bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new dentition-based phylogeny of Litopterna (Mammalia: Placentalia) and ‘archaic’ South American ungulates
Authors: Püschel Hans P , Shelley Sarah L , Williamson Thomas E , Perini Fernando A , Wible John R , Brusatte Stephen L 
Published: September 2024

Abstract
Ever since the discovery of Macrauchenia patachonica by Charles Darwin in 1834, the affinities of litopterns—a group of extinct South American Native Ungulates (SANUs)—have been elusive. In particular, the interfamilial relationships and timing of the familial diversification within the order Litopterna have not been addressed with adequate taxon and character sampling, and modern phylogenetic methods. We address these issues using a new morphological matrix of 703 dental and mandibular characters, scored for the earliest litopterns alongside early SANUs of other orders (Astrapotheria, Notoungulata, Pyrotheria, and Xenungulata). We also included members of families that have been often included within Litopterna, such as Didolodontidae, Protolipternidae, Indaleciidae, and Notonychopidae, the last two sometimes grouped in the order Notopterna. We conducted maximum parsimony and undated and tip-dated Bayesian phylogenetic analyses. Our results indicate that (1) didolodontids, protolipternids, and kollpaniines should be considered early SANUs, but not particularly closely related to any order, (2) Indaleciidae and Notonychopidae usually form a monophyletic group (Notopterna), and (3) Litopterna is a monophyletic unit composed of four families [Adianthidae, Anisolambdidae (subfamilies Anisolambdinae and Sparnotheriodontinae), Macraucheniidae, Proterotheriidae], and tentatively the notoptern families Indaleciidae and Notonychopidae with a probable origin ~64.0 Mya in the Early Palaeocene.
Smoking and Type 1 Versus Type 2 Myocardial Infarction Among People With HIV in the United States: Results from the Center for AIDS Research Network Integrated Clinical Systems Cohort
Authors: Crane Heidi M. , Nance Robin M. , Ruderman Stephanie A. , Drumright Lydia N. , Mixson L. Sarah , Heckbert Susan R. , Feinstein Matthew J. , Budoff Matthew J. , Bamford Laura , Cachay Edward , Napravnik Sonia , Moore Richard D. , Keruly Jeanne , Willig Amanda L. , Burkholder Greer A. , Hahn Andrew , Ma Jimmy , Fredericksen Rob , Saag Michael S. , Chander Geetanjali , Kitahata Mari M. , Crothers Kristina , Mayer Kenneth H. , O'Cleirigh Conall , Cropsey Karen , Whitney Bridget M. , Delaney Joseph A. C. 
Published: September 2024

AbstractSmoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g., intensity, duration) on MI risk. We used Cox proportional hazards regression to compare the association of smoking parameterization with incidents of type 1 and type 2 MI and whether smoking intensity or duration improves MI risk prediction among PWH. Among 11,637 PWH, 37% reported currently smoking, and there were 346 MIs. Current smoking was associated with type 1 (84% increased risk) but not type 2 MI in adjusted analyses. The type 1 MI model with pack years had the best goodness of fit compared with other smoking parameterizations. Ever or never parameterization and smoking diagnosis data had significantly poorer model fit. These results highlight the importance of differentiating MI types and performing patient-based smoking assessments to improve HIV care and research rather than relying on smoking status from diagnoses.
Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence
Authors: Osma-Garcia Ines C. , Maloudi Orlane , Mouysset Mailys , Capitan-Sobrino Dunja , Nguyen Trang-My M. , Aubert Yann , Diaz-Muñoz Manuel D. 
Published: September 2024

SUMMARYImmune protection against new and recurrent infections relies on long-term maintenance of a highly diversified T-cell repertoire. Transcription factors cooperate to enforce T-cell metabolic quiescence and maintenance. However, less is known about the post-transcriptional networks that preserve peripheral naïve T cells. Here we describe the RNA binding proteins TIA1 and TIAL1 as key promoters of CD4 and CD8 T cell quiescence. T cells deficient in TIA1 and TIAL1 undergo uncontrolled cell proliferation in the absence of cognate antigens, leading this to a premature T-cell activation, exhaustion and death. Mechanistically, TIA1 and TIAL1 control the expression of master regulatory transcription factors, FOXP1, LEF1 and TCF1, that restrain homeostatic T-cell proliferation. In summary, our study highlights a previously unrecognised dependency on post-transcriptional gene regulation by TIA1 and TIAL1 for implementing the quiescent transcriptional programs for long survival of T cells.
Foliar application of nano urea results in higher biomass, chlorophyll, and nitrogen content than equimolar bulk urea through differential gene regulation inArabidopsis thaliana
Authors: Dey Arpan , Jangir Neelam , Verma Devanshu , Shekhawat Rajveer Singh , Yadav Pankaj , Sadhukhan Ayan 
Published: September 2024

