bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-resistant ROCK1 expression prolongs survival ofEµ-MycB cell lymphoma mice
Authors: Mardilovich Katerina , Naylor Gregory , Julian Linda , Phinichkusolchit Narisa , Keeshan Karen , Blyth Karen , Olson Michael F 
Published: February 2024

AbstractApoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due toEµ-Myctransgene expression.Eµ-Myc; Rock1 NCmice had significantly fewer bone marrow cells relative toEµ-Mycmice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower inEµ-Myc; Rock1 NCmice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death inEµ-Myc; Rock1 NCmice bone marrows being more inflammatory.Rock1 WTrecipient mice transplanted with pre-neoplasticEµ-Myc; Rock1 NCbone marrow cells survived longer than mice transplanted withEµ-Myc; Rock1 WTcells, indicating that the survival benefit was intrinsic to theEµ-Myc; Rock1 NCbone marrow cells. The results suggest that the apoptotic death ofEµ-Myc; Rock1 NCcells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.
The Bacterial Quorum-Sensing Signal 2-Aminoacetophenone Rewires Immune Cell Bioenergetics through the PGC-1α/ERRα Axis to Mediate Tolerance to Infection
Authors: Chakraborty Arijit , Bandyopadhaya Arunava , Singh Vijay K , Kovacic Filip , Cha Sujin , Oldham William M. , Tzika A. Aria , Rahme Laurence G 
Published: February 2024

AbstractHow bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show thatPseudomonas aeruginosa (PA),a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in macrophages’ mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (MPC1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (ERRα). Consequently, ERRα exhibits weakened binding to the MPC1 promoter. This outcome arises from the impaired interaction between ERRα and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized macrophages. Exogenously added ATP in infected macrophages restores the transcript levels ofMPC1andERR-αandenhances cytokine production and intracellular bacterial clearance. Consistent with thein vitrofindings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association withPApersistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations andPApersistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the PGC-1α/ERRα axis in its influence on MPC1/OXPHOS-dependent energy production andPAclearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.
Experimental evolution in maize with replicated divergent selection identifies plant-height associated SNPs
Authors: Tost Mila , Westhues Cathy , Morrison Ginnie , Kaufmann Dietrich , Beissinger Timothy 
Published: February 2024

AbstractExperimental evolution studies are common in agricultural research, where they are often deemed “long term selection”. These are often used to perform selection mapping, which involves identifying markers which were putatively under selection based on finding signals of selection left in the genome. A challenge of previous selection mapping studies, especially in agricultural research, has been the specification of robust significance thresholds. This is in large part because long term selection studies in crops have rarely included replication. Usually, significance thresholds in long term selection experiments are based on outliers from an empirical distribution. This approach is prone to missing true positives or including false positives. Under laboratory conditions with model species, replicated selection has been shown to be a powerful tool, especially for the specification of significance thresholds. Another challenge is that commonly used single-marker based statistics may identify neutral linked loci which have hitchhiked along with regions that are actually under selection. In this study, we conducted divergent, replicated selection for short and tall plant-height in a random mating maize population under real field conditions. Selection of the 5% tallest and shortest plants was conducted for three generations. Significance thresholds were specified using the false discovery rate for selection (FDRfS) based on a window-based statistic applied on a statistic leveraging replicated selection (FSTSum). Overall, we found 3 significant regions putatively under selection. One region was located on chromosome 3 close to the plant-height genesDwarf1andiAA8. We applied a haplotype block analysis to further dissect the pattern of selection in significant regions of the genome. We observed patterns of strong selection in the subpopulations selected for short plant height on chromosome 3.
Effective population size does not explain long-term variation in genome size and transposable element content in animals
Authors: Marino Alba , Debaecker Gautier , Fiston-Lavier Anna-Sophie , Haudry Annabelle , Nabholz Benoit 
Published: February 2024

AbstractAnimal genomes exhibit a remarkable variation in size, but the evolutionary forces responsible for such variation are still debated. As the effective population size (Ne) reflects the intensity of genetic drift, it is expected to be a key determinant of the fixation rate of nearly-neutral mutations. Accordingly, the Mutational Hazard Hypothesis postulates lineages with low Neto have bigger genome sizes due to the accumulation of slightly deleterious transposable elements (TEs), and those with high Neto maintain streamlined genomes as a consequence of a more effective selection against TEs. However, the existence of both empirical confirmation and refutation using different methods and different scales precludes its general validation. Using high-quality public data, we estimated genome size, TE content and rate of non-synonymous to synonymous substitutions (dN/dS) as Neproxy for 807 species including vertebrates, molluscs and insects. After collecting available life-history traits, we tested the associations among population size proxies, TE content and genome size, while accounting for phylogenetic non-independence. Our results confirm TEs as major drivers of genome size variation, and endorse life-history traits and dN/dS as reliable proxies for Ne. However, we do not find any evidence for increased drift to result in an accumulation of TEs across animals. Within more closely related clades, only a few isolated and weak associations emerge in fishes and birds. Our results outline a scenario where TE dynamics vary according to lineage-specific patterns, lending no support for genetic drift as the predominant force driving long-term genome size evolution in animals.
Endometriosis Online Communities: A Quantitative Analysis
Authors: Bologna Federica , Thalken Rosamond , Pepin Kristen , Wilkens Matthew 
Published: February 2024

