bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Deubiquitylase Ubp15 Couples Transcription to mRNA Export
Authors: Eyboulet Fanny , Jeronimo Célia , Côté Jacques , Robert François 
Published: August 2020

ABSTRACTThe nuclear export of messenger RNAs (mRNAs) is intimately coupled to their synthesis. pre-mRNAs assemble into dynamic ribonucleoparticles as they are being transcribed, processed and exported. The role of ubiquitylation in this process is increasingly recognized as the ubiquitylation of many key players have been shown to affect mRNA nuclear export. While a few E3 ligases have been shown to regulate nuclear export, evidence for deubiquitylases is currently lacking. Here, we identified the deubiquitylase Ubp15 as a regulator of nuclear export inSaccharomyces cerevisiae. Ubp15 interacts both with RNA polymerase II and with the nuclear pore complex, and its deletion reverts the nuclear export defect of mutants of the E3 ligase Rsp5. The deletion ofUBP15leads to hyper-ubiquitylation of the main nuclear export receptor Mex67 and affects its association with THO, a complex coupling transcription to mRNA processing and involved in the recruitment of mRNA export factors to nascent transcripts. Collectively, our data support a role for Ubp15 in coupling transcription to mRNA export.
Nutrients: trace metals, micronutrients, oestrogen and B-vitamin content of Osun River: A River that runs southwestern Nigeria into the Atlantic Gulf of Guinea
Authors: Afolabi-Balogun N.B. , Oni-Babalola O.A. , Adeleke I.I. , Oseni F.A. , Bello R.H. , Bashir M. , Raji B.A 
Published: August 2020

AbstractOsun-Osogbo Grove has a long history of healing and therapeutic claims by adherent believers, in spite of advancement in medicine. Scientists made attempts at investigating the biodiversity of the Grove, till date, there has not been convergence point between science and these indigenous beliefs. This study identified the presence of therapeutic agents in the water of Osun-Osogbo River, paying attention to at least six parameters; vitamin, phosphate, nitrate, amino acid, hormone and trace metal. Water samples were taken from two different sites during pre, during and post raining sessions (April 2017 - September 2019) were analysed using High Performance Liquid Chromatography (HPLC), Gas Chromatography Mass Spectroscopy (GC-MS) and Atomic Absorption Spectrometer (AAS). Trace metal analysis revealed an average of 0.009-0.079 mg/Kg Zinc from site one and lower in site two. The mean value of manganese at both sites was virtually the same at 0.018-0.313 mg/kg, aluminum content was 0.045-0.179mg/Kg at site one, 0.050-0.192mg/kg at site two, cobalt was 0.024 mg/kg at site one, 0.026 mg/kg at site two while nickel was 0.006 mg/kg and 0.004 mg/kg for site one and two respectively. HPLC analysis shows mean Methionine content at both sites is higher than the FDA (56.6 ug/mL); site one had 74.41 ug/mL while site two had 57.11 ug/mL The mean values of two water-soluble vitamins; Thiamine (B1) was 3.758 mg/Kg and 2.355 mg/Kg while Pyridoxine (B6) was 0.108 mg/Kg and 0.072 mg/Kg at site one and two. GCMS analysis of steroidal content revealed values below lowest observed effect level (LOEL), testosterone (4.8 ng/L) and estrogen (2.4 ng/L) were still elevated while ethinylestradiol and estriol were ≥1.5 ng/L. Summarily, site one the major part for spiritual activities showed higher essential nutrient contents than site two which support the enrichment and potential therapeutic properties of the Osun river water. However, further scientific research is required to ensure that these therapeutic potentials supersede the toxicological effect.
A molecular timescale for the origin of red algal-derived plastids
Authors: Strassert Jürgen F. H. , Irisarri Iker , Williams Tom A. , Burki Fabien 
Published: August 2020

