bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early and selective subcortical Tau pathology within the human Papez circuit
Authors: Sárkány Barbara , Dávid Csaba , Hortobágyi Tibor , Gombás Péter , Somogyi Peter , Acsády László , Viney Tim J. 
Published: June 2023

AbstractThe Papez circuit comprises several interconnected brain areas important for spatial navigation and orientation. An early symptom of dementia is disorientation, suggesting that brain regions responsible for providing a sense of direction are adversely affected. We examinedpost-mortemhuman tissue from cases with no cognitive impairment, mild cognitive impairment, and Alzheimer’s disease. A key part of the Papez circuit, the anterodorsal thalamic nucleus (ADn), contained a high density of misfolded pathological Tau (pTau) at all disease stages, including in control cases. Moreover, pTau preferentially accumulated in calretinin-expressing neurons. At the subcellular level, we detected pTau filaments in ADn cell bodies, dendrites, and in specialized presynaptic terminals. Large vesicular-glutamate-transporter-2-containing terminals from the lateral mammillary nucleus, rather than corticothalamic terminals, preferentially contained pTau, suggesting that Tau crosses specific synapses within the Papez circuit. As the ADn contains a high density of head direction cells, pTau may degrade the processing of orientation signals, explaining why people become disorientated years-to-decades before memory deficits emerge.
Atypical Chemokine Receptor 1 (Ackr1)-deficient Mice Resist Lethal SARS-CoV-2 Challenge
Authors: Majumdar Shamik , Weaver Joseph D. , Pontejo Sergio M. , Minai Mahnaz , Georgia-Clark Shalamar , Gao Ji-Liang , Lu Xinping , Zhang Hongwei , Lackemeyer Nicole , Burdette Tracey , Johnson Reed , Kelsall Brian L. , Farber Joshua M. , Alves Derron A. , Murphy Philip M. 
Published: June 2023

AbstractHigh pro-inflammatory chemokine levels have been reported in blood and lung in patients with COVID-19. To investigate specific roles in pathogenesis, we studied the regulation of chemokine ligands and receptors in the lungs of 4-6-month-old wild type C57BL/6 mice infected with the MA10 mouse-adapted strain of SARS-CoV-2. We found that atypical chemokine receptor 1 (Ackr1, also known as Duffy antigen receptor for chemokines/DARC) was the most highly upregulated chemokine receptor in infected lung, where it localized to endothelial cells of veins and arterioles. In a screen of 7 leukocyte chemoattractant or chemoattractant receptor knockout mouse lines,Ackr1-/-mice were unique in having lower mortality after SARS-CoV-2 infection, particularly in males. ACKR1 is a non-signaling chemokine receptor that in addition to endothelium is also expressed on erythrocytes and Purkinje cells of the cerebellum. It binds promiscuously to both inflammatory CC and CXC chemokines and has been reported to control chemokine availability which may influence the shape of chemotactic gradients and the ability of leukocytes to extravasate and produce immunopathology. Of note, erythrocyte ACKR1 deficiency is fixed in sub-Saharan African populations where COVID-19 has been reported to result in low mortality compared to worldwide data. Our data suggest the possibility of a causal contribution of ACKR1 deficiency to low sub-Saharan COVID-19 mortality and identify ACKR1 as a possible drug target in the disease.
The human Y and inactive X chromosomes similarly modulate autosomal gene expression
Authors: San Roman Adrianna K. , Skaletsky Helen , Godfrey Alexander K. , Bokil Neha V. , Teitz Levi , Singh Isani , Blanton Laura V. , Bellott Daniel W. , Pyntikova Tatyana , Lange Julian , Koutseva Natalia , Hughes Jennifer F. , Brown Laura , Phou Sidaly , Buscetta Ashley , Kruszka Paul , Banks Nicole , Dutra Amalia , Pak Evgenia , Lasutschinkow Patricia C. , Keen Colleen , Davis Shanlee M. , Lin Angela E. , Tartaglia Nicole R. , Samango-Sprouse Carole , Muenke Maximilian , Page David C. 
Published: June 2023

