bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients
Authors: Andres Cristina , Garcia-Cehic Damir , Gregori Josep , Piñana Maria , Rodriguez-Frias Francisco , Guerrero-Murillo Mercedes , Esperalba Juliana , Rando Ariadna , Goterris Lidia , Codina Maria Gema , Quer Susanna , Martín Maria Carmen , Campins Magda , Ferrer Ricard , Almirante Benito , Esteban Juan Ignacio , Pumarola Tomás , Antón Andrés , Quer Josep 
Published: June 2020

ABSTRACTThe SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2Sgene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We propose that natural selection has favored a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.
Mutations inBBS2Cause Apparent Nonsyndromic Retinitis Pigmentosa
Authors: DeBenedictis Meghan , Fogerty Joseph , Pauer Gayle , Chiang John , Hagstrom Stephanie A. , Traboulsi Elias I. , Perkins Brian D. 
Published: June 2020

AbstractPurposeTo identify and functionally test the causative mutations in theBBS2gene in a family presenting with retinitis pigmentosa and infertility and to generate abbs2−/−mutant zebrafish.MethodsA female proband and her male sibling were clinically evaluated and genetic testing with targeted next-generation sequencing was performed. Mutations were verified by Sanger sequencing. Protein localization was examined by transient expression and immunocytochemistry in cultured HEK-293T cells. Mutations in the zebrafishbbs2gene were generated by CRISPR/Cas9 and retinal phenotypes were examined by immunohistochemistry.ResultsThe proband and her brother exhibited reduced visual fields, retinal degeneration, and bone spicule deposits, consistent with retinitis pigmentosa. The brother also reported symptoms consistent with infertility. Compound heterozygous mutations in theBBS2gene; namely NM_031885.4 (BBS2):c.823C>T (p.R275X) and NM_031885.4 (BBS2):c.401C>G (p.P134R), were identified in the proband and her brother. Both mutations interfered with ciliary localization of Bbs2 in cell culture. Mutation of the zebrafishbbs2gene resulted in progressive cone degeneration and rhodopsin mislocalization.ConclusionMissense mutations ofBBS2leads to non-syndromic retinitis pigmentosa, but not Bardet-Biedl Syndrome, even though Bbs2 fails to localize to cilia. In zebrafish, the complete loss ofbbs2results in cone degeneration and ciliopathy phenotypes, indicating a requirement for Bbs2 in photoreceptor survival.
TGN/EE SNARE protein SYP61 is ubiquitinated and required for carbon/nitrogen-nutrient responses in Arabidopsis
Authors: Hasegawa Yoko , Reyes Thais Huarancca , Uemura Tomohiro , Fujimaki Akari , Luo Yongming , Morita Yoshie , Saeki Yasushi , Baral Anirban , Maekawa Shugo , Yasuda Shigetaka , Mukuta Koki , Fukao Yoichiro , Tanaka Keiji , Nakano Akihiko , Bhalerao Rishikesh P. , Sato Takeo , Yamaguchi Junji 
Published: June 2020

AbstractUbiquitination is a post-translational modification with reversible attachment of the small protein ubiquitin, which is involved in numerous cellular processes including membrane trafficking. For example, ubiquitination of cargo proteins is known to regulate their subcellular dynamics, and plays important roles in plant growth and stress adaptation. However, the regulatory mechanism of the trafficking machinery components remains elusive. Here, we report Arabidopsistrans-Golgi network/early endosome (TGN/EE) localized solubleN-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein SYP61 as a novel ubiquitination target of a membrane localized ubiquitin ligase ATL31. SYP61 is a key component of membrane trafficking in Arabidopsis. SYP61 was ubiquitinated with K63-linked chain by ATL31in vitroand in plants. The knockdown mutants ofSYP61were hypersensitive to the disrupted carbon (C)/nitrogen (N)-nutrient stress, suggesting its critical role in plant homeostasis in response to nutrients. We also found the ubiquitination status of SYP61 is affected by C/N-nutrient availability. These results provided possibility that ubiquitination of SNARE protein has important role in plant physiology.
Direct and indirect regulation of Pom1 cell size pathway by the protein phosphatase 2C Ptc1
Authors: Gerganova Veneta , Bhatia Payal , Martin Sophie G 
Published: June 2020

