Turns in transmembrane helices – determination of the minimal length of a “helical hairpin” and derivation of a fine-grained turn propensity scale

We have recently reported a first experimental turn propensity scale for transmembrane helices. This scale was derived from measurements of how efficiently a given residue placed in the middle of a 40 residue poly(Leu) stretch induces the formation of a "helical hairpin" with two rather than one transmembrane segment. We have now extended these studies, and have determined the minimum length of a poly(Leu) stretch compatible with the formation of a helical hairpin. We have also derived a more fine-grained turn propensity scale by (i) introducing each of the 20 amino acid residues into the middle of the shortest poly(Leu) stretch compatible with helical hairpin formation, and (ii) introducing pairs of residues in the middle of the 40 residue poly(Leu) stretch. The new turn propensities are consistent with the amino acid frequencies found in short hairpin loops in membrane proteins of known 3D structure

Urgent request on avian influenza

Non peer reviewe

Welcome to the family: Identification of the nad+ transporter of animal mitochondria as member of the solute carrier family slc25

Subcellular compartmentation is a fundamental property of eukaryotic cells. Communication and metabolic and regulatory interconnectivity between organelles require that solutes can be transported across their surrounding membranes. Indeed, in mammals, there are hundreds of genes encoding solute carriers (SLCs) which mediate the selective transport of molecules such as nucleotides, amino acids, and sugars across biological membranes. Research over many years has identified the localization and preferred substrates of a large variety of SLCs. Of particular interest has been the SLC25 family, which includes carriers embedded in the inner membrane of mitochondria to secure the supply of these organelles with major metabolic intermediates and coen-zymes. The substrate specificity of many of these carriers has been established in the past. However, the route by which animal mitochondria are supplied with NAD+ had long remained obscure. Only just recently, the existence of a human mitochondrial NAD+ carrier was firmly established. With the realization that SLC25A51 (or MCART1) represents the major mitochondrial NAD+ carrier in mammals, a long-standing mystery in NAD+ biology has been resolved. Here, we summarize the functional importance and structural features of this carrier as well as the key observations leading to its discovery

Phytochemicals of minthostachys diffusa epling and their health-promoting bioactivities

The genus Minthostachys belonging to the Lamiaceae family, and is an important South American mint genus used commonly in folk medicine as an aroma in cooking. The phytochemical-rich samples of the aerial parts of Minthostachys diffusa Epling. were tested for pharmacological and health-promoting bioactivities using in vitro chemical and enzymatic assays. A range of radical scavenging activities of the samples against biological radicals such as nitric oxide and superoxide anion and against synthetic 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals, the ferric reducing antioxidant power and the lipid peroxidation inhibition were determined and ranked using the 'relative antioxidant capacity index' (RACI). The ethyl acetate fraction showed the highest RACI of +1.12. Analysis of the various fractions' inhibitory ability against enzymes involved in diabetes (α-amylase and α-glucosidase), and against enzymes associated with Parkinson's or Alzheimer's diseases (acetylcholinesterase and butyrylcholinesterase) also suggested that the ethyl acetate fraction was the most active. Liquid chromatography-tandem mass spectrometry analysis of the ethyl acetate fraction showed more than 30 polyphenolic compounds, including triterpenes. The inhibitory cholinesterase effects of the triterpenes identified from M. diffusa were further analysed by in silico docking of these compounds into 3D-structures of acetylcholinesterase and butyrylcholinesterase. This is the first study on pharmacological activities and phytochemical profiling of the aerial parts of M. diffusa, showing that this plant, normally used as food in South America, is also rich in health-promoting phytochemicals

Two novel precursors of the hiv-1 protease inhibitor darunavir target the UPR/proteasome system in human hepatocellular carcinoma cell line HepG2

Background: Several pre-clinical and clinical reports suggest that HIV-1 protease inhibitors, in addition to the antiretroviral properties, possess pleiotropic pharmacological effects including anti-cancer action. Therefore, we investigated the pro-apoptotic activity in tumor cells of two molecules, RDD-19 and RDD-142, which are hydroxyethylamine derivatives’ precursors of darunavir and several HIV-1 protease inhibitors. Methods: Three hepatoma cell lines and one non-pathological cell line were treated with RDD-19 and RDD-142, and cell viability was assessed. The expression levels of several markers for ER stress, autophagy, cellular ubiquitination, and Akt activation were quantified in HepG2 cells treated with RDD-19 and RDD-142 to evaluate apoptotic and non-apoptotic cell death. Results: RDD-19 and RDD-142 showed a greater dose-dependent cytotoxicity towards the hepatic tumor cell line HepG2 compared to the non-pathological hepatic cell line IHH. Both molecules caused two types of cell death, a caspase-dependent apoptosis, which was ascertained by a series of biochemical and morphological assays, and a caspase-independent death that was characterized by the induction of ER stress and autophagy. The strong increase of ubiquitinated proteins inside the cells suggested that the target of these molecules could be the proteasome and in silico molecular docking analysis that was used to support the plausibility of this hypothesis. Furthermore, cells treated with the two compounds displayed decreased levels of p-AKT, which interferes with cell survival and proliferation. Conclusions: These findings demonstrate that two compounds, RDD-19 and RDD-142, have pleiotropic effects and that they may represent promising anticancer candidates

