bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Cell Sequencing Provides Clues about the Developmental Genetic Basis of Evolutionary Adaptations in Syngnathid Fishes
Authors: Healey Hope M. , Penn Hayden B. , Small Clayton M. , Bassham Susan , Goyal Vithika , Woods Micah A. , Cresko William A. 
Published: April 2024

AbstractSeahorses, pipefishes, and seadragons are fishes from the family Syngnathidae that have evolved extraordinary traits including male pregnancy, elongated snouts, loss of teeth, and dermal bony armor. The developmental genetic and cellular changes that led to the evolution of these traits are largely unknown. Recent syngnathid genome assemblies revealed suggestive gene content differences and provide the opportunity for detailed genetic analyses. We created a single cell RNA sequencing atlas of Gulf pipefish embryos to understand the developmental basis of four traits: derived head shape, toothlessness, dermal armor, and male pregnancy. We completed marker gene analyses, built genetic networks, and examined spatial expression of select genes. We identified osteochondrogenic mesenchymal cells in the elongating face that express regulatory genesbmp4, sfrp1a, andprdm16. We found no evidence for tooth primordia cells, and we observed re-deployment of osteoblast genetic networks in developing dermal armor. Finally, we found that epidermal cells expressed nutrient processing and environmental sensing genes, potentially relevant for the brooding environment. The examined pipefish evolutionary innovations are composed of recognizable cell types, suggesting derived features originate from changes within existing gene networks. Future work addressing syngnathid gene networks across multiple stages and species is essential for understanding how their novelties evolved.
Distinct routes to thermotolerance in the fungal pathogenCryptococcus neoformans
Authors: Schwiesow Mara J. W. , Elde Nels C. , Hilbert Zoë A. 
Published: April 2024

AbstractIncreasing temperatures associated with climate change have the potential for far-reaching impact on human health and disease vectors, including fungal pathogens. Pathogenic fungi occupy a wide range of environments across the world, and their ranges have been slowly expanding in recent decades due, in part, to climate change. Despite these links between increasing temperature and higher prevalence of fungal disease, the direct effects of rising environmental temperatures on the evolution of pathogenic fungi remains unclear. In this study, we investigated how increasing temperatures drive adaptive evolution in the human fungal pathogenCryptococcus neoformans. First, we performed serial passages of aC. neoformansenvironmental isolate with gradual changes in temperature over the course of ∼40 days. Through this approach we identified several distinct thermally adapted isolates with competitive growth advantages over the parental strain at high temperatures. We then characterized the phenotypic and genetic changes acquired in several evolved isolates, which include alteration of cell size, colony morphology, and, surprisingly, antifungal resistance. These results highlight the remarkable flexibility of fungi to adapt rapidly to new environments and raise pressing questions about the impacts of rising environmental temperatures on the future of infectious diseases and human health.
Self-Construal and Attentional Biases in Cognitive Processing: Insights from Chinese College Students for Mental Health Contexts
Authors: Li Jing , Liu Sijia , Peng Hongsheng , Tang Liwu , Yuan Lin 
Published: April 2024

AbstractThis study integrates Markus and Kitayama’s self-construal theory with the Biopsychosocial Model to examine the effects of self-construal on cognitive biases and their implications for mental health among Chinese college students. It investigates how independent (IndSC) and interdependent (InterSC) self-construals influence cognitive biases towards positive and negative stimuli, emphasizing the mediating roles of attentional control, self-esteem, cognitive reappraisal, and the need to belong. The research utilizes a hybrid sampling strategy, engaging 748 undergraduate students from diverse majors and universities in Chongqing, China. Participants completed assessments measuring self-construal, attentional control, self-esteem, cognitive reappraisal, need to belong, and cognitive biases. Employing structural equation modeling, the study uncovers that IndSC is positively associated with cognitive biases, favoring positive over negative information, with attentional control and self-esteem serving as significant mediators. InterSC, however, promotes a balanced attention to both positive and negative information, with cognitive reappraisal and the need to belong acting as mediators. These findings underscore the significant role of self-construal within the broader biopsychosocial framework in shaping cognitive processes and highlight the importance of considering these factors in mental health interventions. By leveraging a comprehensive sampling approach, the study ensures a representative sample, enhancing the generalizability of its findings to the broader Chinese college student population. This research not only contributes to the understanding of the complex interplay between cultural psychology and mental health but also suggests the need for mental health interventions that are culturally and individually tailored. Future research should extend to other cultural settings and employ longitudinal designs to further explore the dynamic interactions between self-construal, cognitive biases, and mental health from a biopsychosocial perspective.
Cortical Tau Aggregation Patterns associated with Apraxia in Alzheimer‘s Disease
Authors: Bischof Gérard N. , Jaeger Elena , Giehl Kathrin , Jessen Frank , Onur Oezguer A. , O’Bryant Sid , Kara Esra , Weiss Peter H. , Drzezga Alexander 
Published: April 2024

