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SUMMARY: Achieving optimally balanced gene expression within synthetic operons requires regulatory elements capable of providing a spectrum of expression levels. In this study, we investigate the expression of gfp reporter gene in tobacco chloroplasts, guided by variants of the plastid atpH 5′ UTR, which harbors a binding site for PPR10, a protein that activates atpH at the posttranscriptional level. Our findings reveal that endogenous tobacco PPR10 confers distinct levels of reporter activation when coupled with the tobacco and maize atpH 5′ UTRs in different design contexts. Notably, high GFP expression was not coupled to the stabilization of monocistronic gfp transcripts in dicistronic reporter lines, adding to the evidence that PPR10 activates translation via a mechanism that is independent of its stabilization of monocistronic transcripts. Furthermore, the incorporation of a tRNA upstream of the UTR nearly abolishes gfp mRNA (and GFP protein), presumably by promoting such rapid RNA cleavage and 5′ exonucleolytic degradation that PPR10 had insufficient time to bind and protect gfp RNA, resulting in a substantial reduction in GFP accumulation. When combined with a mutant atpH 5′ UTR, the tRNA leads to an exceptionally low level of transgene expression. Collectively, this approach allows for tuning of reporter gene expression across a wide range, spanning from a mere 0.02–25% of the total soluble cellular protein. These findings highlight the potential of employing cis‐elements from heterologous species and expand the toolbox available for plastid synthetic biology applications requiring multigene expression at varying levels. Significance Statement: Achieving optimally balanced gene expression within synthetic operons requires regulatory elements capable of providing a spectrum of expression levels. We report posttranscriptional tools to tune gene expression in synthetic Nicotiana tabacum (tobacco) chloroplast operons over the range of 0.02–25% of total soluble cellular protein. [ABSTRACT FROM AUTHOR]

SUMMARY: Advancing chloroplast genetic engineering in Chlamydomonas reinhardtii remains challenging, decades after its first successful transformation. This study introduces the development of a chloroplast‐optimized mNeonGreen fluorescent reporter, enabling in vivo observation through a sixfold increase in fluorescence via context‐aware construct engineering. Our research highlights the influence of transcriptional readthrough and antisense mRNA pairing on post‐transcriptional regulation, pointing to novel strategies for optimizing heterologous gene expression. We further demonstrate the applicability of these insights using an accessible experimentation system using glass‐bead transformation and reestablishment of photosynthesis using psbH mutants, focusing on the mitigation of transcriptional readthrough effects. By characterizing heterologous expression using regulatory elements such as PrrnS, 5′atpA, and 3′ rbcL in a sense‐transcriptional context, we further documented up to twofold improvement in fluorescence levels. Our findings contribute new tools for molecular biology research in the chloroplast and evidence fundamental gene regulation processes that could enable the development of more effective chloroplast engineering strategies. This work not only paves the way for more efficient genetic engineering of chloroplasts but also deepens our understanding of the regulatory mechanisms at play. Significance Statement: In this work, we develop a functional fluorescent reporter for Chlamydomonas chloroplast expression, and found construct context‐effects influencing gene expression through formation of antisense dsRNA. These findings will aid in developing more efficient chloroplast genetic strategies and illuminate aspects of chloroplast gene expression. [ABSTRACT FROM AUTHOR]

SUMMARY: Global wheat production amounted to >780 MMT during 2022–2023 whose market size are valued at >$128 billion. Wheat is highly susceptible to high‐temperature stress (HTS) throughout the life cycle and its yield declines 5–7% with the rise in each degree of temperature. Previously, we reported an array of HTS‐response markers from a resilient wheat cv. Unnat Halna and described their putative role in heat acclimation. To complement our previous results and identify the key determinants of thermotolerance, here we examined the cytoplasmic proteome of a sensitive cv. PBW343. The HTS‐triggered metabolite reprograming highlighted how proteostasis defects influence the formation of an integrated stress‐adaptive response. The proteomic analysis identified several promising HTS‐responsive proteins, including a NACα18 protein, designated TaNACα18, whose role in thermotolerance remains unknown. Dual localization of TaNACα18 suggests its crucial functions in the cytoplasm and nucleus. The homodimerization of TaNACα18 anticipated its function as a transcriptional coactivator. The complementation of TaNACα18 in yeast and overexpression in wheat demonstrated its role in thermotolerance across the kingdom. Altogether, our results suggest that TaNACα18 imparts tolerance through tight regulation of gene expression, cell wall remodeling and activation of cell defense responses. [ABSTRACT FROM AUTHOR]

Small non-coding RNAs (sRNAs) are about 50–500 nucleotides in length, regulate the gene expression at both transcriptional and posttranslational levels, and are critical players in microbial adaptation to different environmental conditions. Our current understanding of molecular processes underlying adaptation to harsh environments, including cold environments, is far from being complete. To understand the regulation of gene expression in psychrophilic bacteria and the roles of sRNAs in cold adaptation, we scanned the genome of psychrophilic and halotolerant bacterium Psychrobacter aquaticus using a comparative genomics-based approach. In total, 111 putative cis -regulatory RNAs (cis -sRNAs) exhibiting thermodynamic stability of their secondary structure were predicted, 43 of which were predicted to be able to bind to their respective targets and studied further. Six of the 43 cis -sRNAs, including cis2, cis9, cis19, cis28, cis32, and cis40, were predicted as regulators of regulatory proteins, revealing that regulatory proteins themselves are regulated by sRNAs. A major class of cis -sRNAs are considered regulators of the genes related to synthesizing and transporting amino acids, nucleotides, and other metabolites in Psychrobacter aquaticus. Several cis -sRNAs were identified to putatively function in modulating the expression of genes related to stress responses. Particularly, cis38 was identified as a regulator of the rhlB gene crucial for bacterial adaptation to cold environments and, therefore, was regarded as a cold regulator. A putative cis -sRNA homologous to cis38 was also found in Psychrobacter alimentarius , a psychrophilic bacterium isolated from Antarctica and Korean fermented food. Both cis8 and its homolog shared a conserved domain interacting with their respective targets, mRNAs of the rhlB genes. Understanding the mechanisms of cold regulators will provide future opportunities to engineer bacterial species encoding cold-adapted enzymes for industrial applications. [Display omitted] • sRNAs play important role in microbial adaptation by modulating the gene expression. • Genome-wide identification of sRNAs in Psychrobacter aquaticus was performed. • In total, 111 putative cis -RNAs were predicted, targets for 43 of these were predicted. • Six of the 43 cis -sRNAs were found as regulators of regulatory proteins. • sRNA cis38 having role in cold adaption was identified and regarded as a cold regulator. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb), the tuberculosis-causing agent, exhibits diverse genetic lineages, with known links to virulence. While genomic and transcriptomic variations between modern and ancient Mtb lineages have been explored, the role of small non-coding RNA (sRNA) in post-translational gene regulation remains largely uncharted. In this study, Mtb Lineage 1 (L1) Sabahan strains (n = 3) underwent sRNA sequencing, revealing 351 sRNAs, including 23 known sRNAs and 328 novel ones identified using ANNOgesic. Thirteen sRNAs were selected based on the best average cut-off value of 300, with RT-qPCR revealing significant expression differences for sRNA 1 (p = 0.0132) and sRNA 29 (p = 0.0012) between Mtb L1 and other lineages (L2 and L4, n = 3) (p > 0.05). Further characterization using RACE (rapid amplification of cDNA ends), followed by target prediction with TargetRNA3 unveils that sRNA 1 (55 base pairs) targets Rv0506, Rv0697, and Rv3590c, and sRNA 29 (86 base pairs) targets Rv33859c, Rv3345c, Rv0755c, Rv0107c, Rv1817, Rv2950c, Rv1181, Rv3610c, and Rv3296. Functional characterization with Mycobrowser reveals these targets involved in regulating intermediary metabolism and respiration, cell wall and cell processes, lipid metabolism, information pathways, and PE/PPE. In summary, two novel sRNAs, sRNA 1 and sRNA 29, exhibited differential expression between L1 and other lineages, with predicted roles in essential Mtb functions. These findings offer insights into Mtb regulatory mechanisms, holding promise for the development of improved tuberculosis treatment strategies in the future. [ABSTRACT FROM AUTHOR]

