bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex–associated differences between body mass index and SARS-CoV-2 antibody titers following the BNT162b2 vaccine among 2,435 healthcare workers in Japan
Authors: Yamamoto Shohei , Mizoue Tetsuya , Tanaka Akihito , Oshiro Yusuke , Inamura Natsumi , Konishi Maki , Ozeki Mitsuru , Miyo Kengo , Sugiura Wataru , Sugiyama Haruhito , Ohmagari Norio 
Published: September 2021

AbstractObesity may downregulate vaccine-induced immunogenicity, but the epidemiological evidence for the COVID-19 vaccine is limited, and the sex-associated difference is unknown. It was observed that a higher body mass index was associated with lower titers of spike IgG antibodies against SARS-CoV-2 in men but not in women.
Maximum-likelihood model fitting for quantitative analysis of SMLM data
Authors: Wu Yu-Le , Hoess Philipp , Tschanz Aline , Matti Ulf , Mund Markus , Ries Jonas 
Published: September 2021

AbstractQuantitative analysis is an important part of any single-molecule localization microscopy (SMLM) data analysis workflow to extract biological insights from the coordinates of the single fluorophores, but current approaches are restricted to simple geometries or do not work on heterogenous structures.Here, we present LocMoFit (Localization Model Fit), an open-source framework to fit an arbitrary model directly to the localization coordinates in SMLM data. Using maximum likelihood estimation, this tool extracts the most likely parameters for a given model that best describe the data, and can select the most likely model from alternative models. We demonstrate the versatility of LocMoFit by measuring precise dimensions of the nuclear pore complex and microtubules. We also use LocMoFit to assemble static and dynamic multi-color protein density maps from thousands of snapshots. In case an underlying geometry cannot be postulated, LocMoFit can perform single-particle averaging of super-resolution structures without any assumption about geometry or symmetry. We provide extensive simulation and visualization routines to validate the robustness of LocMoFit and tutorials based on example data to enable any user to increase the information content they can extract from their SMLM data.
Analogs of TIQ-A as inhibitors of human mono-ADP-ribosylating PARPs
Authors: Maksimainen Mirko M. , Murthy Sudarshan , Sowa Sven T. , Galera-Prat Albert , Rolina Elena , Heiskanen Juha P. , Lehtiö Lari 
Published: September 2021

AbstractThe scaffold of TIQ-A, a previously known inhibitor of human poly-ADP-ribosyltransferase PARP1, was utilized to develop inhibitors against human mono-ADP-ribosyltransferases through structure-guided design and activity profiling. By supplementing the TIQ-A scaffold with small structural changes, based on a PARP10 inhibitor OUL35, selectivity changed from poly-ADP-ribosyltransferases towards mono-ADP-ribosyltransferases. Binding modes of analogs were experimentally verified by determining complex crystal structures with mono-ADP-ribosyltransferase PARP15 and with poly-ADP-ribosyltransferase TNKS2. The best analogs of the study achieved 10 – 20-fold selectivity towards mono-ADP-ribosyltransferases PARP10 and PARP15 while maintaining micromolar potencies. The work demonstrates a route to differentiate compound selectivity between mono- and poly-ribosyltransferases of the human ARTD family.
Multiple Sclerosis Patients have an Altered Gut Mycobiome and Increased Fungal to Bacterial Richness
Authors: Yadav Meeta , Ali Soham , Shrode Rachel L. , Shahi Shailesh K. , Jensen Samantha N. , Hoang Jemmie , Cassidy Samuel , Olalde Heena , Guseva Natalya , Paullus Mishelle , Cherwin Catherine , Wang Kai , Cho Tracey , Kamholz John , Mangalam Ashutosh K. 
Published: September 2021

AbstractTrillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in multiple sclerosis (MS), the significance of the fungal microbiome (mycobiome) is an understudied and neglected part of the intestinal microbiome in MS. The aim of this study was to characterize the gut mycobiome of patients with relapsing-remitting multiple sclerosis (RRMS), compare it to healthy controls, and examine its association with changes in the bacterial microbiome. We characterized and compared the mycobiome of 20 RRMS patients and 33 healthy controls (HC) using Internal Transcribed Spacer 2 (ITS2) and compared mycobiome interactions with the bacterial microbiome using 16S rRNA sequencing. Our results demonstrate an altered mycobiome in RRMS patients compared with HC. RRMS patients showed an increased abundance of Basidiomycota and decreased Ascomycota at the phylum level with an increased abundance of Candida and Epicoccum genera along with a decreased abundance of Saccharomyces compared to HC. We also observed an increased ITS2/16S ratio, altered fungal and bacterial associations, and altered fungal functional profiles in MS patients compared to HC.This study demonstrates that RRMS patients had a distinct mycobiome with associated changes in the bacterial microbiome compared to HC. There is an increased fungal to bacterial ratio as well as more diverse fungal-bacterial interactions in RRMS patients compared to HC. Our study is the first step towards future studies in delineating the mechanisms through which the fungal microbiome can influence MS disease.
Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling
Authors: Chen Dahong , McManus Catherine E. , Radmanesh Behram , Matzat Leah H. , Lei Elissa P. 
Published: September 2021

