Front Cell Neurosci. 2023 Aug 8;17:1267913. doi: 10.3389/fncel.2023.1267913. eCollection 2023.

ABSTRACT

[This corrects the article DOI: 10.3389/fncel.2023.1205261.].

PMID:37614912 | PMC:PMC10442933 | DOI:10.3389/fncel.2023.1267913

Microsc Microanal. 2023 Jul 22;29(Supplement_1):1722-1723. doi: 10.1093/micmic/ozad067.890.

NO ABSTRACT

PMID:37613920 | DOI:10.1093/micmic/ozad067.890

Microsc Microanal. 2023 Jul 22;29(Supplement_1):997. doi: 10.1093/micmic/ozad067.500.

NO ABSTRACT

PMID:37613633 | DOI:10.1093/micmic/ozad067.500

Microsc Microanal. 2023 Jul 22;29(Supplement_1):2091-2092. doi: 10.1093/micmic/ozad067.1082.

NO ABSTRACT

PMID:37612944 | DOI:10.1093/micmic/ozad067.1082

Clin Epigenetics. 2023 Aug 24;15(1):133. doi: 10.1186/s13148-023-01546-1.

ABSTRACT

BACKGROUND: Promoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated.

RESULTS: In this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines. As a proof of concept, we combined recent CRISPR-Cas9 epigenome editing tools (dCas9-TET1, dCas9-TET-IM) with a customized arrayed gRNA library to modulate the DNA methylation status of 56 promoters previously linked with strong epigenetic repression in CRC, and we monitored the potential functional consequences of this DNA methylation loss by means of a high-content cell proliferation screen. Overall, the epigenetic modulation of most of these DNA methylated regions had a mild impact on the reactivation of gene expression and on the viability of cancer cells. Interestingly, we found that epigenetic reactivation of RSPO2 in the tumour context was associated with a significant impairment in cell proliferation in p53-/- cancer cell lines, and further validation with human samples demonstrated that the epigenetic silencing of RSPO2 is a mid-late event in the adenoma to carcinoma sequence.

CONCLUSIONS: These results highlight the potential role of DNA methylation as a driver mechanism of CRC and paves the way for the identification of novel therapeutic windows based on the epigenetic reactivation of certain tumour suppressor genes.

PMID:37612734 | DOI:10.1186/s13148-023-01546-1

Nature. 2023 Aug 23. doi: 10.1038/s41586-023-06457-y. Online ahead of print.

ABSTRACT

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications1-3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome4 and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.

PMID:37612512 | DOI:10.1038/s41586-023-06457-y

Nature. 2023 Aug 23. doi: 10.1038/s41586-023-06464-z. Online ahead of print.

ABSTRACT

Chromosomal instability (CIN) is a driver of cancer metastasis1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation.

PMID:37612508 | DOI:10.1038/s41586-023-06464-z

NPJ Sci Food. 2023 Aug 23;7(1):43. doi: 10.1038/s41538-023-00219-w.

ABSTRACT

The prevalence of hypersensitivities towards wheat has increased in the last decades. Apart from celiac disease these include allergic and other inflammatory reactions summarized under the term non-celiac wheat sensitivity. One suspected trigger is the family of amylase/trypsin-inhibitors (ATIs), non-gluten proteins that are prominent wheat allergens and that activate the toll-like receptor 4 on intestinal immune cells to promote intestinal and extra-intestinal inflammation. We therefore quantified 13 ATIs in 60 German hexaploid winter wheat cultivars originating from 1891 to 2010 and harvested in three years by targeted liquid chromatography-tandem mass spectrometry combined with stable isotope dilution assay using specific marker peptides as internal standards. The total ATI content and that of the two major ATIs 0.19 and CM3 did not change from old cultivars (first registered from 1891 to 1950) to modern cultivars (1951-2010). There were also no significant changes in ATI distribution.

