Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction

Mitochondria alter their shape by undergoing cycles of fusion and fission. Changes in mitochondrial morphology impact on the cellular response to stress, and their interactions with other organelles such as the sarcoplasmic reticulum (SR). Inhibiting mitochondrial fission can protect the heart against acute ischemia/reperfusion (I/R) injury. However, the role of the mitochondrial fusion proteins, Mfn1 and Mfn2, in the response of the adult heart to acute I/R injury is not clear, and is investigated in this study. To determine the effect of combined Mfn1/Mfn2 ablation on the susceptibility to acute myocardial I/R injury, cardiac-specific ablation of both Mfn1 and Mfn2 (DKO) was initiated in mice aged 4-6 weeks, leading to knockout of both these proteins in 8-10-week-old animals. This resulted in fragmented mitochondria (electron microscopy), decreased mitochondrial respiratory function (respirometry), and impaired myocardial contractile function (echocardiography). In DKO mice subjected to in vivo regional myocardial ischemia (30 min) followed by 24 h reperfusion, myocardial infarct size (IS, expressed as a % of the area-at-risk) was reduced by 46% compared with wild-type (WT) hearts. In addition, mitochondria from DKO animals had decreased MPTP opening susceptibility (assessed by Ca(2+)-induced mitochondrial swelling), compared with WT hearts. Mfn2 is a key mediator of mitochondrial/SR tethering, and accordingly, the loss of Mfn2 in DKO hearts reduced the number of interactions measured between these organelles (quantified by proximal ligation assay), attenuated mitochondrial calcium overload (Rhod2 confocal microscopy), and decreased reactive oxygen species production (DCF confocal microscopy) in response to acute I/R injury. No differences in isolated mitochondrial ROS emissions (Amplex Red) were detected in response to Ca(2+) and Antimycin A, further implicating disruption of mitochondria/SR tethering as the protective mechanism. In summary, despite apparent mitochondrial dysfunction, hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction due to impaired mitochondria/SR tethering

Logarithmic operators in the SL(2,R) WZNW model

We find some exact solutions of the Knizhnik-Zamolodchikov equation for the four point correlation functions that occur in the SL(2,R) WZNW model. They exhibit logarithmic behaviour in both the Kac-Moody and Virasoro parts. We discuss their implication for the operator product expansion. We also observe the appearance of several symmetries of the correlation functions.Comment: 23 pages, LATEX, Revised Version. More references adde

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

Different Mechanisms Underlie Post-menarchial Increase in Depression and Weight

Contains fulltext : 99254.pdf (publisher's version ) (Open Access)Background Depression and being overweight are correlated health problems in adulthood. Adolescence is a significant period for the onset and increase of depression and obesity, especially among girls. Pubertal development also occurs with concomitant increases in weight. Thus, it is not yet clear whether the association between depression and being overweight can be explained by pubertal development. Purpose We examined the association between depressive mood, body weight, and pubertal status in adolescent girls. Method The design was cross-sectional. In 962 young adolescent Dutch girls (age range, 11.9-15.9) weight and height measurements were used to calculate height, age, and gender-standardized body weight (zBMI). Questionnaires assessed depressive mood (the Center for Epidemiological Studies-Depression, CES-D, inventory) and menarcheal status (pre or post). Results The correlation between menarcheal status and body weight (r = 0.34, p < 0.001) was not affected by depressive mood, and the correlation between menarcheal status and depressive mood (r = 0.20, p < 0.001) was not affected by body weight. A small correlation between depressive mood and body weight (r = 0.12, p < 0.01) largely disappeared after controlling for menarche. Conclusion Menarcheal status largely explains the association between weight and depression. It is independently associated with both BMI and depression, suggesting that different mechanisms underlie the post-menarcheal increased prevalence of depression and overweight.6 p

Insurance data for research in companion animals: benefits and limitations

The primary aim of this article is to review the use of animal health insurance data in the scientific literature, especially in regard to morbidity or mortality in companion animals and horses. Methods and results were compared among studies on similar health conditions from different nations and years. A further objective was to critically evaluate benefits and limitations of such databases, to suggest ways to maximize their utility and to discuss the future use of animal insurance data for research purposes. Examples of studies on morbidity, mortality and survival estimates in dogs and horses, as well as neoplasia in dogs, are discussed

The Association between Mental Health and Violence among a Nationally Representative Sample of College Students from the United States

