Biology, Volume 12, Issue 10 (October 2023) – 88 articles

Motor dysfunction in Parkinson’s disease (PD) is closely linked to the dopaminergic depletion of striatal neurons and altered synaptic plasticity at corticostriatal synapses. Dopamine receptor D1 (DRD1) stimulation is a crucial step in the formation of long-term potentiation (LTP), whereas dopamine receptor D2 (DRD2) stimulation is needed for the formation of long-term depression (LTD) in striatal spiny projection neurons (SPNs). Tropomyosin receptor kinase B (TrkB) and its ligand brain-derived neurotrophic factor (BDNF) are centrally involved in plasticity regulation at the corticostriatal synapses. DRD1 activation enhances TrkB’s sensitivity for BDNF in direct pathway spiny projection neurons (dSPNs). In this study, we showed that the activation of DRD2 in cultured striatal indirect pathway spiny projection neurons (iSPNs) and cholinergic interneurons causes the retraction of TrkB from the plasma membrane. This provides an explanation for the opposing synaptic plasticity changes observed upon DRD1 or DRD2 stimulation. In addition, TrkB was found within intracellular structures in dSPNs and iSPNs from Pitx3^−/− mice, a genetic model of PD with early onset dopaminergic depletion in the dorsolateral striatum (DLS). This dysregulated BDNF/TrkB signaling might contribute to the pathophysiology of direct and indirect pathway striatal projection neurons in PD. Full article

Seasonal water-level fluctuations can profoundly impact nutrient dynamics in aquatic ecosystems, influencing trophic structures and overall ecosystem functions. The Tian-e-Zhou Oxbow of the Yangtze River is China’s first ex situ reserve and the world’s first successful case of ex situ conservation for cetaceans. In order to better protect the Yangtze finless porpoise, the effects of water-level fluctuations on the trophic structure in this oxbow cannot be ignored. Therefore, we employed stable isotope analysis to investigate the changes in the trophic position, trophic niche, and contribution of basal food sources to fish during the wet and dry seasons of 2021–2022. The research results indicate that based on stable isotope analysis of the trophic levels of different dietary fish species, fish trophic levels during the wet season were generally higher than those during the dry season, but the difference was not significant (p > 0.05). Fish communities in the Tian-e-Zhou Oxbow exhibited broader trophic niche space and lower trophic redundancy during the wet season (p < 0.05), indicating a more complex and stable food web structure. In both the wet and dry seasons, fish in the oxbow primarily relied on endogenous carbon sources, but there were significant differences in the way they were utilized between the two seasons (p < 0.05). In light of the changes in the trophic structure of the fish during the wet and dry seasons, and to ensure the stable development of the Yangtze finless porpoise population, we recommend strengthening the connectivity between the Tian-e-Zhou Oxbow and the Yangtze River. Full article

Allogenic graft acceptance is only achieved by life-long immunosuppression, which comes at the cost of significant toxicity. Clinicians face the challenge of adapting the patients’ treatments over long periods to lower the risks associated with these toxicities, permanently leveraging the risk of excessive versus insufficient immunosuppression. A major goal and challenge in the field of solid organ transplantation (SOT) is to attain a state of stable immune tolerance specifically towards the grafted organ. The immune system is equipped with a set of inhibitory co-receptors known as immune checkpoints (ICs), which physiologically regulate numerous effector functions. Insufficient regulation through these ICs can lead to autoimmunity and/or immune-mediated toxicity, while excessive expression of ICs induces stable hypo-responsiveness, especially in T cells, a state sometimes referred to as exhaustion. IC blockade has emerged in the last decade as a powerful therapeutic tool against cancer. The opposite action, i.e., subverting IC for the benefit of establishing a state of specific hypo-responsiveness against auto- or allo-antigens, is still in its infancy. In this review, we will summarize the available literature on the role of ICs in SOT and the relevance of ICs with graft acceptance. We will also discuss the possible influence of current immunosuppressive medications on IC functions. Full article