According to the World Health Organization in 2022, 2.3 million women were diagnosed with breast cancer. Investigating the interaction networks between Bcl‐2‐associated athanogene (Bag)‐1 and other chaperone proteins may further the current understanding of the regulation of protein homeostasis in breast cancer cells and contribute to the development of treatment options. The present study aimed to determine the interactions between Bag‐1 and heat shock proteins (HSPs); namely, HSP90, HSP70 and HSP27, to elucidate their role in promoting heat shock factor‐1 (HSF1)‐dependent survival of breast cancer cells. HER2‐negative (MCF‐7) and HER2‐positive (BT‐474) cell lines were used to examine the impact of Bag‐1 expression on HSF1 and HSPs. We demonstrated that Bag‐1 overexpression promoted HER2 expression in breast cancer cells, thereby resulting in the concurrent constitutive activation of the HSF1–HSP axis. The activation of HSP results in the stabilization of several tumor‐promoting HSP clients such as AKT, mTOR and HSF1 itself, which substantially accelerates tumor development. Our results suggest that Bag‐1 can modulate the chaperone activity of HSPs, such as HSP27, by directly or indirectly regulating the phosphorylation of HSF1. This modulation of chaperone activity can influence the activation of genes involved in cellular homeostasis, thereby protecting cells against stress. [ABSTRACT FROM AUTHOR]

A compelling correlation method linking microbial communities and host gene expression in tissues is currently absent. A novel pipeline is proposed, dubbed Transcriptome Analysis of Host‐Microbiome Crosstalk (TAHMC), designed to concurrently restore both host gene expression and microbial quantification from bulk RNA‐seq data. Employing this approach, it discerned associations between the tissue microbiome and host immunity in the context of Crohn's disease (CD). Further, machine learning is utilized to separately construct networks of associations among host mRNA, long non‐coding RNA, and tissue microbes. Unique host genes and tissue microbes are extracted from these networks for potential utility in CD diagnosis. Experimental validation of the predicted host gene regulation by microbes from the association network is achieved through the co‐culturing of Faecalibacterium prausnitzii with Caco‐2 cells. Collectively, the TAHMC pipeline accurately recovers both host gene expression and microbial quantification from CD RNA‐seq data, thereby illuminating potential causal links between shifts in microbial composition as well as diversity within CD mucosal tissues and aberrant host gene expression. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective was to identify the pivotal genes and upstream regulators, transcription factors (TFs), microRNAs (miRNAs), and pathways implicated in the pathogenesis of vitiligo. Methods: An integrated analysis was conducted using microarray datasets on vitiligo obtained from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were additionally investigated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Various bioinformatics approaches were utilized, making use of publicly accessible databases to identify appropriate TFs and miRNAs. Results: Our investigation identified TYR, MLANA, TYRP1, PMEL, OCA2, SLC45A2, GPR143, DCT, TRPM1, and EDNRB as the most appropriate genes associated with vitiligo. Our suggestion is that the identified biological processes include developmental pigmentation (GO:0048066) and pigment metabolic processes (GO:0042440) as the most suitable biological processes. In contrast, the KEGG pathways that showed significance in our analysis are Tyrosine metabolism (Path: hsa00350) and Melanogenesis (Path: hsa04916). We hypothesized the involvement of ten TFs and 73 miRNAs in the regulation of genes related to vitiligo. Conclusion: TYR, MLANA, TYRP1, PMEL, OCA2, SLC45A2, GPR143, DCT, TRPM1, and EDNRB are the top ten genes that are pivotal in the progression and exhibition of vitiligo. The biological, cellular, molecular, and KEGG pathways of those genes has an imperative role in the pathogenesis of vitiligo. TFs and miRNAs that interact with this gene are listed, shedding light on the regulatory mechanisms governing the expression of these key genes in vitiligo. [ABSTRACT FROM AUTHOR]

Copyright of Acta Agriculturae Zhejiangensis is the property of Acta Agriculturae Zhejiangensis Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cytosine methylation contributes to the regulation of gene expression and normal hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases that include DNMT1, DNMT3A, and DNMT3B. Peripheral T–cell lymphomas (PTCLs) represent aggressive mature T–cell malignancies exhibiting a broad spectrum of clinical features with poor prognosis and inadequately understood molecular pathobiology. To better understand the molecular landscape and identify candidate genes involved in disease maintenance, we profiled DNA methylation and gene expression of PTCLs. We found that the methylation patterns in PTCLs are deregulated and heterogeneous but share 767 hypo- and 567 hypermethylated differentially methylated regions (DMRs) along with 231 genes up- and 91 genes downregulated in all samples, suggesting a potential association with tumor development. We further identified 39 hypomethylated promoters associated with increased gene expression in the majority of PTCLs. This putative oncogenic signature included the TRIP13 (thyroid hormone receptor interactor 13) gene whose genetic and pharmacologic inactivation inhibited the proliferation of T–cell lines by inducing G2-M arrest and apoptosis. Our data thus show that human PTCLs have a significant number of recurrent methylation alterations that may affect the expression of genes critical for proliferation whose targeting might be beneficial in anti-lymphoma treatments. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These systems must be tightly regulated because they can capture DNA fragments from foreign selfish elements, and also occasionally from self-chromosomes, resulting in autoimmunity. Most known species from the halophilic archaeal genus Haloferax contain type I-B CRISPR-Cas systems, and the strongest hotspot for self-spacer acquisition by H. mediterranei was a locus that contained a putative transposable element, as well as the gene HFX_2341, which was a very frequent target for self-targeting spacers. To test whether this gene is CRISPR-associated, we investigated it using bioinformatics, deletion, over-expression, and comparative transcriptomics. We show that HFX_2341 is a global transcriptional regulator that can repress diverse genes, since its deletion results in significantly higher expression of multiple genes, especially those involved in nutrient transport. When over-expressed, HFX_2341 strongly repressed the transcript production of all cas genes tested, both those involved in spacer acquisition (cas1, 2 and 4) and those required for destroying selfish genetic elements (cas3 and 5–8). Considering that HFX_2341 is highly conserved in haloarchaea, with homologs that are present in species that do not encode the CRISPR-Cas system, we conclude that it is a global regulator that is also involved in cas gene regulation, either directly or indirectly. [ABSTRACT FROM AUTHOR]

