Front Plant Sci. 2023 Sep 28;14:1291893. doi: 10.3389/fpls.2023.1291893. eCollection 2023.

NO ABSTRACT

PMID:37841616 | PMC:PMC10575755 | DOI:10.3389/fpls.2023.1291893

Front Plant Sci. 2023 Sep 27;14:1282443. doi: 10.3389/fpls.2023.1282443. eCollection 2023.

ABSTRACT

[This corrects the article DOI: 10.3389/fpls.2023.1158933.].

PMID:37841599 | PMC:PMC10569685 | DOI:10.3389/fpls.2023.1282443

iScience. 2023 Sep 22;26(10):107999. doi: 10.1016/j.isci.2023.107999. eCollection 2023 Oct 20.

ABSTRACT

Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific intestinal microbial circadian rhythms in host metabolism using germ-free and conventionalized mice and manipulation of dietary-derived fat, fiber, and microbiota-accessible carbohydrates. Our findings demonstrate that sex differences in circadian rhythms of genes involved in immunity and metabolism depend on oscillations in microbiota, microbial metabolic functions, and microbial metabolites. Further, we show that consuming an obesogenic, high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. Our results reveal that microbial circadian rhythms contribute to sex differences in immunity and metabolism and that dietary factors can entrain new circadian rhythms and modify the magnitude of sex differences in host-microbe circadian dynamics.

PMID:37841582 | PMC:PMC10568425 | DOI:10.1016/j.isci.2023.107999

Onco (Basel). 2022 Jun;2(2):129-144. doi: 10.3390/onco2020009. Epub 2022 Jun 17.

ABSTRACT

Whole genome sequencing (WGS) has helped to revolutionize biology, but the computational challenge remains for extracting valuable inferences from this information. Here, we present the cancer-associated variants from the Cancer Genome Atlas (TCGA) WGS dataset. This set of data will allow cancer researchers to further expand their analysis beyond the exomic regions of the genome to the entire genome. A total of 1342 WGS alignments available from the consortium were processed with VarScan2 and deposited to the NCI Cancer Cloud. The sample set covers 18 different cancers and reveals 157,313,519 pooled (non-unique) cancer-associated single-nucleotide variations (SNVs) across all samples. There was an average of 117,223 SNVs per sample, with a range from 1111 to 775,470 and a standard deviation of 163,273. The dataset was incorporated into BigQuery, which allows for fast access and cross-mapping, which will allow researchers to enrich their current studies with a plethora of newly available genomic data.

PMID:37841494 | PMC:PMC10571071 | DOI:10.3390/onco2020009

Front Vet Sci. 2023 Sep 29;10:1207950. doi: 10.3389/fvets.2023.1207950. eCollection 2023.

ABSTRACT

Yaks are tough animals living in Tibet's hypoxic stress environment. However, the metabolite composition of yak milk and its role in hypoxic stress tolerance remains largely unexplored. The similarities and differences between yak and human milk in hypoxic stress tolerance are also unclear. This study explored yak colostrum (YC) and yak mature milk (YMM) using GC-MS, and 354 metabolites were identified in yak milk. A comparative metabolomic analysis of yak and human milk metabolites showed that over 70% of metabolites were species-specific. Yak milk relies mainly on essential amino acids- arginine and essential branched-chain amino acids (BCAAs): L-isoleucine, L-leucine, and L-valine tolerate hypoxic stress. To slow hypoxic stress, human breast milk relies primarily on the neuroprotective effects of non-essential amino acids or derivates, such as citrulline, sarcosine, and creatine. In addition, metabolites related to hypoxic stress were significantly enriched in YC than in YMM. These results reveal the unique metabolite composition of yak and human milk and provide practical information for applying yak and human milk to hypoxic stress tolerance.

PMID:37841471 | PMC:PMC10570732 | DOI:10.3389/fvets.2023.1207950

Comput Struct Biotechnol J. 2023 Sep 26;21:4777-4789. doi: 10.1016/j.csbj.2023.09.032. eCollection 2023.

