer cases diagnosed in 2024. This multifactorial disease exhibits substantial variation in incidence and [...] Read more.

Background: Prostate cancer (PCa), is the second most prevalent solid tumor among men worldwide (7.3%), and the leading non-skin cancer in USA where it represents 14.9% of all new cancer cases diagnosed in 2024. This multifactorial disease exhibits substantial variation in incidence and mortality across different ethnic groups and geographic regions. Although prostate-specific antigen (PSA) remains widely used as a biomarker for PCa, its limitations reduce its effectiveness for accurate detection. Consequently, finding molecules that can either complement PSA and other biomarkers is a major goal in PCa research. Methods: Urine samples were collected from healthy donors (n = 5) and patients with low- and high-risk PCa (4 and 7 subjects, respectively) and were analyzed using proteomic data-derived systems and biology approaches. The most promising proteins were further investigated by means of The Cancer Genome Atlas (TCGA) database to assess their associations with clinical and histopathological characteristics in a larger in silico patient population. Results: By evaluating the variations in the urinary proteome as a mirror of the changes occurring in prostate tumor tissue, components of complement and coagulation cascades and glutathione metabolism emerged as hallmarks of low- and high-risk PCa patients, respectively. Moreover, our integrated approach highlighted new potential biomarkers, including CPM, KRT8, ITIH2, and RCN1. Conclusions: The good overlap of our results with what is already reported in the literature supports the new findings in the perspective of improving the knowledge on PCa. Furthermore, they increase the panel of biomarkers that could enhance PCa management. Of course, further investigations on larger patient cohorts are required. Full article

(This article belongs to the Special Issue Computational Discovery Tools in Genomics and Precision Medicine)

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16 pages, 1748 KB

Open AccessEditor’s ChoiceArticle

IL-1 Receptor Antagonist Anakinra Inhibits the Effect of IL-1β- Mediated Osteoclast Formation by Periodontal Ligament Fibroblasts

by Elizabeth Steemers, Wael M. I. Talbi, Jolanda M. A. Hogervorst, Ton Schoenmaker and Teun J. de Vries

Biology 2025, 14(3), 250; https://doi.org/10.3390/biology14030250 - 28 Feb 2025

Viewed by 1223

Abstract

Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1β is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. [...] Read more.

Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1β is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. Anakinra tempers the disease by decreasing bone resorption and it could possibly stimulate bone formation. Here, we investigate the effect of anakinra in a periodontal disease setting on osteoclastogenesis by co-culturing periodontal ligament fibroblasts (PDLFs) and peripheral blood mononuclear cells (PBMCs) that contain monocytes, a source of osteoclast precursors, as well as by culturing PBMCs alone. The effect of anakinra on PDLF-mediated osteogenesis was studied under mineralization conditions. To mimic a chronic infection such as that prevalent in periodontitis, 10 ng/mL of IL-1β was added either alone or with 10 µg/mL of anakinra. Osteoclastogenesis experiments were performed using co-cultures of PDLF and PBMCs and PBMCs only. Osteoclastogenesis was determined through the formation of multinucleated cells in co-cultures of PDLF and PBMCs, as well as PBMCs alone, at day 21, and gene expression through qPCR at day 14. Osteogenesis was determined by measuring alkaline phosphatase activity (ALP) per cell at day 14. Anakinra is effective in downregulating IL-1β mediated leukocyte clustering and osteoclastogenesis in the co-cultures of both PDLF and PMBCs and PBMCs alone. Gene expression analysis shows that IL-1β increases the expression of the osteoclastogenic marker RANKL and its own expression. This higher expression of IL-1β at the RNA level is reduced by anakinra. Moreover, IL-1β downregulates OPG expression, which is upregulated by anakinra. No effects of anakinra on osteogenesis were seen. Clinically, these findings suggest that anakinra could have a beneficial systemic effect on periodontal breakdown in rheumatoid arthritis patients taking anakinra. Full article

(This article belongs to the Special Issue Bone Cell Biology)

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17 pages, 1417 KB

Open AccessEditor’s ChoiceArticle

Effects of Prenatal Herbal Methionine Supplementation on Growth Indices, Onset of Puberty, Blood Metabolites, and Fertility of Alpine Doelings

by Venancio Cuevas-Reyes, Jorge Flores-Sánchez, Esau Ramírez de la Cruz, Juan M. Vázquez-García, Luisa E. S. Hernández-Arteaga, Reagan Sims, Jaime M. Cavazos-Galindo, Miguel Mellado and César A. Rosales-Nieto

Biology 2025, 14(3), 237; https://doi.org/10.3390/biology14030237 - 26 Feb 2025

Cited by 2 | Viewed by 813

Abstract

This study investigated the effects of prenatal herbal methionine supplementation on growth, puberty onset, reproductive efficiency, and blood metabolites in first-generation G1 Alpine doelings. Sixty pregnant multiparous goats (G0), each with at least three parturitions, were assigned during the last trimester of pregnancy [...] Read more.

