Mitochondrial Carrier Homolog 2: A Clue to Cracking the BCL-2 Family Riddle?

BCL-2 family members are pivotal regulators of the apoptotic process. Mitochondria are a major site-of-action for these proteins. Several prominent alterations occur to mitochondria during apoptosis that seem to be part of the “mitochondrial apoptotic program.” The BCL-2 family members are believed to be the major regulators of this program, however their exact mechanism of action still remains a mystery. BID, a pro-apoptotic BCL-2 family member plays an essential role in initiating this program. Recently, we have revealed that in apoptotic cells the activated/truncated form of BID, tBID, interacts with a novel, uncharacterized protein named mitochondrial carrier homolog 2 (Mtch2). Mtch2 is a conserved protein that is similar to members of the mitochondrial carrier protein (MCP) family. This review summarizes the current knowledge regarding BCL-2 family members and the mitochondrial apoptotic program and examines the possible involvement of Mtch2 in this program.     

How Much Is the Whole Really More than the Sum of Its Parts? 1 ? 1?=?2.5: Superlinear Productivity in Collective Group Actions

In a variety of open source software projects, we document a superlinear growth of production intensity () as a function of the number of active developers , with a median value of the exponent , with large dispersions of from slightly less than up to . For a typical project in this class, doubling of the group size multiplies typically the output by a factor , explaining the title. This superlinear law is found to hold for group sizes ranging from 5 to a few hundred developers. We propose two classes of mechanisms, interaction-based and large deviation, along with a cascade model of productive activity, which unifies them. In this common framework, superlinear productivity requires that the involved social groups function at or close to criticality, or in a “superradiance” mode, in the sense of the appearance of a cooperative process and order involving a collective mode of developers defined by the build up of correlation between the contributions of developers. In addition, we report the first empirical test of the renormalization of the exponent of the distribution of the sizes of first generation events into the renormalized exponent of the distribution of clusters resulting from the cascade of triggering over all generation in a critical branching process in the non-meanfield regime. Finally, we document a size effect in the strength and variability of the superlinear effect, with smaller groups exhibiting widely distributed superlinear exponents, some of them characterizing highly productive teams. In contrast, large groups tend to have a smaller superlinearity and less variability.     

Is the treatment of axillary osmidrosis with liposuction better than open surgery?

Axillary osmidrosis is an annoying, although not life-threatening, problem that includes unpleasant odor and the occasional staining of clothing. Suction-assisted lipectomy has been tested as a treatment for axillary osmidrosis with variable success. The authors retrospectively reviewed 134 patients who underwent superficial liposuction for bilateral axillary osmidrosis in their division between June of 1998 and June of 2002. The surgical complications and results were compared with those reported in their previous report of 343 patients (102 available for postoperative result evaluation) who received open surgical treatment with partial excision of axillary skin and subcutaneous tissue. The overall complication rate was 3.73 percent, significantly lower than the 11.08 percent complication rate seen with open surgical treatment. Of their 134 patients, 114 were available for long-term follow-up. Thirteen patients (11.40 percent) had very good results, 79 patients (69.30 percent) had good results, and 22 patients (19.30 percent) had poor results. Significant differences were found between those who underwent superficial liposuction and those who underwent open surgery. The number of patients with very good and good results decreased significantly from 91.18 percent (open surgery) to 80.70 percent (liposuction), and those with little or no improvement increased from 8.82 percent (open surgery) to 19.29 percent (liposuction). Compared with open surgery for the treatment of osmidrosis, liposuction produces significantly fewer complications but is less effective. Of the patients who underwent liposuction for osmidrosis, 80 percent were satisfied with the result. Further study is needed to determine whether liposuction for osmidrosis can be improved.     

Is the PGM1 locus subject to selection?

