bluuebunny/crossref_metadata_2025_split huggingface dataset:
RSYD-BASIC: a bioinformatics pipeline for Routine Sequence analYsis and Data processing of BActerial iSolates for clInical miCrobiology
Authors: Steinke Kat , Thomsen Karina Gravgaard , Hoegh Silje Vermedal , Larsen Sanne Løkkegaard , Kubel Vilhelmsen Karina , Jensen Thøger Gorm , Skov Marianne Nielsine , Sydenham Thomas Vognbjerg 
Published: September 2023

Whole genome sequencing of bacterial isolates is increasingly becoming routine in clinical microbiology; however, subsequent analysis often needs to be started by a bioinformatician even for comprehensive pipelines. With the RSYD-BASIC pipeline, we present a reads-to-results analysis pipeline operated by non-expert users that has already yielded clinically relevant results.
Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status
Authors: Dan Shu , Hall Julia , Holsen Laura M. , Klengel Torsten 
Published: September 2023

AbstractMajor Depressive Disorder (MDD) is a heterogenous and etiologically complex disease encompassing a broad spectrum of psychopathology, presumably arising from distinct pathophysiological mechanisms. Divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) are important clinical characteristics that are closely related to comorbidities, including cardiometabolic disorders. Prior evidence supports the notion that hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of the underlying mechanisms of Hyperphagic and Hypophagic MDD is limited, and knowledge of associated biological correlates of these endophenotypes remain fragmented. We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n=8 and n=13, respectively) and discovered individual genes and gene pathways associated with appetitive phenotypes. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD.
Number of children and mid- to later-life cognitive function and cognitive impairment in rural South Africa: Evidence from “Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI)
Authors: Phillips Meredith L , Kobayashi Lindsay C , Chakraborty Rishika , Wagner Ryan , Mahlalela Nomsa , Harezlak Jaroslaw , Brown Joshua W , Ludema Christina , Rosenberg Molly 
Published: September 2023

AbstractBackgroundCognitive impairment is projected to rise substantially by 2050, particularly in low- and middle-income countries with aging populations. Reproductive life history may be associated with later-life cognitive function. We aim to estimate the association between number of children and mid- to later-life cognitive performance.MethodData were from 5059 older adults (46% men) aged ≥40 years in the population-representative rural cohort of the “Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI). We fit linear regression and modified Poisson models to estimate the associations between number of children and cognitive function. Analyses were stratified by sex/gender, controlling for age, education, literacy, self-reported childhood health, country of birth, and father’s occupation.ResultsAfter adjustment, men with any number of children and women with 5+ children had higher cognitive function compared to those without children (β[95% CI]: Men: 1-2: 0.29[0.13 – 0.45], 3-4: 0.50[0.34 – 0.65], 5+: 0.48[0.33 – 0.63]; Women: 5+: 0.17[0.01 – 0.34]). Results from the adjusted modified Poisson regression models found that for men and women, groups with any number of children showed a lower prevalence of cognitive impairment than the group with 0 children (PR[95% CI] Men: 1-2: 0.48[0.31 – 0.75], 3-4: 0.21[0.12 – 0.37], 5+: 0.28[0.19 – 0.41], Women: 1-2: 0.52[0.31 – 0.88], 3-4: 0.55[0.33 – 0.91], 5+: 0.41[0.25 – 0.69]).ConclusionAmong older rural South African adults, having children was associated with greater cognitive performance and lower prevalence of cognitive impairment. Men tended to have larger protective associations than women, which may be due to sex/gender differences in biological and social roles of childbearing and rearing. Understanding the complex relationship between having children and later-life cognitive function may help identify interventions to reduce the impact of cognitive decline.
Adaptive Functions of Structural Variants in Human Brain Development
Authors: Ding Wanqiu , Li Xiangshang , Zhang Jie , Ji Mingjun , Zhang Mengling , Zhong Xiaoming , Cao Yong , Liu Xiaoge , Li Chunqiong , Xiao Chunfu , Wang Jiaxin , Li Ting , Yu Qing , Mo Fan , Zhang Boya , Qi Jianhuan , Yang Jie-Chun , Qi Juntian , Tian Lu , Xu Xinwei , Peng Qi , Zhou Wei-Zhen , Liu Zhijin , Fu Aisi , Zhang Xiuqin , Zhang Jian-Jun , Sun Yujie , Hu Baoyang , An Ni A. , Zhang Li , Li Chuan-Yun 
Published: September 2023

AbstractQuantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV atlas in a population of 562 rhesus macaques, verified by two public SV benchmarks, an inhouse benchmark of eight macaque genomes with long-read sequencing and another inhouse benchmark of one macaque genome with whole-genome assembly. This accurate, quantitative SV map indicates stronger purifying selection on inversions, one type of poorly-clarified SVs to date, especially for those located on regulatory regions, suggesting a strategy for prioritizing inversions with the most important functions. Based on the distribution and the evolutionary features of these inversions in macaque population, we then identified 75 human-specific inversions, clarified their functional effects and prioritized them. Notably, the top-ranked inversions have substantially shaped the human transcriptome, through their dual-effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof-of-concept, we linkedAPCDD1, located on one of these inversions with the highest rank score and downregulated in human brains, to neuronal maturation. The accumulation of human-specific mutations on its promoter region, accelerated by the formation of the inversion, contributed to the decreased expression in humans. Notably, the overexpression ofAPCDD1could accelerate the neuronal maturation, while its depletion in mice delays the neuronal maturation. This study thus highlights the contribution of SVs, especially the inversions, to the distinct features in human brain development.
A Novel Subtype of Myeloproliferative Neoplasms Driven by a MYC-Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai Vu , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae Hyun , Nakanishi Shima , Ferreira Renan B. , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok 
Published: September 2023

ABSTRACTDespite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPNs) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for triple negative myelofibrosis (MF) patients whose MPNs lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report thatMYCcopy number gain and increased MYC expression frequently occur in triple negative MF, and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves various hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation ofS100A9or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs.SIGNIFICANCEThis study establishes that MYC expression is increased in triple negative MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in triple negative MPN.
Input-specific gating of NMDA amplification via HCN channels in mouse L2/3 pyramidal neurons
Authors: Oláh Viktor János , Wu Jing , Kaczmarek Leonard K. , Rowan Matthew JM 
Published: September 2023

ABSTRACTLayer 2/3 pyramidal cells (L2/3 PCs) play a crucial role in cortical information transfer. Although the dendritic arbors of L2/3 PCs are impressive, they often lack the distinct anatomical compartments characteristic of deeper L5 PCs. For example, many L2/3 PCs do not display an apparent distal tuft region. However, L2/3 PCs receive inputs from both thalamic (bottom-up) and cortical (top-down) inputs, which preferentially synapse onto their proximal and distal dendrites, respectively. Nonuniform organization of channels and NMDA receptors in L2/3 dendrites could serve to independently modulate these information streams to affect learning and behavior, yet whether L2/3 PC dendrites possess this capability has not been established. Here we found a previously unappreciated, non-uniform HCN channel distribution in L2/3 PCs, allowing for pathway-specific gating of NMDA receptor recruitment at bottom-up (proximal) but not top-down (distal) synapses. HCN availability shifted depending on developmental stage and neuromodulation, suggesting that the gain of thalamic and cortical-cortical signals in L2/3 may be independently modifiedin vivoacross different timescales.
Genome-wide family prediction unveils molecular mechanisms underlying the regulation of agronomic traits inUrochloa ruziziensis
Authors: Martins Felipe Bitencourt , Aono Alexandre Hild , Moraes Aline da Costa Lima , Ferreira Rebecca Caroline Ulbricht , Vilela Mariane de Mendonça , Pessoa-Filho Marco , Motta Mariana Rodrigues , Simeão Rosangela Maria , de Souza Anete Pereira 
Published: September 2023

AbstractTropical forage grasses, especially species of the genusUrochloa, play an important role in cattle production and are the main food source for animals in tropical/subtropical regions. Most of the species are apomictic and tetraploid, which gives special importance toU. ruziziensis, a sexual diploid species that can be tetraploidized for use in interspecific crosses with apomictic species. As a means to assist in breeding programs, this study investigates the applicability of genome-wide family prediction (GWFP) inU. ruziziensishalf-sibling families to predict growth and biomass production. Machine learning and feature selection algorithms were used to reduce the necessary number of markers for prediction and to enhance the predictive ability across the phenotypes. Beyond that, to investigate the regulation of agronomic traits, the positions of the markers with more importance for the prediction were considered putatively associated to quantitative trait loci (QTLs), and in a multiomic approach, genes obtained in the species transcriptome were mapped and linked to those markers. Furthermore, a gene coexpression network was modeled, enabling the investigation of not only the mapped genes but also their coexpressed genes. The functional annotation showed that the mapped genes are mainly associated with auxin transport and biosynthesis of lignin, flavonol and folic acid, while the coexpressed genes are associated with DNA metabolism, stress response and circadian rhythm. The results provide a viable marker-assisted breeding approach for tropical forages and identify target regions for future molecular studies on these agronomic traits.
Ensembled best subset selection using summary statistics for polygenic risk prediction
Authors: Chen Tony , Zhang Haoyu , Mazumder Rahul , Lin Xihong 
Published: September 2023

