bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell
Authors: Niesen Maxime , Trotta Nicola , Noel Antoine , Coolen Tim , Fayad Georges , Leurkin-Sterk Gil , Delpierre Isabelle , Henrard Sophie , Sadeghi Niloufar , Goffard Jean-Christophe , Goldman Serge , De Tiège Xavier 
Published: October 2020

AbstractObjectivesSudden loss of smell is a very common symptom of coronavirus disease 19 (COVID-19). This study characterizes the structural and metabolic cerebral correlates of dysosmia in patients with COVID-19.MethodsStructural brain magnetic resonance imaging (MRI) and positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) were prospectively acquired simultaneously on a hybrid PET-MR in twelve patients (2 males, 10 females, mean age: 42.6 years, age range: 23-60 years) with sudden dysosmia and positive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab specimens. FDG-PET data were analysed using a voxel-based approach and compared with that of a group of healthy subjects.ResultsBilateral blocking of the olfactory cleft was observed in six patients, while subtle olfactory bulb asymmetry was found in three patients. No MRI signal abnormality downstream of the olfactory tract was observed. Heterogeneous (decrease or increase) glucose metabolism abnormalities were observed in core olfactory and high-order neocortical areas. A modulation of regional cerebral glucose metabolism by the severity and the duration of COVID-19-related dysosmia was disclosed using correlation analyses.ConclusionsThis PET-MR study shows that sudden loss of smell in COVID-19 is not related to central involvement due to SARS-CoV-2 neuroinvasiveness. Loss of smell is associated with heterogeneous cerebral metabolic changes in core olfactory and high-order cortical areas likely related to combined processes of deafferentation and active functional reorganisation secondary to the lack of olfactory stimulation.
The Response of Pakistani Social Workers amid the COVID-19 Pandemic: A Qualitative Analysis of the Main Challenges
Authors: Abbas Kiran , Ul Haq Muhammad Inam , Zaidi Wareesha Afaq , Kaleem Ahmed , Sohail Hamza , Ahmed Moiz 
Published: October 2020

AbstractThe study aimed to highlight the main challenges faced by the social workers amid the pandemic. A qualitative study was conducted between March 2020 to May 2020 in Karachi, Pakistan. All participants who belonged to a non-profit organization were eligible to participate. Open-ended questions were asked by the participants. The mean age of the participants was 24.8 ± 5.9 years. The main challenges faced by the social workers were: i) resistance from the family and friends, ii) lack of personal protective equipment, iii) mistrust from public, iv) uncooperative government/authorities.
Prevalence and predictors of coronaphobia among frontline hospital and public health nurses
Authors: Labrague Leodoro J. , De Los Santos Janet Alexis A. 
Published: October 2020

AbstractObjectivesTo determine the prevalence rate as well as the predictors of coronaphobia in frontline hospital and public health nurses.DesignThis study used a cross-sectional research study involving 736 nurses working in COVID-19 designated hospitals and health units in Region 8, Philippines. Four structured self-report scales were used, including the Coronavirus Anxiety Scale, the Brief Resilience Scale, the Perceived Social Support Questionnaire, and the single-item measure for perceived health.ResultsThe prevalence rate of coronaphobia was 54.76% (n= 402): 37.04% (n= 130) in hospital nurses and 70.91% (n= 273) in public health nurses. Additionally, nurses’ gender (β= 0.146,p= 0.001), marital status (β= 0.101,p= 0.009), job status (β= 0.132,p= 0.001), and personal resilience (β= −0.154,p= 0.005) were identified as predictors of COVID-19 anxiety. A small proportion of nurses was willing (19.94%,n= 70) and fully prepared (9.40%,n= 33) to manage and care for coronavirus patients.ConclusionCoronaphobia is prevalent among frontline Filipino nurses, particularly among public health nurses. Interventions to address coronaphobia among frontline nurses in the hospital and community should consider the predictors identified. By increasing personal resilience in nurses through theoretically-driven intervention, coronaphobia may be alleviated.
Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization
Authors: Qu Yongcun , Chen Qi , Guo Shanshan , Ma Chiyuan , Lu Yonggang , Shi Junchao , Liu Shichao , Zhou Tong , Noda Taichi , Qian Jingjing , Zhang Liwen , Zhu Xili , Lei Xiaohua , Cao Yujing , Li Wei , Li Wei , Plachta Nicolas , Matzuk Martin M. , Ikawa Masahito , Duan Enkui , Zhang Ying , Wang Hongmei 
Published: October 2020

