Baileyclements7609

Humpback whales are thought to undertake annual migrations between their low latitude breeding grounds and high latitude feeding grounds. However, under specific conditions, humpback whales sometimes change their migratory destination or skip migration overall. Here we document the surprising persistent presence of humpback whales in the Atlantic sector of the Southern Ocean during five years (2011, 2012, 2013, 2017, and 2018) using passive acoustic data. However, in the El Niño years 2015 and 2016, humpback whales were virtually absent. Our data show that humpback whales are systematically present in the Atlantic sector of the Southern Ocean and suggest that these whales are particularly sensitive to climate oscillations which have profound effects on winds, sea ice extent, primary production, and especially krill productivity.The presence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with an unfavorable prognosis. FLT3 inhibitors, such as midostaurin, are used clinically but fail to entirely eradicate FLT3-ITD + AML. This study introduces a new perspective and highlights the impact of RAC1-dependent actin cytoskeleton remodeling on resistance to midostaurin in AML. RAC1 hyperactivation leads resistance via hyperphosphorylation of the positive regulator of actin polymerization N-WASP and antiapoptotic BCL-2. RAC1/N-WASP, through ARP2/3 complex activation, increases the number of actin filaments, cell stiffness and adhesion forces to mesenchymal stromal cells (MSCs) being identified as a biomarker of resistance. Midostaurin resistance can be overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant AML cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate FLT3-ITD + AML.We investigated the mediating roles of activating transcription factor 3 (ATF3), an injury marker, or C-type lectin member 5A (CLEC5A), an inflammatory response molecule, in the induction of endoplasmic reticulum (ER) stress and neuroinflammation in diabetic peripheral neuropathy in ATF3 and CLEC5A genetic knockout (aft3-/- and clec5a-/-, respectively) mice. ATF3 was expressed intranuclearly and was upregulated in mice with diabetic peripheral neuropathy (DN) and clec5a-/- mice. The DN and clec5a-/- groups also exhibited neuropathic behavior, but not in the aft3-/- group. The upregulation profiles of cytoplasmic polyadenylation element-binding protein, a protein translation-regulating molecule, and the ER stress-related molecules of inositol-requiring enzyme 1α and phosphorylated eukaryotic initiation factor 2α in the DN and clec5a-/- groups were correlated with neuropathic behavior. click here Ultrastructural evidence confirmed ER stress induction and neuroinflammation, including microglial enlargement and proinflammatory cytokine release, in the DN and clec5a-/- mice. By contrast, the induction of ER stress and neuroinflammation did not occur in the aft3-/- mice. Furthermore, the mRNA of reactive oxygen species-removing enzymes such as superoxide dismutase, heme oxygenase-1, and catalase were downregulated in the DN and clec5a-/- groups but were not changed in the aft3-/- group. Taken together, the results indicate that intraneuronal ATF3, but not CLEC5A, mediates the induction of ER stress and neuroinflammation associated with diabetic neuropathy.Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by Th17 cells (a subgroup of helper T cells), which is a key factor in the development of atherosclerosis. However, the effect of IL-17A on the senescence of vascular endothelial cells is still unclear. In this study, we aimed to explore the role of IL-17A on endothelial cell senescence and its signaling pathways associated with senescence. The proportion of Th17 cells in the spleen and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 (VCAM-1) in mice of different ages were increased with aging. In vitro experiments showed that proliferation was inhibited, senescent β-galactosidase and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the NF-κB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully inhibited IL-17A-induced expression of senescence-associated proteins. In conclusion, our data reveal a previously unsuspected link between IL-17A and endothelial cell senescence, which was mediated by the NF-κB /p53/Rb pathway.

Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease and bears important prognostic implications. Local inflammation is suggested to promote development of CMD. Epicardial adipose tissue (EAT) is a local visceral fat depot surrounding the heart and the coronary arteries, modifying the inflammatory environment of the heart. We compared EAT in patients with and without CMD.

We retrospectively included consecutive patients undergoing diagnostic coronary angiography as well as transthoracic echocardiography between March and October 2016. EAT thickness was defined as space between the epicardial wall of the myocardium and the visceral layer of the pericardium and EAT index was calculated as EAT thickness/body surface area. Logistic regression analysis was used to determine the association of EAT index with the presence of CMD.

Overall, 399 patients (mean age 60.2 ± 14.0 years, 46% male) were included. EAT thickness was significantlwithout CMD especially in older age groups. Our results support the hypothesis that modulation of local inflammation by epicardial fat is involved in the development of CMD.

Cell diameter, area, and volume are established quantitative measures of adipocyte size. However, these different adipocyte sizing parameters have not yet been directly compared regarding their distributions. Therefore, the study aimed to investigate how these adipocyte size measures differ in their distribution and assessed their correlation with anthropometry and laboratory chemistry. In addition, we were interested to investigate the relationship between fat cell size and adipocyte mitochondrial respiratory chain capacity.

Subcutaneous and visceral histology-based adipocyte size estimates from 188 individuals were analyzed by applying a panel of parameters to describe the underlying cell population. Histology-based adipocyte diameter distributions were compared with adipocyte diameter distributions from collagenase digestion. Associations of mean adipocyte size with body mass index (BMI), glucose, HbA

, blood lipids as well as mature adipocyte mitochondrial respiration were investigated.

All adipocyte area estimates derived from adipose tissue histology were not normally distributed, but rather characterized by positive skewness.