ACS Omega. 2023 Aug 22;8(35):31698-31713. doi: 10.1021/acsomega.3c01909. eCollection 2023 Sep 5.

ABSTRACT

Nipah virus (NiV) is a zoonotic virus that causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. Several NiV outbreaks have been reported since 1999 with nearly annual occurrences in Bangladesh. The outbreaks had high mortality rates ranging from 40 to 90%. No specific vaccine has yet been reported against NiV. Recently, several vaccine candidates and different designs of vaccines composed of epitopes against NiV were proposed. Most of the vaccines target single protein or protein complex subunits of the pathogen. The multiepitope vaccines proposed also cover a largely limited number of epitopes, and hence, their efficiency is still uncertain. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have utilized the "reverse epitomics" approach ("overlapping-epitope-clusters-to-patches" method) to identify "antigenic patches" (Ag-Patches) and utilize them as immunogenic composition for multipatch vaccine (MPV) design. The designed MPVs were analyzed for immunologically crucial parameters, physiochemical properties, and interaction with Toll-like receptor 3 ectodomain. In total, 30 CTL (cytotoxic T lymphocyte) and 27 HTL (helper T lymphocyte) antigenic patches were identified from the entire NiV proteome based on the clusters of overlapping epitopes. These identified Ag-Patches cover a total of discrete 362 CTL and 414 HTL epitopes from the entire proteome of NiV. The antigenic patches were utilized as immunogenic composition for the design of two CTL and two HTL multipatch vaccines. The 57 antigenic patches utilized here cover 776 overlapping epitopes targeting 52 different HLA class I and II alleles, providing a global ethnically distributed human population coverage of 99.71%. Such large number of epitope coverage resulting in large human population coverage cannot be reached with single-protein/subunit or multiepitope based vaccines. The reported antigenic patches also provide potential immunogenic composition for early detection diagnostic kits for NiV infection. Further, all the MPVs and Toll-like receptor ectodomain complexes show a stable nature of molecular interaction with numerous hydrogen bonds, salt bridges, and nonbounded contact formation and acceptable root mean square deviation and fluctuation. The cDNA analysis shows a favorable large-scale expression of the MPV constructs in a human cell line. By utilizing the novel "reverse epitomics" approach, highly immunogenic novel "GaEl antigenic patches" (GaEl Ag-Patches), a synonym term for "antigenic patches", were identified and utilized as immunogenic composition to design four MPVs against NiV. We conclude that the novel multipatch vaccines are potential candidates to combat NiV, with greater effectiveness, high specificity, and large human population coverage worldwide.

PMID:37692250 | PMC:PMC10483669 | DOI:10.1021/acsomega.3c01909

Hortic Res. 2023 Jul 19;10(9):uhad147. doi: 10.1093/hr/uhad147. eCollection 2023 Sep.

ABSTRACT

MicroTom has a short growth cycle and high transformation efficiency, and is a prospective model plant for studying organ development, metabolism, and plant-microbe interactions. Here, with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments, we constructed multiple gene co-expression networks, which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth, e.g. arbuscular mycorrhizal symbiosis and fruit development. Additionally, non-coding RNAs, including miRNAs, lncRNAs, and circRNAs were also identified, together with their potential targets. Interacting networks between different types of non-coding RNAs (miRNA-lncRNA), and non-coding RNAs and genes (miRNA-mRNA and lncRNA-mRNA) were constructed as well. Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit. Lastly, we established a database (http://eplant.njau.edu.cn/microTomBase/) with genomic and transcriptomic data, as well as details of gene co-expression and interacting networks on MicroTom, and this database should be of great value to those who want to adopt MicroTom as a model plant for research.

PMID:37691964 | PMC:PMC10483172 | DOI:10.1093/hr/uhad147

Transl Lung Cancer Res. 2023 Aug 30;12(8):1738-1751. doi: 10.21037/tlcr-23-137. Epub 2023 Aug 16.