AbstractIndian Farmers Fertilizer Cooperative (IFFCO)’s liquid nano urea formulation (NUF) was applied to one-month-oldArabidopsis thalianaplants grown in vermiculite as a 0.4% foliar spray twice at an interval of 10 days and compared with sprays of equimolar bulk urea. NUF resulted in a 51 ± 14.9% increase in biomass, 29.5 ± 9.1% in chlorophyll, 8.4 ± 3.1% in nitrogen, and 4.5 ± 0.3% in amino acid content of the leaves, compared to bulk urea. NUF’s zeta potential of -54.7 mV and particle size of ≃27.7 nm, measured by dynamic light scattering and transmission electron microscopy, make it suitable for stomatal uptake. We conducted a differential gene expression analysis by mRNA sequencing to understand the molecular basis of the phenotypic gains under NUF rather than urea. NUF resulted in significantly higher expression levels of 211 genes (log2fold-change > 0.5,FDR< 0.05) involved in the biosynthesis of carbohydrates, amino acids, nucleotides, lipids, phytohormones, and secondary metabolites, cell wall biosynthesis and modification, growth and developmental processes, cell cycle, and stress response than bulk urea. On the other hand, 1,286 genes (log2fold-change < -0.5) involved in cell death, abscission, senescence, nitrogen transport and metabolism, and biotic stress response showed lower expression levels upon NUF application than bulk urea. Our results suggest that although NUF foliar spray suppresses nitrogen uptake genes, possibly due to nitrogen excess, it enhances growth by up-regulating the synthesis of essential biomolecules and growth-promoting genes, compared to bulk urea.
Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy
Authors: Bridge Jacob , Johnson Matthew J. , Kim Jihyun , Wenthe Sophia , Krueger Joshua , Wick Bryce , Kluesner Mitchell , Crane Andrew T. , Bell Jason , Skeate Joseph G. , Moriarity Branden S. , Webber Beau R. 
Published: September 2024

ABSTRACTGamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their lack of alloreactivity, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods forex vivoexpansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach forex vivomanufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells in support of therapeutic application. Engineered CAR-γδ T cells demonstrate high functionin vitroand andin vivo.Longitudinalin vivopharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacyin vivo.
Ecological and evolutionary impacts of urbanization: applying a causal modeling framework
Authors: Borden Jesse B. , Gibbs James P. , Vanek John P. , Cosentino Bradley J. 
Published: September 2024

AbstractUrbanization, as the fastest growing land use type, shapes biodiversity through a suite of abiotic and biotic changes driven by the profound alteration of environmental conditions in built environments. Understanding the mechanisms behind biodiversity patterns in urban areas requires disentangling the direct and indirect pathways through which urbanization impacts ecological and evolutionary dynamics. We show how a structural causal modeling framework can be used to provide insight into processes generating biodiversity patterns in urban contexts by building structural equation models to disentangle direct and indirect pathways by which urbanization affects abundance and coat color variation in eastern gray squirrels (Sciurus carolinensis). Integrating camera traps and point count surveys across 49 sites, we observed pronounced urban-rural gradients in squirrel abundance and color variation. Human population density affected abundance of color morphs by mediating resource availability, predator activity, habitat amount, and fragmentation. But markedly different mechanisms drove abundance of color morphs across the landscape. Our findings reveal how explicit modeling of multiple pathways of environmental change can deepen our mechanistic understanding of how urbanization alters biodiversity patterns.
Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake
Authors: Sharpe Amanda L. , Liter Laci R. , Donohue Darius , Carter Kelsey A. , Vangeneugden Patricia , Weaver Sofia , Stout Michael B. , Beckstead Michael J. 
Published: September 2024

AbstractAlthough opioid abuse is more prevalent in young individuals, opioid use, overdose, and use disorders continue to climb at a rapid rate among the elderly. Little is known about abuse potential in a healthy aged population, in part due to technical and logistical difficulties testing intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice. Male and female mice were grouped into young (mean: 19 weeks) and old (mean: 101 weeks), and were trained to self-administer intravenous fentanyl or remifentanil in daily sessions. In both old and young mice, acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve (remifentanil) and dose-escalation (fentanyl) were conducted. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also substantially greater in old mice compared to their young counterparts; however, we did not see increased intake of fentanyl with age at either dose tested. Further, compared to young mice, the old mice showed a greater incubation of responding for cues previously associated with remifentanil after a forced abstinence, but again this was not observed with fentanyl. Together these data suggest that an aged population may have an increased drug-abuse vulnerability for opioids compared to young counterparts and underscore the importance of future work on mechanisms responsible for this increased vulnerability.
Computational Study of the Excitation of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes
Authors: Shetty Roshni , Samurkashian Raffi , Tung Leslie 
Published: September 2024

