Glycophorin A somatic cell mutations in a population living in the proximity of the Semipalatinsk nuclear test site

The glycophorin A (GPA) somatic mutation assay was performed to evaluate the magnitude of exposure to ionizing radiation among the human population living in the vicinity of the Semipalatinsk nuclear test site in Kazakhstan. All together, 113 blood samples were analyzed from three generations of people living in villages that were under the trail of the radioactive cloud from the first Soviet surface nuclear test performed in August 1949 and from later tests. The oldest generation (P0) lived in the area at the time of testing, whereas the younger generations (F1, F2) were exposed to smaller doses from the residual fallout and later tests. The GPA assay did not reveal significant differences in the variant cell frequencies for all subjects selected from the Semipalatinsk area compared with 74 matched controls living in a noncontaminated area. However, a significant increase (P < 0.05) in the mean allele-loss ON variant frequency was observed among the exposed P0 generation (12 x 10(-6)) in comparison to controls (7 x 10(-6)). Considering the sensitivity of the GPA assay, the results suggest that the mean dose to the P0 generation of the affected villages was relatively low, a finding which is in accordance to the conclusions obtained from other biological assays performed on the same population.     

Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa)

A series of 3-mercapto-propionic acid derivatives that function as reversible inhibitors of carboxypeptidase U have been prepared. We present a successful design strategy using cyclic, low basicity guanidine mimetics resulting in potent, selective and bioavailable inhibitors of carboxypeptidase U (TAFIa).     

Evolution of Type 2 Vaccine Derived Poliovirus Lineages. Evidence for Codon-Specific Positive Selection at Three Distinct Locations on Capsid Wall

Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003–2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2) were compared to those of type 1 and type 3 wild poliovirus (WPV) lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin) by 12.5–15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv) bias and strikingly lower Ts/Tv rate ratios at the 2^nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2^nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (c)VDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.     

Neurocognitive Function in HIV Infected Patients on Antiretroviral Therapy

Objective

To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy.

Design

We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial.

Main outcome measure

NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression.

Results

Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was −0.5 (−1.2/−0) overall, and −0.3 (−0.7/0.1) and −1.4 (−2/−0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001).

Conclusions

In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised.

Trial registry

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01230580","term_id":"NCT01230580"}}NCT01230580     

The Evolutionary Strategy of Deception

1 A Brief History of Deception
The conceptual roots of deception began to sprout at the dawn of zoology, when Aristotle （350 CE） discussed his observations of the ＇deceitful＇ reproductive tactics of cuckoos and partridges in his classic work The History of Animals. However, the scientific origins of deception were cemented in Descartes＇ （1641） Meditations on First Philosophy, in which he reasoned： All that I have, up to this moment, accepted as possessed of the highest truth and certainty, I received either from or through the senses.     

Genetic Variants and Their Interactions in the Prediction of Increased Pre-Clinical Carotid Atherosclerosis: The Cardiovascular Risk in Young Finns Study

The relative contribution of genetic risk factors to the progression of subclinical atherosclerosis is poorly understood. It is likely that multiple variants are implicated in the development of atherosclerosis, but the subtle genotypic and phenotypic differences are beyond the reach of the conventional case-control designs and the statistical significance testing procedures being used in most association studies. Our objective here was to investigate whether an alternative approach—in which common disorders are treated as quantitative phenotypes that are continuously distributed over a population—can reveal predictive insights into the early atherosclerosis, as assessed using ultrasound imaging-based quantitative measurement of carotid artery intima-media thickness (IMT). Using our population-based follow-up study of atherosclerosis precursors as a basis for sampling subjects with gradually increasing IMT levels, we searched for such subsets of genetic variants and their interactions that are the most predictive of the various risk classes, rather than using exclusively those variants meeting a stringent level of statistical significance. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the variants, and cross-validation was used to assess how well the predictive models will generalize to other subsets of subjects. By means of our predictive modeling framework with machine learning-based SNP selection, we could improve the prediction of the extreme classes of atherosclerosis risk and progression over a 6-year period (average AUC 0.844 and 0.761), compared to that of using conventional cardiovascular risk factors alone (average AUC 0.741 and 0.629), or when combined with the statistically significant variants (average AUC 0.762 and 0.651). The predictive accuracy remained relatively high in an independent validation set of subjects (average decrease of 0.043). These results demonstrate that the modeling framework can utilize the “gray zone” of genetic variation in the classification of subjects with different degrees of risk of developing atherosclerosis.     

Effect of green microalgal extracts exhibiting antibacterial activity on viability of human malignant and non‐malignant cells

Microalgae have been investigated for their ability to produce metabolites that exhibit antibacterial activity. However, as research on antibacterial activity progresses, the effect of microalgal extracts on mammalian cells needs to be also assessed. The in vitro effect of microalgal extracts with demonstrated antibacterial activity against the human opportunistic pathogen Staphylococcus aureus was examined on the viability of non‐malignant (MCF10A and 184B5 cells) and malignant human cell lines (A2780 and MCF7). Direct cell counts indicated that the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) proliferation assay was found to under/overestimate cell viability when specific microalgal extracts and/or concentrations were tested. From direct cell counts, the viability of non‐malignant cells was not reduced after exposure to the extracts, whereas the viability of malignant cells was affected by specific microalgal extracts and concentrations. The results suggest that green microalgae are worthy of further investigation as potential sources of antibiotics, since they did not show a negative effect on the non‐malignant cell lines, MCF10A and 184B5. Additional studies should evaluate the compounds responsible for the anti‐proliferative activity of specific microalgal extracts observed on the malignant cells A2780 and MCF7.     

Effect of Willow Tit Poecile montanus alarm calls on attack rates by Pygmy Owls Glaucidium passerinum

One suggested anti‐predator function of alarm calls is to deliver a message to a predator that it has been detected. Moreover, giving the alarm call could provide a signal to the predator that capturing the individual giving the alarm is more difficult than capturing its silent group members, as the caller is probably the most aware of the predator's location. In an aviary experiment using stuffed dummy Willow Tits Poecile montanus, we assessed whether an authentic alarm call given by Willow Tit affected Pygmy Owl Glaucidium passerinum prey preference. In the experiment, the Owls attacked only the ‘silent’ dummy individuals, suggesting that alarm calling could offer direct fitness benefits to the caller by decreasing the attack risk of the caller relative to its group members.     

Clastogenic plasma factors: a short overview

A large number of studies have revealed that irradiated subjects produce soluble factors found in their blood plasma which, when transferred into cell cultures from non-irradiated individuals, show clastogenic (chromosome breaking) activity. Increased yields of chromatid-type aberrations have been characteristic in most of these studies. Exposed cohorts of various origins have revealed to possess this feature: from A-bomb survivors to patients treated with radiotherapy. It is apparent that the plasma factors are sustainable for long time periods. On the other hand, they seem to be produced very fast after exposure. Considerable variation in the effect has been found between individuals with similar radiation exposure. Further, the phenomenon is not restricted to irradiated populations. Clastogenic plasma has also been observed in patients with inflammatory diseases or congenital chromosome breakage syndromes as well in subjects exposed to other agents than ionizing radiation. Chromosomal aberration inducing substances have been detected not only in vivo, but also in vitro. A common feature to all the conditions is that they are associated with oxidative stress. Studies on the biochemical nature of the clastogenic factor(s) have been conducted, and tumor necrosis factor alpha and lipid peroxidation products, among others, have been suggested as good candidates. The relevance of the plasma factors to health effects remains open. The aim of the paper is to give a short overview on the phenomenon of clastogenic factors—their occurrence and formation as well as possible effectors.