ABSTRACT

BACKGROUND: High-grade fetal adenocarcinoma of the lung (H-FLAC) is a rare variant of pulmonary adenocarcinoma. Our previous study showed a high frequency of KMT2C mutations in lung cancers with an H-FLAC component, showing that KMT2C dysfunction may be associated with the biological features of H-FLACs.

METHODS: In this study, we performed RNA sequencing and immunohistochemical analysis to identify the differentially expressed genes and corresponding pathways associated with H-FLACs, compared with common adenocarcinomas.

RESULTS: Ingenuity pathway analysis based on RNA sequencing data revealed that DNA homologous recombination repair (HRR) pathways were significantly inactivated in H-FLAC. Expression of KMT2C, ATM, ATR, and BRCA2 was significantly lower in H-FLACs than in common adenocarcinomas, and BRCA1 expression showed a decreasing trend. Pearson correlation analyses for all cases revealed that KMT2C expression showed a strong positive correlation (R>0.7) with the expression of ATR, BRCA1, and BRCA2 genes and a moderately positive correlation with ATM expression (R=0.47). Immunohistochemical analysis showed significantly lower levels of KMT2C, ATM, ATR, and BRCA2 expression in H-FLACs than in common adenocarcinomas, and a trend of lower BRCA1 levels. Additionally, KMT2C expression showed a weak to moderate correlation with that of ATM, ATR, BRCA1, and BRCA2.

CONCLUSIONS: Cancers containing H-FLAC components showed lower levels of KMT2C and HRR factors than common lung adenocarcinomas, and their levels exhibited a positive correlation. These results support the hypothesis that loss of KMT2C function decreases the expression of the HRR factors in H-FLACs. H-FLACs with low KMT2C expression may be a good indication for poly (ADP-ribose) polymerase (PARP) inhibitor-based therapy.

PMID:37691868 | PMC:PMC10483084 | DOI:10.21037/tlcr-23-137

Front Cell Dev Biol. 2023 Aug 25;11:1268540. doi: 10.3389/fcell.2023.1268540. eCollection 2023.

ABSTRACT

Organoids are three-dimensional structures derived from stem cells that mimic the organization and function of specific organs, making them valuable tools for studying complex systems in biology. This paper explores the application of complex systems theory to understand and characterize organoids as exemplars of intricate biological systems. By identifying and analyzing common design principles observed across diverse natural, technological, and social complex systems, we can gain insights into the underlying mechanisms governing organoid behavior and function. This review outlines general design principles found in complex systems and demonstrates how these principles manifest within organoids. By acknowledging organoids as representations of complex systems, we can illuminate our understanding of their normal physiological behavior and gain valuable insights into the alterations that can lead to disease. Therefore, incorporating complex systems theory into the study of organoids may foster novel perspectives in biology and pave the way for new avenues of research and therapeutic interventions to improve human health and wellbeing.

PMID:37691827 | PMC:PMC10485618 | DOI:10.3389/fcell.2023.1268540

Cell Rep. 2023 Sep 7;42(9):113075. doi: 10.1016/j.celrep.2023.113075. Online ahead of print.

ABSTRACT

The capacity of animals to respond to hazardous stimuli in their surroundings is crucial for their survival. In mammals, complex evaluations of the environment require large numbers and different subtypes of neurons. The nematode C. elegans avoids hazardous chemicals they encounter by reversing their direction of movement. How does the worms' compact nervous system process the spatial information and direct motion change? We show here that a single interneuron, AVA, receives glutamatergic excitatory and inhibitory signals from head and tail sensory neurons, respectively. AVA integrates the spatially distinct and opposing cues, whose output instructs the animal's behavioral decision. We further find that the differential activation of AVA stems from distinct localization of inhibitory and excitatory glutamate-gated receptors along AVA's process and from different threshold sensitivities of the sensory neurons. Our results thus uncover a cellular mechanism that mediates spatial computation of nociceptive cues for efficient decision-making in C. elegans.

PMID:37691148 | DOI:10.1016/j.celrep.2023.113075

Proteomics. 2023 Sep 10:e2200289. doi: 10.1002/pmic.202200289. Online ahead of print.