AbstractBackgroundEndometriosis is a chronic condition that affects 10% of people with a uterus. Due to the complex social and psychological impacts caused by the condition, people with endometriosis often turn to online health communities (OHCs) for support.ObjectivePrior work identifies a lack of large-scale analyses of endometriosis patient experiences and of OHCs. Our study fills this gap by investigating aspects of the condition and aggregate user needs that emerge from two endometriosis OHCs,r/Endoandr/endometriosis.MethodsWe leverage topic modeling and supervised machine learning to identify associations between a post’s subject matter (“topics”), the people and relationships (“personas”) mentioned, and the type of support the post seeks (“intent”).ResultsThe most discussed topics in posts aremedical stories, medical appointments, sharing symptoms, menstruation, andempathy. In addition, when discussingmedical appointments, users are more likely to mention theendometriosis OHCsthanmedical professionals. Furthermore,medical professionalis the least likely of any persona to be associated withempathy. Posts that mentionpartnerorfamilyare likely to discuss topics from thelife issuescategory, in particularfertility. Lastly, we find that while users seek experiential knowledge regarding treatments and healthcare processes, they also wish to vent and to establish emotional connections about the life-altering aspects of the condition.ConclusionsEndometriosis OHCs provide members a space where they can discuss care pathways, learn to manage symptoms, and receive validation. Our results emphasize the need for greater empathy within clinical settings, easier access to appointments, more information on care pathways, and further support for patient loved ones. In addition, this study demonstrates the value of quantitative analyses of OHCs: they can support and extend findings from small-scale studies about patient experiences and provide insight into hard-to-reach groups. Lastly, analyses of OHCs can help design interventions to improve care, as argued in previous studies.
Associations between Monocyte-to-High Density Lipoprotein Ratio and abdominal aortic calcification: Results of a nationwide survey
Authors: Ran Wei 
Published: February 2024

AbstractBackgroundAbdominal aortic calcification (AAC), a critical marker for cardiovascular disease, is strongly correlated with metabolic disorders like diabetes and hypertension. Recent studies have highlighted the Monocyte-to-High Density Lipoprotein Ratio (MHR) as a potential biomarker for assessing the risk of atherosclerosis and cardiovascular diseases.Methods and ResultsThis cross-sectional study utilized data from the National Health and Nutrition Examination Surveys (NHANES) 2013-2014, focusing on U.S. adults aged 40 years and above. A total of 3017 participants were included, with AAC evaluated using dual-energy X-ray absorptiometry (DXA) scans, and the severity of AAC quantified based on the Kauppila score system. MHR was investigated for its association with AAC severity, employing multiple linear and multivariable logistic regression models to explore the relationship dynamics. After adjusting for potential confounders, including age, sex, race, socioeconomic factors, and other health-related variables, the analysis revealed a significant association between higher MHR levels and increased AAC scores. Participants with elevated MHR exhibited a greater prevalence and severity of AAC.ConclusionsThe study demonstrates a significant association between elevated MHR and the prevalence and severity of AAC, suggesting the utility of MHR as a predictive biomarker for cardiovascular risk assessment. These findings advocate for the inclusion of MHR in cardiovascular disease management and risk stratification protocols.
A single-cell transcriptomics atlas for the parasitic nematodeHeligmosomoides bakeri: Extrapolating model organism information to non-model systems
Authors: Pollo Stephen M. J. , Liu Hongrui , Coria Aralia Leon , Rosin Nicole , Labit Elodie , Biernaskie Jeff , Finney Constance A. M. , Wasmuth James D. 
Published: February 2024