Even “healthy” muscle ageing is often associated with substantial changes in muscle form and function and can lead to increased injury risks and significant negative impacts on quality of life. However, the impacts of healthy muscle ageing on the fibre architecture and microstructure of different muscles and muscle groups throughout the lower limb, and how these are related to their functional capabilities, are not fully understood. Here, a previously established framework of magnetic resonance and diffusion tensor imaging was used to measure the muscle volumes, intramuscular fat, fibre lengths and physiological cross-sectional areas of 12 lower limb muscles in a cohort of healthily aged individuals, which were compared to the same data from a young population. Maximum muscle forces were also measured from an isokinetic dynamometer. The more substantial interpopulation differences in architecture and functional performance were located within the knee extensor muscles, while the aged muscles were also more heterogeneous in muscle fibre type and atrophy. The relationships between architecture and muscle strength were also more significant in the knee extensors compared to other functional groups. These data highlight the importance of the knee extensors as a potential focus for interventions to negate the impacts of muscle ageing. Full article

Carnivorous plants attract animals, trap and kill them, and absorb nutrients from the digested bodies. This unusual (for autotrophs) type of nutrient acquisition evolved through the conversion of photosynthetically active leaves into specialised organs commonly called traps. The genus Nepenthes (pitcher plants) consists of approximately 169 species belonging to the group of carnivorous plants. Pitcher plants are characterised by specialised passive traps filled with a digestive fluid. The digestion that occurs inside the traps of carnivorous plants depends on the activities of many enzymes. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) also participate in the digestive process, but their action is poorly recognised. ROS and RNS, named together as RONS, exhibit concentration-dependent bimodal functions (toxic or signalling). They act as antimicrobial agents, participate in protein modification, and are components of signal transduction cascades. In the human stomach, ROS are considered as the cause of different diseases. RNS have multifaceted functions in the gastrointestinal tract, with both positive and negative impacts on digestion. This review describes the documented and potential impacts of RONS on the digestion in pitcher plant traps, which may be considered as an external stomach. Full article

By relating genetic divergence at neutral loci, phenotypic variation, and geographic and environmental distances, it is possible to dissect micro-evolutionary scenarios involving natural selection and neutral evolution. In this work, we tested the patterns of intraspecific genetic and phenotypic variation along an elevational gradient, using Dianthus virgineus as study system. We genotyped genome-wide SNPs through ddRAD sequencing and quantified phenotypic variation through multivariate morphological variation. We assessed patterns of variation by testing the statistical association between genetic, phenotypic, geographic, and elevational distances and explored the role of genetic drift and selection by comparing the Fst and Pst of morphometric traits. We revealed a weak genetic structure related to geographic distance among populations, but we excluded the predominant role of genetic drift acting on phenotypic traits. A high degree of phenotypic differentiation with respect to genetic divergence at neutral loci allowed us to hypothesize the effect of selection, putatively fuelled by changing conditions at different sites, on morphological traits. Thus, natural selection acting despite low genetic divergence at neutral loci can be hypothesized as a putative driver explaining the observed patterns of variation. Full article

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix–loop–helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 is a core cog of the molecular clockwork and plays a regulatory role on metabolic pathways, is important for the function of the central nervous system in mammals, and is involved in carcinogenesis as well as in normal biological functions and processes, such as cardiovascular function and wound healing. We reviewed the scientific literature addressing the various facets of NPAS2 and framing this gene/protein in several and very different research and clinical fields. Full article

This study aimed to investigate enterococci recovered from eight Portuguese cheeses made with raw ewe’s milk, regarding antibiotic resistance, virulence genes, minimum inhibitory concentration (MIC) of benzalkonium chloride (BAC), biofilm formation capacity, and biofilm eradication (MBEC) by BAC. Antimicrobial resistance against seven antibiotics of five groups was evaluated using the disk diffusion method. The presence of the genes that encode resistance to the antibiotics penicillin (blaZ), erythromycin (ermA, ermB, and ermC), vancomycin (vanA and vanB), aminoglycoside (aac(6′)-Ie-aph(2″)-Ia), and β-lactam (pbp5) and the genes that encode virulence factors, frsB, cylA, gelE, esp, and agg, were investigated via multiplex PCR. The susceptibility of planktonic cells to BAC was evaluated by the MIC and MBC values of the isolates, using the broth microdilution method. To assess the biofilm-forming ability and resistance of biofilms to BAC, biofilms were produced on stainless steel coupons, followed by exposure to BAC. The results showed a high resistance to the antibiotics vancomycin (87.5%), erythromycin (75%), tetracycline (50%), and penicillin (37.5%). Multidrug resistance was observed in 68.8% of the isolates. Genes encoding the virulence factors FrsB (frsB) and gelatinase E (gelE) were detected in all isolates. The esp and cylA genes were found in 56.3% and 37.5% of the isolates, respectively. All isolates exhibited a biofilm-forming ability, regardless of incubation time and temperature tested. However, after 72 h at 37 °C, E. faecium and E. faecalis biofilms showed significant differences (p ≤ 0.05). Although most isolates (62.5%) were susceptible to BAC (MIC ≤ 10 mg/L), biofilms of the same isolates were, generally, resistant to the higher concentration of BAC (80 mg/mL) tested. This study using Enterococcus isolates from a ready-to-eat food, such as cheese, reveals the high percentages of vancomycin resistance and multidrug resistance, associated with the presence of virulence genes, in isolates also capable of producing biofilms resistant to BAC, an important active ingredient of many disinfectants. These results emphasize the need for effective control measures to ensure the safety and quality of dairy products. Full article