ABSTRACT

Heart disease remains a leading cause of death in North America and worldwide. Despite advances in therapies, the chronic nature of cardiovascular diseases ultimately results in frequent hospitalizations and steady rates of mortality. Systems biology approaches have provided a new frontier toward unraveling the underlying mechanisms of cell, tissue, and organ dysfunction in disease. Mapping the complex networks of molecular functions across the genome, transcriptome, proteome, and metabolome has enormous potential to advance our understanding of cardiovascular disease, discover new disease biomarkers, and develop novel therapies. Computational workflows to interpret these data-intensive analyses as well as integration between different levels of interrogation remain important challenges in the advancement and application of systems biology-based analyses in cardiovascular research. This review will focus on summarizing the recent developments in network biology-level profiling in the heart, with particular emphasis on modeling of human heart failure. We will provide new perspectives on integration between different levels of large "omics" datasets, including integration of gene regulatory networks, protein-protein interactions, signaling networks, and metabolic networks in the heart.

PMID:37691071 | DOI:10.1002/pmic.202200289

Trends Genet. 2023 Sep 8:S0168-9525(23)00188-9. doi: 10.1016/j.tig.2023.08.006. Online ahead of print.

ABSTRACT

To date, genome structure and dynamics have been studied mostly independently; their interplay is a notable blind spot of the field. Brückner, Chen, et al. recently demonstrated an integrated experimental approach sensitive to both, uncovering a striking robustness of enhancer-promoter search times (dynamics) to changes in genomic separation (structure).

PMID:37690888 | DOI:10.1016/j.tig.2023.08.006

J Nutr. 2023 Sep 8:S0022-3166(23)72592-3. doi: 10.1016/j.tjnut.2023.09.002. Online ahead of print.

ABSTRACT

BACKGROUND: Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans.

AIMS: To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults.

METHODS: A randomized double-blind placebo-controlled trial allocated participants aged 18-30-years to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2g/day of ginger (four capsules per day totaling 84mg/day of active gingerols/shogaols) for 14-days following a 1-week run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events.

RESULTS: n=51 participants were enrolled and analyzed (71% female; mean age 25 [SD: 3] years; ginger: n=29, placebo: n=22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; Z: -2.1; p=0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (p<0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U:196.0; Z:-2.4; p=0.015). No differences between ginger and placebo groups were found for alpha and beta diversity nor other secondary outcomes. No moderate or severe adverse events were reported.

CONCLUSIONS: Supplementation with ginger root powder was safe and altered aspects of the gastrointestinal bacteria composition; however, did not change alpha- or beta-diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (reference: ACTRN12620000302954p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379178&isReview=true) and the Therapeutic Goods Administration (reference: CT-2020-CTN-00380-1).

PMID:37690779 | DOI:10.1016/j.tjnut.2023.09.002

J Dairy Sci. 2023 Sep 8:S0022-0302(23)00617-3. doi: 10.3168/jds.2022-22951. Online ahead of print.

ABSTRACT

The Resilient Dairy Genome Project (RDGP) is an international large-scale applied research project that aims to generate genomic tools to breed more resilient dairy cows. In this context, improving feed efficiency and reducing greenhouse gases from dairy is a high priority. The inclusion of traits related to feed efficiency (e.g., dry matter intake [DMI]) or greenhouse gases (e.g., methane emissions [CH4]) relies on available genotypes as well as high quality phenotypes. Currently, 7 countries, i.e., Australia [AUS], Canada [CAN], Denmark [DNK], Germany [DEU], Spain [ESP], Switzerland [CHE], and United States of America [USA] contribute with genotypes and phenotypes including DMI and CH4. However, combining data is challenging due to differences in recording protocols, measurement technology, genotyping, and animal management across sources. In this study, we provide an overview of how the RDGP partners address these issues to advance international collaboration to generate genomic tools for resilient dairy. Specifically, we describe the current state of the RDGP database, data collection protocols in each country, and the strategies used for managing the shared data. As of February 2022, the database contains 1,289,593 DMI records from 12,687 cows and 17,403 CH4 records from 3,093 cows and continues to grow as countries upload new data over the coming years. No strong genomic differentiation between the populations was identified in this study, which may be beneficial for eventual across-country genomic predictions. Moreover, our results reinforce the need to account for the heterogeneity in the DMI and CH4 phenotypes in genomic analysis.