ABSTRACT

Small molecules derived from gut microbiota have been increasingly investigated to better understand the functional roles of the human gut microbiome. Microbial metabolites of aromatic amino acids (AAA) have been linked to many diseases, such as metabolic disorders, chronic kidney diseases, inflammatory bowel disease, diabetes, and cancer. Important microbial AAA metabolites are often discovered via global metabolite profiling of biological specimens collected from humans or animal models. Subsequent metabolite identity confirmation and absolute quantification using targeted analysis enable comparisons across different studies, which can lead to the establishment of threshold concentrations of potential metabolite biomarkers. Owing to their excellent selectivity and sensitivity, hyphenated mass spectrometry (MS) techniques are often employed to identify and quantify AAA metabolites in various biological matrices. Here, we summarize the developments over the past five years in MS-based methodology for analyzing gut microbiota-derived AAA. Sample preparation, method validation, analytical performance, and statistical methods for correlation analysis are discussed, along with future perspectives.

PMID:37841334 | PMC:PMC10570628 | DOI:10.1016/j.csbj.2023.09.032

Comput Struct Biotechnol J. 2023 Oct 3;21:4647-4662. doi: 10.1016/j.csbj.2023.09.043. eCollection 2023.

ABSTRACT

Many Bacillus species are essential antibacterial agents, but their antibiosis potential still needs to be elucidated to its full extent. Here, we isolated a soil bacterium, BP9, which has significant antibiosis activity against fungal and bacterial pathogens. BP9 improved the growth of wheat seedlings via active colonization and demonstrated effective biofilm and swarming activity. BP9 sequenced genome contains 4282 genes with a mean G-C content of 45.94% of the whole genome. A single copy concatenated 802 core genes of 28 genomes, and their calculated average nucleotide identity (ANI) discriminated the strain BP9 from Bacillus licheniformis and classified it as Bacillus paralicheniformis. Furthermore, a comparative pan-genome analysis of 40 B. paralicheniformis strains suggested that the genetic repertoire of BP9 belongs to open-type genome species. A comparative analysis of a pan-genome dataset using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Gene groups (COG) revealed the diversity of secondary metabolic pathways, where BP9 distinguishes itself by exhibiting a greater prevalence of loci associated with the metabolism and transportation of organic and inorganic substances, carbohydrate and amino acid for effective inhabitation in diverse environments. The primary secondary metabolites and their genes involved in synthesizing bacillibactin, fencing, bacitracin, and lantibiotics were identified as acquired through a recent Horizontal gene transfer (HGT) event, which contributes to a significant part of the strain`s antimicrobial potential. Finally, we report some genes essential for plant-host interaction identified in BP9, which reduce spore germination and virulence of multiple fungal and bacterial species. The effective colonization, diverse predicted metabolic pathways and secondary metabolites (antibiotics) suggest testing the suitability of strain BP9 as a potential bio-preparation in agricultural fields.

PMID:37841331 | PMC:PMC10568305 | DOI:10.1016/j.csbj.2023.09.043

Chem Mater. 2023 Sep 29;35(19):7957-7966. doi: 10.1021/acs.chemmater.3c01172. eCollection 2023 Oct 10.

ABSTRACT

Ferrofluids have been extensively employed in industrial, environmental, and biomedical areas. Among them, fluorous ferrofluids are of particular interest because of the biorthogonal nature of perfluorocarbons (PFCs). However, the noninteracting nature of PFCs as well as challenges in functionalization of nanoparticle surfaces with fluorous ligands has limited their applications, especially in biomedicine. In particular, commercially available fluorous ferrofluids are stabilized using ionic surfactants with charged groups that physically interact with a wide range of charged biological molecules. In this paper, we developed a unique two-phase ligand attachment strategy to render stable fluorous ferrofluids using nonionic surfactants. The superparamagnetic Fe3O4 or MnFe2O4 core of the magnetic nanoparticles, the magnetic component of the ferrofluid, was coated with a silica shell containing abundant surface hydroxyl groups, thereby enabling the installation of fluorous ligands through stable covalent, neutral, siloxane bonds. We explored chemistry-material relationships between different ligands and PFC solvents and found that low-molecular-weight ligands can assist with the installation of high-molecular-weight ligands (4000-8000 g/mol), allowing us to systematically control the size and thickness of ligand functionalization on the nanoparticle surface. By zero-field-cooled magnetization measurements, we studied how the ligands affect magnetic dipole orientation forces and observed a curve flattening that is only associated with the ferrofluids. This work provided insight into ferrofluids' dependence on interparticle interactions and contributed a methodology to synthesize fluorous ferrofluids with nonionic surfactants that exhibit both magnetic and chemical stability. We believe that the doped MnFe2O4 fluorous ferrofluid has the highest combination of stability and magnetization reported to date.