Summary The placental phosphoglucomutase phenotypes controlled by the first locus of 235 German and 119 non-German samples were determined. Both in the pooled material and in the sample containing German subjects only there was a significant deviation from the expected Hardy-Weinberg equilibrium. A segregation analysis of 1174 families also revealed significant deviations in the phenotypes of the children, though the mating frequencies were as expected. The distribution of the children's phenotypes deviated significantly from Hardy-Weinberg equilibrium though this was not found in the parent samples. The results are discussed.

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Zusammenfassung Placenta-Phosphoglucomutase-Phänotypen des ersten Locus wurden an Hand von 235 deutschen und 119 ausländischen Stichproben bestimmt. Sowohl das Gesamtmaterial als auch die deutsche Stichprobe allein zeigten eine signifikante Abweichung vom angenommenen Hardy-Weinberg-Gleichgewicht. Eine Aufspaltungsanalyse bei 1174 Familien ergab ebenfalls eine signifikante Abweichung bei den Phänotypen der Kinder, obgleich die Elternkombinationshäufigkeiten der Erwartung entsprachen. Die Verteilung der Kinderphänotypen wich signifikant vom Hardy-Weinberg-Gleichgewicht ab, während die Verteilung der Elternphänotypen mit den Erwartungswerten übereinstimmte. Die Ergebnisse werden diskutiert.

     

“When Treatment Is More Challenging than the Disease”: A Qualitative Study of MDR-TB Patient Retention

Background

One-fifth of the patients on multidrug-resistant tuberculosis treatment at the Drug-Resistant-TB (DR-TB) Site in Gujarat are lost-to-follow-up(LFU).

Objective

To understand patients’ and providers'' perspectives on reasons for LFU and their suggestions to improve retention-in-care.

Design

Qualitative study conducted between December 2013-March 2014, including in-depth interviews with LFU patients and DOT-providers, and a focus group discussion with DR-TB site supervisors. A thematic-network analysis approach was utilised.

Results

Three sub-themes emerged: (i) Struggle with prolonged treatment; (ii) Strive against stigma and toward support; (iii) Divergent perceptions and practices. Daily injections, pill burden, DOT, migratory work, social problems, prior TB treatment, and adverse drugs effects were reported as major barriers to treatment adherence and retention-in-care by patients and providers. Some providers felt that despite their best efforts, LFU patients remain. Patient movements between private practitioners and traditional healers further influenced LFU.

Conclusion

The study points to a need for repeated patient counselling and education, improved co-ordination between various tiers of providers engaged in DR-TB care, collaboration between the public, private and traditional practitioners, and promotion of social and economic support to help patients adhere to MDR-TB treatment and avoid LFU.     

Is There a Benefit to Extending the Duration of Helicobacter pylori Sequential Therapy to 14 Days?

Background and Aims: Ten‐day sequential therapy with a proton‐pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori (H. pylori) eradication rates between 90 and 94% (i.e., Grade B success). It has been suggested that prolonging the duration of therapy might improve the treatment success. We tested whether prolonging treatment duration to 14‐days would improve the results to 95% or greater eradication. Methods: This was a multi‐center, single site, pilot study in which H. pylori‐infected patients received a 14‐day sequential therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, clarithromycin, and metronidazole for 7 days). H. pylori status was assessed 8 weeks after therapy. Success was defined as achieving 95% or greater eradication by per‐protocol (PP) analysis. Results: One hundred and twenty‐three subjects received the 14‐day sequential therapy. The eradication rate was 93.9% (95% confidence interval [CI], 89.5–98.3%) by PP and 91.9% (95% CI, 87.1–96.7%) by intention‐to‐treat analysis. Adverse events were experienced by 21.1%; compliance of 90% or greater was 95.9%. Conclusions: Extending sequential therapy to 14 days did not result in improving the treatment outcome to 95% or greater.     

The Association between Overweight and Illegal Drug Consumption in Adolescents: Is There an Underlying Influence of the Sociocultural Environment?