The central role of Italy in the spatial spread of USUTU virus in Europe

USUTU virus (USUV) is an arbovirus maintained in the environment through a bird-mosquito enzootic cycle. Previous surveillance plans highlighted the endemicity of USUV in North-eastern Italy. In this work, we sequenced 138 new USUV full genomes from mosquito pools (Culex pipiens) and wild birds collected in North-eastern Italy and we investigated the evolutionary processes (phylogenetic analysis, selection pressure and evolutionary time-scale analysis) and spatial spread of USUV strains circulating in the European context and in Italy, with a particular focus on North-eastern Italy. Our results confirmed the circulation of viruses belonging to four different lineages in Italy (EU1, EU2, EU3 and EU4), with the newly sequenced viruses from the North-eastern regions, Veneto and Friuli Venezia Giulia, belonging to the EU2 lineage and clustering into two different sub-lineages, EU2-A and EU2-B. Specific mutations characterize each European lineage and geographic location seem to have shaped their phylogenetic structure. By investigating the spatial spread in Europe, we were able to show that Italy acted mainly as donor of USUV to neighbouring countries. At a national level, we identified two geographical clusters mainly circulating in Northern and North-western Italy, spreading both northward and southward. Our analyses provide important information on the spatial and evolutionary dynamics of USUTU virus that can help to improve surveillance plans and control strategies for this virus of increasing concern for human health

Identification of two divergent swine Noroviruses detected at the slaughterhouse in North East Italy

Norovirus (NoV) has emerged as one of the major causative agents of non-bacterial, food- and water-borne gastroenteritis in humans, with the main genogroup involved in human outbreaks (GII), which has been detected worldwide in different animal species including swine. A four-month investigation at the slaughterhouse aiming to examine the presence of NoV in the swine in North-Eastern Italy, enabled the detection of two divergent Noroviruses (NoVs) (GII.P11) in two swine farms. This represents the first study in the swine population of North-Eastern Italy, which has paved the way for future integrated virological and epidemiological investigations on swine NoVs

The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the endoplasmic reticulum membrane

Hepatitis B x antigen up-regulates the liver expression of URG7 that contributes to sustain chronic virus infection and to increase the risk for hepatocellular carcinoma by its anti-apoptotic activity. We have investigated the subcellular localization of URG7 expressed in HepG2 cells and determined its membrane topology by glycosylation mapping in vitro. The results demonstrate that URG7 is N-glycosylated and located to the endoplasmic reticulum membrane with an Nlumen–Ccytosol orientation. The results imply that the anti-apoptotic effect of URG7 could arise from the C-terminal cytosolic tail binding a pro-apoptotic signaling factor and retaining it to the endoplasmic reticulum membrane

Phylogeny and S1 Gene Variation of Infectious Bronchitis Virus Detected in Broilers and Layers in Turkey

Citation: Yilmaz, H., Altan, E., Cizmecigil, U. Y., Gurel, A., Ozturk, G. Y., Bamac, O. E., . . . Turan, N. (2016). Phylogeny and S1 Gene Variation of Infectious Bronchitis Virus Detected in Broilers and Layers in Turkey. Avian Diseases, 60(3), 596-602. doi:10.1637/11346-120915-Reg.1The avian coronavirus infectious bronchitis virus (AvCoV-IBV) is recognized as an important global pathogen because new variants are a continuous threat to the poultry industry worldwide. This study investigates the genetic origin and diversity of AvCoV-IBV by analysis of the S1 sequence derived from 49 broiler flocks and 14 layer flocks in different regions of Turkey. AvCoV-IBV RNA was detected in 41 (83.6%) broiler flocks and nine (64.2%) of the layer flocks by TaqMan real-time RT-PCR. In addition, AvCoV-IBV RNA was detected in the tracheas 27/30 (90%), lungs 31/49 (62.2%), caecal tonsils 7/22 (31.8%), and kidneys 4/49 (8.1%) of broiler flocks examined. Pathologic lesions, hemorrhages, and mononuclear infiltrations were predominantly observed in tracheas and to a lesser extent in the lungs and a few in kidneys. A phylogenetic tree based on partial S1 sequences of the detected AvCoV-IBVs (including isolates) revealed that 1) viruses detected in five broiler flocks were similar to the IBV vaccines Ma5, H120, M41; 2) viruses detected in 24 broiler flocks were similar to those previously reported from Turkey and to Israel variant-2 strains; 3) viruses detected in seven layer flocks were different from those found in any of the broiler flocks but similar to viruses previously reported from Iran, India, and China (similar to Israel variant-1 and 4/91 serotypes); and 4) that the AVCoV-IBV, Israeli variant-2 strain, found to be circulating in Turkey appears to be undergoing molecular evolution. In conclusion, genetically different AvCoV-IBV strains, including vaccine-like strains, based on their partial S1 sequence, are circulating in broiler and layer chicken flocks in Turkey and the Israeli variant-2 strain is undergoing evolution. © 2016 American Association of Avian Pathologists