bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neighborhood income and physical distancing during the COVID-19 pandemic in the U.S.
Authors: Jay Jonathan , Bor Jacob , Nsoesie Elaine , Lipson Sarah Ketchen , Jones David K. , Galea Sandro , Raifman Julia 
Published: June 2020

AbstractIntroductionAlthough physical distancing has been the primary strategy to reduce the spread of COVID-19 in the U.S., people’s ability to distance may vary by socioeconomic characteristics, leading to higher transmission risk in low-income neighborhoods.MethodsWe used mobility data from a large, anonymized sample of smartphone users to assess the relationship between neighborhood median household income and physical distancing during the COVID-19 epidemic. We assessed changes in several behaviors including: spending the day entirely at home; working outside the home; and visits to supermarkets, parks, hospitals, and other locations. We also assessed differences in effects of state policies on physical distancing across neighborhood income levels.ResultsWe found a strong gradient between neighborhood income and physical distancing. Compared to January and February 2020, the proportion of individuals spending the day entirely at home in April 2020 increased by 10.9 percentage points in low-income neighborhoods and by 27.1 percentage points in high-income neighborhoods. During April 2020, people in low-income neighborhoods were more likely to work outside the home, compared to people in higher-income neighborhoods, but not more likely to visit non-work locations. State physical distancing orders were associated with a 1.5 percentage-point increase (95% CI [0.9, 2.1], p < 0.001) in staying home in low-income neighborhoods and a 2.4 percentage point increase (95% CI [1.4, 3.4], p < 0.001) in high-income neighborhoods.DiscussionPeople in lower-income neighborhoods have faced barriers to physical distancing, particularly the need to work outside the home. State physical distancing policies have not mitigated these disparities.
A new subclass of exoribonuclease resistant RNA found in multipleFlaviviridaegenera
Authors: Szucs Matthew J. , Nichols Parker J. , Jones Rachel A. , Vicens Quentin , Kieft Jeffrey S. 
Published: June 2020

ABSTRACTViruses have developed innovative strategies to exploit the cellular machinery and overcome the host antiviral defenses, often using specifically structured RNA elements. Examples are found in flaviviruses; during flaviviral infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) accumulate in the cell. These sfRNAs are formed when a host cell 5’ to 3’ exoribonuclease degrades the viral genomic RNA but is blocked by an exoribonuclease resistant RNA structure (xrRNA) located in the viral genome’s 3’untranslated region (UTR). Although known to exist in severalFlaviviridaegenera the full distribution and diversity of xRNAs in this virus family was unknown. Using the recent high-resolution structure of an xrRNA from the divergent flavivirus Tamana bat virus (TABV) as a reference, we used bioinformatic searches to identify xrRNA in thePegivirus, Pestivirus, and Hepacivirusgenera. We biochemically and structurally characterized several examples, determining that they are genuine xrRNAs with a conserved fold. These new xrRNAs look superficially similar to the previously described xrRNAs but possess structural differences making them distinct from previous classes of xrRNAs. Our findings thus require adjustments of previous xrRNA classification schemes and expand on the previously known distribution of the xrRNA inFlaviviridae, indicating their widespread distribution and illustrating their importance.IMPORTANCETheFlaviviridaecomprise one of the largest families of positive sense single stranded (+ssRNA) and it is divided into theFlavivirus,Pestivirus,Pegivirus, andHepacivirusgenera. The genusFlaviviruscontains many medically relevant viruses such as Zika Virus, Dengue Virus, and Powassan Virus. In these, a part of the virus’s RNA twists up into a very special three-dimensional shape called an xrRNA that blocks the ability of the cell to “chew up” the viral RNA. Hence, part of the virus’ RNA remains intact, and this protected part is important for viral infection. This was known to occur in Flaviviruses but whether it existed in the other members of the family was not known. In this study, we not only identified a new subclass of xrRNA found in Flavivirus but also in the remaining three genera. The fact that this process of viral RNA maturation exists throughout the entireFlaviviridaefamily makes it clear that this is an important but underappreciated part of the infection strategy of these diverse human pathogens.
DeepFRET: Rapid and automated single molecule FRET data classification using deep learning
Authors: Thomsen Johannes , Sletfjerding Magnus B. , Stella Stefano , Paul Bijoya , Jensen Simon Bo , Malle Mette G. , Montoya Guillermo , Petersen Troels C. , Hatzakis Nikos S. 
Published: June 2020

