bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of ecosystem engineers in shaping the diversity and function of arid soil bacterial communities
Authors: Baubin Capucine , Farrell Arielle M. , Šťovíček Adam , Ghazaryan Lusine , Giladi Itamar , Gillor Osnat 
Published: December 2021

ABSTRACTEcosystem engineers (EEs) are present in every environment and are known to strongly influence ecological processes and thus shape the distribution of species and resources. In this study, we assessed the direct and indirect effect of two EEs (perennial shrubs and ant nests), individually and combined, on the composition and function of arid soil bacterial communities. To that end, top soil samples were collected in the Negev Desert Highlands during the dry season from four patch types: (1) barren soil; (2) under shrubs; (3) near ant nests; or (4) near ant nests situated under shrubs. The bacterial composition was evaluated in the soil samples (fourteen replicates per patch type) using 16S rRNA gene amplicon sequencing, together with physico-chemical measures of the soil, and the potential functions of the community. We have found that the EEs differently affected the community composition. Indeed, barren patches supported a soil microbiome, dominated byRubrobacterandProteobacteria, while in EE patches theDeinococcus-Thermusphylum was dominating. The presence of the EEs similarly enhanced the abundance of phototrophic, nitrogen cycle and stress- related genes. In addition, only when both EEs were combined, were the soil characteristics altered. Our results imply that arid landscapes foster unique communities selected by each EE(s), solo or in combination, yet these communities have similar potential biological traits to persist under the harsh arid conditions. Environments with multiple EEs are complicated to study due to the possibility of non-additive effects of EEs and thus further research should be done.IMPORTANCEEcosystem engineers are organisms that can create, modify, or maintain their habitat. They are present in various environments but are particularly conspicuous in desert ecosystems, where their presence is tightly linked to vital resources like water or nutrients. Despite their key role in structuring and controlling desert ecosystems, joint engineering, and their effect on soil function, are unknown. Our study explores the contributions of key ecosystem engineers to the diversity and function of their soil microbiome allowing better understanding of their role in shaping habitats and engineering their activity
Safety and immunogenicity of a heterologous booster of protein subunit vaccine MVC-COV1901 after two doses of adenoviral vector vaccine AZD1222
Authors: Cheng Shu-Hsing , Lin Yi-Chun , Chen Cheng-Pin , Cheng Chien-Yu 
Published: December 2021

AbstractWe report the interim safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 or 24 weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers were 14- and 8.6-fold increased, respectively, when compared to the titer levels on the day of the booster dose. We also observed 5.2- and 5.6-fold increases in neutralizing titer levels against wildtype and Omicron variant pseudovirus after the booster dose, respectively. These interim results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222.
MULTITRAIT ANALYSIS EXPANDS GENETIC RISK FACTORS IN CARDIOEMBOLIC STROKE
Authors: Cárcel-Márquez Jara , Muiño Elena , Gallego-Fabrega Cristina , Cullell Natalia , Lledós Miquel , Llucià-Carol Laia , Sobrino Tomás , Campos Francisco , Castillo José , Freijo Marimar , Arenillas Juan Francisco , Obach Victor , Álvarez-Sabín José , Molina Carlos A. , Ribó Marc , Jiménez-Conde Jordi , Roquer Jaume , Muñoz-Narbona Lucia , Lopez-Cancio Elena , Millán Mònica , Diaz-Navarro Rosa , Vives-Bauza Cristòfol , Serrano-Heras Gemma , Segura Tomás , Ibañez Laura , Heitsch Laura , Delgado Pilar , Dhar Rajat , Krupinski Jerzy , Delgado-Mederos Raquel , Prats-Sánchez Luis , Camps-Renom Pol , Blay Natalia , Sumoy Lauro , de Cid Rafael , Montaner Joan , Cruchaga Carlos , Lee Jin-Moo , Martí-Fàbregas Joan , Férnandez-Cadenas Israel 
Published: December 2021