AbstractObjectivesApraxia is a core feature of Alzheimer’s disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated apraxia profiles in a well-defined group of patients with Alzheimer’s disease (AD; N=32) who additionally underwent PET imaging with the second-generation tau PET tracer [18F]PI-2620. We hypothesized that specific patterns of tau pathology might be related to apraxic deficits.MethodsPatients (N=32) with a biomarker-confirmed diagnosis of Alzheimer’s disease were recruited in addition to a sample cognitively unimpaired controls (CU1; N=41). Both groups underwent in-depth neuropsychological assessment of apraxia (Dementia Apraxia Screening Test; DATE and the Cologne Apraxia Screening; KAS). In addition, static PET imaging with [18F]PI-2620 was performed to assess tau pathology in the AD patients. To specifically investigate the association of apraxia with regional tau-pathology, we compared the PET-data from this group with an independent sample of amyloid-negative cognitively intact participants (CU2;N=54) by generation of z-score-deviation maps as well as voxel- based multiple regression analyses.ResultsWe identified significant clusters of tau-aggregation in praxis-related regions (e.g., supramarginal gyrus, angular gyrus, temporal, parietal and occipital regions) that were associated with apraxia. These regions were similar between the two apraxia assessments. No correlations between tau-tracer uptake in primary motor cortical or subcortical brain regions and apraxia were observed.ConclusionsThese results suggest that tau deposition in specific cortical brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance.
A sociodemographic index identifies non-biological sex-related effects on insomnia in the Hispanic Community Health Study/Study of Latinos
Authors: Sorajja Natali , Chung Joon , Alcántara Carmela , Wassertheil-Smoller Sylvia , Penedo Frank J , Ramos Alberto R , Perreira Krista M , Daviglus Martha L , Suglia Shakira F , Gallo Linda C , Liu Peter Y , Redline Susan , Isasi Carmen R , Sofer Tamar 
Published: April 2024

AbstractBackgroundSex differences are related to both biological factors and the gendered environment. To untangle sex-related effects on health and disease it is important to model sex-related differences better.MethodsData came from the baseline visit of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a longitudinal cohort study following 16,415 individuals recruited at baseline from four study sites: Bronx NY, Miami FL, San Diego CA, and Chicago IL. We applied LASSO penalized logistic regression of male versus female sex over sociodemographic, acculturation, and psychological factors jointly. Two “gendered indices”, GISE and GIPSE, summarizing the sociodemographic environment (GISE, primary) and psychosocial and sociodemographic environment (GIPSE, secondary) associated with sex, were calculated by summing these variables, weighted by their regression coefficients. We examined the association of these indices with insomnia derived from self-reported symptoms assessed via the Women Health Initiative Insomnia Rating Scale (WHIIRS), a phenotype with strong sex differences, in sex-adjusted and sex-stratified analyses. All analyses were adjusted for age, Hispanic/Latino background, and study center.ResultsThe distribution of GISE and GIPSE differed by sex with higher values in male individuals, even when constructing and validating them on separate, independent, subsets of HCHS/SOL individuals. In an association model with insomnia, male sex was associated with lower likelihood of insomnia (odds ratio (OR)=0.60, 95% CI (0.53, 0.67)). Including GISE in the model, the association was slightly weaker (OR=0.63, 95% CI (0.56, 0.70)), and weaker when including instead GIPSE in the association model (OR=0.78, 95% CI (0.69, 0.88)). Higher values of GISE and of GIPSE, more common in male sex, were associated with lower likelihood of insomnia, in analyses adjusted for sex (per 1 standard deviation of the index, GISE OR= 0.92, 95% CI (0.87, 0.99), GIPSE OR=0.65, 95% CI (0.61, 0.70)).ConclusionsNew measures such as GISE and GIPSE capture sex-related differences beyond binary sex and have the potential to better model and inform research studies of health. However, such indices do not account for gender identity and may not well capture the environment experienced by intersex and non-binary persons.
Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells
Authors: Sánchez-Cerrillo I , Popova O , Agudo-Lera M , Tsukalov I , Calvet-Mirabent M , de los Santos I , García-Fraile L , Fuentes P , Delgado-Arévalo C , Alcain J , Sánchez-Gaona N , Lázaro-Díez M , Muñoz-Calleja C , Alfranca Arantzazu , Genescà M , Prado JG , Vbrnac Vladimir , Balazs Alejandro , Buzón MJ , Toribio M.L , Muñoz-Fernández MA , Sánchez-Madrid F , Martín-Gayo E 
Published: April 2024