AbstractSingle molecule Förster Resonance energy transfer (smFRET) is a mature and adaptable method for studying the structure of biomolecules and integrating their dynamics into structural biology. The development of high throughput methodologies and the growth of commercial instrumentation have outpaced the development of rapid, standardized, and fully automated methodologies to objectively analyze the wealth of produced data. Here we present DeepFRET, an automated standalone solution based on deep learning, where the only crucial human intervention in transiting from raw microscope images to histogram of biomolecule behavior, is a user-adjustable quality threshold. Integrating all standard features of smFRET analysis, DeepFRET will consequently output common kinetic information metrics for biomolecules. We validated the utility of DeepFRET by performing quantitative analysis on simulated, ground truth, data and real smFRET data. The accuracy of classification by DeepFRET outperformed human operators and current commonly used hard threshold and reached >95% precision accuracy only requiring a fraction of the time (<1% as compared to human operators) on ground truth data. Its flawless and rapid operation on real data demonstrates its wide applicability. This level of classification was achieved without any preprocessing or parameter setting by human operators, demonstrating DeepFRET’s capacity to objectively quantify biomolecular dynamics. The provided a standalone executable based on open source code capitalises on the widespread adaptation of machine learning and may contribute to the effort of benchmarking smFRET for structural biology insights.
Glycans on the SARS-CoV-2 Spike Control the Receptor Binding Domain Conformation
Authors: Henderson Rory , Edwards Robert J , Mansouri Katayoun , Janowska Katarzyna , Stalls Victoria , Kopp Megan , Haynes Barton F. , Acharya Priyamvada 
Published: June 2020

AbstractThe glycan shield of the beta-coronavirus (β-CoV) Spike (S) glycoprotein provides protection from host immune responses, acting as a steric block to potentially neutralizing antibody responses. The conformationally dynamic S-protein is the primary immunogenic target of vaccine design owing to its role in host-cell fusion, displaying multiple receptor binding domain (RBD) ‘up’ and ‘down’ state configurations. Here, we investigated the potential for RBD adjacent, N-terminal domain (NTD) glycans to influence the conformational equilibrium of these RBD states. Using a combination of antigenic screens and high-resolution cryo-EM structure determination, we show that an N-glycan deletion at position 234 results in a dramatically reduced population of the ‘up’ state RBD position. Conversely, glycan deletion at position N165 results in a discernable increase in ‘up’ state RBDs. This indicates the glycan shield acts not only as a passive hinderance to antibody meditated immunity but also as a conformational control element. Together, our results demonstrate this highly dynamic conformational machine is responsive to glycan modification with implications in viral escape and vaccine design.
The nucleus is a quality control center for non-imported mitochondrial proteins
Authors: Shakya Viplendra P.S. , Barbeau William A. , Xiao Tianyao , Knutson Christina S. , Hughes Adam L. 
Published: June 2020

AbstractMitochondrial import deficiency causes cellular stress due to the accumulation of non-imported mitochondrial precursor proteins. Despite the burden mis-localized mitochondrial precursors place on cells, our understanding of the systems that dispose of these proteins is incomplete. Here, we catalog the location and steady-state abundance of mitochondrial precursor proteins during mitochondrial impairment inS. cerevisiae. We find that a number of non-imported mitochondrial proteins localize to the nucleus, where they are eliminated by proteasome-based nuclear protein quality control. Recognition of mitochondrial precursors by the nuclear quality control machinery requires the presence of an N-terminal mitochondrial targeting sequence (MTS), and impaired breakdown of precursors leads to their buildup in nuclear-associated foci. These results identify the nucleus as a key destination for the disposal of non-imported mitochondrial precursors.
Role of Anti-SARS-CoV-2 antibodies in different cohorts: Can they provide clues for appropriate patient triaging?
Authors: Mutnal Manohar B. , Mohammad Amin A. , Arroliga Alejandro C. , Hua Yinan , Wang Liping , Koss William , Rao Arundhati 
Published: June 2020

