Nat Commun. 2023 Oct 3;14(1):6157. doi: 10.1038/s41467-023-41924-0.

ABSTRACT

BTR1 (SLC4A11) is a NH3 stimulated H+ (OH-) transporter belonging to the SLC4 family. Dysfunction of BTR1 leads to diseases such as congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy (FECD). However, the mechanistic basis of BTR1 activation by alkaline pH, transport activity regulation and pathogenic mutations remains elusive. Here, we present cryo-EM structures of human BTR1 in the outward-facing state in complex with its activating ligands PIP2 and the inward-facing state with the pathogenic R125H mutation. We reveal that PIP2 binds at the interface between the transmembrane domain and the N-terminal cytosolic domain of BTR1. Disruption of either the PIP2 binding site or protonation of PIP2 phosphate groups by acidic pH can transform BTR1 into an inward-facing conformation. Our results provide insights into the mechanisms of how the transport activity and conformation changes of BTR1 are regulated by PIP2 binding and interaction of TMD and NTD.

PMID:37788993 | DOI:10.1038/s41467-023-41924-0

Cold Spring Harb Perspect Biol. 2023 Oct 3:a041673. doi: 10.1101/cshperspect.a041673. Online ahead of print.

ABSTRACT

One of the greatest threats facing the planet is the continued increase in excess greenhouse gasses, with CO2 being the primary driver due to its rapid increase in only a century. Excess CO2 is exacerbating known climate tipping points that will have cascading local and global effects including loss of biodiversity, global warming, and climate migration. However, global reduction of CO2 emissions is not enough. Carbon dioxide removal (CDR) will also be needed to avoid the catastrophic effects of global warming. Although the drawdown and storage of CO2 occur naturally via the coupling of the silicate and carbonate cycles, they operate over geological timescales (thousands of years). Here, we suggest that microbes can be used to accelerate this process, perhaps by orders of magnitude, while simultaneously producing potentially valuable by-products. This could provide both a sustainable pathway for global drawdown of CO2 and an environmentally benign biosynthesis of materials. We discuss several different approaches, all of which involve enhancing the rate of silicate weathering. We use the silicate mineral olivine as a case study because of its favorable weathering properties, global abundance, and growing interest in CDR applications. Extensive research is needed to determine both the upper limit of the rate of silicate dissolution and its potential to economically scale to draw down significant amounts (Mt/Gt) of CO2 Other industrial processes have successfully cultivated microbial consortia to provide valuable services at scale (e.g., wastewater treatment, anaerobic digestion, fermentation), and we argue that similar economies of scale could be achieved from this research.

PMID:37788887 | DOI:10.1101/cshperspect.a041673

Cell Rep Methods. 2023 Sep 26:100601. doi: 10.1016/j.crmeth.2023.100601. Online ahead of print.

ABSTRACT

Advances in high-throughput sequencing technologies have facilitated the large-scale characterization of B cell receptor (BCR) repertoires. However, the vast amount and high diversity of the BCR sequences pose challenges for efficient and biologically meaningful analysis. Here, we introduce fastBCR, an efficient computational approach for inferring B cell clonal families from massive BCR heavy chain sequences. We demonstrate that fastBCR substantially reduces the running time while ensuring high accuracy on simulated datasets with diverse numbers of B cell lineages and varying mutation rates. We apply fastBCR to real BCR sequencing data from peripheral blood samples of COVID-19 patients, showing that the inferred clonal families display disease-associated features, as well as corresponding antigen-binding specificity and affinity. Overall, our results demonstrate the advantages of fastBCR for analyzing BCR repertoire data, which will facilitate the identification of disease-associated antibodies and improve our understanding of the B cell immune response.

PMID:37788671 | DOI:10.1016/j.crmeth.2023.100601

Plant J. 2023 Oct 3. doi: 10.1111/tpj.16483. Online ahead of print.

