bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase separated liquid vimentin droplets stabilize actin fibers through wetting
Authors: Basu Arkaprabha , Krug Tommy , du Pont Benjamin , Huang Qiaoling , Sun Sijie , Adam Stephen A. , Goldman Robert , Weitz David A. 
Published: June 2024

AbstractThe cytoskeleton is composed of F-actin, microtubules, and intermediate filaments (IFs). Vimentin is the most ubiquitous IF. It is involved in wound healing, tissue fibrosis and cancer metastasis, all of which require rapid vimentin filaments assembly. In this paper, we report that un-polymerized vimentin forms liquid condensates that appear to enable rapid filament growth. Given the transient nature of these droplets, we focus on properties of vimentin-Y117L, a mutant which does not form filaments, enabling us to study these droplets in detail. They dissolve under 1,6-Hexanediol treatment and under decreasing concentration, confirming that they are liquid, and phase separated. These condensates extensively wet actin fibers, rendering them resistant to actin-depolymerizing drugs. We show similar behavior occurs in wild type vimentin during its assembly into filaments.
Interpretation of murine models of cardiac disease is enhanced by consideration of divergently expressed human-mouse orthologous genes
Authors: Cappa Oisín , Watson Chris , Simpson David 
Published: June 2024

AbstractHumans and mice share remarkably similar cardiac anatomy and physiology and have many orthologous genes with high sequence similarity. Together with their small size and short lifespan, these factors are major contributors to the popularity of mice as research models. Nonetheless, findings in mice often fail to translate into humans. We propose that this may be due in part to differences in gene expression. Advances in molecular genomics have enabled profiling of gene expression at the level of individual cells through single-cell RNA-sequencing. Large repositories of human and murine data across many organs and tissues, including the heart, are now available. However, there is currently a lack of comparative research which directly quantifies similarities and differences in expression of orthologous genes between human and mouse.This study is the first, to our knowledge, to directly compare celltype-specific expression conservation and divergence between orthologous genes in human and mouse heart. Cardiac data from 7 human and mouse scRNA-seq publications was retrieved, with mouse data converted to equivalent human gene orthologues. The datasets were integrated and subjected to comparative transcriptomic analysis in R using Seurat.Classical celltype markers did not perform equally across species. We have identified species-conserved celltype marker genes, providing a useful resource to identify cardiac cell populations in both species. Further, we have identified and ranked divergence between species for each cardiac celltype, highlighting genes which vary considerably in expression between human and mouse heart. Many of these have been genetically modified to create mouse models or encode proteins targeted by pharmaceutical drugs. Researchers should carefully consider these highly divergent genes when planning, or interpreting data from, mouse models of human biology.
Risk Factors of Multi-Drug Resistant Tuberculosis among Tuberculosis Patients in Province 3, Nepal: A case-control study
Authors: Acharya Puspa , Bhattarai Niraj , Kunwar Bhuban Raj , Sharma Khem Raj , Khanal Vijay Kumar , Yadav Birendra Kumar 
Published: June 2024

AbstractBackgroundDrug-resistant tuberculosis poses a significant threat to global TB control efforts, potentially reversing progress made in reducing TB-related morbidity and mortality. This study aims to identify risk factors for multidrug-resistant TB [MDR-TB] in Province 3, Nepal.MethodologyA case-control study was conducted by matching TB-infected patients undergoing MDR-TB treatment and DS-TB treatment by gender. Data was collected through structured questionnaires and interviews and analyzed using binary logistic regression.ResultsSignificant risk factors for MDR-TB included Pulmonary Tuberculosis [PTB], previous TB treatment history, close contact with DR-TB patients, and subjective feelings of sadness.ConclusionThe study highlights the importance of prevention measures to break transmission chains and infection control in health facilities. Additionally, it underscores the need for mental health support for TB patients.
KHDRBS3 facilitates self-renewal and temozolomide resistance of glioblastoma cell lines
Authors: Somrit Kanokkuan , Krobthong Sucheewin , Yingchutrakul Yodying , Phueakphud Nut , Wongtrakoongate Patompon , Komyod Waraporn 
Published: June 2024

