Microbial production of methyl-uranium via the Wood-Ljungdahl pathway.

The misuse of uranium is a major threat to human health and the environment. In microbial ecosystems, microbes deploy various strategies to cope with uranium-induced stress. However, the exact ecological strategies and mechanisms underlying uranium tolerance in microbes remain unclear. Therefore, this study aimed to investigate the survival strategies and tolerance mechanisms of microbial communities in uranium-contaminated soil and groundwater. Microbial co-occurrence networks and molecular biology techniques were used to analyze the properties of microbes in groundwater and soil samples from various depths of uranium-contaminated areas in Northwest China. Uranium pollution altered microbial ecological strategies. Uranium stress facilitated the formation of microbial community structures, leading to symbiosis. Furthermore, microbes primarily resisted uranium hazards by producing polysaccharides and phosphate groups that chelate uranium, releasing phosphate substances that precipitate uranium, and reducing U(VI) through sulfate- and iron-reducing processes. The relative abundance of metal-methylation genes in soil microorganisms positively correlated with uranium concentration, indicating that soil microorganisms can produce methyl uranium via the Wood-Ljungdahl pathway. Furthermore, soil and groundwater microorganisms demonstrated different responses to uranium stress. This study provides new insights into microbial responses to uranium stress and novel approaches for the bioremediation of uranium-contaminated sites.

RNA 5-Methylcytosine Modification: Regulatory Molecules, Biological Functions, and Human Diseases.

RNA methylation modifications influence gene expression, and disruptions of these processes are often associated with various human diseases. The common RNA methylation modification 5-methylcytosine (m5C), which is dynamically regulated by writers, erasers, and readers, widely occurs in transfer RNAs (tRNAs), messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), enhancer RNAs (eRNAs), and other non-coding RNAs (ncRNAs). RNA m5C modification regulates metabolism, stability, nuclear export, and translation of RNA molecules. An increasing number of studies have revealed the critical roles of the m5C RNA modification and its regulators in the development, diagnosis, prognosis, and treatment of various human diseases. In this review, we summarized the recent studies on RNA m5C modification and discussed the advances in its detection methodologies, distribution, and regulators. Furthermore, we addressed the significance of RNAs modified with m5C marks in essential biological processes as well as in the development of various human disorders, from neurological diseases to cancers. This review provides a new perspective on the diagnosis, treatment, and monitoring of human diseases by elucidating the complex regulatory network of the epigenetic m5C modification.

Biogeochemical cycles of iron: Processes, mechanisms, and environmental implications.

The iron (Fe) biogeochemical cycle is critical for abiotic and biological environmental processes that overlap spatially and may compete with each other. The development of modern molecular biology technologies promoted the understanding of the electron transport mechanisms of Fe-cycling-related microorganisms. Recent studies have revealed a novel pathway for microaerophilic ferrous iron (Fe(II))-oxidizers in extracellular Fe(II) oxidation. In addition, OmcS, OmcZ, and OmcE nanowires on the cell surface have been shown to promote electron transfer between microorganisms and their environment. These processes affect the fate of pollutants in directly or indirectly ways, such as greenhouse gas emissions. In this review, these advances and the environmental implications of the Fe cycle process were discussed, with a particular focus on the mechanisms of intracellular or extracellular electron transport in microorganisms.

Type I arginine methyltransferases play crucial roles in development and pathogenesis of Phytophthora capsici.

Phytophthora capsici, a pathogenic oomycete, poses a serious threat to global vegetable production. This study investigated the role of protein arginine methylation, a notable post-translational modification, in the epigenetic regulation of P. capsici. We identified and characterized five protein arginine methyltransferases (PRMTs) in P. capsici, with a focus on four putative type I PRMTs exhibiting similar functional domain. Deletion of PcPRMT3, a homolog of PRMT3, significantly affected mycelial growth, asexual spore development, pathogenicity, and stress responses in P. capsici. Transcriptome analyses indicated that absence of PcPRMT3 disrupted multiple biological pathways. The PcPRMT3 deletion mutant displayed heightened susceptibility to oxidative stress, correlated with the downregulation of genes involved in peroxidase and peroxisome activities. Additionally, PcPRMT3 acted as a negative regulator, modulating the transcription levels of specific elicitins, which in turn affects the defense response of host plant against P. capsici. Furthermore, PcPRMT3 was found to affect global arginine methylation levels in P. capsici, implying potential alterations in the functions of its substrate proteins.

