Cloning and characterization of the Schizosaccharomyces pombe homologs of the human protein Translin and the Translin-associated protein TRAX

Translin is a human octameric protein that specifically binds the single-stranded microsatellite repeats d(GT)(n) and the corresponding transcripts (GU)(n). It also binds, with lesser affinities, other single-stranded G-rich DNA and RNA sequences. TRAX is a human protein that bears a homology to Translin and interacts with it. Translin and TRAX have been proposed to be involved in DNA recombination, chromosomal translocation and mRNA transport and translation. Both proteins are highly conserved in eukaryotes, including the fission yeast Schizosaccharomyces pombe, which is amenable to genetic analysis. Here, we report the first study of the S.pombe Translin and TRAX homologs. We have deleted the genes encoding Translin and TRAX in S.pombe and found that the proliferation of the mutant cells was slightly stimulated, suggesting that these genes are not essential for the fission yeast. We have also shown that the S.pombe Translin and TRAX interact. Biochemical analysis of the S.pombe Translin, which was cloned and expressed in Escherichia coli, revealed that it is octameric and that it selectively binds d(GT)(n) and d(GTT)(n) microsatellite repeats. However, unlike the human protein, it has much higher affinities for the homologous RNA sequences (GU)(n) and (GUU)(n). These data suggest that the S.pombe Translin is primarily involved in functions related to RNA metabolism

Obesity and Blood Pressure in 17-Year-Old Offspring of Mothers with Gestational Diabetes: Insights from the Jerusalem Perinatal Study

Objective. Gestational diabetes mellitus (GDM) influences fetal development and offspring's metabolic risk. We evaluated this association in 17-year-old offspring adjusting for birth weight (BW) and prepregnancy maternal BMI (mBMI). Study Design. The JPS birth cohort contains extensive data on 92,408 births from 1964 to 1976. Offspring's BMI and blood pressure (BP) were obtained from military records. For a subcohort born between 1974 and 1976, prepregnancy mBMI was available. Offspring were classified as born to mothers with GDM (n = 293) or born to mothers without recorded GDM (n = 59,499). Results. GDM offspring had higher mean BMI and systolic and diastolic BP compared to no-recorded-GDM offspring. After adjusting for BW, GDM remained significantly associated with offspring BMI and diastolic BP (β = 1.169 and 1.520, resp.). In the subcohort, when prepregnancy mBMI was entered to the models, it markedly attenuated the associations with GDM. Conclusions. Maternal characteristics have long-term effects on cardiometabolic outcomes of their offspring aged 17 years

Socioeconomic disparities in breast cancer incidence and survival among parous women: findings from a population-based cohort, 1964–2008

Background Socioeconomic position (SEP) has been associated with breast cancer incidence and survival. We examined the associations between two socioeconomic indicators and long-term breast cancer incidence and survival in a population-based cohort of parous women. Methods Residents of Jerusalem who gave birth between 1964–1976 (n = 40,586) were linked to the Israel Cancer Registry and Israel Population Registry to determine breast cancer incidence and vital status through mid-2008. SEP was assessed by husband’s occupation and the woman’s education. We used log ranks tests to compare incidence and survival curves by SEP, and Cox proportional hazard models to adjust for demographic, reproductive and diagnostic factors and assess effect modification by ethnic origin. Results In multivariable models, women of high SEP had a greater risk of breast cancer compared to women of low SEP (Occupation: HR 1.18, 95 % CI 1.03-1.35; Education: HR 1.39, 95 % CI 1.21-1.60) and women of low SEP had a greater risk of mortality after a breast cancer diagnosis (Occupation: HR 1.33, 95 % CI 1.04-1.70; Education: HR 1.37, 95 % CI 1.06-1.76). The association between education and survival was modified by ethnic origin, with a gradient effect observed only among women of European origin. Women of Asian, North African and Israeli origin showed no such trend. Conclusions SEP was associated with long-term breast cancer incidence and survival among Israeli Jews. Education had a stronger effect on breast cancer outcomes than occupation, suggesting that a behavioral mechanism may underlie disparities. More research is needed to explain the difference in the effect of education on survival among European women compared to women of other ethnicities

A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease-Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson's disease (PD). A cohort study of GBA carriers between 40-75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40-74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7-33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14-32%), Unified Parkinson's Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2-26.4%), smell assessment (12.4%, 95% CI 6.6-20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7-19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as "abnormal". Then we calculated the percentage of "abnormal" tests for each subject; the median (range) was 4.55 (0-43.5%). Twenty-two subjects had more than 15% "abnormal" tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth.