AbstractThe emergence of coronavirus disease 2019 (COVID-19) has become a major global health crisis. Currently, diagnosis is based on molecular techniques, which detect the viral nucleic acids when present at detectable levels. The serum IgG response againstSARS-CoV-2was examined by using an ELISA-based assay. Serum samples, along with nasopharyngeal specimens were collected from various cohorts and analyzed by ELISA and rRT-PCR, respectively. A total of 167 serum samples were tested for serum IgG antibodies againstSARS-CoV-2in outpatient cohorts, 15 (8.9%) were positive by rRT-PCR and the remaining 152 (91%) were negative. We used these data to generate two different assay cutoffs for serum IgG assay and investigated percent concordance with rRT-PCR test results. The emergency department data revealed, out of 151 nasopharyngeal swabs, 4 (2.6%) were positive by rRT-PCR and 18 (11.9%) were positive for serum IgG assay. Among the 18 patients that were positive for serum IgG, 13 (72.2%) exhibited 1-3 symptoms of COVID-19 and 5 (27.7%) patients did not present with any COVID-19 related symptoms, per CDC criteria. All 4 (100%) patients that were positive by rRT-PCR had symptoms of COVID-19 disease. A longitudinal study from the inpatient population suggested there was a sharp increase in the serum IgG titers in 5 patients, a moderate increase in 1 patient and a plateau in 3 patients. Sero-prevalence of COVID-19 disease in pre-procedure patients was 5.5%. Our findings suggest serological tests can be used for appropriate patient triaging when performed as an adjunct to existing molecular testing.
Rational Design of the Remdesivir Binding Site in the RNA-dependent RNA Polymerase of SARS-CoV-2: Implications for Potential Resistance
Authors: Padhi Aditya K. , Shukla Rohit , Tripathi Timir 
Published: June 2020

ABSTRACTSARS-CoV-2 is rapidly evolving with the continuous emergence of new mutations. There is no specific antiviral therapy for COVID-19, and the use of Remdesivir for treating COVID-19 will likely continue before clinical trials are completed. Due to the lengthening pandemic and evolving nature of the virus, predicting potential residues prone to mutations is crucial for the management of Remdesivir resistance. We used a rational ligand-based interface design complemented with mutational mapping to generate a total of 100,000 mutations and provide insight into the functional outcome of mutations in the Remdesivir-binding site in nsp12. After designing 56 residues in the Remdesivir binding site of nsp12, the designs retained 96-98% sequence identity, which suggests that SARS-CoV-2 attains resistance and develops further infectivity with very few mutations in the nsp12. We also identified affinity-attenuating Remdesivir binding designs of nsp12. Several mutants acquired decreased binding affinity with Remdesivir, which suggested drug resistance. These hotspot residues had a higher probability of undergoing selective mutations in the future to develop Remdesivir and related drug-based resistance. A comparison of 21 nsp12 Remdesivir-bound designs to the 13 EIDD-2801-bound nsp12 designs suggested that EIDD-2801 would be more effective in preventing the emergence of resistant mutations and against Remdesivir-resistance strains due to the restricted mutational landscape. Combined with the availability of more genomic data, our information on mutation repertoires is critical to guide scientists to rational structure-based drug discovery. Knowledge of the potential residues prone to mutation improves our understanding and management of drug resistance and disease pathogenesis.
Survey of Anisoptera diversity in flood prone areas in Tirurangadi taluk of Kerala, India
Authors: Kalliyil Arshad , Jasna Sherin MK , Ashiba Amal K , Noushad Nimna , Shibitha P , Hency CT , Fathimath Sahla P , Mathew Bini 
Published: June 2020

AbstractBiodiversity forms the foundation of the vast array of ecosystem that critically contribute to human well being. Biodiversity is important in human managed as well as natural ecosystems. The changing status of insects and other invertebrates is the key indicator of biodiversity and environment that shapes it. The order Odonata comes under the class insecta. Odonata are divided into two suborders; Zygoptera (damselflies) and Anisoptera (dragonflies). Natural calamities can alter the ecosystem and thereby biodiversity drastically. This study was conducted in Tirurangadi taluk of kerala, India which is a flood prone taluk due to the over flow of the Kadalundi river during monsoon season. We reported a total of 12 species belonging to 10 genera and 2 families during the entire study. Sub-order Anisoptera was represented by the families, Libellulidae and Aeshnidae, comprising 11 species of Libellulidae and one species of Aeshnidae. On a long term, we aim at studying the impacts on insect biodiversity caused by floods.
Müller Glia regenerative potential is maintained throughout life despite neurodegeneration and gliosis in the ageing zebrafish retina
Authors: Martins Raquel R. , Zamzam Mazen , Moosajee Mariya , Thummel Ryan , Henriques Catarina M. , MacDonald Ryan B. 
Published: June 2020

