Development Of Organisms Research Articles

Induction of Bone Malformations in Neotropical Fish (Megaleporinus Macrocephalus) Exposed to Pyriproxyfen During Initial Stage of Development

Objective: Megaleporinus macrocephalus, a native species from the Neotropical region, was used as a model to evaluate the effects of pyriproxyfen on larval development at a dose that could be found in the environment. Theoretical Framework: Pyriproxyfen is a compound used to control of the mosquito Aedes aegypti, vector of Neotropical diseases. In insects, pyriproxyfen acts as a juvenile hormone analogue, inhibiting embryogenesis and the development of characteristics of adults through the inhibition of ecdysone. Pyriproxyfen has demonstrated effects on the survival rate, behavior, and morphology during development of non-target organisms. Method: In this study Megaleporinus macrocephalus was exposed to a dose of 2.5μg/L of pyriproxyfen on the 8th day after hatching and the presence of bone malformations was evaluated. For the evaluation was applied technique of diaphanization and radiological imaging. Results and Discussion: Out of the total of the individuals, 43% had some type of bone malformation: 24% had scoliosis and kyphosis of the vertebral column, 9% had reduction of pectoral fins, 5% had malformation in the anal fin and 5% absented at least one of the pelvic fins. These data reinforce the action of pyriproxyfen as a teratogen, acting on larval development in reduced doses, which can be found in the environment. Our study warns that these molecules might interact in the mechanism of gene expression mediated by retinoic acid, important morphogen during embryogenesis and organogenesis. Research Implications: The practical and theoretical implications of this research are discussed, providing insights into how the results can be applied or influence practices in the field of teratology. These implications could encompass control of the vectors, conservation biology and the prevention of embryonic and fetal anomalies. Originality/Value: This study not only does it reinforce the urgency to study how these molecules interact but also suggests caution when using the compound as a controller for vectors until the true security is acknowledged.

The critical role of the iron-sulfur cluster and CTC components in DOG-1/BRIP1 function in Caenorhabditis elegans.

FANCJ/BRIP1, initially identified as DOG-1(Deletions Of G-rich DNA) in Caenorhabditiselegans, plays a critical role in genome integrity by facilitating DNA interstrand cross-link repair and resolving G-quadruplex structures. Its function is tightly linked to a conserved [4Fe-4S] cluster-binding motif, mutations of which contribute to Fanconi anemia and various cancers. This study investigates the critical role of the iron-sulfur (Fe-S) cluster in DOG-1 and its relationship with the cytosolic iron-sulfur protein assembly targeting complex (CTC). We found that a DOG-1 mutant, expected to be defective in Fe-S cluster binding, is primarily localized in the cytoplasm, leading to heightened DNA damage sensitivity and G-rich DNA deletions. We further discovered that the deletion of mms-19, a nonessential CTC component, also resulted in DOG-1 sequestered in cytoplasm and increased DNA damage sensitivity. Additionally, we identified that CIAO-1 and CIAO-2B are vital for DOG-1's stability and repair functions but unlike MMS-19 have essential roles in C. elegans. These findings confirm the CTC and Fe-S cluster as key elements in regulating DOG-1, crucial for genome integrity. Additionally, this study advances our understanding of the CTC's role in Fe-S protein regulation and development in C. elegans, offering a model to study its impact on multicellular organism development.

Molecular Crosstalk Between Adherens Junction Proteins, E-cadherin and Nectin-4

Cell-cell junctions formed by the association of cell adhesion molecules facilitate physiological events necessary for growth and development of multicellular organisms. Among them, cadherins and nectins organize and assemble to form adherens junction, which thereby mechanically couples interacting cells. A detailed understanding of the crosstalk involving these cell adhesion molecules is fundamental to the study of the various developmental processes. Although, cadherins and nectins can recruit each other in the adherens junction through an interplay of cytoplasmic adaptor molecules, here, we report a direct interaction between N-terminal extracellular domains of E-cadherin and nectin-4 as demonstrated by surface plasmon resonance (SPR) and Atomic Force Microscopy (AFM)-based single molecule force spectroscopy (SMFS). Kinetic studies using SPR demonstrate the binding between the ectodomains of E-cadherin and nectin-4 with a KD of 3.7 ± 0.7 µM and KD of 5.4 ± 0.2 µM (reciprocal experiment). AFM-based SMFS experiments also support interaction between the ectodomains of E-cadherin and nectin-4 with the koff value of 31.48 ± 1.53 s−1 and the lifetime of the complex of 0.036 ± 0.0026 s. We thus propose a cell adhesion mechanism mediated by E-cadherin and nectin-4, which can have functional significance in early embryogenesis as evident from the expression pattern of both the proteins during early development.