AbstractSingle-cell atlases aim to collect the gene expression information for every cell type in an organism but can be challenging to perform in non-model organisms. To try to circumvent the problem of having no verified cell type markers in the parasitic nematodeHeligmosomoides bakerito use for an atlas, we attempted to use orthologs of verified markers from the closely related model organismCaenorhabditis elegans. This resulted in a useful comparison between the two worms for each of the cell types recovered in preliminaryH. bakerisingle-cell RNA-sequencing. ForH. bakerimales and females, robustly recovered cell types include the gametes, embryos, and male intestine, while hypodermis, neurons, muscles, and pharyngeal cells were under-represented cell types. The two worms appear to have a similar hypodermis, cuticle, eggshell, and spermatogenesis process. On the other hand, putative cell identities and cell cycle scores suggest the intestine and muscle cells inH. bakerimay still be cycling and dividing, unlike inC. elegans. Additionally, embryogenesis and early development appear to be quite different between the two worms, with only eight out of 94 confirmed paternal contributions to the embryo inC. elegans(with an ortholog) predicted to also be paternal contributions inH. bakeri. Overall, this new dataset allowed me to move beyond the presence or absence of orthologs to include their tissue specificity and expression level similarities and differences when comparing these two worms to better identify biological processes and traits in a parasitic nematode that are modelled well byC. elegans.
Receptor tyrosine kinases CAD96CA and FGFR1 function as the cell membrane receptors of insect juvenile hormone
Authors: Li Yan-Xue , Kang Xin-Le , Li Yan-Li , Wang Xiao-Pei , Yan Qiao , Wang Jin-Xing , Zhao Xiao-Fan 
Published: February 2024

AbstractJuvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insectHelicoverpa armigera(cotton bollworm), a serious agricultural pest, as a model, we determined that receptor tyrosine kinases (RTKs) cadherin 96ca (CAD96CA) and fibroblast growth factor receptor homologue (FGFR1) function as JH cell membrane receptors by their roles in JH-regulated gene expression, larval status maintaining, rapid intracellular calcium increase, phosphorylation of JH intracellular receptor MET1 and cofactor Taiman, and high affinity to JH III. Gene knockout ofCad96caandFgfr1by CRISPR/Cas9 in embryo and knockdown in various insect cells, and overexpression of CAD96CA and FGFR1 in mammalian HEK-293T cells all supported CAD96CA and FGFR1 transmitting JH signal as JH cell membrane receptors.
Decreases in liver cT1 accurately reflect histological improvement induced by therapies in MASH: a multi-centre pooled cohort analysis
Authors: Alkhouri Naim , Beyer Cayden , Shumbayawonda Elizabeth , Andersson Anneli , Yale Kitty , Rolph Timothy , Chung Raymund , Vuppalanchi Raj K , Cusi Kenneth , Loomba Rohit , Dennis Andrea , Pansini Michele 
Published: February 2024

ABSTRACTBackground & AimsIron corrected T1 (cT1) is an MRI derived biomarker of liver disease activity. Emerging data suggest a change in cT1 of ≥ 80 ms reflects histological improvement. We aimed to validate the association between the ≥ 80 ms decline in cT1 and histological improvement, specifically the resolution of MASH.MethodsA retrospective analysis of study participants from three interventional clinical trials with histologically confirmed MASH (n = 150) who underwent multi-parametric MRI to measure cT1 (LiverMultiScan®) and biopsies at baseline and end of study. Histological responders were defined using the four criteria: (1) a decrease in NAFLD Activity score (NAS) ≥ 2 with no worsening in fibrosis, (2) a decrease in fibrosis ≥ 1 stage with no worsening in NAS, (3) both a NAS decrease ≥ 2 and a fibrosis decrease ≥ 1, and (4) MASH resolution with no worsening in fibrosis. Difference in the magnitude of change in cT1 between responders and non-responders was assessed.ResultsSignificant decreases in cT1 were observed in responders for all the histological criteria. The largest decrease was observed for those achieving MASH resolution, and was 119ms, compared to 43ms for non-responders. The optimal reduction in cT1 for separating responders from non-responders for MASH resolution was −74ms (64ms-73ms for the other criteria), in close agreement with the previously predefined threshold of −80ms. Those achieving an ≥ 80 ms reduction in cT1 were substantially more likely to achieve histological response with odds ratios ranging from 2.7 to 6.3.ConclusionsThese results demonstrate that a reduction in cT1 of 80 ms was associated with histological response supporting the utility of cT1 to predict clinical improvement in patients undergoing therapeutic intervention.
Neutrophil-to-Lymphocyte Ratio as a Prognostic Indicator in COVID-19: Evidence from a Northern Tanzanian Cohort
Authors: Kyala Norman J. , Mboya Innocent B. , Shao Elichilia , Sakita Francis M. , Kilonzo Kajiru G. , Shirima Laura J , Sadiq Abid M. , Mkwizu Elifuraha , Chamba Nyasatu , Marandu Annette , Muhali Sophia , Raza Faryal M , Ndale Eliasa , Bayo Damasi F. , Mujuni Daniel P. , Lyamuya Furaha 
Published: February 2024

