New directions in biogeography?

The deduction of biogeographic process from the study of its history is complicated by the fact that history is a singular thing. This singularity allows no estimation of the degree of determinism surrounding the realization of biogeographic processes, and consequently we know almost nothing about the generality of such deductions. Here we discuss a new approach, called 'experimental biogeography', that exploits computers to model faunal build-up repeatedly against a fixed vicariant background over ecological and evolutionary time scales. This new approach enables a biogeographer to be omniscient - to know both vicariant history and actual phylogeny. Moreover, history can be replayed repeatedly to accumulate a sample of multiple phylogenies and to estimate probability density functions for biogeographic variables. Roles of stochastic, historical and ecological processes in adaptive radiations can also be assessed. Experimental biogeography allows examination of the reliability of various methods of recovering historical patterns.     

Ligation of α-Dystroglycan on Podocytes Induces Intracellular Signaling: A New Mechanism for Podocyte Effacement?

Background

α-Dystroglycan is a negatively charged glycoprotein that covers the apical and basolateral membrane of the podocyte. Its transmembrane binding to the cytoskeleton is regulated via tyrosine phosphorylation (pY892) of β-dystroglycan. At the basolateral side α-dystroglycan binds the glomerular basement membrane. At the apical membrane, it plays a role in the maintenance of the filtration slit. In this study, we evaluated whether ligation of α-dystroglycan with specific antibodies or natural ligands induces intracellular signaling, and whether there is an effect on podocyte architecture.

Methodology/Principal Findings

Conditionally immortalized podocytes were exposed in vitro to antibodies to α-dystroglycan, and to fibronectin, biglycan, laminin and agrin. Intracellular calcium fluxes, phosphorylation of β-dystroglycan and podocyte architecture were studied. Antibodies to α-dystroglycan could specifically induce calcium signaling. Fibronectin also induced calcium signaling, and led to dephosphorylation of pY892 in β-dystroglycan. Ligation of α-dystroglycan resulted in an altered actin architecture, a decreased number of podocyte pedicles and a more flattened appearance of the podocyte.

Conclusions/Significance

We conclude that ligation of α-dystroglycan on podocytes induces intracellular calcium signaling, which leads to an altered cytoskeleton architecture akin to the situation of foot process effacement. In particular the ability of fibronectin to induce intracellular signaling events is of interest, since the expression and excretion of this protein is upregulated in several proteinuric diseases. Therefore, fibronectin-induced signaling via dystroglycan may be a novel mechanism for foot process effacement in proteinuric diseases.     

Species-Specific Bacterial Communities in the Phycosphere of Microalgae?

Specific associations of bacteria with phytoplankton have recently been reported in the literature. In our study, we analyzed bacterial communities of microalgal cultures related to algal growth phases. Seven freshly isolated key diatom and dinoflagellate species from Helgoland Roads, North Sea, were investigated. The community composition of associated bacteria as well as the cell numbers, the photosynthetic efficiency of the algae, and the depletion of inorganic nutrients in the medium were recorded over a period of 8 weeks in batch cultures. Diversity and succession of bacterial communities was analyzed by ribosomal intergenic spacer analysis. Phylogenetic analysis of bacterial populations was performed by denaturing gradient gel electrophoresis of 16S rRNA genes followed by DNA sequence analysis. Members of Alphaproteobacteria and Gammaproteobacteria and the Flavobacteria–Sphingobacteria group within the Bacteroidetes phylum predominated in the cultures. Differences in free-living and attached bacterial populations were observed between the phylogenetic groups. Shifts in the bacterial communities could not be correlated to changes of nutrient levels or algal growth phases. Regarding our results, it should not be generalized that the compositions of the bacterial communities are strictly species specific for microalgae. The importance of factors like the composition of exudates is apparent.     

Poor Diet in Shift Workers: A New Occupational Health Hazard?

The PLoS Medicine Editors discuss the link between shift work, diet, and type 2 diabetes, and argue that unhealthy eating should be considered a new form of occupational hazard.     

Tuberin – A New Molecular Target in Alzheimer’s Disease?

Tuberous sclerosis complex (TSC) is a common genetic disorder in which affected individuals develop mental retardation, developmental brain defects and seizures. The TSC gene products, hamartin and tuberin, form a complex, of which tuberin is assumed to be the functional component being involved in a wide variety of different cellular processes. Here we report that tuberin protein levels are decreased in the frontal cortex of patients with Alzheimer’s disease. In addition, tuberin levels are also decreased in Down syndrome brain samples positive for β-amyloid plaques and neurofibrillary tangles. Analysis of NeuN revealed that this regulation is not a consequence of differences in the amount of postmitotic neurons. This first connection of tuberin to another common disease beside TSC stimulates new approaches to investigate the molecular development and to establish new therapeutic strategies.     