AbstractPolygenic risk scores (PRS) enhance population risk stratification and advance personalized medicine, yet existing methods face a tradeoff between predictive power and computational efficiency. We introduce ALL-Sum, a fast and scalable PRS method that combines an efficient summary statistic-based L0L2penalized regression algorithm with an ensembling step that aggregates estimates from different tuning parameters for improved prediction performance. In extensive large-scale simulations across a wide range of polygenicity and genome-wide association studies (GWAS) sample sizes, ALL-Sum consistently outperforms popular alternative methods in terms of prediction accuracy, runtime, and memory usage. We analyze 27 published GWAS summary statistics for 11 complex traits from 9 reputable data sources, including the Global Lipids Genetics Consortium, Breast Cancer Association Consortium, and FinnGen, evaluated using individual-level UKBB data. ALL-Sum achieves the highest accuracy for most traits, particularly for GWAS with large sample sizes. We provide ALL-Sum as a user-friendly command-line software with pre-computed reference data for streamlined user-end analysis.
Systematic comparison of Amber force fields for the mechanical properties of double-stranded DNA
Authors: Roldán-Piñero Carlos , Luengo-Márquez Juan , Assenza Salvatore , Pérez Rubén 
Published: September 2023

AbstractThe response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly-accurate predictions for the fine structural features of the duplex. In contrast, and despite their pivotal function, less attention has been devoted to the accuracy in the prediction of the elastic parameters. Several reports have addressed the flexibility of double-stranded DNA via all-atom molecular dynamics, yet the collected information is insufficient to have a clear understanding of the relative performance of the various force fields. In this work, we fill this gap by performing a systematic study in which several systems, characterized by different sequence contexts, are simulated with the most up-to-date force fields, bcs1 and OL15, in the presence of external forces with increasing magnitude. Analysis of our results, together with their comparison with previous work focused on bsc0, allows us to unveil the differences in the predicted rigidity between the newest force fields, and suggests a road map to test their performance against experiments.
Temporal interference stimulation disrupts spike timing in the primate brain
Authors: Vieira Pedro G. , Krause Matthew R. , Pack Christopher C. 
Published: September 2023

SummaryElectrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only where they overlap. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we show that TI reliably alters the timing of spiking activity. However, we find that the strategies which improve the focality of TI — high frequencies, multiple electrodes, and amplitude-modulated waveforms — also limit its effectiveness. Combined, they make TI 80% weaker than other forms of non-invasive brain stimulation. Although this is too weak to cause widespread neuronal entrainment, it may be ideally suited for disrupting pathological synchronization, a hallmark of many neurological disorders.
Nuclear lamin A-associated proteins are required for centromere assembly
Authors: Landeros Adriana , Wallace Destiny A. , Rahi Amit , Magdongon Christine B. , Suraneni Praveen , Amin Mohammed A. , Chakraborty Manas , Adam Stephen A. , Foltz Daniel R. , Varma Dileep 
Published: September 2023

SummaryMany Lamin A-associated proteins (LAAP’s) that are key constituents of the nuclear envelope (NE), assemble at the “core” domains of chromosomes during NE reformation and mitotic exit. However, the identity and function of the chromosomal core domains remain ill-defined. Here, we show that a distinct section of the core domain overlaps with the centromeres/kinetochores of chromosomes during mitotic telophase. The core domain can thus be demarcated into a kinetochore proximal core (KPC) on one side of the segregated chromosomes and the kinetochore distal core (KDC) on the opposite side, close to the central spindle. We next tested if centromere assembly is connected to NE re-formation. We find that centromere assembly is markedly perturbed after inhibiting the function of LMNA and the core-localized LAAPs, BANF1 and Emerin. We also find that the LAAPs exhibit multiple biochemical interactions with the centromere and inner kinetochore proteins. Consistent with this, normal mitotic progression and chromosome segregation was severely impeded after inhibiting LAAP function. Intriguingly, the inhibition of centromere function also interferes with the assembly of LAAP components at the core domain, suggesting a mutual dependence of LAAP and centromeres for their assembly at the core domains. Finally, we find that the localization of key proteins involved in the centromeric loading of CENP-A, including the Mis18 complex and HJURP were markedly affected in LAAP-inhibited cells. Our evidence points to a model where LAAP assembly at the core domain serves a key function in loading new copies of centromeric proteins during or immediately after mitotic exit.
From buds to shoots: Insights into grapevine development from the Witch’s Broom bud sport
Authors: Ritter Eleanore J. , Cousins Peter , Quigley Michelle , Kile Aidan , Raju Sunil K. Kenchanmane , Chitwood Daniel H. , Niederhuth Chad 
Published: September 2023