AbstractGlioblastoma is a deadly tumor which possesses glioblastoma stem cell populations involved in temozolomide resistance. To gain insight into the mechanisms of self-renewing and therapy-resistant cancer stem cells, subcellular proteomics was utilized to identify proteins whose expression is enriched in U251-derived glioblastoma stem-like cells. The RNA binding protein KHDRBS3 was successfully identified as a gene up-regulated in the cancer stem cell population compared with its differentiated derivatives. Depletion of KHDRBS3 by RNA silencing led to a decrease in cell proliferation, neurosphere formation, migration, and expression of genes involved in glioblastoma stemness. Importantly, temozolomide sensitivity can be induced by the gene knockdown. Collectively, our results highlight KHDRBS3 as a novel factor associated with self-renewal of glioblastoma stem-like cells and temozolomide resistance. As a consequence, targeting KHDRBS3 may help eradicate glioblastoma stem-like cells.
Comparison of three tiled amplicon sequencing approaches for SARS-CoV-2 variant detection from wastewater
Authors: Lott Megan E. J. , Sullivan Amanda H. , Lariscy Leah M. , Norfolk William A. , Dillon Katie C. , Beaudry Megan S. , Glenn Travis C. , Lipp Erin K. 
Published: June 2024

ABSTRACTDuring the COVID-19 pandemic, the detection and sequencing of SARS-CoV-2 from wastewater proved to be a valuable tool in assessing trends at the community level. Several whole genome enrichment methods have been proposed for sequencing SARS-CoV-2 from the mixed wastewater community, but there is little consensus on the most appropriate sequencing methods for variant detection or abundance estimations. Few studies have elucidated the errors associated with these methods or have established minimum sequencing requirements for correct interpretation of the results. To address these needs, we systematically assessed the efficacy of three tiled amplicon enrichment methods (Freed/Midnight, ARTIC V4, NEB VarSkip) for whole genome sequencing of SARS-CoV-2 variants using mock wastewater communities with variants at known proportions. We found the ARTIC V4 approach yielded the most accurate results for variant identification and variant abundance estimation, followed by the NEB VarSkip approach. Conversely, the NEB VarSkip method obtained the highest genomic coverage, with the ARTIC V4 method achieving the second highest coverage. Finally, we determined that the Freed/Midnight library preparation methods are not well-suited for use with short read sequencing. Based on the present results, the ARTIC V4 workflow appears to be the most robust and cost-effective approach for monitoring circulating SARS-CoV-2 variants with wastewater surveillance.IMPORTANCEThis work is informative for practitioners of wastewater-based epidemiology. Here, we detail a systematic comparison of three tiled amplicon sequencing approaches for enrichment of SARS-CoV-2 variants from wastewater. Using mock communities of known variant composition, we validate the analysis methods previously published by Baaijens et al. in Genome Biology (2022) for estimating variant abundance from wastewater using an RNAseq pipeline, kallisto. We provide recommendations for minimum sequencing requirements for accurate abundance estimates of SARS-CoV-2 variants in wastewater. The sequences generated from the mock communities have been uploaded to NCBI’s Sequence Read Archive and will be useful to other practitioners seeking to validate their sequencing methods or bioinformatic pipelines.
The Cystic Fibrosis Transmembrane Regulator Controls Tolerogenic Responses to Food Allergens in Mice and Humans
Authors: Emmenegger Marc , Zografou Chryssa , Dai Yile , Hoyt Laura R. , Gudneppanavar Ravindra , Chincisan Andra , Rehrauer Hubert , Noé Falko J. , Zajac Natalia , Meisl Georg , Schneider Matthias M. , Nguyen Hang , Höpker Katja , Knowles Tuomas P. J. , Sospedra Mireia , Martin Roland , Ring Aaron M. , Leeds Stephanie , Eisenbarth Stephanie C. , Egan Marie E. , Bruscia Emanuela M. , Aguzzi Adriano 
Published: June 2024

