bluuebunny/crossref_metadata_2025 huggingface dataset:
Mindfulness-Based College: A Stage 1 Randomized Controlled Trial for University Student Well-Being
Authors: Loucks Eric B. , Nardi William R. , Gutman Roee , Saadeh Frances B. , Li Yu , Vago David R. , Fiske Lauren B. , Spas Jayson J. , Harrison Abigail
Published: September 2020

Objective

To evaluate effects of a mindfulness-based program, adapted to the young adult life course stage (age, 18–29 years), named Mindfulness-Based College (MB-College). The primary outcome was a young adult health summary score, composed of key health risk factors: body mass index, physical activity, fruit and vegetable intake, alcohol consumption, stress, loneliness, and sleep duration. Secondary outcomes were hypothesized self-regulation mechanisms, including attention control, interoceptive awareness, and emotion regulation.

Methods

This was a stage 1 randomized controlled trial of the 9-week MB-College program (n = 47) versus enhanced usual care control (n = 49) including students from three universities. Assessments were at baseline, during the beginning of the college term when stress is typically lower, and at MB-College completion (3-month follow-up), when term-related stress is typically higher. Intention-to-treat, linear regression analyses estimated the marginal effects of MB-College versus control on the outcomes.

Results

MB-College participants (mean age = 20 years, 68% female, 37% racial minorities) demonstrated improved health summary scores at follow-up compared with control participants whose health summary scores worsened (marginal effect for MB-College versus control = 0.23; p = .004). Effects on loneliness were pronounced (marginal effect = −3.11 for the Revised University of Los Angeles Loneliness Scale score; p = .03). Secondary analyses showed significant impacts of MB-College on hypothesized self-regulation mechanisms (e.g., Sustained Attention to Response Task correct no-go percent, p = .0008; Multidimensional Assessment of Interoceptive Awareness, p < .0001; Center for Epidemiologic Studies—Depression scale, p = .03).

Conclusions

Findings of this early stage clinical trial suggest that MB-College may foster well-being in young adults.

Trial Registration: NCT03124446
Death of a Parent During Childhood and the Risk of Ischemic Heart Disease and Stroke in Adult Men
Authors: Chen Hua , Hemmingsson Tomas , Forsell Yvonne , Rostila Mikael , Janszky Imre , László Krisztina D.
Published: September 2020

Objective

The death of a parent during childhood is a severe life event with potentially long-term consequences. Earlier studies have shown an increased risk of cardiovascular diseases (CVD) after the death of a spouse, child, or sibling. Whether parental death during childhood is associated with an increased risk of incident CVD is unknown and was investigated in this study.

Methods

We studied 48,992 men born 1949 to 1951 and enlisted for military conscription in 1969 to 1970. We obtained information on death of a parent during childhood, CVD up to 2008, and covariates by linking the questionnaire and the clinical examination data from conscription with nationwide socioeconomic and health registers.

Results

Men who lost a parent during childhood had an increased risk of ischemic heart disease (IHD; adjusted hazard ratio (HR) and 95% confidence interval [CI] = 1.30 [1.13–1.49]) but not of stroke during the 39-year follow-up (adjusted HR [95% CI] = 0.87 [0.66–1.15]). Maternal death was associated with IHD both when the loss was due to cardiovascular (adjusted HR [95% CI] = 2.04 [1.02–4.08]) and unnatural causes (adjusted HR [95% CI] = 2.50 [1.42–4.42]); in case of paternal death, an increased IHD risk was observed only when the loss was due to cardiovascular causes (adjusted HR [95% CI] = 1.82 [1.37–2.42]). There were no substantial differences in CVD according to the child’s age at the loss.

Conclusions

Parental death during childhood was associated with an increased risk of IHD in men. If these associations are confirmed in future studies, the long-term effects of childhood bereavement may warrant attention.
Evaluation of Quality of Life in Adult Individuals With Cleft Lip and/or Palate
Authors: Aljohani Marwan , Yates Julian , Ashley Martin , O’Malley Lucy
Published: September 2020

Objectives:

The purpose of the present study was to systematically review literature relating to the quality of life (QoL) in adult individuals with cleft lip and/or palate (CLP) and identify which aspect of QoL adults with CLP find to be the most problematic, in comparison to a general non-cleft population.

Design:

Different databases were searched for this review including the Cochrane Central Register of Controlled Trials, Ovid MEDLINE and Embase. Five domains of QoL were identified to evaluate the overall results of these QoL measures. These domains were; physical function, physical pain, psychological implications and self-esteem, self-perception in relation to facial aesthetics, and social function. The studies included underwent critical appraisal and different types of bias were assessed based on the Cochrane handbook for systematic reviews of interventions.

Results:

Ten studies were included in this review. The total number of participants was 541. The most common QoL measure for adults with CLP was Short-Form (SF-36). Seven studies out of 10 reported statistically significantly worse scores (P < 0.05) in the psychological implications and self-esteem domains of QoL in adults with CLP, indicating lower QoL in terms of these domains. The least affected QoL domain was physical function. A high heterogeneity was found among the studies, including variation in the QoL measures, types of orofacial clefts, types of treatment and comparison groups.