AbstractHuman induced pluripotent stem-cell derived cardiomyocytes (hiPSC-CMs) have proven to be a revolutionary advance for tissue engineering, disease modeling, and drug testing and discovery. Computational modeling enables a detailed electrophysiological analysis that is otherwise difficult or impossible to achieve under strictly experimental settings. Action potential characteristics of hiPSC-CMs measured in our lab at four different pacing rates were used it to modify the computational Kernik-Clancy hiPSC-CM model. The modified model was used to compare the excitation of single hiPSC-CMs with that of single human ventricular cardiomyocytes (hV-CMs) under varying conditions, including at stimulation at different strengths, rates and pulse durations. The physiological stimulation of both hiPSC-CMs and hV-CMs embedded within a tissue strand involves a biphasic waveform during which time excitatory currents (particularlyINa, but alsoICaTandICaLfor hiPSC-CMs andINaLandICaLfor hV-CMs) are activated during both phases of the waveform.INain particular activated more slowly and with diminished amplitude under conditions of increasing pacing rate or increasing intracellular resistance. Lastly, histograms characterizing the relative amounts of excitatory currents in a population of hiPSC-CMs become broader with increasing levels ofINablock, withICaTandICaLworking in tandem to excite cells whereINahas failed to activate. In general, hiPSC-CMs were found to be more excitable from rest compared with hV-CMs owing to their more depolarized resting potential and intrinsic automaticity despite a lower sodium channel density. Such a mismatch should be taken into consideration for applications using these cells, particularly for cardiac repair.Key PointsCardiomyocytes (CMs) generated from human stem cells derived from blood or skin have great potential for cardiac repair, safety pharmacology and disease modeling, but understanding their excitability is crucial for their proper application.Computational modeling reveals greater excitability of these cells in terms of various metrics compared with that of human adult ventricular CMs at multiple pacing rates.The excitation of CMs within a strand differs substantially from that usually used to study single isolated CMs and is dissected in terms of the underlying ionic currents.Computational modeling also predicts how a heterogeneous population of stem cell-derived CMs and their underlying ionic currents could respond to varying levels of reduced sodium current.Our study presents a cautionary note for applications using these cells, particularly for cardiac repair.
Knocking out the carboxyltransferase interactor 1 (CTI1) in Chlamydomonas boosted oil content by fivefold without affecting cell growth
Authors: Li Zhongze , Kim Minjae , da Silva Nascimento Jose Roberto , Legeret Bertrand , Jorge Gabriel Lemes , Bertrand Marie , Beisson Fred , Thelen Jay J , Li-Beisson Yonghua 
Published: September 2024

ABSTRACTThe first step in chloroplastde novofatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACCase). As the rate-limiting step for this pathway, ACCase is subject to both positive and negative regulation. In this study, we identify a Chlamydomonas homolog of the plant carboxyltransferase interactor 1 (CrCTI1) and show that this protein, interacts with the Chlamydomonas α-carboxyltransferase (Crα-CT) subunit of the ACCase by yeast two-hybrid protein-protein interaction assay. Three independent CRISPR-Cas9 mediated knock-out mutants for CrCTI1 each produced an “enhanced oil” phenotype, accumulating 25% more total fatty acids and storing up to five-fold more triacylglycerols (TAGs) in lipid droplets. The TAG phenotype of thecrcti1mutants was not influenced by light but was affected by trophic growth conditions. By growing cells under heterotrophic conditions, we observed a crucial function of CrCTI1 in balancing lipid accumulation and cell growth. Mutating a previously mappedin vivophosphorylation site (CrCTI1 Ser108 to either Ala or to Asp), did not affect the interaction with Crα-CT. However, mutating all six predicted phosphorylation sites within Crα-CT to create a phosphomimetic mutant reduced significantly this pairwise interaction. Comparative proteomic analyses of thecrcti1mutants and WT suggested a role for CrCTI1 in regulating carbon flux by coordinating carbon metabolism, antioxidant and fatty acid β-oxidation pathways, to enable cells adapt to carbon availability. Taken together, this study identifies CrCTI1 as a negative regulator of fatty acid synthesis in algae and provides a new molecular brick for genetic engineering of microalgae for biotechnology purposes.
Claudin-4 remodeling of nucleus-cell cycle crosstalk maintains ovarian tumor genome stability and drives resistance to genomic instability-inducing agents
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G. 
Published: September 2024

