bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel adaptation to geothermally-warmed habitats due to common structural variation and functional developmental pathways
Authors: Brachmann Matthew K. , Costa Ana P. B. , Robertson Shaun , Donoghue Kate , Pilakouta Natalie , Whitehead Mark , Liu Xuan , Kristjansson Bjarni , Skulason Skuli , Selman Colin , Parsons Kevin 
Published: February 2025

AbstractClimate change is causing rapid increases in temperature which drives genomic changes tied to adaptation. However, predicting the outcomes of climate change presents challenges as the anticipated conditions have yet to be experienced by natural populations. Modelling and lab experiments suggest that natural populations will experience shifts in life history, physiology, phenology, and ecology, but the underlying genomic mechanisms involved are unknown. However, some contemporary natural populations experience habitat warming through geothermal activity and can provide valuable insights into evolutionary responses. Geothermally warmed habitats should impose strong selection on ectotherms compared to ambient habitats as they increase metabolic demands, alter developmental processes, and offer novel ecological conditions. We leveraged Icelandic threespine sticklebacks (Gasterosteus aculeatus) from populations that have adaptively diverged along a geothermal/ambient habitat axis. We obtained 173,485 single nucleotide polymorphisms (SNPs) across four independent instances of population divergence using whole genome sequencing. While the majority of genomic differentiation between geothermal/ambient ecotypes was non-parallel, the MAPK signalling pathway appeared across all ecotype pairs. We also identified a putative inversion located on chromosome XXI which appears to drive parallel genomic differentiation between geothermal and ambient ecotypes. Candidate genes within the putative inversion correspond to metabolic adaptations, including regulation of appetite and fat content. Appetite level showed strong heritable divergence between ecotypes, while the rate of weight loss during starvation and fat levels differed between ecotypes. Overall, both polygenic adaptation and parallel structural variation appeared to be key genomic mechanisms for adaptation to geothermally warmed environments. While allelic divergence was largely unique across populations, it resulted in similar functional phenotypic outcomes. Thus, structural and allelic variation both operate to facilitate adaptation to warming environments. Therefore, while management from a genomic perspective will play a role in mitigating the effects of climate change, this study suggests that consideration of functional molecular pathways will be key to conservation but with precise changes being difficult to predict due to the highly polygenic nature of thermal adaptation.
Effects of a Sequential Application of Plant Protection Products on Soil Microbes and Free-Living Nematodes in a Field Experiment
Authors: Drocco Camilla , Fernandes Saúl , Xie Liyan , Devers Marion , Förster Bernhard , Martin-Laurent Fabrice , Romdhane Sana , Spor Aymé , Thiour-Mauprivez Clémence , Coors Anja 
Published: February 2025

AbstractDuring crop growth cycle, often several different plant protection products (PPPs) are applied, in combination or sequentially. Such sequential applications result in unintentional mixtures of residues that may affect ecosystem services supported by non-target organisms such as soil microbes and nematodes. This scenario of sequential PPP application is frequent in agricultural practice but rarely addressed experimentally at field scale with regard to environmental impacts. The objective of this study was to evaluate the effect of individual and sequential application of three PPPs (the herbicide clopyralid, the insecticide zeta-cypermethrin, and the fungicide pyraclostrobin) on soil microbial communities, and on the abundance of free-living nematode. Single applications (at 1× or 10× the agronomical dose) were made to triplicated field plots with each one of the PPPs or all three PPPs in sequence, with untreated plots serving as controls. Plots were sampled prior to each application, and 7 and 28 days thereafter. The fungal community’s composition and abundance were found to be more susceptible than the bacterial community to PPP applications, while the bacterial was mainly driven by the in-field heterogeneity of soil properties. Transient effects of PPP applications were detected on nematode abundance. Higher tier ecotoxicological studies offer greater ecological relevance compared to the standard laboratory tests but are challenged by environmental variations that should be accounted for when evaluating the ecotoxicity of pesticides on soil organisms.
Transcriptome analysis of the winter tick (Dermacentor albipictus) reveals sex-specific expression patterns
Authors: Edwards Rhodri T.M. , Antoshechkin Igor , Hill Eddie , Perry Michael W. , Olafson Pia U. , Saelao Perot , Lohmeyer Kimberly H. , Akbari Omar S. 
Published: February 2025

