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At least 793 records · Page 44Linked to original sources
PubMed2026

Tahoe-100M: Mapping drug-induced molecular phenotypes at single-cell resolution.

We present Tahoe-100M, a giga-scale single-cell perturbation atlas comprising 100 million transcriptomes from 50 diverse cancer cell lines treated with 1,100 drug-dose conditions. This parallel profiling of thousands of perturbations at single-cell resolution with minimal batch effects is enabled by the Mosaic platform, which multiplexes genetically distinct cell models into balanced "cell villages." Beyond cataloging transcriptomic shifts, Tahoe-100M systematically quantifies cellular phenotypes, including proliferation, cytotoxicity, lineage-specific vulnerabilities, and cell-cycle changes. It captures population-level transcriptomic heterogeneity, characterizing whether drug responses drive cells toward divergent fates or convergent states. Pathway-based signatures define drug-induced expression programs, classify mechanisms of action, reveal off-target activities, and expose adaptive stress responses associated with resistance. By unifying cellular and molecular readouts, this broadly applicable perturbation atlas advances our ability to model gene regulation, drug response, and network dynamics. Its public release enables the training of AI frameworks to advance predictive models of cell behavior.

Humans↗
PubMed2025

Integrating mutation, copy number, and gene expression data to identify driver genes of recurrent chromosome-arm losses.

Aneuploidy is a hallmark of cancer, yet the genes driving recurrent chromosome-arm losses remain largely unknown. We present a systematic framework integrating mutation, copy number, and gene expression data to identify candidate driver genes of cancer type-specific recurrent chromosome-arm losses across 20 cancer types, using ∼7,500 tumors from The Cancer Genome Atlas. By analyzing focal deletions and point mutations that co-occur, or are mutually exclusive, with chromosome-arm losses, we pinpoint 322 candidate drivers associated with 159 recurring events. Our approach identifies known aneuploidy drivers such as TP53 and PTEN, while revealing multiple additional candidates, including tumor suppressors not previously linked to aneuploidy. We leverage expression changes associated with chromosome-arm losses to propose cancer-promoting pathway-level alterations. Integrating these findings highlights key candidate drivers that underlie the observed expression alterations, reinforcing their biological relevance. We provide a comprehensive catalog of candidate driver genes for recurrently lost chromosome-arms in human cancer.

Humans↗
PubMed2025

Health-associated key gut microbiota drives the variation in community metabolic interactions in non-human primates.

Gut microbiota often undergo metabolic cross-feeding and resource competition. However, our understanding of global variations in these interactions and their implications for host health remain elusive. By analyzing a microbial genome catalog from 841 fecal metagenomes across 53 primate species worldwide, we identified key microbiota assigned to two taxa, i.e., Bacillota_A and Pseudomonadota, which well predicted the trade-off of community-level interaction types between metabolic competition and cooperation. Specifically, Bacillota_A species were inherently competitive and amino acid auxotrophic and typically found in anaerobic habitats. In contrast, members of Pseudomonadota were inherently cooperative, siderophore producers, and more abundant in aerobic conditions. Random forest models successfully distinguished unhealthy gut samples from healthy samples through the key competitive and cooperative microbiota, suggesting potential links between community metabolic interactions and host health. Together, this study enhances our mechanistic understanding of microbial interaction dynamism within complex gut ecosystems, offering new targets for understanding host health.

Animals↗
PubMed2026

Type IV-C CRISPR-Cas effector complexes recognize double-stranded DNA and switch on collateral cleavage of ssDNA and RNA.