Background

The aims of the study were to: a) Examine the distribution of gender-stratified body mass index (BMI), eating attitudes and use of addictive substances, under the hypothesis of a confluent prevalence of weight abnormalities, eating disorders and substance abuse. b) Demonstrate the extent to which family, peer-related and psychosocial factors are common elements in categories of compulsive behaviour.

Methodology/Principal Findings

In the present cross-sectional study, data were collected through self reported questionnaires administered to a large sample of 33,185 15–19 years old adolescents (ESPAD®Italia), divided into weight categories based on the BMI percentile distribution. Multinomial analyses were adopted to address the influence of social, family, leisure time factors, Eating Attitude Test (EAT26) on the association between weight categories and drug use.Recent drugs use was more frequent in overweight and underweight adolescents (p<0.05), especially in females. An EAT26 score ≥20 was more common in overweight adolescents. Multinomial analysis abolished the relationship between overweight and the use of most drugs, implicating self-esteem, parents'' educational level, and friendships as mediators of the association. Within the overweight category, adolescents reporting recent drug use, showed greater frequency of having drug-abusing friends (∼80%), and severe problems with parents and school (∼30%) compared to overweight adolescents without recent drug use.

Conclusion

The frequent association of overweight and substance use and the presence of common underlying social factors, highlights the need for an interdisciplinary approach involving individual-focused treatment models as well as public health, social and environmental changes to reduce food- and substances-related problems.     

Is the COL5A1 rs12722 Gene Polymorphism Associated with Running Economy?

The COL5A1 rs12722 polymorphism is considered to be a novel genetic marker for endurance running performance. It has been postulated that COL5A1 rs12722 may influence the elasticity of tendons and the energetic cost of running. To date, there are no experimental data in the literature supporting the relationship between range of motion, running economy, and the COL5A1 rs12722 gene polymorphism. Therefore, the main purpose of the current study was to analyze the influence of the COL5A1rs12722 polymorphism on running economy and range of motion. One hundred and fifty (n = 150) physically active young men performed the following tests: a) a maximal incremental treadmill test, b) two constant-speed running tests (10 km•h⁻¹ and 12 km•h⁻¹) to determine the running economy, and c) a sit-and-reach test to determine the range of motion. All of the subjects were genotyped for the COL5A1 rs12722 single-nucleotide polymorphism. The genotype frequencies were TT = 27.9%, CT = 55.8%, and CC = 16.3%. There were no significant differences between COL5A1 genotypes for running economy measured at 10 km•h⁻¹ (p = 0.232) and 12 km•h⁻¹ (p = 0.259). Similarly, there were no significant differences between COL5A1 genotypes for range of motion (p = 0.337). These findings suggest that the previous relationship reported between COL5A1 rs12722 genotypes and running endurance performance might not be mediated by the energetic cost of running.     

The Recombinant Amyloid-β Peptide Aβ1-42 Aggregates Faster and Is More Neurotoxic than Synthetic Aβ1-42

Aggregation of the amyloid-β (Aβ) peptide is considered a central event in the pathogenesis of Alzheimer's disease (AD). In order to bypass methodological bias related to a variety of impurities commonly present in typical preparations of synthetic Aβ, we developed a simple, generally applicable method for recombinant production of human Aβ and Aβ variants in Escherichia coli that provides milligram quantities of Aβ in very high purity and yield. Amyloid fibril formation in vitro by human Aβ1-42, the key amyloidogenic Aβ species in AD, was completed threefold faster with recombinant Aβ1-42 compared to synthetic preparations. In addition, recombinant Aβ1-42 was significantly more toxic to cultured rat primary cortical neurons, and it was more toxic in vivo, as shown by strongly increased induction of abnormal phosphorylation of tau and tau aggregation into neurofibrillary tangles in brains of P301L tau transgenic mice. We conclude that even small amounts of impurities in synthetic Aβ—including a significant fraction of racemized peptides that cannot be avoided due to the technical limitations of peptide synthesis—prevent or slow Aβ incorporation into the regular quaternary structure of growing β-amyloid fibrils. The results validate the use of recombinant Aβ1-42 for both in vitro and in vivo studies addressing the mechanisms underlying Aβ aggregation and its related biological consequences for the pathophysiology, therapy, and prevention of AD.     