AbstractThe fission yeast cellsSchizosaccharomyces pombedivide at constant cell size regulated by environmental stimuli. An important pathway of cell size control involves the membrane-associated DYRK-family kinase Pom1, which forms decreasing concentration gradients from cell poles and inhibits mitotic inducers at mid-cell. Here, we identify the phosphatase 2C Ptc1 as negative regulator of Pom1. Ptc1 localizes to cell poles in a manner dependent on polarity and cell-wall integrity factors. We show that Ptc1 directly binds Pom1 and can dephosphorylate it in vitro but modulates Pom1 localization indirectly upon growth in low glucose conditions by influencing microtubule stability. Thus, Ptc1 phosphatase plays both direct and indirect roles in the Pom1 cell size control pathway.
Proteogenomics analysis of CUG codon translation in the human pathogenCandida albicans
Authors: Mühlhausen Stefanie , Schmitt Hans Dieter , Plessmann Uwe , Mienkus Peter , Sternisek Pia , Perl Thorsten , Weig Michael , Urlaub Henning , Bader Oliver , Kollmar Martin 
Published: June 2020

AbstractCandidayeasts causing human infections are spread across the yeast phylum withCandida glabratabeing related toSaccharomyces cerevisiae, Candida kruseigrouping toPichia spp., andCandida albicans, Candida parapsilosisandCandida tropicalisbelonging to the CTG-clade. The latter lineage contains yeasts with an altered genetic code translating CUG codons as serine using a serine-tRNA with a mutated anticodon. It has been suggested that the CTG-clade CUG codons are mistranslated to a small extent as leucine due to mischarging of the serine-tRNA(CAG). The mistranslation was suggested to result in variable surface proteins explaining fast host adaptation and pathogenicity. Here, we re-assessed this potential mistranslation by high-resolution mass spectrometry-based proteogenomics of multiple CTG-clade yeasts, variousC. albicansstrains, isolated from colonized and from infected human body sites, andC. albicansgrown in yeast and hyphal forms. Ourin vivodata do not support CUG codon mistranslation by leucine. Instead, (i) CUG codons are mistranslated only to the extent of ribosomal mistranslation with no preference for specific amino acids, (ii) CUG codons are as unambiguous (or ambiguous) as the related CUU leucine and UCC serine codons, (iii) tRNA anticodon loop variation across the CTG-clade yeasts does not result in any difference of the mistranslation level, and (iv) CUG codon unambiguity is independent ofC. albicans’ strain pathogenicity or growth form.
Distinct gene expression profiles in leukocortical demyelinated white and grey matter areas of Multiple Sclerosis patients
Authors: van Wageningen T.A. , Gerrits E. , Geleijnse A. , Brouwer N. , Geurts J.J.G. , Eggen B.J.L. , Boddeke H.W.G.M. , van Dam A-M. 
Published: June 2020

ABSTRACTDemyelination of the CNS is a prominent pathological hallmark of Multiple Sclerosis (MS) and affects both white (WM) and grey matter (GM). However, demyelinated WM and GM areas exhibit clear pathological differences, most notably the presence or absence of inflammation and activated glial cells in WM and GM, respectively. In order to gain more insight into the differential pathology of demyelinated WM and GM areas, we micro-dissected neighbouring WM and GM demyelinated areas as well as normal appearing matter from leukocortical lesions of human post-mortem material and used these samples for RNA-sequencing. Our data show that even neighbouring WM and GM demyelinated areas share only 10% overlap in gene expression, implying a distinct gene expression profile, which is extending to a specific glial cell related signature. We propose that, based on their distinct expression profile, pathological processes in neighbouring WM and GM are likely different which could have implications for the efficacy of current MS treatments.
Antagonism Between Brain Regions Relevant for Cognitive Control and Emotional Memory Facilitates the Generation of Humorous Ideas
Authors: Bitsch Florian , Berger Philipp , Fink Andreas , Nagels Arne , Straube Benjamin , Falkenberg Irina 
Published: June 2020

