Description of Turritopsoides marhei sp. nov. (Hydrozoa,Anthoathecata) from the Maldives and its phylogenetic position

Turritopsoides marhei, a new species of the hydrozoan family Oceaniidae, is described from the Maldives. This species can be distinguished from the only other member of the genus by the presence of more branched colonies, branches not being adnate to pedicels, longer pedicels, larger nematocysts, nematocyst-rich nematophore-like outgrowths from pedicels, smaller male gonophores, and a different geographic distribution. This finding represents the first record of the genus outside the type locality of its type species, in Belize. Molecular phylogenetic analyses show that, as expected, T. marhei belongs to the clade Filifera IV. However, the phylogenetic hypothesis based on both mitochondrial and nuclear DNA sequences reveals that most of the families of this group are polyphyletic, including Oceaniidae, and suggests that the morphological characters used to discriminate among filiferan families need to be revised thoroughly.

http://zoobank.org/urn:lsid:zoobank.org:pub:CE901E0D-B125-4A87-BB97-8020C0658B5D     

Extragastric Manifestations of Helicobacter pylori Infection: Other Helicobacters

The finding that Helicobacter pylori is the main cause of gastritis and peptic ulcer disease has opened a new era in the gastrointestinal world. Today there is evidence that H. pylori may also play a role in different nongastric diseases, opening the new "extragastric manifestations of H. pylori infection" field. Concerning this, several studies have been published in the last year. The most convincing data arise from those investigating idiopathic thrombocytopenic purpura and sideropenic anemia, while there is also an increasing evidence for a possible association with atherosclerotic disease. Furthermore, the discovery of a number of other novel Helicobacter species has stimulated the research in different extragastric diseases, in which an infectious hypothesis is plausible. In particular, several species have been studied for a potential role in different liver and intestinal diseases with interesting findings.     

Bone alterations during HIV infection

Osteopenia and osteoporosis are common in HIV-1-infected individuals and represent a challenge in clinical and therapeutic management. Since the mechanisms underlying this degenerative process are largely unsettled and it has not yet been determined whether bone dysfunction is linked to HIV-1-mediated direct and/or indirect effects on osteoblasts/osteoclasts cross-talk regulation, this brief review analyzes an array of mechanisms that could account for the dramatic bone derangement (bone loss and osteopenia/osteoporosis) during the course of HIV-1 infection.     

The involvement of the tyrosine kinase c-Src in the regulation of reactive oxygen species generation mediated by NADPH oxidase-1

NADPH oxidase (Nox) family enzymes are one of the main sources of cellular reactive oxygen species (ROS), which have been shown to function as second messenger molecules. To date, seven members of this family have been reported, including Nox1-5 and Duox1 and -2. With the exception of Nox2, the regulation of the Nox enzymes is still poorly understood. Nox1 is highly expressed in the colon, and it requires two cytosolic regulators, NoxO1 and NoxA1, as well as the binding of Rac1 GTPase, for its activity. In this study, we investigate the role of the tyrosine kinase c-Src in the regulation of ROS formation by Nox1. We show that c-Src induces Nox1-mediated ROS generation in the HT29 human colon carcinoma cell line through a Rac-dependent mechanism. Treatment of HT29 cells with the Src inhibitor PP2, expression of a kinase-inactive form of c-Src, and c-Src depletion by small interfering RNA (siRNA) reduce both ROS generation and the levels of active Rac1. This is associated with decreased Src-mediated phosphorylation and activation of the Rac1-guanine nucleotide exchange factor Vav2. Consistent with this, Vav2 siRNA that specifically reduces endogenous Vav2 protein is able to dramatically decrease Nox1-dependent ROS generation and abolish c-Src-induced Nox1 activity. Together, these results establish c-Src as an important regulator of Nox1 activity, and they may provide insight into the mechanisms of tumor formation in colon cancers.     

The Yku70-Yku80 complex contributes to regulate double-strand break processing and checkpoint activation during the cell cycle

DNA double-strand breaks (DSBs) are repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). HR requires 5' DSB end degradation that occurs in the presence of cyclin-dependent kinase (CDK) activity. Here, we show that a lack of any of the NHEJ proteins Yku (Yku70-Yku80), Lif1 or DNA ligase IV (Dnl4) increases 5' DSB end degradation in G1 phase, with ykuDelta cells showing the strongest effect. This increase depends on MRX, the recruitment of which at DSBs is enhanced in ykuDelta G1 cells. DSB processing in G2 is not influenced by the absence of Yku, but it is delayed by Yku overproduction, which also decreases MRX loading on DSBs. Moreover, DSB resection in ykuDelta cells occurs independently of CDK activity, suggesting that it might be promoted by CDK-dependent inhibition of Yku.     