ABSTRACTDuring development, looping of an enhancer to a promoter is frequently observed in conjunction with temporal and tissue-specific transcriptional activation. The chromatin insulator-associated protein Shep promotes Drosophila post-mitotic neuronal remodeling by repressing transcription of master developmental regulators, such as brain tumor (brat), specifically in maturing neurons. Since insulator proteins can promote looping, we hypothesized that Shep antagonizes brat promoter interaction with an as yet unidentified enhancer. Using chromatin conformation capture and reporter assays, we identified two novel enhancer regions that increase in looping frequency with the brat promoter specifically in pupal brains after Shep depletion. The brat promoters and enhancers function independently of Shep, ruling out direct repression of these elements. Moreover, ATAC-seq in isolated neurons demonstrated that Shep restricts chromatin accessibility of a key brat enhancer as well as other enhancers genome-wide in remodeling pupal but not larval neurons. These enhancers are enriched for chromatin targets of Shep and are located at Shep-inhibited genes, suggesting direct Shep inhibition of enhancer accessibility and gene expression during neuronal remodeling. Our results provide evidence for temporal regulation of chromatin looping and enhancer accessibility during neuronal maturation.
Diurnal activity budget and conservation implication of Hippopotamus amphibius at Bui National Park, Ghana
Authors: Bempah Godfred , Osei Marie , Gyimah Alice , Nsoah Winnifred 
Published: September 2021

AbstractAnimals apportion time for their daily behavioral activities. We studied the activity budget of Hippopotamus amphibius at the Black Volta River in the Bui National Park, Ghana. We performed instantaneous scan sample using ground count survey between August 2020 to July 2021. We observed that H. amphibius spent most of their day time resting (54.75 %), followed by feeding (22.93 %), walking (19.2 %) and touching (3.12 %). We found significant difference in the time spent between the daily activities (H = 41.67; p < 0.0001). Except activities involving touching, we found no significant seasonal differences in feeding, resting and walking activities by H. amphibius. Understanding the behavioral activities of H. amphibius will enhance management and conservation of the animals.
β-glucan imprinting remodels macrophage function in response to environmental cues
Authors: Piffer Alícia C. , Camilli Giorgio , Bohm Mathieu , Lavenir Rachel , Quintin Jessica 
Published: September 2021

AbstractIn vitro, exposure of human primary monocytes to the fungal β-glucan enhances their pro-inflammatory responsiveness towards several pathogens. Yet, the role of environmental condition of this process remains unclear. Here we found that β-glucan-induced innate immune memory counteract the anti-inflammatory status of the macrophages. In response to β-glucan imprinting, M-CSF-(M2-like-) macrophages increase their pro-inflammatory responsiveness to secondary stimuli associated with decrease of the M-CSF differentiation hallmarks. In contrast, in GM-CSF-(M1-like-) environment, β-glucan imprinting reduced the pro-inflammatory canonical feature of the macrophages, together with their terminal differentiation marks. Comparing M-CSF and GM-CSF environment, we observed that β-glucan-imprinted macrophages present comparable functions in terms of cytokine responses, phagocytosis, oxidative burst, and angiogenesis. This effect is mediated through Dectin-1 and associated with altered expression of the master regulators of macrophage terminal differentiation, IRF5 and IRF3. β-glucan-induced innate immune memory skews the commitment of the macrophages in complex environment towards similar and less terminally differentiated cells. Together, these observations suggest a potential therapeutic role for β-glucan-induced modulation of innate memory in different pathological contexts.
“Axonal Length Determines distinct homeostatic phenotypes in human iPSC derived motor neurons on a bioengineered platform”
Authors: Hagemann Cathleen , Gonzalez Carmen Moreno , Guetta Ludovica , Tyzack Giulia , Chiappini Ciro , Legati Andrea , Patani Rickie , Serio Andrea 
Published: September 2021

