Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans

Background

Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia.

Results

Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades.

Conclusions

Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.     

Variable overoxidation of peroxiredoxins in human lung cells in severe oxidative stress

Peroxiredoxins (Prxs) are a group of thiol containing proteins that participate both in signal transduction and in the breakdown of hydrogen peroxide (H(2)O(2)) during oxidative stress. Six distinct Prxs have been characterized in human cells (Prxs I-VI). Prxs I-IV form dimers held together by disulfide bonds, Prx V forms intramolecular bond, but the mechanism of Prx VI, so-called 1-Cys Prx, is still unclear. Here we describe the regulation of all six Prxs in cultured human lung A549 and BEAS-2B cells. The cells were exposed to variable concentrations of H(2)O(2), menadione, tumor necrosis factor-alpha or transforming growth factor-beta. To evoke glutathione depletion, the cells were furthermore treated with buthionine sulfoximine. Only high concentrations (300 microM) of H(2)O(2) caused a minor increase (<28%, 4 h) in the expression of Prxs I, IV, and VI. Severe oxidant stress (250-500 microM H(2)O(2)) caused a significant increase in the proportion of the monomeric forms of Prxs I-IV; this was reversible at lower H(2)O(2) concentrations (< or =250 microM). This recovery of Prx overoxidation differed among the various Prxs; Prx I was recovered within 24 h, but recovery required 48 h for Prx III. Overall, Prxs are not significantly modulated by mild oxidant stress or cytokines, but there is variable, though reversible, overoxidation in these proteins during severe oxidant exposure.     

Oral infections as predictors of mortality

Objective: Oral infections may increase the levels of cytokines in the blood which, in turn, are associated with early mortality in the elderly. We investigated the possible association between oral infections and mortality. Design: Prospective cohort study over a 5‐year follow‐up. Setting: Research laboratory. Participants: A cohort born in 1910 (n = 94) was examined in the year 1995. Five years later mortality data were obtained from the population register for 49 deceased subjects. Main outcome measures: Urgent need of dental treatment, lifetime, erythrocyte sedimentation rate (ESR). Results: The multivariate analysis adjusted for general health and lifestyle factors showed that the risk for death of subjects in urgent need of dental treatments was 3.9 times higher than that of the other subjects. Among men ESR correlated significantly with urgent need of dental treatment. Conclusions: Oral infections among frail elderly people may be a sign of early mortality.     

Predictors of light-limited growth and competition of phytoplankton in a well-mixed water column

Based on a model of light limited growth, Huisman and Weissing found that in a well mixed water column with constant light supply (energy reaching the water surface), equilibrium growth and competition of phytoplankton for light can be characterised by a critical light intensity at the base of the column (I*out). The present study attempts to give a further insight into this model. We first analyse the dependence of the critical light intensity on four parameters: initial slope of the photosynthesis-intensity (p-I) curve, maximal photosynthetic rate, the light-saturated parameter Ikand specific carbon loss rate. Increases in the first two parameters tend to reduce the critical light intensity and increases in the last two tend to increase the critical light intensity. Then we analyse the performance of a model under variable light supply with a time-scale of 1 day (24 hr). Within this time-scale, the critical light intensity changes with time. However, the equilibrium growth and the outcome of competition for light can be adequately characterised by critical light extinction defined as the upper limit of total light extinction due to both biomass and non-living matter in the water column. Under constant light supply, a critical light intensity uniquely corresponds to a critical light extinction. Therefore, critical light extinction can be utilised to predict the equilibrium growth and the outcome of competition under both constant and variable light supply. By changing the maximal light supply at noon, seasonal succession of species composition of communities is investigated. The possible effect of two typical photoresponses, photoadaptation and photoinhibition, on growth and competiton are discussed. Copyright 1999 Academic Press.     

Seasonal changes in intra- and interorgan occurrence of rodlet cells in freshwater bream

Significant seasonal differences in intra- and interorgan prevalence, abundance and distribution of rodlet cells (RC) were observed in freshwater bream caught in May and August 1997 from a PCB-polluted lake, Lake Kernaala, Finland. In May, the majority of RCs in liver were seen in blood vessel endothelium, while in August most cells were located in the epithelium of the intrahepatic biliary ducts. In kidney, a significant increase in RCs in the columnar epithelium of the collecting ducts was observed from May to August. RCs in spleen were extremely rare in May, but were seen frequently in the endothelium of the splenic blood vessels in August. In gill and intestine, RCs were found in every tissue sample studied, with no statistical differences in their abundance or distribution between seasons. No RCs were seen in gonads. Total numbers of RCs increased dramatically from May to August in kidney and in spleen. The frequency of RCs corresponded strongly with the current phase of parasitic infections in liver, kidney, and spleen. It is concluded that RCs play a role in host defence mechanisms in fish, displaying induced expression at the times of peak parasitic prevalences.     

