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Refugee Psychological Wellness, Global Wellness Insurance plan, and the Syrian Crisis.
Asb2, ankyrin repeat, and SOCS box protein 2 form an E3 ubiquitin ligase complex. Asb2 ubiquitin ligase activity drives the degradation of filamins, which have essential functions in humans. The placenta is a temporary organ that forms during pregnancy, and normal placentation is important for survival and growth of the fetus. Recent studies have shown that approximately 25-30% of knockout (KO) mice have non-viable offspring, and 68% of knockout lines exhibit placental dysmorphologies. There are very few studies on Asb2, with insufficient research on its role in placental development. Therefore, we generated Asb2 knockout mice and undertook to investigate Asb2 expression during organogenesis, and to identify its role in early embryonic and placental development. The external morphology of KO embryos revealed abnormal phenotypes including growth retardation, pericardial effusion, pale color, and especially heart beat defect from E 9.5. Furthermore, Asb2 expression was observed in the heart from E 9.5, indicating that it is specifically expressed during early heart formation, resulting in embryonic lethality. Histological analysis of E 10.5 KO heart showed malformations such as failure of chamber formation, reduction in trabeculated myocardium length, absence of mesenchymal cells, and destruction of myocardium wall. Moreover, the histological results of Asb2-deficient placenta showed abnormal phenotypes including small labyrinth and reduced vascular complexity, indicating that failure to establish mature circulatory pattern affects the embryonic development and results in early mortality. Collectively, our results demonstrate that Asb2 knockout mice have placental defects, that subsequently result in failure to form a normal cardiac septum, and thereby result in embryo mortality in utero at around E 9.5.Wnt5a is a non-canonical Wnt ligand that is essential for normal embryonic development in mammals. The role of Wnt5a in early intestinal development has been examined in gene ablation models, where Wnt5a-/- mice exhibit strikingly shortened intestines. However, the exact cellular source of Wnt5a has remained elusive, until a recent study found that FoxL1-expressing mesenchymal cells (FoxL1+ cells), which are localized directly beneath the intestinal epithelium, express Wnt5a. To determine whether FoxL1+ cells are a required source of Wnt5a during intestinal development, we derived FoxL1-Cre; Wnt5af/f mice, which is the first mouse model to ablate Wnt5a in a cell type-specific manner in the intestine in vivo. Our results show that Wnt5a deletion in FoxL1+ cells during fetal life causes a shortened gut phenotype in neonatal mice, and that our model is sufficient to increase rate of apoptosis in the elongating epithelium, thus explaining the shortened gut phenotype. However, in contrast to previous studies using Wnt5a null mice, we did not observe dysregulation of epithelial structure or apical-basal protein localization. Altogether, our findings establish a developmental role for FoxL1+ mesenchymal cells in controlling non-canonical Wnt signaling during midgut elongation.
Acute myocardial infarction (MI) is a common cause of the morbidity and mortality of cardiovascular diseases in the world. Acute MI lead to cardiovascular output after formation of myocardial ischemia and circulatory arrest in coronary heart diseases. However, the mechanisms underlying MI injury are poorly understood. Saracatinib We explored the part played by miR-26a in myocardial infarction (MI).

Decreased miR-26a expression in H
O
-treated newborn murine ventricular cardiomyocytes (NMVCs) was observed, as well as in the infarcted heart of MI mouse model, compared to untreated NMVCs and healthy mouse heart tissue, respectively. Conversely, the upregulation of phosphatase and tensin homolog (PTEN) was observed in H
O
-treated NMVCs, and in infarcted hearts. An MTT assay and BrdU staining showed that H
O
treatment attenuated cell viability in NMVCs, whereas miR-26a overexpression increased cell viability. Both TUNEL assay and flow cytometry (FC) displayed that miR-26a expression suppressed H
O
-induced cell apoptosis. Besides, miR-26a overexpression suppressed the upregulation of PTEN expression in H
O
-treated NMVCs by directly binding to PTEN 3'-UTR.

PI3K/Akt and JAK/STAT signal transduction pathways were found to be regulated through cross-talk between miR-26a and PTEN. Furthermore, agomiR-26a treatment in MI mouse model considerably suppressed the size of the infarcted regions, and improved cardiac activity.

MiR-26a expression in MI cardiac tissues was downregulated in response to H
O
stress, whereas it could still protect against cell death by modulation of the PI3K/Akt and JAK/STAT signal transduction pathways by directly targeting PTEN.
MiR-26a expression in MI cardiac tissues was downregulated in response to H2O2 stress, whereas it could still protect against cell death by modulation of the PI3K/Akt and JAK/STAT signal transduction pathways by directly targeting PTEN.The Notch signaling pathway is highly conserved and regulates various fundamental development events. Activation of Notch signaling relies on production of the Notch intracellular domain (NICD), which assembles a transcription factor complex to turn on down-stream targets expression. The mastermind (mam) gene encodes an essential co-activator that permits NICD activity in the cell nucleus. During a somatic mosaic screen in Drosophila, an uncharacterized gene l(2)S9998 is identified as a positive regulator of the Notch signaling pathway. Genetic analysis demonstrates that l(2)S9998 functions at the level of transcriptional activation of Notch targets in the signal receiving cells. Whole genome sequencing reveals that l(2)S9998 is a novel allele of the mam gene, which is further confirmed by complementation tests. Along with three molecularly defined transposon insertions isolated from the screen, four mutants of mam are shown to modulate Notch signaling during fly wing development. Our analysis provides additional genetic resources for understanding mam function and Notch signaling regulation.
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