ABSTRACT

Gene regulatory networks (GRNs) represent the interactions between transcription factors (TF) and their target genes. Plant GRNs control transcriptional programs involved in growth, development, and stress responses, ultimately affecting diverse agricultural traits. While recent developments in accessible chromatin (AC) profiling technologies make it possible to identify context-specific regulatory DNA, learning the underlying GRNs remains a major challenge. We developed MINI-AC (Motif-Informed Network Inference based on Accessible Chromatin), a method that combines AC data from bulk or single-cell experiments with TF binding site (TFBS) information to learn GRNs in plants. We benchmarked MINI-AC using bulk AC datasets from different Arabidopsis thaliana tissues and showed that it outperforms other methods to identify correct TFBS. In maize, a crop with a complex genome and abundant distal AC regions, MINI-AC successfully inferred leaf GRNs with experimentally confirmed, both proximal and distal, TF-target gene interactions. Furthermore, we showed that both AC regions and footprints are valid alternatives to infer AC-based GRNs with MINI-AC. Finally, we combined MINI-AC predictions from bulk and single-cell AC datasets to identify general and cell-type specific maize leaf regulators. Focusing on C4 metabolism, we identified diverse regulatory interactions in specialized cell types for this photosynthetic pathway. MINI-AC represents a powerful tool for inferring accurate AC-derived GRNs in plants and identifying known and novel candidate regulators, improving our understanding of gene regulation in plants.

PMID:37788349 | DOI:10.1111/tpj.16483

Proc Natl Acad Sci U S A. 2023 Oct 10;120(41):e2305451120. doi: 10.1073/pnas.2305451120. Epub 2023 Oct 3.

ABSTRACT

In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multiscale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing. Considering SARS-CoV-2 as a case study, we quantify the within-host dynamics using data from individuals with omicron variant infections. We demonstrate that regular antigen testing reduces, but may not eliminate, the outbreak risk, depending on characteristics of local transmission. In our baseline analysis, daily antigen testing reduces the outbreak risk by 45% compared to a scenario without antigen testing. Additionally, we show that accounting for heterogeneity in within-host dynamics between individuals affects outbreak risk estimates and assessments of the impact of antigen testing. Our results therefore highlight important factors to consider when using multiscale models to design pre-emptive interventions against SARS-CoV-2 and other viruses.

PMID:37788317 | DOI:10.1073/pnas.2305451120

Proc Natl Acad Sci U S A. 2023 Oct 10;120(41):e2307289120. doi: 10.1073/pnas.2307289120. Epub 2023 Oct 3.

ABSTRACT

The importance of whole-genome duplication (WGD) for evolution is controversial. Whereas some view WGD mainly as detrimental and an evolutionary dead end, there is growing evidence that polyploidization can help overcome environmental change, stressful conditions, or periods of extinction. However, despite much research, the mechanistic underpinnings of why and how polyploids might be able to outcompete or outlive nonpolyploids at times of environmental upheaval remain elusive, especially for autopolyploids, in which heterosis effects are limited. On the longer term, WGD might increase both mutational and environmental robustness due to redundancy and increased genetic variation, but on the short-or even immediate-term, selective advantages of WGDs are harder to explain. Here, by duplicating artificially generated Gene Regulatory Networks (GRNs), we show that duplicated GRNs-and thus duplicated genomes-show higher signal output variation than nonduplicated GRNs. This increased variation leads to niche expansion and can provide polyploid populations with substantial advantages to survive environmental turmoil. In contrast, under stable environments, GRNs might be maladaptive to changes, a phenomenon that is exacerbated in duplicated GRNs. We believe that these results provide insights into how genome duplication and (auto)polyploidy might help organisms to adapt quickly to novel conditions and to survive ecological uproar or even cataclysmic events.

PMID:37788315 | DOI:10.1073/pnas.2307289120

STAR Protoc. 2023 Oct 2;4(4):102623. doi: 10.1016/j.xpro.2023.102623. Online ahead of print.

ABSTRACT

In internal fertilization animals, maintaining a copulation posture facilitates the process of transporting gametes from male to female. Here, we present a protocol to investigate the neural basis for copulation posture of fruit flies using a closed-loop real-time optogenetic system. We describe steps for using deep learning analysis to enable optogenetic manipulation of neural activity only during copulation with high efficiency. This system can be applied to various animal behaviors other than copulation. For complete details on the use and execution of this protocol, please refer to Yamanouchi et al. (2023).1.