AbstractThe winter tick,Dermacentor albipictus, is a significant ectoparasite of ruminants across North America, posing health risks to wildlife and occasionally humans. Despite its ecological importance, limited genomic resources exist for this species. This study provides the first comprehensive transcriptome analysis ofD. albipictus, focusing on early-stage embryos, sexed adults, dissected ovaries, and dissected male reproductive systems. Differential gene expression analyses revealed significant sex-biased expression patterns, and functional annotations identified candidate genes involved in sex determination. Notably, we identified the first documented case of sex-specific splicing of a doublesex-like gene in chelicerates, a mechanism previously thought to be absent in this group. This discovery suggests that ticks may share more insect-like features of sexual differentiation, with implications for understanding the evolution of sex determination pathways in arthropods These transcriptome data serve as a critical resource for understanding the biology ofD. albipictusand will facilitate the development of novel genetic control strategies.
Calcineurin controls the cytokinesis machinery during thermal stress inCryptococcus deneoformans
Authors: Yadav Vikas , Averette Anna Floyd , Upadhya Rajendra , Heitman Joseph 
Published: February 2025

AbstractCalcineurin is a highly conserved phosphatase that plays a central role in sensing calcium and governing transcriptional, post-transcriptional, and post-translational signaling networks. Calcineurin is a heterodimer consisting of a catalytic A subunit and a regulatory B subunit. Through downstream effectors, calcineurin signaling drives myriad responses in different organisms. In the fungal pathogenicCryptococcusspecies complex that infects humans, calcineurin governs thermotolerance and is essential for growth at high temperature and pathogenesis. InCryptococcus deneoformans, the underlying molecular functions of this critical signaling cascade are not well understood. In this study, we conducted a genetic screen and identified genetic changes that suppress the requirement for calcineurin during high-temperature growth. Our results identified two mechanisms that bypass the requirement for calcineurin function. The first mechanism involves segmental aneuploidy via both amplification as well as loss of chromosome fragments. The second mechanism involves dominant amino acid substitution mutations in the genes encoding three proteins, Chs6, Imp2, and Cts1, which function in a complex required for septation and budding. Loss of calcineurin activity causes chitin and chitosan accumulation and severe budding defects, whereas suppressor mutations restore largely normal growth and cytokinesis in the absence of calcineurin. These findings reveal the calcineurin signaling cascade controls a conserved cytokinesis machinery at the mitotic exit network during thermal stress.
The forkhead transcription factor FKH-7/FOXP acts in chemosensory neurons to regulate developmental decision-making
Authors: Chai Cynthia M. , Taylor Seth R. , Tischbirek Carsten H. , Wong Wan-Rong , Cai Long , Miller David M. , Sternberg Paul W. 
Published: February 2025

SUMMARYAutism is a complex neurodevelopmental disorder with many associated genetic factors, including the forkhead transcription factor FOXP1. Although FOXP1’s neuronal role is well-studied, the specific molecular consequences of different FOXP1 pathogenic variants in physiologically-relevant contexts are unknown. Here we ascribe the first function to Caenorhabditis elegans FKH-7/FOXP, which acts in two chemosensory neuron classes to promote the larval decision to enter the alternative, developmentally-arrested dauer life stage. We demonstrate that human FOXP1 can functionally substitute for C. elegans FKH-7 in these neurons and that engineering analogous FOXP1 hypomorphic missense mutations in the endogenous fkh-7 locus also impairs developmental decision-making. In a fkh-7/FOXP1 missense variant, single-cell transcriptomics identifies downregulated expression of autism-associated kcnl-2/KCNN2 calcium-activated potassium channel in a serotonergic sensory neuron. Our findings establish a novel framework linking two evolutionarily-conserved autism-associated genes for deeper characterization of variant-specific molecular pathology at single neuron resolution in the context of a developmental decision-making paradigm.
Covariate Adjusted Logit Model (CALM) for Generating Dose-Response Curves from Observational Data with Applications to Vaccine Effectiveness Trials
Authors: Shang Nong , Schrag Stephanie , Kahn Rebecca , Rhodes Julia 
Published: February 2025

