Heat shock cognate protein 70 is involved in rotavirus cell entry

In this work, we have identified the heat shock cognate protein (hsc70) as a receptor candidate for rotaviruses. hsc70 was shown to be present on the surface of MA104 cells, and antibodies to this protein blocked rotavirus infectivity, while not affecting the infectivity of reovirus and poliovirus. Preincubation of the hsc70 protein with the viruses also inhibited their infectivity. Triple-layered particles (mature virions), but not double-layered particles, bound hsc70 in a solid-phase assay, and this interaction was blocked by monoclonal antibodies to the virus surface proteins VP4 and VP7. Rotaviruses were shown to interact with hsc70 at a postattachment step, since antibodies to hsc70 and the protein itself did not inhibit the virus attachment to cells. We propose that the functional rotavirus receptor is a complex of several cell surface molecules that include, among others, hsc70.     

Absence of association between mannose-binding lectin gene polymorphisms and HIV-1 infection in a Colombian population

Mannose-binding lectin (MBL) is a calcium-dependent lectin shown to play an important role in innate immunity to infection by activating the classical complement pathway and phagocytosis. In vitro studies have shown that MBL is able to bind to the gp120 HIV-1 surface antigen, and variants of the gene are associated with increased risk of HIV infection among Scandinavians. We investigated the association of genetic MBL variants and HIV-1 infection in 278 Colombian HIV-infected and control individuals. MBL genotype frequencies were similar for both groups, and no association was detected between MBL alleles B, C, and D and susceptibility to HIV-1 infection ( P=1.0). Since there is a well-documented link between the tested MBL alleles and very low MBL serum concentration, these results do not support the hypothesis that MBL levels are a risk factor for HIV-1 infection in Colombia.     

Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression

The mechanisms by which excessive glucocorticoids cause muscular atrophy remain unclear. We previously demonstrated that dexamethasone increases the expression of myostatin, a negative regulator of skeletal muscle mass, in vitro. In the present study, we tested the hypothesis that dexamethasone-induced muscle loss is associated with increased myostatin expression in vivo. Daily administration (60, 600, 1,200 micro g/kg body wt) of dexamethasone for 5 days resulted in rapid, dose-dependent loss of body weight (-4.0, -13.4, -17.2%, respectively, P < 0.05 for each comparison), and muscle atrophy (6.3, 15.0, 16.6% below controls, respectively). These changes were associated with dose-dependent, marked induction of intramuscular myostatin mRNA (66.3, 450, 527.6% increase above controls, P < 0.05 for each comparison) and protein expression (0.0, 260.5, 318.4% increase above controls, P < 0.05). We found that the effect of dexamethasone on body weight and muscle loss and upregulation of intramuscular myostatin expression was time dependent. When dexamethasone treatment (600 micro g. kg-1. day-1) was extended from 5 to 10 days, the rate of body weight loss was markedly reduced to approximately 2% within this extended period. The concentrations of intramuscular myosin heavy chain type II in dexamethasone-treated rats were significantly lower (-43% after 5-day treatment, -14% after 10-day treatment) than their respective corresponding controls. The intramuscular myostatin concentration in rats treated with dexamethasone for 10 days returned to basal level. Concurrent treatment with RU-486 blocked dexamethasone-induced myostatin expression and significantly attenuated body loss and muscle atrophy. We propose that dexamethasone-induced muscle loss is mediated, at least in part, by the upregulation of myostatin expression through a glucocorticoid receptor-mediated pathway.     

First record for the European Ichthyofauna of Dentex (Cheimerius) canariensis Steindachner, 1881

Dentex ( Cheimerius ) canariensis is recorded for the first time for European waters, on the basis of four specimens captured on the coast of Cádiz (SW Iberian peninsula).     

Glycerol 3-phosphate inhibits swarming and aggregation of Myxococcus xanthus

We have cloned a gene of Myxococcus xanthus with similarities to the permease for glycerol 3-phosphate (G3P) of other bacteria. Expression of the gene increased significantly during the first hours of starvation. Swarming of the wild-type strain was inhibited and aggregation was delayed by G3P. Conversely, a DeltaglpT strain aggregated even on rich medium. These results indicate that G3P may function to regulate the timing of aggregation in M. xanthus.     