ABSTRACTPremise of StudyDevelopment is relatively understudied in woody vines, such as grapevine (Vitis vinifera). We used the Witch’s Broom bud sport in grapevine to understand the developmental trajectories of the bud sports, as well as the potential genetic basis of the bud sport.MethodsWe phenotyped shoots, buds, and leaves of two independent cases of the Witch’s Broom bud sport, in the Dakapo and Merlot varieties of grapevine, alongside wild-type counterparts of the same variety. We also performed Illumina and Oxford Nanopore sequencing on the two independent cases and two wild-type counterparts of the same variety.Key ResultsThe Dakapo and Merlot cases of Witch’s Broom displayed severe developmental defects, with no fruit/clusters formed and dwarf vegetative features. However, the Dakapo and Merlot cases of Witch’s Broom studied were also phenotypically different from one another, with distinct differences in bud and leaf development. We were able to identify unique genetic mutations in our two Witch’s Broom cases that are strong candidates for the genetic basis of the bud sports.ConclusionsThe Witch’s Broom bud sport in grapevine serves as a useful natural mutant in which to study grapevine development. The Witch’s Broom bud sports in both varieties studied had dwarf phenotypes, but the two instances studied were also vastly different from one another. Future work on Witch’s Broom bud sports in grapevine could provide more insight into development and the genetic pathways involved in grapevine.
A suite of engineered mice for interrogating psychedelic drug actions
Authors: Chiu Yi-Ting , Deutch Ariel Y. , Wang Wei , Schmitz Gavin P , Huang Karen Lu , Kocak D. Dewran , Llorach Pierre , Bowyer Kasey , Liu Bei , Sciaky Noah , Hua Kunjie , Chen Chongguang , Mott Sarah E. , Niehaus Jesse , DiBerto Jeffrey F. , English Justin , Walsh Jessica J. , Scherrer Grégory , Herman Melissa A , Wu Zhuhao , Wetsel William C , Roth Bryan L 
Published: September 2023

ABSTRACTPsychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a suite of engineered mice useful for clarifying the role of HTR2A and HTR2A-expressing neurons in psychedelic drug actions. We first generatedHtr2a-EGFP-CT-IRES-CreERT2 mice (CT:C-terminus) to independently identify both HTR2A-EGFP-CT receptors and HTR2A-containing cells thereby providing a detailed anatomical map of HTR2A and identifying cell types that express HTR2A. We also generated a humanizedHtr2amouse line and an additional constitutiveHtr2A-Cre mouse line. Psychedelics induced a variety of known behavioral changes in our mice validating their utility for behavioral studies. Finally, electrophysiology studies revealed that extracellular 5-HT elicited a HTR2A-mediated robust increase in firing of genetically-identified pyramidal neurons--consistent with a plasma membrane localization and mode of action. These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugsin vivo.
IRAK1 is a critical mediator of low molecular weight hyaluronic acid-induced stemness in high-grade serous ovarian cancer
Authors: Standing David , Dandawate Prasad , Gunewardena Sumedha , Covarrubias-Zambrano Obdulia , Roby Katherine F. , Khabele Dineo , Jewell Andrea , Tawfik Ossama , Bossmann Stefan H. , Godwin Andrew K. , Weir Scott J. , Jensen Roy A. , Anant Shrikant 
Published: September 2023

AbstractAdvanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ∼25% surviving beyond 5 years. Evidence suggests that cancer stem cells (CSCs) contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. IRAK1 andBRCA1/2mutation status are mutually exclusive. Moreover, low molecular weight hyaluronic acid (LMW HA), which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown ofIRAK1impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growthin vitroandin vivoboth as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.