Emergence of large-scale cell death through ferroptotic trigger waves

Large-scale cell death is commonly observed during organismal development and in human pathologies1–5. These cell death events extend over great distances to eliminate large populations of cells, raising the question of how cell death can be coordinated in space and time. One mechanism that enables long-range signal transmission is trigger waves6, but how this mechanism might be used for death events in cell populations remains unclear. Here we demonstrate that ferroptosis, an iron- and lipid-peroxidation-dependent form of cell death, can propagate across human cells over long distances (≥5 mm) at constant speeds (around 5.5 μm min−1) through trigger waves of reactive oxygen species (ROS). Chemical and genetic perturbations indicate a primary role of ROS feedback loops (Fenton reaction, NADPH oxidase signalling and glutathione synthesis) in controlling the progression of ferroptotic trigger waves. We show that introducing ferroptotic stress through suppression of cystine uptake activates these ROS feedback loops, converting cellular redox systems from being monostable to being bistable and thereby priming cell populations to become bistable media over which ROS propagate. Furthermore, we demonstrate that ferroptosis and its propagation accompany the massive, yet spatially restricted, cell death events during muscle remodelling of the embryonic avian limb, substantiating its use as a tissue-sculpting strategy during embryogenesis. Our findings highlight the role of ferroptosis in coordinating global cell death events, providing a paradigm for investigating large-scale cell death in embryonic development and human pathologies.

Lysophosphatidic acid metabolism and signaling in heart disease.

Lysophosphatidic acid (LPA) is a bioactive lipid that is mainly produced by the secreted lysophospholipase D, autotaxin (ATX), and signals through at least six G protein-coupled receptors (LPA1-6). Extracellular LPA is degraded through lipid phosphate phosphatases (LPP1, LPP2, and LPP3) at the plasmamembrane, terminating LPA receptor signaling. The ATX-LPA-LPP3 pathway is critically involved in a wide range of physiological processes, including cell survival, migration, proliferation, angiogenesis, and organismal development. Similarly, dysregulation of this pathway has been linked to many pathological processes, including cardiovascular disease. This review summarizes and interprets current literature examining the regulation and role of the ATX-LPA-LPP3 axis in heart disease. Specifically, the contribution of altered LPA metabolism via ATX and LPP3 and resulting changes to LPA receptor signaling in obesity cardiomyopathy, cardiac mitochondrial dysfunction, myocardial infarction/ischemia-reperfusion injury, hypertrophic cardiomyopathy, and aortic valve stenosis is discussed.

Actin cytoskeletal regulation of ciliogenesis in development and disease.

Primary cilia are antenna-like sensory organelles that are evolutionarily conserved in nearly all modern eukaryotes, from the single-celled green alga, Chlamydomonas reinhardtii, to vertebrates and mammals. Cilia are microtubule-based cellular projections that have adapted to perform a broad range of species-specific functions, from cell motility to detection of light and the transduction of extracellular mechanical and chemical signals. These functions render cilia essential for organismal development and survival. The high conservation of cilia has allowed for discoveries in C. reinhardtii to inform our understanding of the basic biology of mammalian primary cilia, and to provide insight into the genetic etiology of ciliopathies. Over the last two decades, a growing number of studies has revealed that multiple aspects of ciliary homeostasis are regulated by the actin cytoskeleton, including centrosome migration and positioning, vesicle transport to the basal body, ectocytosis, and ciliary-mediated signaling. Here, we review actin regulation of ciliary homeostasis, and highlight conserved and divergent mechanisms in C. reinhardtii and mammalian cells. Further, we compare the disease manifestations of patients with ciliopathies to those with mutations in actin and actin-associated genes, and propose that primary cilia defects caused by genetic alteration of the actin cytoskeleton may underlie certain birth defects.

A prognostic model for anoikis-related genes in pancreatic cancer

Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expression data were obtained from the Genotype-Tissue Expression (GTEx) project. The R package was used to construct anoikis-related PC prognostic models, which were later validated with the ICGC-PACA database. Survival analyses demonstrated a poorer prognosis for patients in the high-risk group, consistent across both TCGA-PAAD and ICGC-PACA datasets. A nomogram was designed as a predictive tool to estimate patient mortality. The study also analyzed tumor mutations and immune infiltration across various risk groups, uncovering notable differences in tumor mutation patterns and immune landscapes between high- and low-risk groups. In conclusion, this research successfully developed a prognostic model centered on anoikis-related genes, offering a novel tool for predicting the clinical trajectory of PC patients.