Type IV-C CRISPR-Cas systems remain enigmatic compared to other class 1 systems. Here, we expand the type IV-C catalog, identifying two phylogenetically distinct clades primarily found in archaea (IV-C1) or bacteria (IV-C2), distinguishable by the Cas10IVc subunit architecture. We functionally and structurally characterize type IV-C1 systems from Thermococcus onnurineus (Ton) and Pyrococcus abyssi (Pab). Type IV-C complexes assemble with crRNAs derived from distinct CRISPR arrays and recognize a 5'-GGG-3' protospacer adjacent motif (PAM) to bind double-stranded DNA targets. Target recognition activates the HD domain of Cas10IVc, triggering metal-dependent collateral cleavage of single-stranded DNA and RNA. This behavior is explained by allosteric alignment of the HD active site, triggered by PAM-dependent R-loop formation, as revealed by cryo-EM. Together, our findings suggest that type IV-C systems provide immunity via non-specific cleavage of nucleic acids generated during mobile genetic element replication or transcription.

CP: molecular biology↗
PubMed2005

Low pH changes the profile of nodulation factors produced by Rhizobium tropici CIAT899.

Rhizobium tropici CIAT899 has been cataloged as a nodulator of bean, a plant often growing in areas characterized by highly acidic soils. The purpose of this work was to explore the effects of acidity on the production of Nod factors by this strain and their impact on the establishment of effective symbioses. We report that acidity increases rhizobial Nod factors production, and we exhaustively study the nodulation factor structures produced under abiotic stress. Significant differences were observed between the structures produced at acid and neutral pH: 52 different molecules were produced at acid pH, 29 at neutral pH, and only 15 are common to bacteria grown at pH 7.0 or 4.5. The results indicate that R. tropici CIAT899 has successfully adapted to life in acidic soils and is a good inoculant for the bean under these conditions.

Adaptation, Physiological↗
PubMed2023

Profiling of drug resistance in Src kinase at scale uncovers a regulatory network coupling autoinhibition and catalytic domain dynamics.

Kinase inhibitors are effective cancer therapies, but resistance often limits clinical efficacy. Despite the cataloging of numerous resistance mutations, our understanding of kinase inhibitor resistance is still incomplete. Here, we comprehensively profiled the resistance of ∼3,500 Src tyrosine kinase mutants to four different ATP-competitive inhibitors. We found that ATP-competitive inhibitor resistance mutations are distributed throughout Src's catalytic domain. In addition to inhibitor contact residues, residues that participate in regulating Src's phosphotransferase activity were prone to the development of resistance. Unexpectedly, we found that a resistance-prone cluster of residues located on the top face of the N-terminal lobe of Src's catalytic domain contributes to autoinhibition by reducing catalytic domain dynamics, and mutations in this cluster led to resistance by lowering inhibitor affinity and promoting kinase hyperactivation. Together, our studies demonstrate how drug resistance profiling can be used to define potential resistance pathways and uncover new mechanisms of kinase regulation.

src-Family Kinases↗
PubMed2004

Gender differences in empathy in parents at high- and low-risk of child physical abuse.

OBJECTIVES: The present research was designed to study empathy in high-risk parents for child physical abuse. The main objective was to study if high-risk mothers and fathers, compared to low-risk mothers and fathers, presented more Personal distress, less Perspective-taking, less Empathic concern and a deficit in dispositional empathy toward their partner and children. METHOD: Based on their scores on the Abuse Scale of the CAP Inventory [J.S. Milner, The Child Abuse Potential Inventory: Manual, 2nd ed., Psytec Corporation, Webster, NC], 19 (9 fathers and 10 mothers) high- and 26 (12 fathers and 14 mothers) low-risk parents for child physical abuse were selected from a total sample of 331 parents of the Spanish general population. Both groups were statistically matched on sociodemographic variables. The Interpersonal Reactivity Index (IRI) [Catalog of Selected Documents in Psychology 10 (1980) 85] and the Parent/Partner Empathy Scale (PPES) [N.D. Feshbach, N. Caskey, A new scale for measuring parent empathy and partner empathy: factorial structure, correlates and clinical discrimination, 1985] were used to assess dispositional empathy. RESULTS: An interaction between risk status and gender for "Personal distress" and "Perspective-taking" was found. High-risk mothers for child physical abuse showed more "Personal distress" than low-risk mothers and low-risk fathers. High-risk fathers for child physical abuse showed less "Perspective-taking" than low-risk mothers and low-risk fathers. No difference between both groups was found for the IRI "Empathic concern" dimension. Moreover, high-risk, compared to low-risk, parents showed lower scores both on the "Empathy toward the partner" and on the "Empathy toward the child" dimensions of the PPES. No interaction between risk status and gender was found for the PPES dimensions. CONCLUSIONS: Findings of the present study supported the hypothesis that high-risk parents for child physical abuse show a deficit both in general empathy and in empathy toward their family members. Moreover, findings suggested the existence of a different pattern of deficits in empathy for high-risk fathers and high-risk mothers.