Bacterial adhesion and biofilm maturation is significantly influenced by surface properties, encompassing both bare surfaces and single or multi-layered coatings. Hence, there is an utmost interest in exploring the intricacies of gene regulation in sulfate-reducing bacteria (SRB) on copper and graphene-coated copper surfaces. In this study, Oleidesulfovibrio alaskensis G20 was used as the model SRB to elucidate the pathways that govern pivotal roles during biofilm formation on the graphene layers. Employing a potent reporter green fluorescent protein (GFP) tagged to O. alaskensis G20, the spatial structure of O. alaskensis G20 biofilm on copper foil (CuF), single-layer graphene-coated copper (Cu-GrI), and double-layer graphene-coated copper (Cu-GrII) surfaces was investigated. Biofilm formation on CuF, Cu-GrI, and Cu-GrII surfaces was quantified using CLSM z-stack images within COMSTAT v2 software. The results revealed that CuF, Cu-GrI, and Cu-GrII did not affect the formation of the GFP-tagged O. alaskensis G20 biofilm architecture. qPCR expression showed insignificant fold changes for outer membrane components regulating the quorum-sensing system, and global regulatory proteins between the uncoated and coated surfaces. Notably, a significant expression was observed within the sulfate reduction pathway confined to dissimilatory sulfite reductases on the Cu-GrII surface compared to the CuF and Cu-GrI surfaces. [ABSTRACT FROM AUTHOR]

Frontonasal malformations are caused by a failure in the growth of the frontonasal prominence during development. Although genetic studies have identified genes that are crucial for frontonasal development, it remains largely unknown how these genes are regulated during this process. Here, we show that microRNAs, which are short non-coding RNAs capable of targeting their target mRNAs for degradation or silencing their expression, play a crucial role in the regulation of genes related to frontonasal development in mice. Using the Mouse Genome Informatics (MGI) database, we curated a total of 25 mouse genes related to frontonasal malformations, including frontonasal hypoplasia, frontonasal dysplasia, and hypotelorism. MicroRNAs regulating the expression of these genes were predicted through bioinformatic analysis. We then experimentally evaluated the top three candidate miRNAs (miR-338-5p, miR-653-5p, and miR-374c-5p) for their effect on cell proliferation and target gene regulation in O9-1 cells, a neural crest cell line. Overexpression of these miRNAs significantly inhibited cell proliferation, and the genes related to frontonasal malformations (Alx1, Lrp2, and Sirt1 for miR-338-5p; Alx1, Cdc42, Sirt1, and Zic2 for miR-374c-5p; and Fgfr2, Pgap1, Rdh10, Sirt1, and Zic2 for miR-653-5p) were directly regulated by these miRNAs in a dose-dependent manner. Taken together, our results highlight miR-338-5p, miR-653-5p, and miR-374c-5p as pathogenic miRNAs related to the development of frontonasal malformations. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Liver fibrosis remains a complication derived from a chronic Hepatitis C Virus (HCV) infection even when it is resolved, and no liver antifibrotic drug has been approved. Molecular mechanisms on hepatocytes and activation of hepatic stellate cells (HSCs) play a central role in liver fibrogenesis. To elucidate molecular mechanisms, it is important to analyze pathway regulation during HSC activation and HCV infection. Materials and Methods: We evaluate the fibrosis-associated molecular mechanisms during a co-culture of human HSCs (LX2), with human hepatocytes (Huh7) that express HCV NS5A or Core protein. We evaluated LX2 activation induced by HCV NS5A or Core expression in Huh7 cells during co-culture. We determined a fibrosis-associated gene expression profile in Huh7 that expresses NS5A or Core proteins during the co-culture with LX2. Results: We observed that NS5A induced 8.3-, 6.7- and 4-fold changes and that Core induced 6.5-, 1.8-, and 6.2-fold changes in the collagen1, TGFb1, and timp1 gene expression, respectively, in LX2 co-cultured with transfected Huh7. In addition, NS5A induced the expression of 30 genes while Core induced 41 genes and reduced the expression of 30 genes related to fibrosis in Huh7 cells during the co-culture with LX2, compared to control. The molecular pathways enriched from the gene expression profile were involved in TGFB signaling and the organization of extracellular matrix. Conclusions: We demonstrated that HCV NS5A and Core protein expression regulate LX2 activation. NS5A and Core-induced LX2 activation, in turn, regulates diverse fibrosis-related gene expression at different levels in Huh7, which can be further analyzed as potential antifibrotic targets during HCV infection. [ABSTRACT FROM AUTHOR]

Supra-optimal temperature adversely affects plant growth and development. Among different growth phases, the reproductive stage of plants is highly sensitive to high temperature stress. The heat tolerance of plants is reliant on a complex interplay of various factors, including the activation of heat stress responses, downstream signaling pathways, and biosynthesis of plant hormones. This intricate network of mechanisms results in the production of several secondary metabolites, which play a crucial role in enhancing the plant's ability to cope with high temperature stress. Many of these secondary metabolites are crucial for the reproductive performance of plants, as they are involved in the attraction of pollinators, pollen germination, pollen tube growth, pollen viability, pollen fertility, and fertilization. Reproductive tissues of plants are highly vulnerable to heat stress, but increased biosynthesis of secondary metabolites (flavonoids, polyamines, glutathione, etc.) induces reproductive thermotolerance through reactive oxygen species homeostasis, protecting the cellular membranes, improving pollen fertility, reducing anther abortion, regulating cellular signaling and activation of genes/transcription factors associated with metabolic pathway network. The identification and engineering of some genes controlling the secondary metabolic pathways network have proved effective in inducing terminal heat stress tolerance in transgenic plants. This review highlights the effect of heat stress on plant secondary metabolism and the role of different plant secondary metabolites in contributing to heat stress tolerance in reproductive tissues. The engineering of genes involved in plant secondary metabolic pathway and their effect on heat stress tolerance has also been discussed. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a regulatory and protective mechanism that plays a crucial role in the growth, development, and control of plant responses to pathogens and abiotic stresses. In spray-induced gene silencing (SIGS), exogenous double-stranded RNAs (dsRNA) are used to efficiently regulate target genes via plant surface treatment. In this study, we aimed to evaluate the effect of specific exogenous dsRNAs on silencing different regions (promoter, protein-coding and intron) of the target SlTRY tomato gene, encoding an R3-type MYB repressor of anthocyanin biosynthesis. We also assessed the impact of targeting different SlTRY regions on the expression of genes involved in anthocyanin and flavonoid biosynthesis. This study demonstrated the critical importance of selecting the appropriate gene target region for dsRNA action. The highest inhibition of the SlTRY gene expression and activation of anthocyanin biosynthesis was achieved by dsRNA complementary to the protein-coding region of SlTRY gene, compared with dsRNAs targeting the SlTRY promoter or intron regions. Silencing the SlTRY gene increased the content of anthocyanins and boosted levels of other substances in the phenylpropanoid pathway, such as caffeoyl putrescine, chlorogenic acid, ferulic acid glucoside, feruloyl quinic acid, and rutin. This study is the first to examine the effects of four different dsRNAs targeting various regions of the SlTRY gene, an important negative regulator of anthocyanin biosynthesis. [ABSTRACT FROM AUTHOR]