PMID:37612428 | DOI:10.1038/s41538-023-00219-w

Nat Commun. 2023 Aug 23;14(1):5130. doi: 10.1038/s41467-023-40137-9.

ABSTRACT

Bacteria colonize almost all parts of the human body and can differ significantly. However, the population level transcriptomics measurements can only describe the average bacteria population behaviors, ignoring the heterogeneity among bacteria. Here, we report a droplet-based high-throughput single-microbe RNA-seq assay (smRandom-seq), using random primers for in situ cDNA generation, droplets for single-microbe barcoding, and CRISPR-based rRNA depletion for mRNA enrichment. smRandom-seq showed a high species specificity (99%), a minor doublet rate (1.6%), a reduced rRNA percentage (32%), and a sensitive gene detection (a median of ~1000 genes per single E. coli). Furthermore, smRandom-seq successfully captured transcriptome changes of thousands of individual E. coli and discovered a few antibiotic resistant subpopulations displaying distinct gene expression patterns of SOS response and metabolic pathways in E. coli population upon antibiotic stress. smRandom-seq provides a high-throughput single-microbe transcriptome profiling tool that will facilitate future discoveries in microbial resistance, persistence, microbe-host interaction, and microbiome research.

PMID:37612289 | DOI:10.1038/s41467-023-40137-9

Cell Death Dis. 2023 Aug 23;14(8):547. doi: 10.1038/s41419-023-06082-7.

ABSTRACT

Although most cell membrane proteins are modified by glycosylation, our understanding of the role and actions of protein glycosylation is still very limited. β1,3galactosyltransferase (C1GalT1) is a key glycosyltransferase that controls the biosynthesis of the Core 1 structure of O-linked mucin type glycans and is overexpressed by many common types of epithelial cancers. This study reports that suppression of C1GalT1 expression in human colon cancer cells caused substantial changes of protein glycosylation of cell membrane proteins, many of which were ligands of the galactoside-binding galectin-3 and the macrophage galactose-type lectin (MGL). This led to significant reduction of cancer cell proliferation, adhesion, migration and the ability of tumour cells to form colonies. Crucially, C1GalT1 suppression significantly reduced galectin-3-mediated tumour cell-cell interaction and galectin-3-promoted tumour cell activities. In the meantime, C1GalT1 suppression substantially increased MGL-mediated macrophage-tumour cell interaction and macrophage-tumour cell phagocytosis and cytokine secretion. C1GalT1-expressing cancer cells implanted in chick embryos resulted in the formation of significantly bigger tumours than C1GalT1-suppressed cells and the presence of galectin-3 increased tumour growth of C1GalT1-expressing but not C1GalT1-suppressed cells. More MGL-expressing macrophages and dendritic cells were seen to be attracted to the tumour microenvironment in ME C1galt1-/-/Erb mice than in C1galt1f/f /Erb mice. These results indicate that expression of C1GalT1 by tumour cells reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression. C1GalT1 overexpression in epithelial cancers therefore may represent a fundamental mechanism in cancer promotion and in reduction of immune response/surveillance in cancer progression.

PMID:37612278 | DOI:10.1038/s41419-023-06082-7

Nat Commun. 2023 Aug 23;14(1):5128. doi: 10.1038/s41467-023-40833-6.

NO ABSTRACT

PMID:37612270 | DOI:10.1038/s41467-023-40833-6

Cold Spring Harb Protoc. 2023 Aug 23. doi: 10.1101/pdb.top107680. Online ahead of print.