The contribution of circadian clock to the biological processes.

All organisms have various circadian, behavioral, and physiological 24-h periodic rhythms, which are controlled by the circadian clock. The circadian clock controls various behavioral and physiological rhythms. In mammals, the primary circadian clock is present in the suprachiasmatic nucleus of the hypothalamus. The rhythm of the circadian clock is controlled by the interaction between negative and positive feedback loops, consisting of crucial clock regulators (including Bmal1 and Clock), three cycles (mPer1, mPer2, and mPer3), and two cryptochromes (Cry1 and Cry2). The development of early mammalian embryos is an ordered and complex biological process that includes stages from fertilized eggs to blastocysts and undergoes important morphological changes, such as blastocyst formation, cell multiplication, and compaction. The circadian clock affects the onset and timing of embryonic development. The circadian clock affects many biological processes, including eating time, immune function, sleep, energy metabolism, and endocrinology, therefore, it is also crucial for overall health, growth and development after birth. This review summarized the effects of the circadian clock in the body's physiological activities. A new strategy is proposed for the prevention of malformations or diseases by regulating the circadian clock or changing circadian rhythms.

Analysis of huanglongbing-associated RNA-seq data reveals disturbances in biological processes within Citrus spp. triggered by Candidatus Liberibacter asiaticus infection.

Introduction: Huanglongbing (HLB), a disease that's ubiquitous worldwide, wreaks havoc on the citrus industry. The primary culprit of HLB is the gram-negative bacterium Candidatus Liberibacter asiaticus (CLas) that infects the phloem, but its damaging mechanism is yet to be fully understood. Methods and results: In this study, a multitude of tools including weighted correlation network analysis (WGCNA), protein-protein interaction (PPI) network analysis and gene expression profiling are employed to unravel the intricacies of its pathogenesis. The investigation pinpoints various central genes, such as the ethylene-responsive transcription factor 9 (ERF9) and thioredoxin reductase 1 (TrxR1), that are associated with CLas invasion and resultant disturbances in numerous biological operations. Additionally, the study uncovers a range of responses through the detection of differential expressed genes (DEGs) across different experiments. The discovery of core DEGs leads to the identification of pivotal genes such as the sieve element occlusion (SEO) and the wall-associated receptor kinase-like 15 (WAKL15). PPI network analysis highlights potential vital proteins, while GO and KEGG pathway enrichment analysis illustrate a significant impact on multiple defensive and metabolic pathways. Gene set enrichment analysis (GSEA) indicates significant alterations in biological processes such as leaf senescence and response to biotic stimuli. Discussion: This all-encompassing approach extends valuable understanding into the pathogenesis of CLas, potentially aiding future research and therapeutic strategies for HLB.

Role of calcium nutrition in plant Physiology: Advances in research and insights into acidic soil conditions - A comprehensive review.

Plant mineral nutrition has immense significance for crop productivity and human well-being. Soil acidity plays a major role in determining the nutrient availability that influences plant growth. The importance of calcium (Ca) in biological processes, such as signaling, metabolism, and cell growth, underlines its critical role in plant growth and development. This review focuses on soil acidification, a gradual process resulting from cation leaching, fertilizer utilization, and drainage issues. Soil acidification significantly hampers global crop production by modifying nutrient accessibility. In acidic soils, essential nutrients, such as nitrogen (N), phosphorus (P), potassium (K), magnesium (Mg), and Ca become less accessible, establishing a correlation between soil pH and plant nutrition. Cutting-edge Ca nutrition technologies, including nanotechnology, genetic engineering, and genome sequencing, offer the potential to deliver Ca and reduce the reliance on conventional soluble fertilizers. These fertilizers not only contribute to environmental contamination but also impose economic burdens on farmers. Nanotechnology can enhance nutrient uptake, and Ca nanoparticles improve nutrient absorption and release. Genetic engineering enables the cultivation of acid-tolerant crop varieties by manipulating Ca-related genes. High-throughput technologies such as next-generation sequencing and microarrays aid in identifying the microbial structures, functions, and biosynthetic pathways involved in managing plant nutritional stress. The ultimate goal is to shed light on the importance of Ca, problems associated with soil acidity, and potential of emerging technologies to enhance crop production while minimizing the environmental impact and economic burden on farmers.