PMID:37788165 | DOI:10.1016/j.xpro.2023.102623

Proteomics Clin Appl. 2023 Oct 3:e2200054. doi: 10.1002/prca.202200054. Online ahead of print.

ABSTRACT

AIM: Hypoxic Ischemic Encephalopathy (HIE) is one of the principal causes of neonatal mortality and long-term morbidity worldwide. The neonatal signs of mild cerebral injury are subtle, making an early precise diagnosis difficult. Delayed detection, poor prognosis, and lack of specific biomarkers for the disease are increasing mortality rates. In this study, we intended to identify specific biomarkers using comparative proteomic analysis to predict the severity of perinatal asphyxia so that its outcome can also be prevented.

EXPERIMENTAL DESIGN: A case-control study was conducted on 38 neonates, and urine samples were collected within 24 and 72 h of life. A tandem mass spectrometry-based quantitative proteomics approach, followed by validation via sandwich ELISA, was performed.

RESULTS: The LC-MS/MS-based proteomics analysis resulted in the identification of 1201 proteins in urine, with 229, 244, and 426 being differentially expressed in HIE-1, HIE-2, and HIE-3, respectively. Axon guidance, Diseases of programmed cell death, and Detoxification of reactive oxygen species pathways were significantly enriched in mild HIE versus severe HIE. Among the differentially expressed proteins in various stages of HIE, we chose to validate four proteins - APP, AGT, FABP1, and FN1 - via sandwich ELISA. Individual and cumulative ROC curves were plotted. AGT and FABP1 together showed high sensitivity, specificity, and accuracy as potential biomarkers for early diagnosis of HIE.

CONCLUSION: Establishing putative urinary biomarkers will facilitate clinicians to more accurately screen neonates for brain injury and monitor the disease progression. Prompt treatment of neonates may reduce mortality and neurodevelopmental impairment.

PMID:37787895 | DOI:10.1002/prca.202200054

Elife. 2023 Oct 3;12:RP88229. doi: 10.7554/eLife.88229.

ABSTRACT

Many proteins remain poorly characterized even in well-studied organisms, presenting a bottleneck for research. We applied phenomics and machine-learning approaches with Schizosaccharomyces pombe for broad cues on protein functions. We assayed colony-growth phenotypes to measure the fitness of deletion mutants for 3509 non-essential genes in 131 conditions with different nutrients, drugs, and stresses. These analyses exposed phenotypes for 3492 mutants, including 124 mutants of 'priority unstudied' proteins conserved in humans, providing varied functional clues. For example, over 900 proteins were newly implicated in the resistance to oxidative stress. Phenotype-correlation networks suggested roles for poorly characterized proteins through 'guilt by association' with known proteins. For complementary functional insights, we predicted Gene Ontology (GO) terms using machine learning methods exploiting protein-network and protein-homology data (NET-FF). We obtained 56,594 high-scoring GO predictions, of which 22,060 also featured high information content. Our phenotype-correlation data and NET-FF predictions showed a strong concordance with existing PomBase GO annotations and protein networks, with integrated analyses revealing 1675 novel GO predictions for 783 genes, including 47 predictions for 23 priority unstudied proteins. Experimental validation identified new proteins involved in cellular aging, showing that these predictions and phenomics data provide a rich resource to uncover new protein functions.

PMID:37787768 | DOI:10.7554/eLife.88229

Elife. 2023 Oct 3;12:e91997. doi: 10.7554/eLife.91997. Online ahead of print.