ABSTRACT

Analysis of taste sensory responses has been a powerful approach for understanding principles of taste detection and coding. The shared architecture of external taste sensing units, called sensilla, in insects opened up the study of tastant-evoked responses in any model of choice using a single-sensillum tip recording method that was developed in the mid-1900s. Early studies in blowflies were instrumental for identifying distinct taste neurons based on their responses to specific categories of chemicals. Broader system-wide analyses of whole organs have since been performed in the genetic model insect Drosophila melanogaster, revealing principles of stereotypical organization and function that appear to be evolutionarily conserved. Although limited in scope, investigations of taste sensory responses in mosquitoes showcase conservation in sensillar organization, as well as in groupings of functionally distinct taste neurons in each sensillum. The field is now poised for more thorough dissections of mosquito taste function, which should be of immense value in understanding close-range chemosensory interactions of mosquitoes with their hosts and environment. Here, we provide an introduction to the basic structure of a taste sensillum and functional analysis of the chemosensory neurons within it.

PMID:37612144 | DOI:10.1101/pdb.top107680

Cold Spring Harb Protoc. 2023 Aug 23. doi: 10.1101/pdb.prot108195. Online ahead of print.

ABSTRACT

In insects, gustatory neurons sense chemicals upon contact and directly inform many behaviors critical for survival and reproduction, including biting, feeding, mating, and egg laying. However, the taste sensory system is underexplored in many anthropophilic disease vectors such as mosquitoes, which acquire and transmit human pathogens during blood feeding from human hosts. This results in a big gap in vector biology-the study of organisms that spread disease by transmitting pathogens-because insect vectors closely interact with humans while selecting suitable individuals and appropriate bite sites for blood meals. Human sweat and skin-associated chemistries are rich in nonvolatile compounds that can be sensed by the mosquito's taste system when she lands on the skin. Taste sensory units, called sensilla, are distributed in many organs across the mosquito body, including the mouthparts, legs, and ovipositors (female-specific structures used to lay eggs). Each sensillum is innervated by as many as five taste neurons, which allow detection and discrimination between various tastants such as water, sugars, salts, amino acids, and plant-derived compounds that taste bitter to humans. Single-sensillum recordings provide a robust way to survey taste responsiveness of individual sensilla to various diagnostic and ecologically relevant chemicals. Such analyses are of immense value for understanding links between mosquito taste responses and behaviors to specific chemical cues and can provide insights into why mosquitoes prefer certain hosts. The results can also aid development of strategies to disrupt close-range mosquito-human interactions to control disease transmission. Here we describe a protocol that is curated for electrophysiological recordings from taste sensilla in mosquitoes and sure to yield exciting results for the field.

PMID:37612142 | DOI:10.1101/pdb.prot108195

J Invest Dermatol. 2023 Sep;143(9):1667-1677. doi: 10.1016/j.jid.2023.03.1679.

ABSTRACT

Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.

PMID:37612031 | DOI:10.1016/j.jid.2023.03.1679

J Invest Dermatol. 2023 Sep;143(9):1638-1645. doi: 10.1016/j.jid.2023.04.015.

ABSTRACT

Researchers should be aware that hair growth cycle drives prominent molecular, cellular, and morphological changes to the entire skin. Thus, hair growth constitutes a major experimental variable that influences the interpretation of dermatological studies. Hair growth in mice is neither asynchronous nor fully synchronized; rather, it occurs in waves that dynamically propagate across the skin. In consequence, any given area of mouse skin can contain hair follicles in different stages of the cycle in close physical proximity. Furthermore, hair growth waves in mice are initiated by probabilistic events at different time points and across stochastic locations. The consequence of such stochasticity is that precise patterns of hair growth waves differ from mouse to mouse, even in littermates of the same sex. However, such physiological stochasticity is commonly misconstrued as a significant hair growth phenotype in mutant mice or in drug-treated mice. The purpose of this article is to provide a set of guidelines for designing reliably interpretable murine studies on hair growth and to highlight key experimental caveats to be avoided. It also informs on how to account for and minimize the impact of physiological hair cycle differences when designing and interpreting nonhair growth dermatological studies in mice.

PMID:37612030 | DOI:10.1016/j.jid.2023.04.015

J Glob Antimicrob Resist. 2023 Aug 21:S2213-7165(23)00133-9. doi: 10.1016/j.jgar.2023.08.007. Online ahead of print.