DnaJ proteins, also known as HSP40s, play a key role in plant growth and development, and response to environmental stress. However, little comprehensive research has been conducted on the DnaJ gene family in maize. Here, we identify 91 ZmDnaJ genes from maize, which are likely distributed in the chloroplast, nucleus, and cytoplasm. Our analysis revealed that ZmDnaJs were classified into three types, with conserved protein motifs and gene structures within the same type, particularly among members of the same subfamily. Gene duplication events have likely contributed to the expansion of the ZmDnaJ family in maize. Analysis of cis-regulatory elements in ZmDnaJ promoters suggested involvement in stress responses, growth and development, and phytohormone sensitivity in maize. Specifically, four cis-acting regulatory elements associated with stress responses and phytohormone regulation indicated a role in adaptation. RNA-seq analysis showed constitutive expression of most ZmDnaJ genes, some specifically in pollen and endosperm. More importantly, certain genes also responded to salt, heat, and cold stresses, indicating potential interaction between stress regulatory networks. Furthermore, early responses to heat stress varied among five inbred lines, with upregulation of almost tested ZmDnaJ genes in B73 and B104 after 6 h, and fewer genes upregulated in QB1314, MD108, and Zheng58. After 72 h, most ZmDnaJ genes in the heat-sensitive inbred lines (B73 and B104) returned to normal levels, while many genes, including ZmDnaJ55, 79, 88, 90, and 91, remained upregulated in the heat-tolerant inbred lines (QB1314, MD108, and Zheng58) suggesting a synergistic function for prolonged protection against heat stress. In conclusion, our study provides a comprehensive analysis of the ZmDnaJ family in maize and demonstrates a correlation between heat stress tolerance and the regulation of gene expression within this family. These offer a theoretical basis for future functional validation of these genes. [ABSTRACT FROM AUTHOR]

Cereal crops account for a large proportion of human caloric demand for billions of people worldwide. However, harmful heavy metal accumulation in grain, i.e., cadmium (Cd), creates a widespread problem in threatening human health directly or indirectly through the food chain. In contrast to Cd, zinc (Zn)—an essential element chemically similar to Cd—is usually lower in concentration in consumed cereals than the amount needed to meet dietary needs, leading to malnutrition in many developing countries. As genetics and functional genomics data become increasingly available, a large body of studies has been conducted for Cd and Zn separately in different cereal crops, making it possible to perform a comparative analysis to reveal the shared or unique metal accumulation and transport mechanisms from genetic and genomics perspectives. Here, we reviewed recent efforts in dissecting the molecular mechanisms and genetic regulations regarding metal accumulation in cereal crops, mainly focusing on the two chemically similar metals—the toxic heavy metal Cd and the essential micronutrient Zn. Based on the literature study, we highlight a potential metal accumulation pathway that can be used as a benchmark to ascertain the functional roles of transporters across species to decrease Cd accumulation, increase Zn concentrations, and provide our view into the metal composition improvement in cereal crops. [ABSTRACT FROM AUTHOR]

Epigenetics research in evolutionary biology encompasses a variety of research areas, from regulation of gene expression to inheritance of environmentally mediated phenotypes. Such divergent research foci can occasionally render the umbrella term "epigenetics" ambiguous. Here I discuss several areas of contemporary epigenetics research in the context of evolutionary biology, aiming to provide balanced views across timescales and molecular mechanisms. The importance of epigenetics in development is now being assessed in many nonmodel species. These studies not only confirm the importance of epigenetic marks in developmental processes, but also highlight the significant diversity in epigenetic regulatory mechanisms across taxa. Further, these comparative epigenomic studies have begun to show promise toward enhancing our understanding of how regulatory programs evolve. A key property of epigenetic marks is that they can be inherited along mitotic cell lineages, and epigenetic differences that occur during early development can have lasting consequences on the organismal phenotypes. Thus, epigenetic marks may play roles in short-term (within an organism's lifetime or to the next generation) adaptation and phenotypic plasticity. However, the extent to which observed epigenetic variation occurs independently of genetic influences remains uncertain, due to the widespread impact of genetics on epigenetic variation and the limited availability of comprehensive (epi)genomic resources from most species. While epigenetic marks can be inherited independently of genetic sequences in some species, there is little evidence that such "transgenerational inheritance" is a general phenomenon. Rather, molecular mechanisms of epigenetic inheritance are highly variable between species. [ABSTRACT FROM AUTHOR]

The prevalence of autoimmune diseases ranks as the third most common disease category globally, following cancer and heart disease. Numerous studies indicate that long non-coding RNA (lncRNA) plays a pivotal role in regulating human growth, development, and the pathogenesis of various diseases. It is more than 200 nucleotides in length and is mostly involve in the regulation of gene expression. Furthermore, lncRNAs are crucial in the development and activation of immune cells, with an expanding body of research exploring their association with autoimmune disorders in humans. LncRNA Ifng antisense RNA 1 (IFNG-AS1), a key regulatory factor in the immune system, also named NeST or TMEVPG1, is proximally located to IFNG and participates in the regulation of it. The dysregulation of IFNG-AS1 is implicated in the pathogenesis of several autoimmune diseases. This study examines the role and mechanism of IFNG-AS1 in various autoimmune diseases and considers its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Coping with stress is essential for mental well-being and can be critical for highly sensitive individuals, characterized by a deeper perception and processing of stimuli. So far, the molecular bases characterizing high-sensitivity traits have not been completely investigated and gene × environment interactions might play a key role in making some people more susceptible than others. Methods: In this study, 104 young adult university students, subjects that might face overwhelming experiences more than others, were evaluated for the genetics and epigenetics of dopamine (DAT1) and serotonin (SERT) transporter genes, in addition to the expression of miR-132, miR-491, miR-16, and miR-135. Results: We found an increase in DNA methylation at one specific CpG site at DAT1 5'UTR in highly sensitive students reporting high levels of perceived stress when compared to those less sensitive and/or less stressed. Moreover, considering DAT1 VNTR at 3'UTR, we observed that this effect was even more pronounced in university students having the 9/9 genotype when compared to those with the 9/10 genotype. These data are corroborated by the higher levels of miR-491, targeting DAT1, in highly sensitive subjects with high levels of perceived stress. SERT gene DNA methylation at one specific CpG site was reported to instead be higher in subjects reporting lower perceived stress when compared to more stressed subjects. Consistently, miR-135 expression, regulating SERT, was lower in subjects with higher perceived stress. Conclusions: We here suggest that the correlation of DAT1 and SERT genetic and epigenetic data with the analysis of stress and sensitivity might be useful to suggest possible biomarkers to monitor mental health wellness in vulnerable subjects. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are recognized as key molecular regulators in most of intracellular processes essential for plant adaptation to environmental changes. microRNAs can mediate regulation of gene expression involved in development, acquisition of nutrients, defense and interactions with soil microorganisms to enhance stress tolerance of plants. Accumulating evidences indicate that microRNAs are also transferred within cells, organs or whole plant and released in soil as stress signals of the plant-microbiome communication. However, little information is available about how mobile microRNAs are conveyed from plants to the rhizosphere. To understand whether this intriguing phenomenon occurs through root secretion, morphological changes, Peroxidase (POX), superoxide dismutase (SOD) and catalase (CAT) antioxidant enzymes activities, as well as the expression profiles of developmental and oxidative stress responsive microRNAs were analyzed in root tissues and exudates collected from wheat (triticum aestivum) exposed to bisphenol A (BPA) at low and high concentrations (0.1 and 5000 mg. kg−1 soil). BPA contamination significantly affected aerial and root biomass, and miR164, miR167 and miR398 expression in roots of the group that received the highest dose. The presence of miR156, miR164, miR167 was detected in root exudates of controls and contaminated plants while BPA exposure increased miR 167 levels in exudates at high dose. Collectively, this experiment provided first results reporting microRNAs regulatory network participation in the BPA stress response of wheat. The identification of microRNAs as integral component of the root exudates will extend our knowledge about the molecular signaling in plant—soil microbiome interactions. [ABSTRACT FROM AUTHOR]