Adult↗
PubMedDate not supplied

Psychosocial aspects of beauty: how and why to look good.

It is difficult to pick up a paper or magazine today or turn on the television without being reminded that ours is a culture of youth and beauty. Bookstore shelves sag under the weight of enticing tomes devoted to the subject. We are bombarded with advertisements for any one of thousands of different products, both prescription and over-the-counter, that claim to be able to restore our youthful appearance, banish wrinkles, tone skin, and remove cellulite, among other promises that often sound, and probably are, too good to be true. Health food stores and sales catalogs are replete with myriad products, so that one wonders how the average person, in face of such bombardment, can either resist the temptation to buy or make an informed selection from the veritable feast of goodies put before them. Billions of dollars are expended each year, and false claims abound, but fortunately, there are many preparations and procedures that, in skilled hands, can really make a difference.

Beauty↗
PubMed2003

Advances in flux balance analysis.

Biology is going through a paradigm shift from reductionist to holistic, systems-based approaches. The complete genome sequence for a number of organisms is available and the analysis of genome sequence data is proving very useful. Thus, genome sequencing projects and bioinformatic analyses are leading to a complete 'parts catalog' of the molecular components in many organisms. The next challenge will be to reconstruct and simulate overall cellular functions based on the extensive reductionist information. Recent advances have been made in the area of flux balance analysis, a mathematical modeling approach often utilized by metabolic engineers to quantitatively simulate microbial metabolism.

Computational Biology↗
PubMed2005

The evolution of IncP catabolic plasmids.

The recent adoption of whole plasmid genome sequencing as a routine analytical technique has provided the basis for cataloging the historical events through which plasmids are assembled from the available families of modular plasmid components. Horizontal gene transfer mediated by plasmids plays an important role in the adaptation of bacteria to the presence of specific metabolizable compounds, including man-made chemicals, in the surrounding environment. Bacterial plasmid genome sequence comparisons indicate that plasmids have complex genetic histories resulting from transposition, homologous recombination, and illegitimate recombinational events. Evidence from IncP plasmid genome sequences indicates that cryptic plasmid backbones acquire diverse catabolic pathways through gene capture and horizontal gene transfer.

Evolution, Molecular↗
PubMedDate not supplied

The NIA cDNA project in mouse stem cells and early embryos.

A catalog of mouse genes expressed in early embryos, embryonic and adult stem cells was assembled, including 250000 ESTs, representing approximately 39000 unique transcripts. The cDNA libraries, enriched in full-length clones, were condensed into the NIA 15 and 7.4K clone sets, freely distributed to the research community, providing a standard platform for expression studies using microarrays. They are essential tools for studying mammalian development and stem cell biology, and to provide hints about the differential nature of embryonic and adult stem cells.

Animals↗
PubMed2026

Mapping and measuring addiction recovery: Recommended protocols through the PHENX toolkit.