Conclusion:

The presence of CLP did seem to negatively affect the QoL for adults with CLP, mainly in terms of psychological implications and self-esteem.
Clinical evolution of COVID-19 during pregnancy at different altitudes: a population-based study
Authors: Leon-Abarca Juan Alonso , Peña-Gallardo Maria Teresa , Soliz Jorge , Accinelli Roberto
Published: September 2020

Background

The impact of influenza and various types of coronaviruses (SARS-CoV and MERS-CoV) on pregnancy has been reported. However, the current pandemic caused by SARS-CoV-2 continues to reveal important data for understanding its behavior in pregnant women.

Methods

We analyzed the records of 326,586 non-pregnant women of reproductive age and 7,444 pregnant women with no other risk factor who also had a SARS-CoV-2 RT-PCR result to estimate adjusted prevalence (aP) and adjusted prevalence ratios (aPR) of COVID-19 and its requirement of hospitalization, intubation, ICU admission and case-fatality rates. Adjustment was done through Poisson regressions for age and altitude of residence and birth. Generalized binomial models were used to generate probability plots to display how each outcome varied across ages and altitudes.

Results

Pregnancy was independently associated with a 15% higher probability of COVID-19 (aPR: 1.15), a 116% higher probability of its following admission (aPR: 2.169) and a 127% higher probability of ICU admission (aPR: 2.275). Also, pregnancy was associated with 84.2% higher probability of developing pneumonia (aPR: 1.842) and a 163% higher probability of its following admission (aPR: 2.639). There were no significant differences in COVID-19 case-fatality rates between pregnant and non pregnant women (1.178, 95% CI: 0.68-1.67).

Conclusion

Pregnancy was associated with a higher probability of COVID-19, developing of pneumonia, hospitalization, and ICU admission. Our results also suggest that the risk of COVID-19 and its related outcomes, except for intubation, decrease with altitude.
rRNA analysis based on long-read high-throughput sequencing reveals a more accurate diagnostic for the bacterial infection of ascites
Authors: Yu Xiaoling , Jiang Wenqian , Huang Xinhui , Lin Jun , Ye Hanhui , Liu Baorong
Published: September 2020

Traditional pathogenic diagnosis presents defects such as a low positivity rate, inability to identify uncultured microorganisms, and time-consuming nature. Clinical metagenomics next-generation sequencing can be used to detect any pathogen, compensating for the shortcomings of traditional pathogenic diagnosis. We report third-generation long-read sequencing results and second-generation short-read sequencing results for ascitic fluid from a patient with liver ascites and compared the two types of sequencing results with the results of traditional clinical microbial culture. The distribution of pathogenic microbial species revealed by the two types of sequencing results was quite different, and the third-generation sequencing results were consistent with the results of traditional microbial culture, which can effectively guide subsequent treatment. Short reads, the lack of amplification and enrichment to amplify signals from trace pathogens, and host background noise may be the reasons for high error in the second-generation short-read sequencing results. Therefore, we propose that long-read-based rRNA analysis technology is superior to the short-read shotgun-based metagenomics method in the identification of pathogenic bacteria.
Improved estimation of time-varying reproduction numbers at low case incidence and between epidemic waves
Authors: Parag Kris V
Published: September 2020

We construct a recursive Bayesian smoother, termed EpiFilter, for estimating the effective reproduction number, R, from the incidence of an infectious disease in real time and retrospectively. Our approach borrows from Kalman filtering theory, is quick and easy to compute, generalisable, deterministic and unlike many current methods, requires no change-point or window size assumptions. We model R as a flexible, hidden Markov state process and exactly solve forward-backward algorithms, to derive R estimates that incorporate all available incidence information. This unifies and extends two popular methods, EpiEstim, which considers past incidence, and the Wallinga-Teunis method, which looks forward in time. We find that this combination of maximising information and minimising assumptions significantly reduces the bias and variance of R estimates. Moreover, these properties make EpiFilter more statistically robust in periods of low incidence, where existing methods can become destabilised. As a result, EpiFilter offers improved inference of time-varying transmission patterns that are especially advantageous for assessing the risk of upcoming waves of infection in real time and at various spatial scales.

Author Summary

Inferring changes in the transmissibility of an infectious disease is crucial for understanding and controlling epidemic spread. The effective reproduction number, R, is widely used to assess transmissibility. R measures the average number of secondary cases caused by a primary case and has provided insight into many diseases including COVID-19. An upsurge in R can forewarn of upcoming infections, while suppression of R can indicate if public health interventions are working. Reliable estimates of temporal changes in R can contribute important evidence to policymaking. Popular R-inference methods, while powerful, can struggle when cases are few because data are noisy. This can limit detection of crucial variations in transmissibility that may occur, for example, when infections are waning or when analysing transmissibility over fine geographic scales. In this paper we improve the general reliability of R-estimates and specifically increase robustness when cases are few. By adapting principles from control engineering, we formulate EpiFilter, a novel method for inferring R in real time and retrospectively. EpiFilter can potentially double the information extracted from epidemic time-series (when compared to popular approaches), significantly filtering the noise within data to minimise both bias and uncertainty of R-estimates and enhance the detection of salient changepoints in transmissibility.
Effects of Randomized Corruption Audits on Early-Life Mortality in Brazil
Authors: Nichter Simeon , Ramos Antonio P. , Gao Leiwen , Weiss Robert E.
Published: September 2020

Background

Various studies suggest that corruption affects public health systems across the world. However, the extant literature lacks causal evidence about whether anti-corruption interventions can improve health outcomes. We examine the impact of randomized anti-corruption audits on early-life mortality in Brazil.