AbstractThe ability to generate humor gives rise to positive emotions and thus facilitate the successful resolution of adversity. Although there is consensus that inhibitory processes might be related to broaden the way of thinking, the neural underpinnings of these mechanisms are largely unknown. Here, we use functional Magnetic Resonance Imaging, a humorous alternative uses task and a stroop task, to investigate the brain mechanisms underlying the emergence of humorous ideas in 24 subjects. Neuroimaging results indicate that greater cognitive control abilities are associated with increased activation in the amygdala, the hippocampus and the superior and medial frontal gyrus during the generation of humorous ideas. Examining the neural mechanisms more closely shows that the downregulation of frontal brain regions is associated with an upregulation in the amygdala, which is concurrently linked with an increased number of humorous ideas and enhanced amygdala responses during the task. Our data therefore suggests that a neural antagonism previously related to the emergence and regulation of negative affective responses, is linked with the generation of emotionally positive ideas and may represent an important neural pathway supporting mental health.
Landscape heterogeneity buffers biodiversity of meta-food-webs under global change through rescue and drainage effects
Authors: Ryser Remo , Hirt Myriam R. , Häussler Johanna , Gravel Dominique , Brose Ulrich 
Published: June 2020

SummaryThe impacts of habitat fragmentation and eutrophication on biodiversity have been studied in different scientific realms. Metacommunity research1–5has shown that reduction in landscape connectivity may cause biodiversity loss in fragmentated landscapes. Food-web research addressed how eutrophication increases biomass accumulations at high trophic levels causing the breakdown of local biodiversity6–9. However, there is very limited understanding of their cumulative impacts as they could amplify or cancel each other. Here, we show with simulations of meta-food-webs that landscape heterogeneity provides a buffering capacity against increasing nutrient eutrophication. An interaction between eutrophication and landscape homogenization precipitates the decline of biodiversity. We attribute our results to two complementary mechanisms related to source and sink dynamics. First, the “rescue effect” maintains local biodiversity by rapid recolonization after a local crash in population densities. Second, the “drainage effect” allows a more uniform spreading of biomass across the landscape, reducing overall interaction strengths and therefore stabilizing dynamics. In complex food webs on large spatial networks of habitat patches, these effects yield systematically higher biodiversity in heterogeneous than in homogeneous landscapes. Our meta-food-web approach reveals a strong interaction between habitat fragmentation and eutrophication and provides a mechanistic explanation of how landscape heterogeneity promotes biodiversity.
Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow
Authors: Li Jingjing , Quan Weipeng , Yan Shuge , Wu Shuangju , Qin Jianhu , Yang Tingting , Liang Fan , Wang Depeng , Liang Yu 
Published: June 2020

AbstractThe ongoing novel coronavirus (COVID-19) outbreak as a global public health emergency infected by SARC-CoV-2 has caused devastating loss around the world. Currently, a lot of diagnosis methods have been used to detect the infection. The nucleic acid (NA) testing is reported to be the clinical standard for COVID-19 infection. Evidence shows that a faster and more convenient method to detect in the early phase will control the spreading of SARS-CoV-2. Here, we propose a method to detect SARC-Cov-2 infection within two hours combined with Loop-mediated Isothermal Amplification (LAMP) reaction and nanopore Flongle workflow. In this approach, RNA reverse transcription and nucleic acid amplification reaction with one step in 30 minutes at 60-65°C constant temperature environment, nanopore Flongle rapidly adapter ligated within 10 minutes. Flongle flow cell sequencing and analysis in real-time. This method described here has the advantages of rapid amplification, convenient operation and real-time detection which is the most important for rapid and reliable clinical diagnosis of COVID-19. Moreover, this approach not only can be used for SARS-CoV-2 detection but also can be extended to other respiratory viruses and pathogens.
C. eleganspharyngeal pumping provides a whole organism bio-assay to investigate anti-cholinesterase intoxication and antidotes
Authors: Izquierdo Patricia G. , O’Connor Vincent , Green Christopher , Holden-Dye Lindy , Tattersall John 
Published: June 2020