AbstractStem cell-based experimental platforms for neuroscience can effectively model key mechanistic aspects of human development and disease. However, conventional culture systems often overlook the engineering constraints that cells face in vivo. This is particularly relevant for neurons covering long range connections such as spinal motor neurons (MNs). The axons of these neurons extend up to 1m in length and require a complex interplay of mechanisms to maintain cellular homeostasis. It follows that shorter axons in conventional cultures may not faithfully capture important aspects of their longer counterparts. Here we directly address this issue by establishing a bioengineered platform to assemble arrays of human axons ranging from micrometers to centimeters, permitting systematic investigation of the effects of length on human axonal biology for the first time. With this approach, we reveal a link between length and metabolism in human MNs in vitro, where axons above a “threshold” size induce specific molecular adaptations in cytoskeleton composition, functional properties, local translation and mitochondrial homeostasis. Our findings specifically demonstrate the existence of a length-dependent mechanism that switches homeostatic processes within human MNs in order to sustain long axons. Our findings have critical implications for in vitro modelling of several neurodegenerative disorders and reinforce the importance of modelling cell shape and biophysical constraints with fidelity and precision in vitro.
Mutually Antagonistic Protein Pairs of Cancer
Authors: Dalgıç Ertuğrul 
Published: September 2021

AbstractSwitch-like behavior of tumorigenesis could be governed by antagonistic gene and protein pairs with mutual inhibition. Unlike extensive analysis of gene expression, search for protein level antagonistic pairs has been limited. Here, potential cancer type specific antagonist protein pairs with mutual inhibition were obtained from large scale datasets. Cancer samples or cancer types were compared to retrieve potential protein pairs with contrasting differential expression patterns. Analysis of two different protein expression datasets showed that a few proteins participate in most of the mutually antagonistic relationships. Some proteins with highly antagonistic profile were identified, which could not be attained from a differential expression or a correlation based analysis. The antagonistic protein pairs are sparsely connected by molecular interactions. Glioma, melanoma, and cervical cancer, are more frequently associated with antagonistic proteins than most of the other cancer types. Integrative analysis of mutually antagonist protein pairs contributes to our understanding of systems level changes of cancer.
Yap/Taz-Activated Tert-Expressing Acinar Cells Are Required for Pancreatic Regeneration
Authors: Suh Han Na , Kim Moon Jong , Lee Sung Ho , Jun Sohee , Zhang Jie , Johnson Randy L. , Park Jae-Il 
Published: September 2021

ABSTRACTThe expression of TERT (telomerase reverse transcriptase) has been implicated in stem and progenitor cells, which are essential for tissue homeostasis and regeneration. However, the roles of TERT-expressing cells in the pancreas remain elusive. Employing genetically engineered Tert knock-in mouse model, herein, we located a rare population of Tert+ acinar cells. While Tert+ cells are quiescent in normal conditions, acinar cell injury leads to mitotic activation of Tert+ cells and subsequent generation of new acinar cells. Moreover, the genetic ablation of Tert+ cells impairs pancreatic regeneration. We further found that Yap/Taz activation is required for the expansion of Tert+ acinar cells. Our results identified Tert+ acinar cells as a distinct subset of acinar cells, which contributes to pancreatic regeneration via Yap/Taz activation.
Efficient ancestry and mutation simulation with msprime 1.0
Authors: Baumdicker Franz , Bisschop Gertjan , Goldstein Daniel , Gower Graham , Ragsdale Aaron P. , Tsambos Georgia , Zhu Sha , Eldon Bjarki , Ellerman E. Castedo , Galloway Jared G. , Gladstein Ariella L. , Gorjanc Gregor , Guo Bing , Jeffery Ben , Kretzschmar Warren W. , Lohse Konrad , Matschiner Michael , Nelson Dominic , Pope Nathaniel S. , Quinto-Cortés Consuelo D. , Rodrigues Murillo F. , Saunack Kumar , Sellinger Thibaut , Thornton Kevin , van Kemenade Hugo , Wohns Anthony W. , Wong Yan , Gravel Simon , Kern Andrew D. , Koskela Jere , Ralph Peter L. , Kelleher Jerome 
Published: September 2021

AbstractStochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this necessity, a large number of specialised simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introducemsprimeversion 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure andtskitlibrary. We summarisemsprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialised alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.
Only females show a stable association between neuroticism and microstructural asymmetry of the cingulum across childhood and adolescence: A longitudinal DTI study
Authors: Plachti Anna , Baaré William FC , Johansen Louise Baruël , Thompson Wesley K. , Siebner Hartwig R. , Madsen Kathrine Skak 
Published: September 2021