ABSTRACTBackground and PurposeThe genetic architecture of cardioembolic stroke (CES) is still poorly understood. Atrial fibrillation (AF) is the main cause of CES, with which it shares heritability. We aimed to discover novel loci associated with CES by performing a Multitrait Analysis of the GWAS (MTAG) with atrial fibrillation genetic data.MethodsFor the MTAG analysis we used the MEGASTROKE cohort, which comprises European patients with CES and controls (n=362,661) and an AF cohort composed of 1,030,836 subjects. Regional genetic pleiotropy of the significant results was explored using an alternative Bayesian approach with GWAS-pairwise method. A replication was performed in an independent European cohort comprising 9,105 subjects using a Genome Wide Association Study (GWAS).ResultsMTAG-CES analysis revealed 40 novel and significant loci (p-value<5×10−8) associated with CES, four of which had not previously been associated with AF. A significant replication was assessed for eight novel loci: CAV1, IGF1R, KIAA1755, NEURL1, PRRX1, SYNE2, TEX41 and WIPF1, showing a p-value<0.05 in the CES vs controls independent analysis. KIAA1755, a locus not previously described associated with AF. Interestingly, 51 AF risk loci were not associated with CES according to GWAS-pairwise analysis. Gene Ontology (GO) analysis revealed that these exclusive AF genes from the 51 loci participate in processes related mainly to cardiac development, whereas genes associated with AF and CES participate mainly in muscle contraction and the conduction of electrical impulses.ConclusionsWe found eight new loci associated with CES. In addition, this study provides novel insights into the pathogenesis of CES, highlighting multiple candidate genes for future functional experiments.
The 3D architecture of the pepper (Capsicum annum) genome and its relationship to function and evolution
Authors: Liao Yi , Wang Juntao , Zhu Zhangsheng , Liu Yuanlong , Chen Jinfeng , Zhou Yongfeng , Liu Feng , Lei Jianjun , Gaut Brandon S. , Cao Bihao , Emerson J.J. , Chen Changming 
Published: December 2021

AbstractThe architecture of topologically associating domains (TADs) varies across plant genomes. Understanding the functional consequences of this diversity requires insights into the pattern, structure, and function of TADs. Here, we present a comprehensive investigation of the 3D genome organization of pepper (Capsicum annuum) and its association with gene expression and genomic variants. We report the first chromosome-scale long-read genome assembly of pepper and generate Hi-C contact maps for four tissues. The contact maps indicate that 3D structure varies somewhat across tissues, but generally the genome was segregated into subcompartments that were correlated with transcriptional state. In addition, chromosomes were almost continuously spanned by TADs, with the most prominent found in large genomic regions that were rich in retrotransposons. A substantial fraction of TAD boundaries were demarcated by chromatin loops, suggesting loop extrusion is a major mechanism for TAD formation; many of these loops were bordered by genes, especially in highly repetitive regions, resulting in gene clustering in three dimensional space. Integrated analysis of Hi-C profiles and transcriptomes showed that change in 3D chromatin structures (e.g. subcompartments, TADs, and loops) was not the primary mechanism contributing to differential gene expression between tissues, but chromatin structure does play a role in transcription stability. TAD boundaries were significantly enriched for breaks of synteny and depletion of sequence variation, suggesting that TADs constrain patterns of genome structural evolution in plants. Together, our work provides insights into principles of 3D genome folding in large plant genomes and its association with function and evolution.
Polyclonal pathogen populations accelerate the evolution of antibiotic resistance in patients
Authors: Caballero Julio Diaz , Wheatley Rachel M. , Kapel Natalia , López-Causapé Carla , Van der Schalk Thomas , Quinn Angus , Recanatini Claudia , Xavier Basil Britto , Timbermont Leen , Kluytmans Jan , Ruzin Alexey , Esser Mark , Malhotra-Kumar Surbhi , Oliver Antonio , MacLean R. Craig ,   WP3A working group
Published: December 2021

AbstractAntibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection forde novovariants. Here we show that pulmonary populations of the opportunistic pathogenP. aeruginosaare often polyclonal. Crucially, resistance evolves rapidly in patients colonized by polyclonal populations through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by monoclonal populations due to selection for novel resistance mutations. However, strong trade-offs between resistance and fitness occur in polyclonal populations that can drive the loss of resistant strains. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.One sentence summaryAntibiotic resistance evolves quickly in patients colonized by polyclonal pathogen populations.
Manipulating Histone Acetylation Leads to Adverse Effects in Hemangiosarcoma Cells
Authors: Suzuki Tamami , Aoshima Keisuke , Yamazaki Jumpei , Kobayashi Atsushi , Kimura Takashi 
Published: December 2021

