bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastatic Giant Cell Tumor Causing Small Bowel Intussusception on 18F-FDG PET/CT
Authors: Walcutt Julie E. , Johnson Craig M. , Ly Quan P. , Downey Ryan T. 
Published: July 2022

Abstract
An 89-year-old man with a history of a malignant giant cell tumor of soft parts in the right thigh with recurrent/metastatic tumor in the right pelvis was found to have pulmonary nodules concerning for metastatic disease. Subsequent PET/CT unexpectedly demonstrated a right lower quadrant intussusception with a hypermetabolic mass serving as a lead point. Pathology of the resected mass causing the intussusception was compatible with a metastasis from the patient's malignant giant cell tumor of soft parts.
Chromosome level reference genome for European flat oyster (Ostrea edulis L.)
Authors: Gundappa Manu Kumar , Peñaloza Carolina , Regan Tim , Boutet Isabelle , Tanguy Arnaud , Houston Ross D. , Bean Tim P. , Macqueen Daniel J. 
Published: July 2022

AbstractThe European flat oyster (Ostrea edulis L.) is a bivalve naturally distributed across Europe that was an integral part of human diets for centuries, until anthropogenic activities and disease outbreaks severely reduced wild populations. Despite a growing interest in genetic applications to support population management and aquaculture, a reference genome for this species is lacking to date. Here we report a chromosome-level assembly and annotation for the European Flat oyster genome, generated using Oxford Nanopore, Illumina, Dovetail OmniC™ proximity ligation and RNA sequencing. A contig assembly (N50: 2.38Mb) was scaffolded into the expected karyotype of 10 pseudo-chromosomes. The final assembly is 935.13 Mb, with a scaffold-N50 of 95.56 Mb, with a predicted repeat landscape dominated by unclassified elements specific to O. edulis. The assembly was verified for accuracy and completeness using multiple approaches, including a novel linkage map built with ddRAD-Seq technology, comprising 4,016 SNPs from four full-sib families (8 parents and 163 F1 offspring). Annotation of the genome integrating multi-tissue transcriptome data, comparative protein evidence and ab-initio gene prediction identified 35,699 protein-coding genes. Chromosome level synteny was demonstrated against multiple high-quality bivalve genome assemblies, including an O. edulis genome generated independently for a French O. edulis individual. Comparative genomics was used to characterize gene family expansions during Ostrea evolution that potentially facilitated adaptation. This new reference genome for European flat oyster will enable high-resolution genomics in support of conservation and aquaculture initiatives, and improves our understanding of bivalve genome evolution.
Time-resolved transcriptomic profiling of senescence-associated secretory phenotype (SASP) in multiple senescent cell subtypes
Authors: Razali Nurhanani , Moriyama Yohsuke , Chiu Yatzu , Suda Kojiro , Kono Keiko 
Published: July 2022

ABSTRACTCellular senescence, irreversible cell cycle arrest, is induced by various triggers including telomere shortening, oncogene activation, and DNA damage. Senescent cells exhibit the senescence-associated secretory phenotype (SASP), a pathological feature that contributes to organismal aging. We previously showed that transient plasma membrane damage (PMD) induces a novel subtype of cellular senescence (PMDS) accompanied by SASP, but the overall expression profiles of SASP during PMDS induction was unknown. Here, using mRNA-seq, qPCR, and bioinformatics, we revealed the time-resolved SASP transcriptomic profile in PMDS in comparison with calcium influx-induced senescence, DNA damage response-induced senescence, and replicative senescence. Although the expression of SASP factors was postulated to increase steadily during senescence, we counterintuitively found that the variety of SASP peaks in early PMDS. The pathway comparison analyses and Ingenuity Pathway Analysis suggest that, in early PMDS, wound-healing SASP factors, namelyIl-6,Mmp1, andMmp3,inhibit the GPVI collagen signaling pathway, which in turn further upregulates the same SASP factors, forming a feedback loop. At late senescence, common SASP factors includingIl-6andCcl2 are upregulated in all senescent cell subtypes. Thus, SASP is diverse at early senescence and becomes relatively uniform at late senescence. Diverse SASP may contribute to senescent cell subtype-specific paracrine/autocrine functions in vivo.
A model-based analysis reveals three-dimensional genome organization heterogeneity and functional sub-compartments in cell populations
Authors: Zheng Xiaobin , Tran Joseph R. , Zheng Yixian 
Published: July 2022