Homeodomain‐only protein homeobox (HOPX) mainly exerts its transcriptional repression by physically sequestering the serum co‐repressor and recruiting histone deacetylase (HDAC), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). HDACs play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether HOPX affects AML progression by interacting with HDAC2 protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker HOPX. The interaction network of HOPX was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between HOPX and HDAC2 was observed using endogenous and exogenous immunoprecipitation. HOPX is highly expressed in AML cells. Further research uncovered that low expression of HOPX can repress the proliferation activity, anti‐apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, HOPX induced AML differentiation blockage and malignant progression through interaction with HDAC. HOPX can serve as a prognostic marker for AML and can interact with HDAC2 to induce AML differentiation blockage and malignant progression. [ABSTRACT FROM AUTHOR]

Improving seed germination and seedling development can potentially increase crop yield and improve quality in direct-seeded rice. This study aimed to detect loci or genes associated with rice seed germination. We reported the phenotypic analysis of seed germination in 103 rice accessions across two years, and a genome-wide association study (GWAS) was conducted to identify loci underlying the genetic regulation of seed germination. A total of seven genetic loci were found to be associated with seed germination, including five loci that overlapped with the previously reported loci/genes, and two novel loci. Of these, two loci (qGP2 and qGP4.1) were stable across different environments. GP4 (Germination percentage 4), encoding a 9-cis-epoxycarotenoid dioxygenase, was identified as the candidate gene of the major locus qGP4.1. A sequence analysis of GP4 revealed that four functional polymorphic sites in the coding region were significantly associated with germination percentage. The disruption of GP4 by gene editing resulted in faster seed germination and seedling establishment. Taken together, we have identified GP4 as a novel gene involved in rice seed germination, and we provide a potential target gene for improving rice seed vigor via gene editing or molecular breeding. [ABSTRACT FROM AUTHOR]

PIWI‐interacting RNAs (piRNAs) are a typical class of small non‐coding RNAs, which are essential for gene regulation, genome stability and so on. Accumulating studies have revealed that piRNAs have significant potential as biomarkers and therapeutic targets for a variety of diseases. However current computational methods face the challenge in effectively capturing piRNA‐disease associations (PDAs) from limited data. In this study, we propose a novel method, MRDPDA, for predicting PDAs based on limited data from multiple sources. Specifically, MRDPDA integrates a deep factorization machine (deepFM) model with regularizations derived from multiple yet limited datasets, utilizing separate Laplacians instead of a simple average similarity network. Moreover, a unified objective function to combine embedding loss about similarities is proposed to ensure that the embedding is suitable for the prediction task. In addition, a balanced benchmark dataset based on piRPheno is constructed and a deep autoencoder is applied for creating reliable negative set from the unlabeled dataset. Compared with three latest methods, MRDPDA achieves the best performance on the pirpheno dataset in terms of the five‐fold cross validation test and independent test set, and case studies further demonstrate the effectiveness of MRDPDA. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) provide a prime example of genetic conflict because they can proliferate in genomes and populations even if they harm the host. However, numerous studies have shown that TEs, though typically harmful, can also provide fuel for adaptation. This is because they code functional sequences that can be useful for the host in which they reside. In this review, I summarize the "how" and "why" of adaptation enabled by the genetic conflict between TEs and hosts. In addition, focusing on mechanisms of TE control by small piwi-interacting RNAs (piRNAs), I highlight an indirect form of adaptation enabled by conflict. In this case, mechanisms of host defense that regulate TEs have been redeployed for endogenous gene regulation. I propose that the genetic conflict released by meiosis in early eukaryotes may have been important because, among other reasons, it spurred evolutionary innovation on multiple interwoven trajectories - on the part of hosts and also embedded genetic parasites. This form of evolution may function as a complexity generating engine that was a critical player in eukaryotic evolution. [ABSTRACT FROM AUTHOR]

Nitrite constitutes a significant pollutant that impedes the growth of P. vannamei. Conventional treatments are primarily geared toward decreasing nitrite concentrations from an environmental standpoint. Nevertheless, investigating methodologies to enhance the ability of Pacific white shrimp to withstand nitrite-induced stresses on an individual basis remains an unexplored topic. The present study examines the impact of autophagy on Pacific white shrimp's response to high nitrite environments through rapamycin injection. The research findings indicate that activating autophagy can effectively enhance the survival rate of Pacific white shrimp under high nitrite conditions. Additionally, total hemocyte count (THC) results in the hemolymph demonstrate that autophagy can alleviate the reduction in blood cell count caused by nitrite stress. The transcriptome results show that upregulation of 718 genes and downregulation of 1071 genes after nitrite stress. The majority of these differentially expressed genes (DEGs) were related to physiological processes, including oxidative stress, energy metabolism, and lysosomes. In addition, there were 911 upregulated genes and 713 downregulated genes upon activation of autophagy. These DEGs are associated with immune responses, specifically involving glutathione metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450, lysosomes, autophagy, phagosomes, melanization, and MAPK signaling pathways. These pathways can reduce oxidative stress and promote the metabolism of harmful substances in the body, in shrimp, thereby improving their survival rates. These findings provide new insights for research aimed at enhancing nitrite tolerance in Pacific white shrimp. [ABSTRACT FROM AUTHOR]

Objectives: Thyroid cancer (THCA) is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide. And the number of patients dying from THCA has also gradually risen because the incidence continues to increase, so the mechanisms related to effective targets is necessary to improve the survival. This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer (THCA) cell proliferation and the associated pathways. Methods: Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development. COL4A2 expression in THCA tissues was analyzed using immunohistochemistry, and survival information was determined via Kaplan--Meier curves. The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses. Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity, respectively. Downstream of COL4A2 was identified by Gene set enrichment analysis (GSEA). The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model. Results: Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2. THCA patients with high COL4A2 expression had shorter recurrence-free survival. Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity. The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines. The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival. Conclusions: COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA. [ABSTRACT FROM AUTHOR]

The incorporation of epigenetics (i.e., change in gene activity without change in DNA sequence) into studies of gene regulation and phenotypic expression has contributed to a significant improvement in our understanding of the evolution of life history traits. One important epigenetic mechanism is DNA methylation, which in vertebrates generally means the addition of a methyl group to a cytosine thus altering gene expression. Here, we discuss progress and gaps in our knowledge of the role of DNA methylation in facilitating diversity across four life history trait classes in fishes: developmental processes, size and growth rates, aging and sexual maturity, and sex regulation. We discuss insights into the regulatory aspect of gene expression in fish which can ultimately influence phenotypic diversity and speciation. We discuss how temperature influences methylation patterns affecting multiple traits. DNA methylation influence on gene expression varies depending on tissue types and the location within the genome of the methylated site (i.e., DNA methylation can increase or decrease gene expression). The role of DNA methyltransferases is also a common denominator across all tissue types in influencing the global methylome status regardless of species or environmental stressor. Organismal development stage is equally important, a decrease in global methylation throughout early development generally corresponds to elevated gene expression associated with growth and development. Finally, we discuss general limitations of DNA methylation studies with a focus on fish. We then provide recommendations for future research. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWASs) have identified genetic susceptibility loci associated with juvenile dermatomyositis (JDM). Single nucleotide polymorphisms related to phosphorylation (phosSNPs) are critical nonsynonymous mutations exerting substantial influence on gene expression regulation. The aim of this study was to identify JDM susceptibility genes in the GWAS loci by the use of phosSNPs. We explored quantitative trait loci (QTLs) among the phosSNPs associated with JDM using data from eQTL (bulk tissues and single-cell) and pQTL studies. For gene expression and protein levels significantly influenced by JDM-associated phosSNPs, we assessed their associations with JDM through MR analyses. Additionally, we conducted differential expression gene analyses, incorporating single-cell transcriptomic profiling of 6 JDM cases and 11 juvenile controls (99,396 cells). We identified 31 phosSNPs situated in the 6p21 locus that were associated with JDM. Half of these phosSNPs showed effects on gene expression in various cells and circulating protein levels. In MR analyses, we established associations between the expression levels of pivotal JDM-associated genes, including MICB, C4A, HLA-DRB1, HLA-DRB5, and PSMB9, in skin, muscle, or blood cells and circulating levels of C4A, with JDM. Utilizing single-cell eQTL data, we identified a total of 276 association signals across 14 distinct immune cell types for 28 phosSNPs. Further insights were gained through single-cell differential expression analysis, revealing differential expression of PSMB9, HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DQB1, and HLA-DRB1 in immune cells. The present study pinpointed phosSNPs within susceptibility genes for JDM and unraveled the intricate relationships among these SNPs, gene expression levels, and JDM. [ABSTRACT FROM AUTHOR]