SUMMARYSomatic cells of human males and females have 45 chromosomes in common, including the “active” X chromosome. In males the 46thchromosome is a Y; in females it is an “inactive” X (Xi). Through linear modeling of autosomal gene expression in cells from individuals with zero to three Xi and zero to four Y chromosomes, we found that Xi and Y impact autosomal expression broadly and with remarkably similar effects. Studying sex-chromosome structural anomalies, promoters of Xi- and Y-responsive genes, and CRISPR inhibition, we traced part of this shared effect to homologous transcription factors –ZFXandZFY– encoded by Chr X and Y. This demonstrates sex-shared mechanisms by which Xi and Y modulate autosomal expression. Combined with earlier analyses of sex-linked gene expression, our studies show that 21% of all genes expressed in lymphoblastoid cells or fibroblasts change expression significantly in response to Xi or Y chromosomes.
Evaluation of haplotype-aware long-read error correction with hifieval
Authors: Guo Yujie , Feng Xiaowen , Li Heng 
Published: June 2023

AbstractSummaryThe PacBio High-Fidelity (HiFi) sequencing technology produces long reads of>99% in accuracy. It has enabled the development of a new generation ofde novosequence assemblers, which all have sequencing error correction as the first step. As HiFi is a new data type, this critical step has not been evaluated before. Here, we introduced hifieval, a new command-line tool for measuring over- and under-corrections produced by error correction algorithms. We assessed the accuracy of the error correction components of existing HiFi assemblers on the CHM13 and the HG002 datasets and further investigated the performance of error correction methods in challenging regions such as homopolymer regions, centromeric regions, and segmental duplications. Hifieval will help HiFi assemblers to improve error correction and assembly quality in the long run.Availability and implementationThe source code is available athttps://github.com/magspho/hifievalContacthli@ds.dfci.harvard.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Loss ofOsARF18confers glufosinate ammonium herbicide resistance in rice
Authors: Xia Jin-Qiu , He Da-Yu , Liang Qin-Yu , Zhang Zheng-Yi , Wu Jie , Zhang Zi-Sheng , Zhang Jing , Zhao Ping-Xia , Xiang Cheng-Bin 
Published: June 2023

ABSTRACTWeed is one of the major biotic stresses that causes severe loss of crop yield. Herbicide is one of the most cost-effective ways to control weeds. Thus, the development of herbicide-resistant crops is critical for the application of herbicides. To isolate new glufosinate ammonium resistance loci, we screened a rice ethyl methyl sulfonate-mutagenized library and obtained theglufosinateammonium-resistant mutantgar1-1.GAR1encodes auxin response factor 18 (OsARF18). A G-to-A substitution in the coding region ofOsARF18results in loss of function ofOsARF18and thereby enhances glufosinate ammonium resistance ofgar1-1, which was confirmed by three additional CRISPR/Cas9-editedgar1alleles.GLUTAMINE SYNTHETASE 1;1(OsGS1;1) andGLUTAMINE SYNTHETASE 1;2(OsGS1;2) were upregulated ingar1-1upon glufosinate ammonium treatment, directly contributing to increased GS activity that enhances glufosinate ammonium herbicide resistance. We further show that OsARF18 suppressesOsGS1;1andOsGS1;2expression.Comparative transcriptomic analyses reveal a huge shift in the gene expression profile involved in stress tolerance and growth. A large number of detoxification-related genes are enriched ingar1-1, which may also contribute to enhanced herbicide resistance. Moreover, stress tolerance-related genes are upregulated and growth-related genes are downregulated ingar1-1, consistent with the improved tolerance to salt and osmotic stress ofgar1mutants. Taken together, our study demonstrates thatOsARF18is a negative regulator of glufosinate ammonium resistance as well as salt and osmotic stress tolerance, suggesting a role in balancing the stress response and growth.
Not all movements are equal: Differences in variability of trunk motor behavior between people with and without low back pain - A Systematic Review
Authors: Bakar Florian Abu , Staal J. Bart , van Cingel Robert , Saito Hiroki , Ostelo Raymond , van Dieën Jaap H. 
Published: June 2023