PMID:37690718 | DOI:10.3168/jds.2022-22951

J Infect. 2023 Sep 8:S0163-4453(23)00506-6. doi: 10.1016/j.jinf.2023.09.004. Online ahead of print.

ABSTRACT

Lung inflammation indicated by 18F-labeled fluorodeoxyglucose (FDG) in patients with tuberculosis is associated with disease severity and relapse risk upon treatment completion. We revealed the heterogeneity and intercellular crosstalk in lung tissues with 18F-FDG avidity and adjacent uninvolved tissues from 6 tuberculosis patients by single-cell RNA-sequencing. Tuberculous lungs had an influx of regulatory T cells (Treg), exhausted CD8 T cells, immunosuppressive myeloid cells, conventional DC, plasmacytoid DC, and neutrophils. Immune cells in inflamed lungs showed general up-regulation of ATP synthesis and interferon-mediated signaling. Immunosuppressive myeloid and Treg cells strongly displayed transcriptions of genes related to tuberculosis disease progression. Intensive crosstalk between IL4I1-expressing myeloid cells and Treg cells involving chemokines, costimulatory molecules, and immune checkpoints, some of which being specific in 18F-FDG-avid lungs, were found. Our analysis provides insights into the transcriptomic heterogeneity and cellular crosstalk in pulmonary tuberculosis and guide unveiling cellular and molecular targets for tuberculosis therapy.

PMID:37690670 | DOI:10.1016/j.jinf.2023.09.004

Mol Cell Probes. 2023 Sep 8:101930. doi: 10.1016/j.mcp.2023.101930. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer (BC) has been identified as a significant contributor to the rising number of female cancer deaths. As, it has become clear that breast cancer development depends on the interplay of several biological factors against a single molecule. This research aimed to use proteomics to gain a regulatory and metabolic understanding of BC pathophysiology.

METHOD: For the study, a breast cancer proteomics dataset was downloaded from ProteomeXchange and then analyzed by employing MaxQuant and Perseus. Functional enrichment analysis through Metascape and Cytoscape software showed DEPs related biomedical phenomena with potential abruption. The expression of selected lncRNA in terms of the highest connectivity parameters was then quantitatively assessed through RT-PCR in 30 tumor tissues of breast cancer patients, as compared to the adjacent healthy ones.

RESULT: The results indicated that among the 3048 identified proteins, 1149 were differentially expressed, which could be mainly enriched in several key terms. Furthermore, the obtained findings revealed that ITGB1-DT was significantly overexpressed in tumor tissues. Moreover, we found five potential compounds that could be attributed to ITGB1-DT targets (ATN-161, Firategrast, SB-683698, dabigatran-etexilate, and tranexamic-acid).

CONCLUSION: These analyses proposed that ITGB1-DT could be employed as a differentiated factor to identify breast tumor tissues in healthy samples. Besides this, Firategrast could be introduced as a potential remedial agent for breast cancer patients. Overall, from the analysis of a proteomics dataset, an integrative map was generated, and a novel biomarker that may have been implicated in the early detection of BC was introduced.

PMID:37690573 | DOI:10.1016/j.mcp.2023.101930

Plant Physiol Biochem. 2023 Sep 6;203:108008. doi: 10.1016/j.plaphy.2023.108008. Online ahead of print.

