Diabetes mellitus is a metabolic disease with multiple complications that causes serious diseases over the years. The condition leads to severe economic consequences and is reaching pandemic level globally. Much research is being carried out to address this disease and its underlying molecular mechanism. This review focuses on the diverse role and mechanism of ceramide, a prime sphingolipid signaling molecule, in the pathogenesis of type 1 and type 2 diabetes and its complications. Studies using cultured cells, animal models, and human subjects demonstrate that ceramide is a key player in the induction of β-cell apoptosis, insulin resistance, and reduction of insulin gene expression. Ceramide induces β-cell apoptosis by multiple mechanisms namely; activation of extrinsic apoptotic pathway, increasing cytochrome c release, free radical generation, induction of endoplasmic reticulum stress and inhibition of Akt. Ceramide also modulates many of the insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramide reduces the synthesis of insulin hormone by attenuation of insulin gene expression. Better understanding of this area will increase our understanding of the contribution of ceramide to the pathogenesis of diabetes, and further help in identifying potential therapeutic targets for the management of diabetes mellitus and its complications.
Recent years have witnessed a rapid growth in the number and diversity of prokaryotic proteins shown to carry N- and/or O-glycans, with protein glycosylation now considered as fundamental to the biology of these organisms as it is in eukaryotic systems. This article overviews the major glycosylation pathways that are known to exist in eukarya, bacteria and archaea. These are (i) oligosaccharyltransferase (OST)-mediated N-glycosylation which is abundant in eukarya and archaea, but is restricted to a limited range of bacteria; (ii) stepwise cytoplasmic N-glycosylation that has so far only been confirmed in the bacterial domain; (iii) OST-mediated O-glycosylation which appears to be characteristic of bacteria; and (iv) stepwise O-glycosylation which is common in eukarya and bacteria. A key aim of the review is to integrate information from the three domains of life in order to highlight commonalities in glycosylation processes. We show how the OST-mediated N- and O-glycosylation pathways share cytoplasmic assembly of lipid-linked oligosaccharides, flipping across the ER/periplasmic/cytoplasmic membranes, and transferring “en bloc” to the protein acceptor. Moreover these hallmarks are mirrored in lipopolysaccharide biosynthesis. Like in eukaryotes, stepwise O-glycosylation occurs on diverse bacterial proteins including flagellins, adhesins, autotransporters and lipoproteins, with O-glycosylation chain extension often coupled with secretory mechanisms.
The prevalence of suicidal ideation and attempts among medical students in the UAE was in the lower range in international comparison. Negative attitudes toward suicide were accompanied by a strong support for a suicidal friend, and both were related to religiosity.
Objectives: To our knowledge, this study is the first in the United Arab Emirates (UAE) to investigate the prevalence of child maltreatment in relation to depressive symptoms and self-esteem. Study design: Exposure to physical maltreatment, emotional abuse and neglect was evaluated in 518 adolescents (86% response rate) randomly selected from schools in Al Ain in the Emirate of Abu Dhabi. The Rosenberg self-esteem scale and the Beck Depression Inventory were used to measure self-esteem and depressive symptoms by using multivariate logistic regression analyses. Results: The mean age of study participants was 14.3 years. Emotional abuse was the most frequent form of maltreatment (33.9%), physical abuse (12.6%) and neglect (12.1%) followed. Male sex was a positive predictor of physical abuse (OR ¼ 2.12; 95% CI 1.18-3.77), whilst higher maternal level of education was protective (OR ¼ 0.40; 95% CI 0.19-0.86). Daily screen time (OR ¼ 2.77; 95% CI 1.17-6.56) and tobacco smoking (OR ¼ 1.86; 95% CI 1.09-3.18) positively predicted emotional abuse. Emotionally maltreated and neglected participants were less likely to report high level of self-esteem and more likely to report symptoms of depression. Conclusions: Child maltreatment in the UAE is of a similar magnitude to what reported in other countries around the world and significantly associated with low self-esteem and depressive symptoms.
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