ABSTRACTNatural Killer (NK) cells are promising tools for the development of immunotherapies targeting persistently infected CD4+ T cells to potentially achieve remission in people with HIV-1 (PWH). However, the chronicity of HIV-1 infection limits the functional properties of NK cells, and additional approaches are needed to potentiate their cytotoxic activity against HIV-1-infected cells. In the present study, we analyzed the reinvigoration of functional NK cells from PWH after priming with autologous dendritic cells (DC) stimulated with nanoparticles containing Poly I:C (Nano-PIC). We show that improved natural cytotoxic function in NK cell from PWH associates with increased proportions of NKG2C+CD57- precursors of memory NK, which eliminate HIV-1 infected CD4+ T cells mainly through the TRAIL receptor. In addition, expression of TIGIT but not TIM3 limited increase in NKG2C+ memory NK cell precursors and associated with persistent dysfunctionality of NK cells after stimulation with Nano PIC-DC. Blockade of TIGIT restored functional capacities of NK cell from PWH eliminating HIV-1 infected cellsin vitro. Moreover, combining of NK cell and Nano-PIC-DC with anti-TIGIT mAbs immunotherapy limited the expansion of HIV-1 infected cells in humanized immunodeficient NSG mice transplanted with CD4+ T cells from PWHin vivo. Such viral control was associated with preserved NKG2C memory NK cell precursors, increased expression of granzyme B and TRAIL on NK in tissue from transplanted NSG mice. Together, combination of Nano-PIC DC and anti-TIGIT antibodies may be a promising strategy to increase the efficacy of immunotherapies aimed at HIV-1 cure.One sentence summaryStimulation of memory NK with a combination of DC and anti-TIGIT antibodies increase their ability to eliminate HIV-1 infected CD4+ T cellsin vitroandin vivo.
Characterizing nascent transcription patterns of PROMPTs, eRNAs, and readthrough transcripts in the ENCODE4 deeply profiled cell lines
Authors: McShane Ariel , Narayanan Ishwarya Venkata , Paulsen Michelle T. , Ashaka Mario , Blinkiewicz Hailey , Yang Nina T. , Magnuson Brian , Bedi Karan , Wilson Thomas E. , Ljungman Mats 
Published: April 2024

SummaryArising as co-products of canonical gene expression, transcription-associated lincRNAs, such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and readthrough (RT) transcripts, are often regarded as byproducts of transcription, although they may be important for the expression of nearby genes. We identified regions of nascent expression of these lincRNA in 16 human cell lines using Bru-seq techniques, and found distinctly regulated patterns of PROMPT, eRNA, and RT transcription using the diverse biochemical approaches in the ENCODE4 deeply profiled cell lines collection. Transcription of these lincRNAs was influenced by sequence-specific features and the local or 3D chromatin landscape. However, these sequence and chromatin features do not describe the full spectrum of lincRNA expression variability we identify, highlighting the complexity of their regulation. This may suggest that transcription-associated lincRNAs are not merely byproducts, but rather that the transcript itself, or the act of its transcription, is important for genomic function.
Global, asynchronous partial sweeps at multiple insecticide resistance genes inAedesmosquitoes
Authors: Schmidt Thomas L , Endersby-Harshman Nancy M , van Rooyen Anthony RJ , Katusele Michelle , Vinit Rebecca , Robinson Leanne J. , Laman Moses , Karl Stephan , Hoffmann Ary A 
Published: April 2024

