Search Results (82)

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article

Background/Objectives: Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics in livestock, offering a sustainable strategy for controlling bacterial pathogens in food production systems. In addition to their direct antimicrobial effects, AMPs play a key role in modulating host-associated microbiomes, influencing both microbial composition and function. Advances in metagenomic sequencing and bioinformatic tools now enable comprehensive exploration of AMP diversity and activity within complex microbial ecosystems. Methods: In this study, we employed Illumina-based next-generation sequencing (NGS) to analyze intestinal contents from six gut sections of broiler chickens obtained from a Spanish slaughterhouse. Results: Through de novo assembly and bioinformatic annotation, we identified biosynthetic gene clusters (BGCs) encoding ribosomally synthesized and post-translationally modified peptides (RiPPs), other specialized bioactive secondary metabolites, antimicrobial resistance genes (ARGs), virulence factor genes (VFGs), and a diverse microbial community. Among all gut sections, the cecum exhibited the highest genetic richness, characterized by a high diversity of RiPP-like clusters and antimicrobial resistance determinants. Conclusions: These findings highlight the poultry gut, particularly the cecum, as a significant reservoir of antimicrobial peptides (AMPs) with potential implications in antibiotic-free poultry production and enhanced food safety. Full article

The papers introduced in the Commentary present new insights and review aspects of current knowledge concerning the competition between viruses and their hosts for the cellular translation apparatus. Viruses depend on this apparatus and utilize diverse mechanisms to usurp it for the translation of viral mRNAs and to suppress synthesis of cellular proteins. Virus-induced modification of translation factors, selective abrogation of mRNA binding to ribosomes and degradation of cellular mRNAs all impair elements of the innate immune response, thereby undermining host defenses against infection. Various cellular mechanisms prevent translation of viral mRNAs, by modifying components of the translation apparatus to effect a generalized shut-off of translation or by binding of host proteins to viral mRNAs to induce their degradation or to prevent their engagement with the translation apparatus. Viruses have in turn evolved countermeasures to evade these defenses, for example by encoding proteins that impair the activity of host factors or via alterations in the sequence and structure of viral mRNAs. Such changes enable viral mRNAs to avoid recognition by host factors or to support translation initiation by specialized mechanisms that involve only a subset of the factors that are required by cellular mRNAs. Full article

Ribosomal proteins (RPs) were traditionally considered as ribosome building blocks, serving exclusively in ribosome assembly. However, contemporary research highlights their involvement in additional translational roles, as well as diverse non-ribosomal activities. The functional diversity of RPs is further enriched by the presence of 2–7 paralogs per RP family in plants, suggesting that these proteins may perform distinct, specialized functions. The spatiotemporal expression of RP paralogs allows for the assembly of unique ribosomes (ribosome heterogeneity), enabling the selective translation of specific mRNAs, and producing specialized proteins essential for plant functioning. Additionally, RPs that operate independently of ribosomes as free molecules may regulate a wide range of physiological processes. RPs involved in protein biosynthesis within the cytosol, mitochondria, or plastids are encoded by distinct genes, which account for their functional specialization. Notably, RPs associated with plastid or mitochondrial ribosomes, beyond their canonical roles in these organelles, also contribute to overall plant development and functionality, akin to their cytosolic counterparts. This review explores the roles of RPs in different cellular compartments, the presumed molecular mechanisms underlying their functions, and the involvement of other molecular factors that cooperate with RPs in these processes. In addition to the new RP nomenclature introduced in 2022/2023, the old names are also applied. Full article

The simplest cyclo-peptides, also known as diketopiperazines (DKPs), are widespread in nature. The growing interest in these simplest cyclo-peptides is driven by their significant potential for therapeutic applications. In this study, we identified a biosynthetic gene cluster from Aspergillus aculeatus CRI323-04 through genome mining and heterologous expression in Aspergillus nidulans. The two core genes, aacA and aacB, within the gene cluster were characterized for their role in the biossoynthesis of aspkyncin, a novel DKP compound that incorporates a l-kynurenine (l-Kyn) unit. Furthermore, we successfully reconstituted the activities of the minimal bimodular non-ribosomal peptide synthetase (NRPS) AacA and the methyltransferase AacB both in vivo and in vitro. Our findings demonstrate that AacA catalyzes the condensation and cyclization of two non-proteinogenic amino acids, l-Kyn and N-methyl-l-alanine, to produce aspkyncin without the involvement of any release domain. Notably, the N-methyl-l-alanine is generated by a specialized l-alanine N-methyltransferase AacB prior to NRP assembly. This study reveals an unconventional pathway for the biosynthesis of fungal DKPs. Full article