ABSTRACT

Eukaryotic genes are interrupted by introns that are removed from transcribed RNAs by splicing. Patterns of splicing complexity differ between species, but it is unclear how these differences arise. We used inter-species association mapping with Saccharomycotina species to correlate splicing signal phenotypes with the presence or absence of splicing factors. Here we show that variation in 5' splice site sequence preferences correlate with the presence of the U6 snRNA N6-methyladenosine methyltransferase METTL16 and the splicing factor SNRNP27K. The greatest variation in 5' splice site sequence occurred at the +4 position and involved a preference switch between adenosine and uridine. Loss of METTL16 and SNRNP27K orthologs, or a single SNRNP27K methionine residue, was associated with a preference for +4U. These findings are consistent with splicing analyses of mutants defective in either METTL16 or SNRNP27K orthologs and models derived from spliceosome structures, demonstrating that inter-species association mapping is a powerful orthogonal approach to molecular studies. We identified variation between species in the occurrence of two major classes of 5' splice sites, defined by distinct interaction potentials with U5 and U6 snRNAs, that correlates with intron number. We conclude that variation in concerted processes of 5' splice site selection by U6 snRNA is associated with evolutionary changes in splicing signal phenotypes.

PMID:37787376 | DOI:10.7554/eLife.91997

Mol Carcinog. 2023 Oct 3. doi: 10.1002/mc.23628. Online ahead of print.

ABSTRACT

An anticancer drug known as Rapamycin acts by inhibiting the mammalian target of the Rapamycin pathway. This agent has recently been investigated for its potential therapeutic benefits in sensitizing drug-resistant breast cancer (BC) treatment. The molecular mechanism underlying these effects, however, is still a mystery. Using a systems biology method and in vitro experiment, this study sought to discover essential genes and microRNAs (miRNAs) targeted by Rapamycin in triple-negative BC (TNBC) cells to aid prospective new medications with less adverse effects in BC treatment. We developed the transcription factor-miRNA-gene and protein-protein interaction networks using the freely accessible microarray data sets. FANMOD and MCODE were utilized to identify critical regulatory motifs, clusters, and seeds. Then, functional enrichment analyses were conducted. Using topological analysis and motif detection, the most important genes and miRNAs were discovered. We used quantitative real-time polymerase chain reaction (qRT-PCR) to examine the effect of Rapamycin on the expression of the selected genes and miRNAs to verify our findings. We performed flow cytometry to investigate Rapamycin's impact on cell cycle and apoptosis. Furthermore, wound healing and migration assays were done. Three downregulated (PTGS2, EGFR, VEGFA) and three upregulated (c-MYC, MAPK1, PIK3R1) genes were chosen as candidates for additional experimental verification. There were also three upregulated miRNAs (miR-92a, miR-16, miR-20a) and three downregulated miRNAs (miR-146a, miR-145, miR-27a) among the six selected miRNAs. The qRT-PCR findings in MDA-MB-231 cells indicated that c-MYC, MAPK1, PIK3R1, miR-92a, miR-16, and miR-20a expression levels were considerably elevated following Rapamycin treatment, whereas PTGS2, EGFR, VEGFA, miR-146a, and miR-145 expression levels were dramatically lowered (p < 0.05). These genes are engaged in cancer pathways, transcriptional dysregulation in cancer, and cell cycle, according to the top pathway enrichment findings. Migration and wound healing abilities of the cells declined after Rapamycin treatment, and the number of apoptotic cells increased. We demonstrated that Rapamycin suppresses cell migration and metastasis in the TNBC cell line. In addition, our data indicated that Rapamycin induces apoptosis in this cell line. The discovered vital genes and miRNAs affected by Rapamycin are anticipated to have crucial roles in the pathogenesis of TNBC and its therapeutic resistance.

PMID:37787375 | DOI:10.1002/mc.23628

New Phytol. 2023 Oct 3. doi: 10.1111/nph.19292. Online ahead of print.

ABSTRACT

Upon exposure to light, etiolated Arabidopsis seedlings form adventitious roots (AR) along the hypocotyl. While processes underlying lateral root formation are studied intensively, comparatively little is known about the molecular processes involved in the initiation of hypocotyl AR. AR and LR formation were studied using a small molecule named Hypocotyl Specific Adventitious Root INducer (HYSPARIN) that strongly induces AR but not LR formation. HYSPARIN does not trigger rapid DR5-reporter activation, DII-Venus degradation or Ca2+ signalling. Transcriptome analysis, auxin signalling reporter lines and mutants show that HYSPARIN AR induction involves nuclear TIR1/AFB and plasma membrane TMK auxin signalling, as well as multiple downstream LR development genes (SHY2/IAA3, PUCHI, MAKR4 and GATA23). Comparison of the AR and LR induction transcriptome identified SAURs, AGC kinases and OFP transcription factors as specifically upregulated by HYSPARIN. Members of the SAUR19 subfamily, OFP4 and AGC2 suppress HYS-induced AR formation. While SAUR19 and OFP subfamily members also mildly modulate LR formation, AGC2 regulates only AR induction. Analysis of HYSPARIN-induced AR formation uncovers an evolutionary conservation of auxin signalling controlling LR and AR induction in Arabidopsis seedlings and identifies SAUR19, OFP4 and AGC2 kinase as novel regulators of AR formation.