ABSTRACT

Plants encounter combinations of different abiotic stresses such as salinity (S) and high light (HL). These environmental conditions have a detrimental effect on plant growth and development, posing a threat to agricultural production. Metabolic changes play a crucial role in enabling plants to adapt to fluctuations in their environment. Furthermore, hormones such as abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) have been previously identified as regulators of plant responses to different abiotic stresses. Here we studied the response of Arabidopsis wild type (Col and Ler) plants and mutants impaired in hormone biosynthesis (aba2-11 and aba1-1 in ABA, aos in JA and sid2 in SA) to the combination of S and HL (S + HL). Our findings showed that aba2-11 plants displayed reduced growth, impaired photosystem II (PSII) function, increased leaf damage, and decreased survival compared to Col when subjected to stress combination. However, aos and sid2 mutants did not display significant changes in response to S + HL compared to Col, indicating a key role for ABA in promoting plant tolerance to S + HL and suggesting a marginal role for JA and SA in this process. In addition, we revealed differences in the metabolic response of plants to S + HL compared to S or HL. The analysis of altered metabolic pathways under S + HL suggested that the accumulation of flavonoids is ABA-dependent, whereas the accumulation of branched-chain amino acids (BCAAs) and proline is ABA-independent. Therefore, our study uncovered a key function for ABA in regulating the accumulation of different flavonoids in plants during S + HL.

PMID:37690143 | DOI:10.1016/j.plaphy.2023.108008

J Neuroinflammation. 2023 Sep 9;20(1):206. doi: 10.1186/s12974-023-02867-x.

ABSTRACT

BACKGROUND: Retinal degeneration is a disease affecting the eye, which is an immune-privileged site because of its anatomical and physiological properties. Alterations in retinal homeostasis-because of injury, disease, or aging-initiate inflammatory cascades, where peripheral leukocytes (PL) infiltrate the parenchyma, leading to retinal degeneration. So far, research on PL's role in retinal degeneration was limited to observing a few cell types at specific times or sectioning the tissue. This restricted our understanding of immune cell interactions and response duration.

METHODS: In vivo microscopy in preclinical mouse models can overcome these limitations enabling the spatio-temporal characterization of PL dynamics. Through in vivo imaging, we assessed structural and fluorescence changes in response to a focal injury at a defined location over time. We also utilized minimally invasive techniques, pharmacological interventions, and knockout (KO) mice to determine the role of PL in local inflammation. Furthermore, we investigated PL abundance and localization during retinal degeneration in human eyes by histological analysis to assess to which extent our preclinical study translates to human retinal degeneration.

RESULTS: We demonstrate that PL, especially T cells, play a detrimental role during retinal injury response. In mice, we observed the recruitment of helper and cytotoxic T cells in the parenchyma post-injury, and T cells also resided in the macula and peripheral retina in pathological conditions in humans. Additionally, we found that the pharmacological PL reduction and genetic depletion of T-cells reduced injured areas in murine retinas and rescued the blood-retina barrier (BRB) integrity. Both conditions promoted morphological changes of Cx3cr1+ cells, including microglial cells, toward an amoeboid phenotype during injury response. Interestingly, selective depletion of CD8+ T cells accelerated recovery of the BRB compared to broader depletions. After anti-CD8 treatment, the retinal function improved, concomitant to a beneficial immune response.

CONCLUSIONS: Our data provide novel insights into the adaptive immune response to retinal injury in mice and human retinal degeneration. Such information is fundamental to understanding retinal disorders and developing therapeutics to modulate immune responses to retinal degeneration safely.

PMID:37689689 | DOI:10.1186/s12974-023-02867-x

Food Microbiol. 2023 Dec;116:104366. doi: 10.1016/j.fm.2023.104366. Epub 2023 Aug 25.

ABSTRACT

Sherry wines are film wines produced in the Jerez-Xérès-Sherry and Montilla-Moriles regions in southern Spain which require an aging process under flor biofilms, known as "biological aging". The presence of mites in Sherry wine wineries has been reported and associated with improved wine volatile properties. This work analyzes the microbial diversity in flor biofilms and mites in Sherry wine wineries using Matrix-Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) and ITS/gene amplification. Two mite species, Carpoglyphus lactis and Tyrophagus putrescentiae, were spotted in the sampled winery and 32 microorganism species were identified in their exoskeleton or surrounding biofilms. To our knowledge, 26 of these species were never described before in sherry wine environments. We hypothesized that mites feed on the flor biofilms as well as another type of biofilm located in barrel cracks, known by winemakers as "natas" (cream in English). These non-studied biofilms showed the highest microbiome diversity among all samples (followed by C. lactis spotted nearby) thus, representing a niche of microorganisms with potential biotechnological interest. Besides mites, Drosophila flies were spotted in the sampling areas. The role of flies and mites as vectors that transport microorganisms among different niches (i.e., flor biofilms and natas) is discussed.