Olive mill wastewater treatment strategies to obtain quality water for irrigation: A review.

The olive mill industry is a relevant sector in the economy of Mediterranean countries, while it involves high consumption of water and the production of effluents with high environmental impact. The efficient treatment of olive mill wastewater (OMW) is of high relevance, particularly for these countries. Climate changes are leading to increasing periods of droughts, and water recovery from polluted streams is essential to ensure the sustainability of this scarce resource. A combination of various technologies involving physical, chemical, and biological processes has been developed for OMW treatment. However, the treatments studied have limitations such as the operation costs, difficulty of industrial scale-up, and the fact that the vast majority do not lead to suitable treated water for discharge/reuse. As such, it is urgent to develop a solution capable of efficiently treating this effluent, overcoming the disadvantages of existing processes to convert OMW from a serious environmental problem into a valuable source of water and nutrients. In this review, several studies based on the OMW treatment are critically discussed, from conventional approaches such as the physical (e.g. centrifugation, filtration, and adsorption) and biological (anaerobic digestion and anaerobic co-digestion) processes, to the most recent technologies such as advanced membrane filtration, advanced oxidation processes (AOPs) and sulfate radical based AOPs (SR-AOPs). Due to the complexity of the effluent, OMW cannot be efficiently treated by a single process, requiring a sequence of technologies before reaching the required characteristics for discharge into water courses or use in crop irrigation. Reviewing the published results in this matter, it seems that the sequence of processes encompassing ozonation, anaerobic digestion, and SR-AOPs could be the ideal combination for this purpose. However, membrane technologies may be necessary in the final stage of treatment so that the effluent meets legal discharge or irrigation limits.

Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.

Alzheimer's disease (AD) manifests as a complex systems pathology with intricate interplay among various genes and biological processes. Traditional differential gene expression (DEG) analysis, while commonly employed to characterize AD-driven perturbations, does not sufficiently capture the full spectrum of underlying biological processes. Utilizing single-nucleus RNA-sequencing data from postmortem brain samples across key regions-middle temporal gyrus, superior frontal gyrus, and entorhinal cortex-we provide a comprehensive systematic analysis of disrupted processes in AD. We go beyond the DEG-centric analysis by integrating pathway activity analysis with weighted gene co-expression patterns to comprehensively map gene interconnectivity, identifying region- and cell-type-specific drivers of biological processes associated with AD. Our analysis reveals profound modular heterogeneity in neurons and glia as well as extensive AD-related functional disruptions. Co-expression networks highlighted the extended involvement of astrocytes and microglia in biological processes beyond neuroinflammation, such as calcium homeostasis, glutamate regulation, lipid metabolism, vesicle-mediated transport, and TOR signaling. We find limited representation of DEGs within dysregulated pathways across neurons and glial cells, indicating that differential gene expression alone may not adequately represent the disease complexity. Further dissection of inferred gene modules revealed distinct dynamics of hub DEGs in neurons versus glia, highlighting the differential impact of DEGs on neurons compared to glial cells in driving modular dysregulations underlying perturbed biological processes. Interestingly, we note an overall downregulation of both astrocyte and microglia modules in AD across all brain regions, suggesting a prevailing trend of functional repression in glial cells across these regions. Notable genes, including those of the CALM and HSP90 family genes emerged as hub genes across neuronal modules in all brain regions, indicating conserved roles as drivers of synaptic dysfunction in AD. Our findings demonstrate the importance of an integrated, systems-oriented approach combining pathway and network analysis for a comprehensive understanding of the cell-type-specific roles of genes in AD-related biological processes.