AbstractIgE antibodies against the allergen Ara-h2 can cause life-threatening anaphylaxis upon exposure to peanuts. Desensitization strategies aim at inducing IgG responses against Ara-h2 which may compete with anaphylactogenic IgE. Here we assessed anti-Ara-h2 titers in an unselected cohort of 24,536 adult patients admitted to a general hospital for disparate medical reasons. Surprisingly, adult (n=177) and pediatric (n=76) patients with cystic fibrosis (pwCF) had IgG4, but not IgE, against several peanut and soybean allergens, yet did not suffer from peanut allergy. Antibody repertoires were not globally perturbed in pwCF, and heterozygous Cystic Fibrosis Transmembrane Regulator (CFTR) mutation carriers had the same prevalence of food allergies as pwCF. Peanut sensitisation ofCftr-/-mice failed to induce IgE and was associated with elevated IFN-γ. We conclude that CFTR is a key regulator of anaphylactogenic and tolerogenic responses to food allergens. CFTR-controlled cytokine responses including IFN-γ, in combination with a compromised epithelial barrier, may trigger a preferential IgG4 response resulting in tolerance to food allergens.HighlightsWe investigated serum IgG against Ara-h2 in 24,536 patients and identified 133 seropositives.Seropositivity was associated with cystic fibrosis, and these patients had IgG4 but not IgE.We reproduced these results in a paediatric validation cohort and in aCftr-/-mouse model.A compromised epithelial barrier and the cytokine milieu might explain this phenotype.
Eccentric Vessel Wall Enhancement and hs-CRP as Prognostic Markers in Acute Ischemic Stroke: A Prospective Cohort Study
Authors: Na Seunghee , Kim Taewon , Lee Jung-hwi , Koo Jaseong , Hong Yun Jeong , Kim Seong-Hoon 
Published: June 2024

AbstractBackground and PurposeEccentric vessel wall enhancement (EVWE) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers associated with atherosclerotic disease. We investigated their prognostic value in patients with acute ischemic stroke receiving guideline-adherent medical treatment.MethodsIn this prospective observational cohort study, patients with acute non-cardioembolic ischemic stroke underwent vessel wall MRI and hs-CRP testing. The primary outcome was subsequent ischemic stroke during the follow-up period. The median follow-up duration was 21 months. Kaplan-Meier survival and Cox regression analysis was used to determine the associations between EVWE, hs-CRP levels, and subsequent ischemic stroke.ResultsAmong 191 patients, 81 (42.4%) had EVWE. EVWE positivity showed a trend towards a lower risk of subsequent ischemic stroke compared to EVWE negativity (HR 0.32, 95% CI 0.12-0.87; P=0.061). Hs-CRP levels were not significantly associated with recurrent stroke risk. The combination of EVWE positivity and low hs-CRP levels (<1.25 mg/L) was associated with the most favorable outcome, while EVWE negativity and high hs-CRP levels (≥1.25 mg/L) were associated with the worst outcome (HR 0.143, 95% CI 0.04-0.50; P=0.031).ConclusionsIn patients with acute ischemic stroke receiving optimal medical therapy, EVWE positivity may paradoxically indicate a lower risk of recurrent stroke. The combination of EVWE and hs-CRP status provides prognostic information, with EVWE positivity and low hs-CRP levels associated with the most favorable outcome. These findings highlight the potential role of integrating imaging and serum inflammatory biomarkers in risk stratification and management of acute ischemic stroke patients.
Social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults
Authors: Girolamo Teresa , Escobedo Alicia , Butler Lindsay , Larson Caroline A. , Campos Iván , Greene-Pendelton Kyle 
Published: June 2024

