bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and phylogenetic analysis of dissimilatory iodate-reducing bacteria identifies potential niches across the world’s oceans
Authors: Reyes-Umana Victor , Henning Zachary , Lee Kristina , Barnum Tyler P. , Coates John D. 
Published: December 2020

AbstractIodine is oxidized and reduced as part of a biogeochemical cycle that is especially pronounced in the oceans, where the element naturally concentrates. The use of oxidized iodine in the form of iodate (IO3-) as an electron acceptor by microorganisms is poorly understood. Here, we outline genetic, physiological, and ecological models for dissimilatory IO3-reduction to iodide (I-) by a novel estuarine bacterium,Denitromonas iodocresceransstrain IR-12,sp. nov. Our results show that dissimilatory iodate reduction (DIR) by strain IR-12 is molybdenum-dependent and requires an IO3-reductase (idrA) and likely other genes in a mobile cluster with a conserved association across known and predicted DIR microorganisms (DIRM). Based on genetic and physiological data, IO3-is likely reduced to hypoiodous acid (HIO), which rapidly disproportionates into IO3-and iodide (I-), in a respiratory pathway that provides an energy yield equivalent to that of nitrate or perchlorate respiration. Consistent with the ecological niche expected of such a metabolism,idrAis enriched in the metagenome sequence databases of marine sites with a specific biogeochemical signature and diminished oxygen. Taken together, these data suggest that DIRM help explain the disequilibrium of the IO3-:I-concentration ratio above oxygen minimum zones and support a widespread iodine redox cycle mediated by microbiology.
Ticks convert pathogenicCoxiellainto endosymbionts
Authors: Brenner Amanda E. , Muñoz-Leal Sebastián , Sachan Madhur , Labruna Marcelo B. , Raghavan Rahul 
Published: December 2020

ABSTRACTBoth symbiotic and pathogenic bacteria in the family Coxiellaceae cause morbidity and mortality in humans and animals. For instance,Coxiella-like endosymbionts (CLEs) improve the reproductive success of ticks — a major disease vector, whileCoxiella burnetiiis the etiological agent of human Q fever and uncharacterized coxiellae cause infections in both animals and humans. To better understand the evolution of pathogenesis and symbiosis in this group of intracellular bacteria, we sequenced the genome of a CLE present in the soft tickOrnithodoros amblus(CLEOA) and compared it to the genomes of other bacteria in the order Legionellales. Our analyses confirmed that CLEOA is more closely related toC. burnetii, the human pathogen, than to CLEs in hard ticks, and showed that most clades of CLEs contain both endosymbionts and pathogens, indicating that several CLE lineages have evolved independently from pathogenicCoxiella. We also determined that the last common ancestor of CLEOA andC. burnetiiwas equipped to infect macrophages, and that even though HGT contributed significantly to the evolution ofC. burnetii, most acquisition events occurred primarily in ancestors predating the CLEOA-C. burnetiidivergence. These discoveries clarify the evolution ofC. burnetii, which previously was assumed to have emerged when an avirulent tick endosymbiont recently gained virulence factors via HGT. Finally, we identified several metabolic pathways, including heme biosynthesis, that are likely critical to the intracellular growth of the human pathogen but not the tick symbiont, and show that the use of heme analogs is a promising approach to controllingC. burnetiiinfections.
Effect of An Inverted Seated Position with Upper Arm Blood Flow Restriction on Measures of Elbow Flexors Neuromuscular Performance
Authors: Ahmadi Hamid , Herat Nehara , Alizadeh Shahab , Button Duane C , Granacher Urs , Behm David G. 
Published: December 2020

