bluuebunny/crossref_metadata_2025_split huggingface dataset:
What do blind people “see” with retinal prostheses? Observations and qualitative reports of epiretinal implant users
Authors: Erickson-Davis Cordelia , Korzybska Helma 
Published: February 2020

AbstractIntroduction: Retinal implants have now been approved and commercially available for certain clinical populations for over 5 years, with hundreds of individuals implanted, scores of them closely followed in research trials. Despite these numbers, however, few data are available that would help us answer basic questions regarding the nature and outcomes of artificial vision: what do participants see when the device is turned on for the first time, and how does that change over time?Methods: Semi-structured interviews and observations were undertaken at two sites in France and the UK with 16 participants who had received either the Argus II or IRIS II devices. Data were collected at various time points in the process that implant recipients went through in receiving and learning to use the device, including initial evaluation, implantation, initial activation and systems fitting, re-education and finally post-education. These data were supplemented with data from interviews conducted with vision rehabilitation specialists at the clinical sites and clinical researchers at the device manufacturers (Second Sight and Pixium Vision). Observational and interview data were transcribed, coded and analyzed using an approach guided by Interpretative Phenomenological Analysis (IPA).Results: Implant recipients described the perceptual experience produced by their epiretinal implants as fundamentally, qualitatively different than natural vision. All used terms that invoked electrical stimuli to describe the appearance of their percepts, yet the characteristics used to describe the percepts varied significantly between participants. Artificial vision for these participants was a highly specific, learned skill-set that combined particular bodily techniques, associative learning and deductive reasoning in order to build a “lexicon of flashes” - a distinct perceptual vocabulary that they then used to decompose, recompose and interpret their surroundings. The percept did not transform over time; rather, the participant became better at interpreting the signals they received. The process of using the device never ceased to be cognitively fatiguing, and did not come without risk or cost to the participant. In exchange, participants received hope and purpose through participation, as well as a new kind of sensory signal that may not have afforded practical or functional use in daily life but, for some, provided a kind of “contemplative perception” that participants tailored to individualized activities.Conclusion: Attending to the qualitative reports of participants regarding the experience of artificial vision provides valuable information not captured by extant clinical outcome measures. These data can both inform device design and rehabilitative techniques, as well as grant a more holistic understanding of the phenomenon of artificial vision.
Beef cattle that respond differently to fescue toxicosis have distinct gastrointestinal tract microbiota
Authors: Koester Lucas R , Poole Daniel H , Serão Nick VL , Schmitz-Esser Stephan 
Published: February 2020

AbstractTall fescue (Lolium arundinaceum) is a widely used forage grass which shares a symbiosis with the endophytic fungusEpichloë coenophiala. The endophyte produces an alkaloid toxin that provides herbivory, heat and drought resistance to the grass, but can cause fescue toxicosis in grazing livestock. Fescue toxicosis can lead to reduced weight gain and milk yields resulting in significant losses to the livestock industry. In this trial, 149 Angus cows across two farms were continuously exposed to toxic, endophyte-infected, fescue for a total of 13 weeks. Of those 149 cows, 40 were classified into either high (HT) or low (LT) tolerance groups according to their growth performance (weight gain). 20 HT and 20 LT cattle balanced by farm were selected for 16S rRNA gene and ITS1 region Illumina MiSeq amplicon sequencing to compare the fecal microbiota of the two tolerance groups. This study reveals significantly (P<0.05) different bacterial and fungal microbiota between HT and LT cattle, and indicates that fungal phylotypes may be important for an animal’s response to fescue toxicosis: We found that fungal phylotypes affiliating to the Neocallimastigaceae, which are known to be important fiber-degrading fungi, were consistently more abundant in the HT cattle. Whereas fungal phylotypes related to the genusTheleboluswere more abundant in the LT cattle. This study also found more pronounced shifts in the microbiota in animals receiving higher amounts of the toxin. We identified fungal phylotypes which were consistently more abundant either in HT or LT cattle and may thus be associated with the respective animal’s response to fescue toxicosis. Our results thus suggest that some fungal phylotypes might be involved in mitigating fescue toxicosis. The results of our study provide a basis for investigating the functional role of the gastrointestinal microbiota in fescue toxicosis in more detail in the future.
Prior hypoxia exposure enhances murine microglial inflammatory gene expressionin vitrowithout concomitant H3K4me3 enrichment
Authors: Kiernan Elizabeth A. , Ewald Andrea C. , Ouellette Jonathan N. , Wang Tao , Roopra Avtar , Watters Jyoti J. 
Published: February 2020