Methods

The Brazilian government conducted audits in 1,949 randomly selected municipalities between 2003 and 2015. To identify the causal effect of anti-corruption audits on early-life mortality, we analyse data on health outcomes from individual-level vital statistics (DATASUS) collected by Brazil’s government before and after the random audits. Data on the audit intervention are from the Controladoria-Geral da Uniao, the government agency responsible for the anti-corruption audits. Outcomes are neonatal mortality, infant mortality, child mortality, preterm births, and prenatal visits. Analyses examine aggregate effects for each outcome, as well as effects by race, cause of death, and years since the intervention.

Results

Anti-corruption audits significantly decreased early-life mortality in Brazil. Expressed in relative terms, audits reduced neonatal mortality by 6.7% (95% CI −8.3%, −5.0%), reduced infant mortality by 7.3% (−8.6%, −5.9%), and reduced child mortality by 7.3% (−8.5%, −6.0%). This reduction in early mortality was higher for nonwhite Brazilians, who face significant health disparities. Effects are greater when we look at deaths from preventable causes, and show temporal persistence with large effects even a decade after audits. In addition, analyses show that the intervention led to a 12.1% (−13.4%, −10.6%) reduction in women receiving no prenatal care, as well as a 7.4% (−9.4%, −5.5%) reduction in preterm births; these effects are likewise higher for nonwhites and are persistent over time. All effects are robust to various alternative specifications.

Interpretation

Governments have the potential to improve health outcomes through anti-corruption interventions. Such interventions can reduce early-life mortality and mitigate health disparities. The impact of anti-corruption audits should be investigated in other countries, and further research should further explore the mechanisms by which combating corruption affects the health sector.
Genetically proxied inhibition of interleukin-6 signaling: opposing associations with susceptibility to COVID-19 and pneumonia
Authors: Larsson Susanna C. , Burgess Stephen , Gill Dipender
Published: September 2020

The inflammatory cytokine interleukin-6 (IL-6) is pivotal for orchestrating the immune response. Inhibitors of IL-6 signaling are being investigated as treatments for severe coronavirus disease 2019 (COVID-19). We conducted a Mendelian randomization study investigating the effect of IL-6 signaling on susceptibility to COVID-19 and pneumonia. Our results showed that genetically proxied inhibition of IL-6 signaling was associated with reduced risk of COVID-19, but also with increased risk of pneumonia. Respiratory disease is a main feature of severe COVID-19, and the potential of IL-6 signaling inhibitors to increase risk of pneumonia warrants vigilance and caution in their application to treat COVID-19.
SARS-CoV-2 reactive antibodies in unexposed individuals revealed by a high sensitivity, low noise serologic assay
Authors: Yuen Rachel R. , Steiner Dylan , Pihl Riley M.F. , Chavez Elizabeth , Olson Alex , Baird Lillia A. , Korkmaz Filiz , Urick Patricia , Sagar Manish , Berrigan Jacob L. , Gummuluru Suryaram , Corley Ronald B. , Quillen Karen , Belkina Anna C. , Mostoslavsky Gustavo , Rifkin Ian , Kataria Yachana , Cappione Amedeo J. , Lin Nina H. , Bhadelia Nahid , Snyder-Cappione Jennifer E.
Published: September 2020

The COVID-19 pandemic has significantly impacted work, economy, and way of life. The SARS-CoV-2 virus displays unique features including widely varying symptoms and outcomes between infected individuals. Sensitive measurement of SARS-CoV-2 specific antibodies would provide new insight into virus transmission dynamics, pre-existing cross-reactive immunity, and the nuances of SARS-CoV-2 pathogenesis. To date, existing SARS-CoV-2 serology tests have limited utility due to insufficient detection of antibody levels lower than what is typically present after several days of symptoms. To measure lower quantities of SARS-CoV-2 IgM, IgG, and IgA with higher resolution than existing assays, we developed a new ELISA protocol with a distinct plate washing procedure and timed plate development via use of a standard curve. This ‘BU ELISA’ method exhibits very low signal from plasma or serum samples added to uncoated wells at as low as a 1:5 dilution. Use of this method revealed circulating SARS-CoV-2 receptor binding domain (RBD) and nucleocapsid protein (NP) reactive antibodies from blood samples drawn prior to May 2019. Of our prepandemic cohort, no SARS-CoV-2 RBD-reactive IgG antibodies were detected in subjects over 70 years of age, and SARS-CoV-2 NP-reactive antibodies were present at similar levels to infected subjects in some individuals and very low in others. Also, samples drawn in May 2020 from two individuals with no symptoms or no known virus exposure contained SARS-CoV-2 RBD-reactive antibodies at intermediate amounts compared with other subject groups (higher than pre-pandemic and lower than confirmed SARS-CoV-2 infected). The one asymptomatic SARS-CoV-2 convalescent subject in our study possessed comparable amounts of SARS-CoV-2 NP-specific IgM and IgG but drastically lower IgA than the symptomatic counterparts. Also, our assay detected positive signal from samples that gave negative results in a commercially available Lateral Flow Device (LFD) and the EUA approved Abbott IgG chemiluminescent microparticle immunoassay for SARS-CoV-2 antibody detection. We propose that this improved ELISA protocol, which is straightforward to perform, low cost, and uses readily available commercial reagents, is a useful tool to elucidate new information about SARS-CoV-2 infection and has promising implications for improved detection of all analytes measurable by this platform.
Comparative profiling of epigenetic modifications among individuals living in different high and low air pollution zones: A pilot study from India
Authors: Mishra Pradyumna Kumar , Bunkar Neha , Singh Radha Dutt , Kumar Rajat , Gupta Pushpendra Kumar , Tiwari Rajnarayan , Lodhi Lalit , Bhargava Arpit , Chaudhury Koel
Published: September 2020

