bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Longitudinal Study of Executive Function in Daily Life in Male Fragile X Premutation Carriers and Association with FXTAS Conversion
Authors: Hessl David , Rojas Karina Mandujano , Ferrer Emilio , Espinal Glenda , Famula Jessica , Schneider Andrea , Hagerman Randi , Tassone Flora , Rivera Susan M. 
Published: September 2023

BackgroundMen with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies have made it difficult to address this hypothesis.MethodsThis study included 66 FMR1 premutation carriers (PC) ranging from 40-78 years (Mean=59.5) and 31 well-matched healthy controls (HC) ages 40-75 (Mean 57.7) at baseline. Eighty-four participants returned for 2-5 follow up visits over a duration of 1 to 9 years (Mean=4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit.ResultsLongitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, BRIEF-A executive function problems at baseline significantly predicted later development of FXTAS.ConclusionsThese findings suggest that executive function changes represent a prodrome of the later movement disorder.
Upregulation of ARHGAP9 is correlated with poor prognosis and immune infiltration in clear cell renal cell carcinoma
Authors: Xiong Yu-ling , Peng Chao , Tian Yue 
Published: September 2023

AbstractBackgroundRho GTPase Activating Protein (ARHGAP) family genes play critical roles in the onset and progression of human cancer. Rho GTPase Activating Protein 9 (ARHGAP9) is upregulated in various tumors. However, far too little attention has been paid to the prognostic value of ARHGAP9 and correlation with immune infiltration in clear cell renal cell carcinoma. Our aim is to evaluate the prognostic significance of ARHGAP9 expression and its correlation with immune infiltration in clear cell renal cell carcinoma.MethodsTranscriptional expression profiles of ARHGAP9 between clear cell renal cell carcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The ARHGAP9 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Receiver operating characteristic (ROC) curve was used to differentiate clear cell renal cell carcinoma from adjacent normal tissues. The Kaplan-Meier method was conducted to assess the effect of ARHGAP9 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the "ClusterProfiler" package. The immune infiltration patterns were evaluated via the tumor immune estimation resource 2.0 (TIMER 2.0) and TISIDB database.ResultsARHGAP9 expression was substantially higher in clear cell renal cell carcinoma tissues than in adjacent normal tissues. Increased ARHGAP9 mRNA expression was shown to be linked to high TNM stage and lymph node metastases. The diagnostic value of ARHGAP9 gene expression data was assessed using ROC curve analysis. The survival analysis module of GEPIA2 and the Kaplan-Meier plotter both showed clear cell renal cell carcinoma patients with high-ARHGAP9 had a worse prognosis than those with low-ARHGAP9. Correlation analysis indicated ARHGAP9 mRNA expression was significantly correlated with tumor purity and immune infiltrates.ConclusionThese findings demonstrate that up-regulated ARHGAP9 indicates poor prognosis and immune infiltration in clear cell renal cell carcinoma. The current findings suggest that ARHGAP9 can be an effective biomarker and potential therapeutic strategy for ccRCC.
Application of MALDI-MS and Machine Learning to Detection of SARS-CoV-2 and non-SARS-CoV-2 Respiratory Infections
Authors: Yegorov Sergey , Kadyrova Irina , Korshukov Ilya , Sultanbekova Aidana , Barkhanskaya Valentina , Bashirova Tatiana , Zhunusov Yerzhan , Li Yevgeniya , Parakhina Viktoriya , Kolesnichenko Svetlana , Baiken Yeldar , Matkarimov Bakhyt , Vazenmiller Dmitriy , Miller Matthew S. , Hortelano Gonzalo H. , Turmuhambetova Anar , Chesca Antonella E. , Babenko Dmitriy 
Published: September 2023

AbstractBackgroundMatrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) could aid the diagnosis of acute respiratory infections (ARI) owing to its affordability and high-throughput capacity. MALDI-MS has been proposed for use on commonly available respiratory samples, without specialized sample preparation, making this technology especially attractive for implementation in low-resource regions. Here, we assessed the utility of MALDI-MS in differentiating SARS-CoV-2 versus non-COVID acute respiratory infections (NCARI) in a clinical lab setting of Kazakhstan.MethodsNasopharyngeal swabs were collected from in- and outpatients with respiratory symptoms and from asymptomatic controls (AC) in 2020-2022. PCR was used to differentiate SARS-CoV-2+ and NCARI cases. MALDI-MS spectra were obtained for a total of 252 samples (115 SARS-CoV-2+, 98 NCARI and 39 AC) without specialized sample preparation. In our first sub-analysis, we followed a published protocol for peak preprocessing and Machine Learning (ML), trained on publicly available spectra from South American SARS-CoV-2+ and NCARI samples. In our second sub-analysis, we trained ML models on a peak intensity matrix representative of both South American (SA) and Kazakhstan (Kaz) samples.ResultsApplying the established MALDI-MS pipeline ”as is” resulted in a high detection rate for SARS-CoV-2+ samples (91.0%), but low accuracy for NCARI (48.0%) and AC (67.0%) by the top-performing random forest model. After re-training of the ML algorithms on the SA-Kaz peak intensity matrix, the accuracy of detection by the top-performing Support Vector Machine with radial basis function kernel model was at 88.0, 95.0 and 78% for the Kazakhstan SARS-CoV-2+, NCARI, and AC subjects, respectively with a SARS-CoV-2 vs. rest ROC AUC of 0.983 [0.958, 0.987]; a high differentiation accuracy was maintained for the South American SARS-CoV-2 and NCARI.ConclusionsMALDI-MS/ML is a feasible approach for the differentiation of ARI without a specialized sample preparation. The implementation of MALDI-MS/ML in a real clinical lab setting will necessitate continuous optimization to keep up with the rapidly evolving landscape of ARI.
Comparison of dental topography of marmosets and tamarins (Callitrichidae) to other platyrrhine primates using a novel freeware pipeline
Authors: de Vries Dorien , Janiak Mareike C. , Batista Romina , Boubli Jean P. , Goodhead Ian B. , Ridgway Emma , Boyer Doug M. , St. Clair Elizabeth , Beck Robin M.D. 
Published: September 2023

AbstractDental topographic metrics (DTMs), which quantify different aspects of the shape of teeth, are powerful tools for studying dietary adaptation and evolution in mammals. However, comparative samples of scanned mammal teeth suitable for analysis with DTMs remain limited in size and scope, with little or no representation of some major lineages, even within well-studied clades such as primates. In addition, current DTM protocols usually rely on proprietary software, which may be unavailable to many researchers for reasons of cost. We address these issues in the context of a DTM analysis of the primate clade Platyrrhini (“New World monkeys”) by: 1) presenting a large comparative sample of scanned second lower molars (m2s) of callitrichids (marmosets and tamarins), which were previously underrepresented in publicly available platyrrhine datasets; and 2) giving full details of an entirely freeware pipeline for DTM analysis. We also present an updated discrete dietary classification scheme for extant platyrrhines, based on cluster analysis of dietary data extracted from 98 primary studies. Our freeware pipeline performs equally well in dietary classification accuracy of an existing sample of platyrrhine m2s (excluding callitrichids) as a published protocol that uses proprietary software, at least when multiple DTMs are combined. Individual DTMs however, sometimes showed very different results in classification accuracies between that of our freeware pipeline and that of the proprietary protocol, most likely due to the differences in the smoothing functions used. The addition of callitrichids still resulted in high classification accuracy in predicting diet with combined DTMs, although accuracy was considerably higher when molar size was included (90%) than excluded (73%). We conclude that our new freeware DTM pipeline is capable of accurately predicting diet in platyrrhines based on tooth shape and size, and so is suitable for inferring probable diet of taxa for which direct dietary information is unavailable, such as fossil species.
Dysregulation of γδ intraepithelial lymphocytes precedes Crohn’s disease-like ileitis
Authors: Xu Weili , Golovchenko Natasha B. , Fong Andrew , Achi Sajan , Bucar Edie B. , Vidmar Kaylynn J. , Zhang Lanjing , Frey Mark R. , Prinz Immo , Pizarro Theresa T. , Kollias George , Edelblum Karen L. 
Published: September 2023

SummaryIntraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) provide immunosurveillance of the intestinal barrier. Interestingly, γδ IEL number is reduced in patients with active Crohn’s disease (CD). Here, we report an underappreciated role for γδ IELs in maintaining mucosal tolerance during the onset and progression of CD-like ileitis using the TNFΔARE/+mouse model. Decreased epithelial HNF4G/BTNL expression is followed by a loss of ileal γδ IELs and impaired barrier surveillance prior to the histological onset of disease. A reduction of immunoregulatory CD39+γδ IELs coincides with the influx of immature, peripheral CD39-γδ T cells into the epithelium leading to an expansion of induced IELs, while an earlier depletion of γδ IELs correlates with accelerated onset of ileal inflammation. Our findings identify multiple layers of γδ IEL dysregulation prior to ileitis development indicating that the loss of tissue-resident immunoregulatory γδ IELs may contribute to the initiation of ileal CD.
Human gut metagenomic mining reveals an untapped source of peptide antibiotics
Authors: Torres Marcelo D. T. , Brooks Erin , Cesaro Angela , Sberro Hila , Nicolaou Cosmos , Bhatt Ami S. , de la Fuente-Nunez Cesar 
Published: September 2023

AbstractDrug-resistant bacteria are outpacing traditional antibiotic discovery efforts. Here, we computationally mined 444,054 families of putative small proteins from 1,773 human gut metagenomes, identifying 323 peptide antibiotics encoded in small open reading frames (smORFs). To test our computational predictions, 78 peptides were synthesized and screened for antimicrobial activityin vitro, with 59% displaying activity against either pathogens or commensals. Since these peptides were unique compared to previously reported antimicrobial peptides, we termed themsmORF-encoded peptides (SEPs). SEPs killed bacteria by targeting their membrane, synergized with each other, and modulated gut commensals, indicating that they may play a role in reconfiguring microbiome communities in addition to counteracting pathogens. The lead candidates were anti-infective in both murine skin abscess and deep thigh infection models. Notably, prevotellin-2 fromPrevotella copripresented activity comparable to the commonly used antibiotic polymyxin B. We report the discovery of hundreds of peptide sequences in the human gut.
Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats
Authors: Kuebler Isabel R.K. , Liu Youxi , Bueno Álvarez Bárbara S. , Huber Noah M. , Jolton Joshua A. , Dasari Raaga , Wakabayashi Ken T. 
Published: September 2023

AbstractNicotine is a significant public health concern because it is the primary pharmacological agent in tobacco use disorder. One neural system that has been implicated in the symptoms of several substance use disorders is the melanin-concentrating hormone (MCH) system. MCH regulates various motivated behaviors depending on sex, yet little is known of how this interaction affects experience with drugs of abuse, particularly nicotine. The goal of this study was to determine the effect of MCH receptor antagonism on experience-dependent nicotine-induced locomotion after chronic exposure, particularly on the expression of locomotor sensitization. Adult female and male Wistar rats were given saline then cumulative doses of nicotine (0.1, 0.32, 0.56, and 1.0 mg/kg) intraperitoneally to determine the acute effects of nicotine (day 1). Next, rats were treated with 1.0 mg/kg nicotine for 6 days, given an identical series of cumulative doses (day 8), and then kept in a drug-free state for 6 days. On day 15, rats were pretreated with vehicle or the MCH receptor antagonist GW803430 (10 or 30 mg/kg) before another series of cumulative doses to assess response to chronic nicotine. After vehicle, male rats increased nicotine locomotor activation from day 1 to day 15, and both sexes showed a sensitized response when normalized to saline. The lower dose of GW803430 decreased locomotion compared to vehicle in females, while the higher dose decreased locomotion in males. Both sexes showed nicotine dose-dependent effects of GW803430, strongest at lower doses of nicotine. Controlling for sex-based locomotor differences revealed that females are more sensitive to GW803430. The high dose of GW803430 also decreased saline locomotion in males. Together, the results of our study suggest that MCH is involved in the expression of nicotine locomotor sensitization, and that MCH regulates these nicotine behavioral symptoms differently across sex.
Flexible neural representations of abstract structural knowledge in the human Entorhinal Cortex
Authors: Mark S. , Schwartenbeck P. , Hahamy A , Samborska V , Baram AB. , Behrens TEJ 
Published: September 2023