LBD transcription factors are critical regulators of plant growth and development. Recent studies highlighted their significant role in the transcriptional regulation of plant growth and metabolism. Thus, identifying the CeLBD gene in Cymbidium ensifolium, a species abundant in floral scent metabolites, could provide deeper insights into its functional significance. A total of 34 LBD genes were identified in C. ensifolium. These CeLBDs fell into two major groups: Class I and Class II. The Class I group contained 30 genes, while the Class II group included only 4 genes. Among the 30 Class I genes, several genes in the Ie branch exhibited structural variations or partial deletions (CeLBD20 and CeLBD21) in the coiled-coil motif (LX₆LX₃LX₆L). These changes may contribute to the difficulty in root hair formation in C. ensifolium. The variations may prevent normal transcription, leading to low or absent expression, which may explain the fleshy and corona-like root system of C. ensifolium without prominent lateral roots. The expansion for CeLBDs was largely due to special WGD events in orchids during evolution, or by segmental duplication and tandem duplication. CeLBDs in different branches exhibit similar functions and expression characteristics. Promoter analysis enriched environmental response elements, such as AP2/ERF, potentially mediating the specific expression of CeLBDs under different stresses. CeLBDs were predicted to interact with multiple transcription factors or ribosomal proteins, forming complex regulatory networks. CeLBD20 was localized in the cytoplasm, it may act as a signaling factor to activate other transcription factors. CeLBD6 in Class II was significantly up-regulated under cold, drought, and ABA treatments, suggesting its role in environmental responses. Furthermore, metabolic correlation analysis revealed that its expression was associated with the release of major aromatic compounds, such as MeJA. These findings offer valuable insights for further functional studies of CeLBD genes in C. ensifolium. Full article

The pervasive and often indiscriminate use of antibiotics has accelerated the emergence of drug-resistant bacterial strains, thus presenting an acute threat to global public health. Despite a growing acknowledgment of the severity of this crisis, the current suite of strategies to mitigate antimicrobial resistance remains markedly inadequate. This paper asserts the paramount need for the swift development of groundbreaking antimicrobial strategies and provides a comprehensive review of an array of innovative techniques currently under scrutiny. Among these, nano-antimicrobials, antimicrobials derived from ribosomal proteins, CRISPR/Cas-based systems, agents that undermine bacterial bioenergetics, and antimicrobial polysaccharides hold particular promise. This analysis gives special attention to CRISPR/Cas-based antimicrobials, scrutinizing their underlying mechanisms, exploring their potential applications, delineating their distinct advantages, and noting their likely limitations. Furthermore, we extend our exploration by proposing theoretical advancements in antimicrobial technology and evaluating feasible methods for the effective delivery of these agents. This includes leveraging these advances for broader biomedical applications, potentially revolutionizing how we confront bacterial pathogens in the future, and laying a foundation for extended research in multimodal therapeutic strategies. Full article

Anaerobic digesters host a variety of microorganisms, and they work together to produce biogas. While bacterial and archaeal communities have been well explored using molecular techniques, fungal community structures remain relatively understudied. The present study aims to investigate the dynamics and potential ecological functions of the predominant fungi in bacteria-bioaugmented anaerobic digesters. Eight different anaerobic digesters that contained chopped water hyacinth and cow dung as feedstock at 2% total solids were respectively inoculated with eight different bacterial strains and digested anaerobically in controlled conditions. The diversity and dynamics of the fungal community of the digesters before and after digestion were monitored using high-throughput sequencing of the fungal ITS2 sub-region of the ribosomal gene. The functional potential of the fungal community was predicted using ecological guild analysis. The dominant fungal phyla were (with relative abundance ≥1%) Ascomycota and Neocallimastigomycota. Ascomycota exhibited over 90% dominance in all treatments after anaerobic digestion (AD). Aspergillus sp. was consistently dominant across treatments during AD, while prominent anaerobic fungal genera Anaeromyces, Cyllamyces, and Caeomyces decreased. Ecological guild analysis at genus level showed that the majority of the identified fungi were saprophytes, and diversity indices indicated decreased richness and diversity after AD, suggesting a negative impact of AD on fungal communities in the anaerobic digesters. The multivariate structure of the fungal communities showed clustering of treatments with similar fungal taxa. The findings from this study provide insights into the fungal ecological guild of different bacteria-bioaugmented anaerobic digesters, highlighting their potentials in bacteria-augmented systems. Identification of an anaerobic fungal group within the phylum Ascomycota, beyond the well-known fungal phylum Neocallimastigomycota, offers a new perspective in optimizing the AD processes in specialized ecosystems. Full article