AbstractInhibition of acetylcholinesterase by either organophosphates or carbamates causes anti-cholinesterase poisoning. This arises through a wide range of neurotoxic effects triggered by the overstimulation of the cholinergic receptors at synapses and neuromuscular junctions. Without intervention, this poisoning can lead to profound toxic effects, including death, and the incomplete efficacy of the current treatments, particularly for oxime-insensitive agents, provokes the need to find better antidotes. Here we show how the non-parasitic nematodeCaenorhabditis elegansoffers an excellent tool for investigating the acetylcholinesterase intoxication. TheC. elegansneuromuscular junctions show a high degree of molecular and functional conservation with the cholinergic transmission that operates in the autonomic, central and neuromuscular synapses in mammals. In fact, the anti-cholinesterase intoxication of the worm’s body wall neuromuscular junction has been unprecedented in understanding molecular determinants of cholinergic function in nematodes and other organisms. We extend the use of the model organism’s feeding behaviour as a tool to investigate carbamate and organophosphate mode of action. We show that inhibition of the cholinergic-dependent rhythmic pumping of the pharyngeal muscle correlates with the inhibition of the acetylcholinesterase activity caused by aldicarb, paraoxons and DFP exposure. Further, this bio-assay allows one to address oxime dependent reversal of cholinesterase inhibition in the context of whole organism recovery. Interestingly, the recovery of the pharyngeal function after such anti-cholinesterase poisoning represents a sensitive and easily quantifiable phenotype that is indicative of the spontaneous recovery or irreversible modification of the worm acetylcholinesterase after inhibition. These observations highlight the pharynx ofC. elegansas a new tractable approach to explore anti-cholinesterase intoxication and recovery with the potential to resolve critical genetic determinants of these neurotoxins’ mode of action.
Small dendritic synapses enhance temporal coding in a model of cochlear nucleus bushy cells
Authors: Koert Elisabeth , Kuenzel Thomas 
Published: June 2020

AbstractSpherical bushy cells (SBC) in the the anteroventral cochlear nucleus can improve the temporal precision of the auditory nerve spiking activity despite receiving sometimes only a single suprathreshold axosomatic input. The interaction with small dendritic inputs could provide a possible explanation for this phenomenon. In a compartment model of spherical bushy cells with a stylized or realistic three-dimensional representation of the bushy dendrite we explored this proposal. Phase-locked dendritic inputs caused both a tonic depolarization and a modulation of the SBC membrane potential at the frequency of the stimulus but for plausible model parameters do not cause output action potentials (AP). The tonic depolarization increased the excitability of the SBC model. The modulation of the membrane potential caused a phase-dependent increase in the efficacy of the main axosomatic input to cause output AP. These effects increased the rate and the temporal precision of output AP. Rate was mainly increased for stimulus frequencies at and below the characteristic frequency of the main input. Precision mostly increased for higher frequencies above about 1 kHz. Dendritic morphological parameters, biophysical parameters of the dendrite and the synaptic inputs and tonotopic parameters of the inputs all affected the impact of dendritic synapses. This suggested the possibility of fine tuning of the effect the dendritic inputs have for different coding demands or input frequency ranges. Excitatory dendritic inputs modulate the processing of the main input and are thus a plausible mechanism for the improvement of temporal precision in spherical bushy cells.
Clustering of loci controlling species differences in male chemical bouquets of sympatricHeliconiusbutterflies
Authors: Byers Kelsey J. R. P. , Darragh Kathy , Garza Sylvia Fernanda , Almeida Diana Abondano , Warren Ian A. , Rastas Pasi M. A. , Merrill Richard M. , Schulz Stefan , McMillan W. Owen , Jiggins Chris D. 
Published: June 2020