BioDeepfuse: a hybrid deep learning approach with integrated feature extraction techniques for enhanced non-coding RNA classification.

The accurate classification of non-coding RNA (ncRNA) sequences is pivotal for advanced non-coding genome annotation and analysis, a fundamental aspect of genomics that facilitates understanding of ncRNA functions and regulatory mechanisms in various biological processes. While traditional machine learning approaches have been employed for distinguishing ncRNA, these often necessitate extensive feature engineering. Recently, deep learning algorithms have provided advancements in ncRNA classification. This study presents BioDeepFuse, a hybrid deep learning framework integrating convolutional neural networks (CNN) or bidirectional long short-term memory (BiLSTM) networks with handcrafted features for enhanced accuracy. This framework employs a combination of k-mer one-hot, k-mer dictionary, and feature extraction techniques for input representation. Extracted features, when embedded into the deep network, enable optimal utilization of spatial and sequential nuances of ncRNA sequences. Using benchmark datasets and real-world RNA samples from bacterial organisms, we evaluated the performance of BioDeepFuse. Results exhibited high accuracy in ncRNA classification, underscoring the robustness of our tool in addressing complex ncRNA sequence data challenges. The effective melding of CNN or BiLSTM with external features heralds promising directions for future research, particularly in refining ncRNA classifiers and deepening insights into ncRNAs in cellular processes and disease manifestations. In addition to its original application in the context of bacterial organisms, the methodologies and techniques integrated into our framework can potentially render BioDeepFuse effective in various and broader domains.

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region-to-region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell-signalling/modification and transcription factors. We validate these patterns out-of-sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta-analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|ß| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health-related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.

The Role of Circular RNA for Early Diagnosis and Improved Management of Patients with Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are responsible for approximately 17.9 million deaths every year. There is growing evidence that circular RNAs (circRNAs) may play a significant role in the early diagnosis and treatment of cardiovascular diseases. As regulatory molecules, circular RNAs regulate gene expression, interact with proteins and miRNAs, and are translated into proteins that play a key role in a wide variety of biological processes, including the division and proliferation of cells, as well as the growth and development of individuals. An overview of the properties, expression profiles, classification, and functions of circRNAs is presented here, along with an explanation of their implications in cardiovascular diseases including heart failure, hypertension, ischemia/reperfusion injury, myocardial infarction, cardiomyopathies, atherosclerosis, and arrhythmia.

The Impact of miR-122 on Cancer.

MiRNAs are confirmed to be a kind of short and eminently conserved noncoding RNAs, which regulate gene expression at the post-transcriptional level via binding to the 3'- untranslated region (3'-UTR) of targeting multiple target messenger RNAs. Recently, growing evidence stresses the point that they play a crucial role in a variety of pathological processes, including human cancers. Dysregulated miRNAs act as oncogenes or tumor suppressor genes in many cancer types. Among them, we noticed that miR-122 has been widely reported to significantly influence carcinogenicity in a variety of tumors by regulating target genes and signaling pathways. Here, we focused on the expression of miR-122 in regulatory mechanisms and tumor biological processes. We also discussed the effects of miR-122 dysregulation in various types of human malignancies and the potential to develop new molecular miR-122-targeted therapies. The present review suggests that miR-122 may be a potentially useful cancer diagnosis and treatment biomarker. More clinical diagnoses need to be further launched in the future. A promising direction to improve the outcomes for cancer patients will likely combine miR-122 with other traditional tumor biomarkers.

Biosystem-Inspired Engineering of Nanozymes for Biomedical Applications.