The aim of the present research is the isolation and morphological and molecular–phenological identification of nematophagous fungi of Southern Kazakhstan for the production of effective bionematicides on their basis. Nematophagous fungi, which include nematode-trapping, ovicidal, endoparasitic, toxin-producing, and special substance-producing fungi, are among the most effective biological agents in controlling phytoparasitic nematodes. To isolate and characterize nematophagous fungi, soil samples were collected at 12 sites in three regions of Southern Kazakhstan. The samples were collected using the envelope method. The content of nematophagous fungi in the samples was determined using the standard surface sowing technique. The obtained strains of nematophagous fungi were identified. The attractive and nematophagous activity of the obtained fungal strains was determined by using standard methods. In experiments on the isolation and morphological identification of nematophagous fungi, the nematode species Meloidogyne incognita was used. Identification of the strains was carried out by the method of determining the direct nucleotide sequence of the region of the nuclear ribosomal internal transcribed spacer, followed by determination of nucleotide identity with sequences deposited in the international GeneBank database. As a result, the following species of nematophagous fungi living in the soils of agricultural lands in Southern Kazakhstan were identified: Orbilia oligospora, Duddingtonia flagrans, Orbilia oligospora, and Arthrobotrys superba. Full article

Olfactory sensitivity to odorant molecules is a complex biological function influenced by both endogenous factors, such as genetic background and physiological state, and exogenous factors, such as environmental conditions. In animals, this vital ability is mediated by olfactory sensory neurons (OSNs), which are distributed across several specialized olfactory subsystems depending on the species. Using the phosphorylation of the ribosomal protein S6 (rpS6) in OSNs following sensory stimulation, we developed an ex vivo assay allowing the simultaneous conditioning and odorant stimulation of different mouse olfactory subsystems, including the main olfactory epithelium, the vomeronasal organ, and the Grueneberg ganglion. This approach enabled us to observe odorant-induced neuronal activity within the different olfactory subsystems and to demonstrate the impact of environmental conditioning, such as temperature variations, on olfactory sensitivity, specifically in the Grueneberg ganglion. We further applied our rpS6-based assay to the human olfactory system and demonstrated its feasibility. Our findings show that analyzing rpS6 signal intensity is a robust and highly reproducible indicator of neuronal activity across various olfactory systems, while avoiding stress and some experimental limitations associated with in vivo exposure. The potential extension of this assay to other conditioning paradigms and olfactory systems, as well as its application to other animal species, including human olfactory diagnostics, is also discussed. Full article

Bacillus sp. THPS1 is a novel strain isolated from a high-temperature hot spring in Thailand, exhibiting distinctive genomic features that enable adaptation to an extreme environment. This study aimed to characterize the genomic and functional attributes of Bacillus sp. THPS1 to understand its adaptation strategies and evaluate its potential for biotechnological applications. The draft genome is 5.38 Mbp with a GC content of 35.67%, encoding 5606 genes, including those linked to stress response and sporulation, which are essential for survival in high-temperature conditions. Phylogenetic analysis and average nucleotide identity (ANI) values confirmed its classification as a distinct species within the Bacillus genus. Pangenome analysis involving 19 others closely related thermophilic Bacillus species identified 1888 singleton genes associated with heat resistance, sporulation, and specialized metabolism, suggesting adaptation to nutrient-deficient, high-temperature environments. Genomic analysis revealed 12 biosynthetic gene clusters (BGCs), including those for polyketides and non-ribosomal peptides, highlighting its potential for synthesizing secondary metabolites that may facilitate its adaptation. Additionally, the presence of three Siphoviridae phage regions and 96 mobile genetic elements (MGEs) suggests significant genomic plasticity, whereas the existence of five CRISPR arrays implies an advanced defense mechanism against phage infections, contributing to genomic stability. The distinctive genomic features and functional capacities of Bacillus sp. THPS1 make it a promising candidate for biotechnological applications, particularly in the production of heat-stable enzymes and the development of resilient bioformulations. Full article

