The Role of Queuine Deficient tRNA in Translational Control

The purpose of this research was to study the effect of the level of tRNA modification with respect to queuine on translational efficiency. Transfer RNA from neoplastic cells is generally deficient with regard to certain hypermodified nucleosides found in normal cells. The hypothesis that was examined is whether or not the altered efficiency of translation can be correlated to the presence of queuine hypomodified tRNA. The loss of queuine in the anticodon may change the interaction of the tRNA\u27s anticodon with its codon. Therefore, the translational complex may stall looking for a rare tRNA, or the stability of the complex adding an amino acid to a peptide chain may be changed by the loss of queuine in the wobble position of the tRNA. Because of the codons contained in the mRNA, these influences may slow or prevent the translation of common genes, but may not affect, or may even increase, the rate for oncogenes or growth-related genes which contain long 5\u27-untranslated leader sequences. This form of translational control may also be exerted on the minicistrons of the 5\u27-leader sequences. This approach used different populations of tRNA to supplement rabbit reticulocyte lysate translation assays. The mRNA was produced in a transcription assay using the bacteriophage T3 polymerase to transcribe the cDNA of genes associated with growth and transformation. This allowed a comparison of the amount of protein produced with normal and hypomodified tRNA. Two genes were used; Nmyc, an oncogene, and murine ornithine decarboxylase, a growth-related gene. These proteins are produced in quantity in cells with hypomodified tRNA and have been shown to be subject to translational controls. Rabbit globin mRNA was used as a control. Nmyc cDNA was not obtained in a transcription vector. It was cloned into the plasmid pIBI30 downstream of the T3 promoter. Ornithine decarboxylase was obtained in a suitable transcription vector. The results shown here indicate that queuine levels in tRNA may have only a minor effect in translation of Nmyc and ornithine decarboxylase. However, the effect on globin translation was striking in queuine deficient HFF tRNA, contradicting an earlier study

Annual Survey of Virginia Law: Domestic Relations

This article reviews some of the important developments in the area of domestic relations law between May 1995 and July 1996. Of particular significance were opinions by the Court of Appeals of Virginia regarding issues of imputed income, the definition of a day for shared custody purposes, and the role of marital fault in equitable distribution determinations. The majority of bills passed in the 1996 Session of the General Assembly simply fine-tuned existing law. However, notable statutory revisions were made in the areas of child support and domestic violence. Although the legislature replaced the term spousal abuse with family abuse, child abuse is addressed in another article

Quality of Feedback in Higher Education: A Review of Literature

In raising the standards for professional educators, higher educators must be prepared to provide the highest quality feedback on student performance and work products toward improved outcomes. This review of the literature examined the major findings of 70 quantitative, mixed methods, or qualitative studies found in higher education journals across a range of disciplines. Multiple recommendations and results for feedback emerged which fall into the categories described by Susan Brookhart. This review found research for each of Brookhart’s categories, with results indicating dierences between the perceptions of adherence to sound feedback practices versus the reality of implementation, the potential for innovative tool use, and a disagreement about the eectiveness of peers for providing eective feedback. Indicators for quality within the research confirmed the importance of commonly accepted standards such as positivity, specificity, timeliness, and encouraging active student participation. Additionally, trends and themes indicated a need for the consistent implementation of the feedback exchange process and flexibility to account for student input/preferences. Greater consistency toward the application of these quality indicators should be undertaken when determining the quality of higher education feedback for preservice teachers prior to undertaking summative licensure assessments

Pancreas sparing duodenectomy as an emergency procedure

<p>Abstract</p> <p>Background</p> <p>The operative techniques to close extensive wounds to the duodenum are well described. However, postoperative morbidity is common and includes suture line leak and the formation of fistulae. The aim of this case series is to present pancreas sparing duodenectomy as a safe and viable alternative procedure in the emergency milieu.</p> <p>Methods</p> <p>Five patients underwent emergency pancreas sparing duodenal excisions. Re-implantation of the papilla of Vater or the papilla with a surrounding mucosal patch was performed in two patients. In one, the procedure was further supplemented with a duodenocholangiostomy, stapled pyloric exclusion and enterogastrostomy to defunction the pylorus. In another three patients, distal duodenal excisions were done.</p> <p>Results</p> <p>In four patients, an uneventful recovery was made. One patient died following a myocardial infarction. The surgery lasted meanly 160 minutes with average blood loss of approximately 500 milliliters. The mean hospital stay was 12 days. Enteral nutrition was introduced within the 20 hours after the surgery. Long term follow-up of all surviving patients confirmed a good outcome and normal nutritional status.</p> <p>Conclusion</p> <p>Based on the presented series of patients, we suggest that pancreas-sparing duodenectomy can be considered in selected patients with laceration of the duodenum deemed unsuitable for surgical reconstruction.</p