AbstractThe computational inference of genome organization based on Hi-C sequencing has greatly aided the understanding of chromatin and nuclear organization in three dimensions (3D). However, existing computational methods used to infer sub-compartments from Hi-C data fail to address the cell population heterogeneity. Here we describe a model-based method, called CscoreTool-M, which uses probabilistic modeling to build multiple 3D genome sub-compartments from Hi-C data. The compartment scores inferred using CscoreTool-M directly represents the probability of a genomic region locating in a specific sub-compartment. Compared to published methods, CscoreTool-M is more accurate in inferring local sub-compartment containing heterochromatin marked by Histone lysine trimethylation (H3K27me3) surrounded by the actively transcribed euchromatic regions. The compartment scores calculated by CscoreTool-M also help to quantify the levels of heterogeneity in sub-compartment localization within cell populations for different genomic regions. By comparing proliferating cells and terminally differentiated non-proliferating cells, we show that the proliferating cells have higher genome organization heterogeneity, which is likely caused by cells at different cell-cycle stages. By analyzing 10 sub-compartments, we found a sub-compartment containing chromatin potentially related to the early-G1 chromatin regions proximal to the nuclear lamina in HCT116 cells, suggesting the method can deconvolve cell cycle stage-specific genome organization among asynchronously dividing cells. Finally, we show that CscoreTool-M can further identify sub-compartments that contain genes enriched in housekeeping or cell-type-specific functions.
The Interictal Suppression Hypothesis in Focal Epilepsy: Electrographic and Structural Evaluation
Authors: Johnson Graham W. , Doss Derek J. , Morgan Victoria L. , Shless Jared S. , Paulo Danika L. , Kang Hakmook , Bick Sarah K. , Roberson Shawniqua Williams , Wallace Mark T. , Englot Dario J. 
Published: July 2022

AbstractWhy are people with focal epilepsy not constantly seizing? Previous molecular work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is the high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure onset zones have an increased inward connectivity. Accordingly, we hypothesize that seizure onset zones are actively suppressed by the rest of the brain network during interictal states.We tested this hypothesis on 81 subjects with drug resistant focal epilepsy undergoing presurgical evaluation. We utilized intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, propagative, and non-involved regions. We then utilized diffusion imaging to acquire estimates of white matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, using our observations, we generated a resting-state classification model to assist clinicians in detecting seizure onset and propagative zones without the need for multiple ictal recordings.Our findings indicate that seizure onset and propagative zones demonstrate markedly increased inward connectivity and decreased outward connectivity on both resting-state and neurostimulation analyses. When controlling for distance between regions, the difference between inward vs. outward connectivity remained stable up to 80 mm between brain connections. Structure-function coupling analyses revealed that seizure onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue. Using these observations, our classification models achieved a maximum held-out testing set accuracy of 92.0±2.2%.These results indicate that seizure onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure onset zones. These findings have implications for the identification of seizure onset zones using only brief resting-sate recordings to reduce patient morbidity and augment the presurgical evaluation of drug resistant epilepsy. Furthermore, testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative, and neuromodulation approaches to improve surgical success rates in those suffering from drug resistant focal epilepsy.
Involvement of CaV2.2 channels and α2δ-1 in hippocampal homeostatic synaptic plasticity
Authors: Pilch Kjara S , Ramgoolam Krishma H , Dolphin Annette C 
Published: July 2022

AbstractIn the mammalian brain, presynaptic CaV2 channels play a pivotal role for synaptic transmission by mediating fast neurotransmitter exocytosis via influx of Ca2+ into the active zone of presynaptic terminals. However, the distribution and modulation of CaV2.2 channels at highly plastic hippocampal synapses remains to be elucidated. Here, we assess CaV2.2 channels during homeostatic synaptic plasticity, a compensatory form of homeostatic control preventing excessive or insufficient neuronal activity during which extensive active zone remodelling has been described. We show that chronic silencing of neuronal activity in mature hippocampal cultures resulted in elevated presynaptic Ca2+ transients, mediated by increased levels of CaV2.2 channels at the presynaptic site. This work focussed further on the role of α2δ-1 subunits, important regulators of synaptic transmission and CaV2.2 channel abundance at the presynaptic membrane. We find that α2δ-1-overexpression reduces the contribution of CaV2.2 channels to total Ca2+ flux without altering the amplitude of the Ca2+ transients. Levels of endogenous α2δ-1 decreased during homeostatic synaptic plasticity, whereas the overexpression of α2δ-1 prevented homeostatic synaptic plasticity in hippocampal neurons. Together, this study reveals a key role for CaV2.2 channels and novel roles for α2δ-1 during synaptic plastic adaptation.
Investigating Leptospira dynamics in a multi-host community using an agent-based modeling approach
Authors: Belsare Aniruddha V. , Gompper Matthew E. , Mason Meghan , Munoz-Zanzi Claudia 
Published: July 2022