This study investigated the effects of prenatal herbal methionine supplementation on growth, puberty onset, reproductive efficiency, and blood metabolites in first-generation G1 Alpine doelings. Sixty pregnant multiparous goats (G0), each with at least three parturitions, were assigned during the last trimester of pregnancy to either herbal methionine (H-MET-G0; 1% Optimethione^®; n = 30) or a control group (CTL-G0; n = 30). Only female offspring (G1 doelings) were studied (H-MET-G1:19; CTL-G1:25) from weaning (45 days old) to 10 months (first breeding). G1 doelings were weighed and monitored weekly for metabolites, IGF-1, insulin, and progesterone. Ovulation of the G1 doelings was induced using vasectomized bucks, followed by breeding with intact bucks. Postweaning growth, age at puberty (H-MET-G1:216 vs. CTL-G1:229 days), and live weight at puberty (H-MET-G1:20.5 vs. CTL-G1:21.0 kg) did not significantly differ (p > 0.05). Age at puberty and conception were negatively correlated with live weight (p < 0.001). First-cycle conception rates were 81% in CTL-G1 and 66% in H-MET-G1, with similar days to conception (p > 0.05). The number of pregnant doelings and the number of kids in utero did not significantly differ (p > 0.05) between treatments. Plasma IGF-1 and insulin levels were significantly higher (p < 0.001) in H-MET-G1 doelings, whereas plasma metabolites related to nutrition showed no differences between groups (p > 0.05). Prenatal herbal methionine supplementation had no carry-over effect on growth, puberty onset, or reproductive efficiency. Age at puberty and conception were negatively correlated with live weight and positively correlated with IGF-1 and insulin levels. Full article

(This article belongs to the Section Developmental and Reproductive Biology)

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19 pages, 2451 KB

Open AccessEditor’s ChoiceArticle

Zebrafish (Danio rerio) Prefer Undisturbed Shoals over Shoals Exposed to the Synthetic Alarm Substance Hypoxanthine-3N-oxide (C₅H₄N₄O₂)

by Andrew Velkey, Kaitlyn Kinslow, Megan Bowers, Ethan Hoffman, Jamie Martin and Bandhavi Surisetty

Biology 2025, 14(3), 233; https://doi.org/10.3390/biology14030233 - 25 Feb 2025

Viewed by 1379

Abstract

As an anti-predation behavior, shoaling enhances survival among prey species by reducing individual predation risk through mechanisms like the dilution effect and collective vigilance. Zebrafish—a highly social and genetically tractable species—are valuable for studying these behaviors. The present study examined zebrafish’s social preferences [...] Read more.

As an anti-predation behavior, shoaling enhances survival among prey species by reducing individual predation risk through mechanisms like the dilution effect and collective vigilance. Zebrafish—a highly social and genetically tractable species—are valuable for studying these behaviors. The present study examined zebrafish’s social preferences in a 3-chamber open-tank free-swim task, assessing whether visual cues alone could distinguish between an intact and an alarmed shoal exposed to the synthetic alarm substance H3NO. Subjects were allowed to freely associate with either shoal while their behaviors were recorded and analyzed. The results reveal a significant preference for proximity to the intact shoal, indicating zebrafish’s ability to visually discern threat levels. Subjects spent nearly twice as much time in the zone near the intact shoal, with reduced freezing and faster movement velocities compared to the alarmed shoal zone. Males exhibited more freezing behavior than females, consistent with sex-specific strategies in threat response. These findings underscore zebrafish’s reliance on visual cues for social responding under predatory threat and highlight sex-based differences in threat perception. This research expands the understanding of zebrafish’s social dynamics and provides a robust framework for future exploration of the neural mechanisms underlying social behavior and threat assessment in zebrafish. Full article

(This article belongs to the Special Issue Social Behavior in Zebrafish)

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29 pages, 5393 KB

Open AccessEditor’s ChoiceArticle

Spatial Distribution Patterns, Environmental Drivers, and Hotspot Dynamics of the European Rabbit on a Mediterranean Island: Implications for Conservation and Management

by Yiannis G. Zevgolis, Foto Konsola, Athanasia-Zoi Bouloutsi, Niki-Nektaria Douskou, Ioanna Emmanouilidou, Maria-Alexandra Kordatou, Anastasia Lekka, Maria-Eirini Limnioti, Maria Loupou, Despoina Papageorgiou, Michailia-Theodora Papamakariou, Eleni Tsiripli, Panagiotis Tzedopoulos, Christos Xagoraris, Alexandros D. Kouris and Panayiotis G. Dimitrakopoulos

Biology 2025, 14(3), 225; https://doi.org/10.3390/biology14030225 - 20 Feb 2025

Cited by 1 | Viewed by 1469

Abstract

The European rabbit (Oryctolagus cuniculus) presents a significant conservation and management challenge in Greece. While it has been listed in national biodiversity assessments, its population dynamics on the island of Lemnos demonstrate the characteristics of a highly adaptable and rapidly expanding [...] Read more.