AbstractNeuroticism is characterized by a tendency to experience negative and anxious emotions. This personality trait is linked to an increased risk of anxiety and mood disorders. In a cross-sectional 3T diffusion tensor imaging (DTI) study in children and adolescents, we found an association between neuroticism and a relative imbalance between left and right (i.e., asymmetry) fractional anisotropy (FA) in the cingulum and white matter underlying the ventromedial prefrontal cortex with opposite directions in females and males. Here we analyzed the longitudinal follow-up DTI data, which was acquired in 76 typically-developing 7- to 18-year-olds, including up to 11 scans per subject. Neuroticism was assessed up to four times. Our longitudinal DTI measurements substantiate robust associations between higher neuroticism scores and increased left relative to right cingulum FA in females and decreased left relative to right cingulum FA in males. In females, the association was already present in late childhood and with a stable expression across childhood and adolescence. In males, the association gradually emerged during adolescence. Future longitudinal studies should clarify which neurobiological factors (e.g., genetic variation, prenatal stress, sex hormones) contribute to the sex-specific associations in the relationship between neuroticism and interhemispheric microstructural asymmetry of the cingulum.HighlightWe analyzed a unique longitudinal DTI dataset covering late childhood and adolescence.In the cingulum, left-right fractional anisotropy (FA) asymmetry scaled with neuroticism.Females displayed a stable association of neuroticism with increased cingulum asymmetry.Males showed an association between neuroticism and decreased cingulum FA asymmetry.The association in males became more accentuated during adolescence
The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking
Authors: Sehl Olivia C. , Foster Paula J. 
Published: September 2021

AbstractPurposeMagnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells.MethodsCells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes.ResultsUsing the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 × 101619F atoms) were detected with 19F MRI, with SNR > 5. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number.ConclusionMPI has the potential to be more sensitive than 19F MRI for cell tracking. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.
Synergistic Effect of Serotonin 1A and Serotonin 1B/D Receptor Agonists in the Treatment of L-DOPA-Induced Dyskinesia in 6-Hydroxydopamine-Lesioned Rats
Authors: Thomsen Mikael , Stoica Anca , Christensen Kenneth Vielsted , Mikkelsen Jens , Hansen John Bondo 
Published: September 2021

AbstractBackgroundThe gold standard for symptomatic relief of Parkinson’s disease is L-DOPA. However, long-term treatment often leads to motor complications such as L-DOPA-induced dyskinesia (LID). While amantadine (Gocovri™) is the only approved therapy for dyskinesia in people with Parkinson’s disease on the American market, it is associated with neurological side effects and limited efficacy. Thus, there remains a high unmet need for addressing LID in Parkinson’s disease patients worldwide.ObjectiveThe objective of this study was to evaluate the efficacy, safety and performance compared to approved treatments of the serotonin receptor 1A (5-HT1A) and 5-HT1B/D agonists buspirone and zolmitriptan in the 6-hydroxydopamine unilaterally lesioned rat model for Parkinson’s disease.MethodsThe hemi-parkinsonian 6-OHDA lesioned rats underwent chronic treatment with L-DOPA to induce dyskinesia and were subsequently used for efficacy testing of buspirone, zolmitriptan and comparison with amantadine, measured as abnormal involuntary movement (AIM) scores after L-DOPA challenge. Safety testing was performed in model and naive animals using forelimb adjusting, rotarod and open field tests.Results5-HT1A and 5-HT1B/D agonism effectively reduced AIM scores in a synergistic manner. The drug combination of buspirone and zolmitriptan was safe and did not lead to tolerance development following sub-chronic administration. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in the model.ConclusionsThe strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan a potential clinical candidate for LID in Parkinson’s disease.
Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor
Authors: Capraz Tümay , Kienzl Nikolaus F. , Laurent Elisabeth , Perthold Jan W. , Föderl-Höbenreich Esther , Grünwald-Gruber Clemens , Maresch Daniel , Monteil Vanessa , Niederhöfer Janine , Wirnsberger Gerald , Mirazimi Ali , Zatloukal Kurt , Mach Lukas , Penninger Josef M. , Oostenbrink Chris , Stadlmann Johannes 
Published: September 2021

AbstractInfection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells. Glycosylation of both proteins is critical for this interaction. Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19. We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation. Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein. Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
Impending anthropogenic threats and protected area prioritization for the largest Neotropical apex predator in its Amazonian stronghold
Authors: Bogoni Juliano A. , Boron Valeria , Peres Carlos A. , Coelho Maria Eduarda M. S. , Morato Ronaldo G. , Oliveira-da-Costa Marcelo 
Published: September 2021

AbstractJaguars (Panthera onca) exert critical top-down control over large vertebrates across the Neotropics and have been declining due to multiple threats. Based on geospatial layers, we extracted socio-environmental variables for 447 protected areas across the Brazilian Amazon to identify protected areas that merit short-term high-priority efforts to maximize jaguar persistence. Data were analyzed using descriptive statistics, structural equations and regression modeling. Our results reveal that areas containing the largest jaguar densities and estimated population sizes are precisely those confronting most anthropogenic threats. We reveal that jaguars in the world’s largest tropical forest biome are threatened by deforestation associated with anthropogenic fires, and subsequent establishment of pastures. We provide a shortlist of protected areas that should be prioritized for short-term jaguar conservation. The future predicament of jaguar populations can only be ensured if protected areas can be proofed against downgrading and downsizing geopolitical pressures and external anthropogenic threats.