Spliceosomal snRNAs, the Essential Players in pre-mRNA Processing in Eukaryotic Nucleus: From Biogenesis to Functions and Spatiotemporal Characteristics.

Spliceosomal small nuclear RNAs (snRNAs) are a fundamental class of non-coding small RNAs abundant in the nucleoplasm of eukaryotic cells, playing a crucial role in splicing precursor messenger RNAs (pre-mRNAs). They are transcribed by DNA-dependent RNA polymerase II (Pol II) or III (Pol III), and undergo subsequent processing and 3' end cleavage to become mature snRNAs. Numerous protein factors are involved in the transcription initiation, elongation, termination, splicing, cellular localization, and terminal modification processes of snRNAs. The transcription and processing of snRNAs are regulated spatiotemporally by various mechanisms, and the homeostatic balance of snRNAs within cells is of great significance for the growth and development of organisms. snRNAs assemble with specific accessory proteins to form small nuclear ribonucleoprotein particles (snRNPs) that are the basal components of spliceosomes responsible for pre-mRNA maturation. This article provides an overview of the biological functions, biosynthesis, terminal structure, and tissue-specific regulation of snRNAs.

Fatecode enables cell fate regulator prediction using classification-supervised autoencoder perturbation

Cell reprogramming, which guides the conversion between cell states, is a promising technology for tissue repair and regeneration, with the ultimate goal of accelerating recovery from diseases or injuries. To accomplish this, regulators must be identified and manipulated to control cell fate. We propose Fatecode, a computational method that predicts cell fate regulators based only on single-cell RNA sequencing (scRNA-seq) data. Fatecode learns a latent representation of the scRNA-seq data using a deep learning-based classification-supervised autoencoder and then performs in silico perturbation experiments on the latent representation to predict genes that, when perturbed, would alter the original cell type distribution to increase or decrease the population size of a cell type of interest. We assessed Fatecode's performance using simulations from a mechanistic gene-regulatory network model and scRNA-seq data mapping blood and brain development of different organisms. Our results suggest that Fatecode can detect known cell fate regulators from single-cell transcriptomics datasets.

Pyraclostrobin induces developmental toxicity and cardiotoxicity through oxidative stress and inflammation in zebrafish embryos

Pyraclostrobin, a typical representative of strobilurin fungicides, is extensively used in agriculture to control fungi and is often detected in water bodies and food. However, the comprehensive toxicological molecular mechanism of pyraclostrobin requires further study. To assess the toxic effects and underlying mechanisms of pyraclostrobin on aquatic organisms, zebrafish embryos were exposed to pyraclostrobin (20, 40, and 60 μg/L) until 96 h post fertilization (hpf). These results indicated that exposure to pyraclostrobin induces morphological alterations, including spinal curvature, shortened body length, and smaller eyes. Furthermore, heart developmental malformations, such as pericardial edema and bradycardia, were observed. This indicated severe cardiotoxicity induced by pyraclostrobin in zebrafish embryos, which was confirmed by the dysregulation of genes related to heart development. Besides, our findings also demonstrated that pyraclostrobin enhanced the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), up-regulated catalase (CAT) activity, but inhibited superoxide dismutase (SOD) activity. Subsequently, the NF-κb signaling pathway was further studied, and the results indicated that the up-regulation of tnf-α, tlr-4, and myd88 activated the NF-κb signaling pathway and up-regulated the relative expression level of pro-inflammatory cytokines, such as cc-chemokine, ifn-γ, and cxcl-clc. Collectively, this study revealed that pyraclostrobin exposure induces developmental toxicity and cardiotoxicity, which may result from a combination of oxidative stress and inflammatory responses. These findings provide a basis for continued evaluation of the effects and ecological risks of pyraclostrobin on the early development of aquatic organisms.