The European rabbit (Oryctolagus cuniculus) presents a significant conservation and management challenge in Greece. While it has been listed in national biodiversity assessments, its population dynamics on the island of Lemnos demonstrate the characteristics of a highly adaptable and rapidly expanding species, exerting substantial ecological and economic impacts. Addressing this issue requires a spatially explicit understanding of its distribution patterns and habitat preferences, particularly given its extensive population growth over the past three decades. To this end, we conducted 40 field surveys across the island, documenting 1534 presence records of the species. We applied Kernel Density Estimation, Getis-Ord Gi *, and Anselin Local Moran’s I to identify the spatial distribution patterns and significant hotspots. A spatial lag model was used to quantify hotspot intensity and clustering dynamics, while abiotic, biotic, and anthropogenic factors were analyzed to assess habitat associations. Our results revealed that rabbit hotspots are predominantly concentrated in fertile lowland agroecosystems, with nearly 60% of high-density areas overlapping conservation zones. Soil and field conditions, grazing-supporting landscapes, and arable and subsidized agricultural areas emerged as significant predictors of O. cuniculus presence. The observed spatial dependencies indicated that while hotspot intensities and clustering dynamics are influenced by the conditions in neighboring areas, habitat characteristics remain fundamental in shaping their distribution, highlighting the broader landscape-scale spatial patterns affecting rabbit populations. These findings underscore the necessity of adopting spatially informed management strategies that mitigate agricultural impacts while accounting for interconnected spatial dynamics, providing a foundation for informed decision-making to manage rabbit populations while balancing conservation and agricultural priorities. Full article

(This article belongs to the Special Issue Advances in Wildlife Conservation and Habitat Management in the Anthropocene)

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19 pages, 15587 KB

Open AccessEditor’s ChoiceArticle

Long-Term Engraftment of Cryopreserved Human Neurons for In Vivo Disease Modeling in Neurodegenerative Disease

by David J. Marmion, Peter Deng, Benjamin M. Hiller, Rachel L. Lewis, Lisa J. Harms, David L. Cameron, Jan A. Nolta, Jeffrey H. Kordower, Kyle D. Fink and Dustin R. Wakeman

Biology 2025, 14(2), 217; https://doi.org/10.3390/biology14020217 - 19 Feb 2025

Viewed by 1341

Abstract

The transplantation of human neurons into the central nervous system (CNS) offers transformative opportunities for modeling neurodegenerative diseases in vivo. This study evaluated the survival, integration, and functional properties of cryopreserved forebrain GABAergic neurons (iGABAs) derived from human induced pluripotent stem cells (iPSCs) [...] Read more.

The transplantation of human neurons into the central nervous system (CNS) offers transformative opportunities for modeling neurodegenerative diseases in vivo. This study evaluated the survival, integration, and functional properties of cryopreserved forebrain GABAergic neurons (iGABAs) derived from human induced pluripotent stem cells (iPSCs) across three species used in translational research. iGABAs were stereotactically injected into the striatum of Sprague–Dawley rats, immunodeficient RNU rats, R6/2 Huntington’s disease (HD) mice, wild-type controls, and Cynomolgus monkeys. Post-transplantation, long-term assessments revealed robust neuronal survival, extensive neurite outgrowth, and integration with host CNS environments. In immunodeficient rats, iGABAs innervated the neuraxis, extending from the prefrontal cortex to the midbrain, while maintaining mature neuronal phenotypes without uncontrolled proliferation. Similarly, grafts in nonhuman primates showed localized survival and stable phenotype at one month. In the neurodegenerative milieu of HD mice, iGABAs survived up to six months, projecting into the host striatum and white matter, with evidence of mutant huntingtin aggregates localized within the graft, indicating pathological protein transfer. These findings underscore the utility of cryopreserved iGABAs as a reproducible, scalable model for disease-specific CNS investigations and mechanistic studies of proteinopathic propagation. This work establishes a critical platform for studying neurodegenerative diseases and developing therapeutic interventions. Full article

(This article belongs to the Special Issue Stem Cells in Neurological Disorders: Challenges and Opportunities)

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13 pages, 4606 KB

Open AccessEditor’s ChoiceArticle

Minimizing Stress in White Sharks: Non-Invasive Epidermal Biopsies for Isotopic and Vitellogenin Analyses

by Guia Consales, Tommaso Campani, Agata Di Noi, Marco Garofalo, Eduardo Di Marcantonio, Francesca Romana Reinero, Silvia Casini, Luigi Dallai, Emilio Sperone, Letizia Marsili and Primo Micarelli

Biology 2025, 14(2), 192; https://doi.org/10.3390/biology14020192 - 13 Feb 2025

Viewed by 1100

Abstract

The great white shark (Carcharodon carcharias), a keystone predator vital to marine ecosystem stability, is increasingly exposed to anthropogenic threats, including endocrine-disrupting chemicals (EDCs). This study highlights the use of non-invasive epidermal biopsies to assess physiological and ecological parameters in 28 [...] Read more.