The lack of a widely accessible method for expressing genes of interest in wild-type embryos is a fundamental obstacle to understanding genetic regulation during embryonic development. In particular, only a few methods are available for introducing gene expression vectors into cells prior to neural tube closure, which is a period of drastic development for many tissues. In this study, we present a simple technique for injecting vectors into the amniotic cavity and allowing them to reach the ectodermal cells and the epithelia of endodermal organs of mouse embryos at E8.0 via in utero injection, using only a widely used optical fiber with an illuminator. Using this technique, retroviruses can be introduced to facilitate the labeling of cells in various tissues, including the brain, spinal cord, epidermis, and digestive and respiratory organs. We also demonstrated in utero electroporation of plasmid DNA into E7.0 and E8.0 embryos. Taking advantage of this method, we reveal the association between Ldb1 and the activity of the Neurog2 transcription factor in the mouse neocortex. This technique can aid in analyzing the roles of genes of interest during endo- and ectodermal development prior to neural tube closure. [Display omitted] • New gene transfection method for embryos at E7 and E8 before neural tube closure. • Only optical fiber and injector needed. • Gene transfection into progenitors in ecto- and endodermal tissues. • Useful to analyze the role of lethal genes during embryogenesis, such as Ldb1. [ABSTRACT FROM AUTHOR]

Promoters are important cis-regulatory elements for the regulation of gene expression, and their accurate predictions are crucial for elucidating the biological functions and potential mechanisms of genes. Many previous prokaryotic promoter prediction methods are encouraging in terms of the prediction performance, but most of them focus on the recognition of promoters in only one or a few bacterial species. Moreover, due to ignoring the promoter sequence motifs, the interpretability of predictions with existing methods is limited. In this work, we present a generalized method Prompt (Promoters in multiple prokaryotes) to predict promoters in 16 prokaryotes and improve the interpretability of prediction results. Prompt integrates three methods including RSK (Regression based on Selected k-mer), CL (Contrastive Learning) and MLP (Multilayer Perception), and employs a voting strategy to divide the datasets into high-confidence and low-confidence categories. Results on the promoter prediction tasks in 16 prokaryotes show that the accuracy (Accuracy, Matthews correlation coefficient) of Prompt is greater than 80% in highly credible datasets of 16 prokaryotes, and is greater than 90% in 12 prokaryotes, and Prompt performs the best compared with other existing methods. Moreover, by identifying promoter sequence motifs, Prompt can improve the interpretability of the predictions. Prompt is freely available at https://github.com/duqimeng/PromptPrompt, and will contribute to the research of promoters in prokaryote. Key points: • Promoters are important cis-regulatory elements for the regulation of gene expression. • We developed a generalized method Prompt (Promoters in multiple prokaryotes) to predict promoters in 16 prokaryotes. • Prompt integrates three methods including RSK (Regression based on Selected K-mer), CL (Contrastive Learning) and MLP (Multilayer Perception). • By identifying promoter sequence motifs, Prompt can improve the interpretability of the predictions. [ABSTRACT FROM AUTHOR]

Canine mammary tumors (CMTs) represent a significant health concern in dogs, with a high incidence among intact female dogs. CMTs are a promising comparative model for human breast cancer, due to sharing several pathophysiological features. Additionally, CMTs have a strong genetic correlation with their human counterpart, including the expression of microRNAs (miRNAs). MiRNAs are a class of non-coding RNAs that play important roles in post-translational regulation of gene expression, being implicated in carcinogenesis, tumor progression, and metastasis. Moreover, miRNAs hold promise as diagnostic, prognostic, and metastatic biomarkers. Understanding the molecular mechanisms underlying CMTs is crucial for improving diagnosis, prognosis, and monitoring of treatments. Herein, we provide a comprehensive overview of the current knowledge on miRNAs in CMTs, highlighting their roles in carcinogenesis and their potential as biomarkers. Additionally, we highlight the current limitations and critically discuss the overarching challenges in this field, emphasizing the need for future research to translate miRNA findings into veterinary clinical practice. [ABSTRACT FROM AUTHOR]

Birds and bats have long lifespans relative to their body size compared with non-flying animals. However, the genomic basis associated with longer lifespan of flying species despite their higher metabolism was unclear. In this study, we hypothesized that genes involved in the regulation of metabolism and lifespan changed with the acquisition of flight and searched for genes that show specific evolutionary patterns in flying species. As a result, we identified several genes that show different evolutionary rates in bird and bat lineages. Genes in pathways involved in lifespan regulation were conserved in birds, while they evolved at an accelerated rate in bats. We also searched for genes in which convergent amino acid substitutions occurred in birds and bats and found such substitutions in genes involved in cancer, reactive oxygen species control and immunity. Our study revealed genomic changes associated with the acquisition of flight in birds and bats and suggested that multiple genes involved in the regulation of lifespan and metabolism support both high metabolism and longevity in flying species. [ABSTRACT FROM AUTHOR]

In organisms with complex life cycles, life stages that are most susceptible to environmental stress may determine species persistence in the face of climate change. Early embryos of Drosophila melanogaster are particularly sensitive to acute heat stress, yet tropical embryos have higher heat tolerance than temperate embryos, suggesting adaptive variation in embryonic heat tolerance. We compared transcriptomic responses to heat stress among tropical and temperate embryos to elucidate the gene regulatory basis of divergence in embryonic heat tolerance. The transcriptomes of tropical and temperate embryos differed in both constitutive and heat-stress-induced responses of the expression of relatively few genes, including genes involved in oxidative stress. Most of the transcriptomic response to heat stress was shared among all embryos. Embryos shifted the expression of thousands of genes, including increases in the expression of heat shock genes, suggesting robust zygotic gene activation and demonstrating that, contrary to previous reports, early embryos are not transcriptionally silent. The involvement of oxidative stress genes corroborates recent reports on the critical role of redox homeostasis in coordinating developmental transitions. By characterizing adaptive variation in the transcriptomic basis of embryonic heat tolerance, this study is a novel contribution to the literature on developmental physiology and developmental genetics. [ABSTRACT FROM AUTHOR]

Irreversibility, in which a transient perturbation leaves a system in a new state, is an emergent property in systems of interacting entities. This property has well-established implications in statistical physics but remains underexplored in biological networks, especially for bacteria and other prokaryotes whose regulation of gene expression occurs predominantly at the transcriptional level. Focusing on the reconstructed regulatory network of Escherichia coli, we examine network responses to transient single-gene perturbations. We predict irreversibility in numerous cases and find that the incidence of irreversibility increases with the proximity of the perturbed gene to positive circuits in the network. Comparison with experimental data suggests a connection between the predicted irreversibility to transient perturbations and the evolutionary response to permanent perturbations. [ABSTRACT FROM AUTHOR]