PMID:37840777 | PMC:PMC10569041 | DOI:10.1021/acs.chemmater.3c01172

Front Microbiol. 2023 Sep 29;14:1272734. doi: 10.3389/fmicb.2023.1272734. eCollection 2023.

ABSTRACT

INTRODUCTION: Staphylococcus capitis naturally colonizes the human skin but as an opportunistic pathogen, it can also cause biofilm-associated infections and bloodstream infections in newborns. Previously, we found that two strains from the subspecies S. capitis subsp. capitis produce yellow carotenoids despite the initial species description, reporting this subspecies as non-pigmented. In Staphylococcus aureus, the golden pigment staphyloxanthin is an important virulence factor, protecting cells against reactive oxygen species and modulating membrane fluidity.

METHODS: In this study, we used two pigmented (DSM 111179 and DSM 113836) and two non-pigmented S. capitis subsp. capitis strains (DSM 20326T and DSM 31028) to identify the pigment, determine conditions under which pigment-production occurs and investigate whether pigmented strains show increased resistance to ROS and temperature stress.

RESULTS: We found that the non-pigmented strains remained colorless regardless of the type of medium, whereas intensity of pigmentation in the two pigmented strains increased under low nutrient conditions and with longer incubation times. We were able to detect and identify staphyloxanthin and its derivates in the two pigmented strains but found that methanol cell extracts from all four strains showed ROS scavenging activity regardless of staphyloxanthin production. Increased survival to cold temperatures (-20°C) was detected in the two pigmented strains only after long-term storage compared to the non-pigmented strains.

CONCLUSION: The identification of staphyloxanthin in S. capitis is of clinical relevance and could be used, in the same way as in S. aureus, as a possible target for anti-virulence drug design.

PMID:37840735 | PMC:PMC10570620 | DOI:10.3389/fmicb.2023.1272734

Trends Analyt Chem. 2023 Nov;168:117300. doi: 10.1016/j.trac.2023.117300. Epub 2023 Sep 20.

ABSTRACT

Metabolic assays serve as pivotal tools in biomedical research, offering keen insights into cellular physiological and pathological states. While mass spectrometry (MS)-based metabolomics remains the gold standard for comprehensive, multiplexed analyses of cellular metabolites, innovative technologies are now emerging for the targeted, quantitative scrutiny of metabolites and metabolic pathways at the single-cell level. In this review, we elucidate an array of these advanced methodologies, spanning synthetic and surface chemistry techniques, imaging-based methods, and electrochemical approaches. We summarize the rationale, design principles, and practical applications for each method, and underscore the synergistic benefits of integrating single-cell metabolomics (scMet) with other single-cell omics technologies. Concluding, we identify prevailing challenges in the targeted scMet arena and offer a forward-looking commentary on future avenues and opportunities in this rapidly evolving field.

PMID:37840599 | PMC:PMC10569257 | DOI:10.1016/j.trac.2023.117300

J Alzheimers Dis. 2023 Oct 6. doi: 10.3233/JAD-230403. Online ahead of print.

ABSTRACT

BACKGROUND: Comprehensive treatment of Alzheimer's disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. Personalized, multimodal therapies are needed to best prevent and treat Alzheimer's disease (AD).

OBJECTIVE: The Coaching for Cognition in Alzheimer's (COCOA) trial was a prospective randomized controlled trial to test the hypothesis that a remotely coached multimodal lifestyle intervention would improve early-stage AD.

METHODS: Participants with early-stage AD were randomized into two arms. Arm 1 (N = 24) received standard of care. Arm 2 (N = 31) additionally received telephonic personalized coaching for multiple lifestyle interventions. The primary outcome was a test of the hypothesis that the Memory Performance Index (MPI) change over time would be better in the intervention arm than in the control arm. The Functional Assessment Staging Test was assessed for a secondary outcome. COCOA collected psychometric, clinical, lifestyle, genomic, proteomic, metabolomic, and microbiome data at multiple timepoints (dynamic dense data) across two years for each participant.