The great white shark (Carcharodon carcharias), a keystone predator vital to marine ecosystem stability, is increasingly exposed to anthropogenic threats, including endocrine-disrupting chemicals (EDCs). This study highlights the use of non-invasive epidermal biopsies to assess physiological and ecological parameters in 28 live specimens sampled from the Dyer Island Nature Reserve, South Africa. Epidermal tissue was analyzed for vitellogenin (Vtg), a biomarker of estrogenic exposure, while dermal tissue was used for stable isotope analyses of carbon and nitrogen, essential for understanding the feeding habitat of white sharks. Vitellogenin, typically restricted to sexually mature females, was unexpectedly detected in males and immature females, indicating significant exposure to estrogenic pollutants. This finding raises concerns about the potential reproductive and population-level impacts on this vulnerable species. Stable isotope analyses confirmed that dermal tissue alone is sufficient for trophic studies, eliminating the need for deeper muscle sampling. By demonstrating that epidermal and dermal tissues provide critical data for both biomarkers and isotopic studies, this research supports the adoption of minimally invasive techniques. Shallower biopsies reduce stress on the animals, making this method a valuable tool for conservation research and management of C. carcharias. Full article

(This article belongs to the Special Issue The Future of Marine Megafauna)

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17 pages, 6453 KB

Open AccessEditor’s ChoiceArticle

Tethya wilhelma (Porifera) Is Highly Resistant to Radiation Exposure and Possibly Cancer

by Angelo Fortunato, Jake Taylor, Jonathan Scirone, Sareh Seyedi, Athena Aktipis and Carlo C. Maley

Biology 2025, 14(2), 171; https://doi.org/10.3390/biology14020171 - 7 Feb 2025

Cited by 1 | Viewed by 1622

Abstract

There are no reports of cancer in sponges, despite them having somatic cell turnover, long lifespans, and no specialized adaptive immune cells. In order to investigate whether sponges are cancer resistant, we exposed a species of sponge, Tethya wilhelma, to X-rays. We [...] Read more.

There are no reports of cancer in sponges, despite them having somatic cell turnover, long lifespans, and no specialized adaptive immune cells. In order to investigate whether sponges are cancer resistant, we exposed a species of sponge, Tethya wilhelma, to X-rays. We found that T. wilhelma can withstand 518 Gy of X-ray radiation. That is approximately 100 times the lethal dose for humans. A single high dose of X-rays did not induce cancer in T. wilhelma, providing the first experimental evidence of cancer resistance in the phylum Porifera. Following X-ray exposure, we found an overexpression of genes involved in DNA repair, signaling transduction pathways, and epithelial-to-mesenchymal transition. T. wilhelma has the highest level of radiation resistance that has yet been observed in animals that have sustained somatic cell turnover. This may make them an excellent model system for studying cancer resistance and developing new approaches for cancer prevention and treatment. Full article

(This article belongs to the Section Marine Biology)

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19 pages, 3897 KB

Open AccessEditor’s ChoiceArticle

Seasonal Dynamics of Benthic Infauna Communities in Zostera marina Meadows: Effects of Plant Density Gradients

by Natalia Anna Gintowt, Halina Kendzierska and Urszula Janas

Biology 2025, 14(2), 153; https://doi.org/10.3390/biology14020153 - 3 Feb 2025

Cited by 1 | Viewed by 1048

Abstract

Zostera marina meadows play a key role in the Baltic Sea ecosystem. They are characterized by high primary production and provide feeding and reproduction grounds for organisms. These characteristics vary due to year-round environmental changes and may be due to the characteristics of [...] Read more.

Zostera marina meadows play a key role in the Baltic Sea ecosystem. They are characterized by high primary production and provide feeding and reproduction grounds for organisms. These characteristics vary due to year-round environmental changes and may be due to the characteristics of the meadows themselves. Organisms inhabiting seagrass meadows are involved in the transformation of substances from terrestrial runoff, and, through bioturbation and bioirrigation, affect biogeochemical processes in the sediments. This study aimed to determine the structure of benthic communities inhabiting Z. marina meadows and their bioturbation (BP_C) and bioirrigation (IP_C) potential as affected by seagrass density and seasonal changes. This study shows a positive correlation between the density of Z. marina and the structure of macrozoobenthos, as well as the bioturbation and bioirrigation potential of the studied communities. The autumn season stimulated the density of macrofauna and recorded the highest values of their potential activities indices. The presence of Z. marina positively affects macrozoobenthic communities and their functioning regardless of seagrass density, indicating that seagrass meadows inhabited by macrofauna are key biotopes that can support biogeochemical processes in the coastal zone more effectively than bare sand. Full article

(This article belongs to the Special Issue Benthic Biodiversity from Microbes to Multicellular Organisms and Its Functional Interplays)

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14 pages, 2482 KB

Open AccessEditor’s ChoiceArticle

Selectively Blocking Small Conductance Ca²⁺-Activated K⁺ Channels Improves Cognition in Aged Mice

by Jessie Ong, H. Craig Heller and Elsa Pittaras

Biology 2025, 14(2), 149; https://doi.org/10.3390/biology14020149 - 1 Feb 2025

Viewed by 826

Abstract

Aging is associated with decreased neuronal sensitivity and activity that creates deficits in cognitive processes, including learning, memory, motivation, general activity, and other behaviors. These effects are due in part to decreased intracellular Ca²⁺ homeostasis, increasing hyperpolarization of the resting potential in [...] Read more.