PMID:37689427 | DOI:10.1016/j.fm.2023.104366

Neurobiol Dis. 2023 Sep 7:106286. doi: 10.1016/j.nbd.2023.106286. Online ahead of print.

ABSTRACT

Cognitive impairment in the elderly features complex molecular pathophysiology extending beyond the hallmark pathologies of traditional disease classification. Molecular subtyping using large-scale -omic strategies can help resolve this biological heterogeneity. Using quantitative mass spectrometry, we measured ~8000 proteins across >600 dorsolateral prefrontal cortex tissues with clinical diagnoses of no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia. Unbiased classification of MCI and AD cases based on individual proteomic profiles resolved three classes with expression differences across numerous cell types and biological ontologies. Two classes displayed molecular signatures atypical of AD neurodegeneration, such as elevated synaptic and decreased inflammatory markers. In one class, these atypical proteomic features were associated with clinical and pathological hallmarks of cognitive resilience. We were able to replicate these classes and their clinicopathological phenotypes across two additional tissue cohorts. These results promise to better define the molecular heterogeneity of cognitive impairment and meaningfully impact its diagnostic and therapeutic precision.

PMID:37689213 | DOI:10.1016/j.nbd.2023.106286

Neurosci Biobehav Rev. 2023 Sep 7:105381. doi: 10.1016/j.neubiorev.2023.105381. Online ahead of print.

ABSTRACT

In this review, we discuss the possible utility of zebrafish in research on psilocybin, a psychedelic drug whose recreational use as well as possible clinical application are gaining increasing interest. First, we review behavioral tests with zebrafish, focussing on anxiety and social behavior, which have particular relevance in the context of psilocybin research. Next, we briefly consider methods of genetic manipulations with which psilocybin's phenotypical effects and underlying mechanisms may be investigated in zebrafish. We briefly review the known mechanisms of psilocybin, and also discuss what we know about its safety and toxicity profile. Last, we discuss examples of how psilocybin may be employed for testing treatment efficacy in preclinical research for affective disorders in zebrafish. We conclude that zebrafish has a promising future in preclinical research on psychedelic drugs.

PMID:37689090 | DOI:10.1016/j.neubiorev.2023.105381

Cell Syst. 2023 Sep 8:S2405-4712(23)00216-8. doi: 10.1016/j.cels.2023.08.001. Online ahead of print.

ABSTRACT

During development, cells undergo symmetry breaking into differentiated subpopulations that self-organize into complex structures.1,2,3,4,5 However, few tools exist to recapitulate these behaviors in a controllable and coupled manner.6,7,8,9 Here, we engineer a stochastic recombinase genetic switch tunable by small molecules to induce programmable symmetry breaking, commitment to downstream cell fates, and morphological self-organization. Inducers determine commitment probabilities, generating tunable subpopulations as a function of inducer dosage. We use this switch to control the cell-cell adhesion properties of cells committed to each fate.10,11 We generate a wide variety of 3D morphologies from a monoclonal population and develop a computational model showing high concordance with experimental results, yielding new quantitative insights into the relationship between cell-cell adhesion strengths and downstream morphologies. We expect that programmable symmetry breaking, generating precise and tunable subpopulation ratios and coupled to structure formation, will serve as an integral component of the toolbox for complex tissue and organoid engineering.

PMID:37689062 | DOI:10.1016/j.cels.2023.08.001

Bioinformatics. 2023 Sep 9:btad556. doi: 10.1093/bioinformatics/btad556. Online ahead of print.