AbstractCanine hemangiosarcoma (HSA) is a malignant tumour derived from endothelial cells. No effective treatment has yet been developed because of the lack of understanding of its pathogenesis. Histone acetylation, an epigenetic modification, is highly associated with cancer pathogenesis. Manipulating histone acetylation by histone deacetylase inhibitors (HDACi) or bromodomain and extraterminal domain inhibitors (BETi) is one approach to treat various cancers. However, the role of histone acetylation in HSA remains unknown. This study aimed to investigate how histone acetylation functions in HSA pathogenesis using two HDACi, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), and one BETi, JQ1, in vitro and in vivo. Histone acetylation levels were high in cell lines and heterogeneous in clinical cases. SAHA and JQ1 induced apoptosis in HSA cell lines. SAHA and VPA treatment in HSA cell lines upregulated inflammatory-related genes, thereby attracting macrophages. This implies that SAHA and VPA can induce anti-tumour immunity. JQ1 stimulated autophagy and inhibited the cell cycle. Finally, JQ1 suppressed HSA tumour cell proliferation in vivo. These results suggest that HDACi and BETi can be alternative drugs for HSA treatment. Although further research is required, this study provides useful insights for developing new treatments for HSA.
Ketamine Sedation Facilitates Asleep DBS: a multicenter retrospective study
Authors: Erdman Halen Baker , Kornilov Evgeniya , Kahana Eilat , Zarchi Omer , Reiner Johnathan , Socher Achinoam , Strauss Ido , Israel Zvi , Bergman Hagai , Tamir Idit 
Published: December 2021

AbstractDeep brain stimulation (DBS) is commonly and safely performed for selective Parkinson’s disease patients. Many centers perform DBS lead positioning exclusively under local anesthesia, to allow for brain microelectrode recordings (MER) and testing of stimulation-related therapeutic and side effects. These measures enable physiological identification of the DBS targets based on electrophysiological properties like firing rates and patterns, optimization of lead placement accuracy, and intra-operative evaluation of therapeutic window. Nevertheless, due to the challenges of awake surgery, some centers use sedation or general anesthesia, despite the distortion of discharge properties, and potential impact on clinical outcomes. Thus, there is a need for a novel anesthesia regimen that enables sedation without compromising intra-operative monitoring. This study investigates the use of low-dose ketamine for conscious sedation during lead positioning in subthalamic nucleus (STN) DBS for Parkinson’s disease patients.Three anesthetic regimens were retrospectively compared in 38 surgeries across three DBS centers: 1) Interleaved propofol-ketamine (PK), 2) Interleaved propofol-awake (PA), and 3) Fully awake (AA).All anesthesia regimens achieved satisfactory MER. Automatic detection of STN borders and subdomains using a Hidden Markov Model was similar between the groups. Patients’ symptoms and cooperation during stimulation testing in the ketamine group was not altered. No major adverse effects were reported in the different anesthesia protocols.These results support the use of low-dose ketamine as a novel alternative for the existing DBS anesthesia regimens, optimizing patient’s experience while preserving lead placement accuracy. A prospective study should be performed to confirm these findings.
The impact of the COVID-19 school closure on adolescents’ use of mental healthcare services in Sweden
Authors: Svaleryd Helena , Björkegren Evelina , Vlachos Jonas 
Published: December 2021