The cell cycle, essential for growth, reproduction, and genetic stability, is regulated by a complex network of cyclins, Cyclin-Dependent Kinases (CDKs), phosphatases, and checkpoints that ensure accurate cell division. CDKs and phosphatases are crucial for controlling cell cycle progression, with CDKs promoting it and phosphatases counteracting their activity to maintain balance. The nucleolus, as a biomolecular condensate, plays a key regulatory role by serving as a hub for ribosome biogenesis and the sequestration and release of various cell cycle regulators. This phase separation characteristic of the nucleolus is vital for the specific and timely release of Cdc14, required for most essential functions of phosphatase in the cell cycle. While mitosis distributes chromosomes to daughter cells, meiosis is a specialized division process that produces gametes and introduces genetic diversity. Central to meiosis is meiotic recombination, which enhances genetic diversity by generating crossover and non-crossover products. This process begins with the introduction of double-strand breaks, which are then processed by numerous repair enzymes. Meiotic recombination and progression are regulated by proteins and feedback mechanisms. CDKs and polo-like kinase Cdc5 drive recombination through positive feedback, while phosphatases like Cdc14 are crucial for activating Yen1, a Holliday junction resolvase involved in repairing unresolved recombination intermediates in both mitosis and meiosis. Cdc14 is released from the nucleolus in a regulated manner, especially during the transition between meiosis I and II, where it helps inactivate CDK activity and promote proper chromosome segregation. This review integrates current knowledge, providing a synthesis of these interconnected processes and an overview of the mechanisms governing cell cycle regulation and meiotic recombination. Full article

Ribosomes were known to be multicomponent complexes as early as the 1960s. Nonetheless, the prevailing view for decades considered active ribosomes to be a monolithic population, in which all ribosomes are identical in composition and function. This implied that ribosomes themselves did not actively contribute to the regulation of protein synthesis. In this perspective, I review evidence for a different model, based on results showing that ribosomes can harbor different types of ribosomal RNA (rRNA) and ribosomal proteins (r-proteins) and, furthermore, need not contain a complete set of r-proteins. I also summarize recent results favoring the notion that such distinct types of ribosomes have different affinities for specific messenger RNAs and may execute the translation process differently. Thus, ribosomes should be considered active contributors to the regulation of protein synthesis. Full article

The biosynthesis of antibiotics and other secondary metabolites (also named special metabolites) is regulated by multiple regulatory networks and cascades that act by binding transcriptional factors to the promoter regions of different biosynthetic gene clusters. The binding affinity of transcriptional factors is frequently modulated by their interaction with specific ligand molecules. In the last decades, it was found that the biosynthesis of penicillin is induced by two different molecules, 1,3-diaminopropane and spermidine, but not by putrescine (1,4-diaminobutane) or spermine. 1,3-diaminopropane and spermidine induce the expression of penicillin biosynthetic genes in Penicillium chrysogenum. Proteomic studies clearly identified two different proteins that respond to the addition to cultures of these inducers and are involved in β-alanine and pantothenic acid biosynthesis. These compounds are intermediates in the biosynthesis of phosphopantetheine that is required for the activation of non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. These large-size multidomain enzymes are inactive in the “apo” form and are activated by covalent addition of the phosphopantetheine prosthetic group by phosphopantetheinyl transferases. Both 1,3-diaminopropane and spermidine have a similar effect on the biosynthesis of cephalosporin by Acremonium chrysogenum and lovastatin by Aspergillus terreus, suggesting that this is a common regulatory mechanism in the biosynthesis of bioactive secondary metabolites/natural products. Full article

The rapid evolution of drug resistance is one of the greatest health issues of the 21st century. There is an alarming situation to find new therapeutic strategies or candidate drugs to tackle ongoing multi-drug resistance development. The marine environment is one of the prime natural ecosystems on Earth, the majority of which is still unexplored, especially when it comes to the microbes. A wide variety of bioactive compounds have been obtained from a varied range of marine organisms; however, marine bacteria-produced bacteriocins are still undermined. Owing to the distinct environmental stresses that marine bacterial communities encounter, their bioactive compounds frequently undergo distinct adaptations that confer on them a variety of shapes and functions, setting them apart from their terrestrial counterparts. Bacterially produced ribosomally synthesized and posttranslationally modified peptides (RiPPs), known as bacteriocins, are one of the special interests to be considered as an alternative to conventional antibiotics because of their variety in structure and diverse potential biological activities. Additionally, the gut microbiome of marine creatures are a largely unexplored source of new bacteriocins with promising activities. There is a huge possibility of novel bacteriocins from marine bacterial communities that might come out as efficient candidates to fight against antibiotic resistance, especially in light of the growing pressure from antibiotic-resistant diseases and industrial desire for innovative treatments. The present review summarizes known and fully characterized marine bacteriocins, their evolutionary aspects, challenges, and the huge possibilities of unexplored novel bacteriocins from marine bacterial communities present in diverse marine ecosystems. Full article