Homocysteine concentrations in the cognitive progression of Alzheimer’s disease

Objectives: Hyperhomocysteinemia in Alzheimer’s disease (AD) is widely reported and appears to worsen as the disease progresses. While active dietary intervention with vitamins B12 and folate decreases homocysteine blood levels, with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far has not been replicated in established AD populations. The aim of the study is to explore the relationship between hyperhomocystenemia and relevant vitamins as the disease progresses. Methods: In this longitudinal cohort study, 38 participants with mild to moderate AD were followed for an average period of 13 months. Plasma folate, vitamin B12 and homocysteine concentrations were measured at baseline and at follow-up. Dietary intake of B vitamins was also measured. Spearman’s correlations were conducted by homocysteine and B vitamin status. Results: As expected, cognitive status significantly declined over the follow-up period and this was paralleled by a significant increase in homocysteine concentrations (p=0.006). However, during this follow-up period there was no significant decline in neither dietary intake, nor the corresponding blood concentrations of vitamin B12/folate, with both remaining within normal values. Changes in blood concentrations of B vitamins were not associated with changes in homocysteine levels (p>0.05). Conclusion: In this study, the increase in homocysteine observed in AD patients as the disease progresses cannot be solely explained by dietary and blood levels of folate and vitamin B12. Other dietary and non-dietary factors may contribute to hyperhomocysteinemia and its toxic effect in AD, which needs to be explored to optimise timely intervention strategies

Dietary Intake of Children with Type 1 Diabetes in Bahrain: A Case-Control Study

Background &amp; Objectives: Bahrain is reported to rank amongst the top 10 countries for diabetes prevalence worldwide. In particular, growing numbers of children are being diagnosed with Type 1 diabetes mellitus (T1DM). The objective of this study was to describe the dietary intake of Bahraini children with T1DM as compared to a sample of healthy counterparts and to determine whether the nutrient intakes of Bahraini children with T1DM meet the current recommendations.Design &amp; Setting: This was a case-control study. Dietary intake, estimated using a24-hour dietary recall, for the cases was gathered from the Pediatric Endocrine and Diabetes Unit at the Salmaniya Medical Complex and compared to the 24-hour recalls of children without diabetes recruited from Local Health Centers.Patients &amp; Methods: 50 children aged 6-12 years receiving a confirmed diagnosis of T1DM in the years 2009 and 2010 compared with 55 healthy comparators.Results: Children with T1DM consumed significantly more calories than controls (p&lt;0.001) and significantly more protein relative to their RDA (p&lt;0.029). Both groups failed to meet the RDA values for dietary fiber and for Vitamin D. Sodium intakes were in excess of RDA values although no significant difference was observed between groups (p=0.403).Conclusion: The diets of both children with and without T1DM were found to contain excess protein and sodium and inadequate fiber, vitamin D and calcium. Children with T1DM also appeared to consume excess energy and fat. There is a need to endorse existing dietary guidelines for children with T1DM

Modelling proteins’ hidden conformations to predict antibiotic resistance

AbstractTEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM’s specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models’ prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.</jats:p

Correlates of sociometric status in Russian preschoolers: Aggression, victimization, and sociability

© 2016 Elsevier Ltd. Few studies have assessed behavioral correlates of preschool children\u27s peer sociometric status in cultures outside North America. This study focuses on 221 Russian preschoolers (108 boys, 113 girls). Correlates included physical and relational forms of aggression/victimization and sociable behavior. Confirmatory Factor Analyses (CFA) established that study instruments originally developed with U.S. preschoolers worked well in Russia. Findings in regard to aggression, sociability, and victimization were generally consistent with previous research with American and Italian preschoolers, particularly in regard to controversial status children. Our findings further challenge the notion that controversial children are consistently savvy in their social interactions. They and rejected children were most likely to be physically and relationally victimized by their peers

Psycho-social factors associated with type two diabetes remission through lifestyle intervention: A scoping review

Objectives: There is growing evidence that type 2 diabetes (T2D) can be put into remission through lifestyle intervention. Current focus on remission in terms of physiological considerations and biomedical scales, means there is limited understanding of the role psycho-social factors play in moderating the efficacy of lifestyle interventions for T2D remission. In the current review we aimed to synthesise the emerging literature on psycho-social factors associated with T2D remission, specifically from lifestyle interventions. Methods: Five databases (EMBASE, MEDLINE, CINAHL ultimate, PsychINFO and PsycArticles) were searched to identify studies from 2009 onwards that reported remission outcomes from lifestyle interventions in participants ≥ 18years old, with a clinical diagnosis of T2D. Studies included were of an interventional or observational design and restricted to English language. Screening and data extraction was performed independently by two reviewers using prespecified criteria. Results: In total 6106 studies were screened, 36 studies meeting the inclusion criteria were included. Studies were globally diverse, with 30 (83%) being published ≥ 2017. Psycho-social scales were under-utilised with 22 (67%) of studies failing to include any psycho-social measures. Single arm, prospective studies were most frequently utilised, however study quality was perceived to be heterogeneous. Further disparity in the quality, content and delineation of the psycho-social interventions was also identified. Education and self-monitoring interventions were the most frequently incorporated. Self-monitoring was also identified as an important facilitator to remission, in addition to social support. Conclusions: Our findings indicate that psycho-social factors in T2D remission are under-explored. We have identified a number of methodological issues (comparability, conflicting remission criteria and poorly defined psycho-social interventions) suggesting knowledge gaps which could inform the methodology of future research design. There is significant opportunity for future research to incorporate the social model of disease, conceptualise remission more holistically, and build a more comprehensive evidence base to guide clinical practice