AbstractIn modern oceans, eukaryotic phytoplankton is dominated by lineages with red algal-derived plastids such as diatoms, dinoflagellates, and coccolithophores. These lineages and countless others representing a huge diversity of forms and lifestyles all belong to four algal groups: cryptophytes, ochrophytes, haptophytes, and myzozoans. Despite the ecological importance of these groups, we still lack a comprehensive understanding of their evolution and how they obtained their plastids. Over the last years, new hypotheses have emerged to explain the acquisition of red algal-derived plastids by serial endosymbiosis, but the chronology of these putative independent plastid acquisitions remains untested. Here, we have established a timeframe for the origin of red algal-derived plastids under scenarios of serial endosymbiosis, using a taxon- and gene-rich phylogenomic dataset combined to Bayesian molecular clock analyses. We find that the hypotheses of serial endosymbiosis are chronologically possible, as the stem lineages of all red plastid-containing groups overlapped in time. This period in the Meso- and Neoproterozoic Eras set the stage for the later expansion to dominance of red algal-derived primary production in the contemporary oceans, which has profoundly altered the global geochemical and ecological conditions of the Earth.
Circuit reorganization in theDrosophilamushroom body calyx accompanies memory consolidation
Authors: Baltruschat Lothar , Ranft Philipp , Prisco Luigi , Lauritzen J. Scott , Fiala André , Bock Davi D. , Tavosanis Gaia 
Published: August 2020

SummaryThe capacity of utilizing past experience to guide future action is a fundamental and conserved function of the nervous system. Associative memory formation initiated by the coincident detection of a conditioned stimulus (CS, e.g. odour) and an unconditioned stimulus (US, e.g. sugar reward) can lead to a short-lived memory trace (STM) within distinct circuits [1-5]. Memories can be consolidated into long-term memories (LTM) through processes that are not fully understood, but depend onde-novoprotein synthesis [6, 7], require structural modifications within the involved neuronal circuits and might lead to the recruitment of additional ones [8-17]. Compared to modulation of existing connections, the reorganization of circuits affords the unique possibility of sampling for potential new partners [18-20]. Nonetheless, only few examples of rewiring associated with learning have been established thus far [14, 21-24]. Here, we report that memory consolidation is associated with the structural and functional reorganization of an identified circuit in the adult fly brain. The formation and retrieval of olfactory associative memories inDrosophilarequires the mushroom body (MB) [25]. We identified the individual synapses of olfactory projection neurons (PNs) that deliver a conditioned odour to the MB and reconstructed the complexity of the microcircuit they form. Combining behavioural experiments with high-resolution microscopy and functional imaging, we demonstrated that the consolidation of appetitive olfactory memories closely correlates with an increase in the number of synaptic complexes formed by the PNs that deliver the conditioned stimulus and their postsynaptic partners. These structural changes result in additional functional synaptic connections.
In Silico Modeling of Virus Particle Propagation and Infectivity along the Respiratory Tract: A Case Study for SARS-COV-2
Authors: Vimalajeewa Dixon , Balasubramaniam Sasitharan , Berry Donagh P. , Barry Gerald 
Published: August 2020

AbstractRespiratory viruses including Respiratory syncytial virus (RSV), influenza virus and cornaviruses such as Middle Eastern respiratory virus (MERS) and SARS-CoV-2 infect and cause serious and sometimes fatal disease in thousands of people annually. It is critical to understand virus propagation dynamics within the respiratory system because new insights will increase our understanding of virus pathogenesis and enable infection patterns to be more predictablein vivo, which will enhance targeting of vaccines and drug delivery. This study presents a computational model of virus propagation within the respiratory tract network. The model includes the generation network branch structure of the respiratory tract, biophysical and infectivity properties of the virus, as well as air flow models that aid the circulation of the virus particles. The model can also consider the impact of the immune response aim to inhibit virus replication and spread. The model was applied to the SARS-CoV-2 virus by integrating data on its life-cycle, as well as density of Angiotensin Converting Enzyme (ACE2) expressing cells along the respiratory tract network. Using physiological data associated with the respiratory rate and virus load that is inhaled, the model can improve our understanding of the concentration and spatiotemporal dynamics of virus.
Optogenetic activation of nonhuman primate cortical and subcortical brain circuits highlights detection capabilities of MEG source imaging
Authors: Alberto GE , Stapleton-Kotloski JR , Klorig DC , Rogers ER , Constantinidis C , Daunais JB , Godwin DW 
Published: August 2020