PHOR1: A U-Box GA Signaling Component With a Role in Proteasome Degradation?

Recent identification of U-box proteins as E3 ubiquitin ligases suggests that the U-box arm-repeat protein PHOR1, for which we have demonstrated a role in GA signal transduction, may play a role in GA signaling by ubiquitinating one or more components of the GA response pathway to target them for proteasome degradation. Here we show that PHOR1 function in GA signaling is not exclusive of potato plants, but it is also conserved in Arabidopsis. Three PHOR1-homologs have been identified in this plant species, which would correspond to PHOR1-orthologs. Experimental evidence has recently been obtained for the involvement of proteasome-dependent protein degradation in GA-mediated destabilization of the SLN1 DELLA protein, thus pointing to this repressor as a likely substrate for ubiquitination by the PHOR1 ubiquitin ligase activity.     

Rhabdomyolysis in Community Acquired Bacterial Sepsis – A Retrospective Cohort Study

Background and Objectives

Rhabdomyolysis is often associated with sepsis and gram positive bacterial pathogens are reported to be the most frequent cause of sepsis induced rhabdomyolysis. We report the pattern of infecting bacterial pathogens and associated causal factors in a South-Indian cohort.

Design, Setting, Participants & Measurements

Retrospective cohort study of adult patients with community acquired bacterial sepsis complicated by rhabdomyolysis from March 2003 - August 2008. Rhabdomyolysis was defined as serum creatine kinase >2000 IU/L. The study population was divided into group-I (sepsis with gram positive pathogens), group–II (sepsis with gram negative pathogens) and group-III (culture negative sepsis).

Results

103 patients (group I -15, group II- 34 and group III- 54) formed the study cohort. Mean age was 55 years and two-third had diabetes. Mean creatine kinase was 7114 IU/L and mean serum creatinine on admission was 2.4 mg/dl. Causative pathogen of sepsis was identified in 47.5%. Gram negative pathogens were more frequently (33%) associated with rhabdomyolysis than gram positive pathogens (14.5%). Lung was the commonest foci of sepsis (38.8%). 78.6% of the study population had one or more additional causal factor for rhabdomyolysis like statin intake, chronic alcoholism, hypokalemia, hypernatremia and hypophosphatemia. Mortality was 59%.

Conclusions

Gram negative bacterial pathogens were more frequently associated with rhabdomyolysis than gram positive pathogens. Rhabdomyolysis in patients with sepsis is multifactorial and is associated with high mortality.     

A New Tandem Repeat in Bovine Fibrinogen Aα Gene

In this study, we describe intraspecies variation in the αC connector region of the bovine fibrinogen Aα gene. Sequencing and genotyping of six bovine breeds revealed 7 to 10 tandem repeats in the αC connector region. In addition, we observed length differences between B. indicus and B. taurus, with the B. indicus having longer fibrinogen αC connectors (10-repeat alleles) than B. taurus (7- and 9-repeats). The difference in tandem repeats may be related to the function of blood coagulation system.     

Wnt Signaling in Remyelination in Multiple Sclerosis: Friend or Foe?

Myelination is critical to normal functioning of the vertebrate nervous system. In demyelinating diseases such as multiple sclerosis, oligodendrocytes, the myelinating cells in the central nervous system, are targeted, resulting in myelin loss, axonal damage, and severe functional impairment. While spontaneous remyelination has been proven a failure in multiple sclerosis, understanding the molecular mechanism underlying oligodendrocyte biology, myelination, and remyelination becomes crucial. To date, a series of signaling pathways in regulating oligodendrocyte development and remyelination have been suggested and, among them, the Wnt/β-catenin/Tcf pathway has been considered a negative factor in the myelinating process. However, this notion has been challenged by recent studies, which showed a pro-myelinating effect of this pathway. This review summarizes the current contradictory concepts concerning the role of the Wnt pathway in the oligodendrocyte development and remyelination process, attempts to address the potential mechanism underlying this controversy, and recommends caution in targeting the Wnt pathway as a potential demyelinating therapy.     