An overview of pancreatic beta-cell defects in human type 2 diabetes: implications for treatment

Type 2 diabetes is the most common form of diabetes in humans. It results from a combination of factors that impair beta-cell function and tissue insulin sensitivity. However, growing evidence is showing that the beta-cell is central to the development and progression of this form of diabetes. Reduced islet and/or insulin-containing cell mass or volume in Type 2 diabetes has been reported by several authors. Furthermore, studies with isolated Type 2 diabetic islets have consistently shown both quantitative and qualitative defects of glucose-stimulated insulin secretion. The impact of genotype in affecting beta-cell function and survival is a very fast growing field or research, and several gene polymorphisms have been associated with this form of diabetes. Among acquired factors, glucotoxicity, lipotoxicity and altered IAPP processing are likely to play an important role. Interestingly, however, pharmacological intervention can improve several defects of Type 2 diabetes islet cells in vitro, suggesting that progression of the disease might not be relentless.     

The role of Li+, Na+, and K+ in the ligand binding inside the human acetylcholinesterase gorge

Alkali cations can affect the catalytic efficiency of enzymes. This is particularly true when dealing with enzymes whose substrate bears a formal positive charge. Computational and biochemical approaches have been combined to shed light on the atomic aspects of the role of Li(+), Na(+), and K(+) on human acetylcholinesterase (hAChE) ligand binding. In this respect, molecular dynamics simulations and our recently developed metadynamics method were applied to study the entrance of the three cations in the gorge of hAChE, and their effect on the dynamical motion of a ligand (tetramethylammonium) from the bulk of the solvent into the deep narrow enzyme gorge. Furthermore, in order to support the theoretical results, K(M) and k(cat) for the acetylcholine hydrolysis in the presence of the three cations were evaluated by using an approach based on the Ellman's method. The combination of computational and biochemical experiments clearly showed that Li(+), Na(+), and K(+) may influence the ligand binding at the hAChE gorge.     

Deorphanisation of G protein-coupled receptors: A tool to provide new insights in nervous system pathophysiology and new targets for psycho-active drugs

G protein-coupled receptors represent the largest family of membrane receptors translating extracellular into intracellular signals. Endogenous ligands for these receptors range from physical stimuli (e.g., light and odorants) to ions and chemical transmitters, such as "classical" biogenic amines, nucleotides and peptides. Some of these receptors are pathologically altered in neurodegenerative and psychiatric diseases and indeed represent the target for a variety of already marketed psycho-active drugs. With the publication of the human genome, it has become evident that there still are many "orphan" G protein-coupled receptors, i.e., receptors responding to yet-unidentified endogenous ligands. A large amount of these receptors are expressed in nervous tissues, but, apart from their molecular structure, we have no information concerning their physiological roles and alterations in disease states. In this review, we summarise the advancements and pitfalls of the strategies that have been exploited in recent years to "deorphanise" some of these receptors. We also show how, in some cases, this deorphanisation process has resulted in the identification of new potential targets for drug development as well as in the discovery of previously unknown neurotransmitters, including bioactive peptides and substances that had been merely known as metabolic intermediates. We envisage that the deorphanisation of the remaining orphan G protein-coupled receptors will further advance our knowledge of nervous system pathophysiology and unveil additional targets for new therapeutic approaches to human diseases, including psychosis, depression, anxiety, pain and aging-associated neurodegenerative disorders.     

Dinosaurs and the Cretaceous Terrestrial Revolution

The observed diversity of dinosaurs reached its highest peak during the mid- and Late Cretaceous, the 50 Myr that preceded their extinction, and yet this explosion of dinosaur diversity may be explained largely by sampling bias. It has long been debated whether dinosaurs were part of the Cretaceous Terrestrial Revolution (KTR), from 125-80 Myr ago, when flowering plants, herbivorous and social insects, squamates, birds and mammals all underwent a rapid expansion. Although an apparent explosion of dinosaur diversity occurred in the mid-Cretaceous, coinciding with the emergence of new groups (e.g. neoceratopsians, ankylosaurid ankylosaurs, hadrosaurids and pachycephalosaurs), results from the first quantitative study of diversification applied to a new supertree of dinosaurs show that this apparent burst in dinosaurian diversity in the last 18 Myr of the Cretaceous is a sampling artefact. Indeed, major diversification shifts occurred largely in the first one-third of the group's history. Despite the appearance of new clades of medium to large herbivores and carnivores later in dinosaur history, these new originations do not correspond to significant diversification shifts. Instead, the overall geometry of the Cretaceous part of the dinosaur tree does not depart from the null hypothesis of an equal rates model of lineage branching. Furthermore, we conclude that dinosaurs did not experience a progressive decline at the end of the Cretaceous, nor was their evolution driven directly by the KTR.