Epigenetic modifications act as an important bridge to regulate the complex network of gene-environment interaction. As these mechanisms determines the gene-expression patterns via regulating the transcriptomic machinery, environmental stress induced epigenetic modifications may interrupt distinct cellular functions resulting into generation of diseased phenotypes. In the present study, we used a multi-city approach to compare the epigenomic signatures of individuals living in two tiers of Indian cities categorized as low-risk and high-risk air pollution zones. The high-risk group reported marked changes in the expression levels of epigenetic modifiers (DNMT1, DNMT3a, EZH2, EHMT2 and HAT), that maintains the levels of specific epigenetic marks essential for appropriate gene functioning. These results also coincided with the observed alterations in the levels of DNA methylation (LINE-1 and % 5mC), and histone modifications (H3 and H4), among the high-risk group. In addition, higher degree of changes reported in the expression profile of a selected miRNA panel in the high-risk group indicated the probability of deregulated transcriptional machinery. This was further confirmed by the analysis of a target gene panel involved in various signalling pathways, which revealed differential expression of the gene transcripts regulating cell cycle, inflammation, cell survival, apoptosis and cell adhesion. Together, our results provide first insights of epigenetic modifications among individuals living in different high and low levels of air pollution zones of India. However, further steps to develop a point-of-care epigenomic assay for human bio-monitoring may be immensely beneficial to reduce the health burden of air pollution especially in lower-middle-income countries.
COVID-19 incidence and mortality in the Metropolitan Region, Chile: time, space, and structural factors
Authors: Dintrans Pablo Villalobos , Castillo Claudio , Fuente Felipe De La , Maddaleno Matilde
Published: September 2020

Chile has been heavily affected by the COVID-19 pandemic. This article analyzes the association of different groups of factors—demographic, health-related, and socioeconomic—on COVID-19-related outcomes. Using the municipalities of the Metropolitan Region the study looks at the role of time dynamics, space and place in cases and deaths during a 100-days period.

Results show that common and idiosyncratic elements that explain the prevalence and dynamics of infections and mortality, with an important role of social determinants of health, particularly multidimensional poverty index and use of public transportation, in explaining differences in outcomes.

The article contributes to the understanding of the determinants of COVID-19 outcomes in a specific region, but also highligths the need to consider time-space dynamics and social determinants as key in the analysis. The results are specially relevant for similar research in unequal settings.
Superspreaders provide essential clues for mitigation of COVID-19
Authors: Nielsen Bjarke Frost , Sneppen Kim
Published: September 2020

Although coronavirus disease 2019 (COVID-19) has caused severe suffering in many countries around the world, the efficacy of non-pharmaceutical interventions such as policies of social distancing has been greater than models have predicted. Meanwhile, evidence is mounting that the pandemic is characterized by superspreading, where a small fraction account for the majority of infections. Capturing this phenomenon theoretically requires modeling at the scale of individuals. Using a mathematical model, we show that superspreading represents an Achilles’ heel of COVID-19, and drastically improves the efficacy of mitigations which reduce the personal contact number, even when this is done without changing the average social contact time.
An Application of Logistic Formula to Deaths by COVID-19 in Japan
Authors: Saito Takesi
Published: September 2020

A logistic formula in biology is applied to analyze deaths by COVID-19 for both of the first and the second waves in Japan. We then discuss ends of both waves and their mortality ratios. The meaning of population N in an epidemic is discussed.
Early Release Estimates for SARS-CoV-2 Prevalence and Antibody Response Interim Weighting for Probability-Based Sample Surveys
Authors: Bradley Heather , Fahimi Mansour , Sanchez Travis , Lopman Ben , Frankel Martin , Kelley Colleen F. , Rothenberg Richard , Siegler Aaron J , Sullivan Patrick S
Published: September 2020

