mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species

Reconstructions of the human-African great ape phylogeny by using mitochondrial DNA (mtDNA) have been subject to considerable debate. One confounding factor may be the lack of data on intraspecific variation. To test this hypothesis, we examined the effect of intraspecific mtDNA diversity on the phylogenetic reconstruction of another Plio- Pleistocene radiation of higher primates, the fascicularis group of macaque (Macaca) monkey species. Fifteen endonucleases were used to identify 10 haplotypes of 40-47 restriction sites in M. mulatta, which were compared with similar data for the other members of this species group. Interpopulational, intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of divergence time and branching order incorporating this variation were substantially different from those based on single representatives of each species. We conclude that intraspecific mtDNA diversity is substantial in at least some primate species. Consequently, without prior information on the extent of genetic diversity within a particular species, intraspecific variation must be assessed and accounted for when reconstructing primate phylogenies. Further, we question the reliability of hominoid mtDNA phylogenies, based as they are on one or a few representatives of each species, in an already depauperate superfamily of primates.      

Lipid peroxidation rate and the antioxidant protection system during a three-day dry immersion experiment

The content of lipid peroxidation products (diene conjugates, malondialdehyde, Schiff bases) and antioxidant defense system indices (the main lipid antioxidant tocopherol and the level of general antioxidant activity) were measured in the blood serum of five male volunteers aged 25?C40 years in a three-day dry immersion experiment. During the immersion test, no deviations of indices from the background values were found. An increase in the tocopherol concentration within 2 h after the beginning of the experiment was the only exception. A significant increase in the concentration of lipid peroxidation products, particularly, diene conjugates, was observed 2 h after immersion completion during the reconditioning period. However, the tocopherol content was significantly lower than the background values. It is concluded that the subjects?? adaptation to simulated microgravity conditions displays no pronounced stress component, whereas bringing back to normal vital functions after exposure to immersion induces a pronounced stress reaction illustrated by a significant increase in the lipid peroxidation product levels against a background of a decrease in the functional activity of the antioxidant defense system.     

Molecular Mechanisms of Stabilization of Proteolytic Enzymes: A Model of Thermolysin-Like Microbial Metalloproteases

The molecular mechanisms that ensure the stability of proteolytic proteins are discussed. The autolytic pathway of protease degradation is emphasized. Experiments aimed at increasing the thermal stability of thermolysin-like metalloproteases are comprehensively described.     

Reference values of the hemostasis system indices in cosmonauts

The values of 11 diagnostically significant hemostasis system indices were determined during the preflight (30–45 days before start) clinical and physiological examination of 39 cosmonauts aged 35 to 54 years, who were the members of the main and backup crews of missions to the International Space Station (ISS) during the period from 2007 to 2014. Since most of the cosmonauts performed several flights over this period and were repeatedly included in backup crews, each of them underwent examinations one to five times. The reference values were calculated for each of the studied indices. It was found that the reference ranges for the parameters indicative of the integral pro- and anticoagulant and fibrinolytic blood plasma potential were somewhat narrowed and close to the boundaries of general population ranges, which indicates that the cosmonauts had a relatively decreased procoagulant potential and increased regulative potential of the hemostasis system. This was probably due to the criteria of selection, physical training status, and emotional status of crew members during the preflight professional activity, when adaptive changes against stressinducing effects occur in the body. The cosmonauts who underwent strict medical examination may also have some genetic features in which they differ from the general population and which provide higher body resistance and more rapid adaptation processes.     

An invisible ubiquitin conformation is required for efficient phosphorylation by PINK1

The Ser/Thr protein kinase PINK1 phosphorylates the well‐folded, globular protein ubiquitin (Ub) at a relatively protected site, Ser65. We previously showed that Ser65 phosphorylation results in a conformational change in which Ub adopts a dynamic equilibrium between the known, common Ub conformation and a distinct, second conformation wherein the last β‐strand is retracted to extend the Ser65 loop and shorten the C‐terminal tail. We show using chemical exchange saturation transfer (CEST) nuclear magnetic resonance experiments that a similar, C‐terminally retracted (Ub‐CR) conformation also exists at low population in wild‐type Ub. Point mutations in the moving β5 and neighbouring β‐strands shift the Ub/Ub‐CR equilibrium. This enabled functional studies of the two states, and we show that while the Ub‐CR conformation is defective for conjugation, it demonstrates improved binding to PINK1 through its extended Ser65 loop, and is a superior PINK1 substrate. Together our data suggest that PINK1 utilises a lowly populated yet more suitable Ub‐CR conformation of Ub for efficient phosphorylation. Our findings could be relevant for many kinases that phosphorylate residues in folded protein domains.     

The dynamics of blood biochemical parameters in an experiment with seven-day immersion

In an experiment with seven-day immersion, blood samples were taken from eight volunteers (21 to 26 years old) seven days prior to immersion, on days 3 and 7 of immersion and on days 1 and 8 of recovery. Blood serum was analyzed for 38 biochemical markers of the functional state of the myocardium, skeletal muscles, hepatobiliary system, kidneys, pancreas, gastrointestinal tract, prostate, and protein-nucleic, carbohydrate, electrolyte, and mineral metabolisms. Seven-day immersion was shown to alter the biochemical parameters within the range of the physiological norm. The observed changes included lower activities of enzymes associated with muscular and myocardial constellation, shifts in electrolytes (K, Na, Mg), and an increase in the biliary function parameters. Increased concentrations of the parameters of lipid metabolism suggest a higher risk of atherogenesis. Biochemical parameters of bone tissues and erythrocyte activity were practically unchanged. Most of the parameters returned to the preexperimental values by day 8 of recovery.     

From recommendation to action: psychosocial factors influencing physician intention to use Health Technology Assessment (HTA) recommendations

Background

The Evidence-Based Practice (EBP) Project has been investigating the implementation of evidence-based mental health practices (Assertive Community Treatment, Family Psychoeducation, Integrated Dual Diagnosis Treatment, Illness Management and Recovery, and Supported Employment) in state public mental health systems in the United States since 2001. To date, Project findings have yielded valuable insights into implementation strategy characteristics and effectiveness. This paper reports results of an effort to identify and classify state-level implementation activities and strategies employed across the eight states participating in the Project.

Methods

Content analysis and Greenhalgh et al's (2004) definition of innovation were used to identify and classify state-level activities employed during three phases of EBP implementation: Pre-Implementation, Initial Implementation and Sustainability Planning. Activities were coded from site visit reports created from documents and notes from key informant interviews conducted during two periods, Fall 2002 – Spring 2003, and Spring 2004. Frequency counts and rank-order analyses were used to examine patterns of implementation activities and strategies employed across the three phases of implementation.

Results

One hundred and six discreet implementation activities and strategies were identified as innovative and were classified into five categories: 1) state infrastructure building and commitment, 2) stakeholder relationship building and communications, 3) financing, 4) continuous quality management, and 5) service delivery practices and training. Implementation activities from different categories were employed at different phases of implementation.

Conclusion

Insights into effective strategies for implementing EBPs in mental health and other health sectors require qualitative and quantitative research that seeks to: a) empirically test the effects of tools and methods used to implement EBPs, and b) establish a stronger evidence-base from which to plan, implement and sustain such efforts. This paper offers a classification scheme and list of innovative implementation activities and strategies. The classification scheme offers potential value for future studies that seek to assess the effects of various implementation processes, and helps establish widely accepted standards and criteria that can be used to assess the value of innovative activities and strategies.