AbstractSperm cooperation has been observed in multiple species, yet its existence and benefit for reproductive success in mammals remains underexplored. Here, combining tissue-clearing with deep three-dimensional imaging, we demonstrate that postcopulatory mouse sperm congregate into unidirectional sperm cooperative clusters at the utero-tubal junction (UTJ), a key physical barrier for passage into the oviduct. Reducing sperm number in male mice by unilateral vasoligation or busulfan-treatment impairs sperm cluster formation and oviduct entry. Interestingly, sperm derived fromTex101−/−mouse has normal number, motility and morphology, yet they cannot form sperm cluster and fail to pass through the UTJ, which is at least in part due to the altered tail beating pattern of theTex101−/−sperm. Moreover,Tex101−/−sperm’s defect in oviduct entry cannot be rescued by the presence of wild-type (WT) sperm in the same uteri by sequential mating, suggesting sperm cooperative cluster as an essential behavior contributing to male fertility, which could be related to human infertility or subfertility.
Structural coordination between active sites of a Cas6-reverse transcriptase-Cas1—Cas2 CRISPR integrase complex
Authors: Wang Joy Y. , Hoel Christopher M. , Al-Shayeb Basem , Banfield Jillian F. , Brohawn Stephen G. , Doudna Jennifer A. 
Published: October 2020

ABSTRACTCRISPR-Cas systems provide adaptive immunity in bacteria and archaea by targeting foreign DNA for destruction using CRISPR RNA-guided enzymes. CRISPR immunity begins with integration of foreign sequences into the host CRISPR genomic locus, followed by transcription and maturation of CRISPR RNAs. In a few CRISPR systems, the Cas1 integrase and a Cas6 nuclease are fused to a reverse transcriptase that enables viral sequence acquisition from both DNA and RNA sources. To determine how these components work together, we determined a 3.7 Å resolution cryo-EM structure of a Cas6-RT-Cas1 protein complexed with Cas2, a subunit of the CRISPR integrase. The structure and accompanying mutagenesis experiments provide evidence of bidirectional crosstalk between the Cas1 and RT active sites and unidirectional crosstalk from Cas6 to the Cas1 and RT active sites. Together, these findings suggest regulated structural rearrangements that may coordinate the complex’s different enzymatic activities.
Expanding diversity of Asgard archaea and the elusive ancestry of eukaryotes
Authors: Liu Yang , Makarova Kira S. , Huang Wen-Cong , Wolf Yuri I. , Nikolskaya Anastasia , Zhang Xinxu , Cai Mingwei , Zhang Cui-Jing , Xu Wei , Luo Zhuhua , Cheng Lei , Koonin Eugene V. , Li Meng 
Published: October 2020

AbstractComparative analysis of 162 (nearly) complete genomes of Asgard archaea, including 75 not reported previously, substantially expands the phylogenetic and metabolic diversity of the Asgard superphylum, with six additional phyla proposed. Phylogenetic analysis does not strongly support origin of eukaryotes from within Asgard, leaning instead towards a three-domain topology, with eukaryotes branching outside archaea. Comprehensive protein domain analysis in the 162 Asgard genomes results in a major expansion of the set of eukaryote signature proteins (ESPs). The Asgard ESPs show variable phyletic distributions and domain architectures, suggestive of dynamic evolution via horizontal gene transfer (HGT), gene loss, gene duplication and domain shuffling. The results appear best compatible with the origin of the conserved core of eukaryote genes from an unknown ancestral lineage deep within or outside the extant archaeal diversity. Such hypothetical ancestors would accumulate components of the mobile archaeal ‘eukaryome’ via extensive HGT, eventually, giving rise to eukaryote-like cells.
Structure of a transcribing RNA polymerase II–U1 snRNP complex
Authors: Zhang Suyang , Aibara Shintaro , Vos Seychelle M. , Agafonov Dmitry E. , Lührmann Reinhard , Cramer Patrick 
Published: October 2020