Seasonal changes in vitamin A metabolism-related factors in the oviduct of Chinese brown frog (Rana dybowskii)

The oviduct of the Chinese brown frog (Rana dybowskii) expands during pre-brumation rather than the breeding period, exhibiting a special physiological feature. Vitamin A is essential for the proper growth and development of many organisms, including the reproductive system such as ovary and oviduct. Vitamin A is metabolized into retinoic acid, which is crucial for oviduct formation. This study examined the relationship between oviducal expansion and vitamin A metabolism. We observed a significant increase in the weight and diameter of the oviduct in Rana dybowskii during pre-brumation. Vitamin A and its active metabolite, retinoic acid, notably increased during pre-brumation. The mRNA levels of retinol binding protein 4 (rbp4) and its receptor stra6 gene, involved in vitamin A transport, were elevated during pre-brumation compared to the breeding period. In the vitamin A metabolic pathway, the mRNA expression level of retinoic acid synthase aldh1a2 decreased significantly during pre-brumation, while the mRNA levels of retinoic acid α receptor (rarα) and the retinoic acid catabolic enzyme cyp26a1 increased significantly during pre-brumation, but not during the breeding period. Immunohistochemical results showed that Rbp4, Stra6, Aldh1a2, Rarα, and Cyp26a1 were expressed in ampulla region of the oviduct. Western blot results indicated that Aldh1a2 expression was lower, while Rbp4, Stra6, RARα, and Cyp26a1 were higher during pre-brumation compared to the breeding period. Transcriptome analyses further identified differential genes in the oviduct and found enrichment of differential genes in the vitamin A metabolism pathway, providing evidences for our study. These results suggest that the vitamin A metabolic pathway is more active during pre-brumation compared to the breeding period, and retinoic acid may regulate pre-brumation oviductal expansion through Rarα-mediated autocrine/paracrine modulation.

Understanding niche construction and phenotypic plasticity as causes of natural selection

AbstractFor many evolutionary biologists, fitness differences cause trait frequency changes in populations, and natural selection explains the evolution of adaptations. Treating fitness differences as a cause, however, is more scientific convention rather than decree, and analyses of the causes of natural selection potentially afford richer evolutionary explanations. Unfortunately, the historical assumptions that the complexities of development leave the origins of phenotypic variation unpredictable, and that ecological processes are idiosyncratic, have hindered detailed analysis of the developmental bases of natural selection. A poorly appreciated consequence is that explanations reliant on selection potentially mask particular causal patterns important in evolution. Here, using examples of environmental modification and regulation by organisms (‘niche construction’, a.k.a. ‘ecosystem engineering’), and developmental plastic responses to environmental conditions (‘phenotypic plasticity’), I will highlight how the development and activities of organisms create developmental biases that co‐determine the nature of the response to selection, in an often surprisingly well‐regulated manner. Niche construction biases the phenotypic variation exposed to selection, often generating axes of covariation with plastically expressed morphological traits. Taxonomically shared developmental mechanisms aggregate across populations to generate statistical regularities that are easy to miss because the developmental causes of fitness differences are not currently central to the study of evolution. Recent theory and experiments suggest that how organisms develop and what organisms do cause and strengthen the relationship between key traits and fitness, thereby part‐determining the characteristics of natural selection. The findings have implications for understanding parallel evolution, macroevolutionary trends and variation in evolvability.

How to overcome constraints imposed by microsporidian genome features to ensure gene prediction?

Since the advent of sequencing techniques and due to their continuous evolution, it has become easier and less expensive to obtain the complete genome sequence of any organism. Nevertheless, to elucidate all biological processes governing organism development, quality annotation is essential. In genome annotation, predicting gene structure is one of the most important and captivating challenges for computational biology. This aspect of annotation requires continual optimization, particularly for genomes as unusual as those of microsporidia. Indeed, this group of fungal-related parasites exhibits specific features (highly reduced gene sizes, sequences with high rate of evolution) linked to their evolution as intracellular parasites, requiring the implementation of specific annotation approaches to consider all these features. This review aimed to outline these characteristics and to assess the increasingly efficient approaches and tools that have enhanced the accuracy of gene prediction for microsporidia, both in terms of sensitivity and specificity. Subsequently, a final part will be dedicated to postgenomic approaches aimed at reinforcing the annotation data generated by prediction software. These approaches include the characterization of other understudied genes, such as those encoding regulatory noncoding RNAs or very small proteins, which also play crucial roles in the life cycle of these microorganisms.