PMID:37787103 | DOI:10.1111/nph.19292

Exp Biol Med (Maywood). 2023 Oct 3:15353702231191195. doi: 10.1177/15353702231191195. Online ahead of print.

ABSTRACT

Chronic liver disease is one of the most common diseases worldwide, and its prevalence is particularly high among adults aged 40-60 years; it takes a toll on productivity and causes significant economic burden. However, there are still no effective treatments that can fundamentally treat chronic liver disease. Although liver transplantation is considered the only effective treatment for chronic liver disease, it has limitations in that the pool of available donors is vastly insufficient for the number of potential recipients. Even if a patient undergoes liver transplantation, side effects such as immune rejection or bile duct complications could occur. In addition, impaired liver regeneration due to various causes, such as aging and metabolic disorders, may cause liver failure after liver resection, even leading to death. Therefore, further research on the liver regeneration process and therapeutic strategies to improve liver regeneration are needed. In this review, we describe the process of liver regeneration after hepatectomy, focusing on various cytokines and signaling pathways. In addition, we review treatment strategies that have been studied to date to improve liver regeneration, such as promotion of hepatocyte proliferation and metabolism and transplantation of mesenchymal stem cells. This review helps to understand the physiological processes involved in liver regeneration and provides basic knowledge for developing treatments for successful liver regeneration.

PMID:37786387 | DOI:10.1177/15353702231191195

Gene. 2023 Sep 30:147865. doi: 10.1016/j.gene.2023.147865. Online ahead of print.

ABSTRACT

Clostridium botulinum Loch Maree expresses an extremely potent botulinum neurotoxin subtype, A3 causing botulism and several gastrointestinal disorders in mammals. Several recombinant vaccines have been developed for human botulism and no vaccine is currently available for the treatment of diseases caused by other virulence factors. Hence, we designed, constructed, and characterized a multi-epitope vaccine from new virulence proteins identified from this organism using an immunoinformatics approach. The vaccine construct used in this study was designed from 6 B cell linear epitopes, 12 cytotoxic T cell lymphocyte epitopes, and 15 helper T cell lymphocyte epitopes, with a defensin adjuvant and adjusting linker sequences. A molecular modeling approach was used to model, refine, and validate the 3D structure of the vaccine construct. Molecular docking studies were performed to determine the stability of the molecular interactions between the vaccine construct and human toll-like receptor 7. The in silico molecular cloning was used to clone a codon-optimized synthetic vaccine gene in pCYB1 vector and expressed in Escherichia coli. The results of this study identified six new virulence proteins: peptidoglycan hydrolase, SCP-like extracellular protein, N-acetylmuramoyl-l-alanine amidase, putative membrane protein, drug/metabolite exporter, and bacillolysin. The top B-cell, cytotoxic T-cell lymphocyte, and helper T-lymphocyte epitopes were predicted from these virulence proteins with greater accuracy and reliability. HLA-A*02:01 and HLA-A*03:01 were identified as HLA-A-binding alleles for cytotoxic T-cell lymphocyte epitopes. DRB1*0110 and DRB1*0115 are the dominant alleles that bind to helper T-cell lymphocyte epitopes. The synthetic gene construct was highly expressed in a heterologous host and produced considerable amounts of antigenic protein. The multi-epitope vaccine is more conservative in the sequence-structure-function link, immunogenic with less allergenicity, and possibly provokes cellular and humoral immunity. The present study suggests that the designed multi-epitope vaccine is a promising prophylactic candidate for the virulence and intoxication caused by subtype A3 strains.