The INO80D protein, a component of the INO80 chromatin remodeling complex, plays a pivotal role in chromatin remodeling, gene expression, and DNA repair within mammalian sperm. In contrast to the condensed nuclear structure of mammalian sperm, Chinese mitten crab, Eriocheir sinensis, exhibits a distinctively decondensed sperm nucleus. The distribution and function of INO80D during the E. sinensis spermatogenesis were previously enigmatic. Our research endeavored to elucidate the distribution and function of INO80D, thereby enhancing our comprehension of sperm decondensation and the process of spermatogenesis in this species. Employing transcriptome sequencing, RT-qPCR, western blot analysis, and immunofluorescence techniques, we observed a pronounced upregulation of INO80D in the adult E. sinensis in comparison to the juvenile. The protein predominantly resides in the cellular nucleus, with high levels in spermatogonia and spermatocytes, less in stage I and III spermatids, and lowest in mature sperm. The results indicated that INO80D is initially instrumental in chromatin decondensation to facilitate gene accessibility and DNA repair during the early phases of spermatogenesis. Its role subsequently shifts to maintaining decondensed chromatin stability and genetic integrity during spermiogenesis. The sustained presence of INO80D during spermiogenesis is essential for the ultimate maturation of the decondensed sperm nucleus, imperative for preserving the unique decondensed state and the protection of genetic material in E. sinensis. Our study concludes that INO80D exerts a multifaceted influence on the spermatogenesis of E. sinensis, impacting chromatin decondensation, genetic integrity, and the regulation of early gene expression. This understanding could potentially improve crab breeding in aquaculture. [ABSTRACT FROM AUTHOR]

Gene expression levels in rice (Oryza sativa L.) and other plant species are determined by the promoters, which directly control phenotypic characteristics. As essential components of genes, promoters regulate the intensity, location, and timing of gene expression. They contain numerous regulatory elements and serve as binding sites for proteins that modulate transcription, including transcription factors and RNA polymerases. Genome editing can alter promoter sequences, thereby precisely modifying the expression patterns of specific genes, and ultimately affecting the morphology, quality, and resistance of rice. This paper summarizes research on rice promoter editing conducted in recent years, focusing on improvements in yield, heading date, quality, and disease resistance. It is expected to inform the application of promoter editing and encourage further research and development in crop genetic improvement with promote. [ABSTRACT FROM AUTHOR]

AbstractSuper-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed RUNX1expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC50s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying RUNX1 mutations. In the present study, we demonstrated that IC50s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes c-MYC expression. We showed that RUNX1 expression is regulated via SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL. [ABSTRACT FROM AUTHOR]

Increased knowledge of heritable traits in Atlantic Salmon (Salmo salar) is important to overcome bottlenecks in salmonid aquaculture. Atlantic salmonid populations, both landlocked and anadromous, represent an interesting model to gain insight into anadromy related traits, most notably, the probability to smoltify. While a previous study has identified several genomic regions diverging between anadromous and landlocked populations across the species range, the present study explores these data further with the aim to uncover if some of these genomic regions are linked to beneficial genetic traits associated with smoltification. In this study 17 of these loci were monitored in 669 anadromous salmon originating from 36 full-sibling families that had been reared under common garden conditions. The Smolt Index was calculated, using multiple visual markers, and provided a means of assessing smoltification stage. One SNP, located in Ssa04, showed a significant association with probability to smoltify, where individuals homozygous for the landlocked variant (LL) displayed a decrease in probability of smoltifying after one winter when compared with the homozygous for the anadromous variant (AA). This effect was independent of individual fish size. A separate common garden study comprising 200 individuals from either anadromous or landlocked strains showed that expression levels of ncor1, a thyroid mediator hormone located on the same chromosomal region (Ssa04), were significantly reduced in landlocked individuals post smoltification but remained constant in their anadromous counterparts. This study therefore suggests that while size is still the most important trigger for the induction of smoltification, there may also be an additional genetic component or trigger that has been 'lost' during the years deprived of SW transfer. In conclusion, the LL genotype identified here could potentially be used by the industry to delay smoltification and may also represent one of the first clues to the genetic regulation of smoltification in Atlantic salmon. [ABSTRACT FROM AUTHOR]

The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D: IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer's disease, notably apolipoprotein-e. Using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 (ZBP1) as a target of IRF3 that is relevant across various neuroinflammatory disorders. Lastly, we show IRF3 phosphorylation and IRF3-dependent ZBP1 induction in response to Aβ in primary microglia cultures. Together, our results identify IRF3 as an important regulator of LPS and Aβ -mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

The REQUIRED FOR ARBUSCULAR MYCORRHIZATION1 (RAM1) transcription factor from the GRAS family is well known for its role as a master regulator of the arbuscular mycorrhizal (AM) symbiosis in dicotyledonous and monocotyledonous species, being essential in transcriptional reprogramming for the development and functionality of the arbuscules. In tomato, SlGRAS27 is the putative orthologue of RAM1 (here named SlRAM1), but has not yet been characterized. A reduced colonization of the root and impaired arbuscule formation were observed in SlRAM1 -silenced plants, confirming the functional conservation of the RAM1 orthologue in tomato. However, unexpectedly, SlRAM1 -overexpressing (UBIL:SlRAM1) plants also showed decreased mycorrhizal colonization. Analysis of non-mycorrhizal UBIL:SlRAM1 roots revealed an overall regulation of AM-related genes and a reduction of strigolactone biosynthesis. Moreover, external application of the strigolactone analogue GR244DO almost completely reversed the negative effects of SlRAM1 overexpression on the frequency of mycorrhization. However, it only partially recovered the pattern of arbuscule distribution observed in control plants. Our results strongly suggest that SlRAM1 has a dual regulatory role during mycorrhization and, in addition to its recognized action as a positive regulator of arbuscule development, it is also involved in different mechanisms for the negative regulation of mycorrhization, including the repression of strigolactone biosynthesis. [ABSTRACT FROM AUTHOR]

TFEB and TFE3 (TFEB/3), key regulators of lysosomal biogenesis and autophagy, play diverse roles depending on cell type. This study highlights a hitherto unrecognized role of TFEB/3 crucial for peripheral nerve repair. Specifically, they promote the generation of progenitor-like repair Schwann cells after axonal injury. In Schwann cell-specific TFEB/3 double knock-out mice of either sex, the TFEB/3 loss disrupts the transcriptomic reprogramming that is essential for the formation of repair Schwann cells. Consequently, mutant mice fail to populate the injured nerve with repair Schwann cells and exhibit defects in axon regrowth, target reinnervation, and functional recovery. TFEB/3 deficiency inhibits the expression of injury-responsive repair Schwann cell genes, despite the continued expression of c-jun, a previously identified regulator of repair Schwann cell function. TFEB/3 binding motifs are enriched in the enhancer regions of injury-responsive genes, suggesting their role in repair gene activation. Autophagy-dependent myelin breakdown is not impaired despite TFEB/3 deficiency. These findings underscore a unique role of TFEB/3 in adult Schwann cells that is required for proper peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Background: The yield of major crops is generally limited by sink capacity and source strength. Cucumber is a typical raffinose family oligosaccharides (RFOs)–transporting crop. Non-coding RNAs and alternative polyadenylation (APA) play important roles in the regulation of growth process in plants. However, their roles on the sink‒source regulation have not been demonstrated in RFOs–translocating species. Results: Here, whole–transcriptome sequencing was applied to compare the leaves of cucumber under different sink strength, that is, no fruit-carrying leaves (NFNLs) and fruit-carrying leaves (FNLs) at 12th node from the bottom. The results show that 1101 differentially expressed (DE) mRNAs, 79 DE long non–coding RNAs (lncRNAs) and 23 DE miRNAs were identified, which were enriched in photosynthesis, energy production and conversion, plant hormone signal transduction, starch and carbohydrate metabolism and protein synthesis pathways. Potential co–expression networks like, DE lncRNAs–DE mRNAs/ DE miRNAs–DE mRNAs, and competing endogenous RNA (ceRNA) regulation models (DE lncRNAs–DE miRNAs–DE mRNAs) associated with sink‒source allocation, were constructed. Furthermore, 37 and 48 DE genes, which enriched in MAPK signaling and plant hormone signal transduction pathway, exist differentially APA, and SPS (CsaV3_2G033300), GBSS1 (CsaV3_5G001560), ERS1 (CsaV3_7G029600), PNO1 (CsaV3_3G003950) and Myb (CsaV3_3G022290) may be regulated by both ncRNAs and APA between FNLs and NFNLs, speculating that ncRNAs and APA are involved in the regulation of gene expression of cucumber sink‒source carbon partitioning. Conclusions: These results reveal a comprehensive network among mRNAs, ncRNAs, and APA in cucumber sink–source relationships. Our findings also provide valuable information for further research on the molecular mechanism of ncRNA and APA to enhance cucumber yield. [ABSTRACT FROM AUTHOR]

