bluuebunny/crossref_metadata_2025 huggingface dataset:
Halostreptopolyspora alba gen. nov., sp. nov., a halophilic actinobacterium isolated from saline soil of Xinjiang, Northwest of China
Authors: Li Rui , Tang Xiao-Jing , Feng Yu-Zhou , Ji Yang , Wang Yun , Miao Cui-Ping , Tang Mei , wang Ke-ke , Chunyu Wei-Xun , Zhao Li-Xing , Tang Shu-Kun
Published: October 2024

A Gram-stain-positive, aerobic, moderate halophilic actinobacterium, designated strain YIM 96095T, was isolated from a saline soil sample collected from Aiding Lake, Xinjiang, North-western China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate belonged to the family Nocardiopsidaceae, formed a distinct subclade, and was most closely related to Lipingzhangella halophila DSM 102030T and Allosalinactinospora lopnorensis DSM 45697T with sequence identity values of 95.8 and 95.1%, respectively. Optimal growth occurred at 37 °C, pH 7.0–8.0 and with 5–16% (w/v) NaCl, with well-developed, non-fragmented substrate mycelia and single-, double-, or triple-wrinkled spore(s) on the mature aerial hyphae. The chemical analysis presented meso-diaminopimelic acid as the diagnostic diamino acid of the cell-wall peptidoglycan, and glucose, galactose and rhamnose as the major whole-cell sugars, and iso-C15 : 0 and anteiso-C15 : 0 as the major fatty acids. The phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, unidentified phospholipids and unidentified glycolipid. The menaquinones were MK-10(H8), MK-10(H6) and MK-9(H10). Its G+C content was 69.7 mol% in the determined genome sequence. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, a novel genus and species named Halostreptopolyspora alba gen. nov., sp. nov. is proposed for isolate YIM 96095T (=KCTC 49266T=CGMCC 4.7636T).
Description of Rhodobacter flavimaris sp. nov. and proposal of the genera Paenirhodobacter, Sedimentimonas, and Sinirhodobacter as synonyms of Rhodobacter
Authors: Huang Meng-Han , Zhang Dao-Feng , Wang Hong-Chuan , He Wei , Song Xiao-Rui
Published: October 2024

Two Gram-stain-negative, aerobic, ovoid to short rod-shaped bacterial strains, designated as WL0062T and WL0115, were isolated from coastal zone of the Yellow Sea, Jiangsu Province, PR China, respectively. Strain WL0062T grew optimally at 28 °C, pH 7.0–8.0 and with 1.0–3.0% (w/v) NaCl. Strain WL0115 grew optimally at 28 °C, pH 6.0–7.0 and with 1.0–3.0% (w/v) NaCl. In the bac120 tree, strains WL0062T and WL0115 clustered together with Sedimentimonas flavescens B57T. The respiratory quinone of both strains was ubiquinone-10. The major polar lipids of both strains were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, glycolipid, phosphatidylmonomethylethanolamine, and one unidentified polar lipid. The major fatty acids of strain WL0062T were summed features 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c). The major fatty acids of strain WL0115 were summed features 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c), C18 : 0, iso-C17 : 1
 ω5c and C20 : 4
 ω6/9/12/15c (arachidonic acid). The G+C content of genomic DNA of strains WL0062T and WL0115 was 64.0 mol% in both of them. Combined with the analysis of average nucleotide identity, average amino acid identity, and digital DNA–DNA hybridization, strain WL0062T represents a novel species of the genus Rhodobacter, for which the name Rhodobacter flavimaris sp. nov is proposed. The type strain is WL0062T (=MCCC 1K06014T=JCM 34676T=GDMCC 1.2427T). Strain WL0115 (=MCCC 1K07531=JCM 35568=GDMCC 1.3088) should belong to the same species as Sedimentimonas flavescens B57T. In addition, on the basis of phylogenomic relationship and phenotypical characteristics, the genera Paenirhodobacter, Sedimentimonas, and Sinirhodobacter are proposed as synonyms of Rhodobacter.
Effect of simethicone on the bactericidal efficacy of a high-level disinfectant
Authors: Anderson Gregory G. , Segars Katharine , Sanchez Anastacia M. , Weeks Jon W. , Haugen Shanil P. , Pandey Ruchi
Published: October 2024

Introduction. Simethicone is an over-the-counter product that is frequently used by clinicians during endoscopic procedures to reduce foaming and improve visualization. Published studies have found simethicone residue on endoscopes after cleaning and disinfecting the devices as per the manufacturer’s instructions. Some literature suggests that simethicone residue may reduce disinfection efficacy and increase the risk of patient infections.

Gap Statement. However, there appears to be a lack of direct evidence in the literature to either disprove this or correlate simethicone presence with an increased microbial risk.

Aim: Research was conducted to evaluate the in vitro impact of simethicone on disinfection efficacy.

Methodology. Bacteria were grown in a microtitre plate assay in the presence of a range of simethicone concentrations and then treated with a disinfectant. Bacterial growth was assessed by spotting each microtitre well onto an agar plate.

Results. The results demonstrated that, under the conditions tested, simethicone did not reduce the efficacy of Cidex ortho-phthalaldehyde disinfectant, which demonstrated at least a 6-log unit reduction in bacterial viability. Additional experiments showed that direct exposure to 66 mg ml−1 of simethicone reduced bacterial viability.