To examine the effect of leaf chemical composition on selective herbivory by the Japanese giant flying squirrels (Petaurista leucogenys), we measured and compared the total phenolic, glucose, and water contents of leaves among their main food tree species, deciduous Quercus acutissima, and evergreen Q. sessilifolia and Phonitia serratifolia. Leaves of these three tree species were available in the warm season (April to October), but the flying squirrels mostly preferred the leaves of Q. acutissima, having higher glucose and water contents than those of the other two tree species. In the cold season (November to the next March), the two evergreen tree species were available, and the flying squirrels used both leaves without any apparent influence of the chemical compositions. On the other hand, the favorite parts of a single leaf differed among the three tree species. Flying squirrels dropped the individual leaves after partial consumption. Their feeding marks on the dropped leaves were distinguished into four types: apical, basal, central, and marginal parts of consumption. The basal parts of consumption were most frequent in Q. acutissima leaves in which more water was contained at the basal part, and the central part consumption followed, which may be related to a lower phenolic content and more glucose and water at the leaf center than its margin. In contrast, the apically consumed leaves dominated in Q. sessilifolia, with relatively homogeneous leaf chemical distribution except for more water at the center. In P. serratifolia, leaves consumed at the center were frequent, but those with marginal consumption were also observed, which may be related to its specific chemical distribution with less phenolics and more glucose at the leaf margin. Thus, the chemical distributions within the single leaf differ among tree species, and the flying squirrel’s selectivity of the tree species and the part of each leaf depends partly on the relative compositions of preferable glucose and water and unpreferable phenolics. Full article

Cobalt (Co), copper (Cu), manganese (Mn), molybdenum (Mo), and zinc (Zn) are essential trace elements (ETEs) and important cofactors for intermediary metabolism or redox balance. These ETEs are crucial during pregnancy, their role on specific pregnancy outcomes is largely unknown. This prospective study (#NCT04010708) aimed to assess urinary levels of these ETEs in pregnancy and to evaluate their association with pregnancy outcomes. First trimester pregnant women of Porto and Lisbon provided a random spot urine sample, and sociodemographic and lifestyle data. Clinical data were obtained from clinical records. Urinary ETEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS). A total of 635 mother:child pairs were included. Having urinary Zn levels above the 50th percentile (P50) was an independent risk factor for pre-eclampsia (PE) (aOR [95% CI]: 5.350 [1.044–27.423], p = 0.044). Urinary Zn levels above the P50 decreased the risk of small for gestational age (SGA) birth head circumference (aOR [95% CI]: 0.315 [0.113–0.883], p = 0.028), but it increased the risk SGA length (aOR [95% CI]: 2.531 [1.057–6.062], p = 0.037). This study may provide valuable information for public health policies related to prenatal nutrition, while informing future efforts to de-fine urinary reference intervals for ETEs in pregnant women. Full article

High-risk neuroblastoma (HR-NB) patients remain far from obtaining optimal outcomes, with more than 50% relapse/regrowth rate despite current intensive multimodal therapy. This originated from the activation/proliferation of chemoresistant minimal residual disease (MRD). MRD with a significant prognostic was reported by several quantitative PCR (qPCR) or droplet digital PCR (ddPCR) assays quantitating different sets of NB-associated mRNAs (NB-mRNAs). The 7NB-mRNAs ddPCR assay quantitating CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs was reported to outperform other qPCR assays by a retrospective in-house observational study. In the present study, the Japan Children’s Cancer Group (JCCG) Neuroblastoma Committee conducted a prospective multicenter observational study aimed at evaluating a prognostic value of MRD in bone marrow (BM-MRD) and peripheral blood (PB-MRD) detected by 7NB-mRNAs ddPCR assay. Between August 2018 and August 2022, 7 HR-NB patients who registered for JCCG clinical trials (JN-H-11 and JN-H-15) were enrolled. A total of 19 BM and 19 PB samples were collected, and 4/15 BM and 4/15 PB samples were classified as progressive disease (PD)/non-PD samples. BM-MRD and PB-MRD estimated area under curve (AUC) of 0.767 and 0.800 with a significant accuracy (AUC > 0.7). The present study validated a prognostic value of BM-MRD obtained by a previous study (AUC 0.723) and revealed the significant accuracy of PB-MRD as well as BM-MRD. Full article

