Tag: nevin manimala

PLoS Pathog. 2022 Apr 28;18(4):e1010504. doi: 10.1371/journal.ppat.1010504. Online ahead of print.

ABSTRACT

RSK1, an essential cellular kinase for Kaposi’s sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosphorylation via two separated functional regions: SIMs and amino acid 17-90, respectively, which do not affect each other. Similar to KSHV ORF45, ORF45 of Rhesus Macaque Rhadinovirus has only one SIM and also increases RSK1 SUMOylation in a SIM-dependent manner, while other ORF45 homologues do not have this function. Our work characterized ORF45 as a novel virus encoded SUMO E3 ligase, which is required for ORF45-RSK1 axis-mediated KSHV lytic gene expression.

PMID:35482828 | DOI:10.1371/journal.ppat.1010504

PLoS One. 2022 Apr 28;17(4):e0260911. doi: 10.1371/journal.pone.0260911. eCollection 2022.

ABSTRACT

There has been an increasing interest in joint analysis of multiple phenotypes in genome-wide association studies (GWAS) because jointly analyzing multiple phenotypes may increase statistical power to detect genetic variants associated with complex diseases or traits. Recently, many statistical methods have been developed for joint analysis of multiple phenotypes in genetic association studies, including the Clustering Linear Combination (CLC) method. The CLC method works particularly well with phenotypes that have natural groupings, but due to the unknown number of clusters for a given data, the final test statistic of CLC method is the minimum p-value among all p-values of the CLC test statistics obtained from each possible number of clusters. Therefore, a simulation procedure needs to be used to evaluate the p-value of the final test statistic. This makes the CLC method computationally demanding. We develop a new method called computationally efficient CLC (ceCLC) to test the association between multiple phenotypes and a genetic variant. Instead of using the minimum p-value as the test statistic in the CLC method, ceCLC uses the Cauchy combination test to combine all p-values of the CLC test statistics obtained from each possible number of clusters. The test statistic of ceCLC approximately follows a standard Cauchy distribution, so the p-value can be obtained from the cumulative density function without the need for the simulation procedure. Through extensive simulation studies and application on the COPDGene data, the results demonstrate that the type I error rates of ceCLC are effectively controlled in different simulation settings and ceCLC either outperforms all other methods or has statistical power that is very close to the most powerful method with which it has been compared.

PMID:35482827 | DOI:10.1371/journal.pone.0260911

PLoS One. 2022 Apr 28;17(4):e0265443. doi: 10.1371/journal.pone.0265443. eCollection 2022.

ABSTRACT

The flow of nanofluid over a variable thickened stretching sheet is studied in this article. Non-Fourier’s heat flux and non-Fick’s mass flux are incorporated for heat and mass flow analysis. Silver (Ag) and Copper (Cu) are considered nanoparticles with water as base fluid. The resulting equations are transformed into the dimensionless form using similarity transformation and solved by RK-4 with the shooting method. The impact of the governing parameters on the dimensionless velocity, temperature, concentration, skin friction coefficient, streamlines, and finally isotherms are incorporated. It is observed that increment in power-law index parameter uplifts the fluid flow, heat, and mass transfer. The increase in the magnitude of skin friction coefficient in (x-direction) with wall thickness parameter is high for nanofluid containing silver nanoparticles as compared to copper nanoparticles.

PMID:35482823 | DOI:10.1371/journal.pone.0265443

PLoS One. 2022 Apr 28;17(4):e0267297. doi: 10.1371/journal.pone.0267297. eCollection 2022.

ABSTRACT

Using real-time eye-movement measures, we asked how a fantastical discourse context competes with stored representations of real-world events to influence the moment-by-moment interpretation of a story by 7-year-old children and adults. Seven-year-olds were less effective at bypassing stored real-world knowledge during real-time interpretation than adults. Our results suggest that children privilege stored semantic knowledge over situation-specific information presented in a fictional story context. We suggest that 7-year-olds’ canonical semantic and conceptual relations are sufficiently strongly rooted in statistical patterns in language that have consolidated over time that they overwhelm new and unexpected information even when the latter is fantastical and highly salient.

PMID:35482807 | DOI:10.1371/journal.pone.0267297

PLoS One. 2022 Apr 28;17(4):e0267718. doi: 10.1371/journal.pone.0267718. eCollection 2022.