Conclusion. These results indicate that simethicone may not reduce the bactericidal efficacy of disinfectant during reprocessing, under certain conditions.
HLAIIPred: Cross-Attention Mechanism for Modeling the Interaction of HLA Class II Molecules with Peptides
Authors: Haghighatlari Mojtaba , Marze Nick , Seward Robert , Ciarla Andrew , Dhule Santosh , Hindin Rachel , Calderini Jennifer , Keenan Benjamin , Hall-Swan Sarah , Hickling Timothy P. , Bennett Eric , Rai Brajesh , Tourdot Sophie
Published: October 2024

We introduce HLAIIPred, a deep learning model to predict peptides presented by class II human leukocyte antigens (HLAII) on the surface of antigen presenting cells. HLAIIPred is trained using a Transformer-based neural network and a dataset comprising of HLAII-presented peptides identified by mass spectrometry. In addition to predicting peptide presentation, the model can also provide important insights into peptide-HLAII interactions by identifying core peptide residues that form such interactions. We evaluate the performance of HLAIIPred on three different tasks, peptide presentation in monoallelic samples, immunogenicity prediction of therapeutic antibodies, and neoantigen prioritization for cancer immunotherapy. Additionally, we created a new dataset of biotherapeutics HLAII peptides presented by human dendritic cells. This data is used to develop screening strategies to predict the unwanted immunogenic segments of therapeutic antibodies by HLAII presentation models. HLAIIPred demonstrates superior or equivalent performance when compared to the latest models across all evaluated benchmark datasets. We achieve a 16% increase in prediction of presented peptides compared to the second-best model on a set of unseen peptides presented by less frequent alleles. The model also improves the area under the precision-recall curve by 3% for distinguishing between immunogenic and non-immunogenic antibodies. We show that HLAIIPred can identify epitopes in therapeutic antibodies and prioritize neoantigens with high accuracy.

HIGHLIGHTS

*

We developed a new deep learning model to address the shortcomings of existing models for the prediction of peptides presented by HLAII molecules.

*

The model is end-to-end and context-free, requiring only a peptide sequence and available HLAII alleles as input.

*

HLAIIPred outperforms the state-of-the-art models on multiple benchmark datasets.

*

The model is able to predict the core residues of peptides that interact with HLAIIs.

*

We created experimental data and developed screening strategies to accurately predict the immunogenic hotspots in therapeutic antibodies.
Double-Blind Randomized Placebo Controlled Trial of aLactobacillusProbiotic Blend in Chronic Obstructive Pulmonary Disease
Authors: Nicola Teodora , Wenger Nancy M. , Evans Michael , Yang Youfeng , Chen Dongquan , Van Der Pol William J. , Walia Amar , Lefkowitz Elliot J. , Wang Jun , LeMoire Ashley , Lin Lois , Morrow Casey , Ambalavanan Namasivayam , Gaggar Amit , Lal Charitharth Vivek
Published: October 2024

Rationale

The gut-lung axis describes the crosstalk between the gut and lung wherein microbiota in the gut modulate systemic anti-inflammatory and immune responses in the lungs.Objectives:We hypothesized that a blend of probiotic bacteria (Lactobacilli) combined with herbal extracts (resB®) could improve quality of life in COPD patients.

Methods

We conducted a randomized, double-blinded, placebo-controlled study (NCT05523180) evaluating the safety and impact of resB® on quality of life in volunteers with COPD. Participants took two capsules of resB® or placebo orally daily for 12 weeks. The primary endpoint was quality of life changes by Saint George’s Respiratory Questionnaire (SGRQ). In addition to safety, exploratory endpoints included changes in serum and sputum biomarkers as well as sputum and stool microbiome.

Measurements and Main Results

resB® was well tolerated by all participants, with no related adverse events reported. Participants who received resB® had improvement in their SGRQ symptom scores from baseline to final visit (P<0.05), while the change in SGRQ symptom scores in those receiving placebo was not significant. Serum and sputum concentrations of matrix metalloproteinase 9, serum c-reactive protein, and serum interleukin 6 decreased (P<0.05) between baseline and final visit in the resB® group, corresponding with an increase in stoolLactobacilliabundance. Relative abundance ofVeillonellaalso increased in stool and sputum in the resB® group.

Conclusions

Participants with COPD who received resB® improved in respiratory symptoms over a 12-week course. Serum and sputum biomarkers suggest administration of the probiotic and herbal blend reduces inflammation and may thereby attenuate symptoms.
Ethnic Discrimination is Related to Increased Substance Use and Intentions to Use Across Diverse Groups of Adolescents
Authors: Rosales Robert , Veliz Philip , Jardine John , Weigard Alexander , McCabe Sean Esteban
Published: October 2024

Introduction

In recent years, adolescents of color report greater use of selected substances than white adolescents, including alcohol, tobacco, and cannabis. Increased levels of discrimination during the COVID-19 pandemic may have added to the chronic burden associated with increased substance use among adolescents of color. This study assessed the prevalence of substance use (alcohol, tobacco and cannabis) and intentions to use among adolescents by race/ethnicity and assessed associations between discrimination and substance use outcomes across groups.

Methods

The data come from the national panel of 11,868 adolescents in the Adolescent Brain Cognitive Development study (baseline through 4thfollow-up). We tested the prevalence rates of substance use and intentions by race/ethnicity. Multivariable longitudinal analyses tested whether 1) discrimination was connected to substance use and intentions, and 2) whether that relationship differed by race/ethnicity.