AbstractBackgroundIn treatment of low-back pain (LBP), motor control exercises have shown to be superior to minimal interventions, but not to any other form of exercise therapy. Knowledge about variability in trunk motor behavior may help to identify patients that may be more likely to benefit from motor control exercises.ObjectiveThis systematic review aims to answer the question: Is variability of trunk motor behavior different between people with and without LBP and if so, do people with LBP show more or less variability? Furthermore, we addressed the question whether the results are dependent on characteristics of the patient group, the task performed and the type of variability measure.MethodsThis study was registered in PROSPERO (CRD42020180003). Studies were eligible if they (1) included a LBP group and a control group, (2) included adults with non-specific low back pain of any duration and (3) measured kinematic variability, EMG variability and/or kinetic variability. Risk of Bias was evaluated and a descriptive synthesis was performed.ResultsThirty-nine studies were included, thirty-one of which were included in the descriptive synthesis. In most studies and experimental conditions, variability did not significantly differ between groups. When significant differences were found, less variability in patients with LBP was more frequently reported than more variability, especially in gait-related tasks.ConclusionsGiven the considerable risk of bias of the included studies and the clinical characteristics of the participants with low severity scores for pain, disability and psychological measures, there is insufficient evidence to draw firm conclusions.
Improved Seizure Onset-Zone Lateralization in Temporal Lobe Epilepsy using 7T Resting-State fMRI: A Direct Comparison with 3T
Authors: Lucas Alfredo , Cornblath Eli J. , Sinha Nishant , Caciagli Lorenzo , Hadar Peter , Tranquille Ashley , Stein Joel M. , Das Sandhitsu , Davis Kathryn A. 
Published: June 2023

AbstractObjective:Resting-state functional magnetic resonance imaging (rs-fMRI) at ultra high-field strengths (≥7T) is known to provide superior signal-to-noise and statistical power than comparable acquisitions at lower field strengths. In this study, we aim to provide a direct comparison of the seizure onset-zone (SOZ) lateralizing ability of 7T rs-fMRI and 3T rs-fMRI.Methods:We investigated a cohort of 70 temporal lobe epilepsy (TLE) patients. A paired cohort of 19 patients had 3T and 7T rs-fMRI acquisitions for direct comparison between the two field strengths. Forty-three patients had only 3T, and 8 patients had only 7T rs-fMRI acquisitions. We quantified the functional connectivity between the hippocampus and other nodes within the default mode network (DMN) using seed-to-voxel connectivity, and measured how hippocampo-DMN connectivity could inform SOZ lateralization at 7T and 3T field strengths.Results:Differences between hippocampo-DMN connectivity ipsilateral and contralateral to the SOZ were significantly higher at 7T (pFDR=0.008) than at 3T (pFDR=0.80) when measured in the same subjects. We found that our ability to lateralize the SOZ, by distinguishing subjects with left TLE from subjects with right TLE, was superior at 7T (AUC = 0.97) than 3T (AUC = 0.68). Our findings were reproduced in extended cohorts of subjects scanned at either 3T or 7T. Our rs-fMRI findings at 7T, but not 3T, are consistent and highly correlated (Spearman Rho=0.65) with clinical FDG-PET lateralizing hypometabolism.Significance:We show superior SOZ lateralization in TLE patients when using 7T relative to 3T rs-fMRI, supporting the adoption of high-field strength functional imaging in the epilepsy presurgical evaluation.
Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study
Authors: Sharkey Rachel J. , Bacon Chelsea , Peterson Zeru , Rootes-Murdy Kelly , Salvador Raymond , Pomarol-Clotet Edith , Karuk Andriana , Homan Philipp , Ji Ellen , Omlor Wolfgang , Homan Stephanie , Georgiadis Foivos , Kaiser Stefan , Kirschner Matthias , Ehrlich Stefan , Dannlowski Udo , Grotegerd Dominik , Goltermann Janik , Meinert Susanne , Kircher Tilo , Stein Frederike , Brosch Katharina , Krug Axel , Nenadić Igor , Sim Kang , Spalletta Gianfranco , Piras Fabrizio , Banaj Nerisa , Sponheim Scott R , Demro Caroline , Ramsay Ian S , King Margaret , Quidé Yann , Green Melissa J. , Nguyen Dana , Preda Adrian , Calhoun Vince D. , Turner Jessica A. , van Erp Theo G.M. , Nickl-Jockschat Thomas 
Published: June 2023

