Characteristics of an Environmentally Monitored Prolonged Type 2 Vaccine Derived Poliovirus Shedding Episode that Stopped without Intervention

Vaccine derived poliovirus (VDPV) type 2 strains strongly divergent from the corresponding vaccine strain, Sabin 2, were repeatedly isolated from sewage in Slovakia over a period of 22 months in 2003–2005. Cell cultures of stool specimens from known immune deficient patients and from an identified putative source population of 500 people failed to identify the potential excretor(s) of the virus. The occurrence of VDPV in sewage stopped without any intervention. No paralytic cases were reported in Slovakia during the episode. According to a GenBank search and similarity plotting-analysis, the closest known relative of the first isolate PV2/03/SVK/E783 through all main sections of the genome was the type 2 poliovirus Sabin strain, with nucleotide identities in 5′UTR, P1, P2, P3, and 3′UTR parts of the genome of 88.6, 85.9, 87.3, 88.5, and 94.0 percent, respectively. Phenotypic properties of selected Slovakian aVDPV strains resembled those of VDPV strains isolated from immune deficient individuals with prolonged PV infection (iVDPV), including antigenic changes and moderate neurovirulence in the transgenic mouse model. One hundred and two unique VP1 coding sequences were determined from VDPV strains isolated from 34 sewage specimens. Nucleotide differences from Sabin 2 in the VP1 coding region ranged from 12.5 to 15.6 percent, and reached a maximum of 9.6 percent between the VDPV strains under study. Most of the nucleotide substitutions were synonymous but as many as 93 amino acid positions out of 301 in VP1 showed substitutions. We conclude that (1) individuals with prolonged poliovirus infection are not as rare as suggested by the studies on immune deficient patients known to the health care systems and (2) genetic divergence of VDPV strains may remain extensive during years long replication in humans.     

Carbon storage change and δ13C transitions of peat columns in a partially forestry-drained boreal bog

Background and aims

In forestry-drained peatlands, drying leads to changes in C cycling which could affect peat δ¹³C. Furthermore, the δ¹³C profile of the entire peat column may reveal effects of earlier climatic periods.

Methods

We measured peat δ¹³C and C inventories in adjacent peat profiles, two collected from undrained and two from the drained side of a bog that was partially ditch-drained 37 years earlier. The cores were sliced into 10-cm subsamples for analyses; matching of the profiles based on surface levelling, peat stratigraphic correlation and a horizontal ash layer found in both profiles.

Results

Surface subsidence of 30 cm was observed in the dried site and the uppermost 160 cm in the undrained site contained an excess of 5.9 kg m⁻² of C compared with the corresponding strata of the ditch-drained site. The δ¹³C values increased but markedly only in the thin surface layer of the drained site, indicating low δ¹³C of the missing C (ca. –30‰). In the deeper strata, dating to Mid-Holocene, high dry bulk density, C%, N%, humification index and low C/N ratio were connected to low δ¹³C of peat.

Conclusions

Drainage of 37 years increased δ¹³C values in the upper peat profile of the drained bog and led to the selective loss of ¹³C depleted C. Results indicate that C balance studies can be aided by C isotope analyses. Low δ¹³C values in the peat profile indicate the existence of a wet fen stage during the moist and warm period during Mid-Holocene.

     

Solution structure of the soluble receptor for advanced glycation end products (sRAGE)

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor involved in various human diseases, as it binds to numerous molecules and proteins that modulate the activity of other proteins. Elucidating the three-dimensional structure of this receptor is therefore most important for understanding its function during activation and cellular signaling. The major alternative splice product of RAGE comprises its extracellular region that occurs as a soluble protein (sRAGE). Although the structures of sRAGE domains were available, their assembly into the functional full-length protein remained unknown. We observed that the protein has concentration-dependent oligomerization behavior, and this is also mediated by the presence of Ca(2+) ions. Moreover, using synchrotron small angle x-ray scattering, the solution structure of human sRAGE was determined in the monomeric and dimeric forms. The model for the monomer displays a J-like shape, whereas the dimer is formed through the association of the two N-terminal domains and has an elongated structure. These results provide insights into the assembly of the RAGE homodimer, which is essential for signal transduction, and the sRAGE:RAGE heterodimer that leads to blockage of the receptor signaling, paving the way for the design of therapeutic strategies for a large number of different pathologies.     