AbstractDuring cancer development, the interplay between the nucleus and the cell cycle leads to a state of genomic instability, often accompanied by observable morphological aberrations. These aberrations can be controlled by tumor cells to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer (EOC), overexpression of the multifunctional protein claudin-4 is a key contributor to therapy resistance through mechanisms associated with genomic instability. However, the molecular mechanisms underlying claudin-4 overexpression in EOC remain poorly understood. Here, we altered claudin-4 expression and employed a unique claudin-4 targeting peptide (CMP) to manipulate the function of claudin-4. We found that claudin-4 facilitates genome maintenance by linking the nuclear envelope and cytoskeleton dynamics with cell cycle progression. Claudin-4 caused nuclei constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, associated with remodeling nuclear architecture, thus altering nuclear envelope dynamics. Consequently, cell cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability. Importantly, disrupting biological interactions of claudin-4 using CMP and forskolin altered oxidative stress cellular response and increased the efficacy of PARP inhibitor treatment. Our data indicate that claudin-4 protects tumor genome integrity by remodeling the crosstalk between the nuclei and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability-inducing agents.Abstract FigureGraphical abstractClaudin-4 plays a crucial role in remodeling the cytoskeleton, particularly influencing nuclear architecture. This remodeling appears to act as a regulatory mechanism, limiting the progression of ovarian cancer cells into the S-phase and correlating with reduced genomic instability in ovarian tumors. Moreover, since olaparib treatment triggered a cellular oxidative response, it is likely that this claudin-4-mediated remodeling contributes to resistance against the effects of the PARP inhibitor.
Exploring the effect of capsaicin on gene expression and chemotherapy sensitization in gastric cancer cells
Authors: Meng Weijian , Xie Sophia , Zhang Rui , Shen Jie 
Published: September 2024

AbstractPurposeCapsaicin has previously been demonstrated to exhibit anti-tumor effect in various cancer type. However, the effect of capsaicin on gene expression and its potential mechanism on chemotherapy sensitization were still uncertain.MethodHuman AGS gastric cancer cell line was treated with different concentrations of capsaicin, 5-fluorouracil and oxaliplatin. Cell viability was assessed using cell viability assay. High throughput RNA sequencing was used to screen differentially expressed genes triggered by capsaicin in AGS cells. qPCR and Western blotting were used to detect the expression of mRNAs and proteins induced by capsaicin.ResultCapsaicin could significantly inhibit cell viability at a dose-depend manner in AGS gastric cancer cell line. Through high-throughput RNA sequencing, genes regulating DNA repair, DNA replication and chromosome assemble pathways were analyzed to be down-regulated by capsaicin. qPCR and western blot assay demonstrated that capsaicin could inhibit expression of the key enzymes (FEN1, LIG1 and PARP1) which play critical roles in DNA damage response and chemotherapy resistance. In vitro assay demonstrated that capsaicin could significantly induce chemo-sensitivity of 5-FU and Oxaliplatin at low dose.ConclusionCapsaicin could inhibit DNA repair pathway, which might contribute to cell growth inhibition and improvement of chemotherapy sensitization. These results revealed a novel function of capsaicin in DNA damage repair and provided new potential targets in cancer therapy.
Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases
Authors: Tokavanich Nicha , Chan Byron , Strauss Katelyn , Castro Andrade Christian D. , Arai Yuki , Nagata Mizuki , Foretz Marc , Brooks Daniel J. , Ono Noriaki , Ono Wanida , Wein Marc N. 
Published: September 2024

AbstractAlveolar bone supports and anchors teeth. The parathyroid hormone-related protein (PTHrP) pathway plays a key role in alveolar bone biology. Salt inducible kinases (SIKs) are important downstream regulators of PTH/PTHrP signaling in the appendicular skeleton where SIK inhibition increases bone formation and trabecular bone mass. However, the function of these kinases in alveolar bone remains unknown. Here, we report a critical role for SIK2/SIK3 in alveolar bone development, homeostasis, and socket healing after tooth extraction. Inducible SIK2/SIK3 deletion led to dramatic alveolar bone defects without changes in tooth eruption. Ablating these kinases impairs alveolar bone formation due to disrupted osteoblast maturation, a finding associated with ectopic periostin expression by fibrous cells in regions of absent alveolar bone at steady state and following molar extraction. Distinct phenotypic consequences of SIK2/SIK3 deletion in appendicular versus craniofacial bones prompted us to identify a specific transcriptomic signature in alveolar versus long bone osteoblasts. Thus, SIK2/SIK3 deletion illuminates a key role for these kinases in alveolar bone biology and highlights the emerging concept that different osteoblast subsets utilize unique genetic programs.Summary statementSIK2/SIK3 deletion in alveolar bone reduces bone formation and mass by impairing osteoblast maturation, unlike in long bones, where it increases bone formation and mass.