AbstractFormal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.
Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies
Authors: Lu Xiuyuan , Hayashi Hiroki , Ishikawa Eri , Takeuchi Yukiko , Dychiao Julian Vincent Tabora , Nakagami Hironori , Yamasaki Sho 
Published: June 2023

AbstractSARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). In donors exhibiting sustained anti-S antibody titers (designated as “sustainers”), S-reactive T cell clonotypes detected immediately after 2nd vaccination polarized to follicular helper T (Tfh)-like cells, which was less obvious in “decliners”. Even before vaccination, S-reactive CD4+T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest thatde novoacquisition of memory Tfh-like cells upon vaccination contributes to the longevity of anti-S antibody titers.
Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury
Authors: Todd Brittany P. , Luo Zili , Gilkes Noah , Chimenti Michael S. , Peterson Zeru , Mix Madison , Harty John T. , Nickl-Jockschat Thomas , Ferguson Polly J. , Bassuk Alexander G. , Newell Elizabeth A. 
Published: June 2023

AbstractAccumulating evidence suggests that type I interferon (IFN-I) signaling is a key contributor to immune cell-mediated neuropathology in neurodegenerative diseases. Recently, we demonstrated a robust upregulation of type I interferon-stimulated genes in microglia and astrocytes following experimental traumatic brain injury (TBI). The specific molecular and cellular mechanisms by which IFN-I signaling impacts the neuroimmune response and neuropathology following TBI remains unknown. Using the lateral fluid percussion injury model (FPI) in adult male mice, we demonstrated that IFN α/β receptor (IFNAR) deficiency resulted in selective and sustained blockade of type I interferon-stimulated genes following TBI as well as decreased microgliosis and monocyte infiltration. Phenotypic alteration of reactive microglia also occurred with diminished expression of molecules needed for MHC class I antigen processing and presentation following TBI. This was associated with decreased accumulation of cytotoxic T cells in the brain. The IFNAR-dependent modulation of the neuroimmune response was accompanied by protection from secondary neuronal death, white matter disruption, and neurobehavioral dysfunction. These data support further efforts to leverage the IFN-I pathway for novel, targeted therapy of TBI.
The consequences of tetraploidy onCaenorhabditis elegansphysiology and sensitivity to chemotherapeutics
Authors: Misare Kelly R. , Ampolini Elizabeth A. , Gonzalez Hyland C. , Sullivan Kaitlan A. , Li Xin , Miller Camille , Sosseh Bintou , Dunne Jaclyn B. , Voelkel-Johnson Christina , Gordon Kacy L. , Hartman Jessica H. 
Published: June 2023

ABSTRACTPolyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid.C. elegansnematodes are typically diploid, but stressors such as heat shock and starvation can trigger the production of tetraploid offspring. In this study, we utilized a recently published protocol to generate stable tetraploid strains ofC. elegansand compared their physiological traits and sensitivity to two DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. As prior studies have shown, tetraploid worms are approximately 30% longer, shorter-lived, and have a smaller brood size than diploids. We investigated the reproductive defect further, determining that tetraploid worms have a shorter overall germline length, a higher rate of germ cell apoptosis, more aneuploidy in oocytes and offspring, and larger oocytes and embryos. We also found that tetraploid worms are modestly protected from growth delay from the chemotherapeutics but are similarly or more sensitive to reproductive toxicity. Transcriptomic analysis revealed differentially expressed pathways that may contribute to sensitivity to stress. Overall, this study reveals the phenotypic consequences of whole-animal tetraploidy inC. elegans.
Continuous Measures of Decision-Difficulty Captured Remotely: I. Mouse-tracking sensitivity extends to tablets and smartphones
Authors: Zuk Alexandra A. Ouellette , Bertrand Jennifer K. , Chapman Craig S. 
Published: June 2023

AbstractAs decisions require actions to have an effect on the world, measures derived from movements such as using a mouse to control a cursor on a screen provide powerful and dynamic indices of decision-making. In this first of a set of two studies, we replicated classic reach-decision paradigms across computers, tablets, and smartphones, we show that portable touch-devices can sensitively capture decision-difficulty. We see this in pre- and during-movement temporal and motoric measures across diverse decision domains. We found touchscreen interactions to more sensitively reflect decision-difficulty during movement compared to computer interactions, and the latter to be more sensitive before movement initiation. Paired with additional evidence for the flexibility and unique utility of pre- and during-movement measures, this substantiates the use of widely available touch-devices to massively extend the reach of decision science. We build upon this in the second study in this series (Bertrand et al., 2023) with the use of webcam eye-tracking to further elucidate, earlier in time, the decision process. This subsequent work provides additional support for tools that enable remote collection of rich decision data in ecologically-valid environments.
Reducing the Bacterial Lag Phase Through Methylated Compounds: Insights from Algal-Bacterial Interactions
Authors: Sperfeld Martin , Narváez-Barragán Delia A. , Malitsky Sergey , Frydman Veronica , Yuda Lilach , Rocha Jorge , Segev Einat 
Published: June 2023

AbstractThe bacterial lag phase is a key period for resuming growth. Despite its significance, the lag phase remains underexplored, particularly in environmental bacteria. Here, we explore the lag phase of the model marine bacteriumPhaeobacter inhibenswhen it transitions from starvation to growth with a microalgal partner. Utilizing transcriptomics and13C-labeled metabolomics, our study reveals that methylated compounds, which are abundantly produced by microalgae, shorten the bacterial lag phase. Our findings underscore the significance of methyl groups as a limiting factor during the lag phase and demonstrate that methyl groups can be harvested from algal compounds and assimilated through the methionine cycle. Furthermore, we show that methylated compounds, characteristic of photosynthetic organisms, induce variable reductions in lag times among bacteria associated with algae and plants. These findings highlight the adjustability of the bacterial lag phase and emphasize the importance of studying bacteria in an environmental context.One-Sentence Summary:Bacteria use algal compounds as a metabolic shortcut to transition from starvation to growth.
Catalytic growth in a shared enzyme pool ensures robust control of centrosome size
Authors: Banerjee Deb Sankar , Banerjee Shiladitya 
Published: June 2023

AbstractAccurate regulation of centrosome size is essential for ensuring error-free cell division, and dysregulation of centrosome size has been linked to various pathologies, including developmental defects and cancer. While a universally accepted model for centrosome size regulation is lacking, prior theoretical and experimental works suggest a centrosome growth model involving autocatalytic assembly of the pericentriolar material. Here we show that the autocatalytic assembly model fails to explain the attainment of equal centrosome sizes, which is crucial for error-free cell division. Incorporating latest experimental findings into the molecular mechanisms governing centrosome assembly, we introduce a new quantitative theory for centrosome growth involving catalytic assembly within a shared pool of enzymes. Our model successfully achieves robust size equality between maturing centrosome pairs, mirroring cooperative growth dynamics observed in experiments. To validate our theoretical predictions, we compare them with available experimental data and demonstrate the broad applicability of the catalytic growth model across different organisms, which exhibit distinct growth dynamics and size scaling characteristics.