Rapidly evolving marmoset MSMB genes are differently expressed in the male genital tract

BACKGROUND: Beta-microseminoprotein, an abundant component in prostatic fluid, is encoded by the potential tumor suppressor gene MSMB. Some New World monkeys carry several copies of this gene, in contrast to most mammals, including humans, which have one only. Here we have investigated the background for the species difference by analyzing the chromosomal organization and expression of MSMB in the common marmoset (Callithrix jacchus). METHODS: Genes were identified in the Callithrix jacchus genome database using bioinformatics and transcripts were analyzed by RT-PCR and quantified by real time PCR in the presence of SYBR green. RESULTS: The common marmoset has five MSMB: one processed pseudogene and four functional genes. The latter encompass homologous genomic regions of 32-35 kb, containing the genes of 12-14 kb and conserved upstream and downstream regions of 14-19 kb and 3-4 kb. One gene, MSMB1, occupies the same position on the chromosome as the single human gene. On the same chromosome, but several Mb away, is another MSMB locus situated with MSMB2, MSMB3 and MSMB4 arranged in tandem. Measurements of transcripts demonstrated that all functional genes are expressed in the male genital tract, generating very high transcript levels in the prostate. The transcript levels in seminal vesicles and testis are two and four orders of magnitude lower. A single gene, MSMB3, accounts for more than 90% of MSMB transcripts in both the prostate and the seminal vesicles, whereas in the testis around half of the transcripts originate from MSMB2. These genes display rapid evolution with a skewed distribution of mutated nucleotides; in MSMB2 they affect nucleotides encoding the N-terminal Greek key domain, whereas in MSMB3 it is the C-terminal MSMB-unique domain that is affected. CONCLUSION: Callitrichide monkeys have four functional MSMB that are all expressed in the male genital tract, but the product from one gene, MSMB3, will predominate in seminal plasma. This gene and MSMB2, the predominating testicular gene, have accumulated mutations that affect different parts of the translation products, suggesting an ongoing molecular specialization that presumably yields functional differences in accessory sex glands and testis

Quantum Smoluchowski equation: Escape from a metastable state

We develop a quantum Smoluchowski equation in terms of a true probability distribution function to describe quantum Brownian motion in configuration space in large friction limit at arbitrary temperature and derive the rate of barrier crossing and tunneling within an unified scheme. The present treatment is independent of path integral formalism and is based on canonical quantization procedure.Comment: 10 pages, To appear in the Proceedings of Statphys - Kolkata I

Early repolarization in children with unexplained syncope

Introduction: It has traditionally been believed that early repolarization (ER) is benign. Significant association between ER and sudden cardiac arrest due to idiopathic ventricular fibrillation was recently found in a large cohort of adult survivors of sudden cardiac arrest. In some prior studies, unexplained syncope has been linked to risk of sudden death, but the mechanisms remain speculative.We assessed herein the prevalence of ER in children referred to our center for unexplained syncope. Methods: We evaluated retrospectively electrocardiograms from such children (n = 29; mean age, 12.1 years; range, 7-18 years) for presence of ER, which was defined as an elevation of the QRS-ST junction (J-point) in at least 2 leads of at least 1 mm (0.1 mV) above the baseline level. The anterior precordial leads (V1-V3) were excluded from the analysis to avoid inclusion of patients with right ventricular dysplasia or Brugada syndrome. Agematched children (n = 33; mean age, 12.3 years; range, 7-16 years) with noncardiac chest pain were included as controls. Results: Early repolarization was detected in 45% (13/29) of children with unexplained syncope vs 24% (8/33) in the chest pain group. Among children with syncope, ER was far more frequent in males than in females (8/12 vs 5/ 17, respectively). Echocardiography showed normal functional and structural findings in all children. Conclusion: In this relatively small-scale retrospective study of children with unexplained syncope with otherwise normal cardiac findings, we found particularly among those of male gender a greater prevalence of ER than in controls (noncardiac chest pain).With view to earlier findings of Haisaguerre et al (NEJM 2008), this intriguing association warrants further prospective studies addressing its precise clinical implication and underlying mechanisms

Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season : A Swedish National Study

Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006–2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD

MYBPC3 hypertrophic cardiomyopathy can be detected by using advanced ECG in children and young adults

Introduction The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity. Methods Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2 years, range 0-30 years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1 month-30 years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy. Results Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p <0.05). Use of the same score also demonstrated superior specificity in a set of 198 healthy controls (94% vs. 87% for conventional ECG criteria; p <0.01) including in a subset of 36 healthy, young endurance-trained athletes (100% vs. 69% for conventional ECG criteria, p <0.001). Conclusions In children and young adults, a 2-parameter 12-lead A-ECG score is retrospectively significantly more sensitive and specific than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM and in distinguishing such patients from healthy controls, including endurance-trained athletes