The muscular systems of echinoderms play important roles in various physiological and behavioral processes, including feeding, reproduction, movement, respiration, and excretion. Like vertebrates, echinoderm muscle systems can be subdivided into two major divisions, somatic and visceral musculature. The former usually has a myoepithelial organization, while the latter contains muscle bundles formed by the aggregation of myocytes. Neurons and their processes are also detected between these myoepithelial cells and myocytes, which are capable of releasing a variety of neurotransmitters and neuropeptides to regulate muscle activity. Although many studies have reported the pharmacological effects of these chemical messengers on various muscles of echinoderms, there has been limited research on their receptors and their signaling pathways. The muscle physiology of echinoderms is similar to that of chordates, both of which have the deuterostome mode of development. Studies of muscle regulation in echinoderms can provide new insights into the evolution of myoregulatory systems in deuterostomes. Full article

One of the little-studied ways that climate warming or temperature increases in aquaculture could affect aquatic animals is through accelerated aging. This study is dedicated to understanding the principles of molecular and cellular aging in the target tissues of juvenile whitefishes (Yenisei hump-snout whitefish and its hybrid) under the influence of acute heat stress (up to 26 °C), and the effects of thermal preconditioning as pre-adaptation. Non-adapted stressed hump-snout whitefish showed a higher induction threshold for functionally active mitochondria in the blood and a decrease in telomerase activity in the liver after heat shock exposure as a long-term compensatory response to prevent telomere shortening. However, we observed heat-induced telomere shortening in non-adapted hybrids, which can be explained by a decrease in mitochondrial membrane stability and a gradual increase in energy demand, leading to a decrease in protective telomerase activity. The pre-adapted groups of hump-snout whitefish and hybrids showed a long-term or delayed response of telomerase activity to heat shock, which served as a therapeutic mechanism against telomere shortening. We concluded that the telomerase and telomere responses to thermal stress demonstrate plasticity of tolerance limits and greater stability in hump-snout whitefish compared with hybrids. Full article

Invasive plants generally present a significant enhancement in aboveground vegetative growth, which is mainly caused by variation in secondary cell wall (SCW) deposition and vascular tissue development. However, the coordination of the transcriptional regulators of SCW biosynthesis is complex, and a comprehensive regulation map has not yet been clarified at a transcriptional level to explain the invasive mechanism of S. canadensis. Here, RNA sequencing was performed in the phloem and xylem of two typical native (US01) and invasive (CN25) S. canadensis populations with different stem morphologies. A total of 296.14 million high-quality clean reads were generated; 438,605 transcripts and 156,968 unigenes were assembled; and 66,648 and 19,510 differential expression genes (DEGs) were identified in the phloem and xylem, respectively. Bioinformatics analysis indicated that the SCW transcriptional network was dramatically altered during the successful invasion of S.canadensis. Based on a comprehensive analysis of SCW deposition gene expression profiles, we revealed that the invasive population is dedicated to synthesizing cellulose and reducing lignification, leading to an SCW with high cellulose content and low lignin content. A hypothesis thus has been proposed to explain the enhanced stem growth of S. canadensis through the modification of the SCW composition. Full article