Many months into the SARS-CoV-2 pandemic, basic epidemiologic parameters describing burden of disease are lacking. To reduce selection bias in current burden of disease estimates derived from diagnostic testing data or serologic testing in convenience samples, we are conducting a national probability-based sample SARS-CoV-2 serosurvey. Sampling from a national address-based frame and using mailed recruitment materials and test kits will allow us to estimate national prevalence of SARS-CoV-2 infection and antibodies, overall and by demographic, behavioral, and clinical characteristics. Data will be weighted for unequal selection probabilities and non-response and will be adjusted to population benchmarks. Due to the urgent need for these estimates, expedited interim weighting of serosurvey responses will be undertaken to produce early release estimates, which will be published on the study website, COVIDVu.org. Here, we describe a process for computing interim survey weights and guidelines for release of interim estimates.
Mobile EEG reveals functionally dissociable dynamic processes supporting real-world ambulatory obstacle avoidance: Evidence for early proactive control
Authors: Mustile Magda , Kourtis Dimitrios , Ladouce Simon , Learmonth Gemma , Donaldson David I. , Ietswaart Magdalena
Published: September 2020

The ability to safely negotiate the world on foot takes years to develop in human infants, reflecting the huge cognitive demands associated with real-time dynamic planning and control of walking. Despite the importance of walking, surprisingly little is known about the neural and cognitive processes that support ambulatory motor control in humans. In particular, methodological limitations have, to date, largely prevented study of the neural processes involved in detecting and avoiding obstacles during walking. Here, using mobile EEG during real-world ambulatory obstacle avoidance, we captured the dynamic oscillatory response to changes in the environment. Time-frequency analysis of EEG data revealed clear neural markers of proactive and reactive forms of movement control (occurring before and after crossing an obstacle), visible as increases in frontal theta and centro-parietal beta power respectively. Critically, the temporal profile of changes in frontal theta allowed us to arbitrate between early selection and late correction mechanisms of proactive control: our data show that motor plans are updated as soon as an upcoming obstacle appears, rather than when the obstacle is reached, as previously thought. In addition, regardless of whether motor plans required updating, a clear beta rebound was present after obstacles were crossed, reflecting the resetting of the motor system. Overall, our use of mobile EEG during real-world walking provides novel insight into the cognitive and neural basis of dynamic motor control in humans, suggesting new routes to the monitoring and rehabilitation of motor disorders such as dyspraxia and Parkinson’s disease.
Interaction of habitat isolation and seasonality: impact of fragmentation in dynamic landscapes on local and regional population variability in meta-food chains
Authors: Stark Markus , Bach Moritz , Guill Christian
Published: September 2020

While habitat loss is a known key driver of biodiversity decline, the effect of habitat fragmentation ‘per se’ is far less clear. Environmental perturbations, e.g. due to seasonality, potentially interact with effects of habitat fragmentation, thus making the latter even more difficult to assess. In order to analyze how the dynamic stability of local and metapopulations is affected by habitat fragmentation, we simulate a meta-food chain with three species on complex networks of habitat patches and evaluate the average variability of the local populations and the metapopulations as well as the level of synchronization between the patches. To account for environmental perturbations, we contrast simulations of static landscapes with simulations of dynamic landscapes, where 30 percent of the patches periodically become unavailable as habitats. We find that it depends on the parameterization of the food chain whether higher dispersal rates in less fragmented landscapes synchronize the dynamics or not. Even if the dynamics synchronize, local population variability can decrease due to indirect effects of dispersal mortality, thereby stabilizing metapopulation dynamics and reducing the risk of extinction. In dynamic landscapes, periodic external perturbations often fully synchronize the dynamics even if they act on a much slower time scale than the ecological interactions. Furthermore, they not only increase the variability of local and metapopulations, but also mostly overrule the effects of habitat fragmentation. This may explain why in nature effects of habitat fragmentation are often small and inconclusive.
The role of miR-31-5p in the development of intervertebral disc degeneration and its therapeutic potential
Authors: Zhou Yong , Su Jiqing , Deng Mingsi , Zhang Wei , Liu Dongbiao , Wang Zhengguang
Published: September 2020

Intervertebral disc degeneration (IDD) refers to the abnormal response of cell-mediated progressive structural failure. In order to understand the molecular mechanism of the maintenance and destruction of the intervertebral disc, new IDD treatment methods are developed. Here, we first analyzed the key regulators of IDD through miRNA microarrays. The cell structure and morphology were discovered by Histological and radiographic. Then, the level of miR-31-5p was disclosed by qRT-PCR. The association between miR-31-5p and SDF-1/CXCR7 axis was discovered by 3′-Untranslated region (UTR) cloning and luciferase assay. The apoptosis of cells under different treatments was disclosed by Flow cytometer. The cell proliferation was discovered by EdU assay. Finally, the protein levels of SDF-1, CXCR7, ADAMTS-5, Col II, Aggrecan and MMP13 were discovered by Western blot. The results show that miR-31-5p is a key regulator of IDD and its level is down-regulated in IDD. Overexpression of miR-31-5p facilitates NP cell proliferation, inhibits apoptosis, facilitates ECM formation and inhibits the level of matrix degrading enzymes in NP cells. The SDF-1/CXCR7 axis is the direct target of miR-31-5p. miR-31-5p acts on IDD by regulating SDF-1/CXCR7. In vitro experiments further verified that the up-regulation of miR-31-5p prevented the development of IDD. In conclusion, overexpression of miR-31-5p can inhibit IDD by regulating SDF-1/CXCR7.
Functional dynamics of de-afferented early visual cortex in glaucoma
Authors: Prabhakaran Gokulraj T. , Al-Nosairy Khaldoon O. , Tempelmann Claus , Wagner Markus , Thieme Hagen , Hoffmann Michael B.
Published: September 2020