RESULTS: The intervention arm ameliorated 2.1 [1.0] MPI points (mean [SD], p = 0.016) compared to the control over the two-year intervention. No important adverse events or side effects were observed.

CONCLUSION: Multimodal lifestyle interventions are effective for ameliorating cognitive decline and have a larger effect size than pharmacological interventions. Dietary changes and exercise are likely to be beneficial components of multimodal interventions in many individuals. Remote coaching is an effective intervention for early stage ADRD. Remote interventions were effective during the COVID pandemic.

PMID:37840487 | DOI:10.3233/JAD-230403

Trends Plant Sci. 2023 Oct 13:S1360-1385(23)00307-2. doi: 10.1016/j.tplants.2023.09.014. Online ahead of print.

ABSTRACT

The European Commission (EC) recently published a legislative proposal that hints at a science-based approach to the regulation of genome-editing applications in crops in the EU. This would be in line with legislation in an increasing number of countries worldwide, but further science-based advice on implementation will be essential.

PMID:37839926 | DOI:10.1016/j.tplants.2023.09.014

Mol Cell Proteomics. 2023 Oct 13:100666. doi: 10.1016/j.mcpro.2023.100666. Online ahead of print.

ABSTRACT

The application of integrated systems biology to the field of structural biology is a promising new direction, although it is still in the infant stages of development. Here we report the use of single particle cryo-electron microscopy (cryo-EM) to identify multiple proteins from three enriched heterogeneous fractions prepared from human liver mitochondrial lysate. We simultaneously identify and solve high-resolution structures of nine essential mitochondrial enzymes with key metabolic functions, including fatty acid catabolism, reactive oxidative species clearance and amino acid metabolism. Our methodology also identified multiple distinct members of the acyl-CoA dehydrogenase family. This work highlights the potential of cryo-EM to explore tissue proteomics at the atomic level.

PMID:37839702 | DOI:10.1016/j.mcpro.2023.100666

J Plant Physiol. 2023 Oct 7;290:154116. doi: 10.1016/j.jplph.2023.154116. Online ahead of print.

ABSTRACT

A plant's genome encodes enzymes, transporters and many other proteins which constitute metabolism. Interactions of plants with their environment shape their growth, development and resilience towards adverse conditions. Although genome sequencing technologies and applications have experienced triumphantly rapid development during the last decades, enabling nowadays a fast and cheap sequencing of full genomes, prediction of metabolic phenotypes from genotype × environment interactions remains, at best, very incomplete. The main reasons are a lack of understanding of how different levels of molecular organisation depend on each other, and how they are constituted and expressed within a setup of growth conditions. Phenotypic plasticity, e.g., of the genetic model plant Arabidopsis thaliana, has provided important insights into plant-environment interactions and the resulting genotype x phenotype relationships. Here, we summarize previous and current findings about plant development in a changing environment and how this might be shaped and reflected in metabolism and its regulation. We identify current challenges in the study of plant development and metabolic regulation and provide an outlook of how methodological workflows might support the application of findings made in model systems to crops and their cultivation.

PMID:37839392 | DOI:10.1016/j.jplph.2023.154116

Biophys J. 2023 Oct 13:S0006-3495(23)00649-5. doi: 10.1016/j.bpj.2023.10.013. Online ahead of print.

ABSTRACT

The immune response is orchestrated by elaborate protein interaction networks that interweave ligand-mediated receptor reorganization with signaling cascades. While the biochemical processes have been extensively investigated, delineating the biophysical principles governing immune receptor activation has remained challenging due to design limitations of traditional ligand display platforms. These constraints have been overcome by advances in DNA origami nanotechnology, enabling unprecedented control over ligand geometry on configurable scaffolds. It is now possible to systematically dissect the independent roles of ligand stoichiometry, spatial distribution, and rigidity in immune receptor activation, signaling, and cooperativity. In this review, we highlight pioneering efforts in manipulating the ligand presentation landscape to understand immune receptor triggering and to engineer functional immune responses.

PMID:37838832 | DOI:10.1016/j.bpj.2023.10.013

Cell Biosci. 2023 Oct 14;13(1):191. doi: 10.1186/s13578-023-01141-0.

ABSTRACT

BACKGROUND: c-Jun is a proto-oncogene functioning as a transcription factor to activate gene expression under many physiological and pathological conditions, particularly in somatic cells. However, its role in early embryonic development remains unknown.

