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Sterile alpha motif and HD domain 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that restricts the infection of a variety of RNA and DNA viruses, including herpesviruses. The anti-viral function of SAMHD1 is associated with its dNTPase activity, which is regulated by several post-translational modifications, including phosphorylation, acetylation and ubiquitination. Our recent studies also demonstrated that the E3 SUMO ligase PIAS1 functions as an Epstein-Barr virus (EBV) restriction factor. However, whether SAMHD1 is regulated by PIAS1 to restrict EBV replication remains unknown.
In this study, we showed that PIAS1 interacts with SAMHD1 and promotes its SUMOylation. We identified three lysine residues (K469, K595 and K622) located on the surface of SAMHD1 as the major SUMOylation sites. We demonstrated that phosphorylated SAMHD1 can be SUMOylated by PIAS1 and SUMOylated SAMHD1 can also be phosphorylated by viral protein kinases. We showed that SUMOylation-deficient SAMHD1 loses its anti-EBV activity. Furthermore, we demonstrated that SAMHD1 is associated with EBV genome in a PIAS1-dependent manner.
Our study reveals that PIAS1 synergizes with SAMHD1 to inhibit EBV lytic replication through protein-protein interaction and SUMOylation.
Our study reveals that PIAS1 synergizes with SAMHD1 to inhibit EBV lytic replication through protein-protein interaction and SUMOylation.
Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores.
Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. see more In a subset of these subjects (n = 43), samples were collected thricis result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects).
These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.
These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.
A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma.
Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups.
Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8.
Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality.
Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality.
Most injuries in track and field are caused by overuse with conflicting reports concerning the underlying mechanisms. The purpose of this study was to evaluate how biomechanical and clinical factors relate to the risk of overuse injuries, and to investigate whether the relationships between potential risk factors and injury become stronger if injuries are grouped by location.
The study is a prospective cohort study conducted during a Swedish track and field season over eleven months, from October to August. The cohort consisted of elite male and female track and field athletes competing in either middle- and long-distance running, sprinting, jumping, or throwing events (n = 96). Athletes performed a baseline screening at enrollment consisting of a clinical examination, running, and strength tests. Injury data was collected during the season by medical professionals and divided according to their anatomical location into upper-body, thigh/hip, knee, or foot/shank injuries.
Thirty-four (54.8%) injuries wh grouping appears to increase effect size for certain risk factors. Athletes with a slower knee flexion velocity during stance phase were more likely to become injured (p-value less then .03, rpb = .37). An increased cohort size to further sub-divide injuries into specific diagnoses is needed.
The Regional Economic Partnership Agreement (RCEP) is a mega regional trade agreement signed by fifteen countries on 15 November 2020 after 8 years of negotiation. Signatories include the ten members of the Association of South East Asian Nations (ASEAN) plus China, New Zealand, Japan, South Korea and Australia. India was a negotiating party until it withdrew from the negotiations in November 2019. The RCEP negotiations were initially framed as focused on the needs of low income countries. Public health concerns emerged however when draft negotiating chapters were leaked online, revealing pressures on countries to agree to intellectual property and investment measures that could exacerbate issues of access to medicines and seeds, and protecting regulatory space for public health. A concerted Asia Pacific civil society campaign emerged in response to these concerns, and in 2019, media and government reporting suggested that several of these measures had been taken off the table, which was subsequently confirmed in the release of the signed text in November 2020.