fMRI studies in macular degeneration (MD) and retinitis pigmentosa (RP) demonstrated that responses in the lesion projection zones (LPZ) of V1 are task related, indicating significant limits of bottom-up visual system plasticity in MD and RP. In advanced glaucoma (GL), a prevalent eye disease and leading cause of blindness, the scope of visual system plasticity is currently unknown. We performed 3T fMRI in patients with extensive visual field defects due to GL (n=5), RP (n=2) and healthy controls (n=7; with simulated defects). Participants viewed contrast patterns drifting in 8 directions alternating with uniform gray and performed 3 tasks: (1) passive viewing (PV), (2) one-back task (OBT) and (3) fixation-dot task (FDT). During PV, they passively viewed the stimulus with central fixation, during OBT they reported the succession of the same two motion directions, and during FDT a change in the fixation color. In GL, LPZ responses of the early visual cortex (V1, V2 and V3) shifted from negative during PV to positive for OBT [p (corrected): V1(0.006); V2(0.04); V3(0.008)], while they were negative in the controls’ simulated LPZ for all stimulation conditions. For RP a similar pattern as for GL was observed. Consequently, activity in the de-afferented visual cortex in glaucoma is, similar to MD and RP, task-related. In conclusion, the lack of bottom-up plasticity appears to be a general feature of the human visual system. These insights are of importance for the development of treatment and rehabilitation schemes in glaucoma.

Highlights

Functional dynamics of early visual cortex LPZ depend on task demands in glaucoma

Brain activity in deprived visual cortex suggests absence of large-scale remapping

Limited scope of bottom-up plasticity is a general feature of human visual system

Visual system stability and plasticity is of relevance for therapeutic advances
Impairment in O-acetylserine-(thiol) lyase A and B, but not C, confers higher selenate sensitivity and uncovers role for A, B and C as L-Cys and L-SeCys desulfhydrases inArabidopsis
Authors: Kurmanbayeva Assylay , Bekturova Aizat , Soltabayeva Aigerim , Srivastava Sudhakar , Oshanova Dinara , Nurbekova Zhadyrassyn , Sagi Moshe
Published: September 2020

The role of the cytosolic O-acetylserine-(thiol) lyase A (OASTLA), chloroplastic OASTLB and mitochondrion OASTLC in plant resistance/sensitivity to selenate was studied inArabidopsisplants. Impairment in OASTLA and B resulted in reduced biomass, chlorophyll and soluble protein levels compared with impaired OASTL C and Wild-Type treated with selenate. The lower organic-Se and protein-Se levels followed by decreased organic-S, S in proteins and total glutathione inoastlAandoastlBcompared to Wild-Type andoastlCare indicative that Se accumulation is not the main cause for the stress symptoms, but rather the interference of Se with the S-reduction pathway. The increase in sulfite oxidase, adenosine 5′-phosphosulfate reductase, sulfite reductase and OASTL activity levels, followed by enhanced sulfite and sulfide, indicate a futile anabolic S-starvation response to selenate-induced organic-S catabolism inoastlAandoastlBcompared to Wild-Type andoastlC.

Additionally, the catabolic pathway of L-cysteine degradation was enhanced by selenate, and similar to L-cysteine producing activity,oastlAandBexhibited a significant decrease in L-cysteine desulfhydrase (DES) activity, compared with WT, indicating a major role of OASTLs in L-cysteine degradation. This notion was further evidenced by sulfide dependent DES in-gel activity, immunoblotting, immunoprecipitation with specific antibodies and identification of unique peptides in activity bands generated by OASTLA, B and C. Similar responses of the OASTLs in Seleno-Cysteine degradation was demonstrated in selenate stressed plants. Notably, no L-cysteine and L-Seleno-Cysteine DES activity bands but those related to OASTLs were evident. These results indicate the significance of OASTLs in degrading L-cysteine and L-SelenoCysteine inArabidopsis.

The cytosolic OASTLA and chloroplastic OASTLB have significantly higher desulfhydrase activity rates than the cytosolic DES1 and are able to degrade L-Cys and L-SeCys to sulfide and selenide, respectively inArabidopsis.
HGNChelper: identification and correction of invalid gene symbols for human and mouse
Authors: Oh Sehyun , Abdelnabi Jasmine , Al-Dulaimi Ragheed , Aggarwal Ayush , Ramos Marcel , Davis Sean , Riester Markus , Waldron Levi
Published: September 2020