Brightness-constant solvatochromic dye for ratiometric fluorescent imaging of lipid dynamics in developing zebrafish

Lipids play a crucial role in the growth and development of organisms. However, the lack of effective chemical tools for lipid imaging has hindered a comprehensive understanding of the dynamic changes in lipid content and types in organisms. Here, we introduce a brightness-constant, lipid droplet-targeting ratiometric fluorescent probe called PAA for visualizing dynamic lipid changes during zebrafish growth and development. PAA was an ultra-stable dimer composed of two carbonylpyrenes. Despite variations in polarity, its absorption spectra, quantum yield and fluorescence brightness remained consistent. However, only fluorescence emission wavelength underwent redshift with increasing polarity. These properties enabled stable lipid imaging throughout the entire live zebrafish and allowed for the identification of lipid polarity using ratiometric fluorescence. Furthermore, PAA revealed changes of lipid composition in developing zebrafish. From 3–5 days post fertilization (dpf), zebrafish with undeveloped digestive organs exhibited a gradual decrease in overall lipid content and a reduction in lipid polarity. Subsequently, as the digestive organs fully developed (6–8 dpf), zebrafish were fed with paramecium, resulting in a gradual increase in overall lipid content and lipid polarity. Moreover, starvation experiments indicated that overall lipid content and polar lipids increased in zebrafish fed with paramecium. The successful application of PAA in visualizing lipid dynamics in zebrafish provides new avenues for studying lipid physiology and pathophysiology in living systems.

Dynamics of DNA Methylation During Gametogenesis: Insights and Detection Methods

For many years, scientific research has dedicated significant attention to unraveling the complexities of inheritance, the process by which traits are passed from one generation to the next. At the heart of this exploration lies DNA methylation, a pivotal mechanism that exerts profound influence over gene expression, cellular identity, and the overarching development of organisms. This in-depth review meticulously probes the intricate dynamics of DNA methylation, meticulously dissecting its multifaceted impact on inheritance patterns and the spectrum of phenotypic variations observed. The review scrutinizes the underlying mechanisms governing the establishment and maintenance of DNA methylation, offering a nuanced understanding of its regulatory roles. Through a synthesis of insights gleaned from the fields of molecular biology, epigenetics, and genomics, it illuminates the far-reaching implications of DNA methylation for both health and disease. By peering into the molecular machinery that orchestrates these epigenetic modifications, the review provides a comprehensive framework for comprehending the interplay between DNA methylation and the transmission of hereditary traits. Moreover, by contextualizing these findings within the broader landscape of genetics and inheritance, the review offers valuable perspectives for guiding future research endeavors. These insights not only deepen our understanding of the intricate processes underlying heredity but also hold potential implications for the development of novel therapeutic interventions aimed at modulating DNA methylation patterns. In essence, this review serves as a cornerstone in the ongoing quest to unravel the mysteries of inheritance, paving the way for innovative approaches to address complex biological phenomena.

ATAD3 is a limiting factor in mitochondrial biogenesis and adipogenesis of white adipocyte-like 3T3-L1 cells.

ATAD3 is a vital ATPase of the inner mitochondrial membrane of pluri-cellular eukaryotes, with largely unknown functions but early required for organism development as necessary for mitochondrial biogenesis. ATAD3 knock-down in C. elegans inhibits at first the development of adipocyte-like intestinal tissue so we used mouse adipocyte model 3T3-L1 cells to analyze ATAD3 functions during adipogenesis and lipogenesis in a mammalian model. ATAD3 function was studied by stable and transient modulation of ATAD3 expression in adipogenesis- induced 3T3-L1 cells using Knock-Down and overexpression strategies, exploring different steps of adipocyte differentiation and lipogenesis. We show that (i) an increase in ATAD3 is preceding differentiation-induced mitochondrial biogenesis; (ii) downregulation of ATAD3 inhibits adipogenesis, lipogenesis, and impedes overexpression of many mitochondrial proteins; (iii) ATAD3 re-expression rescues the phenotype of ATAD3 KD, and (iv) differentiation and lipogenesis are accelerated by ATAD3 overexpression, but inhibited by expression of a dominant-negative mutant. We further show that the ATAD3 KD phenotype is not due to altered insulin signal but involves a limitation of mitochondrial biogenesis linked to Drp1. These results demonstrate that ATAD3 is limiting for in vitro mitochondrial biogenesis and adipogenesis/lipogenesis and therefore that ATAD3 mutation/over- or under-expression could be involved in adipogenic and lipogenic pathologies.

De novo TANGLED1 recruitment from the phragmoplast to aberrant cell plate fusion sites in maize.