PMID:37783297 | DOI:10.1016/j.gene.2023.147865

Life Sci. 2023 Sep 30:122139. doi: 10.1016/j.lfs.2023.122139. Online ahead of print.

ABSTRACT

AIMS: Pain is a profoundly debilitating symptom in cancer patients, leading to disability, immobility, and a marked decline in their quality of life. This study aimed to investigate the potential roles of miR-199a-3p in a murine model of bone cancer pain induced by tumor cell implantation in the medullary cavity of the femur.

MATERIALS AND METHODS: We assessed pain-related behaviors, including the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF). To investigate miRNA expression and its targets in astrocytes, we employed a combination of RNA-seq analysis, qRT-PCR, Western blotting, EdU, TUNEL, ChIP, ELISA, and luciferase reporter assays in mice (C3H/HeJ) with bone cancer pain and control groups.

KEY FINDINGS: On days 10, 14, 21, and 28 post-surgery, we observed significant differences in PWTL, PWMT, and NSF when compared to the sham group (P < 0.001). qRT-PCR assays and miRNA sequencing results confirmed reduced miR-199a-3p expression in astrocytes of mice with bone cancer pain. Gain- and loss-of-function experiments demonstrated that miR-199a-3p suppressed astrocyte activation and the expression of inflammatory cytokines. In vitro investigations revealed that miR-199a-3p mimics reduced the levels of inflammatory factors in astrocytes and MyD88/NF-κB proteins. Furthermore, treatment with a miR-199a-3p agonist resulted in reduced expression of MyD88, TAK1, p-p65, and inflammatory mediators, along with decreased astrocyte activation in the spinal cord.

SIGNIFICANCE: Collectively, these findings demonstrate that upregulation of miR-199a-3p may offer a therapeutic avenue for mitigating bone cancer pain in mice by suppressing neuroinflammation and inhibiting the MyD88/NF-κB signaling pathway.

PMID:37783266 | DOI:10.1016/j.lfs.2023.122139

Nature. 2023 Oct 2. doi: 10.1038/s41586-023-06665-6. Online ahead of print.

ABSTRACT

Argonaute (Ago) mediates RNA or DNA guided inhibition of nucleic acids1,2. Although the mechanisms underlying eukaryotic (eAgos) and long prokaryotic Ago (pAgos) proteins are known, that of short pAgos remains elusive. Here, we determined cryo-EM structures of short pAgo and the associated TIR-APAZ proteins (SPARTA) from Crenotalea thermophila (Crt): a free-state Crt-SPARTA (3.27 Å), a guide RNA / target DNA loaded Crt-SPARTA (3.27 Å), two Crt-SPARTA dimers with distinct TIR organization (3.49 Å and 3.50 Å), and a Crt-SPARTA tetramer (3.41 Å). These structures reveal that the Crt-SPARTA is composed of a bilobal-fold Ago lobe connecting with a TIR lobe. Whereas the Crt-Ago harbors a MID and a PIWI domains, Crt-TIR-APAZ harbors a TIR, a N-like, a Linker and a Trigger domains. The bound RNA/DNA duplex adopts a B-form conformation that is recognized by base-specific contacts. Nucleic acid binding causes conformational changes because the Trigger acts as a roadblock preventing the guide RNA 5'- and the target DNA 3'-ends from reaching their canonical pockets, which disorders the MID domain and promotes Crt-SPARTA dimerization. Two RNA/DNA-loaded Crt-SPARTA dimers form a tetramer through their TIR domains. Four Crt-TIR assemble into two parallel, head-to-tail TIR organization, indicating a NADase-active conformation, which is supported by our mutagenesis study. Our results reveal the structural basis of short pAgos in defensing invading nucleic acids and provide insights for optimizing SPARTA-based programmable DNA sequences detection.

PMID:37783228 | DOI:10.1038/s41586-023-06665-6

Nat Microbiol. 2023 Oct 2. doi: 10.1038/s41564-023-01484-x. Online ahead of print.