In purple bacteria, the genes of the carotenoid pathways are part of photosynthesis gene clusters which were distributed among different species by horizontal gene transfer. Their close organisation facilitated the first-time cloning of carotenogenic genes and promoted the molecular investigation of spheroidene and spirilloxanthin biosynthesis. This review highlights the cloning of the spheroidene and spirilloxanthin pathway genes and presents the current knowledge on the enzymes involved in the carotenoid biosynthesis of purple sulphur and non-sulphur bacteria. Mostly, spheroidene or spirilloxanthin biosynthesis exists in purple non-sulphur bacteria but both pathways operate simultaneously in Rubrivivax gelatinosus. In the following years, genes from other bacteria including purple sulphur bacteria with an okenone pathway were cloned. The individual steps were investigated by kinetic studies with heterologously expressed pathway genes which supported the establishment of the reaction mechanisms. In particular, the substrate and product specificities revealed the sequential order of the speroidene and spiriloxanthin pathways as well as their interactions. Information on the enzymes involved revealed that the phytoene desaturase determines the type of pathway by the formation of different products. By selection of mutants with amino acid exchanges in the putative substrate-binding site, the neurosporene-forming phytoene desaturase could be changed into a lycopene-producing enzyme and vice versa. Concerning the oxygen groups in neurosporene and lycopene, the tertiary alcohol group at C1 is formed from water and not by oxygenation, and the C2 or C4 keto groups are inserted differently by an oxygen-dependent or oxygen-independent ketolation reaction, respectively. Full article

Induced molting is a common method to obtain a new life in laying hens, in which periodic changes in feathers are the prominent feature. Nevertheless, its precise molecular mechanism remains unclear. In this study, feather and hair follicle samples were collected during fasting-induced physiological remodeling for hematoxylin–eosin staining, hormone changes and follicle traits, and transcriptome sequencing. Feather shedding was observed in F13 to R25, while newborns were observed in R3 to R32. Triiodothyronine and tetraiodothyronine were significantly elevated during feather shedding. The calcium content was significantly higher, and the ash content was significantly lower after the changeover. The determination of hair follicle traits revealed an increasing trend in pore density and a decrease in pore diameter after the resumption of feeding. According to RNA-seq results, several core genes were identified, including DSP, CDH1, PKP1, and PPCKB, which may have an impact on hair follicle growth. The focus was to discover that starvation may trigger changes in thyroid hormones, which in turn regulate feather molting through thyroid hormone synthesis, calcium signaling, and thyroid hormone signaling pathways. These data provide a valuable resource for the analysis of the molecular mechanisms underlying the cyclical growth of hair follicles in the skin during induced molting. Full article

Text mining methods are being developed to assimilate the volume of biomedical textual materials that are continually expanding. Understanding protein–protein interaction (PPI) deficits would assist in explaining the genesis of diseases. In this study, we designed an automated system to extract PPIs from the biomedical literature that uses a deep learning sentence classification model, a pretrained word embedding, and a BiLSTM recurrent neural network with additional layers, a conditional random field (CRF) named entity recognition (NER) model, and shortest-dependency path (SDP) model using the SpaCy library in Python. The automated system ensures that it targets sentences that contain PPIs and not just these proteins mentioned in the framework of disease discovery or other context. Our first model achieved 13% greater precision on the Aimed/BioInfr benchmark corpus than the previous state-of-the-art BiLSTM neural network models. The NER model presented in this study achieved 98% precision on the Aimed/BioInfr corpus over previous models. In order to facilitate the production of an accurate representation of the PPI network, the processes were developed to systematically map the protein interactions in the texts. Overall, evaluating our system through the use of 6027 abstracts pertaining to seven proteins associated with Autism Spectrum Disorder completed the manually curated PPI network for these proteins. When it comes to complicated diseases, these networks would assist in understanding how PPI deficits contribute to disease development while also emphasizing the influence of interactions on protein function and biological processes. Full article

Salinity is a pressing and widespread abiotic stress, adversely affecting agriculture productivity and plant growth worldwide. Seed germination is the most critical stage to seedling growth and establishing plant species in harsh environments, including saline stress. However, seed germination characteristics and stress tolerance may vary among geographical locations, such as various provenances. Suaeda salsa (Linn.) Pall. (S. salsa) is a halophytic plant that exhibits high salt tolerance and is often considered a pioneer species for the restoration of grasslands. Understanding the germination characteristics and stress tolerance of the species could be helpful in the vegetation restoration of saline–alkali land. In this study, we collected S. salsa seeds from seven different saline–alkali habitats (S1–S7) in the Songnen Plain region to assess the germination and seedling growth responses to NaCl, Na₂CO_3, and NaHCO₃, and to observe the recovery of seed germination after relieving the salt stress. We observed significant differences in germination and seedling growth under three salt stresses and among seven provenances. Resistance to Na₂CO₃ and NaHCO₃ stress was considerably higher during seedling growth than seed germination, while the opposite responses were observed for NaCl resistance. Seeds from S1 and S7 showed the highest tolerance to all three salt stress treatments, while S6 exhibited the lowest tolerance. Seeds from S2 exhibited low germination under control conditions, while low NaCl concentration and pretreatment improved germination. Ungerminated seeds under high salt concentrations germinated after relieving the salt stress. Germination of ungerminated seeds after the abatement of salt stress is an important adaptation strategy for black S. salsa seeds. While seeds from most provenances regerminated under NaCl, under Na₂CO₃ and NaHCO₃, only seeds from S4 and S7 regerminated. These findings highlight the importance of soil salinity in the maternal environment for successful seed germination and seedling growth under various salinity-alkali stresses. Therefore, seed sources and provenance should be considered for vegetation restoration. Full article

