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The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19.

This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staSARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission.

Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted.

Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.

Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.Mitochondria are highly dynamic organelles that continuously grow, divide, and fuse. The division of mitochondria is crucial for human health. During mitochondrial division, the mechano-guanosine triphosphatase (GTPase) dynamin-related protein (Drp1) severs mitochondria at endoplasmic reticulum (ER)-mitochondria contact sites, where peripheral ER tubules interact with mitochondria. Here, we report that Drp1 directly shapes peripheral ER tubules in human and mouse cells. This ER-shaping activity is independent of GTP hydrolysis and located in a highly conserved peptide of 18 amino acids (termed D-octadecapeptide), which is predicted to form an amphipathic α helix. Synthetic D-octadecapeptide tubulates liposomes in vitro and the ER in cells. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.Knowledge of fundamental differences between breast cancer subtypes has driven therapeutic advances; however, basal-like breast cancer (BLBC) remains clinically intractable. Because BLBC exhibits alterations in DNA repair enzymes and cell-cycle checkpoints, elucidation of factors enabling the genomic instability present in this subtype has the potential to reveal novel anti-cancer strategies. Here, we demonstrate that BLBC is especially sensitive to suppression of iron-sulfur cluster (ISC) biosynthesis and identify DNA polymerase epsilon (POLE) as an ISC-containing protein that underlies this phenotype. In BLBC cells, POLE suppression leads to replication fork stalling, DNA damage, and a senescence-like state or cell death. In contrast, luminal breast cancer and non-transformed mammary cells maintain viability upon POLE suppression but become dependent upon an ATR/CHK1/CDC25A/CDK2 DNA damage response axis. Guanosine price We find that CDK1/2 targets exhibit hyperphosphorylation selectively in BLBC tumors, indicating that CDK2 hyperactivity is a genome integrity vulnerability exploitable by targeting POLE.Behavioral control is not unitary. It comprises parallel systems, model based and model free, that respectively generate flexible and habitual behaviors. Model-based decisions use predictions of the specific consequences of actions, but how these are implemented in the brain is poorly understood. We used calcium imaging and optogenetics in a sequential decision task for mice to show that the anterior cingulate cortex (ACC) predicts the state that actions will lead to, not simply whether they are good or bad, and monitors whether outcomes match these predictions. ACC represents the complete state space of the task, with reward signals that depend strongly on the state where reward is obtained but minimally on the preceding choice. Accordingly, ACC is necessary only for updating model-based strategies, not for basic reward-driven action reinforcement. These results reveal that ACC is a critical node in model-based control, with a specific role in predicting future states given chosen actions.The TRPA1 ion channel is activated by electrophilic compounds through the covalent modification of intracellular cysteine residues. How non-covalent agonists activate the channel and whether covalent and non-covalent agonists elicit the same physiological responses are not understood. Here, we report the discovery of a non-covalent agonist, GNE551, and determine a cryo-EM structure of the TRPA1-GNE551 complex, revealing a distinct binding pocket and ligand-interaction mechanism. Unlike the covalent agonist allyl isothiocyanate, which elicits channel desensitization, tachyphylaxis, and transient pain, GNE551 activates TRPA1 into a distinct conducting state without desensitization and induces persistent pain. Furthermore, GNE551-evoked pain is relatively insensitive to antagonist treatment. Thus, we demonstrate the biased agonism of TRPA1, a finding that has important implications for the discovery of effective drugs tailored to different disease etiologies.

To quantify the relationship between substance use behaviors before and after traumatic brain injury (TBI), to identify populations that may benefit more from targeted interventions to reduce the effect of substance use on TBI recovery, and to establish areas for further study.

Studies were identified via literature searches using MEDLINE, PsychInfo, PsychArticles, PubMed, and GoogleScholar (published before January 2019), as well as reference section reviews and forward searches. Searches were conducted using search terms for TBI and substance use behaviors.

Studies were included if they (1) contained both a measure of TBI and a measure of substance use behaviors; (2) reported an effect size representing the relationship between substance use behaviors before and after TBI, compared TBI vs non-TBI groups on substance use behaviors controlling for pre-TBI substance use, or compared groups with differing TBI severity on subsequent substance use behaviors controlling for pre-TBI substance use; (3) were written in English; and (4) were human subjects research.