ABSTRACT

Microbiome data, metadata and analytical workflows have become 'big' in terms of volume and complexity. Although the infrastructure and technologies to share data have been established, the interdisciplinary and multi-omic nature of the field can make resources difficult to identify and use. Following best practices for data deposition requires substantial effort, with sometimes little obvious reward. Gaps remain where microbiome-specific resources for data sharing or reproducibility do not yet exist. We outline available best practices, challenges to their adoption and opportunities in data sharing in microbiome research. We showcase examples of best practices and advocate for their enforcement and incentivization for data sharing. This includes recognition of data curation and sharing endeavours by individuals, institutions, journals and funders. Opportunities for progress include enabling microbiome-specific databases to incorporate future methods for data analysis, integration and reuse.

PMID:37783751 | DOI:10.1038/s41564-023-01484-x

Sci Rep. 2023 Oct 2;13(1):16544. doi: 10.1038/s41598-023-43541-9.

ABSTRACT

In the last one-hundred years, the exponential expansion of wine making has artificialized the agricultural landscape as well as its microbial diversity, spreading human selected Saccharomyces cerevisiae strains. Evidence showed that social wasps can harbor a significant fraction of the yeast phenotypic diversity of a given area of wine production, allowing different strains to overwinter and mate in their gut. The integrity of the wasp-yeast ecological interaction is of paramount importance to maintain the resilience of microbial populations associated to wine aromatic profiles. In a field experiment, we verified whether Polistes dominula wasps, reared in laboratory and fed with a traceable S. cerevisiae strain, could be a useful tool to drive the controlled yeast dispersion directly on grapes. The demonstration of the biotechnological potential of social insects in organic wine farming lays the foundations for multiple applications including maintenance of microbial biodiversity and rewilding vineyards through the introduction of wasp associated microbiomes.

PMID:37783736 | DOI:10.1038/s41598-023-43541-9

Curr Opin Cell Biol. 2023 Sep 30;85:102246. doi: 10.1016/j.ceb.2023.102246. Online ahead of print.

ABSTRACT

Vimentin is a cytoskeletal protein important for many cellular processes, including proliferation, migration, invasion, stress resistance, signaling, and many more. The vimentin-deficient mouse has revealed many of these functions as it has numerous severe phenotypes, many of which are found only following a suitable challenge or stress. While these functions are usually related to vimentin as a major intracellular protein, vimentin is also emerging as an extracellular protein, exposed at the cell surface in an oligomeric form or secreted to the extracellular environment in soluble and vesicle-bound forms. Thus, this review explores the roles of the extracellular pool of vimentin (eVIM), identified in both normal and pathological states. It focuses specifically on the recent advances regarding the role of eVIM in wound healing and cancer. Finally, it discusses new technologies and future perspectives for the clinical application of eVIM.

PMID:37783033 | DOI:10.1016/j.ceb.2023.102246

PLoS Comput Biol. 2023 Oct 2;19(10):e1011536. doi: 10.1371/journal.pcbi.1011536. Online ahead of print.

ABSTRACT

How the locus-specificity of epigenetic modifications is regulated remains an unanswered question. A contributing mechanism is that epigenetic enzymes are recruited to specific loci by DNA binding factors recognizing particular sequence motifs (referred to as epi-motifs). Using these motifs to predict biological outputs depending on local epigenetic state such as somatic mutation rates would confirm their functionality. Here, we used DNA motifs including known TF motifs and epi-motifs as a surrogate of epigenetic signals to predict somatic mutation rates in 13 cancers at an average 23kbp resolution. We implemented an interpretable neural network model, called contextual regression, to successfully learn the universal relationship between mutations and DNA motifs, and uncovered motifs that are most impactful on the regional mutation rates such as TP53 and epi-motifs associated with H3K9me3. Furthermore, we identified genomic regions with significantly higher mutation rates than the expected values in each individual tumor and demonstrated that such cancer-related regions can accurately predict cancer types. Interestingly, we found that the same mutation signatures often have different contributions to cancer-related and cancer-independent regions, and we also identified the motifs with the most contribution to each mutation signature.

PMID:37782656 | DOI:10.1371/journal.pcbi.1011536