In New Zealand, during the hottest periods of the year, some salmon farms in the Marlborough Sounds reach water temperatures above the optimal range for Chinook salmon. High levels of mortality are recorded during these periods, emphasising the importance of understanding thermal stress in this species. In this study, the responses of Chinook salmon (Oncorhynchus tshawytscha) to chronic, long-term changes in temperature and dissolved oxygen were investigated. This is a unique investigation due to the duration of the stress events the fish were exposed to. Health and haematological parameters were analysed alongside gene expression results to determine the effects of thermal stress on Chinook salmon. Six copies of heat shock protein 90 (HSP90) were discovered and characterised: HSP90AA1.1a, HSP90AA1.2a, HSP90AA1.1b, HSP90AA1.2b, HSP90AB1a and HSP90AB1b, as well as two copies of SOD1, named SOD1a and SOD1b. The amino acid sequences contained features similar to those found in other vertebrate HSP90 and SOD1 sequences, and the phylogenetic tree and synteny analysis provided conclusive evidence of their relationship to other vertebrate HSP90 and SOD1 genes. Primers were designed for qPCR to enable the expression of all copies of HSP90 and SOD1 to be analysed. The expression studies showed that HSP90 and SOD1 were downregulated in the liver and spleen in response to longer term exposure to high temperatures and lower dissolved oxygen. HSP90 was also downregulated in the gill; however, the results for SOD1 expression in the gill were not conclusive. This study provides important insights into the physiological and genetic responses of Chinook salmon to temperature and oxygen stress, which are critical for developing sustainable fish aquaculture in an era of changing global climates. Full article

Here, we describe the nervous system structures from pediveligers of eight bivalve species (Callista brevisiphonata, Mactromeris polynyma, Crenomytilus grayanus, Kellia japonica, Mizuhopecten yessoensis, and Azumapecten farreri) with different modes of life in their adult stages, corresponding to the ecological niches that they occupy (burrowing, cemented, byssally attached, and mobile forms). We have identified neuromorphological features of the central and peripheral nervous systems in larval bivalves. We show that the unpaired sensory apical organ is still present in pediveligers along with the developing paired cerebral ganglia characteristic of an adult mollusk. Pediveligers have the pleural ganglia connected to the pedal ganglia via the pedal nerve cords and to the visceral ganglia via the lateral nerve cords. We have found a number of structures of the peripheral nervous system whose presence varies between pediveligers of different species. Mactromeris, Callista, and Pododesmus have 5-HT-immunopositive stomatogastric neurons, whereas the Yesso and Farrer’s scallops have an FMRFamide-immunopositive enteric nervous system. The innervation of the anterior part of the velum is connected to a system of the apical organ and cerebral ganglia, and the innervation of the posterior part is connected to the visceral ganglia. Most differences in the structure of the peripheral elements of the nervous system are species-specific and weakly depend on the ecological niche that pediveligers occupy. Full article

Immunity to Ascaris lumbricoides influences the pathogenesis of allergic diseases. Antibody responses to its proteins have been found to be associated with asthma presentation; however, helminth products that induce immunosuppression have been reported, which also raise specific antibodies. We aimed to evaluate antibody responses (IgE, IgG4 and IgG) to two A. lumbricoides molecules, Asc l 5 and Al-CPI (an anti-inflammatory Cysteine Protease Inhibitor), in an endemic population, exploring their relationships with the infection and asthma. The two molecules were produced as recombinant proteins in E. coli expression systems. Specific antibodies were detected by ELISA. Lower human IgE, but higher IgG4 and IgG antibody levels were observed for Al-CPI than for rAsc l 5. The IgE/IgG4 isotype ratio was significantly higher for Asc l 5 than for Al-CPI. In humans Al-CPI did not induce basophil activation as has been previously described for Asc l 5. In mice, Al-CPI induced fewer IgE responses, but more IgG2a antibody titers than rAsc l 5. Our results suggest that these molecules elicit different patterns of immune response to A. lumbricoides. Full article