AbstractTo initiate co-transcriptional splicing, RNA polymerase II (Pol II) recruits U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent pre-mRNA. Here we report the cryo-EM structure of a mammalian transcribing Pol II-U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the 5’ splice site in pre-mRNA near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5’ splice site, leading to formation of an intron loop. Loop formation may facilitate scanning of the nascent pre-mRNA for the 3’ splice site and enable prespliceosome assembly and functional pairing of distant intron ends. Our results provide a starting point for a mechanistic analysis of co-transcriptional splicing and the biogenesis of mRNA isoforms during alternative splicing.
Activation by Cleavage of the Epithelial Na+Channel α and γ Subunits Independently Coevolved with the Vertebrate Terrestrial Migration
Authors: Wang Xue-Ping , Balchak Deidra M. , Gentilcore Clayton , Clark Nathan L. , Kashlan Ossama B. 
Published: October 2020

AbstractVertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel’s α and γ subunits. We found that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation observed in mammals. Polybasic tract pairs evolved with the terrestrial migration and the appearance of lungs, coincident with the ENaC activator aldosterone, and appeared independently in the α and γ subunits. In summary, sites within ENaC for protease activation developed in vertebrates when renal Na+conservation and alveolar gas exchange was required for terrestrial survival.
The active repertoire ofEscherichia colipeptidoglycan amidases varies with physiochemical environment
Authors: Mueller Elizabeth A. , Iken Abbygail G. , Öztürk Mehmet Ali , Schmitz Mirko , Di Ventura Barbara , Levin Petra Anne 
Published: October 2020

ABSTRACTNearly all bacteria are encased in a peptidoglycan cell wall, an essential crosslinked matrix of polysaccharide strands and short peptide stems. In the Gram-negative model organismEscherichia coli, more than forty cell wall synthases and autolysins coordinate the growth and division of the peptidoglycan sacculus in the periplasm. The precise contribution of many of these enzymes to cell wall metabolism remains unclear due to significant apparent redundancy, particularly among the cell wall autolysins.E. coliproduces three major LytC-type-N-acetylmuramoyl-L-alanine amidases, which share a role in separating the newly formed daughter cells during cytokinesis. Here, we reveal two of the three amidases exhibit growth medium-dependent changes in activity. Specifically, we report acidic growth conditions stimulate AmiB—and to a lesser extent, AmiC—activity. Combining computational and genetic analysis, we demonstrate that low pH-dependent stimulation of AmiB requires three periplasmic amidase activators: EnvC, NlpD, and YgeR. Altogether, our findings support overlapping, but not redundant, roles for theE. coliamidases in cell separation and illuminate the physiochemical environment as an important mediator of cell wall enzyme activity.IMPORTANCEPenicillin and related β-lactam antibiotics targeting the bacterial cell wall synthesis are among the most commonly prescribed antimicrobials worldwide. However, rising rates of antibiotic resistance and tolerance jeopardize their continued clinical use. Development of new cell wall active therapeutics, including those targeting cell wall autolysins, has been stymied in part due to high levels of apparent enzymatic redundancy. In this study, we report a subset ofE. coliamidases involved in cell separation during cell division are not redundant and instead are preferentially active during growth in distinct pH environments. Specifically, we discoverE. coliamidases AmiB and AmiC are activated by acidic pH. Three semi-redundant periplasmic regulators—NlpD, EnvC, and YgeR—collectively mediate low pH-dependent stimulation of amidase activity. This discovery contributes to our understanding of how the cell wall remains robust across diverse environmental conditions and reveals opportunities for the development of condition-specific antimicrobial agents.
3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease
Authors: Domínguez-Álvaro M , Montero-Crespo M , Blazquez-Llorca L , Plaza-Alonso S , Cano-Astorga N , DeFelipe J , Alonso-Nanclares L 
Published: October 2020