Results

White adolescents reported the greatest use and curiosity about alcohol. Black adolescents reported the highest rates of being willing to try any of the substances. Hispanic adolescents reported the highest rates of cannabis use. Multiracial adolescents reported the highest rates of tobacco use, curiosity about tobacco, and curiosity about cannabis. Discrimination was found to be associated with greater substance use among all racial/ethnic groups, except Black adolescents for alcohol use and Asian adolescents for alcohol use and tobacco use.

Conclusion

This study supports national trends about substance use disparities among adolescents of color. Findings from this study also show that discrimination may explain some of these increased trends through intentions to use substances.
Blood Culture Utilization Optimization: Data-Driven Approaches to Guide Stewardship During Critical Supply Shortages
Authors: Amrollahi Fatemeh , Marshall Nicholas P. , Chang Amy , Deresinski Stanley , Banaei Niaz , Ma Stephen , Chen Jonathan H.
Published: October 2024

Amidst the global blood culture bottle shortage, there is an urgent need to reduce unnecessary blood cultures. This study developed BSICalc and BSIScore, data-driven models using electronic health record (EHR) data, to guide blood culture ordering in the emergency department at the point-of-care, enhancing stewardship efforts and supporting clinical decision-making.
SpO2/FiO2Ratio as a Better Metric for Assessment of RBC Transfusion Effectiveness in Non-traumatic Critically Ill Patients with Physiologic Derangements
Authors: Choudhary Tilendra , Smith Geoffrey , Roback John D. , Patel Ravi M. , Josephson Cassandra D. , Kamaleswaran Rishikesan
Published: October 2024

Identifying critically ill patients who are likely to improve their respiratory physiology following RBC blood transfusion is dynamic and difficult. Current decision tools are over-reliant on hemoglobin transfusion thresholds, without considering respiratory measures that may reflect physiologic effects of anemia and functional responses to RBC transfusion. Further, routine clinical measures to determine transfusion efficacy beyond hemoglobin increment are lacking to identify patients as responders or non-responders. We present a two-center retrospective cohort study aiming to determine a potential biomarker to assess the physiologic response of RBC transfusion for ICU patients. The study was performed with 13,274 eligible admissions at the first center. Another 3,757 from the second center were used for validation purpose. We introduced a comparative analysis of two respiratory measures, SpO2and SpO2/FiO2(SF) ratio, in addition to hemoglobin, to assess individual patient responses to RBC transfusion. A statistical study was performed to analyze the change in these markers before and after the transfusion interval. Based on quantitative statistical analyses, we found SF ratio to be a more effective biomarker than hemoglobin alone for revealing RBC transfusion efficacy. There existed an inverse correlation between pre-transfusion SF and transfusion efficacy. The results were consistent across both centers, revealing generalizability.
Controlled colonization of the human gut with a genetically engineered microbial medicine
Authors: Whitaker Weston R. , Russ Zachary N. , Shepherd Elizabeth Stanley , Popov Lauren M. , Louie Alexander , Lam Kathy , Zong David M. , Gill Clare C. C. , Gehrig Jeanette , Rishi Harneet S. , Tan Jessica A. , Buness Areta , Godoy Janeth , Banta Domenique , Jaidka Sonia , Wilson Katheryne , Flood Jake , Bukshpun Polina , Yocum Richard , Cook David N. , Warsi Tariq , McLean Lachy , Sonnenburg Justin L. , Deloache William C.
Published: October 2024

Precision microbiome programming for therapeutic applications has been limited by challenges in achieving reproducible colonization of the colon. Previously, we used a porphyran prebiotic to create a synthetic niche to engraft engineered bacteria into diverse microbiota in mice. Here we extend that work with biocontainment that links essential gene expression to porphyran presence yielding a platform for controlled colonization and decolonization of humans with engineeredBacteroides. We engineered this chassis with a five-gene oxalate degradation pathway, creating a therapeutic candidate that reduces hyperoxaluria, a cause of kidney stones, in pre-clinical models. Our Phase 1/2a clinical trial demonstrates tunable and reversible engraftment in humans, shows promising oxalate reductions, highlights addressable challenges in this novel modality for therapeutics, and queries key questions in microbiome science.
PET/CT guided tuberculosis treatment shortening: a randomized trial
Authors: Malherbe Stephanus T. , Chen Ray Y. , Yu Xiang , Smith Bronwyn , Liu Xin , Gao Jingcai , Diacon Andreas H. , Dawson Rodney , Tameris Michele , Zhu Hong , Qu Yahong , Jin Hongjian , Pan Shouguo , Dodd Lori E. , Wang Jing , Goldfeder Lisa C. , Cai Ying , Arora Kriti , Vincent Joel , Narunsky Kim , Serole Keboile , Goliath Rene T. , Da Costa Laylah , Taliep Arshad , Aziz Saalikha , Daroowala Remy , Thienemann Friedrich , Mukasa Sandra , Court Richard , Sossen Bianca , Ahlers Petri , Mendelsohn Simon C. , White Lisa , Gouel Aurélie , Lau Chuen-Yen , Hassan Samy , Liang Lili , Duan Hongfei , Moghaddam Gita K. , Paripati Praveen , Lahouar Saher , Harris Michael , Wollenberg Kurt , Jeffrey Brendan , Tartakovsky Mike , Rosenthal Alex , Duvenhage Michael , Armstrong Derek T. , Song Taeksun , Winter Jill , Gao Qian , Via Laura E. , Wilkinson Robert J. , Walzl Gerhard , Barry Clifton E.
Published: October 2024

