Role for polo-like kinase 4 in mediation of cytokinesis.

The mitotic protein polo-like kinase 4 (PLK4) plays a critical role in centrosome duplication for cell division. By using immunofluorescence, we confirm that PLK4 is localized to centrosomes. In addition, we find that phospho-PLK4 (pPLK4) is cleaved and distributed to kinetochores (metaphase and anaphase), spindle midzone/cleavage furrow (anaphase and telophase), and midbody (cytokinesis) during cell division in immortalized epithelial cells as well as breast, ovarian, and colorectal cancer cells. The distribution of pPLK4 midzone/cleavage furrow and midbody positions pPLK4 to play a functional role in cytokinesis. Indeed, we found that inhibition of PLK4 kinase activity with a small-molecule inhibitor, CFI-400945, prevents translocation to the spindle midzone/cleavage furrow and prevents cellular abscission, leading to the generation of cells with polyploidy, increased numbers of duplicated centrosomes, and vulnerability to anaphase or mitotic catastrophe. The regulatory role of PLK4 in cytokinesis makes it a potential target for therapeutic intervention in appropriately selected cancers

A global analysis of the impact of COVID-19 stay-at-home restrictions on crime

The implementation of COVID-19 stay-at-home policies was associated with a considerable drop in urban crime in 27 cities across 23 countries. More stringent restrictions over movement in public space were predictive of larger declines in crime. The stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.Peer reviewe

Role for polo-like kinase 4 in mediation of cytokinesis.

The mitotic protein polo-like kinase 4 (PLK4) plays a critical role in centrosome duplication for cell division. By using immunofluorescence, we confirm that PLK4 is localized to centrosomes. In addition, we find that phospho-PLK4 (pPLK4) is cleaved and distributed to kinetochores (metaphase and anaphase), spindle midzone/cleavage furrow (anaphase and telophase), and midbody (cytokinesis) during cell division in immortalized epithelial cells as well as breast, ovarian, and colorectal cancer cells. The distribution of pPLK4 midzone/cleavage furrow and midbody positions pPLK4 to play a functional role in cytokinesis. Indeed, we found that inhibition of PLK4 kinase activity with a small-molecule inhibitor, CFI-400945, prevents translocation to the spindle midzone/cleavage furrow and prevents cellular abscission, leading to the generation of cells with polyploidy, increased numbers of duplicated centrosomes, and vulnerability to anaphase or mitotic catastrophe. The regulatory role of PLK4 in cytokinesis makes it a potential target for therapeutic intervention in appropriately selected cancers

Is supine exercise associated with adverse maternal and fetal outcomes? A systematic review

Objective Theoretical concerns regarding the supine position at rest due to the gravid uterus obstructing aorta and vena caval flow may impinge uterine blood flow (UBF) to the fetus and maternal venous return. Design Systematic review. Data sources Online databases up to 11 December 2017. Study criteria Eligible population (pregnant without contraindication to exercise), intervention (frequency, intensity, duration, volume or type of supine exercise), comparator (no exercise or exercise in left lateral rest position, upright posture or other supine exercise), outcomes (potentially adverse effects on maternal blood pressure, cardiac output, heart rate, oxygen saturation, fetal movements, UBF, fetal heart rate (FHR) patterns; adverse events such as bradycardia, low birth weight, intrauterine growth restriction, perinatal mortality and other adverse events as documented by study authors), and study design (except case studies and reviews) published in English, Spanish, French or Portuguese. Results Seven studies (n=1759) were included. \u27Very low\u27 to \u27low\u27 quality evidence from three randomised controlled trials indicated no association between supervised exercise interventions that included supine exercise and low birth weight compared with no exercise. There was \u27very low\u27 to \u27low\u27 quality evidence from four observational studies that showed no adverse events in the mother; however, there were abnormal FHR patterns (as defined by study authors) in 20 of 65 (31%) fetuses during an acute bout of supine exercise. UBF decreased (13%) when women moved from left lateral rest to acute dynamic supine exercise. Conclusion There was insufficient evidence to ascertain whether maternal exercise in the supine position is safe or should be avoided during pregnancy