ABSTRACTMagnetoencephalography (MEG) measures neuromagnetic activity with high temporal, and theoretically, high spatial resolution. However, the ability of magnetic source imaging (MSI) to localize deep sources is uncertain. We developed an experimental platform combining MEG-compatible optogenetic techniques in non-human primates (NHPs) to test the ability of MEG/MSI to image deep signals. We demonstrate localization of optogenetically-evoked signals to known sources in the superficial arcuate sulcus of cortex and in CA3 of hippocampus at a resolution of 750 µm3. In response to stimulation of arcuate sulcus and hippocampus, we detected activation in subcortical and thalamic structures, or extended temporal networks, respectively. This is the first demonstration of accurate localization of deep sources within an intact brain using a novel combination of optogenetics with MEG/MSI. This approach is suitable for exploring causal relationships between discrete brain regions through precise optogenetic control and simultaneous whole brain recording.
Dynamics of mechanically coupled hair-cell bundles of the inner ear
Authors: Roongthumskul Y. , Faber J. , Bozovic D. 
Published: August 2020

ABSTRACTThe high sensitivity and effective frequency discrimination of sound detection performed by the auditory system rely on the dynamics of a system of hair cells. In the inner ear, these acoustic receptors are primarily attached to an overlying structure which provides mechanical coupling between the hair bundles. While the dynamics of individual hair bundles have been extensively investigated, the influence of mechanical coupling on the motility of the system of bundles remains underdetermined. We developed a technique of mechanically coupling two active hair bundles, enabling us to probe the dynamics of the coupled system experimentally. We demonstrated that the coupling could enhance the coherence of hair bundles’ spontaneous oscillation as well as their phase-locked response to sinusoidal stimuli, at the calcium concentration in the surrounding fluid near the physiological level. The empirical data were consistent with numerical results from a model of two coupled nonisochronous oscillators, each displaying a supercritical Hopf bifurcation. The model revealed that weak coupling can poise the system of unstable oscillators closer to the bifurcation by a shift in the critical point. In addition, the dynamics of strongly coupled oscillators far from criticality suggested that individual hair bundles may be regarded as nonisochronous oscillators. An optimal degree of nonisochronicity was required for the observed tuning behavior in the coherence of autonomous motion of the coupled system.STATEMENT OF SIGNIFICANCEHair cells of the inner ear transduce acoustic energy into electrical signals via a deflection of hair bundles. Unlike a passive mechanical antenna, a free-standing hair bundle behaves as an active oscillator that can sustain autonomous oscillations, as well as amplify a low-level stimulus. Hair bundles under physiological conditions are elastically coupled to each other via an extracellular matrix. Therefore, the dynamics of coupled nonlinear oscillators underlie the performance of the peripheral auditory system. Despite extensive theoretical investigations, there are limited experimental evidence that support the significance of coupling on hair bundle motility. We develop a technique to mechanically couple hair bundles and demonstrate the benefits of coupling on hair bundle spontaneous motility.
Morphometry of SARS-CoV and SARS-CoV-2 particles in ultrathin plastic sections of infected Vero cell cultures
Authors: Laue Michael , Kauter Anne , Hoffmann Tobias , Möller Lars , Michel Janine , Nitsche Andreas 
Published: August 2020

