The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.     

Heat shock response in the thermophilic fungus Rhizomucor miehei

Changes in the composition of the membrane lipids and cytosol carbohydrates of the thermophilic fungus Rhizomucor miehei in response to heat shock were studied. Under optimal conditions (41–43°C), high trehalose content (8–11%) was found at all stages of growth of submerged culture. Heat shock (51–53°C) for 1 h did not result in enhanced trehalose synthesis, while increase in shock duration to 3 h resulted in a significant increase in trehalose content. The share of sterols and phosphatidic acids in the membrane lipids increased, while the share of phosphatidylcholines and phosphatidylethanolamines decreased. These processes resulted in increased content of non-bilayer lipids, while the unsaturation degree of the fatty acids of the major phospholipids did not decrease. Comparison of resistance to lethal heat shock in the control and experimental variants of R. miehei revealed that this thermophilic fungus exhibited no acquired heat resistance.     

A simple method for the preparation of (5Z,8Z,11Z,14Z)-16-hydroxyeicosa-5,8,11,14-tetraenoic acid enantiomers and the corresponding 14,15-dehydro analogues: role of the 16-hydroxy group for the lipoxygenase reaction

(5Z,8Z,11Z,13E)-15-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) is not well oxygenated by arachidonate 15-lipoxygenases because of two structural reasons: (i) it contains a hydrophilic OH-group in close proximity to its methyl end and (ii) it lacks the bisallylic methylene at C(13). We synthesized racemic (5Z,8Z,11Z,14Z)-16-hydroxy-5,8,11,14-eicosatetraenoic acid (16-HETE) which still contains the bisallylic C(13), separated the enantiomers reaching an optical purity of >99% and tested them as substrates for 5- and 15-lipoxygenases. Our synthetic pathway, which is based on stereospecific hydrogenation of a polyacetylenic precursor, yielded substantial amounts (30%) of 14,15-dehydro-16-HETE in addition to 16-HETE. When 16-HETE was tested as lipoxygenase substrate, we found that it is well oxygenated by the soybean 15-lipoxygenase and by the recombinant human 5-lipoxygenase. Analysis of the reaction products suggested an arachidonic acid-like alignment at the active site of the two enzymes. In contrast, the product pattern of 16-HETE methyl ester oxygenation by the soybean lipoxygenase (5-lipoxygenation) may be explained by an inverse head to tail substrate orientation.     

AmylPepPred: Amyloidogenic Peptide Prediction tool

We present an efficient computational architecture designed using supervised machine learning model to predict amyloid fibril forming protein segments, named AmylPepPred. The proposed prediction model is based on bio-physio-chemical properties of primary sequences and auto-correlation function of their amino acid indices. AmylPepPred provides a user friendly web interface for the researchers to easily observe the fibril forming and non-fibril forming hexmers in a given protein sequence. We expect that this stratagem will be highly encouraging in discovering fibril forming regions in proteins thereby benefit in finding therapeutic agents that specifically aim these sequences for the inhibition and cure of amyloid illnesses.

Availability

AmylPepPred is available freely for academic use at www.zoommicro.in/amylpeppred     

Intensified grazing affects endemic plant and gastropod diversity in alpine grasslands of the Southern Carpathian mountains (Romania)

Alpine grasslands in the Southern Carpathian Mts, Romania, harbour an extraordinarily high diversity of plants and invertebrates, including Carpathic endemics. In the past decades, intensive sheep grazing has caused a dramatic decrease in biodiversity and even led to eroded soils at many places in the Carpathians. Because of limited food resources, sheep are increasingly forced to graze on steep slopes, which were formerly not grazed by livestock and are considered as local biodiversity hotspots. We examined species richness, abundance and number of endemic vascular plants and terrestrial gastropods on steep slopes that were either grazed by sheep or ungrazed by livestock in two areas of the Southern Carpathians. On calcareous soils in the Bucegi Mts, a total of 177 vascular plant and 19 gastropod species were recorded. Twelve plant species (6.8%) and three gastropod species (15.8%) were endemic to the Carpathians. Grazed sites had lower plant and gastropod species richness than ungrazed sites. Furthermore, grazed sites harboured fewer gastropod species endemic to the Carpathians than ungrazed sites. On acid soils in the Fagaras Mts, a total of 96 vascular plant and nine gastropod species were found. In this mountain area, however, grazed and ungrazed sites did not differ in species richness, abundance and number of endemic plant and gastropod species. Our findings confirm the high biodiversity of grasslands on steep slopes in the Southern Carpathian Mts and caution against increasing grazing pressure in these refuges for relic plants and gastropods as well as for other invertebrates.     

The cyclooxygenases

Cyclooxygenases (COXs) catalyze the rate-limiting step in the production of prostaglandins, bioactive compounds involved in processes such as fever and sensitivity to pain, and are the target of aspirin-like drugs. COX genes have been cloned from coral, tunicates and vertebrates, and in all the phyla where they are found, there are two genes encoding two COX isoenzymes; it is unclear whether these genes arose from an early single duplication event or from multiple independent duplications in evolution. The intron-exon arrangement of COX genes is completely conserved in vertebrates and mostly conserved in all species. Exon boundaries largely define the four functional domains of the encoded protein: the amino-terminal hydrophobic signal peptide, the dimerization domain, the membrane-binding domain, and the catalytic domain. The catalytic domain of each enzyme contains distinct peroxidase and cyclooxygenase active sites; COXs are classified as members of the myeloperoxidase family. All COXs are homodimers and monotopic membrane proteins (inserted into only one leaflet of the membrane), and they appear to be targeted to the lumenal membrane of the endoplasmic reticulum, where they are N-glycosylated. In mammals, the two COX genes encode a constitutive isoenzyme (COX-1) and an inducible isoenzyme (COX-2); both are of significant pharmacological importance.