RESULTS: Here, we show that c-Jun acts as a one-way valve to preserve the primed state and impair reversion to the naïve state. c-Jun is induced during the naive to primed transition, and it works to stabilize the chromatin structure and inhibit the reverse transition. Loss of c-Jun has surprisingly little effect on the naïve to primed transition, and no phenotypic effect on primed cells, however, in primed cells the loss of c-Jun leads to a failure to correctly close naïve-specific enhancers. When the primed cells are induced to reprogram to a naïve state, these enhancers are more rapidly activated when c-Jun is lost or impaired, and the conversion is more efficient.

CONCLUSIONS: The results of this study indicate that c-Jun can function as a chromatin stabilizer in primed EpiSCs, to maintain the epigenetic cell type state and act as a one-way valve for cell fate conversions.

PMID:37838693 | DOI:10.1186/s13578-023-01141-0

Trends Plant Sci. 2023 Oct 12:S1360-1385(23)00334-5. doi: 10.1016/j.tplants.2023.10.007. Online ahead of print.

ABSTRACT

Wood is an abundant and renewable feedstock for pulping and biorefining, but the aromatic polymer lignin greatly limits its efficient use. Sulis et al. recently reported a multiplex CRISPR editing strategy targeting multiple lignin biosynthetic genes to achieve combined lignin modifications, improve wood properties, and make pulping more sustainable.

PMID:37838517 | DOI:10.1016/j.tplants.2023.10.007

Radiother Oncol. 2023 Oct 12:109951. doi: 10.1016/j.radonc.2023.109951. Online ahead of print.

ABSTRACT

Radiotherapy is a widely used treatment modality against cancer, and although survival rates are increasing, radioresistant properties of tumours remain a significant barrier for curative treatment. Tumour hypoxia is one of the main contributors to radioresistance and is common in most solid tumours. Hypoxia is responsible for many molecular changes within the cell which helps tumours to survive under such challenging conditions. These hypoxia-induced molecular changes are predominantly coordinated by the hypoxia inducible factor (HIF) and have been linked with the ability to confer resistance to radiation-induced cell death. To overcome this obstacle research has been directed towards autophagy, a cellular process involved in self degradation and recycling of macromolecules, as HIF plays a large role in its coordination under hypoxic conditions. The role that autophagy has following radiotherapy treatment is conflicted with evidence of both cytoprotective and cytotoxic effects. This literature review aims to explore the intricate relationship between radiotherapy, hypoxia, and autophagy in the context of cancer treatment. It provides valuable insights into the potential of targeting autophagy as a therapeutic strategy to improve the response of hypoxic tumours to radiotherapy.

PMID:37838322 | DOI:10.1016/j.radonc.2023.109951

Diagnostics (Basel). 2023 Sep 25;13(19):3038. doi: 10.3390/diagnostics13193038.

ABSTRACT

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases.

PMID:37835781 | DOI:10.3390/diagnostics13193038

Cancers (Basel). 2023 Oct 6;15(19):4870. doi: 10.3390/cancers15194870.

ABSTRACT

A wide panel of microtubule-associated proteins and kinases is involved in coordinated regulation of the microtubule cytoskeleton and may thus represent valuable molecular markers contributing to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that are differentially expressed in breast tumors showing resistance to taxane-based chemotherapy. In the present study, we evaluated the expression, prognostic value and functional impact of these genes in breast cancer. We show that 14 MT-Rel genes (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B, KIFC1, AURKB, KIF2C, GTSE1, KIF15, KIF11, RACGAP1, STMN1) are up-regulated in breast tumors compared with adjacent normal tissue. Six of them (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B) are overexpressed by more than 10-fold in tumor samples and four of them (KIF11, AURKB, TPX2 and KIFC1) are essential for cell survival. Overexpression of all 14 genes, and underexpression of 3 other MT-Rel genes (MAST4, MAPT and MTUS1) are associated with poor breast cancer patient survival. A Systems Biology approach highlighted three major functional networks connecting the 17 MT-Rel genes and their partners, which are centered on spindle assembly, chromosome segregation and cytokinesis. Our studies identified mitotic Aurora kinases and their substrates as major targets for therapeutic approaches against breast cancer.

PMID:37835564 | DOI:10.3390/cancers15194870