AbstractLeptospirosis, a neglected bacterial zoonosis, is a global public health issue disproportionately affecting impoverished communities such as urban slums in the developing world. A variety of animal species, including peridomestic rodents and dogs, can be infected with different strains of leptospirosis. Humans contract leptospirosis via exposure to water or soil contaminated with the urine of infected animals. Due to the unavailability of safe and effective vaccines, preventive strategies mainly focus on minimizing human exposure to contaminated environment. In marginalized communities, this approach is ineffective due to infrastructure deficiencies and the difficulties in implementing sanitation and hygiene practices. Moreover, continuing expansion of urban slums worldwide will likely contribute to the increase in outbreaks of leptospirosis. Effective prevention of leptospirosis outbreaks will therefore require a thorough understanding of Leptospira transmission dynamics in impoverished, high-density settings. We developed the agent-based model MHMSLeptoDy to investigate Leptospira dynamics in a realistic, in silico high-density community of rodents, dogs, and human hosts, and two host-adapted Leptospira strains. Virtual explorations using MHMSLeptoDy were undertaken to evaluate alternate interventions and to assess the zoonotic transmission risk of leptospirosis. A key finding from model explorations is that rodents are the main contributors of rodent-adapted as well as dog-adapted strains in the environment, while dogs play an important role in distributing the rodent-adapted strain. Assessment of alternate leptospirosis control strategies using model iterations revealed that dog vaccination and rodent control interventions had the most impact on lowering human outbreak probability. Our open-source, customizable agent-based model provides a sophisticated mechanism to quantitatively evaluate nuanced intervention strategies and inform the design of rational, locally relevant leptospirosis control programs.
Invasive streptococcal infection can lead to the generation of cross-strain opsonic antibodies
Authors: de Neergaard Therese , Bläckberg Anna , Ivarsson Hanna , Thomasson Sofia , Ahnlide Vibha Kumra , Chowdhury Sounak , Khakzad Hamed , Malmström Johan , Rasmussen Magnus , Nordenfelt Pontus 
Published: July 2022

AbstractIntroductionThe human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain-specific or more broadly protective. Here, we quantified the opsonic antibody response following invasive S. pyogenes infection.Materials and MethodsFour patients with S. pyogenes bacteremia between 2018-2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute and convalescent sera were obtained, and the S. pyogenes isolates were genome-sequenced (emm118, emm85, and two emm1). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection.ResultsAntibody binding increased modestly against the infecting isolate and across emm types in convalescent compared to acute sera for all patients. For two patients, phagocytosis increased in convalescent serum for both the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed.ConclusionInvasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both non-functional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections.
Thalamocortical contribution to cognitive task activity
Authors: Sorenson Evan , Shine James M. , Cole Michael W. , Hwang Kai 
Published: July 2022

AbstractThalamocortical interaction is a ubiquitous functional motif in the mammalian brain. Previously (Hwang et al., 2021), we reported that lesions to network hubs in the human thalamus are associated with multi-domain behavioral impairments in language, memory, and executive functions. Here we show how task-evoked thalamic activity and thalamocortical interactions are organized to support these broad cognitive abilities. To address this question, we analyzed functional MRI data from human subjects that performed 127 tasks encompassing a broad range of cognitive representations. We first investigated the spatial organization of task-evoked activity and found that multi-task thalamic activity converged onto a low-dimensional structure, through which a basis set of activity patterns are evoked to support processing needs of each task. Specifically, the anterior, medial, and posterior-medial thalamus exhibit hub-like activity profiles that are suggestive of broad functional participation. These thalamic task hubs overlapped with network hubs interlinking cortical systems. To further determine the cognitive relevance of thalamocortical interactions, we built a data-driven thalamocortical interaction model to test whether thalamocortical functional connectivity transformed thalamic activity to cortical task activity. The thalamocortical model predicted task-specific cortical activity patterns, and outperformed comparison models built on cortical, hippocampal, and striatal regions. Simulated lesions to low-dimensional, multi-task thalamic hub regions impaired task activity prediction. This simulation result was further supported by profiles of neuropsychological impairments in human patients with focal thalamic lesions. In summary, our results suggest a general organizational principle of how thalamocortical interactions support cognitive task activity.Impact StatementHuman thalamic activity transformed via thalamocortical functional connectivity to support task representations across functional domains.
Mutations in a set of ancient matrisomal glycoprotein genes across neoplasia predispose to disruption of morphogenetic transduction
Authors: Langthasa Jimpi , Mishra Satyarthi , Monica U , Kalal Ronak , Bhat Ramray 
Published: July 2022