AbstractHumans’ ability for generalisation is outstanding. It is flexible enough to identify cases where knowledge from prior tasks is relevant, even when many features of the current task are different, such as the sensory stimuli or the size of the task state space. We have previously shown that in abstract tasks, humans can generalise knowledge in cases where the only cross-task shared feature is the statistical rules that govern the task’s state-state relationships. Here, we hypothesized that this capacity is associated with generalisable representations in the entorhinal cortex (EC). This hypothesis was based on the EC’s generalisable representations in spatial tasks and recent discoveries about its role in the representation of abstract tasks. We first develop an analysis method capable of testing for such representations in fMRI data, explain why other common methods would have failed for our task, and validate our method through a combination of electrophysiological data analysis, simulations and fMRI sanity checks. We then show with fMRI that EC representations generalise across complex non-spatial tasks that share a hexagonal grid structural form but differ in their size and sensory stimuli, i.e. their only shared feature is the rules governing their statistical structure. There was no clear evidence for such generalisation in EC for non-spatial tasks with clustered, as opposed to planar, structure.
Genome report: Whole genome sequence and annotation ofPenstemon davidsonii
Authors: Ostevik Kate L. , Alabady Magdy , Zhang Mengrui , Rausher Mark D. 
Published: September 2023

AbstractPenstemonis the most speciose flowering plant genus endemic to North America.Penstemonspecies’ diverse morphology and adaptation to various environments have made them a valuable model system for studying evolution, but the absence of publicly available reference genomes limits possible research directions. Here we report the first reference genome assembly and annotation forPenstemon davidsonii. Using PacBio long-read sequencing and Hi-C scaffolding technology, we constructed a de novo reference genome of 437,568,744 bases, with a contig N50 of 40 Mb and L50 of 5. The annotation includes 18,199 gene models, and both the genome and transcriptome assembly contain over 95% complete eudicot BUSCOs. This genome assembly will serve as a valuable reference for studying the evolutionary history and genetic diversity of thePenstemongenus.
Illuminating the Terminal Nerve: Uncovering the Link between GnRH-1 and Olfactory Development
Authors: Amato Enrico , Taroc Ed Zandro M , Forni Paolo E. 
Published: September 2023

