Endothelial cell calcium flux is critical for leukocyte transendothelial migration (TEM), which in turn is essential for the inflammatory response. Intravital microscopy of endothelial cell calcium dynamics reveals that calcium increases locally and transiently around the transmigration pore during TEM. Endothelial calmodulin (CaM), a key calcium signaling protein, interacts with the IQ domain of IQGAP1, which is localized to endothelial junctions and is required for TEM. In the presence of calcium, CaM binds endothelial calcium/calmodulin kinase IIδ (CaMKIIδ). Disrupting the function of CaM or CaMKII with small-molecule inhibitors, expression of a CaMKII inhibitory peptide, or expression of dominant negative CaMKIIδ significantly reduces TEM by interfering with the delivery of the lateral border recycling compartment (LBRC) to the site of TEM. Endothelial CaMKII is also required for TEM in vivo as shown in two independent mouse models. These findings highlight novel roles for endothelial CaM and CaMKIIδ in transducing the spatiotemporally restricted calcium signaling required for TEM.Taraxacum syriacum (TS) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen (APAP). The aim of the present study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine (NAC) as a standard drug. Thirty male Wistar rat were randomly divided into five groups. Control group; APAP (1g/kg) group; APAP-NAC (160 mg/kg) group and APAP-TS100 and APAP-TS200 groups APAP plus 100 and 200 mg/kg of TS extract, respectively. After 7 days treatment, serum and liver and kidney tissues were prepared and evaluated. TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats. Moreover, treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment. This study suggests that the extract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its free radical scavenging and antioxidant properties. The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC. Lower nurse staffing levels are associated with increased hospital mortality. click here Older patients with cognitive impairments (CI) have higher mortality rates than similar patients without CI and may be additionally vulnerable to low staffing. To explore associations between registered nurse (RN) and nursing assistant (NA) staffing levels, mortality and readmission in older patients admitted to general medical/surgical wards. Retrospective cohort. All unscheduled admissions to an English hospital of people aged ≥75 with cognitive screening over 14months. The exposure was defined as deviation in staffing hours from the ward daily mean, averaged across the patient stay. Outcomes were mortality in hospital/within 30days of discharge and 30-day re-admission. Analyses were stratified by CI. 12,544 admissions were included. Patients with CI (33.2%) were exposed to similar levels of staffing as those without. An additional 0.5 RN hours per day was associated with 10% reduction in the odds of death overall (odds ratio 0.90 [95% CI 0.84-0.97]) 15% in patients with CI (OR 0.85 [0.74-0.98]) and 7% in patients without (OR 0.93 [0.85-1.02]). An additional 0.5 NA hours per day was associated with a 15% increase in mortality in patients with no impairment. Readmissions decreased by 6% for an additional 0.5 RN hours in patients with CI. Although exposure to low staffing was similar, the impact on mortality and readmission for patients with CI was greater. Increased mortality with higher NA staffing in patients without CI needs exploration.Although exposure to low staffing was similar, the impact on mortality and readmission for patients with CI was greater. Increased mortality with higher NA staffing in patients without CI needs exploration.Recent advances in super-resolution imaging techniques, together with new fluorescent probes have enhanced our understanding of bacterial pathogenesis and their interplay within the host. In this review, we provide an overview of what these techniques have taught us about the bacterial lifestyle, the nucleoid organization, its complex protein secretion systems, as well as the secreted virulence factors.Vertebrate dentitions are often collapsed into a few discrete categories, obscuring both potentially important functional differences between them and insight into their evolution. The terms homodonty and heterodonty typically conflate tooth morphology with tooth function, and require context-dependent subcategories to take on any specific meaning. Qualifiers like incipient, transient, or phylogenetic homodonty attempt to provide a more rigorous definition but instead highlight the difficulties in categorizing dentitions. To address these issues, we recently proposed a method for quantifying the function of dental batteries based on the estimated stress of each tooth (inferred using surface area) standardized for jaw out-lever (inferred using tooth position). This method reveals a homodonty-heterodonty functional continuum where small and large teeth work together to transmit forces to a prey item. Morphological homodonty or heterodonty refers to morphology, whereas functional homodonty or heterodonty refers species.Inflammasomes are multiprotein complexes of the innate immune system. Their activation leads to robust secretion of exosomes. In this issue, Wozniak et al. (2020. J. Cell Biol. https//doi.org/10.1083/jcb.201912074) reveal a connection between inflammasome-mediated cleavage of Rab-interacting lysosomal protein (RILP) and sequence-specific loading of miRNAs into exosomes.A subset of peroxisomes is retained at the mother cell cortex by the Pex3-Inp1 complex. We identify Inp1 as the first known plasma membrane-peroxisome (PM-PER) tether by demonstrating that Inp1 meets the predefined criteria that a contact site tether protein must adhere to. We show that Inp1 is present in the correct subcellular location to interact with both the plasma membrane and peroxisomal membrane and has the structural and functional capacity to be a PM-PER tether. Additionally, expression of artificial PM-PER tethers is sufficient to restore retention in inp1Δ cells. We show that Inp1 mediates peroxisome retention via an N-terminal domain that binds PI(4,5)P2 and a C-terminal Pex3-binding domain, forming a bridge between the peroxisomal membrane and the plasma membrane. We provide the first molecular characterization of the PM-PER tether and show it anchors peroxisomes at the mother cell cortex, suggesting a new model for peroxisome retention.