Aging is associated with decreased neuronal sensitivity and activity that creates deficits in cognitive processes, including learning, memory, motivation, general activity, and other behaviors. These effects are due in part to decreased intracellular Ca²⁺ homeostasis, increasing hyperpolarization of the resting potential in aged neurons and therefore decreasing their excitability. To reduce hyperpolarization in aged mice, we used apamin, a selective small conductance Ca²⁺-activated K⁺ (sK_Ca) channel blocker. By blocking the sK_Ca channels, apamin decreases the egress of the K⁺ out of the cell, reducing its hyperpolarization and causing it to be closer to threshold potential. As a result, neurons should be more sensitive to excitatory stimuli and more active. We evaluated the performance of aged mice in a selection of cognitive and behavioral tests prior to and after systemic applications of apamin or the vehicle saline. Apamin improved performance in short-term memory, increased attention to tasks, and decreased anhedonia. Apamin had no significant effect on long-term spatial and recognition memory, risk-taking behavior, sociability, and anxiety. Our results are compatible with the known effects of sK_Ca channel blockade on neuronal sensitivity and activity; however, these short-term effects were not reflected in longer-term alterations of neural plasticity responsible for long-term spatial and recognition memory or other more complex cognitive processes we evaluated. Full article

(This article belongs to the Section Behavioural Biology)

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19 pages, 2390 KB

Open AccessEditor’s ChoiceArticle

The Drivers of Mesozoic Neoselachian Success and Resilience

by Manuel Andreas Staggl, Carlos De Gracia, Faviel A. López-Romero, Sebastian Stumpf, Eduardo Villalobos-Segura, Michael J. Benton and Jürgen Kriwet

Biology 2025, 14(2), 142; https://doi.org/10.3390/biology14020142 - 30 Jan 2025

Viewed by 3033

Abstract

The modern diversity of sharks, skates, and rays (Neoselachii) is the result of various diversification and extinction events during the Mesozoic (252–66 Ma). However, the key drivers of their diversity patterns remain poorly understood despite all the progress that has been accomplished in [...] Read more.

The modern diversity of sharks, skates, and rays (Neoselachii) is the result of various diversification and extinction events during the Mesozoic (252–66 Ma). However, the key drivers of their diversity patterns remain poorly understood despite all the progress that has been accomplished in recent years. Here, we show that the interplay of climatic- and tectonic-linked trajectories, resulting in a high shallow marine habitat availability and lower atmospheric CO₂ concentration, were significant drivers and sustainers of Mesozoic neoselachian diversity. We show, for the first time, that higher atmospheric CO₂ content negatively affected neoselachian diversity in the past. The recognized gradual faunal changes throughout the Mesozoic and the two major diversification events during the Jurassic and Cretaceous, respectively, ultimately cumulated in an all-time diversity high in the Palaeogene despite the events during the end-Cretaceous extinction event, highlighting their remarkable resilience and adaptability despite severe environmental challenges. We thus provide novel perspectives on the processes underlying neoselachian diversification since the Mesozoic that contribute importantly to a better understanding of the selective forces that have shaped the long-term evolution and diversification of neoselachians. Given their vital role in modern ecosystems, our results provide information about possible future trends in the face of the current climate crisis. Full article

(This article belongs to the Section Zoology)

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16 pages, 1617 KB

Open AccessEditor’s ChoiceArticle

Impact of Ad Libitum Hydration on Muscle and Liver Damage and Electrolyte Balance in Ultra-Trail Events: A Heatmap Analysis of Biomarkers and Event Characteristics—A Pilot Study

by Alejandro García-Giménez, Francisco Pradas, Miguel Lecina, Nicolae Ochiana and Carlos Castellar-Otín

Biology 2025, 14(2), 136; https://doi.org/10.3390/biology14020136 - 28 Jan 2025

Viewed by 1362

Abstract

Ultra-trail events (UTs) pose significant challenges to maintaining hydration and electrolyte balance, with risks of dehydration (DH), overhydration (OH), exercise-associated hyponatremia (EAH), and exertional rhabdomyolysis (ER). This study examined the effects of ad libitum (ADL) hydration on hydration status and muscle damage during [...] Read more.

Ultra-trail events (UTs) pose significant challenges to maintaining hydration and electrolyte balance, with risks of dehydration (DH), overhydration (OH), exercise-associated hyponatremia (EAH), and exertional rhabdomyolysis (ER). This study examined the effects of ad libitum (ADL) hydration on hydration status and muscle damage during a nine-stage UT (635 km, 40,586 m elevation gain). Four highly trained male athletes participated. Hydration was assessed via body weight loss (BWL), urine specific gravity (U_sg), and serum sodium ([Na+]), while muscle damage markers included creatine kinase (CK), lactate dehydrogenase (LDH), and calcium (Ca), and liver damage biomarkers included aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Our results showed no cases of EAH or hypernatremia ([Na+] > 145 mmol·L⁻¹), with serum [Na+] maintained above 135 mmol·L⁻¹. BWL exceeded the 2% DH threshold in early stages (p = 0.029), and U_sg remained elevated (>1.020 g·mL⁻¹). LDH and CK significantly increased at all stages (p < 0.05), persisting for 48 h post-event. Correlations showed BWL aggravated muscle damage (r = 0.47 with CK) and hypocalcemia (r = −0.68 with Ca). Elevation gain/loss amplified fluid loss and muscle injury. While ADL hydration mitigated EAH, it did not fully address DH or muscle damage. Personalized hydration and recovery protocols are crucial to optimizing performance and health in UT events. Full article

(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)

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34 pages, 4118 KB

Open AccessEditor’s ChoiceReview

The Important Role of p21-Activated Kinases in Pancreatic Exocrine Function

by Irene Ramos-Alvarez and Robert T. Jensen

Biology 2025, 14(2), 113; https://doi.org/10.3390/biology14020113 - 22 Jan 2025

Cited by 2 | Viewed by 1881

Abstract

The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1–3) and group II (PAK4–6). Both groups of PAKs have been well studied [...] Read more.

