Quantitative regularities for clinical manifestations of radiation injury in large-sized laboratory animals exposed to supralethal radiation doses Gamma-neutron and electron biological effectiveness as influenced by exposure conditions and dose distribution in the animal body

The damaging effect of gamma-neutron radiation over a wide neutron-energy range, with average values of 0.37 and 1.2 MeV, and that of electrons with an average electron energy of 25 MeV have been compared in dogs and two monkey species exposed to a broad range of supralethal doses. An analysis of absorbed dose distribution in critical organs and systems has shown the highest effect of gamma-neutron radiation with an average neutron energy of 1.2 MeV. With severity of early clinical manifestations of damage as a criterion, electrons have appeared the most effective. The radiosensitivity of animals grew in the order as follows: dog-->M. fascicularis-->P. hamadryas.     

Isolation and characterization of highly pathogenic avian influenza virus subtype H5N1 from donkeys

Background  

The highly pathogenic H5N1 is a major avian pathogen that crosses species barriers and seriously affects humans as well as some mammals. It mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Centrosomal Chk2 in DNA damage responses and cell cycle progession

Two major control systems regulate early stages of mitosis: activation of Cdk1 and anaphase control through assembly and disassembly of the mitotic spindle. In parallel to cell cycle progression, centrosomal duplication is regulated through proteins including Nek2. Recent studies suggest that centrosome-localized Chk1 forestalls premature activation of centrosomal Cdc25b and Cdk1 for mitotic entry, whereas Chk2 binds centrosomes and arrests mitosis only after activation by ATM and ATR in response to DNA damage. Here, we show that Chk2 centrosomal binding does not require DNA damage, but varies according to cell cycle progression. These and other data suggest a model in which binding of Chk2 to the centrosome at multiple cell cycle junctures controls co-localization of Chk2 with other cell cycle and centrosomal regulators.Key words: Chk2, centrosome, checkpoint, DNA damage, wild type, kinase-defective     

Microtubule-binding proteins CLASP1 and CLASP2 interact with actin filaments

Cell morphogenesis requires dynamic communication between actin filaments and microtubules which is mediated, at least in part, by direct structural links between the two cytoskeletal systems. Here, we examined interaction between the CLIP-associated proteins (CLASP) CLASP1 and CLASP2, and actin filaments. We demonstrate that, in addition to a well-established association with the distal ends of microtubules, CLASP2alpha co-localizes with stress fibers, and that both CLASP1alpha and CLASP2alpha co-immunoprecipitate with actin. GFP-CLASP2alpha exhibits retrograde flow in the lamellipodia of Xenopus primary fibroblasts and in the filopodia of Xenopus spinal cord neurons. A deletion mapping analysis reveals that both the microtubule-binding domain of CLASP2 (which is homologous between all CLASPs) and the N-terminal dis1/TOG domain of CLASP2alpha (which is homologous between alpha isoforms) possess actin-binding activity. Fluorescence resonance energy transfer experiments demonstrate significant energy transfer between YFP-CLASP2alpha and CFP-actin. Our results indicate that CLASPs function as actin/microtubule crosslinkers in interphase cells. We propose that CLASPs facilitate recognition of actin filaments by the plus ends of growing microtubules at the initial stages of actin-microtubule interaction. Cell Motil.     

Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents

Molecular Biology - Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic...     

20S proteasomal degradation of ornithine decarboxylase is regulated by NQO1

Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is a very labile protein. ODC is a homodimeric enzyme that undergoes ubiquitin-independent proteasomal degradation via direct interaction with antizyme, a polyamine-induced protein. Binding of antizyme promotes the dissociation of ODC homodimers and marks ODC for degradation by the 26S proteasomes. We describe here an alternative pathway for ODC degradation that is regulated by NAD(P)H quinone oxidoreductase 1 (NQO1). We show that NQO1 binds and stabilizes ODC. Dicoumarol, an inhibitor of NQO1, dissociates ODC-NQO1 interaction and enhances ubiquitin-independent ODC proteasomal degradation. We further show that dicoumarol sensitizes ODC monomers to proteasomal degradation in an antizyme-independent manner. This process of NQO1-regulated ODC degradation was recapitulated in vitro by using purified 20S proteasomes. Finally, we show that the regulation of ODC stability by NQO1 is especially prominent under oxidative stress. Our findings assign to NQO1 a role in regulating ubiquitin-independent degradation of ODC by the 20S proteasomes.     

Spatiotemporal asymmetry of associative synaptic plasticity in fear conditioning pathways

Input-specific long-term potentiation (LTP) in afferent inputs to the amygdala serves an essential function in the acquisition of fear memory. Factors underlying input specificity of synaptic modifications implicated in information transfer in fear conditioning pathways remain unclear. Here we show that the strength of naive synapses in two auditory inputs converging on a single neuron in the lateral nucleus of the amygdala (LA) is only modified when a postsynaptic action potential closely follows a synaptic response. The stronger inhibitory drive in thalamic pathway, as compared with cortical input, hampers the induction of LTP at thalamo-amygdala synapses, contributing to the spatial specificity of LTP in convergent inputs. These results indicate that spike timing-dependent synaptic plasticity in afferent projections to the LA is both temporarily and spatially asymmetric, thus providing a mechanism for the conditioned stimulus discrimination during fear behavior.     

The accuracy of several multiple sequence alignment programs for proteins

Background  

There have been many algorithms and software programs implemented for the inference of multiple sequence alignments of protein and DNA sequences. The "true" alignment is usually unknown due to the incomplete knowledge of the evolutionary history of the sequences, making it difficult to gauge the relative accuracy of the programs.