ABSTRACT

SUMMARY: DNA changes that cause premature termination codons (PTCs) represent a large fraction of clinically relevant pathogenic genomic variation. Typically, PTCs induce transcript degradation by nonsense-mediated mRNA decay (NMD) and render such changes loss-of-function alleles. However, certain PTC-containing transcripts escape NMD and can exert dominant-negative or gain-of-function (DN/GOF) effects. Therefore, systematic identification of human PTC-causing variants and their susceptibility to NMD contributes to the investigation of the role of DN/GOF alleles in human disease.Here we present aenmd, a software for annotating PTC-containing transcript-variant pairs for predicted escape from NMD. aenmd is user-friendly and self-contained. It of-fers functionality not currently available in other methods and is based on established and experimentally validated rules for NMD escape; the software is designed to work at scale, and to integrate seamlessly with existing analysis workflows. We applied aenmd to variants in the gnomAD, Clinvar, and GWAS catalog databases and report the prevalence of human PTC-causing variants in these databases, and the subset of these variants that could exert DN/GOF effects via NMD escape.

AVAILABILITY AND IMPLEMENTATION: aenmd is implemented in the R programming language. Code is available on GitHub as an R package (github.com/kostkalab/aenmd.git), and as a containerized command-line interface (github.com/kostkalab/aenmd_cli.git).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:37688563 | DOI:10.1093/bioinformatics/btad556

Plants (Basel). 2023 Sep 4;12(17):3169. doi: 10.3390/plants12173169.

ABSTRACT

A contribution to the nomenclature of the genus Sagina is presented. The following 10 taxa are recognized as being part of the Italian flora: S. alexandrae, S. apetala, S. glabra, S. maritima, S. micropetala, S. nodosa, S. pilifera, S. procumbens, S. revelierei, and S. saginoides subsp. saginoides. The names S. apetala var. decumbens (=S. apetala subsp. apetala), S. bryoides (=S. procumbens), S. patula (=S. apetala subsp. apetala), S. revelierei, Spergula glabra (=S. glabra), Spergula pilifera (=S. pilifera), and Spergella subulata var. macrocarpa (=S. saginoides subsp. saginoides) are here typified. Specimens deposited at B-W, C, E, and LY, and illustrations by Reichenbach were considered for the typifications. Specifically, two Reichenbach's illustrations are chosen for S. bryoides and S. saginoides var. macrocarpa. A specimen at B-W is designated as the lectotype of S. glabra. Two specimens at C and G are designated as the lectotypes of S. apetala var. decumbens and S. revelierei, respectively. A specimen at LY is designated for S. patula. As we did not find original material, a neotype at G is designated for S. pilifera.

PMID:37687415 | DOI:10.3390/plants12173169

Nutrients. 2023 Aug 28;15(17):3762. doi: 10.3390/nu15173762.

ABSTRACT

Aging results from gradual accumulation of damage to the cellular functions caused by biochemical processes such as oxidative stress, inflammation-driven prolonged cellular senescence state, immune system malfunction, psychological stress, and epigenetic changes due to exposure to environmental toxins. Plant-derived bioactive molecules have been shown to ameliorate the damage from oxidative stress. This research seeks to uncover the mechanisms of action of how phytochemicals from fruit/berry/vegetable (FBV) juice powder mitigate oxidative stress. The study uses a computational systems biology approach to (1) identify biomolecular pathways of oxidative stress; (2) identify phytochemicals from FBV juice powder and their specific action on oxidative stress mechanisms; and (3) quantitatively estimate the effects of FBV juice powder bioactive compounds on oxidative stress. The compounds in FBV affected two oxidative stress molecular pathways: (1) reactive oxygen species (ROS) production and (2) antioxidant enzyme production. Six bioactive compounds including cyanidin, delphinidin, ellagic acid, kaempherol, malvidin, and rutin in FBV significantly lowered production of ROS and increased the production of antioxidant enzymes such as catalase, heme oxygenase-1, superoxide dismutase, and glutathione peroxidase. FBV juice powder provides a combination of bioactive compounds that attenuate aging by affecting multiple pathways of oxidative stress.

PMID:37686794 | DOI:10.3390/nu15173762