Novel small RNA (sRNA) landscape of the starvation-stress response transcriptome of Salmonella enterica serovar typhimurium.

Small RNAs (sRNAs) are short (∼50-200 nucleotides) noncoding RNAs that regulate cellular activities across bacteria. Salmonella enterica starved of a carbon-energy (C) source experience a host of genetic and physiological changes broadly referred to as the starvation-stress response (SSR). In an attempt to identify novel sRNAs contributing to SSR control, we grew log-phase, 5-h C-starved and 24-h C-starved cultures of the virulent Salmonella enterica subspecies enterica serovar Typhimurium strain SL1344 and comprehensively sequenced their small RNA transcriptomes. Strikingly, after employing a novel strategy for sRNA discovery based on identifying dynamic transcripts arising from "gene-empty" regions, we identify 58 wholly undescribed Salmonella sRNA genes potentially regulating SSR averaging an ∼1,000-fold change in expression between log-phase and C-starved cells. Importantly, the expressions of individual sRNA loci were confirmed by both comprehensive transcriptome analyses and northern blotting of select candidates. Of note, we find 43 candidate sRNAs share significant sequence identity to characterized sRNAs in other bacteria, and ∼70% of our sRNAs likely assume characteristic sRNA structural conformations. In addition, we find 53 of our 58 candidate sRNAs either overlap neighboring mRNA loci or share significant sequence complementarity to mRNAs transcribed elsewhere in the SL1344 genome strongly suggesting they regulate the expression of transcripts via antisense base-pairing. Finally, in addition to this work resulting in the identification of 58 entirely novel Salmonella enterica genes likely participating in the SSR, we also find evidence suggesting that sRNAs are significantly more prevalent than currently appreciated and that Salmonella sRNAs may actually number in the thousands.

Microstructural corpus callosum anomalies in children with prenatal alcohol exposure: an extension of previous diffusion tensor imaging findings.

BACKGROUND: Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter-hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full-criteria fetal alcohol syndrome (FAS). METHODS: Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology. RESULTS: In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid-body, the isthmus, and the splenium. A trend-level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual-perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant. CONCLUSIONS: Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics.

White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study.

Diffusion tensor imaging was used to evaluate cerebral white matter in eight patients (ages 10-17), with myotonic dystrophy type 1 (3 congenital-onset, 5 juvenile-onset) compared to eight controls matched for age and sex. Four regions of interest were examined: inferior frontal, superior frontal, supracallosal, and occipital. The myotonic dystrophy group showed white matter abnormalities compared to controls in all regions. All indices of white matter integrity were abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. With no evidence of regional variation, correlations between whole cerebrum white matter fractional anisotropy and neurocognitive functioning were examined in the patients. Strong correlations were observed between whole cerebrum fractional anisotropy and full-scale intelligence and a measure of executive functioning. Results indicate that significant white matter abnormality is characteristic of young patients with myotonic dystrophy type 1 and that the white matter abnormality seen with neuroimaging has implications for cognitive functioning.

Who are the next generation of genetic counselors? A survey of students.

Genetic counseling students were surveyed about their backgrounds, application process to genetic counseling programs, and career motivations and plans. Program directors from 27 accredited programs were asked to distribute 362 surveys to students. Fifty-two survey items assess demographics; sources of support for pursuing a genetic counseling career (information about genetic counseling, encouragement/discouragement from others); career motivations (reasons for applying and for becoming a genetic counselor); and career certainty. Two hundred and thirty-five usable surveys were returned (64.9% usable return rate). Most respondents were Caucasian females (mean age = 25.4 years). About 13% identified as ethnic minorities, and about one-third reported family histories of a genetic condition(s). Most respondents learned about the field in classes, and most were strongly encouraged by family and friends to pursue genetic counseling. Reasons rated as most important for becoming a genetic counselor included helping others and intellectual stimulation. Recruitment, training, and research recommendations are given.

Does receiving genetic counseling impact genetic counselor practice?

This study was an investigation of whether genetic counselors have received genetic counseling and if so, how they believe it affects their practice. One thousand genetic counselors were mailed surveys about the nature of genetic counseling services received, impact on their clinical practice, frequency and reasons for disclosing about their receipt of counseling to their clients, and demographics. Ninety-three of the 510 respondents reported receiving genetic counseling. Of these, almost three-fourths were practicing genetic counselors while receiving services. Reasons for services include prenatal concerns, family history of cancer, and history/risk of other genetic conditions. Frequently endorsed effects on practice include increased empathy and understanding of client decisions, feeling more connected with clients, greater emphasis on psychosocial support, and sympathy. Forty-six respondents disclosed to clients about their receipt of genetic counseling. Prevalent reasons include client asked, help clients feel they are not alone, demonstrate counselor understanding, decrease client anxiety, build rapport, and normalize client feelings. Practice and research recommendations are given.

Metoprolol and coronary artery bypass grafting surgery: does intraoperative metoprolol attenuate acute beta-adrenergic receptor desensitization during cardiac surgery?

UNLABELLED: Cardiac surgery results in significant impairment of beta-adrenergic receptor (beta AR) function and is a cause of depressed myocardial function after surgery. We previously demonstrated that acute administration of beta AR blocker during cardiopulmonary bypass (CPB) in an animal model of coronary artery bypass grafting (CABG) surgery attenuates beta AR desensitization, whereas chronic oral beta-blockade therapy in patients undergoing CABG surgery does not prevent it. Therefore we hypothesized that acute administration of metoprolol during CABG surgery would prevent acute myocardial beta AR desensitization. A placebo-controlled initial phase (n = 72) was performed whereby patients were randomized to either metoprolol 10 mg or placebo immediately before CPB. Then a second dose-finding study was performed where patients received 20 mg (n = 20) or 30 mg (n = 20) of metoprolol. Hemodynamic monitoring, atrial membrane adenylyl cyclase activity, atrial beta AR density, and postoperative outcomes were measured. All groups showed similar decreases in isoproterenol-stimulated adenylyl cyclase activity (13%-24%). Cardiac output remained similar in all 4 groups throughout the intraoperative and postoperative period. In addition, patients receiving metoprolol 20 or 30 mg had less supraventricular arrhythmias 24 h postoperatively compared with patients receiving metoprolol 10 mg or placebo. Therefore, unlike our previous animal model of CABG surgery, metoprolol did not attenuate myocardial beta AR desensitization. IMPLICATIONS: We investigated whether IV metoprolol given during cardiac surgery attenuates myocardial beta-adrenergic receptor (beta AR) desensitization. Although metoprolol did not reduce beta AR desensitization, the incidence of supraventricular arrhythmias was reduced by 75% in patients receiving 20 mg or 30 mg metoprolol.