Fragile X Syndrome (FXS) is a genetic neurodevelopmental disorder closely associated with intellectual disability and autism spectrum disorders. The core of the disease lies in the abnormal expansion of the CGG trinucleotide repeat sequence at the 5'end of the FMR1 gene. When the repetition exceeds 200 times, it causes the silencing of the FMR1 gene, leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). Although the detailed mechanism by which the CGG repeat expansion triggers gene silencing is yet to be fully elucidated, it is known that this process does not alter the promoter region or the coding sequence of the FMR1 gene. This discovery provides a scientific basis for the potential reversal of FMR1 gene silencing through interventional approaches, thereby improving the symptoms of FXS. Epigenetics, a mechanism of genetic regulation that does not depend on changes in the DNA sequence, has become a new focus in FXS research by modulating gene expression in a reversible manner. The latest progress in molecular genetics has revealed that epigenetics plays a key role in the pathogenesis and pathophysiological processes of FXS. This article compiles the existing research findings on the role of epigenetics in Fragile X Syndrome (FXS) with the aim of deepening the understanding of the pathogenesis of FXS to identify potential targets for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Rhodnius prolixus is a hematophagous insect and one of the main vectors for Trypanosoma cruzi and Trypanosoma rangeli parasites in Latin America. Gut microbiota and insect immune responses affect T. cruzi and T. rangeli infection within triatomines. Particularly the Toll and IMD signaling pathways activations and how they orchestrate the antimicrobial peptides (AMPs) expressions in R. prolixus, especially when infected by T. rangeli. Objectives: Examine how T. rangeli infection modulates R. prolixus cellular and humoral immunity and its impacts on insect microbiota. Methods: R. prolixus was fed on blood containing epimastigotes of T. rangeli, and infection was quantified in insect tissues. The gene expression of dorsal, cactus, relish, PGRP, and AMPs was examined in the midgut, fat body, and salivary glands by quantitative real-time PCR. Microbiota composition was analyzed using RT-q PCR targeting specific bacterial species. Hemocyte numbers and phenoloxidase activity were quantified to assess cellular immune responses. Results: T. rangeli infection modulated triatomine immunity in midgut and hemocoel, activating the expression of the NF-kB gene dorsal, associated with the Toll pathway; increasing expression of the gene encoding PGRP receptor, a component involved in the IMD pathway, both in the intestine and fat body; repressing the expression of the relish transcription factor, mainly in salivary glands. Among the R. prolixus AMPs studied, T. rangeli infection repressed all AMP gene expression, other than defensin Cwhich increasedmRNA levels. The PO activity was enhanced in the hemolymph of infected insects. T. rangeli infection did not induce hemocyte number alterations compared to control insects. However, an increase in hemocyte microaggregation was detected in infected insects. Discussion: R. prolixus recognizes T. rangeli infection and triggers humoral and cellular immune responses involving Toll pathway activation, defensin C synthesis, increased phenoloxidase activity, and enhanced hemocyte aggregation. On the other hand, T. rangeli infection suppressed some IMD pathway components, suggesting that, in R. prolixus, this pathway is involved in defensins A and B gene regulation. Importantly, these immune responses altered the bacterial microbiota composition, potentially favoring T. rangeli establishment in the insect vector. [ABSTRACT FROM AUTHOR]

Background: The chestnut blight fungus, Cryphonectria parasitica, and its Cryphonectria hypovirus 1 (CHV1) comprise a useful model system to study fungus–virus interactions. CHV1 infection results in various phenotypic changes in the fungal host, including hypovirulence and other associated symptoms. Many studies have investigated the effects of hypoviral infection and how this infection affects physiological and biochemical states: however, no studies have examined volatile organic compounds (VOCs). Results: This study characterized the global profile of VOCs released from C. parasitica, and by comparing CHV1-free with CHV1-infected isogenic strains, proved that CHV1 infection significantly affects the composition and levels of VOCs. We demonstrated that these VOC alterations were caused by viral regulation of the expression of fungal genes encoding enzymes responsible for the production of VOCs. The changed VOC profile resulting from CHV1 infection was more attractive to insects than the VOC profile from the virus-free strain, suggesting differences in the efficacy of fungal dissemination by the insect vector. Conclusions: We characterized VOCs from C. parasitica and demonstrated that mycovirus (CHV1) infection affects fungal VOCs. We provided evidences that these alterations are caused by the modulation of the corresponding gene expression by CHV1 and resulted in changes in attractiveness to insects, suggesting the improved efficacy of hypovirulent C. parasitica for insect-borne dissemination. [ABSTRACT FROM AUTHOR]

Introduction: Osteoclasts determine bone tissue turnover. Their increased activity causes osteoporosis, their dysfunction osteopetrosis. Methods and Results: Murine monocytic ER-Hoxb8 cells differentiate into OCs upon treatment with M-CSF and RANKL and upregulate the collagen-binding integrin α2β1 distinctly earlier than other OC markers, such as the OC-associated receptor, OSCAR. Integrin α2β1 promotes OC differentiation at multiple levels by stimulating differentiation-relevant genes, by regulating cell matrix adhesion and the formation of adhesion-promoting protrusions, and by the upregulation of proteins involved in precursor cell fusion. The two key factors in osteoclastogenesis, RANK and NFATc1, were essentially unaffected after knocking out the ITGA2 gene encoding integrin α2 subunit. However, compared to integrin α2β1 expressing ER-Hoxb8 cells, ITGA2-deficient cells adhered differently with more branched filopodia and significantly longer tunneling nanotubes. Despite the higher number of fusion-relevant TNTs, they form fewer syncytia. They also resorb less hydroxyapatite, because integrin α2β1 regulates expression of lacuna proteins necessary for bone matrix resorption. The impaired syncytia formation of ITGA2-deficient OC precursor cells also correlated with reduced gene activation of fusion-supporting DC-STAMP and with an almost abolished transcription of tetraspanin CD9. CD9 only partially colocalized with integrin α2β1 in TNTs and filopodia of integrin α2β1-expressing OC precursors. [ABSTRACT FROM AUTHOR]