AbstractEstablishing dose-response relationships with observational data is challenging due to confounding covariates and selection bias, particularly when the bias causes marginal distributions of confounding covariates to differ between the sample and the target population. In this scenario, standard causal analysis approaches like g-formula are not applicable without further modeling of the dose-response relationship. To address this limitation, we extend the log-linear structure mean model for binary treatments into a Covariate Adjusted Logit Model (CALM) for continuous treatments, introducing a new causal estimand that measures relative dose-response relationship. Based on one interpretation of vaccine effectiveness, the relative dose response curve can be described as a function that reduces susceptibility to disease, making the adjustment for confounding covariates equivalent to revealing latent susceptibility status. Accordingly, we leverage a Gibbs sampler called the All-or-Nothing (AoN) algorithm for Bayesian and non-parametric estimation of the relative response curve, providing new options beyond regular causal techniques, such as those based on generalized propensity scores. In the context of vaccine effectiveness (VE) clinical trials, CALM addresses the issue of confounding covariates that affect dose-response relationships differently in placebo and vaccine arms. While deriving a common absolute dose-response curve for both arms to evaluate VE is generally infeasible, our model provides a common relative dose-response curve for this purpose. Simulation studies confirm that CALM outperforms alternative methods in scenarios with confounding factors, making it a valuable tool for future immunological response-based vaccine trials.
Earlier Detection of Brain Injury Using Optical Brain Pulse Monitoring in Critically Ill Patients Following Cardiac Arrest
Authors: Teo Elliot J. , Petautschnig Sigrid , Hellerstedt Jack , Chung Sung W , Udy Andrew , Smith Paul , Haydon Tim , Dixon Barry 
Published: February 2025

AbstractIMPORTANCEPoint-of-care, non-invasive brain monitoring in critically ill patients following cardiac arrest could provide earlier detection of neurological injury and, when combined with earlier treatments, limit brain injury. Point-of-care monitoring could also enable better neuro-prognostication.OBJECTIVESThe study assessed the time to detection of brain injury using optical brain pulse monitoring (OBPM) compared to routine brain monitoring. The association of OBPM signals with more severe forms of brain injury was also assessed.DESIGNRetrospective analysis of patients enrolled in an observational study.SETTINGCritical care unit of a tertiary academic hospital.PARTICIPANTSAdult patients requiring mechanical ventilation in a critical care unit following a cardiac arrest.MAIN OUTCOMES AND MEASURESOBPM uses red and infrared light to capture brain pulse waveforms whose morphology reflects the relative arteriole and venous pressure levels driving microvascular blood flow in the brain. The OBPM sensors were placed bilaterally on the anterior temporal region of the scalp, over the middle cerebral artery territories. Time to brain injury detection was defined as the period from cardiac arrest to the first detection of brain injury by OBPM or routine monitoring.RESULTSTwelve patients were enrolled, three required veno-arterial extra-corporeal membrane oxygenator support. In-hospital mortality was 83% and eight patients developed global hypoxic-ischemic brain injury. The median time to detection of brain injury was 57 hours earlier using OBPM compared to routine monitoring (P < 0.01). In brain injured patients OBPM brain pulse morphologies changed over time and were often different between hemispheres, high amplitude respiratory waves were also present. Known poor prognostic brain pulse waveform morphologies were present in some patients with severe brain injury.CONCLUSIONS AND RELEVANCEOBPM detected brain injury earlier compared to routine brain monitoring. Earlier detection of neurological injury could improve patient outcomes through earlier treatment and better neuro-prognostication.KEY POINTSQuestionCan point-of-care non-invasive optical brain pulse monitoring (OBPM) in critically ill patients following cardiac arrest provide earlier detection of brain injury compared to routine monitoring?FindingsIn this observational study of 12 patients the median time to detection of brain injury was 57 hours earlier using OBPM compared to routine monitoring.MeaningEarlier detection of brain injury could improve patient outcomes through earlier treatment and better neuro-prognostication.
Effects of Socioeconomic Status in Colorectal Cancer Incidence and Clinical Outcome Differences Among Asian American Populations: A Systematic Review
Authors: Sakazaki Amy , Lui Austin , Wang Melody , Ngo Katherine , Lugue Maria Theresa , Aligireddy Himani , Nguyen Maria , Murakami Shin 
Published: February 2025