ABSTRACT

Transcutaneous spinal direct current stimulation (tsDCS) is an effective non-invasive spinal cord electrical stimulation technique to induce neuromodulation of local and distal neural circuits of the central nervous system (CNS). Applied to the spinal cord lumbosacral region, tsDCS changes electrophysiological responses of the motor, proprioceptive and nociceptive pathways, alters the performance of some lower limb motor tasks and can even modulate the behavior of supramedullary neuronal networks. In this study an experimental protocol was conducted to verify if tsDCS (5 mA, 20 minutes) of two different polarizations, applied over the lumbosacral region (tenth thoracic vertebrae (T10)), can induce changes in postural sway oscillations of young healthy individuals during quiet standing. A novel initialization of the electrical stimulation was developed to improve subject blinding to the different stimulus conditions including the sham trials. Measures of postural sway, both global and structural, were computed before, during and following the DC stimulation period. The results indicated that, for the adopted conditions, tsDCS did not induce statistically significant changes in postural sway of young healthy individuals during quiet standing.

PMID:35482798 | DOI:10.1371/journal.pone.0267718

PLoS One. 2022 Apr 28;17(4):e0267708. doi: 10.1371/journal.pone.0267708. eCollection 2022.

ABSTRACT

User committees, such as Health Facility Governing Committees, are popular platforms for representing communities and civil society in holding service providers accountable. Fiscal decentralization via various arrangements such as Direct Health Facility Financing is thought to strengthen Health Facility Governing Committees in improving accountability in carrying out the devolved tasks and mandates. The purpose of this study was to analyze the status of accountability of Health Facility Governing Committees in Tanzania under the Direct Health Facility Financing setting as perceived by the supply side. In 32 different health institutions, a cross-sectional design was used to collect both qualitative and quantitative data at one point in time. Data was collected through a closed-ended questionnaire, an in-depth interview, and a Focus Group Discussion. Descriptive statistics, multiple logistic regression, and theme analysis were used to analyze the data. According to the findings, Health Facility Governing Committees’ accountability is 78%. Committees have a high level of accountability in terms of encouraging the community to join community health funds (91.71%), receiving medicines and medical commodities (88.57%), and providing timely health services (84.29%). The health facility governance committee’s responsibility was shown to be substantially connected with the health planning component (p = 0.0048) and the financial management aspect (p = 0.0045). This study found that the fiscal decentralization setting permits Committees to be accountable for carrying out their obligations, resulting in improved health service delivery in developing nations.

PMID:35482793 | DOI:10.1371/journal.pone.0267708

PLoS One. 2022 Apr 28;17(4):e0267032. doi: 10.1371/journal.pone.0267032. eCollection 2022.

ABSTRACT

PURPOSE: The COVID-19 pandemic has put hospital workers around the world in an unprecedented and difficult situation, possibly leading to emotional difficulties and mental health problems. We aimed to analyze psychological symptoms of the hospital employees of the Paris Saint-Joseph Hospital Group a few months after the 1st wave of the pandemic.

PARTICIPANTS AND METHODS: From July 15 to October 1, 2020, a cross-sectional survey was conducted among hospital workers in the two locations of our hospital group using the Hospital Anxiety and Depression Scale (HADS) and Post-Traumatic Stress Disorder (PTSD) Checklist (PCL) to measure anxiety, depression, and PTSD symptoms. Factors independently associated with these symptoms were identified.

RESULTS: In total, 780 participants (47% caregivers, 18% health administrative workers, 16% physicians, and 19% other professionals) completed the survey. Significant symptoms of anxiety, depression, and PTSD were reported by 41%, 21%, and 14% of the participants, respectively. Hierarchical regression analysis showed a higher risk of having psychological symptoms among those (1) who were infected by SARS-CoV-2 or had colleagues or relatives infected by the virus, (2) who retrospectively reported to have had an anxious experience during the first wave, and (3) with a previous history of burnout or depression. In contrast, job satisfaction appeared to be a protective factor. Overall, hospital workers showed the statistically same levels of anxiety, depression, and PTSD symptoms, regardless of their profession and whether they had worked in units with COVID-19 patients or not.

CONCLUSIONS: Our cross-sectional survey of 780 hospital workers shows that after the first wave, hospital employees had a significant burden of mental health symptoms. Specific preventive measures to promote mental well-being among hospital workers exposed to COVID-19 need to be implemented, first among particularly vulnerable staff, and then, for all hospital staff for whom anxiety is detected early, and not only those who were directly exposed to infected patients.

PMID:35482772 | DOI:10.1371/journal.pone.0267032

PLoS One. 2022 Apr 28;17(4):e0266883. doi: 10.1371/journal.pone.0266883. eCollection 2022.