Nanozymes with intrinsic enzyme-mimicking activities have shown great potential to become surrogates of natural enzymes in many fields by virtue of their advantages of high catalytic stability, ease of functionalization, and low cost. However, due to the lack of predictable descriptors, most of the nanozymes reported in the past have been obtained mainly through trial-and-error strategies, and the catalytic efficacy, substrate specificity, as well as practical application effect under physiological conditions, are far inferior to that of natural enzymes. To optimize the catalytic efficacies and functions of nanozymes in biomedical settings, recent studies have introduced biosystem-inspired strategies into nanozyme design. In this review, recent advances in the engineering of biosystem-inspired nanozymes by leveraging the refined catalytic structure of natural enzymes, simulating the behavior changes of natural enzymes in the catalytic process, and mimicking the specific biological processes or living organisms, are introduced. Furthermore, the currently involved biomedical applications of biosystem-inspired nanozymes are summarized. More importantly, the current opportunities and challenges of the design and application of biosystem-inspired nanozymes are discussed. It is hoped that the studies of nanozymes based on bioinspired strategies will be beneficial for constructing the new generation of nanozymes and broadening their biomedical applications.

Differential Proteomic Analysis of Human Sperm: A Systematic Review to Identify Candidate Targets to Monitor Sperm Quality.

PURPOSE: The advent of proteomics provides new opportunities to investigate the molecular mechanisms underlying male infertility. The selection of relevant targets based on a single analysis is not always feasible, due to the growing number of proteomic studies with conflicting results. Thus, this study aimed to systematically review investigations comparing the sperm proteome of normozoospermic and infertile men to define a panel of proteins with the potential to be used to evaluate sperm quality. MATERIALS AND METHODS: A literature search was conducted on PubMed, Web of Science, and Scopus databases following the PRISMA guidelines. To identify proteins systematically reported, first the studies were divided by condition into four groups (asthenozoospermia, low motility, unexplained infertility, and infertility related to risk factors) and then, all studies were analysed simultaneously (poor sperm quality). To gain molecular insights regarding identified proteins, additional searches were performed within the Human Protein Atlas, Mouse Genome Informatics, UniProt, and PubMed databases. RESULTS: Thirty-two studies were included and divided into 4 sub-analysis groups. A total of 2752 proteins were collected, of which 38, 1, 3 and 2 were indicated as potential markers for asthenozoospermia, low motility, unexplained infertility and infertility related to risk factors, respectively, and 58 for poor sperm quality. Among the identified proteins, ACR, ACRBP, ACRV1, ACTL9, AKAP4, ATG3, CCT2, CFAP276, CFAP52, FAM209A, GGH, HPRT1, LYZL4, PRDX6, PRSS37, REEP6, ROPN1B, SPACA3, SOD1, SPEM1, SPESP1, SPINK2, TEKT5, and ZPBP were highlighted due to their roles in male reproductive tissues, association with infertility phenotypes or participation in specific biological functions in spermatozoa. CONCLUSIONS: Sperm proteomics allows the identification of protein markers with the potential to overcome limitations in male infertility diagnosis and to understand changes in sperm function at the molecular level. This study provides a reliable list of systematically reported proteins that could be potential targets for further basic and clinical studies.

A network-based approach to understanding gene-biological processes affecting economically important traits of Nelore cattle.

This study aimed to build gene-biological process networks with differentially expressed genes associated with economically important traits of Nelore cattle from 17 previous studies. The genes were clustered into three groups by evaluated traits: group 1, production traits; group 2, carcass traits; and group 3, meat quality traits. For each group, a gene-biological process network analysis was performed with the differentially expressed genes in common. For production traits, 37 genes were found in common, of which 13 genes were enriched for six Gene Ontology (GO) terms; these terms were not functionally grouped. However, the enriched GO terms were related to homeostasis, the development of muscles and the immune system. For carcass traits, four genes were found in common. Thus, it was not possible to functionally group these genes into a network. For meat quality traits, the analysis revealed 222 genes in common. CSRP3 was the only gene differentially expressed in all three groups. Non-redundant biological terms for clusters of genes were functionally grouped networks, reflecting the cross-talk between all biological processes and genes involved. Many biological processes and pathways related to muscles, the immune system and lipid metabolism were enriched, such as striated muscle cell development and triglyceride metabolic processes. This study provides insights into the genetic mechanisms of production, carcass and meat quality traits of Nelore cattle. This information is fundamental for a better understanding of the complex traits and could help in planning strategies for the production and selection systems of Nelore cattle.