ABSTRACTPurposeThe objective of the investigation was to determine the concomitant effects of upper arm blood flow restriction (BFR) and inversion on elbow flexors neuromuscular responses.MethodsRandomly allocated, 13 volunteers performed four conditions in a within-subject design: rest (control, 1-min upright position without BFR), control (1-min upright with BFR), 1-min inverted (without BFR), and 1-min inverted with BFR. Evoked and voluntary contractile properties, before, during and after a 30-s maximum voluntary contraction (MVC) exercise intervention were examined as well as pain scale.ResultsInversion induced significant pre-exercise intervention decreases in elbow flexors MVC (21.1%,,p=0.02) and resting evoked twitch (29.4%,,p=0.03) forces. The 30-s MVC induced significantly greater pre- to post-test decreases in potentiated twitch force (,p<0.0009) during inversion (↓75%) than upright (↓65.3%) conditions. Overall, BFR decreased MVC force 4.8% (,p=0.05). For upright position, BFR induced 21.0% reductions in M-wave amplitude (,p=0.04). There were no significant differences for electromyographic activity or voluntary activation as measured with the interpolated twitch technique. For all conditions, there was a significant increase in pain scale between the 40-60 s intervals and post-30-s MVC (upright<inversion, and without BFR<BFR).ConclusionThe concomitant application of inversion with elbow flexors BFR only amplified neuromuscular performance impairments to a small degree. Individuals who execute forceful contractions when inverted or with BFR should be cognizant that force output may be impaired.
Placebo analgesia does not reduce empathy for naturalistic depictions of others’ pain in a somatosensory specific way
Authors: Hartmann Helena , Riva Federica , Rütgen Markus , Lamm Claus 
Published: December 2020

AbstractEmpathy for pain involves the affective-motivational and sensory-discriminative pain network. The shared representations account postulates that sharing another’s pain recruits underlying brain functions also engaged during first-hand pain. Critically, causal evidence for this has only been shown for affective pain processing, while the specific contribution of one’s own somatosensory system to empathy remains controversial. Experimental paradigms used in previous studies did not a) direct attention towards a specific body part or b) employed naturalistic depictions of others’ pain, which could explain the absence of somatosensory effects. In this preregistered fMRI study, we thus aimed to test whether a causal manipulation of first-hand pain affects processing of empathy in a somatotopically- matched manner. Forty-five participants underwent a placebo analgesia induction in the right hand and observed pictures of right vs. left hands in pain. We found neither behavioral nor neural evidence for laterality-specific modulation of empathy for pain. However, exploratory analyses revealed a general effect of the placebo on empathy, and higher brain activity in bilateral anterior insula when viewing others’ hands in pain corresponding to one’s own placebo hand. These results refine our knowledge regarding the mechanisms underlying empathy for pain by specifying the influence of first-hand pain on empathic responding.
Heartbeat and Somatosensory Perception
Authors: Al Esra , Iliopoulos Fivos , Nikulin Vadim V. , Villringer Arno 
Published: December 2020

AbstractOur perception of the external world is influenced by internal bodily signals. For example, we recently showed that timing of stimulation along the cardiac cycle and spontaneous fluctuations of heartbeat-evoked potential (HEP) amplitudes influence somatosensory perception and the associated neural processing (Al et al., 2020). While cardiac phase affected detection sensitivity and late components of the somatosensory-evoked potentials (SEPs), HEP amplitudes affected detection criterion and both early and late SEP components. In a new EEG study, we investigate whether these results are replicable in a modified paradigm, which includes two succeeding temporal intervals. Only in one of these intervals, subjects received a weak electrical finger stimulation and then performed a yes/no and two-interval forced-choice detection task. Our results confirm the previously reported cardiac cycle and prestimulus HEP effects on somatosensory perception and evoked potentials. In addition, we obtain two new findings: A source analysis in these two studies shows that the increased likelihood of conscious perception goes along with HEP fluctuations in parietal and posterior cingulate regions, known to play important roles in interoceptive processes. Furthermore, HEP amplitudes are shown to decrease when subjects engage in the somatosensory task compared to their resting state condition. Our findings are consistent with the view that HEP amplitudes are a marker of interoceptive (versus exteroceptive) attention and provide a neural underpinning for this view.
Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation
Authors: Austin Sophie H. L. , Harris Lachlan , Paun Oana , Rigo Piero , Guillemot François , Urbán Noelia 
Published: December 2020