AbstractDespite their importance, little is known about how social drivers of health shape communicative outcomes in autism. Even less is known when considering the intersection of race and language impairment. An understanding of factors in communicative outcomes is key for characterizing developmental trajectories and informing supports. This cross-sectional observational study examined the role of social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults. Participants ages 13 to 30 (N= 73) completed a behavioral assessment protocol, including language and nonverbal cognitive skills, as well as social drivers of health (sense of community, unmet services, barriers to services). Correlational analyses revealed associations between social drivers of health on social communication impairment and real-world communication. Generalized linear mixed-effects modeling revealed that language predicted real-world communication, but sense of community predicted social communication impairment. Findings point to the importance of assessing both individual differences and social drivers of health in outcomes in autism research. Future work should focus on social drivers of health in larger-scale analyses of outcomes in minoritized autistic individuals during the transition to adulthood, considering supports that align with service eligibility and person-centered outcomes.Lay AbstractWhere people live, work, and spend their time is important. Environments can have more or less services or differ in how much they help people feel like they belong to their community. These parts of the environment are called social drivers of health. Social drivers of health are important for outcomes in autism, but we do not know much about them in racially and ethnically minoritized autistic teens or adults. We recruited 73 minoritized autistic teens and adults ages 13 to 30 years and 52 caregivers (parents, grandparents, sibling) to our study. Teens and adults did language and NVIQ tests on Zoom. Teens, adults, and caregivers also answered questionnaires. Sense of community was important for social communication impairment, and language was important for real-world communication. These findings tell us two things. First, thinking about how to create supportive communication environments for autistic teens and adults is important. Second, understanding how social drivers of health shape outcomes is important. In the future, we should focus on how improving environments can help minoritized autistic teens and adults meet their communication goals.
Steering From the Rear: Coordination of Central Pattern Generators Underlying Navigation by Ascending Interneurons
Authors: Jonaitis Julius , Hibbard Karen L. , Layte Kaity McCafferty , Hiramoto Atsuki , Cardona Albert , Truman James W. , Nose Akinao , Zwart Maarten F. , Pulver Stefan R. 
Published: June 2024

ABSTRACTUnderstanding how animals coordinate movements to achieve goals is a fundamental pursuit in neuroscience. Here we explore how neurons that reside in posterior lower-order regions of a locomotor system project to anterior higher-order regions to influence steering and navigation. We characterized the anatomy and functional role of a population of ascending interneurons in the ventral nerve cord ofDrosophilalarvae. Through electron microscopy reconstructions and light microscopy, we determined that the cholinergic 19f cells receive input primarily from premotor interneurons and synapse upon a diverse array of postsynaptic targets within the anterior segments including other 19f cells. Calcium imaging of 19f activity in isolated central nervous system (CNS) preparations in relation to motor neurons revealed that 19f neurons are recruited into most larval motor programmes. 19f activity lags behind motor neuron activity and as a population, the cells encode spatio-temporal patterns of locomotor activity in the larval CNS. Optogenetic manipulations of 19f cell activity in isolated CNS preparations revealed that they coordinate the activity of central pattern generators underlying exploratory headsweeps and forward locomotion in a context and location specific manner. In behaving animals, activating 19f cells suppressed exploratory headsweeps and slowed forward locomotion, while inhibition of 19f activity potentiated headsweeps, slowing forward movement. Inhibiting activity in 19f cells ultimately affected the ability of larvae to remain in the vicinity of an odor source during an olfactory navigation task. Overall, our findings provide insights into how ascending interneurons monitor motor activity and shape interactions amongst rhythm generators underlying complex navigational tasks.
Context-dependent coordination of movement inTribolium castaneumlarvae
Authors: Xu Ying Bella , Zwart Maarten F. , Pulver Stefan R. 
Published: June 2024

AbstractInsect pests, like the red flour beetleTribolium castaneum, destroy up to 20% of stored grain products worldwide, making them a significant threat to food security. Their success hinges upon adapting their movements to unpredictable, heterogeneous environments like flour.Triboliumis well developed as a genetic model system; however, little is known about their natural locomotion and how their nervous systems coordinate adaptive movement. Here, we employed videographic whole-animal and leg tracking to assess howTriboliumlarvae locomote over different substrates and analyze their gait kinematics across speeds. Unlike many hexapods, larvae employed a bilaterally symmetric, posterior-to-anterior wave gait during fast locomotion. At slower speeds, coordination within thoracic segments was disrupted, although intersegmental coordination remained intact. Moreover, larvae used terminal abdominal structures (pygopods) to support challenging movements, such as climbing overhangs. Pygopod placement coincided with leg swing initiation, suggesting a stabilizing role as adaptive anchoring devices. Surgically lesioning the connective between thoracic and abdominal ganglia impaired pygopod engagement and led to escalating impairments in flat-terrain locomotion, climbing and tunnelling. These results suggest that effective movement inTriboliumlarvae requires thoracic-abdominal coordination, and that larval gait and limb recruitment is context-dependent. Our work provides the first kinematic analysis ofTriboliumlarval locomotion and gives insights into its neural control, creating a foundation for future motor control research in a genetically tractable beetle that jeopardizes global food security.Summary statementRed flour beetle larvae walk with a legged wave gait and use their tails as anchors to climb inclines and tunnel into flour.
TheBrachypodium distachyonpangenome highlights Transposable Element dynamics in the species
Authors: Saidi Somia , Blaison Mathieu , del Pilar Rodríguez-Ordóñez María , Confais Johann , Quesneville Hadi 
Published: June 2024