The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1–3) and group II (PAK4–6). Both groups of PAKs have been well studied in apoptosis, protein synthesis, glucose homeostasis, growth (proliferation and survival) and cytoskeletal regulation, as well as in cell motility, proliferation and cycle control. However, little is known about the role of PAKs in the secretory tissues, including in exocrine tissue, such as the exocrine pancreas (except for islet function and pancreatic cancer growth). Recent studies have provided insights supporting the importance of PAKs in exocrine pancreas. This review summarizes the recent insights into the importance of PAKs in the exocrine pancreas by reviewing their presence and activation; the ability of GI hormones/neurotransmitters/GFs/post-receptor activators to activate them; the kinetics of their activation; the participation of exocrine-tissue PAKs in activating the main growth-signaling cascade; their roles in the stimulation of enzyme secretion; finally, their roles in pancreatitis. These insights suggest that PAKs could be more important in exocrine/secretory tissues than currently appreciated and that their roles should be explored in more detail in the future. Full article

(This article belongs to the Special Issue Unveiling Disease Molecular Signaling Pathways: Targeted Drug Discoveries for Pathway Modulation)

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20 pages, 3906 KB

Open AccessEditor’s ChoiceArticle

Beclin 1-Mediated Autophagy Is Potentiated by an Interaction with the Neuronal Adaptor FE65

by Wai Wa Ray Chan, Jessica Chow, Dennis Dik-Long Chau, Yuqi Zhai and Kwok-Fai Lau

Biology 2025, 14(1), 97; https://doi.org/10.3390/biology14010097 - 18 Jan 2025

Cited by 1 | Viewed by 1897

Abstract

Autophagy is a vital cellular pathway in eukaryotic cells, including neurons, where it plays significant roles in neurodevelopment and maintenance. A crucial step in autophagy is the formation of the class III phosphatidylinositol 3-kinase complex 1 (PI3KC3-C1), which is essential for initiating autophagosome [...] Read more.

Autophagy is a vital cellular pathway in eukaryotic cells, including neurons, where it plays significant roles in neurodevelopment and maintenance. A crucial step in autophagy is the formation of the class III phosphatidylinositol 3-kinase complex 1 (PI3KC3-C1), which is essential for initiating autophagosome biogenesis. Beclin 1 is the key component of PI3KC3-C1, and its interactors have been reported to affect autophagy. The brain-enriched adaptor protein FE65 has been shown to interact with Alzheimer’s disease amyloid precursor protein (APP) to alter the processing of APP. Additionally, FE65 has been implicated in various cellular pathways, including autophagy. We demonstrate here that FE65 positively regulates autophagy. FE65, through its C-terminus, has been shown to interact with Beclin 1. Notably, the overexpression of FE65 enhances Beclin 1-mediated autophagy, whereas this process is attenuated in FE65 knockout cells. Moreover, the stimulatory effect of FE65 on Beclin 1-mediated autophagy is diminished by an FE65 C-terminus deletion mutant that disrupts the FE65–Beclin 1 interaction. Lastly, we have found that the FE65-Beclin 1 interaction modulates the kinase activity of the PI3KC3-C1 complex. Together, we have identified FE65 as a novel Beclin 1 interactor, and this interaction potentiates autophagy. Full article

(This article belongs to the Section Biochemistry and Molecular Biology)

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12 pages, 3517 KB

Open AccessEditor’s ChoiceArticle

Morphology and Immunoexpression of Selenoproteins in Term Placenta of Alpaca (Vicugna pacos) from the Peruvian Andes

by Miluska Beatriz Navarrete Zamora, Francisco Acuña, Mônica Duarte da Silva, Thamires Santos-Silva, Matheus Henrique Herminio Garcia, Rodrigo da Silva Nunes Barreto, Alberto Sato Sato, Claudio Gustavo Barbeito and Maria Angelica Miglino

Biology 2025, 14(1), 64; https://doi.org/10.3390/biology14010064 - 14 Jan 2025

Viewed by 3051

Abstract

South American camelids inhabit high-altitude environments characterized by hypoxia, influencing embryonic, fetal, and placental development. This study examined the term placenta morphology of alpacas (Vicugna pacos, N = 12) and the immunoexpression of antioxidant selenoproteins (SP). We hypothesize that the placenta [...] Read more.