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers. Participants with less extensive disease (N=273) were randomly assigned to complete therapy after four months or continue receiving treatment for six months. Amongst participants who received four months of therapy, 17 of 141 (12.1%) experienced unfavorable outcomes compared to only 2 of 132 (1.5%) who completed six months of treatment (treatment success 98.4% in B, 86.7% in C (difference -11.7%, 95% CI, -18.2%, -5.3%)). In the non-randomized arm that included participants with more extensive disease, only 8 of 248 (3.2%) experienced unfavorable outcomes. Total cavity volume and total lesion glycolysis at week 16 were significantly associated with risk of unfavorable outcome in the randomized participants. Based on PET/CT scans at TB recurrence, bacteriological relapses (confirmed by whole genome sequencing) predominantly occurred in the same active cavities originally present at baseline. Automated segmentation of the serial PET/CT scans was later performed, and machine-learning was used to classify participants according to their likelihood of relapse, allowing the development of predictive models with good performance based on CT, PET, microbiological and clinical characteristics. These results open the possibility for more efficient studies of future TB treatment regimens.
Data Missingness in Digital Phenotyping: Implications for Clinical Inference and Decision-Making
Authors: Shen Joanna , Abdelkader Kareem , Isaac Zacharia , Sarno Danielle , Kurz Jennifer , Silbersweig David , Onnela Jukka-Pekka , Barron Daniel
Published: October 2024

Background

Digital phenotyping, the use of personal digital devices to capture and categorize real-world behavioral and physiological data, holds great potential for complementing traditional clinical assessments. However, missing data remains a critical challenge in this field, especially in longitudinal studies where missingness might obscure clinically relevant insights.

Objective

This paper examines the impact of data missingness on digital phenotyping clinical research, proposes a framework for reporting and accounting for data missingness, and explores its implications for clinical inference and decision-making.

Methods

We analyzed digital phenotyping data from a study involving 85 patients with chronic musculoskeletal pain, focusing on active (PROMIS-29 survey responses) and passive (accelerometer and GPS measures) data collected via the Beiwe Research Platform. We assessed data completeness and missingness at different timescales (day, hour, and minute levels), examined the relationship between data missingness and accelerometer measures and imputed GPS summary statistics, and studied the stability of regression models across varying levels of data missingness. We further investigated the association between functional status and day-level data missingness in PROMIS-29 subscores.

Results

Data completeness showed substantial variability across timescales. Accelerometer-based cadence and imputed GPS-based home time and number of significant locations were generally robust to varying levels of data missingness. However, the stability of regression models was affected at higher thresholds (40% for cadence and 60% for home time). We also identified patterns wherein data missingness was associated with functional status.

Conclusion

Data missingness in clinical digital phenotyping studies impacts individual- and group-level analyses. Given these results, we recommend that studies account for and report data at multiple timescales (we recommend day, hour, and minute-level where possible), depending on the clinical goals of data collection. We propose a modified framework for categorizing missingness mechanisms in digital phenotyping, emphasizing the need for clinically relevant reporting and interpretation of missing data. Our framework highlights the importance of integrating clinical with statistical expertise, specifically to ensure that imputing missing data does not obscure but helps capture clinically meaningful changes in functional status.
Metabolic alterations in Crohn’s disease: A Systematic Review
Authors: Dev Atul , Kahlon Sartajdeep , Ruiz Jonathan Javier , Kushwaha Avinash Chandra , Van Noord Megan G. , Adams Sean H. , Barrett Kim Elaine , Arkin Adam Paul , Dave Maneesh
Published: October 2024

Background

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Several studies have identified dysregulated metabolites in patients with CD. However, there is significant variability in the metabolites found to be dysregulated across these studies, making it unclear whether a comprehensive, disease-specific metabolic signature for CD exists.

Objective

To analyze Crohn’s disease-specific metabolomic studies and available datasets to identify a comprehensive signature of dysregulated metabolites and metabolic pathways implicated in human CD.

Design

A comprehensive systematic review was conducted using Medline and Embase databases to identify studies (from inception to May 2024) that employed analytical chemistry techniques to quantify metabolites in various biological samples from Crohn’s disease patients and non-IBD controls. Metabolites that were significantly altered in Crohn’s patients and reported in at least two studies were included for further analysis.

Results

The systematic search identified 3,632 studies, with 88 selected for data extraction. Across these studies, 79 metabolites were consistently reported as significantly altered in Crohn’s disease (CD) patients in two or more studies. These metabolites form a distinct metabolic signature that differentiates CD patients from non-IBD controls, highlighting their relevance in the pathophysiology of the disease.

Conclusion

This systematic review presents a comprehensive and well-defined signature of dysregulated metabolites across various biological samples and provides detailed insight into the perturbed metabolic pathways involved in CD.
Impacts of vaccination on the variant selection of SARS-CoV-2 and the subsequent case hospitalization rate: insights from the first U.S. Omicron wave
Authors: Liang Jingbo , Ding Zhaojun , Zhang Qingpeng , Yuan Hsiang-Yu
Published: October 2024

Background

COVID-19 vaccines, while providing protection against hospitalization, could inadvertently increase selection pressure on new immune-escape variants, impacting case hospitalization rate (CHR).