Firstly, polyphenol oxidase (PPO) was purified from the fruits of Opuntia ficus-indica using Sepharose 4B–L-tyrosine–p-aminobenzoic acid affinity chromatography, and the enzyme was characterized. The PPO was purified 20.59-fold. Thereafter, PPO was performed on sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). The kinetic parameters, optimum pHs, and optimum temperatures were investigated for three substrates. Opuntia ficus-indica PPO’s optimum pH and optimum temperature were 9.0 and 20 °C; 7.5 and 20 °C; and 7.5 and 30 °C, respectively, when using pyrogallol, catechol, and 4-methyl catechol as substrates. For the pyrogallol, catechol, and 4-methyl catechol, the Km, Vmax, and Vmax/Km values were determined as 16.67 mM, 833.33 U/mLmin, and 50 U/mLminmM; 6.33 mM, 126.58 U/mLmin, and 20 U/mLminmM; and 5.38 mM, 107.53 U/mLmin, and 20 U/mLminmM, respectively. As a result, pyrogallol was a more appropriate substrate than catechol and 4-methyl catechol for the PPO from Opuntia ficus-indica. Full article

Translation efficiency modulates gene expression in prokaryotes. The comparative analysis of translation elongation efficiency characteristics of Ralstonia genus bacteria genomes revealed that these characteristics diverge in accordance with the phylogeny of Ralstonia. The first branch of this genus is a group of bacteria commonly found in moist environments such as soil and water that includes the species R. mannitolilytica, R. insidiosa, and R. pickettii, which are also described as nosocomial infection pathogens. In contrast, the second branch is plant pathogenic bacteria consisting of R. solanacearum, R. pseudosolanacearum, and R. syzygii. We found that the soil Ralstonia have a significantly lower number and energy of potential secondary structures in mRNA and an increased role of codon usage bias in the optimization of highly expressed genes’ translation elongation efficiency, not only compared to phytopathogenic Ralstonia but also to Cupriavidus necator, which is closely related to the Ralstonia genus. The observed alterations in translation elongation efficiency of orthologous genes are also reflected in the difference of potentially highly expressed gene’ sets’ content among Ralstonia branches with different lifestyles. Analysis of translation elongation efficiency characteristics can be considered a promising approach for studying complex mechanisms that determine the evolution and adaptation of bacteria in various environments. Full article

Sorafenib, a kinase inhibitor, has shown promising therapeutic efficacy in a subset of patients with acute myeloid leukemia (AML). However, despite its clinical effectiveness, sorafenib resistance is frequently observed in clinical settings, and the mechanisms underlying this resistance as well as effective strategies to overcome it remain unclear. We examined both single-cell and bulk transcription data in sorafenib-resistant and control AML patients and integrated a sorafenib resistance gene signature to predict the sensitivity of AML cells and the clinical outcomes of AML patients undergoing sorafenib therapy. In addition, our drug sensitivity analysis of scRNA-seq data using deconvolution methods showed that venetoclax was effective in targeting sorafenib-resistant AML cells. Mechanistically, sorafenib was found to activate the JAK-STAT3 pathway and upregulate BCL2 expression in sorafenib-resistant AML cells. This upregulation of BCL2 expression rendered the cells vulnerable to the BCL2 inhibitor venetoclax. In conclusion, we developed a platform to predict sorafenib resistance and clinical outcomes in AML patients after therapy. Our findings suggest that the combination of sorafenib and venetoclax could be an effective therapeutic strategy for AML treatment. Full article

The biological membrane surrounding all living cells forms a hydrophobic barrier to the passage of biologically important molecules. Integral membrane proteins called transporters circumvent the cellular barrier and transport molecules across the cell membrane. These molecular transporters enable the uptake and exit of molecules for cell growth and homeostasis. One important collection of related transporters is the major facilitator superfamily (MFS). This large group of proteins harbors passive and secondary active transporters. The transporters of the MFS consist of uniporters, symporters, and antiporters, which share similarities in structures, predicted mechanism of transport, and highly conserved amino acid sequence motifs. In particular, the antiporter motif, called motif C, is found primarily in antiporters of the MFS. The antiporter motif’s molecular elements mediate conformational changes and other molecular physiological roles during substrate transport across the membrane. This review article traces the history of the antiporter motif. It summarizes the physiological evidence reported that supports these biological roles. Full article