ABSTRACTHypoxia is a component of multiple disorders, including stroke and sleep-disordered breathing, that often precede or are comorbid with neurodegenerative diseases. However, little is known about how hypoxia affects the ability of microglia, resident CNS macrophages, to respond to subsequent inflammatory challenges that are often present during neurodegenerative processes. We therefore tested the hypothesis that hypoxia would enhance or “prime” microglial pro-inflammatory gene expression in response to a later inflammatory challenge without programmatically increasing basal levels of pro-inflammatory cytokine expression. To test this, we pre-exposed immortalized N9 and primary microglia to hypoxia (1% O2) for 16 hrs and then challenged them with pro-inflammatory lipopolysaccharide (LPS) either immediately or 3-6 days following hypoxic exposure. We used RNA sequencing coupled with chromatin immunoprecipitation sequencing to analyze primed microglial inflammatory gene expression and modifications to histone H3 lysine 4 trimethylation (H3K4me3) at the promoters of primed genes. We found that microglia exhibited enhanced responses to LPS 3 days and 6 days post-hypoxia. Surprisingly however, the majority of primed genes were not enriched for H3K4me3 acutely following hypoxia exposure. Using the bioinformatics tool MAGICTRICKS and reversible pharmacological inhibition, we found that primed genes required the transcriptional activities of NF-ĸB. These findings provide evidence that hypoxia pre-exposure could lead to persistent and aberrant inflammatory responses in the context of CNS disorders.
Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies
Authors: Ahmed Syed Faraz , Quadeer Ahmed A. , McKay Matthew R. 
Published: February 2020

AbstractThe beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.
Genome-resolved metagenomics and detailed geochemical speciation analyses yield new insights into microbial mercury cycling in geothermal springs
Authors: Gionfriddo Caitlin M. , Stott Matthew B. , Power Jean F. , Ogorek Jacob M. , Krabbenhoft David P. , Wick Ryan , Holt Kathryn , Chen Lin-Xing , Thomas Brian C. , Banfield Jillian F. , Moreau John W. 
Published: February 2020

ABSTRACTGeothermal systems emit substantial amounts of aqueous, gaseous and methylated mercury, but little is known about microbial influences on mercury speciation. Here we report results from genome-resolved metagenomics and mercury speciation analysis of acid warm springs in the Ngawha Geothermal Field (<55 °C, pH < 4.5), Northland Region, Aotearoa (New Zealand). Our aim was to identify the microorganisms genetically equipped for mercury methylation, demethylation, or Hg(II) reduction to volatile Hg(0) in these springs. Dissolved total and methylated mercury concentrations in two adjacent springs with different mercury speciation ranked among the highest reported from natural sources (250–16000 ng L−1and 0.5–13.9 ng L−1, respectively). Total solid mercury concentrations in spring sediments ranged from 1273 to 7000 µg g−1. In the context of such ultra-high mercury levels, the geothermal microbiome was unexpectedly diverse, and dominated by acidophilic and mesophilic sulfur- and iron-cycling bacteria, mercury- and arsenic-resistant bacteria, and thermophilic and acidophilic archaea. Integrating microbiome structure and metagenomic potential with geochemical constraints, we constructed a conceptual model for biogeochemical mercury cycling in geothermal springs. The model includes abiotic and biotic controls on mercury speciation, and illustrates how geothermal mercury cycling may couple to microbial community dynamics and sulfur and iron biogeochemistry.IMPORTANCELittle is currently known about biogeochemical mercury cycling in geothermal systems. This manuscript presents an important new conceptual model, supported by genome-resolved metagenomic analysis and detailed geochemical measurements. This work provides a framework for studying natural geothermal mercury emissions globally. Specifically, our findings have implications for mercury speciation in wastewaters from geothermal power plants and the potential environmental impacts of microbially and abiotically formed mercury species, particularly where mobilized in spring waters that mix with surface- or ground-waters. Furthermore, in the context of thermophilic origins for microbial mercury volatilisation, this report yields new insights into how such processes may have evolved alongside microbial mercury methylation/demethylation, and the environmental constraints imposed by the geochemistry and mineralogy of geothermal systems.
Population movement, city closure and spatial transmission of the 2019-nCoV infection in China
Authors: Ai Siqi , Zhu Guanghu , Tian Fei , Li Huan , Gao Yuan , Wu Yinglin , Liu Qiyong , Lin Hualiang 
Published: February 2020