AbstractThe entorhinal cortex (EC) is especially vulnerable in the early stages of Alzheimer’s disease (AD). In particular, cognitive deficits have been linked to alterations in the upper layers of EC. In the present report, we examined layers II and III from eight human brain autopsies (four subjects with no recorded neurological alterations and four AD cases). We used stereological methods to assess cortical atrophy of the EC, and possible changes in the volume occupied by different cortical elements (neuronal and glial cell bodies; blood vessels; and neuropil). We performed 3D ultrastructural analyses of synapses using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to examine possible alterations related to AD.At the light microscope level, we found a significantly lower volume fraction occupied by neuronal bodies in layer III and a higher volume fraction occupied by glial cell bodies in layer II in AD cases. At the ultrastructural level we observed that (i) there was a significantly lower synaptic density in both layers in AD cases; (ii) synapses were larger and more complex in layer II in AD cases; and (iii) there was a greater proportion of small and simple synapses in layer III in AD cases than in control individuals. These structural differences may play a role in the anatomical basis for the impairment of cognitive functions in AD.Significant StatementAnalysis of the synaptic characteristics provides critical data on synaptic organization. Using 3D electron microscopy, the present study shows the synaptic organization of the neuropil of the human entorhinal cortex (EC) at the ultrastructural level. The EC is especially vulnerable in the early stages of Alzheimer’s disease (AD). Our present results show structural differences that may contribute as anatomical basis for the impairment of cognitive functions in AD. Thus, these results may help to understand the relationship between alterations of the synaptic circuits and the cognitive deterioration in AD.
Dynein-dynactin segregate meiotic chromosomes inC. elegansspermatocytes
Authors: Barbosa Daniel J. , Teixeira Vanessa , Duro Joana , Carvalho Ana X. , Gassmann Reto 
Published: October 2020

ABSTRACTThe dynactin complex is an essential co-factor of the microtubule-based motor dynein. Dynein-dynactin have well-documented roles in spindle assembly and positioning duringC. elegansfemale meiosis and embryonic mitosis, while dynein-dynactin’s contribution to male meiosis has not been investigated. Here, we characterize the G33S mutation in DNC-1’s N-terminal microtubule binding domain, which corresponds to G59S in the human dynactin subunit p150/Glued that causes motor neuron disease. In spermatocytes,dnc-1(G33S)delays spindle assembly and penetrantly inhibits anaphase spindle elongation in meiosis I, which prevents homologous chromosome segregation and generates aneuploid sperm with an extra centrosome. Consequently, embryos produced bydnc-1(G33S)hermaphrodites exhibit a high incidence of tetrapolar mitotic spindles, yetdnc-1(G33S)embryos with bipolar spindles proceed through early mitotic divisions without errors in chromosome segregation. Deletion of the DNC-1 N-terminus shows that defective meiosis indnc-1(G33S)spermatocytes is not due to DNC-1’s inability to interact with microtubules. Rather, our results suggest that the DNC-1(G33S) protein, which is aggregation-pronein vitro, is less stable in spermatocytes than the early embryo, resulting in different phenotypic severity in the two dividing tissues. Thus, the unusual hypomorphic nature of thednc-1(G33S)mutant reveals that dynein-dynactin drive meiotic chromosome segregation in spermatocytes and illustrates that the extent to which protein misfolding leads to loss of function can vary significantly between cell types.
Filopodia-based contact stimulated collective migration drives tissue morphogenesis
Authors: Bischoff Maik C. , Lieb Sebastian , Renkawitz-Pohl Renate , Bogdan Sven 
Published: October 2020

AbstractCells migrate collectively to form tissues and organs during morphogenesis. Contact inhibition of locomotion (CIL) drives collective migration by inhibiting lamellipodial protrusions at cell-cell contacts and promoting polarization at the leading edge. Here, we report on a CIL-related collective cell behavior of myotubes that lack lamellipodial protrusions, but instead use filopodia to move as a cohesive cluster in a formin-dependent manner. Genetic, pharmacological and mechanical perturbation analyses reveal essential roles of Rac2, Cdc42 and Rho1 in myotube migration. They differentially control not only protrusion dynamics but also cell-matrix adhesion formation. Here, active Rho1 GTPase localizes at retracting free edge filopodia. Rok-dependent actomyosin contractility does not mediate a contraction of protrusions at cell-cell contacts but likely plays an important role in the constriction of supracellular actin cables.We propose that contact-dependent asymmetry of cell-matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster.
COVID-19: Variant screening, an important step towards precision epidemiology
Authors: Chattopadhyay Amrita , Lu Tzu-Pin , Shih Ching-Yu , Lai Liang-Chuan , Tsai Mong-Hsun , Chuang Eric Y. 
Published: October 2020