AbstractBackgroundCOVID-19 caused a profound global impact, resulting in significant cases and deaths. The progression of COVID-19 clinical manifestations is influenced by a dysregulated inflammatory response. Early identification of the subclinical progression is crucial for timely intervention and improved patient outcomes. While there are various biomarkers to predict disease severity and outcomes, their accessibility and affordability pose challenges in resource-limited settings. We explored the potentiality of the neutrophil-to-lymphocyte ratio (NLR) as a cost-effective inflammatory marker to predict disease severity, clinical deterioration, and mortality in affected patients.MethodologyA hospital-based retrospective cohort study was conducted at KCMC Hospital among COVID-19 patients followed from admission to discharge between 1stMarch 2020 and 31stMarch 2022. NLR was calculated as the absolute neutrophil count in µL divided by the absolute lymphocyte count in µL. The NLR cut-off value was determined using Receiver Operating Characteristic (ROC) analysis and assessed its predictive ability at admission for in-hospital mortality. The Chi-square test compared the proportion of NLR by patient characteristics. The association of NLR with disease severity and mortality was analyzed using the modified Poisson and Cox regression models, respectively.ResultsThe study included 504 patients, with a median age of 64 years, 57.1% were males, and 68.3% had severe COVID-19. The in-hospital COVID-19 mortality rate was 37.7%. An NLR cutoff value of 6.1 or higher had a sensitivity of 92.1% (95% CI 89.2%–94.0%) and a specificity of 92.0% (95% CI 89.7%–94.4%). Additionally, 39.5% of patients with an NLR value of 6.1 or higher had increased risk of severe disease, subsequent clinical deterioration, and mortality.Conclusion and recommendationAn NLR value of 6.1 or higher at the time of hospital admission associated with severe disease, clinical deterioration, and mortality in patients with COVID-19. Integration of NLR as a prognostic parameter in COVID-19 prognosis scales could improve risk assessment and guide appropriate management strategies for COVID-19 patients, as well as for potential future viral-related pneumonias. Further prospective studies are necessary to validate these findings and evaluate the clinical utility of NLR in larger cohorts of patients.
Designed mosaic nanoparticles enhance cross-reactive immune responses in mice
Authors: Wang Eric , Cohen Alexander A. , Caldera Luis F. , Keeffe Jennifer R. , Rorick Annie V. , Aida Yusuf M. , Gnanapragasam Priyanthi N.P. , Bjorkman Pamela J. , Chakraborty Arup K. 
Published: February 2024

SummaryUsing computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naïve and COVID-19 pre-vaccinated mice revealed that mosaic-7COMelicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COMtargeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COMelicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COMelicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COMto protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.
Gender and leadership evaluations: what happens if we actually measure expectations–behavior incongruence?
Authors: Eichenauer Connor , Ryan Ann Marie 
Published: February 2024

Purpose
Role congruity theory and gender stereotypes research suggests men are expected to engage in agentic behavior and women in communal behavior as leaders, and that role violation results in backlash. However, extant gender and leadership research does not directly measure expectations–behavior incongruence. Further, researchers have only considered one condition of role incongruence – display of counter-role behavior – and have not considered the outcomes of failing to exhibit role-congruent behavior. Additionally, few studies have examined outcomes for male leaders who violate gender role prescriptions. The present study aims to address these shortcomings by conducting a novel empirical test of role congruity theory.

Design/Methodology/approach
This experimental study used polynomial regression to assess how followers evaluated leaders under conditions of incongruence between follower expectations for men and women leaders’ behavior and leaders’ actual behavior (i.e. exceeded and unmet expectations). Respondents read a fictional scenario describing a new male or female supervisor, rated their expectations for the leader’s agentic and communal behavior, read manipulated vignettes describing the leader’s subsequent behavior, rated their perceptions of these behaviors, and evaluated the leader.

Findings
Followers expected higher levels of communal behavior from the female than the male supervisor, but no differences were found in expectations for agentic behavior. Regardless of whether expectations were exceeded or unmet, supervisor gender did not moderate the effects of agentic or communal behavior expectations–perceptions incongruence on leader evaluations in polynomial regression analyses (i.e. male and female supervisors were not evaluated differently when displaying counter-role behavior or failing to display role-congruent behavior).

Originality/value
In addition to providing a novel, direct test of role congruity theory, the study highlighted a double standard in gender role-congruent behavior expectations of men and women leaders. Results failed to support role congruity theory, which has implications for the future of theory in this domain.