Objectives Recent violent attacks on college campuses in the United States have sparked discussions regarding the prevalence of psychiatric disorders and the perpetration of violence among college students. While previous studies have examined the potential association between mental health problems and violent behavior, the overall pattern of findings flowing from this literature remain mixed and no previous studies have examined such associations among college students. Methods The current study makes use of a nationally representative sample of 3,929 college students from the National Epidemiologic Study on Alcohol and Related Conditions (NESARC) to examine the prevalence of seven violent behaviors and 19 psychiatric disorder diagnoses tapping mood, anxiety, personality, and substance use disorders. Associations between individual and composite psychiatric disorder diagnoses and violent behaviors were also examined. Additional analyses were adjusted for the comorbidity of multiple psychiatric diagnoses. Results The results revealed that college students were less likely to have engaged in violent behavior relative to the non-student sample, but a substantial portion of college students had engaged in violent behavior. Age- and sex-standardized prevalence rates indicated that more than 21% of college students reported at least one violent act. In addition, more than 36% of college students had at least one diagnosable psychiatric disorder. Finally, the prevalence of one or more psychiatric disorders significantly increased the odds of violent behavior within the college student sample. Conclusions These findings indicate that violence and psychiatric disorders are prevalent on college campuses in the United States, though perhaps less so than in the general population. In addition, college students who have diagnosable psychiatric disorders are significantly more likely to engage in various forms of violent behavior

Neighborhood Socioeconomic Status and Use of Colonoscopy in an Insured Population – A Retrospective Cohort Study

Background: Low-socioeconomic status (SES) is associated with a higher colorectal cancer (CRC) incidence and mortality. Screening with colonoscopy, the most commonly used test in the US, has been shown to reduce the risk of death from CRC. This study examined if, among insured persons receiving care in integrated healthcare delivery systems, differences exist in colonoscopy use according to neighborhood SES. Methods We assembled a retrospective cohort of 100,566 men and women, 50–74 years old, who had been enrolled in one of three US health plans for $\geq$ 1 year on January 1, 2000. Subjects were followed until the date of first colonoscopy, date of disenrollment from the health plan, or December 31, 2007, whichever occurred first. We obtained data on colonoscopy use from administrative records. We defined screening colonoscopy as an examination that was not preceded by gastrointestinal conditions in the prior 6-month period. Neighborhood SES was measured using the percentage of households in each subject's census-tract with an income below 1999 federal poverty levels based on 2000 US census data. Analyses, adjusted for demographics and comorbidity index, were performed using Weibull regression models. Results: The average age of the cohort was 60 years and 52.7% were female. During 449,738 person-years of follow-up, fewer subjects in the lowest SES quartile (Q1) compared to the highest quartile (Q4) had any colonoscopy (26.7% vs. 37.1%) or a screening colonoscopy (7.6% vs. 13.3%). In regression analyses, compared to Q4, subjects in Q1 were 16% (adjusted HR = 0.84, 95% CI: 0.80–0.88) less likely to undergo any colonoscopy and 30%(adjusted HR = 0.70, CI: 0.65–0.75) less likely to undergo a screening colonoscopy. Conclusion: People in lower-SES neighborhoods are less likely to undergo a colonoscopy, even among insured subjects receiving care in integrated healthcare systems. Removing health insurance barriers alone is unlikely to eliminate disparities in colonoscopy use

Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads

BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach

The trophic importance of epiphytic algae in a freshwater macrophyte system (Potamogeton perfoliatus L.): stable isotope and fatty acid analyses

Stable isotope and fatty acid analyses were used to study carbon sources for animals in a submerged plant bed. Epiphytes growing on Potamogeton perfoliatus, sand microflora, and alder leaves were the most important carbon sources. The most abundant macrophyte, P. perfoliatus was unimportant as a food source. Modelling (IsoSource) showed that epiphytes were the most important food source for the most abundant benthic invertebrates, the isopod Asellus aquaticus (annual mean contribution 64%), the amphipod Gammarus pulex (66%), and the gastropod Potamopyrgus antipodarum (83%). The mean annual contributions of sand microflora were, respectively, 21, 19, and 9%; and of alder leaves, 15, 15, and 8% for these three species. The relative importance of carbon sources varied seasonally. The relative contribution of epiphytes was lowest for all three grazer species in July: A. aquaticus 38%, G. pulex 43%, and P. antipodarum 42%. A decline in epiphyte biomass in summer may have caused this switch to less attractive food sources. P. perfoliatus provided habitat and shelter for consumers, but food was mainly supplied indirectly by providing space for attached epiphytes, which are fast-growing and provide a highly nutritious food source