ABSTRACT

While a substantial amount of research has focused on the abuse of opioids and cannabinoids in human populations, few studies have investigated accidental poisoning events in pet populations. The objective of this study was to identify whether poisoning events involving opioids and cannabinoids clustered in space, time, and space-time, and compare the locations of clusters between the two toxicants. Data were obtained concerning reports of dog poisoning events from the American Society for the Prevention of Cruelty to Animals’ (ASPCA) Animal Poisoning Control Center (APCC), from 2005-2014. The spatial scan statistic was used to identify clusters with a high proportion of these poisoning events. Our analyses show that opioid and cannabinoid poisoning events clustered in space, time, and space-time. The cluster patterns identified for each toxicant were distinct, but both shared some similarities with human use data. This study may help increase awareness to the public, public health, and veterinary communities about where and when dogs were most affected by opioid and cannabinoid poisonings. This study highlights the need to educate dog owners about safeguarding opioid and cannabinoid products from vulnerable populations.

PMID:35482776 | DOI:10.1371/journal.pone.0266883

Med Sci Sports Exerc. 2022 Apr 25. doi: 10.1249/MSS.0000000000002949. Online ahead of print.

ABSTRACT

INTRODUCTION: Individual differences in brain structure and function in older adults are potential proxies of brain reserve or maintenance and may provide mechanistic predictions of adherence to exercise. We hypothesized that multimodal neuroimaging features would predict adherence to a six-month randomized controlled trial of exercise in 131 older adults (aged 65.79 (4.65) years, 63 percent female), alone and in combination with psychosocial, cognitive and health measures.

METHODS: Regularized elastic net regression within a nested cross-validation framework was applied to predict adherence to the intervention in three separate models (brain structure and function only, psychosocial, health and demographic data only, and a multimodal model).

RESULTS: Higher cortical thickness in somatosensory and inferior frontal regions and less surface area in primary visual and inferior frontal regions predicted adherence. Higher nodal functional connectivity (degree count) in default, frontoparietal and attentional networks, and less nodal strength in primary visual and temporoparietal networks predicted exercise adherence (r = 0.24, p = 0.004). Survey and clinical measures of gait and walking self-efficacy, biological sex and perceived stress also predicted adherence (r = 0.17, p = 0.056), however this prediction was not significant when tested against a null test statistic. A combined multimodal model achieved the highest predictive strength (r = 0.28, p = 0.001).

CONCLUSIONS: Our results suggest there is substantial utility of using brain-based measures in future research into precision and individualized exercise interventions older adults.

PMID:35482769 | DOI:10.1249/MSS.0000000000002949

PLoS One. 2022 Apr 28;17(4):e0266277. doi: 10.1371/journal.pone.0266277. eCollection 2022.

ABSTRACT

BACKGROUND: COVID-19 household transmissibility remains unclear in Pakistan. To understand the dynamics of Severe Acute Respiratory Syndrome Coronavirus disease epidemiology, this study estimated Secondary Attack Rate (SAR) among household and close contacts of index cases in Pakistan using a statistical transmission model.

METHODOLOGY: A retrospective cohort study was conducted using an inclusive contact tracing dataset from the provinces of Punjab and Khyber-Pakhtunkhwa to estimate SAR. We considered the probability of an infected person transmitting the infection to close contacts regardless of residential addresses. This means that close contacts were identified irrespective of their relationship with the index case. We assessed demographic determinants of COVID-19 infectivity and transmissibility. For this purpose based on evolving evidence, and as CDC recommends fully vaccinated people get tested 5-7 days after close contact with a person with suspected or confirmed COVID-19. Therefore we followed the same procedure in the close contacts for secondary infection.

FINDINGS: During the study period from 15th May 2020 to 15th Jan 2021, a total of 339 (33.9%) index cases were studied from 1000 cases initially notified. Among close contact groups (n = 739), households were identified with an assumed mean incubation period of 8.2+4.3 days and a maximum incubation period of 15 days. SAR estimated here is among the household contacts. 117 secondary cases from 739 household contacts, with SAR 11.1% (95% CI 9.0-13.6). All together (240) SAR achieved was 32.48% (95% CI; 29.12-37.87) for symptomatic and confirmed cases. The potential risk factors for SAR identified here included; old age group (>45 years of age), male (gender), household members >5, and residency in urban areas and for index cases high age group. Overall local reproductive number (R) based on the observed household contact frequencies for index/primary cases was 0.9 (95% CI 0.47-1.21) in Khyber Pakhtunkhwa and 1.3 (95% CI 0.73-1.56) in Punjab.

CONCLUSIONS: SAR estimated here was high especially in the second phase of the COVID-19 pandemic in Pakistan. The results highlight the need to adopt rigorous preventive measures to cut the chain of viral transmission and prevent another wave of COVID-19.

PMID:35482766 | DOI:10.1371/journal.pone.0266277