AbstractIntroductionColorectal cancer (CRC) is the second leading cause of cancer death in the Asian American and Pacific Islander (API) population, a diverse and rapidly growing minority group in the US. Race, ethnicity, and socioeconomic status (SES) are known to impact outcomes of CRC, but the relationship is unclear in the context of the Asian American cohort and its diverse subgroups. This systemic review aims to gain insight into the relationship between the incidence and clinical outcomes of CRC in the Asian American community.MethodsA systematic literature search was conducted per PRISMA protocol using PubMed, Scopus, EMBASE, Cochrane, CINAHL, and Web of Science databases, accessed on August 13, 2023.ResultsOf the 2225 studies identified, a total of 14 studies were included in the analysis. Four studies concluded that there was no association or variable response to SES measurements in CRC incidence in the Asian American population. However, there was evidence that the incidence of CRC varies among Asian American subgroups, using varying measures of SES. In the eight studies that measured mortality or survival as the primary outcome, seven found decreased mortality and increased survival in the API population despite changes in SES. Out of the six studies that measured incidence, four studies found no association with SES. A study found that Chinese Americans experienced a significant decrease in every socioeconomic status (SES) category. Japanese Americans experienced a significant decrease in the lowest SES category, while Koreans and Filipinos experienced a significant increase in both the lowest and highest SES categories. Therefore, grouping various Asian American ethnicities as a single monolithic “Asian” category is misleading.ConclusionAlthough the incidence of CRC was thought to be low and decreasing, this review found various trends in different Asian American subset groups. For example, there was a decrease in CRC rates in two ethnic groups and an increase in the other two ethnic groups. The potential causes of these varying CRC incidence rates are likely multifactorial and may include inadequate screening rates, lack of CRC education, and cultural barriers. Further studies are needed to understand these mechanisms. This review recommends a more detailed classification of the API ethnic population but not as a single monolithic entity as Asian. It also emphasizes preventative CRC screening within the API communities due to lower rates of CRC screening among them.
Specific neuroblast-derived signals control both cell migration and fate in the rostral migratory stream
Authors: Zhou Wei , Munoz James R. , Ho Hsin-Yi Henry , Hanamura Kenji , Dalva Matthew B. 
Published: February 2025