AbstractBackgroundSchool closures used to contain the COVID-19 pandemic may have negative impacts on students’ mental health but credible evidence is scarce. Sweden moved upper-secondary students to remote learning but, as the only country in the OECD, kept schools at lower levers open throughout the pandemic.MethodsUsing nationwide register data, we estimate the difference in the use of mental healthcare services between upper- and lower-secondary students during the pandemic, and relate this to the same group difference prior to the pandemic. For the main analysis, this difference-in-difference approach is applied to the period April-June 2020 when upper-secondary schools were fully closed. We also study the periods July-December 2020 when upper-secondary schools were largely open, and January-March 2021 when they were partially closed. We study the impact on all contacts with hospitals and specialist psychiatric care due to mental and behavioral disorder, as well as prescriptions for antidepressants, insomnia, and ADHD drugs.FindingsCompared with expected rates, the use of mental healthcare services among upper-secondary students fell by -3.71 [CI95 -5.52 to -1.91] cases per 1000 during April-June 2020, largely due to a reduction in depression and anxiety-related diagnoses (-1.49; CI95 [-2.36 to -0.63]) and prescriptions (-1.80; CI95 [-2.93 to -0.68]). This reduction in the use of mental healthcare services corresponds to a 4.36% CI95 [-6.47 to -2.25]) decrease compared to the level prior to the pandemic. The decrease compared to expected rates persists through July-December 2020 (-3.55%; CI95 [-5.38 to -1.71]) and January-March 2021 (-5.23%; CI95 [-7.24 to -3.21]). The reduction is stronger among students in the 2nd (-5.06%; CI95 [-8.02 to -2.09]) and 3rd (-4.86%; CI95 [-8.19 to -1.53]) year of upper-secondary school. The decrease is concentrated to students who was not in contact with mental healthcare services earlier in the academic year (-16.70%; CI95 [-22.20 to -11.20]). The relative reduction is largest for unplanned care (-13.88%; CI95 [-19.35 to -8.42]) and care at emergency units (-18.19%; CI95 [-26.44 to -9.92]).InterpretationClosing upper-secondary schools in Sweden reduced use of mental healthcare services. There is no indication of this being due to reduced accessibility. In a setting with no strict lockdown, moving to online teaching for a limited period did not worsen mental health among students in upper-secondary schools.
Change in Finances, Peer Access, and Mental Health Among Trans and Non-binary People in Canada During COVID-19
Authors: Ghabrial Monica A. , Scheim Ayden I. , Chih Caiden , Santos Heather , Adams Noah James , Bauer Greta R. 
Published: December 2021

ABSTRACTPurposeCOVID-related stressors associated with loss of income and community are compounded with gender minority stress among trans and non-binary people (TNB) – which may result in mental health burden. The present study examined the effect of COVID-related change in finances and TNB gathering access on anxiety and depression among TNB people.MethodsParticipants were 18 years and older (M age = 30) who completed both pre-pandemic baseline (Fall 2019) and pandemic follow-up (Fall 2020) surveys in the Trans PULSE Canada study. Multivariable regression analyses examined associations between change in (1) finances and (2) access to TNB peers and mental health during the pandemic.ResultsOf 780 participants, 50% reported that COVID had a negative effect on personal income and 58.3% reported loss in access to TNB peer or friend gatherings (in person or online). Depression and anxiety symptoms increased from pre-pandemic to follow-up, and most participants were above measurement cut-offs for clinical levels during the pandemic. Changes in finances and access to peer gatherings were associated with depression symptoms during the pandemic, but effects depended on level of pre-pandemic depression. For participants with high pre-pandemic depression, financial stability was not protective against increased depression at follow-up. Participants experiencing unprecedentedly high levels of depression during COVID may have pursued more TNB gatherings. Neither financial change nor access to TNB gatherings were associated with pandemic anxiety.ConclusionFindings suggest need for a multifaceted approach to mental health programmes and services to address structural barriers, including financial support and meaningful TNB community engagement.
Large-scale osteocyte lacunar morphological analysis of transiliac bone in normal and osteoporotic premenopausal women
Authors: Goff Elliott , Cohen Adi , Shane Elizabeth , Recker Robert R. , Kuhn Gisela , Müller Ralph 
Published: December 2021