International audienceThe precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a(-/-)Myo3b(-/-) mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b(-/-) mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a(-/-)Myo3b(-/-) cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a(-/-)Myo3b(-/-) stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping

Developmental Trajectories in Siblings of Children with Autism: Cognition and Language from 4 Months to 7 Years

We compared the cognitive and language development at 4, 14, 24, 36, 54 months, and 7 years of siblings of children with autism (SIBS-A) to that of siblings of children with typical development (SIBS-TD) using growth curve analyses. At 7 years, 40% of the SIBS-A, compared to 16% of SIBS-TD, were identified with cognitive, language and/or academic difficulties, identified using direct tests and/or parental reports. This sub-group was identified as SIBS-A-broad phenotype (BP). Results indicated that early language scores (14–54 months), but not cognitive scores of SIBS-A-BP and SIBS-A-nonBP were significantly lower compared to the language scores of SIBS-TD, and that the rate of development was also significantly different, thus pinpointing language as a major area of difficulty for SIBS-A during the preschool years

The impact of being involved in a medical adverse event on GP's (General Physicians) professional behavior in an ambulatory healthcare fund

Assurance behavior: performing unnecessary tests so as to deter patients from filing complaints or medical malpractice suits Avoidance behavior: choosing to behave in a way that prevents recurrence of an unpleasant stimulus This thesis examines the impact of involvement in a medical adverse event on the personal and professional behavior of medical staff or "second victims." The second victim concept is relatively new, and was first described by Albert Wu, M.D., M.P.H in 2000. The major contribution of this thesis is that it tests the second victim hypotheses in real life settings without the intervention of the medical organization, and examines the methodological and practical challenges involved. Unlike most studies of this kind that rely solely on self-report questionnaires, especially among care providers in hospitals, the present study tests its hypotheses by measuring real life data. This study is also unique in that it compares the professional functioning of General Practitioners both prior to and following an adverse event. The theoretical hypothesis was that after involvement in an adverse event, physicians would have a greater tendency to practice defensive medicine expressed through avoidance behavior or assurance behavior, as defined above. The results reveal that during the month following involvement in an adverse event there is significant impact on a doctor's functioning. This impact may manifest itself in the adoption of defensive medicine and/or avoidance behavior which can be measured by an increase in referrals of patients to the Emergency Room, a tendency to see fewer patients, and a tendency to see patients less frequently. Recognition of the second victim phenomenon should encourage healthcare organizations to invest resources to support and assist medical staff following involvement in an adverse event, as was the case with the Maccabi Health Care Fund, which decided to implement an intervention program to address this important issue

Mortality after spousal loss: are there socio-demographic differences?

This study evaluates the effect of spousal death on mortality among Israeli adults and examines differences in this effect by duration of bereavement, age, sex, education, ethnic origin, household size, and number of children. Data are taken from the Israel Longitudinal Mortality Study which is based on a linkage of records from a 20% sample of the 1983 census to records of deaths occurring during the period 1983-1992. The study population comprised 49,566 men and 41,264 women, of whom 4,402 (9%) and 11,114 (27%), respectively, were bereaved during the follow-up period. Excess mortality among the bereaved was evident among both men and women, especially after bereavement of short duration. During the first 6 months, the excess mortality was about 50% among women and about 40% among men. For men, the effect of bereavement on mortality decreased linearly with age, with a relative risk of 3 among younger men during early widowhood. Bereavement had a greater impact on the more educated men. The effect of bereavement did not vary by ethnic origin or household size.Bereavement Mortality Widowhood Socio-economic status Israel