Methods

Using epidemiological and genomic sequence data, we calculated daily state-level CHR and the proportion of Omicron mutations in the United States during the first Omicron wave (between December 11, 2021, and March 22, 2022). We derived mathematical formulas to link evolution responses to an increasing population immunity with lagged regression models. Using mediation analysis, together with generalized linear mixed models and distributed lag nonlinear models, we assessed how natural selection, shaped by vaccine coverage, impacts CHR.

Results

The model showed that increasing vaccination coverage from 45% to 70% contributed to a reduction in CHR from 5.8% to 4.4%. Part of the reduction resulted from direct vaccine protection (OR: 0.85, p-value=0.012). However, the higher vaccination coverage was correlated with a 20% increase in the proportion of BA.1/BA.1.1-associated mutations. As the Omicron variants were less severe than their predecessors (Delta), CHR further reduced (OR: 0.87, p-value<0.001). Marginally, this could reduce CHR from 5.8% to 5.1% via the adaptation of Omicron variants as marginal effect without accounting for direct vaccine protection.

Conclusions

The study offers new insight into vaccine strategies for reducing hospitalization risk by shortening [or maintaining] the circulation of more [or less] virulent variants among infectious diseases. Continuous monitoring of variant evolution, including their virulence, is critical.
The Arabidopsis RNA-binding protein SGS3 is recruited to the chromatin remodeler CHR11 to promote siRNA production from protein-coding genes
Authors: Elmayan Taline , Blein Thomas , Elvira-Matelot Emilie , Masson Ivan Le , Christ Aurélie , Bouteiller Nathalie , Crespi Martin D. , Vaucheret Hervé
Published: October 2024

In plants, aberrant RNAs produced by endogenous genes or transgenes are normally degraded by the nuclear and cytosolic RNA quality control (RQC) pathways. Under certain biotic or abiotic stresses, RQC is impaired, and aberrant RNAs are converted into siRNAs that initiate post-transcriptional gene silencing (PTGS) in the cytosol. How aberrant RNAs are selected and brought to the cytoplasm is not known. Here we show that the RNA-binding protein SUPPRESSOR OF GENE SILENCING (SGS)3 shuttles between the cytosol and the nucleus where it associates with the ISWI-like CHROMATIN REMODELER (CHR)11. CHR11 binds to transgenes prone to trigger PTGS. Knocking downCHR11and its paralogCHR17strongly reduces transgene PTGS, suggesting that SGS3 recruitment by CHR11/17 facilitates PTGS initiation. CHR11 is also enriched at endogenous protein-coding genes (PCGs) producing nat-siRNAs and va-siRNAs under biotic or abiotic stresses, and this production is reduced inchr11 chr17double mutants at genome-wide level. Moreover, impairing CHR11 and CHR17 rescues the lethal phenotype caused by the massive production of siRNAs from PCGs in RQC-deficient mutants. We propose that SGS3 recruitment by CHR11/17 allows exporting RNAs to the cytosol to initiate the production of siRNAs.

One Sentence Summary

The plant PTGS component SGS3 is recruited by the chromatin remodeler CHR11 to select nuclear RNAs for export to the cytosol and siRNA production.
Simulated Solute Tempering 2
Authors: Stratmann Dirk , Moroy Gautier , Tuffery Pierre , Murail Samuel
Published: October 2024

Molecular dynamics (MD) simulations are powerful tools for studying the movement and interactions of molecules, but they can be computationally expensive, especially for large biomolecules like proteins. This is problematic because accurately simulating the motions of these molecules is key to understanding their function. Enhanced sampling methods, such as Simulated Tempering (ST), temperature Replica Exchange Molecular Dynamics (REMD) and Replica Exchange with Solute Tempering (REST and REST2), have been developed to overcome this challenge by improving the efficiency of MD simulations. This article presents a new improved sampling method called Simulated Solvent Tempering 2 (SST2), which builds on the strengths of ST and REST2. SST2 selectively scales the interactions within a biomolecule and with its surrounding environment, effectively accelerating the exploration of its different structural states and their stability at different temperatures. SST2 was tested on three different systems (Chignolin CLN025, Trp-Cage, and a protein-peptide complex, p97/PNGase) and was found to achieve comparable or superior sampling efficiency to ST while requiring fewer temperature rungs. In particular, SST2 is well suited to the study of large biomolecular systems, making it a valuable tool for investigating a wide range of biomolecular processes, from protein folding to drug binding.
Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach
Authors: Pearson Lesley-Anne , Petit Alain-Pierre , Mendoza Martinez Cesar , Bellany Fiona , Lin De , Niven Sarah , Swift Rachel , Eadsforth Thomas , Fyfe Paul , Paul Marilyn , Postis Vincent , Hu Xiao , Cowling Victoria H. , Gray David W
Published: October 2024

The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by the HsRNMT (RNA guanine-7 methyltransferase)-RAM (RNA guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, the development of effective drugs is hindered by a limited understanding of the enzyme’s mechanism and a lack of small molecule inhibitors. Following the elucidation of theHsRNMT-RAM molecular mechanism, we report the biophysical characterization of two small molecule hits. Biophysics, biochemistry and structural biology confirm that both compounds bind competitively with cap and bind effectively toHsRNMT-RAM in the presence of the co-product SAM, with a binding affinity (KD) of approximately 1 μM. This stabilisation of the enzyme-product complex results in uncompetitive inhibition. Finally, we describe the properties of the cap pocket and provided suggestions for further development of the tool compounds.
HBN-EEG: The FAIR implementation of the Healthy Brain Network (HBN) electroencephalography dataset
Authors: Shirazi Seyed Yahya , Franco Alexandre , Hoffmann Maurício Scopel , Esper Nathalia B. , Truong Dung , Delorme Arnaud , Milham Michael P. , Makeig Scott
Published: October 2024