AbstractDuring embryonic development, the olfactory placode (OP) generates migratory neurons, including olfactory pioneer neurons, cells of the terminal nerve (TN), Gonadotropin-releasing hormone-1 (GnRH-1) neurons, and other uncharacterized neurons. Pioneer neurons from the olfactory placode induce olfactory bulb morphogenesis.In mice, GnRH-1 neurons appear in the olfactory system around mid-gestation and migrate via the terminal nerve axons to different brain regions. The GnRH-1 neurons are crucial in controlling the hypothalamic-pituitary-gonadal (HPG) axis. Kallmann syndrome is characterized by impaired olfactory system development, defective olfactory bulbs, defective secretion of GnRH-1, and infertility. The precise mechanistic link between the olfactory system and GnRH-1 development remains unclear. Studies in humans and mice highlight the importance of the Prokineticin-2/Prokineticin-Receptor-2 (Prokr2) signaling pathway in olfactory bulb morphogenesis and GnRH-1 neuronal migration.Prokr2loss-of-function mutations can cause Kallmann syndrome, and hence the Prokr2 signaling pathway represents a unique model to decipher the olfactory/GnRH-1 connection. We discovered that Prokr2 is expressed in the TN neurons during the critical period of GnRH-1 neuron formation, migration, and induction of olfactory bulb morphogenesis. Single-cell RNA sequencing identified that the TN is formed by neurons that are distinct from the olfactory neurons. The TN neurons express multiple genes associated with KS. Our study suggests that the aberrant development of pioneer/TN neurons might cause the KS spectrum.Key Points1) Pioneer or terminal nerve neurons play a crucial role in initiating the development of the olfactory bulbs. We found that the Prokineticin Receptor-2 gene, associated with Kallmann syndrome, is expressed by the olfactory pioneer/terminal nerve neurons.2) We genetically traced, isolated, and conducted Single-cell RNA sequencing on terminal nerve neurons of rodents. This analysis revealed a significant enrichment of gene expression related to Kallmann syndrome.3) Our study indicates that the investigation of Pioneer/terminal nerve neurons should be a pivotal focal point for comprehending developmental defects affecting olfactory and GnRH-1 systems.
Losartan rewires ovarian cancer tumor-immune microenvironment and suppresses IGF-1 to amplify chemo-immunotherapy sensitivity
Authors: Sun Yao , Yin Zhenzhen , Wu Limeng , Yue Changli , Zhang Yanling , Subudhi Sonu , Lei Pinji , Muzikansky Alona , Zhang Luo , Rueda Bo R. , Jain Rakesh K. , Xu Lei 
Published: September 2023

AbstractOvarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. Here, using syngeneic OvCa models and genetic and pharmacologic perturbations, we discovered that losartan – a widely prescribed anti-hypertensive drug – exhibits dual effects on both the tumor microenvironment and cancer cells to sensitize OvCa to chemo-immunotherapy. Specifically, losartan treatment i) reprograms the tumor microenvironment leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. The safety and low cost (less than $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.
Tick hemocytes have pleiotropic roles in microbial infection and arthropod fitness
Authors: Rolandelli Agustin , Laukaitis-Yousey Hanna J. , Bogale Haikel N. , Singh Nisha , Samaddar Sourabh , O’Neal Anya J. , Ferraz Camila R. , Butnaru Matthew , Mameli Enzo , Xia Baolong , Mendes M. Tays , Butler L. Rainer , Marnin Liron , Cabrera Paz Francy E. , Valencia Luisa M. , Rana Vipin S. , Skerry Ciaran , Pal Utpal , Mohr Stephanie E. , Perrimon Norbert , Serre David , Pedra Joao H.F. 
Published: September 2023

AbstractUncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here, we describe immune cells or hemocytes from the clinically relevant tickIxodes scapularisusing bulk and single cell RNA sequencing combined with depletion via clodronate liposomes, RNA interference, Clustered Regularly Interspaced Short Palindromic Repeats activation (CRISPRa) and RNA-fluorescencein situhybridization (FISH). We observe molecular alterations in hemocytes upon tick infestation of mammals and infection with either the Lyme disease spirocheteBorrelia burgdorferior the rickettsial agentAnaplasma phagocytophilum. We predict distinct hemocyte lineages and reveal clusters exhibiting defined signatures for immunity, metabolism, and proliferation during hematophagy. Furthermore, we perform a mechanistic characterization of twoI. scapularishemocyte markers:hemocytinandastakine. Depletion of phagocytic hemocytes affectshemocytinandastakinelevels, which impacts blood feeding and molting behavior of ticks. Hemocytin specifically affects the c-Jun N-terminal kinase (JNK) signaling pathway, whereas astakine alters hemocyte proliferation inI. scapularis. Altogether, we uncover the heterogeneity and pleiotropic roles of hemocytes in ticks and provide a valuable resource for comparative biology in arthropods.