Structural and thermodynamic characterization of metal ion binding in Streptococcus suis Dpr

The use of protein cages for the creation of novel inorganic nanomaterials has attracted considerable attention in recent years. Ferritins are among the most commonly used protein cages in nanoscience. Accordingly, the binding of various metals to ferritins has been studied extensively. Dps (DNA-binding protein from starved cells)-like proteins belong to the ferritin superfamily. In contrast to ferritins, Dps-like proteins form 12-mers instead of 24-mers, have a different ferroxidase center, and are able to store a smaller amount of iron atoms in a hollow cavity (up to ∼ 500, instead of the ∼ 4500 iron atoms found in ferritins). With the exception of iron, the binding of other metal cations to Dps proteins has not been studied in detail. Here, the binding of six divalent metal ions (Zn²⁺, Mn²⁺, Ni²⁺, Co²⁺, Cu²⁺, and Mg²⁺) to Streptococcus suisDps-like peroxide resistance protein (SsDpr) was characterized by X-ray crystallography and isothermal titration calorimetry (ITC). All metal cations, except for Mg²⁺, were found to bind to the ferroxidase center similarly to Fe²⁺, with moderate affinity (binding constants between 0.1 × 10⁵ M^− 1 and 5 × 10⁵ M^− 1). The stoichiometry of binding, as deduced by ITC data, suggested the presence of a dication ferroxidase site. No other metal binding sites were identified in the protein. The results presented here demonstrate the ability of SsDpr to bind various metals as substitutes for iron and will help in better understanding protein-metal interactions in the Dps family of proteins as potential metal nanocontainers.     

Strength and power profiles of the lower and upper extremities in master throwers at different ages

Thirty-two master athletes (shot put, discus, and hammer throw) were divided into 4 groups according to their age (T40 [40 years of age], 50 [50 years of age], 60 [60 years of age], and 75 [75 years of age]). Twenty-eight age-matched men served as controls (C40 [40 years of age], 50 [50 years of age], 60 [60 years of age], and 75 [75 years of age]). The subjects were tested for maximal isometric strength of the lower and upper extremities. Power was measured by performing jump squats and bench press in the Smith machine with the load of 60% of 1 repetition maximum. Electromyographic (EMG) activity was recorded from 6 different muscles. The muscle thickness of vastus lateralis and intermedius (VL+VI) and triceps brachii (TB) was measured by ultrasound. Maximal strength differed (p < 0.05- 0.001) in all testing actions between T40 and T60 and T40 and T75 as well as between T and C groups. Both VL+VI and TB thickness in T40 was greater (p < 0.05-0.01) than in T60 and T75 and in T was larger than in C groups. Average force during the first 500 milliseconds (ms) was higher (p < 0.05-0.001) in T40 compared to T50, T60, and T75 in bilateral leg extension, biceps curl, and especially in unilateral knee flexion. T40 produced higher power than the other groups (p < 0.05-0.001). The relative agonist EMG activation (VL) in leg extension during the first 100 ms compared to maximum activation was lower (p < 0.05) in T50, T60, and T75, but not in T40. The present data indicate that maximal strength and muscle thickness as well as explosive strength and power characteristics decline with aging also in master athletes who carry out strength training and throwing exercises actively over several decades. Nevertheless, in master athletes, maximal strength and muscle mass as well as explosive force production of the upper and lower extremities seem to be at remarkably higher levels than those recorded for age-matched control men.     

Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence

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Impact of Age and Gender on the Prevalence and Prognostic Importance of the Metabolic Syndrome and Its Components in Europeans. The MORGAM Prospective Cohort Project

Objective

To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS).

Methods

Using 36 cohorts from the MORGAM-Project with baseline between 1982–1997, 69094 men and women aged 19–78 years, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5.

Results

The prevalence of MetS, according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P<0.0001); with a 5-fold increase in women from ages 19–39 years to 60–78 years (7.4%/7.6% to 35.4%/37.6% for IDF/NCEP-ATPIII) and a 2-fold increase in men (5.3%/10.5% to 11.5%/21.8%). Using multivariate-adjusted Cox regressions, the associations between MetS and all three CVD events were significant (P<0.0001). For IDF/NCEP-ATPIII in men and women, hazard ratio (HR) for CHD was 1.60/1.62 and 1.93/2.03, for CVD mortality 1.73/1.65 and 1.77/2.06, and for stroke 1.51/1.53 and 1.58/1.77. Whereas in men the HRs for CVD events were independent of age (MetS*age, P>0.05), in women the HRs for CHD declined with age (HRs 3.23/3.98 to 1.55/1.56; MetS*age, P = 0.01/P = 0.001 for IDF/NCEP-ATPIII) while the HRs for stroke tended to increase (HRs 1.31/1.25 to 1.55/1.83; MetS*age, P>0.05).

Conclusion

In Europeans, both age and gender influenced the prevalence of MetS and its prognostic significance. The present results emphasise the importance of being critical of MetS in its current form as a marker of CVD especially in women, and advocate for a redefinition of MetS taking into account age especially in women.     

Counting absolute numbers of molecules using unique molecular identifiers

Counting individual RNA or DNA molecules is difficult because they are hard to copy quantitatively for detection. To overcome this limitation, we applied unique molecular identifiers (UMIs), which make each molecule in a population distinct, to genome-scale human karyotyping and mRNA sequencing in Drosophila melanogaster. Use of this method can improve accuracy of almost any next-generation sequencing method, including chromatin immunoprecipitation-sequencing, genome assembly, diagnostics and manufacturing-process control and monitoring.