AbstractAedes aegypti(yellow fever mosquito) andAe. albopictus(Asian tiger mosquito) are globally invasive pests that confer the world’s dengue burden. Insecticide-based man-agement has led to the evolution of insecticide resistance in both species, though the genetic architecture and geographical spread of resistance remains incompletely un-derstood. This study investigates partial selective sweeps at resistance genes on two chromosomes and characterises their spread across populations. Sweeps at the volt-age-sensitive sodium channel gene (VSSC) on chromosome 3 correspond to one nu-cleotide substitution inAe. albopictusand three substitutions inAe. aegypti, including two at the same nucleotide position (F1534C) that have evolved and spread independently. InAe. aegypti, we also identified partial sweeps at a second locus on chromosome 2. This locus contained 15 glutathione S-transferase (GST) epsilon class genes with significant copy number variation among populations and where three distinct genetic backgrounds have spread across the Indo-Pacific region, the Americas, and Australia. Local geographical patterns and linkage networks indicate VSSC and GST backgrounds probably spread at different times and interact locally with different genes to produce resistance phenotypes. These findings highlight the rapid spread of resistance genes globally and are evidence for the critical importance of GST genes in resistance evolution.
Structure of Calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A
Authors: Shaw Alexandria L , Suresh Sushant , Parson Matthew AH , Harris Noah J , Jenkins Meredith L , Yip Calvin K , Burke John E 
Published: April 2024

AbstractPhosphatidylinositol 4-kinase alpha (PI4KA) maintains the PI4P and phosphatidylserine pools of the plasma membrane. A key regulator of PI4KA is its association into a complex with TTC7 and FAM126 proteins. This complex can be regulated by the CNAβ1 isoform of the phosphatase Calcineurin. We previously identified that CNAβ1 directly binds to FAM126A. Here, we report a cryo-EM structure of a truncated PI4KA complex bound to Calcineurin, revealing a direct Calcineurin interaction with PI4KA. Additional HDX-MS and computational analysis show that Calcineurin forms a complex with an evolutionarily conserved IKISVT sequence in PI4KA’s horn domain. We also characterised conserved LTLT and PSISIT Calcineurin binding sequences in the C-terminus of FAM126A. These sites are in close proximity to phosphorylation sites in the PI4KA complex, suggesting key roles of Calcineurin-regulated phosphosites in PI4KA regulation. This work reveals novel insight into how Calcineurin can regulate PI4KA activity.
Control of GSK3β nuclear localization by amino acid signaling requires GATOR1 but is mTORC1-independent
Authors: Schwendener Forkel Diana , Ibazebo Osemudiamen , Soha Sumaiya , Bautista Stephen J. , Impellizzeri Stefania , Botelho Roberto J. , Hesketh Geoffrey , Gingras Anne-Claude , Antonescu Costin N. 
Published: April 2024

AbstractThe availability of certain amino acids regulates cell survival, proliferation, growth, differentiation, and other cellular functions. Sensing of amino acids that converges on the GATOR1 and GATOR2 complexes supports activation of mTORC1 during amino acid replete conditions. Whether amino acid-derived cues regulate additional pathways remains poorly understood. We uncover that amino acid sensing involving GATOR1 and GATOR2 regulates the cellular localization of glycogen synthase kinase 3β (GSK3β). GATOR1 is required to recruit a subset of GSK3β to the lysosome selectively in the presence of amino acids. In addition, while under nutrient replete conditions GSK3β is largely cytosolic, amino acid starvation drives a portion of GSK3β into the nucleus. Acute replenishment of specific amino acids in starved cells triggered nuclear exit of GSK3β. This amino acid-stimulated GSKβ nuclear exit required GATOR1 and GATOR2 but was independent of mTORC1 and its activating RagA/B GTPases. This suggests that GATOR1 has a function that diverges from control of mTORC1 to regulate the nucleocytoplasmic shuttling of GSK3β. Furthermore, experimental restriction of GSK3β to the cytoplasm decreased cell survival in amino acid deficient conditions. This suggests that control of GSK3β nuclear localization by GATOR-dependent signals represents a cellular adaptation to metabolic stress that supports cell survival.
HR3/RORα-mediated cholesterol sensing regulates TOR signaling
Authors: Lassen Mette , Pardee Keith , Pedersen Lisa H. , Kubrak Olga , Koyama Takashi , Necakov Sasha , Liu Suya , Kuksis Arnis , Lajoie Gilles , Edwards Aled , Teleman Aurelio A. , Larsen Martin R. , Krause Henry M. , Texada Michael J. , Rewitz Kim 
Published: April 2024