ABSTRACT

OBJECTIVES: The prevalence of ceftriaxone-resistant Neisseria gonorrhoeae poses a significant threat to the effectiveness of gonorrhea treatment. The aim of the present study was to analyze the characteristics of ceftriaxone-resistant N. gonorrhoeae, with a specific focus on high-level ceftriaxone-resistant strains.

METHODS: A total of 207 strains of N. gonorrhoeae were collected from hospitals in Zhejiang, China, between 2019 and 2020. From this collection, we selected 8 strains of ceftriaxone-resistant N. gonorrhoeae for whole-genome sequencing, genotyping, and molecular profile analysis. For clonal strains (FC428-like), we conducted a phylogenetic analysis to understand their origin and evolutionary path.

RESULTS: Among the selected strains, 5 demonstrated high-level ceftriaxone resistance (MIC 1-2 mg/L). The genotyping results showed that these isolates had a higher diversity of penA alleles than expected. Four isolates had mosaic penA-60.001 allele and the remaining four had different non-mosaic penA alleles. Phylogenetic analysis suggested that the emergence of FC428-like clones containing penA-60.001 may result from further dissemination of different FC428 subclones from different regions of China. The identification of high-level ceftriaxone resistance in non-mosaic penA gonococci, specifically in the ZJ20-3 isolate (penA-21.001) with an MIC of 2 mg/L, is a groundbreaking discovery.

CONCLUSIONS: We present a comprehensive analysis of ceftriaxone-resistant N. gonorrhoeae isolates in Zhejiang, highlighting a significant diversity of penA alleles. The identification of strains exhibiting resistance to ceftriaxone at high levels in our study underscores the potential threat to existing protocols for gonorrhea treatment. Consequently, we strongly emphasize the urgent need to enhance surveillance initiatives focused on ceftriaxone-resistant N. gonorrhoeae.

PMID:37611895 | DOI:10.1016/j.jgar.2023.08.007

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 21:110846. doi: 10.1016/j.pnpbp.2023.110846. Online ahead of print.

ABSTRACT

Associative learning is often studied using food reward as the unconditioned stimulus (US). With warm-blooded species, to get the subject more motivated the solution has been to feed less, making the subject hungrier. Here we show the opposite with zebrafish. We randomly assigned zebrafish to two groups: a once-a-day-fed and a five-times-a-day-fed group, with the same amount of food fed per occasion for fish of both groups, a feeding regimen that lasted for three months. Subsequently, we trained fish by pairing food (US) with a red cue card (the conditioned stimulus, CS), which were placed together in one arm of a plus-maze across eight training sessions. We also ran unpaired training, in which the CS and US were presented in different arms. We found the previously once-a-day-fed zebrafish to consume less food throughout habituation and training sessions compared to the previously five-times-a-day-fed ones. Furthermore, five-times-a-day-fed fish in the paired group swam significantly closer to the CS during a post-training probe trial compared to the five-times-a-day-fed unpaired fish, a paired training effect that was absent in once-a-day-fed fish. Groups did not differ in health or general activity. In sum, elevated chronic feeding improved food consumption and enhanced learning and memory performance without affecting activity levels in adult zebrafish.

PMID:37611652 | DOI:10.1016/j.pnpbp.2023.110846

Ecotoxicol Environ Saf. 2023 Aug 21;263:115393. doi: 10.1016/j.ecoenv.2023.115393. Online ahead of print.