Is There a Twelfth Protein-Coding Gene in the Genome of Influenza A? A Selection-Based Approach to the Detection of Overlapping Genes in Closely Related Sequences

Protein-coding genes often contain long overlapping open-reading frames (ORFs), which may or may not be functional. Current methods that utilize the signature of purifying selection to detect functional overlapping genes are limited to the analysis of sequences from divergent species, thus rendering them inapplicable to genes found only in closely related sequences. Here, we present a method for the detection of selection signatures on overlapping reading frames by using closely related sequences, and apply the method to several known overlapping genes, and to an overlapping ORF on the negative strand of segment 8 of influenza A virus (NEG8), for which the suggestion has been made that it is functional. We find no evidence that NEG8 is under selection, suggesting that the intact reading frame might be non-functional, although we cannot fully exclude the possibility that the method is not sensitive enough to detect the signature of selection acting on this gene. We present the limitations of the method using known overlapping genes and suggest several approaches to improve it in future studies. Finally, we examine alternative explanations for the sequence conservation of NEG8 in the absence of selection. We show that overlap type and genomic context affect the conservation of intact overlapping ORFs and should therefore be considered in any attempt of estimating the signature of selection in overlapping genes.     

Is diversionary feeding a useful tool to avoid human-ungulate conflicts? A case study with the aoudad

Diversionary feeding (i.e. supplementary feeding used to mitigate damage to human activities) is a management tool widely employed to avoid human-wildlife conflicts, which could alter the spatial behaviour of target species and can also affect other species present in the area, among other effects. We evaluated the effect of diversionary feeding in the spatial behaviour of the aoudad (Ammotragus lervia), an exotic ungulate associated with crop damage in the area, and we assessed the use of diversionary feeding stations (DFS) by non-target species. Nine aoudads were tracked with GPS/GSM collars. We compared their core home ranges and number of GPS locations in the DFS before and meanwhile food was available on them. Eight DFS were monitored with cameras to identify which species used the feeding sites. The home ranges changed for some individuals, but this variation was not related to supplementary feeding. Just five out of the nine tracked aoudads used DFS, and the number of GPS locations in the DFS by aoudad increased when food was available. DFS were used by fifteen non-target species of birds and mammals, and especially by the wild boar. Aoudads and wild boars segregated temporally but not spatially in their use of the DFS. Our study suggests that diversionary feeding had a limited effect on the spatial behaviour of the aoudad, suggesting that its effectiveness to reduce crop damage may be restricted.     

Giving More to Humans than to Animals in Need? A Behavioral Measure of Animal–Human Continuity in Large-scale Surveys

Survey research on attitudes and behavior toward animals is affected by the hypothetical character of behavioral measurements and socially desirable responses. Drawing on previous research in the fields of environmental behavior and behavioral economics, we combined the advantages of incentivized behavioral experiments and large-scale surveys by asking 2,299 participants in “dictator games” to allocate 10 euros between a charity for poverty reduction and themselves, as well as between a charity for animal protection and themselves (presented in counterbalanced order, with 200 allocations paid to the charities and participants). On average, participants donated approximately 70% of the 10 euros to each charity but donated slightly more money (0.42 euros) for poverty reduction than animal protection. Interestingly, participants allocated the same amount of money to the first charity (whether for humans or animals), but their second allocation depended on the charity and indicated an anthropocentric bias (i.e., higher allocations to poverty reduction than animal protection). Women donated more for animal protection than men, and stronger pro-animal attitudes were associated with higher donations for animal protection. We also found a positive effect of a “social desirability” scale on incentivized donations. In sum, our study finds that participants gave more to humanitarian than animal charities. However, this difference is less than fifty cents and, consequently, minor in magnitude.