The Child Mind Institute (CMI) Healthy Brain Network (HBN) project has recorded phenotypic, behavioral, and neuroimaging data from ∼5,000 children and young adults between the ages of 5 and 21. Here, we present HBN-EEG, the “analysis-ready” data from its high-density (128-channel) electroencephalographic (EEG) recording sessions formatted as Brain Imaging Data Structure (BIDS) datasets. HBN-EEG also includes behavioral and task-condition events annotated using Hierarchical Event Descriptors (HED), making the datasets analysis-ready for many purposes without ‘forensic’ search for unreported details. We also ensured data consistency and event integrity and marked inconsistencies. HBN-EEG sessions include six tasks, three with no participant behavioral input (passive tasks) and three including button press responses following task instructions (active tasks). Openly available participant information includes age, gender, and four psychopathology dimensions (internalizing, externalizing, attention, and p-factor) derived from a bifactor model of questionnaire data. Currently, HBN-EEG data from more than 2,600 participants is freely available on NEMAR (nemar.org) and OpenNeuro in the form of nine dataset releases, with further dataset releases to follow.
Dietary lipid is largely deposited in skin and rapidly affects insulating properties
Authors: Riley Nick , Kasza Ildiko , Hermsmeyer Isabel DK , Trautman Michaela , Barrett-Wilt Greg , Jain Raghav , Simcox Judith A , Yen Chi-Liang E , MacDougald Ormond A , Lamming Dudley W , Alexander Caroline M
Published: October 2024

Skin has been shown to be a regulatory hub for energy expenditure and metabolism: mutations of skin lipid metabolism enzymes can change the rate of thermogenesis and susceptibility to diet-induced obesity. However, little is known about the physiological basis for this function. Here we show that the thermal properties of skin are highly reactive to diet: within three days, a high fat diet reduces heat transfer through skin. In contrast, a dietary manipulation that prevents obesity accelerates energy loss through skins. We found that skin was the largest target in a mouse body for dietary fat delivery, and that dietary triglyceride was assimilated both by epidermis and by dermal white adipose tissue. Skin from mice calorie-restricted for 3 weeks did not take up circulating lipids and showed a highly depleted stratum corneum. Dietary triglyceride acyl groups persist in skin for weeks after feeding. Using multi-modal lipid profiling, we have implicated both keratinocytes and sebocytes in the altered lipids which correlate with thermal function. In response to high fat feeding, wax diesters and ceramides accumulate, and triglycerides become more saturated. In contrast, in response to the dramatic loss of adipose tissue that accompanies restriction of the branched chain amino acid isoleucine, skin becomes more heat-permeable, resisting changes induced by Western diet feeding, with a signature of depleted signaling lipids. We propose that skin should be routinely included in physiological studies of lipid metabolism, given the size of the skin lipid reservoir and its adaptable functionality
Loss of pleiotropic regulatory functions inTannin1, the sorghum ortholog of Arabidopsis master regulatorTTG1
Authors: Schuh Anthony , Morris Geoffrey P.
Published: October 2024

Transcriptional master regulators are often targeted to improve plant traits, but antagonistic pleiotropic effects of these regulators can hamper this approach. The Myb-bHLH-WDR (MBW) complex is a broadly-conserved transcriptional regulator affecting pigmentation, biotic stress resistance, and abiotic stress tolerance. We investigated the function of sorghum grain pigmentation regulatorTannin1, the ortholog of Arabidopsis pleiotropic WD40 regulatorTTG1, to test for conserved pleiotropic regulatory effects and to better understand the evolution of the MBW complex in Poaceae. We characterized genome-wide differential expression of leaf tissue using RNA sequencing in near-isogenic lines (NILs) that contrasted wildtypeTan1and loss-of-functiontan1-balleles, under optimal temperature and chilling stress. Notably, Gene Ontology analyses revealed no pathways with differential expression betweenTan1andtan1-bNILs, suggesting that, in contrast to ArabidopsisTTG1, Tannin1has no pleiotropic regulatory role in leaves. Further, NILs had no visible difference in anthocyanin pigmentation, and no genes with known or expected function in flavonoid synthesis were differentially expressed. Genome-wide, only 18 total genes were differentially expressed between NILs, with six of these genes located inside the NIL introgression region, an observation most parsimoniously explained bycis-regulatory effects unrelated toTannin1regulation. Comparing our findings with known function ofTTG1orthologs in maize, rice, and Arabidopsis, we conclude that pleiotropic regulatory function in leaf tissue was likely lost in panicoid grass evolution before the sorghum-maize split. These findings inform future molecular breeding of MBW regulated traits and highlight the benefit of subfunctionalization to relieve pleiotropic constraints.
STAMP: Single-Cell Transcriptomics Analysis and Multimodal Profiling through Imaging
Authors: Pitino Emanuele , Pascual-Reguant Anna , Segato-Dezem Felipe , Wise Kellie , Salvador-Martinez Irepan , Crowell Helena Lucia , Courtois Elise , Flynn William F. , Sivajothi Santhosh , Soja Emily , Ruiz Sara , Caratù Ginevra , Sullivan Adrienne E. , Mora Roldan German Atzin , Dredge B. Kate , Marção Maycon , Liu Yutian , Chasteen Hannah , Mohenska Monika , Polo José , Nieto Juan C. , Plummer Jasmine , Heyn Holger , Martelotto Luciano
Published: October 2024