BACKGROUND: Addiction "recovery" has served as a positive conceptual basis for major public health frameworks, communication strategies, and policies. With greater research interest and increasing explication of the recovery construct a multitude of measures have emerged, prompting a need to reach consensus on recommendations to enable better data harmonization and cross-study syntheses. The PhenX (consensus measures for Phenotypes and eXposures) Toolkit (www.phenxtoolkit.org) is a freely accessible catalog of validated protocols designed to promote data comparability across clinical, epidemiological, and genomic research, yet contained no recovery-specific measures. METHOD: In 2024, a Substance Use and Recovery Working Group (SURWG) followed a well-established and detailed PhenX consensus process to identify and recommend protocols suitable for recovery research. Protocols were chosen based on criteria including recovery specificity, brevity, psychometrics, scoring simplicity, and non-proprietary access. The broader scientific community (12 national/regional organizations) provided feedback (respondent N = 86) on the SURWG's preliminary recommendation which was incorporated into final decisions. RESULTS: In 2025, the PhenX Toolkit released 15 new recommended protocols across three broad recovery elements: 1. Biopsychological (post-acute withdrawal; craving), 2. Socio-ecological (social relationships;social network characteristics; substance use goal; recovery identity; recovery capital), 3. Treatment and recovery services (Treatment and Recovery Services Use; Satisfaction; and Happiness in Recovery; Mutual-Help). CONCLUSIONS: This PhenX Toolkit SURWG process resulted in a new Substance Use Recovery Specialty Collection of recommended protocols with specific multidimensional applicability. As such, they provide the field with pre-vetted tools that researchers can employ with some confidence to enhance empirical efficiency and return on national research investment.

Humans↗
PubMed2024

Beyond water and soil: Air emerges as a major reservoir of human pathogens.

Assessing the risk of human pathogens in the environment is crucial for controlling the spread of diseases and safeguarding human health. However, conducting a thorough assessment of low-abundance pathogens in highly complex environmental microbial communities remains challenging. This study compiled a comprehensive catalog of 247 human-pathogenic bacterial taxa from global biosafety agencies and identified more than 78 million genome-specific markers (GSMs) from their 17,470 sequenced genomes. Subsequently, we analyzed these pathogens' types, abundance, and diversity within 474 shotgun metagenomic sequences obtained from diverse environmental sources. The results revealed that among the four habitats studied (air, water, soil, and sediment), the detection rate, diversity, and abundance of detectable pathogens in the air all exceeded those in the other three habitats. Air, sediment, and water environments exhibited identical dominant taxa, indicating that these human pathogens may have unique environmental vectors for their transmission or survival. Furthermore, we observed the impact of human activities on the environmental risk posed by these pathogens, where greater amounts of human activities significantly increased the abundance of human pathogenic bacteria, especially in water and air. These findings have remarkable implications for the environmental risk assessment of human pathogens, providing valuable insights into their presence and distribution across different habitats.

Humans↗
PubMed2026

Microbial diversity, functional activities, and safety risks in fermented tea: a comprehensive review.

Microbial fermented teas are gaining global popularity due to their unique sensory profiles and health benefits. The quality and safety of these products are governed by complex microbial ecosystems that orchestrate the biotransformation of tea leaf components. This review addresses a critical paradox in the field: the same microbial activities that generate desirable bioactive metabolites, such as theabrownins and organic acids, also create ecological niches for mycotoxigenic fungi, posing significant health risks from contaminants like ochratoxin A, citrinin, and aflatoxins. While extensive research has cataloged the microbial diversity in these systems, a comprehensive framework linking processing environments to microbial community assembly, functional outcomes, and quantifiable safety risks remains elusive. This review systematically bridges this gap by synthesizing current knowledge on the microbial consortia-dominated by Aspergillus, Penicillium, Bacillus, and Lactiplantibacillus species-that drive tea fermentation. We critically analyze their functional roles in enhancing flavor, bioactivity, and potential probiotic activity while simultaneously evaluating the mechanisms of mycotoxin production and accumulation. By integrating microbial ecology, biochemistry, and food safety, we propose a forward-looking perspective focused on transitioning the industry from traditional, spontaneous fermentation to modern, controlled biotechnological processes. This approach, centered on the use of defined starter cultures, predictive modeling, and active biocontrol strategies, provides a roadmap for ensuring the consistent quality and safety of fermented tea products, ultimately unlocking their full potential as high-quality functional foods.

Tea↗
PubMed2004

Application of cytochrome b DNA sequences for the authentication of endangered snake species.

