Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident

BackgroundThe excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of ¹³¹I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error.MethodsWe examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996–2004, who had direct thyroid ¹³¹I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied.ResultsThere was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy⁻ (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy⁻ (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy⁻ (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy⁻ (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053–0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2).ConclusionsIn summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.     

The solution structure of a domain from the Neisseria meningitidis lipoprotein PilP reveals a new beta-sandwich fold

Type IV pili are long, thin fibres, which extend from the surface of the bacterial pathogen Neisseria meningitidis; they play a key role in adhesion and colonisation of host cells. PilP is a lipoprotein, suggested to be involved in the assembly and stabilization of an outer membrane protein, PilQ, which is required for pilus formation. Here we describe the expression of a recombinant fragment of PilP, spanning residues 20 to 181, and determination of the solution structure of a folded domain, spanning residues 85 to 163, by NMR. The N-terminal third of the protein, from residues 20 to 84, is apparently unfolded. Protease digestion yielded a 113 residue fragment that contained the folded domain. The domain adopts a simple beta-sandwich type fold, consisting of a three-stranded beta-sheet packed against a four-stranded beta-sheet. There is also a short segment of 3(10) helix at the N-terminal part of the folded domain. We were unable to identify any other proteins that are closely related in structure to the PilP domain, although the fold appears to be distantly related to the lipocalin family. Over 40 homologues of PilP have been identified in Gram-negative bacteria and the majority of conserved residues lie within the folded domain. The fourth beta-strand and adjacent loop regions contain a high proportion of conserved residues, including three glycine residues, which seem to play a role in linking the two beta-sheets. The two beta-sheets pack together to form a crevice, lined with conserved hydrophobic residues: we suggest that this feature could act as a binding site for a small ligand. The results show that PilP and its homologues have a conserved, folded domain at the C-terminal end of the protein that may be involved in mediating binding to hydrophobic ligands.     

重庆市蕨类植物区系调查和分析

重庆市有野生蕨类植物47科120属604种(含变种及以下分类单位)。其科属优势明显,其中蹄盖蕨科、金星蕨科、鳞毛蕨科和水龙骨科4个科包含了49属337种,占重庆市蕨类植物属、种总数的40.83%和55.79%;特有现象明显,地方特有种十分丰富,中国特有种和地方特有种类分别达到164种和33种;蕨类植物区系具有古老、孑遗和原始性等特点,表现出一定的热带性质或热带亲缘。     

Influence of the water heating rate upon thermal tolerance in common carp (Cyprinus carpio L.) during different seasons

For the first time, the dependence of the upper lethal temperature (ULT) level upon the water heating rate was determined in young common carp (Cyprinus carpio) during different seasons and within the wide range of heating rates. The highest ULT values were revealed by using the chronic lethal impact method, with a water heating rate of 1°C/day (or 0.04°C/h). At such a rate, fish can successfully acclimate to a temperature increase. The ULT values determined by that method characterize the fish maximal thermal tolerance. During different seasons these values were differing from each other within a 3°C range. The data on the common carp ULT, along with data on crucian carp (Carassius auratus), evidences that this species belongs to the group of the most thermophilic fish, not only among cyprinids, but also compared to the representatives of other families. Obtained experimental data characterizing the upper thermal limits for fish vital functions may be used for the development of ecological safety criteria near the zones of discharge of heated waters from heating and nuclear power plants, as well as for the forecasting of the potential consequences of global warming.     

Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex

WW domains target proline-tyrosine (PY) motifs and frequently function as tandem pairs. When studied in isolation, single WW domains are notably promiscuous and regulatory mechanisms are undoubtedly required to ensure selective interactions. Here, we show that the fourth WW domain (WW4) of Suppressor of Deltex, a modular Nedd4-like protein that down-regulates the Notch receptor, is the primary mediator of a direct interaction with a Notch-PY motif. A natural Trp to Phe substitution in WW4 reduces its affinity for general PY sequences and enhances selective interaction with the Notch-PY motif via compensatory specificity-determining interactions with PY-flanking residues. When WW4 is paired with WW3, domain-domain association, impeding proper folding, competes with Notch-PY binding to WW4. This novel mode of autoinhibition is relieved by binding of another ligand to WW3. Such cooperativity may facilitate the transient regulatory interactions observed in vivo between Su(dx) and Notch in the endocytic pathway. The highly conserved tandem arrangement of WW domains in Nedd4 proteins, and similar arrangements in more diverse proteins, suggests domain-domain communication may be integral to regulation of their associated cellular activities.     

The effect of the homogenates from different developmental stages of the nematode Protostrongylus rufescens (Leuckart, 1895) on mitochondrial and lipid bilayer membranes

The effect of the homogenates from different developmental stages of the nematode Protostrongylus rufescens on mitochondrial and lipid bilayer membranes has been studied. The homogenate of P. rufescens affects efficiently the cell energy by the inhibition of the mitochondrial respiration in the metabolic state V3, uncouples oxidative phosphorylation and affects the functions of mitochondria at the level of cyclosporine A-sensitive pore by making it highly permeable. Moreover, the nematode homogenate at the concentration of 1 mkg/ml increases efficiently the integral permeability of lipid bilayer membranes. An increase in this permeability is connected apparently with the formation of single ion channels. The channels of lipid bilayer membranes induced by the nematode homogenate show cation selectivity.     

The ecological and evolutionary aspects of thermoregulation behavior on fish

The ecological and evolutionary aspects of the thermoregulation behavior in fish are reviewed. The values of the Final Preference Temperature (“Final Preferendum” or FPT) and their relations with the temperature of species origin are analyzed. The analogy in the thermal niche of the poikilotherm animals and of the FPT zone is shown. The similarity and difference in thermal acclimation and thermoregulation behavior are considered. The seasonal and age-related peculiarities of fish thermoregulation behavior and of its manifestations upon impact of a variety of external factors (food, parasites, etc.) are analyzed. The characteristic is given for relation of thermoregulation behavior with schooling, territorial, and feeding behaviors, as well as a species range. The FPT values for some fish families are given.     

Muscle transcriptomic analyses in Angus cattle with divergent tenderness

Beef tenderness contributes significantly to variation of beef palatability, and is largely influenced by various genetic and environmental factors. To identify candidate genes and pathways related to beef tenderness, we analyzed the longissimus dorsi (LD) muscle of Angus cattle that had different degrees of tenderness, measured by Warner-Bratzler shear force (WBSF). Microarray and RT-PCR analyses identified 53 genes that were differentially expressed in LD samples categorized as either tough or tender, including myosin, heavy chain 3 skeletal muscle embryonic (MYH3), myosin heavy chain 8 skeletal muscle perinatal (MYH8), guanylate binding protein 5 (GBP5), fatty acid binding protein 4 (FABP4), Stearoyl-coenzyme A desaturase (SCD), Fatty acid synthase (FASN), ubiquitin-like with PHD and ring finger domains 1 (UHRF1). Most of these genes are involved in lipid metabolism and skeletal muscle contraction. Employing Gene ontology (GO) and Ingenuity Pathway Analysis (IPA), several GO terms and pathways were found to be related to hydrolase, peptidase and GTPase activity, lipid metabolism, small molecule biochemistry, molecular transport, and tissue development. Overall, this analysis provides insight into the metabolic relationships between muscle biology and beef quality.