Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition

The role of dopamine 2 receptor gene and personality characteristics in alcohol dependence in Turkish population

In this paper, we study the Lehmer's type congruences for lacunary harmonicsums

LC-MS/HRMS analysis, anti-cancer, anti-enzymatic and anti-oxidant effects of Boerhavia diffusa extracts: A potential raw material for functional applications

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation

Erratum: Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome (The American Journal of Human Genetics (2018) 103(3) (431–439), (S0002929718302374), (10.1016/j.ajhg.2018.07.010))

(The American Journal of Human Genetics 103, 431–439; September 6, 2018) Lisa Weixler has been added to the author list for her experimental and scientific contributions to the biophysical analysis of wild-type and mutant proteins. Her contributions were already mentioned in the acknowledgments. The authors apologize for initially only listing her in the acknowledgments and for the inconvenience. The author list has been corrected online and appears correctly here, and Lisa Weixler's affiliation is indicated as footnote 3: Center for Molecular Medicine Cologne, Cologne, Germany

Skeletal muscle fibrosis: an overview

Extracellular matrix (ECM) is an essential component of skeletal muscle. It provides a framework structure that holds myofibers and blood capillaries and nerves supplying the muscle. In addition, it has a principal role in force transmission, maintenance and repair of muscle fibers. Excessive accumulation of ECM components, especially collagens, either due to excessive ECM production, alteration in ECM-degrading activities, or a combination of both is defined as fibrosis. Skeletal muscle fibrosis impairs muscle function, negatively affects muscle regeneration after injury and increases muscle susceptibility to re-injury, therefore, it is considered a major cause of muscle weakness. Fibrosis of skeletal muscle is a hallmark of muscular dystrophies, aging and severe muscle injuries. Thus, a better understanding of the mechanisms of muscle fibrosis will help to advance our knowledge of the events that occur in dystrophic muscle diseases and develop innovative anti-fibrotic therapies to reverse fibrosis in such pathologic conditions. This paper explores an overview of the process of muscle fibrosis, as well as different murine models for studying fibrosis in skeletal muscles. In addition, factors regulating fibrosis and strategies to inhibit muscle fibrosis are discussed.The author is supported by a Postdoctoral Fellowship from the University of Pretoria, South Africa.http://link.springer.com/journal/4412020-11-12hj2018Anatomy and Physiolog