South American camelids inhabit high-altitude environments characterized by hypoxia, influencing embryonic, fetal, and placental development. This study examined the term placenta morphology of alpacas (Vicugna pacos, N = 12) and the immunoexpression of antioxidant selenoproteins (SP). We hypothesize that the placenta of alpacas, adapted to high altitudes, has characteristics with other species also adapted to altitude. Placentas were paraffin-embedded, sectioned (3–5 µm), stained with hematoxylin–eosin (H&E), Masson’s trichrome, and picrosirius red, and analyzed via light and polarized light microscopy. The chorion showed simple cuboidal epithelium with binucleated cells, a subepithelial mesenchyme rich in blood capillaries (area: 124.90 ± 9.82 µm²), and type III collagen fibers. The chorionic villi measured 2740.22 ± 132.75 µm. The allantois contained a simple columnar epithelium and mesenchyme with type I collagen fibers. Immunohistochemistry localized SP-N, SP-P, Dio-3, and GPx-3 in the blood capillaries and mesenchymal tissue of the chorion but not in the allantois. These findings were compared to human and sheep placentas from different altitudes due to a lack of camelid data at low levels. The morphological features resembled adaptations to hypoxia observed in other species. This preliminary study suggests a potential role for selenoproteins in hypoxia adaptation, providing a basis for future functional studies. Full article

(This article belongs to the Special Issue Reproductive Physiology and Pathology in Livestock)

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18 pages, 17025 KB

Open AccessEditor’s ChoiceArticle

FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption

by Lei Wang, Tarun Minocha, Bhaba K. Das, Mikaela D. Kunika, Aarthi Kannan, Ling Gao, Subburaman Mohan, Weirong Xing, Kottayil I. Varughese and Haibo Zhao

Biology 2025, 14(1), 45; https://doi.org/10.3390/biology14010045 - 9 Jan 2025

Viewed by 1162

Abstract

There are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitro. In this [...] Read more.

There are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitro. In this study, we found that all three Fam98 genes were expressed in precursor and mature osteoclasts. While the knockdown of Fam98c by a specific short-hairpin RNA (shRNA) in osteoclast precursors attenuated osteoclastogenesis, depletion of Fam98b by an shRNA specifically disrupted osteoclast lysosome trafficking and bone resorption with phenotypes similar to Fam98a shRNA-knockdown in our previous study. Loss of Fam98a in myeloid osteoclast precursors was dispensable for trabecular and cortical bone mass in mice, as well as osteoclastogenesis/bone resorption in vitro, possibly due to compensation by increased Fam98b expression in Fam98a-null osteoclasts. These findings indicate that the three Fam98 proteins play distinct roles in osteoclastogenesis and osteoclast function and need further investigation in future studies. Full article

(This article belongs to the Special Issue Molecular Basis of Bone Homeostasis and Skeletal Diseases)

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18 pages, 3693 KB

Open AccessEditor’s ChoiceArticle

Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk

by Simona Panni and Roberto Pizzolotto

Biology 2025, 14(1), 43; https://doi.org/10.3390/biology14010043 - 8 Jan 2025

Cited by 2 | Viewed by 1333

Abstract

It is becoming increasingly clear that microRNAs are key players in gene regulatory networks, modulating gene expression at post-transcriptional level. Their involvement in almost all cellular processes predicts their role in diseases, and several microRNA-based therapeutics are currently undergoing clinical testing. Despite their [...] Read more.

It is becoming increasingly clear that microRNAs are key players in gene regulatory networks, modulating gene expression at post-transcriptional level. Their involvement in almost all cellular processes predicts their role in diseases, and several microRNA-based therapeutics are currently undergoing clinical testing. Despite their undeniable relevance and the substantial body of literature demonstrating their role in cancer and other pathologies, the identification of functional interactions is still challenging. To address this issue, several resources have been developed to collect information from the literature, according to different criteria and reliability scores. In the present study, we have constructed a network of verified microRNA-mRNA interactions by integrating strong-evidence couples from different resources. Our analysis of the resulting network reveals that only one-fifth of the human genes exhibits experimental validated regulation by microRNAs. A very small subset of them is controlled by more than 20 microRNAs, and these hubs are highly enriched of pivotal transcription factors and regulatory proteins, strongly suggesting a complex interplay and a combinatorial effect between transcriptional and post-transcriptional gene control. Data analysis also reveals that several microRNAs control multiple targets involved in the same pathway or biological process, likely contributing to the coordinated control of the protein levels. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 3046 KB

Open AccessEditor’s ChoiceArticle

Exploring Brain Size Asymmetry and Its Relationship with Predation Risk Among Chinese Anurans

by Chuan Chen, Ying Jiang, Yiming Wu, Lingsen Cao and Wenbo Liao

Biology 2025, 14(1), 38; https://doi.org/10.3390/biology14010038 - 7 Jan 2025

Viewed by 919

Abstract

Brain size asymmetry differs considerably across species, including humans, vertebrates, and invertebrates. The subtle structural, functional, or size differences between the two brain sides are associated with processing specific cognitive tasks. To evaluate the differences between the sizes of the left and right [...] Read more.