SummaryCells and organisms adjust their growth based on the availability of cholesterol, which is essential for cellular functions. However, the mechanisms by which cells sense cholesterol levels and translate these into growth signals are not fully understood. We report that cholesterol rapidly activates the master growth-regulatory TOR pathway inDrosophilatissues. We identify the nuclear receptor HR3, an ortholog of mammalian RORα, as an essential factor in cholesterol-induced TOR activation. We demonstrate that HR3 binds cholesterol and promotes TOR pathway activation through a non-genomic mechanism acting upstream of the Rag GTPases. Similarly, we find that RORα is necessary for cholesterol-mediated TOR activation in human cells, suggesting that HR3/RORα represents a conserved mechanism for cholesterol sensing that couples cholesterol availability to TOR-pathway activity. These findings advance our understanding of how cholesterol influences cell growth, with implications for cholesterol-related diseases and cancer.HighlightsCholesterol leads to dynamic TOR pathway activation, driving systemic growthHR3 inDrosophilabinds cholesterol and couples its availability to TOR activationHR3 acts upstream of Rag GTPases to activate TOR in response to lysosomal cholesterolMammalian HR3 ortholog RORα is required for cholesterol-induced TOR activation
Mass spectrometry-based proteomic exploration of diverse murine macrophage cellular models
Authors: Gudgeon Jack , Marin Rubio José Luis , Sidgwick Frances , Trost Matthias 
Published: April 2024

AbstractImmortalised cell lines analogous to their primary cell counterparts are fundamental to research, particularly when large cell numbers are required. Here we report that immortalisation of bone marrow-derived macrophages using the J2-virus resulted in the loss of a protein of interest, MSR1, in wild-type cells by an unknown mechanism. This led us to perform an in-depth mass spectrometry-based proteomic characterisation of common murine macrophage cell lines (J774A.1, RAW264.7, and BMA3.1A7), with comparison to the immortalised bone marrow-derived macrophages (iBMDMs), as well as primary BMDMs. This revealed striking differences in protein profiles associated with macrophage polarisation, phagocytosis, pathogen recognition, and IFN signalling. J774A.1 cells were determined to be the most similar to the gold standard primary BMDM model, with BMA3.1A7 cells the least similar due to the reduction in abundance of several proteins related closely to macrophage function. This comprehensive proteomic data offers valuable insights into the selection of specific macrophage cell lines for cell signalling and inflammation research.
Antimicrobial effect of two endemic Dominican plants on microorganisms that cause otitis
Authors: Rivas-Ramírez Julio A. , Morales-Mercedes Michael M. , Guzmán-Recio Juan A. , Infante María I. , Valdez-Disla Alexander , Guzmán-Marte Anel E. , Ramírez Maritza , La Cruz Dolores Mejía-De , Vásquez-Tineo Manuel 
Published: April 2024

SummaryIntroductionOtitis is a condition that typically results from infectious agents causing inflammation of the ear and its surrounding tissues. Common treatment involves the use of antimicrobial drugs to combat the infection and alleviate symptoms. However, the overuse of these medications has led to the development of antimicrobial resistance, limiting treatment options. Currently, there is growing interest in exploring the antimicrobial potential of medicinal plant extracts as an effective alternative to conventional drugs.ObjectiveThis study aimed to assess the antimicrobial capabilities of S. arborescens and S. bahorucana plants against microorganisms isolated from patients exhibiting clinical symptoms suggestive of otitis.Materials and MethodsA cross-sectional, in vitro experimental study was conducted, involving the preparation of extracts from Salvia arborescens and Salvia bahorucana using various organic solvents. We used a modified agar dilution method to test the antimicrobial activity against ATCC microorganisms and clinical strains. The phytochemical composition of the plants was determined using thin-layer chromatography (TLC).ResultsExtracts from S. arborescens exhibited a significant presence of flavonoids and saponins. In contrast, S. bahorucana extracts displayed mild to moderate traces of the analyzed phytochemicals. Both plant extracts demonstrated antimicrobial activity capable of inhibiting the growth of strains, including S. aureus ATCC, S. pyogenes ATCC, and P. aeruginosa ATCC. The ethanolic extracts exhibited satisfactory activity against clinical isolate strains, effectively inhibiting the growth of all tested microorganisms. Notably, the ethanolic extract of S. arborescens exhibited stronger antimicrobial activity.ConclusionsThe results of this study provide a foundation for further research aimed at exploring the mechanisms of action and safety of medicinal plant extracts. This research may pave the way for potential clinical applications in the treatment of otitis and other infectious diseases.