Molecular pathways driving disease-specific alterations of intestinal epithelial cells

Due to the fact that chronic inflammation as well as tumorigenesis in the gut is crucially impacted by the fate of intestinal epithelial cells, our article provides a comprehensive overview of the composition, function, regulation and homeostasis of the gut epithelium. In particular, we focus on those aspects which were found to be altered in the context of inflammatory bowel diseases or colorectal cancer and also discuss potential molecular targets for a disease-specific therapeutic intervention.     

Food niche of Exomalopsis (Exomalopsis) fulvofasciata Smith (Hymenoptera: Apidae) in Brazilian savannah: the importance of oil-producing plant species as pollen sources

Exomalopsis are ground-nesting species, and their food-niche breadth is little known due the difficulty in locating the nests and finding efficient bait plants to attract these bees. Some species of Exomalopsis were recorded as tomato, hot pepper and eggplant pollinators. Information about the food niche could be useful to increase Exomalopsis populations, providing consistent and comparable data for the enrichment of natural and crop areas with adequate plant sources. This study aimed to determine the food niche and the role of pollen size in the diet of E. fulvofasciata. We analysed pollen loads of 28 individuals of E. fulvofasciata collected from bait plants, in two natural areas of the Brazilian savannah. Only five pollen types belonging to the families Malpighiaceae, Solanaceae, Leguminosae, Myrtaceae and Lythraceae were important for this species. This result indicates that E. fulvofasciata is probably a polylectic species. However, we noticed that the Byrsonima used as bait plants contribute significantly for its larval provision, indicating that small pollen grains were more frequently collected.     

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma.     

Spurious Forecasts?

P. C. B. Phillips (1998) demonstrated that deterministic trends are a valid representation of an otherwise stochastic trending mechanism; he remained skeptic, however, about the predictive power of such representations. In this paper we prove that forecasts built upon spurious regression may perform (asymptotically) as well as those issued from a correctly specified regression. We derive the order in probability of several in‐sample and out‐of‐sample predictability criteria ( test, root mean square error, Theil's U‐statistics and R²) using forecasts based upon a least squares‐estimated regression between independent variables generated by a variety of empirically relevant data‐generating processes. It is demonstrated that, when the variables are mean stationary or trend stationary, the order in probability of these criteria is the same whether the regression is spurious or not. Simulation experiments confirm our asymptotic results. Copyright © 2011 John Wiley & Sons, Ltd.     

BAP1 loss defines a new class of renal cell carcinoma

The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10(-5)), and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.     

Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis

Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.     

Intersex in the gonochoristic crustacean Tanais dulongii (Audouin, 1826) (Peracarida: Tanaidacea: Tanaididae): a comparison of external reproductive characteristics

Tanais dulongii (Audouin, 1826) is a small benthic crustacean with separate sexes and a marked sexual dimorphism characterized by a cephalothorax narrowed anteriorly, larger chelae (claws) and a pair of tiny genital cones in males, and ovisacs that form chambers for carrying embryos in females. Recent studies have described the existence of intersexual individuals with a cephalothorax similar to males, large chelae and ovisacs, but, due to their small size, it has not been possible to confirm the presence of genital cones under normal light microscopy. The present study analyses and compares external reproductive structures under scanning electron microscopy, of male and female T. dulongii, to corroborate the presence of both ovisacs and genital cones in potentially intersex individuals. The possible causes, such as hermaphroditism, environmental sex determination, parasitism, genetic aberration or endocrine-disrupting pollutants, are discussed.     

Bostryx tortoranus (Doering, 1879) species complex (Gastropoda: Stylommatophora: Bulimulidae), a review of taxonomy and distribution of endemic species from Argentina

Morphology of the shell, radula, jaw, anatomy and sculpture of the inner wall of the reproductive system are described and compared for three species belonging to the Bostryx tortoranus species complex. On the basis of these characters, the following changes are proposed: Bostryx martinezi (Hylton Scott, 1965) is removed from synonymy with Bostryx tortoranus (Doering, 1879) and Bulimulus (Scansicochlea) cicheroi Hylton Scott, 1967 is transferred from synonymy with B. tortoranus to synonymy with B. martinezi. As a result of these changes, the number of species of Bostryx known from Argentina has increased to 19 species. Bostryx tortoranus and B. martinezi are redescribed, also the radula and anatomy of Bostryx rudisculptus (Parodiz, 1956) are described for the first time. The main distinctive morphological characters of the three species are: the structure of the shell’s protoconch and teleoconch, radular morphology, location of the secondary ureter opening, the length of the free oviduct with respect to the vagina and the epiphallus with respect to the penis and the bursa copulatrix duct’s inner wall sculpture. Bostryx martinezi and B. rudisculptus have restricted distributions and are ecologically endemic, whereas B. tortoranus has a wide distribution and is located in different dry ecoregions.

http://zoobank.org/urn:lsid:zoobank.org:pub:A2F21A37-E0ED-454F-A63D-EEC1804D7DFA     

Myosin II in mechanotransduction: master and commander of cell migration, morphogenesis, and cancer

Mechanotransduction encompasses the role of mechanical forces in controlling cell behavior by activating signal transduction pathways. Most forces at a cellular level are caused by myosin II, which contracts and cross-links actin. Myosin II-dependent forces are transmitted through the actin cytoskeleton to molecular endpoints that promote specific cellular outcomes, e.g., cell proliferation, adhesion, or migration. For example, most adhesive and migratory phenomena are mechanically linked by a molecular clutch comprised of mechanosensitive scaffolds. Myosin II activation and mechanosensitive molecular mechanisms are finely tuned and spatiotemporally integrated to coordinate morphogenetic events during development. Mechanical events dependent on myosin II also participate in tumor cell proliferation, invasion, and metastatic dissemination. Specifically, tumor cells alter the mechanical properties of the microenvironment to create favorable conditions for proliferation and/or dissemination. These observations position myosin II-dependent force generation and mechanotransduction at the crossroads between normal development and cancer.