AbstractBone’s adaptation ability is governed by the network of embedded osteocytes that inhabit individual crevasses called lacunae. The morphology of these lacunae and their resident osteocytes are known to change with age and diseases such as postmenopausal osteoporosis. However, it is unclear whether alterations in lacunar morphology are present in younger populations with osteoporosis. To investigate this, we implemented a previously validated methodology to image and quantify the three-dimensional morphometries of lacunae on a large scale (26.2 million cells) with ultra-high-resolution micro-computed tomography (microCT) in transiliac bone biopsies from three groups of premenopausal women: control n=39; idiopathic osteoporosis (IOP) n=45; idiopathic low BMD (ILBMD) n=19. Important lacunar morphometric parameters were measured in both trabecular and cortical bone: lacunar density (Lc.N/BV), lacunar porosity (Lc.TV/BV), lacunar number (Lc.N), lacunar volume (Lc.V), lacunar surface area (Lc.S), lacunar alignment (Lc.θ), lacunar stretch (Lc.St), lacunar oblateness (Lc.Ob), lacunar equancy (Lc.Eq), and lacunar sphericity (Lc.Sr). These were then compared against each other and also with previously measured tissue morphometries including: bone volume density (BV/TV), trabecular separation (Tb.Sp), trabecular number (Tb.N), and trabecular thickness (Tb.Th), structure model index (SMI), cortical porosity (Ct.Po) and cortical pore spacing (Ct.Sp). We detected no differences in lacunar morphology between the IOP, ILBMD and healthy premenopausal women. In contrast, we did find significant differences between lacunar morphologies in cortical and trabecular regions within all three groups, which was consistent with our previous findings on a subgroup of the healthy group. Furthermore, we discovered strong correlations between Lc.Sr from both trabecular and cortical regions with the measured BV/TV. The findings and comprehensive lacunar dataset we present here will be a crucial foundation for future investigations of the relationship between osteocyte lacunar morphology and disease.
A Fast Lasso-Based Method for Inferring Higher-Order Interactions
Authors: Elmes Kieran , Heywood Astra , Huang Zhiyi , Gavryushkin Alex 
Published: December 2021

AbstractLarge-scale genotype-phenotype screens provide a wealth of data for identifying molecular alterations associated with a phenotype. Epistatic effects play an important role in such association studies. For example, siRNA perturbation screens can be used to identify combinatorial gene-silencing effects. In bacteria, epistasis has practical consequences in determining antimicrobial resistance as the genetic background of a strain plays an important role in determining resistance. Recently developed tools scale to human exome-wide screens for pairwise interactions, but none to date have included the possibility of three-way interactions. Expanding upon recent state-of-the art methods, we make a number of improvements to the performance on large-scale data, making consideration of three-way interactions possible. We demonstrate our proposed method, Pint, on both simulated and real data sets, including antibiotic resistance testing and siRNA perturbation screens. Pint outperforms known methods in simulated data, and identifies a number of biologically plausible gene effects in both the antibiotic and siRNA models. For example, we have identified a combination of known tumor suppressor genes that is predicted (using Pint) to cause a significant increase in cell proliferation.Author SummaryIn recent years, large-scale genetic datasets have become available for analysis. These large datasets often stretch the limits of classic computational methods, requiring too much memory or simply taking a prohibitively long time to run. Due to the enormous number of potential interactions, each gene or variation in the data is often modeled on its own, without considering interactions between them. Recently, methods have been developed to solve regression problems that include these interacting effects. Even the fastest of these cannot include threeway interactions, however. We improve upon one such method, developing an approach that is significantly faster than the current state of the art. Moreover, our method scales to three-way interactions among thousands of genes, while avoiding a number of the limitations of previous approaches. We analyse large-scale simulated data, antibiotic resistance, and gene-silencing datasets to demonstrate the accuracy and performance of our approach.
Spatially distributed computation in cortical circuits
Authors: Gepshtein Sergei , Pawar Ambarish , Kwon Sunwoo , Savel’ev Sergey , Albright Thomas D. 
Published: December 2021

AbstractThe traditional view of neural computation in the cerebral cortex holds that sensory neurons are specialized, i.e., selective for certain dimensions of sensory stimuli. This view was challenged by evidence of contextual interactions between stimulus dimensions in which a neuron’s response to one dimension strongly depends on other dimensions. Here we use methods of mathematical modeling, psychophysics, and electrophysiology to address shortcomings of the traditional view. Using a model of a generic cortical circuit, we begin with the simple demonstration that cortical responses are always distributed among neurons, forming characteristic waveforms, which we call neural waves. When stimulated by patterned stimuli, circuit responses arise by interference of neural waves. Resulting patterns of interference depend on interaction between stimulus dimensions. Comparison of these modeled responses with responses of biological vision makes it clear that the framework of neural wave interference provides a useful alternative to the standard concept of neural computation.TeaserInvestigating interference of neural waves helps to overcome limitations of the traditional view of cortical computation.