Cobalt (Co) is an essential trace element for humans and other animals, but high doses can be harmful to human health. It is present in some foods such as green vegetables, various spices, meat, milk products, seafood, and eggs, and in drinking water. Co is necessary for the metabolism of human beings and animals due to its key role in the formation of vitamin B₁₂, also known as cobalamin, the biological reservoir of Co. In high concentrations, Co may cause some health issues such as vomiting, nausea, diarrhea, bleeding, low blood pressure, heart diseases, thyroid damage, hair loss, bone defects, and the inhibition of some enzyme activities. Conversely, Co deficiency can lead to anorexia, chronic swelling, and detrimental anemia. Co nanoparticles have different and various biomedical applications thanks to their antioxidant, antimicrobial, anticancer, and antidiabetic properties. In addition, Co and cobalt oxide nanoparticles can be used in lithium-ion batteries, as a catalyst, a carrier for targeted drug delivery, a gas sensor, an electronic thin film, and in energy storage. Accumulation of Co in agriculture and humans, due to natural and anthropogenic factors, represents a global problem affecting water quality and human and animal health. Besides the common chelating agents used for Co intoxication, phytoremediation is an interesting environmental technology for cleaning up soil contaminated with Co. The occurrence of Co in the environment is discussed and its involvement in biological processes is underlined. Toxicological aspects related to Co are also examined in this review. Full article

Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine. Full article

Fruits contain many bioactive compounds, including polysaccharides, oligosaccharides, polyphenols, anthocyanins, and flavonoids. All of these bioactives in fruit have potentially beneficial effects on gut microbiota and host health. On the one hand, fruit rich in active ingredients can act as substrates to interact with microorganisms and produce metabolites to regulate the gut microbiota. On the other hand, gut microbes could promote health effects in the host by balancing dysbiosis of gut microbiota. We have extensively analyzed significant information on bioactive components in fruits based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Although the deep mechanism of action of bioactive components in fruits on gut microbiota needs further study, these results also provide supportive information on fruits as a source of dietary active ingredients to provide support for the adjunctive role of fruits in disease prevention and treatment. Full article

Neutrophil extracellular traps (NETs) are major contributors to inflammation and autoimmunity, playing a key role in the development of thrombotic disorders. NETs, composed of DNA, histones, and numerous other proteins serve as scaffolds for thrombus formation and promote platelet activation, coagulation, and endothelial dysfunction. Accumulating evidence indicates that NETs mediate thrombosis in autoimmune diseases, viral and bacterial infections, cancer, and cardiovascular disease. This article reviews the role and mechanisms of immune complexes in NETs formation and their contribution to the generation of a prothrombotic state. Immune complexes are formed by interactions between antigens and antibodies and can induce NETosis by the direct activation of neutrophils via Fc receptors, via platelet activation, and through endothelial inflammation. We discuss the mechanisms by which NETs induced by immune complexes contribute to immune thrombotic processes and consider the potential development of therapeutic strategies. Targeting immune complexes and NETosis hold promise for mitigating thrombotic events and reducing the burden of immune thrombosis. Full article

Based on obtaining mstnb gene knockout in Pelteobagrus fulvidraco, a study on the effect of the mstn gene on skeletal morphology and growth was performed by comparing the number and length of the vertebrae of mutant and wild-type fish in a sibling group of P. fulvidraco, combined with the differences in cells at the level of vertebral skeletal tissue. It was found that mstnb gene knockdown resulted in a reduction in the number of vertebrae, the length, and the intervertebral distance in P. fulvidraco, and these changes may be the underlying cause of the shorter body length in mutant P. fulvidraco. Further, histological comparison of the same sites in the mstn mutant and wild groups of P. fulvidraco also revealed that the number and density of osteocytes were greater in mstnb knockout P. fulvidraco than in wild-type P. fulvidraco. Our results demonstrated that when using genome editing technology to breed new lines, the effects of knockout need to be analyzed comprehensively and may have some unexpected effects due to insufficient study of the function of certain genes. Full article