AbstractThe outbreak of pneumonia caused by a novel coronavirus (2019-nCoV) in Wuhan City of China obtained global concern, the population outflow from Wuhan has contributed to spatial expansion in other parts of China. We examined the effects of population outflow from Wuhan on the 2019-nCoV transmission in other provinces and cities of China, as well as the impacts of the city closure in Wuhan. We observed a significantly positive association between population movement and the number of cases. Further analysis revealed that if the city closure policy was implemented two days earlier, 1420 (95% CI: 1059, 1833) cases could be prevented, and if two days later, 1462 (95% CI: 1090, 1886) more cases would be possible. Our findings suggest that population movement might be one important trigger of the 2019-nCoV infection transmission in China, and the policy of city closure is effective to prevent the epidemic.
Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China
Authors: Boldog Péter , Tekeli Tamás , Vizi Zsolt , Dénes Attila , Bartha Ferenc A. , Röst Gergely 
Published: February 2020

AbstractWe developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number Rloc). We found that in countries with low connectivity to China but with relatively high Rloc, the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low Rloc benefit the most from policies that further reduce Rloc. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.
Dynamic Laser Speckle Imaging meets Machine Learning to enable Rapid Antibacterial Susceptibility Testing (DyRAST)
Authors: Zhou Keren , Zhou Chen , Sapre Anjali , Pavlock Jared Henry , Weaver Ashley , Muralidharan Ritvik , Noble Joshua , Kovac Jasna , Liu Zhiwen , Ebrahimi Aida 
Published: February 2020

ABSTRACTRapid antibacterial susceptibility testing (RAST) methods which measure change of a bacterial phenotype in response to a given treatment are of significant importance in healthcare, as they can assist care-givers in timely administration of the right treatment. Various RAST techniques have been reported for tracking bacterial phenotypes, such as size, shape, motion, and metabolic activity. However, they still require bulky and expensive instruments (which hinders their application in resource-limited environments) and/or utilize labeling reagents (which can interfere with antibiotics and add to cost). Furthermore, the existing ultra-rapid methods do not address possible adaptation of gradual adaptation of bacteria to antibiotics, which can lead to false interpretation of resistance when using ultra-rapid methods. In this work, we present a RAST approach leveraging machine learning analysis of time-resolved dynamic laser speckle imaging (DLSI) results to accurately predict the minimum inhibitory concentration (MIC) of a model strain ofEscherichia coliin 60 minutes, compared to 6 hours using the currently FDA-approved phenotype-based RAST technique. To demonstrate the DLSI performance, we studied the effect of aβ-lactam ampicillin and an aminoglycoside gentamicin onEscherichia colistrain K-12. DLSI captures change of bacterial motion/division in response to treatment. The machine learning algorithm was trained and validated using the overnight results of gold standard, broth microdilution method. Empowered by machine learning, DyRAST can predict MIC with high accuracy comparable to gold standard methods through a voting strategy.
Association ofCDH11with ASD revealed by matched-gene co-expression analysis and mouse behavioral studies
Authors: Wu Nan , Wang Yue , Jia Jing-Yan , Pan Yi-Hsuan , Yuan Xiao-Bing 
Published: February 2020

AbstractA large number of putative risk genes of autism spectrum disorder (ASD) have been reported. The functions of most of these susceptibility genes in developing brains remain unknown, and a causal relationship between their variations and autism traits has not been established. The aim of this study is to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high confidence ASD risk genes (hcASDs). Results showed that three gene features, including gene size, mRNA abundance, and guanine-cytosine content, affect genome-wide co-expression profiles of hcASDs. To circumvent the interference of these gene features on gene co-expression analysis (GCA), we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched genes. This method is referred to as “matched-gene co-expression analysis” (MGCA). With MGCA, we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene prediction. Results of analysis of two recently reported ASD candidate genes,CDH11andCDH9,suggested the involvement ofCDH11, but notCDH9, in ASD. Consistent with this prediction, behavioral studies showed thatCdh11-null mice, but notCdh9-null mice, have multiple autism-like behavioral alterations. This study highlighted the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.
Common variation at the LRRK2 locus is associated with survival in the primary tauopathy progressive supranuclear palsy
Authors: Jabbari Edwin , Tan Manuela M.X. , Reynolds Regina H. , Mok Kin Y. , Ferrari Raffaele , Murphy David P. , Valentino Rebecca R. , Ross Owen A. , Dickson Dennis W. , Al-Sarraj Safa , Gentleman Steve M. , Allinson Kieren S.J. , Jaunmuktane Zane , Holton Janice L. , Revesz Tamas , Warner Thomas T. , Lees Andrew J. , Cookson Mark R. , Gibbs J. Raphael , Ding Jinhui , Chia Ruth , Traynor Bryan J. , Scholz Sonja W. , Pantelyat Alexander , Viollet Coralie , Dalgard Clifton L. , Pletnikova Olga , Troncoso Juan C. , Boxer Adam L. , Respondek Gesine , Höglinger Günter U. , Burn David J. , Pavese Nicola , Gerhard Alexander , Kobylecki Christopher , Leigh P. Nigel , Church Alistair , Hu Michele T.M. , Rowe James B. , Ryten Mina , Hardy John , Shoai Maryam , Morris Huw R. 
Published: February 2020