AbstractThe role of transposable elements (TEs) in host adaptation can be explored with a pangenomic approach. Individuals of the same species undergo independent TE insertions, causing genetic variability upon which natural selection acts. This can lead to improved adaptation of individuals to their environment. The advent of third-generation sequencing has enabled use of multiple whole-genomede novoassemblies for a given species, avoiding bias introduced by a single reference genome. We developed a new pipeline, panREPET, for such data. It compares TE copies between each pair of individuals then identifies copies shared by a group of individuals. This gives the exact sequence and genomic context of each TE copy. We describe here TE insertions shared among 54Brachypodium distachyon genomes. We were able to date two major TE bursts corresponding to major climate events: 22 kya during the Last Glacial Maximum and 10 kya during the Holocene.
The cell cycle oscillator and spindle length set the speed of chromosome separation inDrosophilaembryos
Authors: Xu Yitong , Chao Anna , Rinaldin Melissa , Kickuth Alison , Brugués Jan , Di Talia Stefano 
Published: June 2024

SummaryAnaphase is tightly controlled in space and time to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm. Yet, the relationship between spindle size and chromosome movement remains poorly understood. Here, we address how the movement of chromosomes changes during the cleavage divisions of theDrosophilablastoderm. We show that the speed of chromosome separation gradually decreases during the 4 nuclear divisions of the blastoderm. This reduction in speed is accompanied by a similar reduction in the length of the spindle, thus ensuring that these two quantities are tightly linked. Using a combination of genetic and quantitative imaging approaches, we find that two processes contribute to controlling the speed at which chromosomes move at mitotic exit: the activity of molecular motors important for microtubule depolymerization and sliding, and the cell cycle oscillator. Specifically, we found that the levels of Klp10A, Klp67A, and Klp59C, three kinesin-like proteins important for microtubule depolymerization, and the level of microtubule sliding motor Klp61F (kinesin-5) contribute to setting the speed of chromosome separation. This observation is supported by quantification of microtubule dynamics indicating that poleward flux rate scales with the length of the spindle. Perturbations of the cell cycle oscillator using heterozygous mutants of mitotic kinases and phosphatases revealed that the duration of anaphase increases during the blastoderm cycles and is the major regulator of chromosome velocity. Thus, our work suggests a potential link between the biochemical rate of mitotic exit and the forces exerted by the spindle. Collectively, we propose that the cell cycle oscillator and spindle length set the speed of chromosome separation in anaphase.
A transcription factor quintet orchestrating bundle sheath expression in rice
Authors: Hua Lei , Wang Na , Stanley Susan , Donald Ruth M. , Kumar Eeda Satish , Billakurthi Kumari , Borba Ana Rita , Hibberd Julian M. 
Published: June 2024

AbstractC4photosynthesis has evolved in over sixty plant lineages and improves photosynthetic efficiency by ∼50%. One unifying character of C4plants is photosynthetic activation of a compartment such as the bundle sheath, but gene regulatory networks controlling this cell type are poorly understood. In Arabidopsis a bipartite MYC-MYB transcription factor module restricts gene expression to these cells but in grasses the regulatory logic allowing bundle sheath gene expression has not been defined. Using the global staple and C3crop rice we identified theSULFITE REDUCTASEpromoter as sufficient for strong bundle sheath expression. This promoter encodes an intricatecis-regulatory logic with multiple activators and repressors acting combinatorially. Within this landscape we identified a distal enhancer activated by a quintet of transcription factors from the WRKY, G2-like, MYB-related, IDD and bZIP families. This module is necessary and sufficient to pattern gene expression to the rice bundle sheath. Oligomerisation of the enhancer and fusion to core promoters containing Y-patches allowed activity to be increased 220-fold. This enhancer generates bundle sheath-specific expression inArabidopsisindicating deep conservation in function between monocotyledons and dicotyledons. In summary, we identify an ancient, short, and tuneable enhancer patterning expression to the bundle sheath that we anticipate will be useful for engineering this cell type in various crop species.