We introduce Single-Cell Transcriptomics Analysis and Multimodal Profiling (STAMP), a scalable profiling approach of individual cells. Leveraging transcriptomics and proteomics imaging platforms, STAMP eliminates sequencing costs, to enable single-cell genomics from hundreds to millions of cells at an unprecedented low cost. Stamping cells in suspension onto imaging slides, STAMP supports single-modal (RNA or protein) and multimodal (RNA and protein) profiling and flexible, ultra-high-throughput formats. STAMP allows the analysis of a single or multiple samples within the same experiment, enhancing experimental flexibility, throughput and scale. We tested STAMP with diverse sample types, including peripheral blood mononuclear cells (PBMCs), dissociated cancer cells and differentiated embryonic stem cell cultures, as well as whole cells and nuclei. Combining RNA and protein profiling, we applied immuno-phenotyping of millions of blood cells simultaneously. We also used STAMP to identify ultra-rare cell populations, simulating clinical applications to identify circulating tumor cells (CTCs). Performingin vitrodifferentiation studies, we further showed its potential for large-scale perturbation studies. Together, STAMP establishes a new standard for cost-effective, scalable single-cell analysis. Without the need for sequencing, STAMP makes high-resolution profiling more affordable and accessible. Designed to meet the needs of research labs, diagnostic cores and pharmaceutical companies, STAMP holds the promise to transform our capacity to map human biology, diagnose diseases and drug discovery.
Detection of titanium nanoparticles in human, animal and infant formula milk
Authors: Rivard Camille , Djebrani-Oussedik Nouzha , Cloix Romane , Hue-Beauvais Cathy , Kuszla Nicolas , Ivanova Elitsa , Simon Marie , Dufour Adrien , Launay Frédéric , Gazeau Florence , Acloque Hervé , Parat Sophie , Poupon Joël , Burtey Anne
Published: October 2024

The sustainability of mammals on Earth relies on milk. During lactation, maternal exposure to pollutants like metal nanoparticles (NPs) can affect offspring development and survival. Despite being banned from food applications in Europe due suspected toxicity, titanium dioxide (TiO2) NPs are still massively manufactured for countless other uses. While contamination of ecosystems is well documented, contamination of mammals remains underexplored. Here, we used synchrotron X-ray fluorescence and single particle inductively coupled plasma mass spectrometry to analyse human, animal, and infant formula milk. Titanium containing micro- and nano-particles were detected in all samples, regardless of the species, location, and processing. We identified varying concentrations, sizes, and combinations of rutile and anatase TiO2, ilmenite FeTiO3and possibly titanite CaTiSiO5or pseudobrookite Fe2TiO5. These findings suggest that milk serves as a carrier for titanium-containing nanomaterials to expose newborns on a daily basis until weaning.
Differential effects of conventional transcranial direct current stimulation (tDCS) and high-definition transcranial direct current stimulation (HD-tDCS) of the cerebellum on offset analgesia
Authors: O’Connor Niamh , Ashe Hannah , Wragan Max , O’Flaherty Ruairí , Deevy-Gray Eoin , Witney Alice G.
Published: October 2024

Background

Offset analgesia (OA) describes the large decrease in perceived pain in response to a minor decrease in applied painful thermal stimulus. Here non-invasive brain stimulation (NIBS) is used to modulate the cerebellum, since the cerebellum is known to signal sensory prediction errors and is implicated in pain processing.

Methods

An OA protocol individualized to heat pain threshold (HPT) was applied via TSA-II (Medoc, Israel). NIBS interventions were applied prior to OA. Cathodal cerebellar transcranial direct current stimulation (tDCS) and high-definition (4X1) transcranial direct current stimulation (HD-tDCS) were applied to 46 healthy participants within a sham controlled repeated measures design to examine whether diffuse or focal stimulation differentially modulates OA.

Results

OA induced hypoalgesia was robust, with 90% of responses showing a drop in perceived pain (δVAS) > 10 following the 1°C fall in temperature. This OA response was augmented following a protocol with sham and focal cathodal cerebellar stimulation on four OA parameters (OAlatency, VASminimum, VASmeanand VAS2ndmax) relative to pre-stimulation. This effect was differential to the protocol with sham and conventional tDCS where two OA metrics altered (OAduration, VAS2ndmax).

Conclusion

OA enhancement via cathodal cerebellar NIBS may involve both a placebo effect and sustaining a noxious sensory prediction error. Understanding how the cerebellum is involved in OA could enhance therapies for pain patients.
DYRK1A kinase triplication is the major cause of Otitis Media in Down Syndrome
Authors: Tateossian Hilda , Southern Amy , Vikhe Pratik , Lana-Elola Eva , Watson-Scales Sheona , Gibbins Dorota , Williams Debbie , Purnell Thomas , Mburu Philomena , Parker Andrew , Norris Dominic P , Santos-Cortez Regie Lyn P , Herrmann Brian W , Wells Sara , Lad Heena V , Fisher Elizabeth MC , Tybulewicz Victor LJ , Brown Steve DM
Published: October 2024

