Processing of heparanase is mediated by syndecan-1 cytoplasmic domain and involves syntenin and α-actinin

Heparanase activity plays a decisive role in cell dissemination associated with cancer metastasis. Cellular uptake of heparanase is considered a pre-requisite for the delivery of latent 65-kDa heparanase to lysosomes and its subsequent proteolytic processing and activation into 8- and 50-kDa protein subunits by cathepsin L. Heparan sulfate proteoglycans, and particularly syndecan, are instrumental for heparanase uptake and activation, through a process that has been shown to occur independent of rafts. Nevertheless, the molecular mechanism underlying syndecan-mediated internalization outside of rafts is unclear. Here, we examined the role of syndecan-1 cytoplasmic domain in heparanase processing, utilizing deletion constructs lacking the entire cytoplasmic domain (Delta), the conserved (C1 or C2), or variable (V) regions. Heparanase processing was markedly increased following syndecan-1 over-expression; in contrast, heparanase was retained at the cell membrane and its processing was impaired in cells over-expressing syndecan-1 deleted for the entire cytoplasmic tail. We have next revealed that conserved domain 2 (C2) and variable (V) regions of syndecan-1 cytoplasmic tail mediate heparanase processing. Furthermore, we found that syntenin, known to interact with syndecan C2 domain, and α actinin are essential for heparanase processing.     

Natural history and evolutionary principles of gene duplication in fungi

Gene duplication and loss is a powerful source of functional innovation. However, the general principles that govern this process are still largely unknown. With the growing number of sequenced genomes, it is now possible to examine these events in a comprehensive and unbiased manner. Here, we develop a procedure that resolves the evolutionary history of all genes in a large group of species. We apply our procedure to seventeen fungal genomes to create a genome-wide catalogue of gene trees that determine precise orthology and paralogy relations across these species. We show that gene duplication and loss is highly constrained by the functional properties and interacting partners of genes. In particular, stress-related genes exhibit many duplications and losses, whereas growth-related genes show selection against such changes. Whole-genome duplication circumvents this constraint and relaxes the dichotomy, resulting in an expanded functional scope of gene duplication. By characterizing the functional fate of duplicate genes we show that duplicated genes rarely diverge with respect to biochemical function, but typically diverge with respect to regulatory control. Surprisingly, paralogous modules of genes rarely arise, even after whole-genome duplication. Rather, gene duplication may drive the modularization of functional networks through specialization, thereby disentangling cellular systems.     

Overview of bat species reported in Albania with the first country records for eight species

The bat fauna of Albania, a country located in a Balkan glacial refugium and a Mediterranean biodiversity hotspot, has remained poorly studied although as many as 21 species and representatives of three species complexes had been reported before 2003. It was expected that several new species would be added to the country’s list of fauna, not only due to their occurrence in adjacent regions but to the splitting of already known taxa into sibling species and the discovery of new, cryptic species. Altogether, we recorded 32 bat species in Albania, including all of those previously reported (21) and 11 new species for the country, as a result of field work conducted in 2003–2012. Here, we report on eight bat species including Rhinolophus mehelyi, Nyctalus lasiopterus, Plecotus kolombatovici, Barbastella barbastellus, Myotis brandtii that had not been reported previously in Albania while three species (Pipistrellus pipistrellus, Plecotus austriacus, Myotis mystacinus) had been reported before changes to their taxonomy and so could be treated only as representatives of a particular species complex (i.e. sensu lato). We greatly extended the known geographic ranges of five species in the south of Europe.     

Bayesian inference of ancient human demography from individual genome sequences

Whole-genome sequences provide a rich source of information about human evolution. Here we describe an effort to estimate key evolutionary parameters based on the whole-genome sequences of six individuals from diverse human populations. We used a Bayesian, coalescent-based approach to obtain information about ancestral population sizes, divergence times and migration rates from inferred genealogies at many neutrally evolving loci across the genome. We introduce new methods for accommodating gene flow between populations and integrating over possible phasings of diploid genotypes. We also describe a custom pipeline for genotype inference to mitigate biases from heterogeneous sequencing technologies and coverage levels. Our analysis indicates that the San population of southern Africa diverged from other human populations approximately 108-157 thousand years ago, that Eurasians diverged from an ancestral African population 38-64 thousand years ago, and that the effective population size of the ancestors of all modern humans was ～9,000.     

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.     

Radioprotectors from pyrodextrins

Cornstarch heated in the range of 230–280°C depolymerized into pyrodextrins characterized by two-component EPR signals of relatively stable free radicals. These thermally generated radicals could serve as efficient scavengers for free radicals generated from pyrodextrins with the 200 Gy dose of γ-radiation. The most efficient traps/scavengers were produced from cornstarch at 250–280°C. IR data indicated incorporation of the OH groups to the pyrodextrins. These groups most probably originated from the OH· radicals formed by the radiolysis of water. EPR spectra provided evidence for trapping free radicals generated by γ-irradiation and for their subsequent annihilation on contact with pyrodextrins. Water affected radical processes occurring in pyrodextrins caused by γ-irradiation.     

Assembling and alerting scents produced by the bedbugCimex lectularius L.

Zusammenfassung Es wird gezeigt, dass die Aggregation der Bettwanzen (Cimex lectularius) durch einen von beiden Geschlechtern abgegebenen Versammlungsduft eingeleitet wird. Letzterer ist in Methylalkohol, aber nicht in Diäthyläther löslich, verdampft bei 32°C und lockt unbegattete sowie begattete Wanzen beider Geschlechter an. Die Lockreaktion ist von der Duftmenge abhängig und bleibt bei antennenlosen Wanzen aus. Die Stinkdrüsen gereizter, respektive verletzter Bettwanzen sondern Hex-2-en-1-al und Oct-2-en-1-al als Alarmduft ab, der die Zerstreuung der Wanzengruppen hervorruft.