AbstractAdult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage and has been shown to promote the proliferation of intermediate progenitor cells. However, whether it has a direct role in the regulation of NSCs still remains unclear. Here we used Wnt/β-catenin reporters and transcriptomic data fromin vivoandin vitromodels to show that both active and quiescent adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed neuronal differentiation of active NSCs and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, we found that inhibiting NSCs response to Wnt, by conditionally deleting β-catenin, did not affect their activation or maintenance of their stem cell characteristics. Together, our results indicate that whilst NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which could reconcile some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs.
Investigating expression of a human optimizedcas9transgene inNeurospora crassa
Authors: Burrell Natalie , Rhoades Nicholas A. , Boyd Amy , Mierendorf Jim , Yusifov Aykhan , Harvey Austin , Edwards Kevin , Vogel Laura , Hammond Thomas M. 
Published: December 2020

ABSTRACTThe CRISPR-associated Cas9 enzyme is used in molecular biology to engineer the genomes of a wide range of organisms. While Cas9 can be injected or transfected into a target cell to achieve the desired goal, there are situations where stable expression of Cas9 within a target organism is preferable. Here, we show that the model filamentous fungusNeurospora crassais recalcitrant to heterologous expression of a human-optimized version ofStreptococcus pyogenes cas9. Furthermore, partial optimization ofcas9by synonymous codon exchange failed to improve its expression in the fungus. Finally, we show that transgene expression can be detected whencas9Hssequences are placed in the 3’ UTR regions of transgene-derived mRNAs, but not when the same sequences are in the translated part of the transgene-derived mRNA. This finding suggests that the primary obstacle to highcas9Hsexpression levels inN. crassais translational in nature.
Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence
Authors: Bullen Georgia , Galson Jacob D. , Villar Pedro , Moreels Lien , Ledsgaard Line , Mattiuzzo Giada , Hall Gareth , Bentley Emma M. , Masters Edward W. , Tang David , Millett Sophie , Tongue Danielle , Brown Richard , Diamantopoulos Ioannis , Parthiban Kothai , Tebbutt Claire , Leah Rachael , Chaitanya Krishna , Pazeraitis Deividas , Surade Sachin B. , Ashiru Omodele , Crippa Lucia , Cowan Richard , Bowler Matthew W. , Campbell Jamie I. , Lee Wing-Yiu Jason , Carr Mark D. , Matthews David , Pfeffer Paul , Hufton Simon E. , Sawmynaden Kovilen , Osbourn Jane , McCafferty John , Karatt-Vellatt Aneesh 
Published: December 2020

AbstractPassive immunisation using monoclonal antibodies will play a vital role in the fight against COVID-19. Until now, the majority of anti-SARS-CoV-2 antibody discovery efforts have relied on screening B cells of patients in the convalescent phase. Here, we describe deep-mining of the antibody repertoires of hospitalised COVID-19 patients using a combination of phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralising antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded potent neutralising antibodies with distinct mechanisms of action, including the identification of a novel non-ACE2 receptor blocking antibody that is not expected to be affected by any of the major viral variants reported. The study highlighted the presence of potent neutralising antibodies with near germline sequences within both the IgG and IgM pools at early stages of infection. Furthermore, we highlight a highly convergent antibody response with the same sequences occurring both within this study group and also within the responses described in previously published anti-SARS-CoV-2 studies.
Design of Specific Primer Set for Detection of B.1.1.7 SARS-CoV-2 Variant using Deep Learning
Authors: Lopez-Rincon Alejandro , Perez-Romero Carmina A. , Tonda Alberto , Mendoza-Maldonado Lucero , Claassen Eric , Garssen Johan , Kraneveld Aletta D. 
Published: December 2020