A Cryptic Frizzled Module in Cell Surface Collagen 18 Inhibits Wnt/β?Catenin Signaling

Collagens contain cryptic polypeptide modules that regulate major cell functions, such as cell proliferation or death. Collagen XVIII (C18) exists as three amino terminal end variants with specific amino terminal polypeptide modules. We investigated the function of the variant 3 of C18 (V3C18) containing a frizzled module (FZC18), which carries structural identity with the extracellular cysteine-rich domain of the frizzled receptors. We show that V3C18 is a cell surface heparan sulfate proteoglycan, its topology being mediated by the FZC18 module. V3C18 mRNA was expressed at low levels in 21 normal adult human tissues. Its expression was up-regulated in fibrogenesis and in small well-differentiated liver tumors, but decreased in advanced human liver cancers. Low FZC18 immunostaining in liver cancer nodules correlated with markers of high Wnt/β−catenin activity. V3C18 (M_r = 170 kD) was proteolytically processed into a cell surface FZC18-containing 50 kD glycoprotein precursor that bound Wnt3a in vitro through FZC18 and suppressed Wnt3a-induced stabilization of β−catenin. Ectopic expression of either FZC18 (35 kD) or its 50 kD precursor inhibited Wnt/β−catenin signaling in colorectal and liver cancer cell lines, thus downregulating major cell cycle checkpoint gatekeepers cyclin D1 and c-myc and reducing tumor cell growth. By contrast, full-length V3C18 was unable to inhibit Wnt signaling. In summary, we identified a cell-surface signaling pathway whereby FZC18 inhibits Wnt/β−catenin signaling. The signal, encrypted within cell-surface C18, is released by enzymatic processing as an active frizzled cysteine-rich domain (CRD) that reduces cancer cell growth. Thus, extracellular matrix controls Wnt signaling through a collagen-embedded CRD behaving as a cell-surface sensor of proteolysis, conveying feedback cues to control cancer cell fate.     

Do Honeybees Shape the Bacterial Community Composition in Floral Nectar?

Floral nectar is considered the most important reward animal-pollinated plants offer to attract pollinators. Here we explore whether honeybees, which act as pollinators, affect the composition of bacterial communities in the nectar. Nectar and honeybees were sampled from two plant species: Amygdalus communis and Citrus paradisi. To prevent the contact of nectar with pollinators, C. paradisi flowers were covered with net bags before blooming (covered flowers). Comparative analysis of bacterial communities in the nectar and on the honeybees was performed by the 454-pyrosequencing technique. No significant differences were found among bacterial communities in honeybees captured on the two different plant species. This resemblance may be due to the presence of dominant bacterial OTUs, closely related to the Arsenophonus genus. The bacterial communities of the nectar from the covered and uncovered C. paradisi flowers differed significantly; the bacterial communities on the honeybees differed significantly from those in the covered flowers’ nectar, but not from those in the uncovered flowers’ nectar. We conclude that the honeybees may introduce bacteria into the nectar and/or may be contaminated by bacteria introduced into the nectar by other sources such as other pollinators and nectar thieves.     

Signaling in the plant cytosol: cysteine or sulfide?

Cysteine (Cys) is the first organic compound containing reduced sulfur that is synthesized in the last stage of plant photosynthetic assimilation of sulfate. It is a very important metabolite not only because it is crucial for the structure, function and regulation of proteins but also because it is the precursor molecule of an enormous number of sulfur-containing metabolites essential for plant health and development. The biosynthesis of Cys is accomplished by the sequential reaction of serine acetyltransferase (SAT) and O-acetylserine(thiol)synthase (OASTL). In Arabidopsis thaliana, the analysis of specific mutants of members of the SAT and OASTL families has demonstrated that the cytosol is the compartment where the bulk of Cys synthesis takes place and that the cytosolic OASTL enzyme OAS-A1 is the responsible enzyme. Another member of the OASTL family is DES1, a novel l-cysteine desulfhydrase that catalyzes the desulfuration of Cys to produce sulfide, thus acting in a manner opposite to that of OAS-A1. Detailed studies of the oas-a1 and des1 null mutants have revealed the involvement of the DES1 and OAS-A1 proteins in coordinate regulation of Cys homeostasis and the generation of sulfide in the cytosol for signaling purposes. Thus, the levels of Cys in the cytosol strongly affect plant responses to both abiotic and biotic stress conditions, while sulfide specifically generated from the degradation of Cys negatively regulates autophagy induced in different situations. In conclusion, modulation of the levels of Cys and sulfide is likely critical for plant performance.