AbstractThe degree to which loci promoting reproductive isolation cluster in the genome –i.e.the genetic architecture of reproductive isolation - can influence the tempo and mode of speciation. Tight linkage between these loci can facilitate speciation in the face of gene flow. Pheromones play a role in reproductive isolation in many Lepidoptera species, and the role of endogenously-produced compounds as secondary metabolites decreases the likelihood of pleiotropy associated with many barrier loci.Heliconiusbutterflies use male sex pheromones to both court females (aphrodisiac wing pheromones) and ward off male courtship (male-transferred anti-aphrodisiac genital pheromones), and it is likely that these compounds play a role in reproductive isolation betweenHeliconiusspecies. Using a set of backcross hybrids betweenH. melpomeneandH. cydno, we investigated the genetic architecture of putative male pheromone compound production. We found a set of 40 significant quantitative trait loci (QTL) representing 33 potential pheromone compounds. QTL clustered significantly on two chromosomes, chromosome 8 for genital compounds and chromosome 20 for wing compounds, and chromosome 20 was enriched for potential pheromone biosynthesis genes. There was minimal overlap between pheromone QTL and known QTL for mate choice and color pattern. Nonetheless, we did detect linkage between a QTL for wing androconial area andoptix, a color pattern locus known to play a role in reproductive isolation in these species. This tight clustering of putative pheromone loci might contribute to coincident reproductive isolating barriers, facilitating speciation despite ongoing gene flow.
Tunica intima compensation for reduced stiffness of the tunica media in aging renal arteries as measured with scanning acoustic microscopy
Authors: Miura Katsutoshi 
Published: June 2020

AbstractObjectivesAging causes stiffness and decreased function of the renal artery (RA). Histological study with light microscopy can reveal microscopic structural remodeling but no functional changes. The present study aimed to clarify the association between structural and functional aging of the RA through the use of scanning acoustic microscopy.MethodsFormalin-fixed, paraffin-embedded cross-sections of renal arteries from 64 autopsy cases were examined. Speed-of-sound (SOS) values of three layers, which correspond to the stiffness, were compared among different age groups. SOS of the tunica media was examined in terms of blood pressure (BP) and SOS of the ascending aorta. Vulnerability to proteases was assessed by SOS reduction after collagenase treatment.ResultsThe tunica intima presented inward hypertrophy with luminal narrowing, and the tunica media showed outward hypertrophic remodeling with aging. SOS of the tunica media and internal and external elastic laminae showed a reverse correlation with age. SOS of the tunica media was negatively correlated with BP and strongly associated with that of the aorta. The tunica media of young RAs were more sensitive to collagenase compared with the old ones.ConclusionsScanning acoustic microscopy is useful for observing the aging process of the RA. This technique simultaneously shows structural and mechanical information from each portion of the RA. In the process of aging, the RA loses contractile function and elasticity as a result of protease digestion. The tunica media and the internal and external elastic laminae exhibit reduced stiffness, but the tunica intima stiffens with atherosclerosis. As a consequence, the RA’s outer shape changes from round to oval with inward and outward hypertrophy. This indicates that the inner resistant intima supports the mechanical weakness of the tunica media to compensate for an increase in BP with aging.
Rab2 drives axonal transport of dense core vesicles and lysosomal organelles
Authors: Lund Viktor K. , Lycas Matthew D. , Schack Anders , Andersen Rita C. , Gether Ulrik , Kjaerulff Ole 
Published: June 2020

SUMMARYLong range fast axonal transport of neuropeptide-containing dense core vesicles (DCVs), endolysosomal organelles and presynaptic components is critical for maintaining the functionality of neurons. How the transport of DCVs is orchestrated remains an important unresolved question. The small GTPase Rab2 has previously been shown to mediate DCV biogenesis and endosome-lysosome fusion. Here we use theDrosophilamodel system to demonstrate that Rab2 also plays a critical role in bidirectional axonal transport of DCVs, endosomes and lysosomal organelles, most likely by controlling molecular motors. We further show that the lysosomal motility factor Arl8 is required as well for axonal transport of DCVs, but unlike Rab2 is also critical for DCV exit from cell bodies into axons. Our results uncover the mechanisms responsible for axonal transport of DCVs and reveal surprising parallels between the regulation of DCVs and lysosomal motility.