Electroretinographic findings in day-blind dogs

Cone degeneration (cd; day blindness) is one of the inherited retinal diseases of dogs. Its diagnosis is based on vision testing, fundoscopy, electroretinography (ERG) and, for some breeds, on genetic tests. Typical signs of the disease are day blindness and cone dysfunction during ERG while fundoscopy does not show any abnormalities. The aim of this study was to compare behavioural findings, fundoscopic lesions and electroretinographic alterations in 12 cd-affected dogs (Alaskan Malamute, Labrador Retriever, German Shepherd, Dachshund, Yorkshire Terrier, Shih Tzu, Siberian Husky and crossbreeds) examined at our clinic. None of the examined dogs had any fundoscopic lesions, and all of them had normal scotopic vision with strongly impaired or absent photopic vision. Light-adapted transient, cone-mediated and steady-state, 31-Hz cone flicker ERGs were much below the 5th percentile limits of normality or even unrecordable, while the rod-driven ERGs were within normal values. Vision test and ERG results corresponded to each other and, combined with the results of fundoscopy, were typical of cd. To date, our research is one of the few studies in the world presenting ERG alterations compared with vision test findings and fundoscopic results in the course of cd

Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment

Sunyaev Zel'dovich observations of a statistically complete sample of galaxy clusters with OCRA-p

We present 30 GHz Sunyaev Zel'dovich observations of a statistically complete sample of galaxy clusters with OCRA-p. The clusters are the 18 most X-ray luminous clusters at z > 0.2 in the ROSAT Brightest Cluster Sample. We correct for contaminant radio sources via supplementary observations with the Green Bank Telescope, also at 30 GHz, and remove a cluster that is contaminated by an unresolved X-ray source. All 17 remaining clusters have central SZ effects with Comptonisation parameter y_0 exceeding 1.9x10^-4, and 13 are detected at significance > 3 sigma. We use our data to examine scalings between y_0 and X-ray temperature, X-ray luminosity, and the X-ray mass proxy Y_X, and find good agreement with predictions from self-similar models of cluster formation, with an intrinsic scatter in y_0 of about 25%. We also comment on the success of the observations in the face of the contaminant source population, and the implications for upcoming cm-wave surveys.Comment: 14 pages, 2 figures, accepted by MNRA

Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

The effects of environmental parameters on the microbial activity in peat-bog lakes.

Microbiological activity is an important parameter for understanding the functioning of different environments. Therefore, the purpose of this study was to estimate the quantity and contribution of metabolically active at the single-cell level bacteria in the microbial community in peat-bog lakes. To determine different aspects of the metabolic activity of bacteria, four fluorescent staining methods (Dehydrogenase/Electron Transport System Activity -CTC+, Nucleoid Containing Cells- NuCC+, Active Bacteria with Intact Ribosome Structures- RIB+ and Active Bacteria With an Intact Membrane-MEM+) were applied. We identified four natural peat-bog lakes in Northern Europe to determine which factors-community (bacterial factors) or environment (hydrochemical and physical factors)-have a significant influence on the quantitative dynamics of metabolically active microorganisms, in terms of seasonal and habitat changes. The results show that change in the amount of abiotic components such as DOC, TN, and TOC can result in stress, which may limit a function but does not lead to losing all other metabolic functions in the community-forming bacteria. In nutrient-poor peat bog lakes, nutrients and organic carbon are factors which regulate the overall activity of the community

How dictionary users choose senses in bilingual dictionary entries: An eye-tracking study

We use modern eye-tracking technology to scrutinize the process of sense and equivalent selection in polysemous bilingual entries. Our study subjects, intermediate and advanced Polish learners of English, consulted 26 Polish-to-English dictionary pages prompted with a sentence translation task. Throughout the task, an eye-tracking device unobtrusively recorded their gaze patterns, which are analyzed and discussed. Both successful and unsuccessful searches are examined. Also, we assess the potential of eye-tracking technology in the study of dictionary use.23228254Lexiko