Brain size asymmetry differs considerably across species, including humans, vertebrates, and invertebrates. The subtle structural, functional, or size differences between the two brain sides are associated with processing specific cognitive tasks. To evaluate the differences between the sizes of the left and right sides of the whole brain and brain regions and the effect of predation risk (i.e., snake density) on brain size asymmetry among Chinese anurans, we compared the differences between the left and right hemisphere sizes of the whole brain and brain regions among anuran species and analyzed the correlations between the predation risk and size asymmetry index of the brain and brain regions. We found that when one side of the brain was consistently larger than the other, there was a significant difference between the sizes of the left and right sides of the brain and brain regions, displaying directional asymmetry of the whole brain and brain regions. We also found that total brain size was positively correlated with the size asymmetry index of the olfactory bulb and optic tecta when the left hemispheres of the whole brain and brain regions were larger than the right ones. Meanwhile, the index of telencephalon size asymmetry was positively correlated with predation risk when the right hemispheres of the brain and brain regions were larger than the left ones. However, there were non-significant differences between the sizes of the left and right sides of the brain and brain regions across 99 species of anurans. Our findings suggest that an increased predation risk linked to sociality is likely to drive an increase in right telencephalon size. Full article

(This article belongs to the Section Zoology)

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18 pages, 2515 KB

Open AccessEditor’s ChoiceArticle

NF-κB-Inducing Kinase Is Essential for Effective c-Rel Transactivation and Binding to the Il12b Promoter in Macrophages

by Natalia Cuesta, Anna D. Staniszewska, Cristóbal Moreno, Carmen Punzón and Manuel Fresno

Biology 2025, 14(1), 33; https://doi.org/10.3390/biology14010033 - 3 Jan 2025

Cited by 1 | Viewed by 2017

Abstract

This study investigates the role of NIK in activating specific inflammatory genes in macrophages, focusing on the effect of a mutation in NIK found in alymphoplasia (aly/aly) mice. Mouse peritoneal macrophages from aly/aly mice showed a severe [...] Read more.

This study investigates the role of NIK in activating specific inflammatory genes in macrophages, focusing on the effect of a mutation in NIK found in alymphoplasia (aly/aly) mice. Mouse peritoneal macrophages from aly/aly mice showed a severe defect in the production of some pro-inflammatory cytokines, such as IL-12. This effect seemed to take place at the transcriptional level, as shown by the reduced transcription of Il12b and Il12a in aly/aly macrophages after exposure to the TLR4 agonist LPS. Immunoprecipitation studies showed that the binding of NIK to c-Rel was not efficient in RAW 264.7 cells over-expressing the aly/aly mutation. In addition, the shuttling of c-Rel to the nucleus was shown to be impaired in aly/aly macrophages in response to LPS. When looking more specifically at the regulation of the Il12b promoter, we found that c-Rel bound to the NF-kB consensus sequence in macrophages from WT mice 1 hr. after LPS challenge, whereas in aly/aly macrophages, the transcription factor bound to the promoter was p65. These findings indicate that NIK is essential for efficient c-Rel activation and proper inflammatory responses. NIK dysfunction could lead to weakened immune responses, and targeting this pathway may help in developing therapies for immune-related conditions. Full article

(This article belongs to the Section Biochemistry and Molecular Biology)

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20 pages, 9495 KB

Open AccessEditor’s ChoiceArticle

Dominance of Sulfur-Oxidizing Bacteria, Thiomicrorhabdus, in the Waters Affected by a Shallow-Sea Hydrothermal Plume

by Chih-Ching Chung, Gwo-Ching Gong, Hsiao-Chun Tseng, Wen-Chen Chou and Chuan-Hsin Ho

Biology 2025, 14(1), 28; https://doi.org/10.3390/biology14010028 - 1 Jan 2025

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Abstract

The shallow-sea hydrothermal vent at Guishan Islet, located off the coast of Taiwan, serves as a remarkable natural site for studying microbial ecology in extreme environments. In April 2019, we investigated the composition of prokaryotic picoplankton communities, their gene expression profiles, and the [...] Read more.

The shallow-sea hydrothermal vent at Guishan Islet, located off the coast of Taiwan, serves as a remarkable natural site for studying microbial ecology in extreme environments. In April 2019, we investigated the composition of prokaryotic picoplankton communities, their gene expression profiles, and the dissolved inorganic carbon uptake efficiency. Our results revealed that the chemolithotrophs Thiomicrorhabdus spp. contributed to the majority of primary production in the waters affected by the hydrothermal vent plume. The metatranscriptomic analysis aligned with the primary productivity measurements, indicating the significant gene upregulations associated with carboxysome-mediated carbon fixation in Thiomicrorhabdus. Synechococcus and Prochlorococcus served as the prokaryotic photoautotrophs for primary productivity in the waters with lower influence from hydrothermal vent emissions. Thiomicrorhabdus and picocyanobacteria jointly provided organic carbon for sustaining the shallow-sea hydrothermal vent ecosystem. In addition to the carbon fixation, the upregulation of genes involved in the SOX (sulfur-oxidizing) pathway, and the dissimilatory sulfate reduction indicated that energy generation and detoxification co-occurred in Thiomicrorhabdus. This study improved our understanding of the impacts of shallow-sea hydrothermal vents on the operation of marine ecosystems and biogeochemical cycles. Full article

(This article belongs to the Special Issue Multi-Omics of Extremophilic Organisms)

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