AbstractPrecision epidemiology using genomic technologies allows for a more targeted approach to COVID-19 control and treatment at individual and population level, and is the urgent need of the day. It enables identification of patients who may be at higher risk than others to COVID-19-related mortality, due to their genetic architecture, or who might respond better to a COVID-19 treatment. The COVID-19 virus, similar to SARS-CoV, uses the ACE2 receptor for cell entry and employs the cellular serine protease TMPRSS2 for viral S protein priming. This study aspires to present a multi-omics view of how variations in theACE2andTMPRSS2genes affect COVID-19 infection and disease progression in affected individuals. It reports, for both genes, several variant and gene expression analysis findings, through (i) comparison analysis over single nucleotide polymorphisms (SNPs), that may account for the difference of COVID-19 manifestations among global sub-populations; (ii) calculating prevalence of structural variations (copy number variations (CNVs) / insertions), amongst populations; and (iii) studying expression patterns stratified by gender and age, over all human tissues. This work is a good first step to be followed by additional studies and functional assays towards informed treatment decisions and improved control of the infection rate.
Testing the Role of Δ9-Tetrahydrocannabinol During Adolescence as a Gateway Drug: Behavioural, Brain Imaging and Transcriptomic Studies
Authors: Orihuel Javier , Capellán Roberto , Roura-Martínez David , Ucha Marcos , Gómez-Rubio Laura , Valverde Claudia , Casquero-Veiga Marta , Soto-Montenegro María Luisa , Desco Manuel , Vives Marta Oteo , Moragues Marta Ibáñez , Calvo Natalia Magro , Morcillo Miguel Ángel , Ambrosio Emilio , Higuera-Matas Alejandro 
Published: October 2020

ABSTRACTCannabis is widely consumed by adolescents, and is also a potential prior step leading to the use of other drugs later in life (Gateway Hypothesis); however, the evidence for this hypothesis is controversial. This work aimed to increase our understanding of the long-term consequences of adolescent exposure to Δ9-tetrahydrocannabinol (THC) and to test the Gateway Hypothesis, experimentally. We exposed rats of both sexes to THC and studied its effects on reward-related processes, brain morphology (MRI), metabolism (1H-MRS), function (PET) and the transcriptomic profiles of the nucleus accumbens (RNASeq). Lastly, we studied cocaine-induced cellular activation (c-Fos) and cocaine addiction-like behaviours. THC exposure increased Pavlovian to instrumental transfer in males, goal-tracking (regardless of the sex) and impulsivity, but did not affect habit formation. Adolescent THC reduced striatal volume (in females), commissural integrity and ventricular volume. Also, there were lower levels of choline compounds in the cortex of THC-exposed rats and cerebellar hypoactivation in THC-females. THC also modified some of the gene expression programs of the nucleus accumbens, which could contribute to the behavioural features observed. Lastly, THC exposure increased cocaine-induced c-Fos levels in cortical and hypothalamic areas and increased the motivation for cocaine, followed by a higher rebound of use in THC-females after reestablishing low-effort conditions. Critically, acquisition of cocaine self-administration, compulsive seeking, intake under extended access or the incubation of seeking were unaltered. These results suggest that adolescent THC exposure alters psychological and brain development and that the Gateway Hypothesis does not entirely pass the test of preclinical enquiry.
SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance
Authors: Kutter Jasmin S , de Meulder Dennis , Bestebroer Theo M , Lexmond Pascal , Mulders Ard , Fouchier Ron AM , Herfst Sander 
Published: October 2020

AbstractSARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, a newly developed experimental set-up was used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses caused a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmitted efficiently. Serological assays confirmed all virus transmission events. Although the experiments did not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while travelling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for airborne virus transmission between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.