Down syndrome (DS), which arises from trisomy of the whole or part of chromosome 21 (Hsa21), is one of the most common genetic abnormalities in humans. DS manifests as a broad spectrum of phenotypic features, including hearing loss due to otitis media with effusion (OME), affecting around 50% of children with DS. We employed a panel of mouse models of DS comprising a nested series of duplications covering the regions of the mouse genome syntenic to Hsa21 in order to define the loci involved with OME in DS. We identified a major locus on mouse chromosome 16, containing only 12 genes, that causes OME. Within this region we demonstrate that normalizing the gene dosage ofDyrk1arestored the wild-type phenotype. Investigation of downstream pathways of DYRK1A uncovered a number of pathological mechanisms whereby DYRK1A triplication leads to middle ear inflammation and vascular leak. These include cross-talk of DYRK1A and TGFβ signaling and its impact on proinflammatory cytokines IL-6 and IL-17, as well as raised VEGF levels in the middle ear accompanied by increasedHif1a. We conclude that DYRK1A is a potential therapeutic target for OME in children with DS.
A Targeted Reference Database for Improved Analysis of Environmental 16S rRNA Oxford Nanopore Sequencing Data
Authors: Philip Melcy , Nilsen Tonje , Majaneva Sanna , Pettersen Ragnhild , Stokkan Morten , Ray Jessica Louise , Keeley Nigel , Rudi Knut , Snipen Lars-Gustav
Published: October 2024

The Oxford Nanopore Technologies (ONT) sequencing platform is compact and efficient, making it suitable for rapid biodiversity assessments in remote areas. Despite its long reads, ONT has a higher error rate compared to other platforms, necessitating high-quality reference databases for accurate taxonomic assignments. However, the absence of targeted databases for underexplored habitats, such as the seafloor, limits ONT’s broader applicability for exploratory analysis.

To address this, we propose an approach for building environmentally-targeted databases to improve 16S rRNA gene (16S) analysis using Oxford Nanopore Technologies (ONT), using seafloor sediment samples from the Norwegian coast as an example. We started by using Illumina short-read data to create a database of full-length or near full-length 16S sequences from seafloor samples. Initially, amplicons are mapped to the SILVA database, with matches added to our database. Unmatched amplicons are reconstructed using METASEED and Barrnap methodologies with amplicon and metagenome data. Finally, if the previous strategies did not succeed, we included the short-read sequences in the database. This resulted in AQUAeD-DB, which contains 14 545 16S sequences clustered at 95% identity. Comparative database analysis reveal that AQUAeD-DB provides consistent results for both Illumina and Nanopore read assignments (median correlation coefficient: 0.50), whereas a standard database showed a substantially weaker correlation. These findings also emphasize its potential to recognize both high and low-abundance taxa, which could be key indicators in environmental studies. This work highlights the necessity of targeted databases for environmental analysis, especially for ONT-based studies, and lays foundations for future extension of the database.
Molecular basis of autoimmune disease protection by MDA5 variants
Authors: Singh Rahul , Herrero del Valle Alba , Joiner Joe D , Zwaagstra Marleen , Ferguson Brian J , van Kuppeveld Frank J.M. , Modis Yorgo
Published: October 2024

MDA5 recognizes dsRNA from viruses and retroelements. Cooperative filament formation and ATP-dependent proofreading confer MDA5 with the necessary sensitivity and specificity for dsRNA. The gene encoding MDA5 is a hotspot for disease-associated variants. Many MDA5 variants are associated with protection from autoimmune disease, while increasing the risk of infection and chronic inflammation, but how these variants affect MDA5-dependent RNA sensing remains unclear. Here, we determine the consequences of autoimmune-protective MDA5 variants on the molecular structure and activities of MDA5. The rare variants E627* and I923V reduce the cellular interferon response to picornavirus infection and are deficient in filament formation. The I923V variant is ATPase hyperactive, causing premature dissociation from dsRNA. Cryo-EM structures of MDA5 I923V bound to dsRNA at different stages of ATP hydrolysis reveal smaller RNA binding interfaces, leading to excessive proofreading activity. Variants R843H and T946A, which are genetically linked and cause mild phenotypes, have no effect on dsRNA recognition, suggesting an indirect disease mechanism. We conclude that the autoimmune-protective MDA5 variants lead to a loss of MDA5-dependent signaling via multiple distinct mechanisms.
Same bi-directional modulation of contrast appearance for voluntary presaccadic attention and involuntary exogenous attention
Authors: Zhang Tianyu , Cai Yongchun
Published: October 2024

Different types of attention alter subjective visual perception in fundamentally distinct ways. Previous studies have focused on covert attention without concurrent eye movements, showing that covert exogenous (involuntary) attention enhances contrast appearance of low-contrast stimuli while diminishing that of high-contrast stimuli, whereas covert endogenous (voluntary) attention uniformly enhances contrast appearance. However, the attentional effect preceding saccadic eye movements, a critical component of natural vision, remain understudied. Here, we found that when participants voluntarily initiated saccades, presaccadic attention enhanced the appearance of low-contrast stimuli while attenuating the appearance of high-contrast stimuli (Experiment 1,N= 29 adults). This pattern is surprisingly similar to exogenous attention but distinct from endogenous attention. Notably, the presaccadic attentional attenuation effect accumulated gradually during saccade preparation and remained positively correlated with the exogenous attentional effect (Experiment 2,N= 24 adults). These findings suggest a shared mechanism between presaccadic and exogenous attention in shaping visual perception.