Molecular Signatures Integral to Natural Reprogramming in the Pigment Epithelium Cells after Retinal Detachment in Pleurodeles waltl.

The reprogramming of retinal pigment epithelium (RPE) cells into retinal cells (transdifferentiation) lies in the bases of retinal regeneration in several Urodela. The identification of the key genes involved in this process helps with looking for approaches to the prevention and treatment of RPE-related degenerative diseases of the human retina. The purpose of our study was to examine the transcriptome changes at initial stages of RPE cell reprogramming in adult newt Pleurodeles waltl. RPE was isolated from the eye samples of day 0, 4, and 7 after experimental surgical detachment of the neural retina and was used for a de novo transcriptome assembly through the RNA-Seq method. A total of 1019 transcripts corresponding to the differently expressed genes have been revealed in silico: the 83 increased the expression at an early stage, and 168 increased the expression at a late stage of RPE reprogramming. We have identified up-regulation of classical early response genes, chaperones and co-chaperones, genes involved in the regulation of protein biosynthesis, suppressors of oncogenes, and EMT-related genes. We revealed the growth in the proportion of down-regulated ribosomal and translation-associated genes. Our findings contribute to revealing the molecular mechanism of RPE reprogramming in Urodela.

Analysis of Human microRNA Expression Profiling During Diquat-Induced Renal Proximal Tubular Epithelial Cell Injury.

Background: We established a diquat-induced human kidney-2 cells (HK-2 cells) apoptosis model in this study to identify differentially expressed microRNAs (miRNAs) and signaling pathways involved in diquat poisoning via gene sequencing and bioinformatics analysis and explored the related therapeutic benefits. Methods: The effects of diquat on the viability and apoptosis of HK-2 cells were explored using the CCK-8 and Annexin V-FITC/PI double staining methods. Total RNAs were extracted using the TRizol method and detected by Illumina HiSeq 2500. Bioinformatics analysis was performed to explore differentially expressed (DE) miRNAs, their enriched biological processes, pathways, and potential target genes. The RT-qPCR method was used to verify the reliability of the results. Results: Diquat led to HK-2 cell injury and apoptosis played an important role, hence an HK-2 cell apoptosis model in diquat poisoning was established. Thirty-six DE miRNAs were screened in diquat-treated HK-2 cells. The enriched biological process terms were mainly cell growth, regulation of apoptotic signaling pathway, extrinsic apoptotic signaling pathway, and Ras protein signal transduction. The enriched cellular components were mainly cell-cell junction, cell-substrate junction, ubiquitin ligase complex, and protein kinase complex. The enriched molecular functions were mainly Ras GTPase binding, ubiquitin-like protein transferase activity, DNA-binding transcription factor binding, ubiquitin-protein transferase activity, nucleoside-triphosphatase regulator activity, transcription coactivator activity, and ubiquitin-like protein ligase binding. Signaling pathways such as MAPK, FoxO, Ras, PIK3-Akt, and Wnt were also enriched. Conclusion: These findings aid in understanding the mechanisms of diquat poisoning and the related pathways, where DE miRNAs serve as targets for gene therapy.

Advances and challenges in Bioinformatics and Biomedical Engineering: IWBBIO 2020.

This Supplement issue, presents five research articles which are distributed, mainly due to the subject they address, from the 8th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2020), which was held on line, during September, 30th-2nd October, 2020. These contributions have been chosen because of their quality and the importance of their findings. Those contributions were then invited to participate in this supplement for the following journals of BMC: BMC Bioinformatics and BMC Genomics. In the present Editorial in BMC journal, we summarize the contributions that provide a clear overview of the thematic areas covered by the IWBBIO conference, ranging from theoretical/review aspects to real-world applications of bioinformatic and biomedical engineering.