In order to enforce the conservation program and curbing the illegal trading and consumption of endangered snake species, the value of cytochrome b sequence in the authentication of snake species was evaluated. As an illustration, DNA was extracted, selected cytochrome b DNA sequences amplified and sequenced from six snakes commonly consumed in Hong Kong. Cataloging with sequences available in public, a cytochrome b database containing 90 species of snakes was constructed. In this database, sequence homology between snakes ranged from 70.68 to 95.11%. On the other hand, intraspecific variation of three tested snakes was 0-0.98%. Using the database, we were able to determine the identity of six meat samples confiscated by the Agriculture, Fisheries and Conservation Department, HKSAR.

Animals↗
PubMed2026

The costs of genomic newborn screening in England: A micro-costing analysis from the Generation Study.

PURPOSE: This study estimates the total cost per newborn of delivering genomic newborn screening (gNBS) within the Genomics England-led Generation Study. METHODS: A time-driven activity-based costing approach was used to estimate gNBS costs from recruitment to confirmatory testing. Resource use data were obtained through document review, semi-structured interviews with study staff, and direct observation across six English National Health Service Trusts. Inputs were categorized as labor, consumables, or equipment, with unit costs sourced from published pay scales, catalogs, or literature. Equipment costs were annualized at a discount rate of 3.5%. All costs were estimated in 2025 Great British Pounds (£) from the healthcare providers perspective, including overheads and data storage. A one-way deterministic sensitivity analysis was conducted, varying key cost parameters (±20%) and testing alternative delivery scenarios. RESULTS: gNBS costs £1208 per newborn, with sequencing comprising 58% of the total costs, mainly consumables. The cost was reduced by 20% to £963 when excluding research-specific recruitment and consent activities to reflect the delivery of gNBS as part of routine clinical care. CONCLUSION: This study provides an estimate of gNBS costs, highlighting sequencing as the main cost driver. Combined with evidence on outcomes and health care utilization, these findings will inform future cost-effectiveness analyses, supporting policy decisions regarding national implementation in England.

Neonatal Screening↗
PubMed2004

Assessing graduate programs for healthcare information management/technology (HIM/T) executives.

This paper describes a methodology to assess health/medical informatics graduate-level education curricula. The authors used the Certified Professional in Healthcare Information Management Systems (CPHIMS) exam objectives published by the Healthcare Information and Management Systems Society (HIMSS) as the basis for their assessment. The authors compared the 69 CPHIMS exam objectives against four health/medical informatics program course objectives as stated in the selected program's online graduate catalog. Results showed that the two programs with management as a focus addressed the majority (67 and 59%) of the CPHIMS objectives within core and elective courses combined. Overall, the other two programs addressed closer to a third of the CPHIMS objectives (36 and 32%). This methodology could prove to be useful in assisting students interested in graduate-level training programs with a tool by which to measure the congruence of the curricula of different programs with the mission of the programs and with their own professional interests.

Curriculum↗
PubMed2006

A survey identified publication bias in the secondary literature.

OBJECTIVE: To investigate the existence of publication bias in the translation of evidence from the primary to the secondary literature, using the ACP Journal Club (ACPJC) as a representative of secondary literature and Medline as a representative of primary literature. METHODS: A cross-sectional survey of randomly selected randomized controlled trials of therapy published between 1994 and 2002 in English in Medline and all summaries of therapy trials published by ACPJC between the same dates. The main outcome measure was the rate of positive trials from among those trials aiming to find a difference between groups. RESULTS: 831 trials from Medline and 823 summaries of trials from ACPJC met the inclusion criteria and were included in the study. Compared to trials cataloged in Medline, ACPJC preferentially summarized trials with a positive outcome (P < .001). This bias remained after controlling for other selection biases seen in the ACPJC such as preferentially summarizing multicentered trials with large sample size, no active treatment control, blinding, and in certain disease fields (adjusted odds ratio 2.8, 95% confidence interval 2.02-3.93). CONCLUSION: The ACPJC preferentially summarizes trials with a positive outcome. Efforts should be made to reduce this bias.

Cross-Sectional Studies↗