ABSTRACTThe SARS-CoV-2 variant B.1.1.7 lineage, also known as clade GR from Global Initiative on Sharing All Influenza Data (GISAID), Nextstrain clade 20B, or Variant Under Investigation in December 2020 (VUI – 202012/01), appears to have an increased transmissability in comparison to other variants. Thus, to contain and study this variant of the SARS-CoV-2 virus, it is necessary to develop a specific molecular test to uniquely identify it. Using a completely automated pipeline involving deep learning techniques, we designed a primer set which is specific to SARS-CoV-2 variant B.1.1.7 with >99% accuracy, starting from 8,923 sequences from GISAID. The resulting primer set is in the region of the synonymous mutation C16176T in the ORF1ab gene, using the canonical sequence of the variant B.1.1.7 as a reference. Furtherin-silicotesting shows that the primer set’s sequences do not appear in different viruses, using 20,571 virus samples from the National Center for Biotechnology Information (NCBI), nor in other coronaviruses, using 487 samples from National Genomics Data Center (NGDC). In conclusion, the presented primer set can be exploited as part of a multiplexed approach in the initial diagnosis of Covid-19 patients, or used as a second step of diagnosis in cases already positive to Covid-19, to identify individuals carrying the B.1.1.7 variant.
Genome-wide binding analyses of HOXB1 revealed a novel DNA binding motif associated with gene repression
Authors: Singh Narendra Pratap , De Kumar Bony , Paulson Ariel , Parrish Mark , Scott Carrie , Zhang Ying , Florens Laurence , Krumlauf Robb 
Published: December 2020

AbstractKnowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in ES cells differentiated into neural fates. Unexpectedly, only a small number of HOXB1 bound regions (7%) correlate with binding of the known HOX cofactors PBX and MEIS. In contrast, 22% of the HOXB1 binding peaks display co-occupancy with the transcriptional repressor REST. Analyses revealed that co-binding of HOXB1 with PBX correlates with active histone marks and high levels of expression, while co-occupancy with REST correlates with repressive histone marks and repression of the target genes. Analysis of HOXB1 bound regions uncovered enrichment of a novel 15 base pair HOXB1 binding motifHB1RE(HOXB1responseelement).In vitrotemplate binding assays showed that HOXB1, PBX1 and MEIS can bind to this motif.In vivo,this motif is sufficient to direct expression of a reporter gene and over-expression of HOXB1 selectively represses this activity. Our analyses suggest that HOXB1 has evolved an association with REST in gene regulation and the novelHB1REmotif contributes to HOXB1 function in part through a repressive role in gene expression.
Homology modeling and functional characterization of multidrug effluxor Mta protein from Bacillus Atrophaeus: An explanatory insilico approach
Authors: Rahman Mohammad Rejaur , Chowdhury Ishtiak Malique , Banik Anik , Sajib Emran Hossain 
Published: December 2020

AbstractPhenotypically similar to B. subtilis, Bacillus atrophaeus is a Gram-positive, aerobic, spore-forming bacteria. It is a black-pigmented bacterial genus. Therefore, it is of interest to study the uncharacterized proteins in the genome. For a detailed computational sequence-structure-function analysis using available data and resources, an uncharacterized protein Mta (AKL87074.1) in the genome was selected. In this study, attempts were made to study the physicochemical properties, predict secondary structure, modeling the 3-D protein, pocket identification, protein-protein interaction and phylogenetic analysis of Mta protein. The predicted active site using CASTp is analyzed for understanding their multidrug resistance function. Because Mta is a MerR family member, these investigations on these functional aspects could lead us for better understanding of antibiotic resistance phenomenon.
SARS-CoV-2 highly conserved s2m element dimerizes via a kissing complex and interacts with host miRNA-1307-3p
Authors: Imperatore Joshua A. , Cunningham Caylee L. , Pellegrene Kendy A. , Brinson Robert G. , Marino John P. , Evanseck Jeffrey D. , Mihailescu Mihaela Rita 
Published: December 2020