AbstractSARS-CoV-2 is the causative of the COVID-19 disease, which has spread pandemically around the globe within a few months. It is therefore necessary to collect fundamental information about the disease, its epidemiology and treatment, as well as about the virus itself. While the virus has been identified rapidly, detailed ultrastructural analysis of virus cell biology and architecture is still in its infancy. We therefore studied the virus morphology and morphometry of SARS-CoV-2 in comparison to SARS-CoV as it appears in Vero cell cultures by using conventional thin section electron microscopy and electron tomography. Both virus isolates, SARS-CoV Frankfurt 1 and SARS-CoV-2 Italy-INMI1, were virtually identical at the ultrastructural level and revealed a very similar particle size distribution with a median of about 100 nm without spikes. Maximal spike length of both viruses was 23 nm. The number of spikes per virus particle was about 30% higher in the SARS-CoV than in the SARS-CoV-2 isolate. This result complements a previous qualitative finding, which was related to a lower productivity of SARS-CoV-2 in cell culture in comparison to SARS-CoV.
Mechanisms of signalling-memory governing progression through the eukaryotic cell cycle
Authors: Novák Béla , Tyson John J 
Published: August 2020

AbstractAs cells pass through each replication-division cycle, they must be able to postpone further progression if they detect any threats to genome integrity, such as DNA damage or misaligned chromosomes. Once a ‘decision’ is made to proceed, the cell unequivocally enters into a qualitatively different biochemical state, which makes the transitions from one cell cycle phase to the next switch-like and irreversible. Each transition is governed by a unique signalling network; nonetheless, they share a common characteristic of bistable behaviour, a hallmark of molecular memory devices. Comparing the cell cycle signalling mechanisms acting at the Restriction Point, G1/S, G2/M and meta-to-anaphase transitions, we deduce a generic network motif of coupled positive and negative feedback loops underlying each transition.
Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms
Authors: Bofill-De Ros Xavier , Luke Brian , Guthridge Robert , Mudunuri Uma , Loss Michael , Gu Shuo 
Published: August 2020

ABSTRACTMicroRNAs (miRNAs) function as master regulators of gene expression in many physiological and pathological conditions including cancer. Sequence variants or isoforms (isomiRs) can account for between 40 to 60% of total miRNA counts, yet despite this overwhelming abundance, their function continues to be debated. Recent studies demonstrate that certain isomiRs can regulate unique sets of target mRNAs by altering their seed sequence or stabilizing 3’ pairing, while others are decay intermediates indicating an active miRNA turnover. Given their short sequence length and high heterogeneity, mapping isomiRs can be challenging; without adequate depth and data aggregation, low frequency events are often disregarded. To address these challenges, we present theTumorIsomiREncyclopedia (TIE): a dynamic database of isomiRs from over 10,000 adult and pediatric tumor samples in The Cancer Genome Atlas (TCGA) and The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects. A key novelty of TIE is its ability to annotate heterogeneous isomiR sequences and aggregate the variants obtained across all samples and datasets. The database provides annotation of templated and non-templated nucleotides as well as other advanced analysis. All data can be browsed online or downloaded as simple spreadsheets. Here we show analysis of isomiRs of miR-21 and miR-30a to demonstrate the utility of TIE. TIE search engine and data are hosted athttps://isomir.ccr.cancer.gov/.
Temporal landscape of mutation accumulation in SARS-CoV-2 genomes from Bangladesh: possible implications from the ongoing outbreak in Bangladesh
Authors: Saha Otun , Shatadru Rokaiya Nurani , Rakhi Nadira Naznin , Islam Israt , Hossain Md. Shahadat , Rahaman Md. Mizanur 
Published: August 2020