AbstractMisexpression and remodeling of the extracellular matrix is a canonical hallmark of cancer, although the extent of cancer-associated aberrations in the genes coding for ECM proteins and consequences thereof, are not well understood. In this study, we examined the alterations in core matrisomal genes across a set of nine cancers. These genes, especially the ones encoding for ECM glycoproteins, were observed to be more susceptible to mutations than copy number variations across cancers. We classified the glycoprotein genes based on the ubiquity of their mutations across the nine cancer groups and estimated their evolutionary age using phylostratigraphy. To our surprise, the ECM glycoprotein genes commonly mutated across all cancers were predominantly unicellular in origin, whereas those commonly showing mutations in specific cancers evolved mostly during and after the unicellular-multicellular transition. Pathway annotation for biological interactions revealed that the most pervasively mutated glycoprotein set regulated a larger set of inter-protein interactions and constituted more cohesive interaction networks relative to the cancer-specific mutated set. In addition, ontological prediction revealed the pervasively mutated set to be strongly enriched for basement membrane dynamics. Our results suggest that ancient unicellular-origin ECM glycoproteins were canalized into playing critical tissue morphogenetic roles, and when disrupted through matrisomal gene mutations, associate with neoplastic transformation of a wide set of human tissues.
Circadian regulation of dentate gyrus excitability mediated by G-protein signaling
Authors: Gonzalez Jose Carlos , Lee Haeun , Vincent Angela M , Goode Lacy K , King Gwendalyn D , Gamble Karen L , Wadiche Jacques I , Overstreet-Wadiche Linda 
Published: July 2022

SummaryThe central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm that is driven by intrinsic activity of molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery but whether these molecular programs generate oscillations of membrane properties is unexplored. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-hour oscillation that controls spiking probability. Diurnal changes in excitability are mediated by antiphase G-protein regulation of potassium and sodium conductances to reduce excitability during the light phase. Disruption of the circadian transcriptional machinery by conditional deletion of Bmal1 enhances excitability selectively during the light phase, increasing engram recruitment and spatial discrimination memory. These results reveal that circadian transcriptional machinery regulates intrinsic excitability, highlighting the role of cell-autonomous oscillations in hippocampal function and behavior.HighlightsDentate neurons exhibit a 24-hour oscillation of excitability with low excitability during the Light phaseReduced excitability results from G-protein regulation of passive and active propertiesBmal1 deletion disrupts G-protein regulation to enhance excitability during the LightBmal1 deletion enhances the size of memory engrams and spatial discrimination
Host use does not drive genetic structure of mountain pine beetles in western North America
Authors: Boone Celia K. , Thompson Kirsten M. , Henry Philippe , Murray Brent W. 
Published: July 2022

AbstractThe mountain pine beetle (MPB) is one component of an intensively studied co-evolved host-pest system. We investigated the spatial genetic structure of MPB within its historic and recent geographic range expansion as it relates to host use in western North America using 13 pre-selected microsatellite loci. AMOVA shows that genetic structure is not correlated with the host tree species, arguing against the formation of host-race within this species. STRUCTURE analysis shows 4 main clusters in western North America: Northern - Northern British Columbia/Alberta; Central - Southern British Columbia/Alberta/Washington/Idaho/Montana; Southwest - Oregon/California/Nevada and; Southeast - Utah/Wyoming/Arizona/Colorado/South Dakota. Heterozygosity, allelic richness, and number of private alleles is greatest in the Southwest cluster. This cluster correlates with one of the three refugia hypothesized from a recent analysis of neo-Y haplotypes by Dowle and colleagues and represents an important reservoir of MPB genetic diversity.
Pick-up Single-Cell Proteomic Analysis for Quantifying up to 3000 Proteins in a Tumor Cell
Authors: Wang Yu , Guan Zhi-Ying , Shi Shao-Wen , Jiang Yi-Rong , Wu Qiong , Wu Jie , Chen Jian-Bo , Ying Wei-Xin , Xu Qin-Qin , Fan Qian-Xi , Wang Hui-Feng , Zhou Li , Pan Jian-Zhang , Fang Qun 
Published: July 2022

AbstractThe shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ∼1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a tumor cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 1804-3349, 1778-3049 and 1074-2487 protein groups are quantified in single A549 cells (n= 37), HeLa cells (n= 44) and U2OS cells (n= 27), respectively. Benefiting from the flexible cell picking-up ability, we study tumor cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.