ABSTRACTAgeing is a significant risk factor for degeneration of the retina. Harnessing the regenerative potential of Müller glia cells (MG) in the retina offers great promise for the treatment of blinding conditions. Yet, the impact of ageing on MG regenerative capacity has not yet been considered. Here we show that the zebrafish retina undergoes telomerase-independent age-related neurodegeneration. Yet, this progressive neuronal loss in the ageing retina is insufficient to stimulate the MG regenerative response. Instead, age-related neurodegeneration leads to MG gliosis and loss of vision, similarly to humans. Nevertheless, gliotic MG cells retain Yap expression and the ability to regenerate neurons after acute light damage. Therefore, we identify key differences in the MG response to acute versus chronic damage in the zebrafish retina and show that aged gliotic MG can be stimulated to repair damaged neurons in old age.SUMMARYOur data suggest there are key differences between mechanisms driving regeneration in response to acute damage versus age-related chronic damage. It may be that either the number of cells dying in natural ageing is not enough to stimulate MG to proliferate, or the low number of microglia and respective signals released are not sufficient to trigger MG proliferation. Importantly, we show that gliotic MG cells can be stimulated to repair damaged neurons in old zebrafish retina.
Evidence of recent increased pathogenicity within the AustralianAscochyta rabieipopulation
Authors: Sambasivam P , Mehmood Y , Bar I , Davidson J , Hobson K , Moore K , Ford R 
Published: June 2020

AbstractAscochyta Blight (AB), caused byAscochyta rabiei(synPhoma rabiei), is the major endemic foliar fungal disease affecting the Australian chickpea industry, resulting with potential crop loss and management costs. This study was conducted to better understand the risk posed by the AustralianA. rabieipopulation to current resistance sources and to provide informed decision support for chemical control strategies. Recent changes in the pathogenicity of the population were proposed based on disease severity and histopathological observations on a host set. Controlled environment disease screening of 201 isolates on the host set revealed distinct pathogenicity groups, with 41% of all isolates assessed as highly aggressive and a significant increase in the proportion of isolates able to cause severe damage on resistant and moderately resistant cultivars since 2013. In particular, the frequency of highly aggressive isolates on the widely adopted PBA HatTrick cultivar rose from 18% in 2013 to 68% in 2017. In addition, isolates collected since 2016 caused severe disease on Genesis 090, another widely adopted moderately resistant cultivar and on ICC3996, a commonly used resistance source. Of immediate concern was the 10% of highly aggressive isolates able to severely damage the recently released resistant cultivar PBA Seamer (2016). Histopathology studies revealed that the most aggressive isolates were able to germinate, develop appressoria and invade directly through the epidermis faster than lower aggressive isolates on all hosts assessed, including ICC3996. The fungal invasion triggered a common reactive oxygen species (ROS) and hypersensitive response (HR) on all assessed resistant genotypes with initial biochemical and subsequent structural defence responses initiated within 24 hours of inoculation by the most highly aggressive isolates. These responses were much faster on the less resistant and fastest on the susceptible check host, indicating that speed of recognition was correlated with resistance rating. This will inform fungicide application timing so that infected crops are sprayed with prophylactic chemistries prior to invasion and with systemic chemistries after the pathogen has invaded.
Three-dimensional Multi-site Random Access Photostimulation (3D-MAP)
Authors: Xue Yi , Waller Laura , Adesnik Hillel , Pégard Nicolas 
Published: June 2020