Division plane positioning is crucial for proper growth and development in many organisms. In plants, the division plane is established before mitosis, by accumulation of a cytoskeletal structure called the preprophase band (PPB). The PPB is thought to be essential for recruitment of division site-localized proteins, which remain at the division site after the PPB disassembles. Here, we show that the division site-localized protein TANGLED1 (TAN1) is recruited independently of the PPB to the cell cortex by the plant cytokinetic machinery, the phragmoplast, from experiments using both the PPB-defective mutant discordia1 (dcd1) and chemical treatments that disrupt the phragmoplast in maize. TAN1 recruitment to de novo sites on the cortex is partially dependent on intact actin filaments and the myosin XI motor protein OPAQUE1 (O1). These data imply a yet unknown role for TAN1 and possibly other division site-localized proteins during the last stages of cell division when the phragmoplast touches the cell cortex to complete cytokinesis.

Allelopathic effect of the methanol extract of the weed species-red sorrel (Rumex acetosella L.) on the growth, phytohormone content and antioxidant activity of the cover crop - white clover (Trifolium repens L.)

Allelopathy is a biological process in which one organism releases biochemicals that affect the growth and development of other organisms. The current investigation sought to determine the allelopathic effect of Rumex acetosella on white clover (Trifolium repens) growth and development by using its shoot extract (lower IC50 value) as a foliar treatment. Here, different concentrations (25, 50, 100, and 200 g/L) of shoot extract from Rumex acetosella were used as treatments. With increasing concentrations of shoot extract, the plant growth parameters, chlorophyll and total protein content of Trifolium repens decreased. On the other hand, ROS, such as O2.− and H2O2, and antioxidant enzymes, including SOD, CAT, and POD, increased with increasing shoot extract concentration. A phytohormonal study indicated that increased treatment concentrations increased ABA and SA levels while JA levels were reduced. For the identification of allelochemicals, liquid‒liquid extraction, thin-layer chromatography, and open-column chromatography were conducted using R. acetosella shoot extracts, followed by a seed bioassay on the separated layer. A lower IC50 value was obtained through GC/MS analysis. gammaSitosterol was identified as the most abundant component. The shoot extract of Rumex acetosella has strong allelochemical properties that may significantly impede the growth and development of Trifolium repens. This approach could help to understand the competitive abilities of this weed species and in further research provide an alternate weed management strategy.

Genetic insights into hypoxia tolerance in silver sillago (Sillago sihama) through QTL mapping and SNP association analysis

Oxygen is vital for the survival, growth, development, and reproduction of organisms. This study investigates the genetic basis of hypoxia tolerance in the silver sillago (Sillago sihama), a species highly valued in aquaculture despite its traditional susceptibility to low oxygen environments. By employing quantitative trait locus (QTL) mapping and single nucleotide polymorphism (SNP) association studies, the study enhances our comprehension of the genetic factors involved in hypoxia tolerance. Six QTLs associated with hypoxia tolerance have been identified, spanning five distinct linkage groups. Enrichment analyses highlighted important biological processes and pathways, particularly those related to potassium ion transport and cytochrome P450-mediated drug metabolism, which play a critical role in responding to hypoxia stress. Seven candidate genes have been identified as relevant to hypoxia tolerance: cyp20a1, mgst3b, kcnh2, cluh, adk, xdh, and slc19a2. Notably, the SNP association analysis has identified 13 SNPs within the mgst3b gene, with five SNPs (g.583 T > C, g.611 A > G, g.629 T > A, g.633 T > A, g.937 A > G) showing a significant association with hypoxia tolerance. This study sheds light on the molecular mechanisms underlying hypoxia tolerance and suggests potential genetic markers that could be used to enhance S. sihama's ability to withstand hypoxic conditions through selective breeding, providing valuable insights for the improvement of sustainable aquaculture practices.

The Use of Long-term Antibiotics for Suppression of Bacterial Infections.

Suppressive antibiotic therapy is prescribed when a patient has an infection that is presumed to be incurable by a defined course of therapy or source control. The cohort receiving suppressive antibiotic therapy is typically highly comorbid and the infections often involve retained prosthetic material. In part due to a lack of clear guidelines regarding the use of suppressive antibiotics, and in part due to the complex nature of the infections in question, patients are often prescribed suppressive antibiotics for extremely long, if not indefinite, courses. The risks of prolonged antibiotic exposure in this context are not fully characterized, but they include adverse drug effects ranging from mild to severe, the development of antibiotic-resistant organisms, and perturbations of the gastrointestinal microbiome. In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in 4 common indications, examine the gaps in the current literature, and explore the known and potential risks of this therapy. We also make suggestions for improving the quality of evidence in future studies, particularly by highlighting the need for a standardized term to describe the use of long courses of antibiotics to suppress hard-to-treat infections.