SummaryAlong with intrinsic evolution, adaptation to selective pressure in new environments might have resulted in the circulatory SARS-CoV-2 strains in response to the geoenvironmental conditions of a country and the demographic profile of its population. Thus the analysis of genomic mutations of these circulatory strains may give an insight into the molecular basis of SARS-CoV-2 pathogenesis and evolution favoring the development of effective treatment and containment strategies. With this target, the current study traced the evolutionary route and mutational frequency of 198 Bangladesh originated SARS-CoV-2 genomic sequences available in the GISAID platform over a period of 13 weeks as of 14 July 2020. The analyses were performed using MEGA 7, Swiss Model Repository, Virus Pathogen Resource and Jalview visualization. Our analysis identified that majority of the circulating strains in the country belong to B and/or L type among cluster A to Z and strikingly differ from both the reference genome and the first sequenced genome from Bangladesh. Mutations in Nonspecific protein 2 (NSP2), NSP3, RNA dependent RNA polymerase (RdRp), Helicase, Spike, ORF3a, and Nucleocapsid (N) protein were common in the circulating strains with varying degrees and the most unique mutations(UM) were found in NSP3 (UM-18). But no or limited changes were observed in NSP9, NSP11, E (Envelope), NSP7a, ORF 6, and ORF 7b suggesting the possible conserved functions of those proteins in SARS-CoV-2 propagation. However, along with D614G mutation, more than 20 different mutations in the Spike protein were detected basically in the S2 domain. Besides, mutations in SR-rich region of N protein and P323L in RDRP were also present. However, the mutation accumulation showed an association with sex and age of the COVID-19 positive cases. So, identification of these mutational accumulation patterns may greatly facilitate drug/ vaccine development deciphering the age and the sex dependent differential susceptibility to COVID-19.
Comparative Transcriptomics of heads and tails betweenSteinernema carpocapsaeandCaenorhabditis elegans
Authors: Rodriguez Isaryhia Maya , Clague Lorrayne Serra , McGill Cassandra Joan , Rodriguez Bryan , Mortazavi Ali 
Published: August 2020

AbstractSteinernema nematodeshave been widely studied for insect infection and mutualism, but little is known about the patterns of gene expression along the body of these worms or how these compare to the model organismCaenorhabditis elegans. Here we perform the first comparative analysis between the heads and tail regions ofSteinernema carpocapsaeandC. elegansInfective Juveniles (IJs)/dauers and young adults using single-worm RNA-seq. While we find overall agreement in gene expression there were several sets of genes with substantial differences between the two species. Gene expression in theS. carpocapsaefemale compared to theC. eleganshermaphrodite heads and tails revealed differences in metabolism, aging, and determination of lifespan. Young adult male heads and tails showed major differences in developmental related processes such as morphogenesis as well as neuronal development and signaling. We also found head- and tail-specific gene expression differences betweenS. carpocapsaeIJs andC. elegansdauers for genes related to growth and development as well as neuronal signaling and activity. This study is one of the first comparative transcriptomic analyses of body parts between distantly related species of nematodes and provides insight into both the highly conserved and genetically distinctive characteristics of both species.
COVID-19 and Cholinergic Anti-inflammatory Pathway:In silicoIdentification of an Interaction between α7 Nicotinic Acetylcholine Receptor and the Cryptic Epitopes of SARS-CoV and SARS-CoV-2 Spike Glycoproteins
Authors: Lagoumintzis George , Chasapis Christos T. , Alexandris Nikolaos , Tzartos Socrates , Eliopoulos Elias , Farsalinos Konstantinos , Poulas Konstantinos 
Published: August 2020

ABSTRACTSARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. The observation of a low prevalence of smokers among hospitalized COVID-19 patients has led to the development of a hypothesis that nicotine could have protective effects by enhancing the cholinergic anti-inflammatory pathway. Based on clinical data and on modelling and docking experiments we have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a “toxin-like” epitope on the Spike Glycoprotein, with homology to a sequence of a snake venom toxin. We here present that this epitope coincides with the well-described cryptic epitope for the human antibody CR3022 and with the epitope for the recently described COVA1-16 antibody. Both antibodies are recognizing neighboring epitopes, are not interfering with the ACE2 protein and are not able to inhibit SARS-CoV and SARS-CoV-2 infections. In this study we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike Glycoproteins, at their open or closed conformations, with the molecular model of the human α7 nAChR. We found that the interface of all studied protein complexes involves a large part of the “toxin-like” sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human α7 nAChR.