Wingless modulates the effects of dominant negative notch molecules in the developing wing of Drosophila

The development and patterning of the wing in Drosophila relies on a sequence of cell interactions molecularly driven by a number of ligands and receptors. Genetic analysis indicates that a receptor encoded by the Notch gene and a signal encoded by the wingless gene play a number of interdependent roles in this process and display very strong functional interactions. At certain times and places, during wing development, the expression of wingless requires Notch activity and that of its ligands Delta and Serrate. This has led to the proposal that all the interactions between Notch and wingless can be understood in terms of this regulatory relationship. Here we have tested this proposal by analysing interactions between Delta- and Serrate-activated Notch signalling and Wingless signalling during wing development and patterning. We find that the cell death caused by expressing dominant negative Notch molecules during wing development cannot be rescued by coexpressing Nintra. This suggests that the dominant negative Notch molecules cannot only disrupt Delta and Serrate signalling but can also disrupt signalling through another pathway. One possibility is the Wingless signalling pathway as the cell death caused by expressing dominant negative Notch molecules can be rescued by activating Wingless signalling. Furthermore, we observe that the outcome of the interactions between Notch and Wingless signalling differs when we activate Wingless signalling by expressing either Wingless itself or an activated form of the Armadillo. For example, the effect of expressing the activated form of Armadillo with a dominant negative Notch on the patterning of sense organ precursors in the wing resembles the effects of expressing Wingless alone. This result suggests that signalling activated by Wingless leads to two effects, a reduction of Notch signalling and an activation of Armadillo.     

Mapping of bovine ovulation rate QTL; an analytical approach for three generation pedigrees

Interval mapping was conducted for ovulation rate quantitative trait loci (QTL) using data from two related families from the United States Department of Agriculture, US Meat Animal Research Center twinning cattle herd. Both families are extended, three generation pedigrees from which records of sons, daughters and granddaughters were analysed. Both a method of analysis and results from that analysis are reported herein. Results from one of the two families (839802) were previously reported, but reanalysis here including the second, related family (839803) and a revised statistical model lessens support for the previously reported QTL. Results from interval mapping provided evidence for QTL in regions corresponding to those previously suggested for chromosomes 7 (chromosome-wise P < 0.05) and 19 (chromosome-wise P < 0.01) in the 839802 family, although statistical significance was reduced. In contrast to the previous report, evidence for a chromosome 5 QTL in the same family was greatly reduced while support for a QTL on chromosome 10 increased (chromosome-wise P < 0.01). Analysis of data from the related 839803 family failed to replicate evidence of QTL observed on either chromosome 7 or chromosome 19 in the 839802 family.     

A new dawn for an old connection: development meets the cell

Increasingly, the attention of developmental biologists is being drawn from genes and their products towards cells, from processes mediated by linear pathways in which one protein regulates the activity of another to events that rely on multimolecular machines. Some components of these machines are partially redundant, and some have essential functions in general cellular processes. These observations invite a reassessment of the uses of genetics for analyzing the cell biology of development. In addition, the increasing ability to image live cells and their proteins reveals a complex and interesting world, forcing us to deal with new variables and objects of study. Here, we provide a glimpse of these changes and the challenges they raise.     

High Intensity Light Increases Olfactory Bulb Melatonin in Venezuelan Equine Encephalitis Virus Infection

In mice infected with the Venezuelan equine encephalomyelitis (VEE) virus and exposed to high intensity light (2500 lux) with a 12 h light: 12 h dark photoperiod, a significant increase in the levels of melatonin in the olfactory bulb was observed. The significance of these findings deserves further studies to understand the mechanisms involved in this effect since the olfactory bulbs have been proposed as first portal for VEE virus entry into the CNS. The increase in melatonin content could represent one of the mechanisms of defense against the viral attack.     

Newly synthesized canalicular ABC transporters are directly targeted from the Golgi to the hepatocyte apical domain in rat liver

Newly synthesized canalicular ectoenzymes and a cell adhesion molecule (cCAM105) have been shown to traffic from the Golgi to the basolateral plasma membrane, from where they transcytose to the apical bile canalicular domain. It has been proposed that all canalicular proteins are targeted via this indirect route in hepatocytes. We studied the membrane targeting of rat canalicular proteins by in vivo [(35)S]methionine metabolic labeling followed by preparation of highly purified Golgi membranes and canalicular (CMVs) and sinusoidal/basolateral (SMVs) membrane vesicles and subsequent immunoprecipitation. In particular, we compared membrane targeting of newly synthesized canalicular ABC (ATP-binding cassette) transporters MDR1, MDR2, and SPGP (sister of P-glycoprotein) with that of cCAM105. Significant differences were observed in metabolic pulse-chase labeling experiments with regard to membrane targeting of these apical proteins. After a chase time of 15 min, cCAM105 appeared exclusively in SMVs, peaked at 1 h, and progressively declined thereafter. In CMVs, cCAM105 was first detected after 1 h and subsequently increased for 3 h. This findings confirm the transcytotic targeting of cCAM105 reported in earlier studies. In contrast, at no time point investigated were MDR1, MDR2, and SPGP detected in SMVs. In CMVs, MDR1 and MDR2 appeared after 30 min, whereas SPGP appeared after 2 h of labeling. In Golgi membranes, each of the ABC transporters peaked at 30 min and was virtually absent thereafter. These data suggest rapid, direct targeting of newly synthesized MDR1 and MDR2 from the Golgi to the bile canaliculus and transient sequestering of SPGP in an intracellular pool en route from the Golgi to the apical plasma membrane. This study provides biochemical evidence for direct targeting of newly synthesized apical ABC transporters from the Golgi to the bile canaliculus in vivo.