Preliminary study on phylogenetic position and delimitation of the ciliate arthrodontous genera of the moss family Mniaceae

The history of the generic and sectional concepts in the traditional moss family Mniaceae is summarised. The division of the Mniaceae into nine genera has been generally accepted. A phylogenetic analysis, based on 35 Mniaceae samples as ingroup and one Leptostomataceae and three Bryaceae samples as outgroups was completed. A total of 113 new sequences were obtained and 4139 aligned characters were included in the combined dataset. Bayesian inferences based on the combined data set showed five well supported clades, which, as a whole, form the monophyletic family Mniaceae. The number of genera in the traditional Mniaceae is 9 and the number of species is 74. All the genera appear monophyletic except Plagiomnium; accepting Orthomnion at the generic level makes Plagiomnium paraphyletic. The principle that only monophyletic taxa are allowed and may be named necessitates the uniting of Plagiomnium and Orthomnion. The necessary combinations are made. The taxonomy of the genera and sections is discussed. Rhizomnium section Macromnium T.J.Kop. & Y.Sun, sect. nov. is described and the new combination Rhizomnium chlorophyllosum (Kindb.) T.J.Kop. is made. The controversy of paraphyly – monophyly in accepting and naming taxa is discussed and Plagiomnium versus Orthomnion given as an example. All the present genera and species seem to have diverged in the area of the Laurasian supercontinent and the speciation of most genera took place in the temperate forested areas of western and eastern North America, Europe and south-eastern Asia.     

Systematic Review: Representativeness of Participants in RCTs of Acetylcholinesterase Inhibitors

Objective

To determine whether there are differences in age and sex distribution and presence of comorbidities between participants included in randomized controlled trials of acetylcholinesterase inhibitors and nationwide cohort of persons with Alzheimer’s disease.

Methods

PubMed, Scopus and Cochrane Library databases were searched for original articles from their inception to January 4, 2015. Double-blind randomized controlled trials with donepezil, rivastigmine or galantamine compared to placebo in participants with Alzheimer’s disease were included. Data from a nationwide cohort of persons with clinically verified diagnoses of Alzheimer’s disease was defined as a reference population.

Results

128 full-text articles were assessed for eligibility, 31 of them fulfilled criteria. Mean age of participants in randomized controlled trials (n = 15,032) was 5.8 years lower (95% CI 5.7 to 5.9, P < 0.001), compared to the mean age of 79.7 years in the reference population with Alzheimer’s disease (n = 28,093). Most of the articles did not report age distribution of participants. The proportion of women was 63.2% (9,475/14,991) in randomized controlled trials and 67.8% (19,043/28,093) (P < 0.001) in the reference population. Information on comorbidities and use of concomitant drugs were lacking or poorly reported in most articles.

Conclusions

There is a discrepancy between participants in randomized controlled trials of acetylcholinesterase inhibitors and real-life population with Alzheimer’s disease. Participants in randomized controlled trials were significantly younger. Further, more detailed reporting of age distribution, comorbidities and concomitant drugs would be important information for clinicians when evaluating conclusions from randomized controlled trials to real-life practice. The existing recommendations of inclusion of older people should be followed to ensure safe pharmacotherapy for older people.     

Gene Polymorphism of Toll-Like Receptors and Lung Function at Five to Seven Years of Age after Infant Bronchiolitis

Aim

Toll-like receptors (TLR) play a crucial role in innate immunity, protecting the host from pathogens such as viruses. Genetic variations in TLRs have been associated with the severity of viral bronchiolitis in infancy and with the later occurrence of post-bronchiolitis asthma. The aim of the present study was to evaluate if there are any exploratory associations between TLR gene polymorphisms and lung function at 5 to 7 years of age in former bronchiolitis patients.

Methods

We performed impulse oscillometry (IOS) at the median age of 6.3 years for 103 children who had been hospitalized for bronchiolitis at less than six months of age. The main parameters evaluated were airway resistance and reactance at 5Hz in baseline and post-exercise measurements. Data on single nucleotide polymorphisms (SNP) of TLR1 rs5743618, TLR2 rs5743708, TLR6 rs5743810 and TLR10 rs4129009 (TLR2 subfamily) and TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992 and TLR 9 rs187084 were available for analyses.

Results

The TLR4 rs4986790 wild genotype A/A was associated with a greater Rrs5 response (0.72 vs. -0.42, p = 0.03) to exercise. In TLR6 rs5743810, the minor allele T was associated with greater Rrs5 response (0.80 vs. -0.03, p = 0.04) to exercise. In TLR7 rs179008, the major allele A was associated with baseline decline in dRrs/df (-1.03 vs 0.61, p = 0.01) and increased Fres (2.28 vs. 0.89, p = 0.01) in girls.

Conclusion

Among the nine studied TLRs, only TLR7 rs179008 showed some exploratory associations with post-bronchiolitis lung function deficiency, and polymorphisms of TLR4 rs4986790, and TLR6 rs5743810 in particular, with airway reactivity. These findings call for further confirmatory studies.