Gene symbols are recognizable identifiers for gene names but are unstable and error-prone due to aliasing, manual entry, and unintentional conversion by spreadsheets to date format. Official gene symbol resources such as HUGO Gene Nomenclature Committee (HGNC) for human genes and the Mouse Genome Informatics project (MGI) for mouse genes provide authoritative sources of valid, aliased, and outdated symbols, but lack a programmatic interface and correction of symbols converted by spreadsheets. We present HGNChelper, an R package that identifies known aliases and outdated gene symbols based on the HGNC human and MGI mouse gene symbol databases, in addition to common mislabeling introduced by spreadsheets, and provides corrections where possible. HGNChelper identified invalid gene symbols in the most recent Molecular Signatures Database (mSigDB 7.0) and in platform annotation files of the Gene Expression Omnibus, with prevalence ranging from ∼3% in recent platforms to 30-40% in the earliest platforms from 2002-03. HGNChelper is installable from CRAN, with open development and issue tracking on GitHub and an associated pkgdown sitehttps://waldronlab.io/HGNChelper/.
Inference of recent admixture using genotype data
Authors: Pfaffelhuber Peter , Sester-Huss Elisabeth , Baumdicker Franz , Naue Jana , Lutz-Bonengel Sabine , Staubach Fabian
Published: September 2020

The inference of biogeographic ancestry (BGA) has become a focus of forensic genetics. Misinference of BGA can have profound unwanted consequences for investigations and society. We show that recent admixture can lead to misclassification and erroneous inference of ancestry proportions, using state of the art analysis tools with (i) simulations, (ii) 1000 genomes project data, and (iii) two individuals analyzed using the ForenSeq DNA Signature Prep Kit. Subsequently, we extend existing tools for estimation of individual ancestry (IA) by allowing for different IA in both parents, leading to estimates of parental individual ancestry (PIA), and a statistical test for recent admixture. Estimation of PIA outperforms IA in most scenarios of recent admixture. Furthermore, additional information about parental ancestry can be acquired with PIA that may guide casework.

Highlights

We improve statistical methods as used in STRUCTURE and ADMIXTURE for Biogeographical Ancestry (BGA) inference to account for recent admixture, i.e. different admixture of both parents.

The resulting recent admixture model has a higher accuracy in estimating individual admixture in most cases.

We give a likelihood ratio test for recent admixture, which is both highly specific and sensitive for recent admixture.

We find evidence of recent admixture in the 1000 genomes dataset.

The self-report on recent admixture of two self-sequenced samples was only confirmed in one case.
A Novel DNA Chromatography Method to DistinguishM. abscessusSubspecies and Macrolide Susceptibility
Authors: Yoshida Mitsunori , Sano Sotaro , Chien Jung-Yien , Fukano Hanako , Suzuki Masato , Asakura Takanori , Morimoto Kozo , Murase Yoshiro , Miyamoto Shigehiko , Kurashima Atsuyuki , Hasegawa Naoki , Hsueh Po-Ren , Mitarai Satoshi , Ato Manabu , Hoshino Yoshihiko
Published: September 2020

Rationale

The clinical impact of infection withMycobacterium abscessuscomplex (MABC), a group of emerging non-tuberculosis mycobacteria (NTM), is increasing.Mycobacterium abscessussubsp.abscessus/bolletiifrequently shows natural resistance to macrolide antibiotics, whereasMycobacterium abscessussubsp.massilienseis generally susceptible. Therefore, rapid and accurate discrimination of macrolide-susceptible MABC subgroups is required for effective clinical decisions about macrolide treatments for MABC infection.

Objectives

To develop a simple and rapid diagnostic that can identify MABC isolates showing macrolide susceptibility.

Methods

Whole genome sequencing (WGS) was performed for 148 clinical or environmental MABC isolates from Japan to identify genetic markers that can discriminate three MABC subspecies and the macrolide-susceptibleerm(41) T28C sequevar. Using the identified genetic markers, we established PCR based- or DNA chromatography-based assays. Validation testing was performed using MABC isolates from Taiwan.

Measurements and Main Results

We identified unique sequence regions that could be used to differentiate the three subspecies. Our WGS-based phylogenetic analysis indicated thatM. abscessuscarrying the macrolide-susceptibleerm(41) T28C sequevar were tightly clustered, and identified 11 genes that were significantly associated with the lineage for use as genetic markers. To detect these genetic markers and theerm(41) locus, we developed a DNA chromatography method that identified three subspecies, theerm(41) T28C sequevar and intacterm(41) for MABC in a single assay within one hour. The agreement rate between the DNA chromatography-based and WGS-based identification was 99.7%.

Conclusions

We developed a novel, rapid and simple DNA chromatography method for identification of MABC macrolide susceptibility with high accuracy.
GeneCup: mine PubMed for gene relationships using custom ontology and deep learning
Authors: Gunturkun Mustafa Hakan , Flashner Efraim , Wang Tengfei , Mulligan Megan K. , Williams Robert W. , Prins Pjotr , Chen Hao
Published: September 2020