ABSTRACT

Children are disproportionately represented among those who suffer asthma, which is a kind of chronic airway inflammation. Asthma symptoms might worsen when exposed to the air pollutant particulate matter 2.5 (PM2.5). However, it is becoming more prevalent among older adults, with more asthma-related deaths occurring in this pollution than in any other age group, and symptoms caused by asthma can reduce the quality of life of the elderly, whose asthma is underdiagnosed due to physiological factors. Therefore, in an effort to discover a therapy for older asthma during exposure to air pollution, we sought to ascertain the effects of pre-exposure (PA) and persistent exposure (PAP) to PM2.5 in aged asthma rats. In this study, we exposed aged rats to PM2.5 at different times (PA and PAP) and established an ovalbumin-mediated allergic asthma model. The basic process of elderly asthma caused by PM2.5 exposure was investigated by lung function detection, enzyme-linked immunosorbent assay (ELISA), histopathology, cytology, cytokine microarray, untargeted metabolomics, and gut microbiota analysis. Our findings demonstrated that in the PA and PAP groups, exposure to PM2.5 reduced lung function and exacerbated lung tissue damage, with varying degrees of effect on immunoglobulin levels, the findings of a cytological analysis, cytokines, and chemokines. The PA and PAP rats had higher amounts of polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, 2-methylNaphthalene, 1-methylNaphthalene and flourene. Moreover, exposure to PM2.5 at different times showed different effects on plasma metabolism and gut microbiota. Bioinformatics analysis showed a strong correlation between PAHs, cytokines, and gut microbiota, and PAHs may cause metabolic disorders through the gut microbiota. These findings point to a possible mechanism for the development of asthma in older people exposure to PM2.5 that may be related to past interactions between PAHs, cytokines, gut microbiota, and plasma metabolites.

PMID:37611479 | DOI:10.1016/j.ecoenv.2023.115393

Bioinformatics. 2023 Aug 23:btad523. doi: 10.1093/bioinformatics/btad523. Online ahead of print.

ABSTRACT

MOTIVATION: The method of GWAS and metabolomics combined provide an quantitative approach to pinpoint metabolic pathways and genes linked to specific diseases; however, such analyses require both genomics and metabolomics datasets from the same individuals/samples. In most cases, this approach is not feasible due to high costs, lack of technical infrastructure, unavailability of samples, and other factors. Therefore, an unmet need exists for a bioinformatics tool that can identify gene loci-associated polymorphic variants for metabolite alterations seen in disease states using standalone metabolomics.

RESULTS: Here, we developed a bioinformatics tool, metGWAS 1.0, that integrates independent GWAS data from the GWAS database and standalone metabolomics data using a network-based systems biology approach to identify novel disease/trait-specific metabolite-gene associations. The tool was evaluated using standalone metabolomics datasets extracted from two metabolomics-GWAS case studies. It discovered both the observed and novel gene loci with known single nucleotide polymorphisms when compared to the original studies.

AVAILABILITY AND IMPLEMENTATION: The developed metGWAS 1.0 framework is implemented in an R pipeline and available at: https://github.com/saifurbd28/metGWAS-1.0.

PMID:37610350 | DOI:10.1093/bioinformatics/btad523

iScience. 2023 Jul 4;26(8):107269. doi: 10.1016/j.isci.2023.107269. eCollection 2023 Aug 18.

ABSTRACT

We present DoSurvive, a user-friendly survival analysis web tool and a cancer prognostic biomarker centered database. DoSurvive is the first database that allows users to perform multivariant survival analysis for cancers with customized gene/patient list. DoSurvive offers three survival analysis methods, Log rank test, Cox regression and accelerated failure time model (AFT), for users to analyze five types of quantitative features (mRNA, miRNA, lncRNA, protein and methylation of CpG islands) with four survival types, i.e. overall survival, disease-specific survival, disease-free interval, and progression-free interval, in 33 cancer types. Notably, the implemented AFT model provides an alternative method for genes/features which failed the proportional hazard assumption in Cox regression. With the unprecedented number of survival models implemented and high flexibility in analysis, DoSurvive is a unique platform for the identification of clinically relevant targets for cancer researcher and practitioners. DoSurvive is freely available at http://dosurvive.lab.nycu.edu.tw/.

PMID:37609633 | PMC:PMC10440714 | DOI:10.1016/j.isci.2023.107269