Drosophila ALS regulates growth and metabolism through functional interaction with insulin-like peptides

In metazoans, factors of the insulin family control growth, metabolism, longevity, and fertility in response to environmental cues. In Drosophila, a family of seven insulin-like peptides, called Dilps, activate a common insulin receptor. Some Dilp peptides carry both metabolic and growth functions, raising the possibility that various binding partners specify their functions. Here we identify dALS, the fly ortholog of the vertebrate insulin-like growth factor (IGF)-binding protein acid-labile subunit (ALS), as a Dilp partner that forms a circulating trimeric complex with one molecule of Dilp and one molecule of Imp-L2, an IgG-family molecule distantly related to mammalian IGF-binding proteins (IGFBPs). We further show that dALS antagonizes Dilp function to control animal growth as well as carbohydrate and fat metabolism. These results lead us to propose an evolutionary perspective in which ALS function appeared prior to the separation between metabolic and growth effects that are associated with vertebrate insulin and IGFs.     

Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP) signaling to inhibit steroidogenesis in human granulosa cells

Background  

Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells.     

Lack of CFTR in Skeletal Muscle Predisposes to Muscle Wasting and Diaphragm Muscle Pump Failure in Cystic Fibrosis Mice

Cystic fibrosis (CF) patients often have reduced mass and strength of skeletal muscles, including the diaphragm, the primary muscle of respiration. Here we show that lack of the CF transmembrane conductance regulator (CFTR) plays an intrinsic role in skeletal muscle atrophy and dysfunction. In normal murine and human skeletal muscle, CFTR is expressed and co-localized with sarcoplasmic reticulum-associated proteins. CFTR–deficient myotubes exhibit augmented levels of intracellular calcium after KCl-induced depolarization, and exposure to an inflammatory milieu induces excessive NF-kB translocation and cytokine/chemokine gene upregulation. To determine the effects of an inflammatory environment in vivo, sustained pulmonary infection with Pseudomonas aeruginosa was produced, and under these conditions diaphragmatic force-generating capacity is selectively reduced in Cftr^−/− mice. This is associated with exaggerated pro-inflammatory cytokine expression as well as upregulation of the E3 ubiquitin ligases (MuRF1 and atrogin-1) involved in muscle atrophy. We conclude that an intrinsic alteration of function is linked to the absence of CFTR from skeletal muscle, leading to dysregulated calcium homeostasis, augmented inflammatory/atrophic gene expression signatures, and increased diaphragmatic weakness during pulmonary infection. These findings reveal a previously unrecognized role for CFTR in skeletal muscle function that may have major implications for the pathogenesis of cachexia and respiratory muscle pump failure in CF patients.     

Nitric-oxide-donating NSAIDs as agents for cancer prevention

Nitric-oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs), which consist of an NSAID with an NO-donating moiety covalently attached to it, promise to contribute significantly towards the development of effective chemoprevention strategies against cancer. NO-NSAIDs inhibit the growth of cultured cancer cells 10-6000-fold more potently than their parent NSAIDs and prevent colon cancer in animal tumor models. Clinical data indicate that they are extremely safe. Mechanistically, NO-aspirin, the best-studied NO-NSAID, has pleiotropic effects on cell signaling (it inhibits Wnt signaling, induces nitric oxide synthase and NF-kappaB activation and induces cyclooxygenase-2 expression), and this mechanistic redundancy might be central to its mode of action against cancer. The apparent safety and superior efficacy of NO-NSAIDs makes them promising chemopreventive agents against cancer.     

The ha72 Core Gene of Baculovirus Is Essential for Budded Virus Production and Occlusion-Derived Virus Embedding,and Amino Acid K22 Plays an Important Role in Its Function

ha72 of Helicoverpa armigera nucleopolyhedrovirus (a homologue of ac78) was identified as a conserved late baculovirus gene and characterized. HA72 localizes in the intranuclear ring zone. By generating mutants, we showed that HA72 is essential for budded virus (BD) production and occlusion-derived virus (ODV) embedding. HA72 also interacted with P33, a baculoviral sulfhydryl oxidase. A point mutation of amino acid 22 from lysine to glutamic acid curtailed BV production and precluded ODV occlusion as well as interaction with P33.     

Hepatocellular Damage and Severity of COVID-19 Infection in Iraqi Patients: A Biochemical Study

Background:Infection with COVID-19 can cause hepatic damages. Here, we aimed to examine the effect of COVID-19 infection on the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and procalcitonin (PCT) concentrations as markers to evaluate the liver function.Methods:In this study, 56 patients infected with COVID- 19 and 28 healthy controls was recruited in Private Nursing Home Hospital of the Medical City, Baghdad. Patients were subdivided according to disease severity into severe and non-severe groups.Results:The results showed that the mean±SD value of serum AST activity and serum PCT concentrations were elevated significantly in severe group in comparison to healthy control, (p< 0.01, p< 0.001) respectively. Also, the mean ±SD value of serum ALT activity was higher in severe group compared to the healthy subjects and non-severe ones, significantly (p< 0.0001, p< 0.003) respectively. While the mean value of serum albumin concentration of severe patients and non-severe group were significantly decreased compared to healthy subjects. The receiver operating characteristic curve (ROC) revealed that ROC value of albumin (0.992) differentiates between non-severe infected patients and healthy subjects, while the ROC value of serum ALT activity (0.735) differentiates between severe COVID-19 patients and non- severe ones.Conclusion:Changes of liver function parameters in COVID-19 patients were mild to moderate and measurement of serum ALT activity is the best biomarker in differentiation between non-severe patients and severe ones and albumin concentration is excellent in discrimination between patients and controls.Key Words: Serum aminotransferase enzymes, Albumin, Procalcitonin