AbstractFunctional neuronal circuits require neuroblasts migrate to appropriate locations and then differentiate into neuronal subtypes. However, it remains unknown how neuroblasts in the subventricular zone (SVZ) are guided through the rostral migratory stream (RMS) to the olfactory bulb (OB). Here we define EphB2 as a neuroblast-derived cue that controls migration along the RMS and helps to determine cell fate. Within the RMS, EphB2 is expressed selectively in, kinase-active in, and required for the migration of neuroblasts. As neuroblasts enter the OB and differentiate, EphB kinase activity is down-regulated, and in the granule cell layer (GCL), EphB2 expression is down-regulated. Blocking EphB kinase activity or knocking down EphB2 results in defects in migration and premature cellular differentiation in the RMS. Unexpectedly, premature loss of EphB2 expression causes neuroblasts to stop migrating and differentiate into astrocyte-like cells. Thus, EphB2 kinase activity and expression are linked to migration and specification of neuroblast fate.
A screen to identify antifungal antagonists reveals a variety of pharmacotherapies induce echinocandin tolerance inCandida albicans
Authors: Reitler Parker , DeJarnette Christian A. , Kumar Ravinder , Tucker Katie M. , Peters Tracy L. , Twarog Nathaniel R , Shelat Anang A. , Palmer Glen E. 
Published: February 2025

AbstractThrough screening a comprehensive collection of drugs approved for human use, we identified over 20 that oppose the antifungal activity of the echinocandins upon the infectious yeast,Candida albicans. More detailed evaluation of five such drugs, including the atypical antipsychotic aripiprazole and the tyrosine kinase inhibitor ponatinib, indicated they promoteC. albicanssurvival following exposure to the echinocandin antifungals. The activity of the five selected antagonists was dependent upon the Mkc1p MAPK pathway, however, ponatinib was paradoxically shown to suppress phosphorylation and therefore activation of Mkc1p itself. Components of several other signaling pathways are also required, including those of calcineurin and casein kinase-2, suggesting the observed antagonism required much of the cell wall stress responses previously described forC. albicans. Transcriptome analysis revealed that the antagonists stimulated the expression of genes involved in xenobiotic and antifungal resistance, and suppressed the expression of genes associated with hyphal growth. Thus, the echinocandin antagonistic drugs modulateC. albicansphysiology in ways that could impact its pathogenicity and/or response to therapeutic intervention. Finally, a mutant lacking the Efg1p transcription factor, which has a central role in the activation ofC. albicanshyphal growth was found to have intrinsically high levels of echinocandin tolerance, suggesting a link between modulation of morphogenesis related signaling and echinocandin tolerance.ImportanceWe report a substantial number of previously unknown drug interactions that modulate the echinocandin sensitivity of one of the most prevalent human fungal pathogens,Candida albicans. The echinocandins are the first line therapy for treating disseminated and often lethalCandidainfections, that account for >75% of invasive fungal infections in the U.S.. For largely unknown reasons, a substantial number of patients with invasive candidiasis fail to respond to treatment with these drugs. The finding of this study suggest that co-administered medications have the potential to influence the therapeutic outcomes of invasive fungal infections through modulating antifungal drug tolerance and/or fungal pathogenicity. The potential for echinocandin antagonistic medications to influence therapeutic outcomes is discussed.
Glissandra oviformisn. sp.: a novel predatory flagellate illuminates the character evolution within the eukaryotic clade CRuMs
Authors: Yazaki Euki , Harada Ryo , Isogai Ryu , Bamba Kohei , Ishida Ken-ichiro , Inagaki Yuji , Shiratori Takashi 
Published: February 2025

AbstractCulturing protists offers a powerful approach to exploring eukaryotic diversity, especially for deep-branching lineages. In this study, we cultured and described a novel protist species, namedGlissan-dra oviformisn sp., within the poorly studied and unclassified genusGlissandra. While an SSU rDNA gene phylogeny failed to resolve its phylogenetic placement in the eukaryotic tree, a phylogenomic analysis of 340 proteins indicatedG. oviformisas a deep-branching member of the CRuMs clade. Prior to this study, this clade consisted of diverse het-erotrophic amoeba and flagellates and lacks clear synapomorphies. Ultrastructural observations re-vealed thatG. oviformisshares the characteristics with some CRuMs members, including the pellicle underlying the plasma membrane and an internal sleeve surrounding the central pair of the axoneme at the flagellar transitional region. Our findings suggest potential shared characteristics and synapomorphies for CRuMs and contribute to a deeper understanding of the character evolution within CRuMs.