ABSTRACTThe ongoing COVID-19 pandemic highlights the necessity for a more fundamental understanding of the coronavirus life cycle. The causative agent of the disease, SARS-CoV-2, is being studied extensively from a structural standpoint in order to gain insight into key molecular mechanisms required for its survival. Contained within the untranslated regions of the SARS-CoV-2 genome are various conserved stem-loop elements that are believed to function in RNA replication, viral protein translation, and discontinuous transcription. While the majority of these regions are variable in sequence, a 41-nucleotide s2m element within the 3’ UTR is highly conserved among coronaviruses and three other viral families. In this study, we demonstrate that the s2m element of SARS-CoV-2 dimerizes by forming an intermediate homodimeric kissing complex structure that is subsequently converted to a thermodynamically stable duplex conformation. This process is aided by the viral nucleocapsid protein, potentially indicating a role in mediating genome dimerization. Furthermore, we demonstrate that the s2m element interacts with multiple copies of host cellular miRNA-1307-3p. Taken together, our results highlight the potential significance of the dimer structures formed by the s2m element in key biological processes and implicate the motif as a possible therapeutic drug target for COVID-19 and other coronavirus-related diseases.
Large palindromes on the primate X Chromosome are preserved by natural selection
Authors: Jackson Emily K. , Bellott Daniel W. , Cho Ting-Jan , Skaletsky Helen , Hughes Jennifer F. , Pyntikova Tatyana , Page David C. 
Published: December 2020

ABSTRACTMammalian sex chromosomes carry large palindromes that harbor protein-coding gene families with testis-biased expression. However, there are few known examples of sex-chromosome palindromes conserved between species. We identified 26 palindromes on the human X Chromosome, constituting more than 2% of its sequence, and characterized orthologous palindromes in the chimpanzee and the rhesus macaque using a clone-based sequencing approach that incorporates full-length nanopore reads. Many of these palindromes are missing or misassembled in the current reference assemblies of these species’ genomes. We find that 12 human X palindromes have been conserved for at least 25 million years, with orthologs in both chimpanzee and rhesus macaque. Insertions and deletions between species are significantly depleted within the X palindromes’ protein-coding genes compared to their non-coding sequence, demonstrating that natural selection has preserved these gene families. Unexpectedly, the spacers that separate the left and right arms of palindromes are a site of localized structural instability, with 7 of 12 conserved palindromes showing no spacer orthology between human and rhesus macaque. Analysis of the 1000 Genomes Project dataset revealed that human X-palindrome spacers are enriched for deletions relative to arms and flanking sequence, including a common spacer deletion that affects 13% of human X Chromosomes. This work reveals an abundance of conserved palindromes on primate X Chromosomes, and suggests that protein-coding gene families in palindromes (most of which remain poorly characterized) promote X-palindrome survival in the face of ongoing structural instability.
Meta-analysis of virus-induced host gene expression reveals unique signatures of immune dysregulation induced by SARS-CoV-2
Authors: Kuchi Srikeerthana , Gu Quan , Palmarini Massimo , Wilson Sam J , Robertson David L 
Published: December 2020

AbstractThe clinical outcome of COVID-19 has an extreme age, genetic and comorbidity bias that is thought to be driven by an impaired immune response to SARS-CoV-2, the causative agent of the disease. The unprecedented impact of COVID-19 on global health has resulted in multiple studies generating extensive gene expression datasets in a relatively short period of time. In order to better understand the immune dysregulation induced by SARS-CoV-2, we carried out a meta-analysis of these transcriptomics data available in the published literature. Datasets included both those available from SARS-CoV-2 infected cell linesin vitroand those from patient samples. We focused our analysis on the identification of viral perturbed host functions as captured by co-expressed gene module analysis. Transcriptomics data from lung biopsies and nasopharyngeal samples, as opposed to those available from other clinical samples and infected cell lines, provided key signatures on the role of the host’s immune response on COVID-19 pathogenesis. For example, severity of infection and patients’ age are linked to the absence of stimulation of the RIG-I-like receptor signaling pathway, a known critical immediate line of defense against RNA viral infections that triggers type-I interferon responses. In addition, co-expression analysis of age-stratified transcriptional data provided evidence that signatures of key immune response pathways are perturbed in older COVID-19 patients. In particular, dysregulation of antigen-presenting components, down-regulation of cell cycle mechanisms and signatures of hyper-enriched monocytes were strongly correlated with the age of older individuals infected with SARS-CoV-2. Collectively, our meta-analysis highlights the ability of transcriptomics and gene-module analysis of aggregated datasets to aid our improved understanding of the host-specific disease mechanisms underpinning COVID-19.