Interpreting and integrating results from omics studies typically requires a comprehensive and time consuming survey of extant literature. Here, we introduce GeneCup, an easy to use literature mining web service that searches all PubMed abstracts for user-provided gene symbols in conjunction with a set of custom keywords organized into a customized ontology, as well as results from human genome-wide association studies (GWAS). As an example, we organized over 300 keywords related to drug addiction into seven categories. The literature search is conducted by querying the NIH PubMed server using a programming interface, which is followed by retrieving abstracts from a local copy of the PubMed archive. The main results presented to the user are individual sentences containing the gene symbol, organized by the keywords they also contain. These sentences are presented through an interactive graphical interface or as tables. GWAS results are displayed using a similar method. All results are linked to the original abstract in PubMed. In addition, a convolutional neural network is employed to distinguish sentences describing systemic stress from those describing cellular stress. The automated and comprehensive search strategy provided by GeneCup facilitates the integration of new discoveries from omic studies with existing literature. GeneCup is free and open source software. The source code of GeneCup and the link to a running instance is available athttps://github.com/hakangunturkun/GeneCup
RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion
Authors: Fic Weronika , Bastock Rebecca , Raimondi Francesco , Los Erinn , Inoue Yoshiko , Gallop Jennifer , Russell Robert B. , St Johnston Daniel
Published: September 2020

Cdc42-GTP is required for apical domain formation in epithelial cells where it recruits and activates the Par-6/aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically unclear. We used sequence analysis and 3D structure modelling to determine whichDrosophilaGTPase Activating Proteins (GAPs) are likely to interact with Cdc42 and identified RhoGAP19D as the sole Cdc42GAP required for polarity in the follicle cell epithelium. RhoGAP19D is recruited by α-catenin to lateral E-cadherin adhesion complexes, resulting in exclusion of active Cdc42 from the lateral domain.rhogap19dmutants therefore lead to lateral Cdc42 activity, which expands the apical domain through increased Par-6/aPKC activity and stimulates lateral contractility through the myosin light chain kinase, Genghis khan (MRCK). This causes buckling of the epithelium and invasion into the adjacent tissue, a phenotype resembling that of pre-cancerous breast lesions. Thus, RhoGAP19D couples lateral Cadherin adhesion to the apical localisation of active Cdc42, thereby suppressing epithelial invasion.
Structural and Functional Comparison of SARS-CoV-2-Spike Receptor Binding Domain Produced inPichia pastorisand Mammalian Cells
Authors:   Argentinian AntiCovid Consortium, Arbeitman Claudia R. , Auge Gabriela , Blaustein Matías , Bredeston Luis , Corapi Enrique S. , Craig Patricio O. , Cossio Leandro A. , Dain Liliana , D’Alessio Cecilia , Elias Fernanda , Fernández Natalia B. , Gasulla Javier , Gorojovsky Natalia , Gudesblat Gustavo E. , Herrera María G. , Ibañez Lorena I. , Idrovo Tommy , Randon Matías Iglesias , Kamenetzky Laura , Nadra Alejandro D. , Noseda Diego G. , Paván Carlos H. , Pavan María F. , Pignataro María F. , Roman Ernesto , Ruberto Lucas A. M. , Rubinstein Natalia , Santos Javier , Duarte Francisco Velazquez , Zelada Alicia M.
Published: September 2020

The yeastPichia pastorisis a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from SARS-CoV-2 Spike protein expressed inP. pastorisand in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cells was properly folded, as indicated by UV-absorption, circular dichroism and tryptophan fluorescence. They also had similar stability, as indicated by temperature-induced unfolding (observedTmwere 50 °C and 52 °C for RBD produced inP. pastorisand HEK-293T cells, respectively). Moreover, the stability of both variants was similarly reduced when the ionic strength was increased, in agreement with a computational analysis predicting that a set of ionic interactions may stabilize RBD structure. Further characterization by HPLC, size-exclusion chromatography and mass spectrometry revealed a higher heterogeneity of RBD expressed inP. pastorisrelative to that produced in HEK-293T cells, which disappeared after enzymatic removal of glycans. The production of RBD inP. pastoriswas scaled-up in a bioreactor, with yields above 45 mg/L of 90% pure protein, thus potentially allowing large scale immunizations to produce neutralizing antibodies, as well as the large scale production of serological tests for SARS-CoV-2.
Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication
Authors: Akiyama Benjamin M. , Graham Monica E. , O′Donoghue Zoe , Beckham J. David , Kieft Jeffrey S.
Published: September 2020

Mosquito-borne flaviviruses (MBFVs) including dengue, West Nile, yellow fever, and Zika viruses have an RNA genome encoding one open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). The 3′ UTRs of MBFVs contain regions of high sequence conservation in structured RNA elements known as dumbbells (DBs) that regulate translation and replication of the viral RNA genome, functions proposed to depend on the formation of an RNA pseudoknot. To understand how DB structure provides this function, we used x-ray crystallography and structural modeling to reveal the details of its three-dimensional fold. The structure confirmed the predicted pseudoknot and molecular modeling revealed how conserved sequences form a four-way junction that appears to stabilize the pseudoknot. Single-molecule FRET suggests that the DB pseudoknot is a stable element that can regulate the switch between translation and replication during the viral lifecycle by modulating long-range RNA conformational changes.
Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway inC. elegans
Authors: Ju Shouyong , Chen Hanqiao , Wang Shaoying , Lin Jian , Aroian Raffi V , Peng Donghai , Sun Ming
Published: September 2020

Pathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, usingBacillus thuringiensis-Caenorhabditis elegansas a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reportedC. eleganscan monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.