AbstractOptical control of neural ensemble activity is crucial for understanding brain function and disease, yet no technology can achieve optogenetic control of very large numbers of neurons at extremely fast rate over a large volume. State-of-the-art multiphoton holographic optogenetics requires high power illumination that only addresses relatively small populations of neurons in parallel. Conversely, one-photon holographic techniques can stimulate more neurons with 2-3 orders lower power, but with a trade-off between resolution and addressable volume. Perhaps most problematically, two-photon holographic optogenetic systems are extremely expensive and sophisticated which has precluded their broader adoption in the neuroscience community. To address this technical gap, we introduce a new one-photon light sculpting technique, Three- Dimensional Multi-site random Access Photostimulation (3D-MAP), that overcomes these limitations by modulating light dynamically, both in the spatial and in the angular domain at multi-kHz rates. We use 3D-MAP to interrogate neural circuits in 3D and demonstrate simultaneous photostimulation and imaging of dozens of user-selected neurons in the intact mouse brainin vivowith high spatiotemporal resolution. 3D-MAP could be broadly adopted for high-throughput all-optical interrogation of brain circuits owing to its powerful combination of scale, speed, simplicity, and cost.
Involuntary shifts of spatial attention contribute to distraction - Evidence from oscillatory alpha power and reaction time data
Authors: Weise Annekathrin , Hartmann Thomas , Parmentier Fabrice , Weisz Nathan , Ruhnau Philipp 
Published: June 2020

AbstractImagine you are focusing on the traffic on a busy street to ride your bike safely when suddenly you hear the siren of an ambulance. This unexpected sound involuntarily captures your attention and interferes with ongoing performance. We tested whether this type of distraction involves a spatial shift of attention. We measured behavioral data and magnetoencephalographic alpha power during a crossmodal paradigm that combined an exogenous cueing task and a distraction task. In each trial, a task-irrelevant sound preceded a visual target (left or right). The sound was usually the same animal sound (i.e., standard sound). Rarely, it was replaced by an unexpected environmental sound (i.e., deviant sound). Fifty percent of the deviants occurred on the same side as the target, and 50% occurred on the opposite side. Participants responded to the location of the target. As expected, responses were slower to targets that followed a deviant compared to a standard. Crucially, this distraction effect was mitigated by the spatial relationship between the targets and the deviants: responses were faster when targets followed deviants on the same versus different side, indexing aspatialshift of attention. This was further corroborated by a posterior alpha power modulation that was higher in the hemisphere ipsilateral (vs. contralateral) to the location of the attention-capturing deviant. We suggest that this alpha power lateralization reflects a spatial attention bias. Overall, our data support the contention that spatial shifts of attention contribute to deviant distraction.
FUNGAL DYSBIOSIS CORRELATES WITH THE DEVELOPMENT OF TUMOUR-INDUCED CACHEXIA IN MICE
Authors: Jabes D.L. , de Maria Y.N.L.F. , Aciole Barbosa D. , Santos K.B.N.H. , Carvalho L.M. , Humberto A.C. , Alencar V.C. , Costa de Oliveira R. , Batista M.L. , Menegidio F.B. , Nunes L.R. 
Published: June 2020

ABSTRACTCachexia (CC) is a devastating metabolic syndrome associated with a series of underlying diseases that greatly affects life quality and expectancy among cancer patients. Studies involving mouse models, in which CC was induced through inoculation with tumor cells, originally suggested the existence of a direct correlation between the development of this syndrome and changes in the relative proportions of several bacterial groups present in the digestive tract. However, these analyses have focus solely on the characterization of bacterial dysbiosis, ignoring the possible existence of changes in the relative populations of fungi, during the development of CC. Thus, the present study sought to expand such analyses, by characterizing changes that occur in the gut fungal population (mycobiota) of mice, during the development of cancer-induced cachexia. Our results confirm that cachectic animals display significant differences in their gutmycobiota, when compared to healthy controls. Moreover, identification of dysbiotic fungi showed remarkable consistency across successive levels of taxonomic hierarchy. Many of these fungi have also been associated with dysbioses observed in a series of gut inflammatory diseases, such as obesity, Colorectal Cancer (CRC), Myalgic Encephalomyelitis (ME) and Inflammatory Bowel Disease (IBD). Nonetheless, the CC-associated dysbiosis seems to be unique, presenting features observed in both obesity (reduced proportion ofMucoromycota) and CRC/ME/IBD (increased proportions ofSordariomycetes, SaccharomycetaceaeandMalassezia). One species ofMucoromycota(Rhyzopus oryzae) stands out as a promising probiotic candidate in adjuvant therapies, aimed at treating and/or preventing the development of CC.