AbstractThe genetic basis of variation in the rate of disease progression of primary tauopathies has not been determined. In two independent progressive supranuclear palsy cohorts, we show that common variation at theLRRK2locus determines survival from motor symptom onset to death, possibly through regulation of gene expression. This links together genetic risk in alpha-synuclein and tau disorders, and suggests that modulation of proteostasis and neuro-inflammation by LRRK2 inhibitors may have a therapeutic role across disorders.
eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective effects
Authors: Caviedes Ariel , Maturana Barbara , Corvalán Katherina , Engler Alexander , Gordillo Felipe , Varas-Godoy Manuel , Smalla Karl-Heinz , Batiz Luis Federico , Lafourcade Carlos , Kaehne Thilo , Wyneken Ursula 
Published: February 2020

AbstractCell death by glutamate excitotoxicity, mediated by N-methyl-D-aspartate (NMDA) receptors, negatively impacts brain function, including but not limited to hippocampal neurons. The NF-κB transcription factor (composed mainly of p65/p50 subunits) contributes to neuronal death in excitotoxicity, while its inhibition should improve cell survival. Using the biotin switch method, subcellular fractionation, immunofluorescence and luciferase reporter assays, we found that NMDA stimulated NF-κB activity selectively in hippocampal neurons, while endothelial nitric oxide synthase (eNOS), an enzyme expressed in neurons, is involved in the S-nitrosylation of p65 and consequent NF-κB inhibition in cerebrocortical,i.e., resistant neurons. The S-nitro proteomes of cortical and hippocampal neurons revealed that different biological processes are regulated by S-nitrosylation in susceptible and resistant neurons, bringing to light that protein S-nitrosylation is a ubiquitous post-translational modification, able to influence a variety of biological processes including the homeostatic inhibition of the NF-κB transcriptional activity in cortical neurons exposed to NMDA receptor overstimulation.
Fluorescence-Detected Conformational Changes in Duplex DNA in Open Complex Formation byE. coliRNA Polymerase: Upstream Wrapping and Downstream Bending Precede Clamp Opening and Insertion of the Downstream Duplex
Authors: Sreenivasan Raashi , Shkel Irina A. , Chhabra Munish , Drennan Amanda , Heitkamp Sara , Wang Hao-Che , Sridevi Malavika A. , Plaskon Dylan , McNerney Christina , Callies Katelyn , Cimperman Clare K. , Record M. Thomas 
Published: February 2020

AbstractFRET (fluorescence energy transfer) between far-upstream (−100) and downstream (+14) cyanine dyes showed extensive bending/wrapping of λPRpromoter DNA onE. coliRNA polymerase (RNAP) in closed and open complexes (CC, OC). Here we determine the kinetics and mechanism of DNA bending/wrapping by FRET and of formation of RNAP contacts with −100 and +14 DNA by single-dye fluorescence enhancements (PIFE). FRET/PIFE kinetics exhibit two phases: rapidly-reversible steps forming a CC ensemble ({CC}c of four intermediates (initial (RPC), early (I1E), mid-(I1M), late (I1L)), followed by conversion of {CC} to OC via I1L. FRET and PIFE are first observed for I1E, not RPc. FRET/PIFE together reveal large-scale bending/wrapping of upstream and downstream DNA as RPCadvances to I1E, reducing −100/+14 distance to ∼75Å and making RNAP-DNA contacts at −100 and +14. We propose that far-upstream DNA wraps on the upper β’-clamp while downstream DNA contacts the top of the β-pincer in I1E. Converting I1Eto I1M(~1s time-scale)reducesFRET efficiency with little change in −100/+14PIFE, interpreted as clamp-opening that moves far-upstream DNA (on β’) away from downstream DNA (on β) to increase the −100/+14 distance by ~14Å. FRET increases greatly in converting I1Mto I1L, indicating bending of downstream duplex DNA into the clamp and clamp-closing to reduce the −100/+14 distance by ~21Å. In the subsequent rate-determining DNA-opening step, in which the clamp may also open, I1Lconverts to the initial unstable OC (I2). Implications for facilitation of CC-to-OC isomerization by upstream DNA and upstream-binding, DNA-bending transcription activators are discussed.Abstract Figure