A study of the question of subsidization of privately controlled schools by the federal government

https://place.asburyseminary.edu/ecommonsatsdissertations/2296/thumbnail.jp

Genomic Imprinting: CTCF Protects the Boundaries

AbstractThe DNA-binding protein CTCF, which acts as a chromatin ‘insulator’, regulates imprinting of the mammalian Igf2 and H19 genes in a methylation-sensitive manner. It has now been shown that CTCF is also required for protection against de novo methylation of the differentially methylated domain of H19 in the female germline

Developing a conversation: A strategy to engage faculty in pedagogical change

Personal interviews were conducted with biochemistry faculty during which they were presented with student performances on a content survey. From these interviews, four themes that reflect faculty responses to the surveys emerged: awareness of student understanding, self reflection on teaching practice, planned collaboration with colleagues, and emotional reactions. Here, we discuss these themes and their implications for creating conversation designed to promote reflection on biochemistry teaching

SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr

<p>Abstract</p> <p>Background</p> <p>Heterozygous and homozygous carriers of <it>SCN5A</it>-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death. We hypothesized that some heterozygous carriers may have unequal expression of wild-type and variant alleles and secondarily that predominance of the variant gene copy could further increase risk for sudden death in this population.</p> <p>Methods</p> <p>We quantified allele-specific expression of <it>SCN5A</it>-p.Ser1103Tyr by real-time reverse-transcription polymerase chain reaction (RT-PCR) in heart tissue from heterozygous African-American infants, who died from sudden infant death syndrome (SIDS) or from other causes, to test for allelic expression imbalance.</p> <p>Results</p> <p>We observed significant allelic expression imbalance in 13 of 26 (50%) African-American infant hearts heterozygous for <it>SCN5A</it>-p.Ser1103Tyr, and a significant (p < 0.0001) bimodal distribution of log₂allelic expression ratios. However, <b>t</b>here were no significant differences in the mean log₂allelic expression ratios in hearts of infants dying from SIDS as compared to infants dying from other causes and no significant difference in the proportion of cases with greater expression of the variant allele.</p> <p>Conclusions</p> <p>Our data provide evidence that <it>SCN5A </it>allelic expression imbalance occurs in African-Americans heterozygous for p.Ser1103Tyr, but this phenomenon alone does not appear to be a marker for risk of SIDS.</p

An 18F-labeled poly(ADP-ribose) polymerase positron emission tomography imaging agent

Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [18F]20, was synthesized and evaluated as a potential PARP PET radiotracer in mice bearing subcutaneous glioblastoma xenografts using ex vivo biodistribution and PET−magnetic resonance imaging techniques. Results showed that [18F]20 could be produced in a good radioactivity yield and exhibited specific PARP binding allowing visualization of tumors overexpressing PARP. [18F]20 is therefore a potential candidate radiotracer for in vivo PARP PET imaging

Recruiting and Retaining Family Caregivers to a Randomized Controlled Trial on Mindfulness-Based Stress Reduction

Caregivers for a family member with dementia experience chronic long-term stress that may benefit from new complementary therapies such as mindfulness-based stress reduction. Little is known however, about the challenges of recruiting and retaining family caregivers to research on mind–body based complementary therapies. Our pilot study is the first of its kind to successfully recruit caregivers for a family member with dementia to a randomized controlled pilot study of mindfulness-based stress reduction. The study used an array of recruitment strategies and techniques that were tailored to fit the unique features of our recruitment sources and employed retention strategies that placed high value on establishing early and ongoing communication with potential participants. Innovative recruitment methods including conducting outreach to health plan members and generating press coverage were combined with standard methods of community outreach and paid advertising. We were successful in exceeding our recruitment goal and retained 92% of the study participants at post-intervention (2 months) and 90% at 6 months. Recruitment and retention for family caregiver interventions employing mind–body based complementary therapies can be successful despite many challenges. Barriers include cultural perceptions about the use and benefit of complementary therapies, cultural differences with how the role of family caregiver is perceived, the use of group-based designs requiring significant time commitment by participants, and travel and respite care needs for busy family caregivers

Apc Min/+ tumours and normal mouse small intestines show linear metabolite concentration and DNA cytosine hydroxymethylation gradients from pylorus to colon

Abstract: Topographical variations of metabolite concentrations have been reported in the duodenum, jejunum and ileum of the small intestine, and in human intestinal tumours from those regions, but there are no published metabolite concentrations measurements correlated with linear position in the mouse small intestine or intestinal tumours. Since DNA methylation dynamics are influenced by metabolite concentrations, they too could show linear anatomical variation. We measured metabolites by HR-MAS 1H NMR spectroscopy and DNA cytosine modifications by LC/MS, in normal small intestines of C57BL/6J wild-type mice, and in normal and tumour samples from ApcMin/+ mice. Wild-type mouse intestines showed approximately linear, negative concentration gradations from the pylorus (i.e. the junction with the stomach) of alanine, choline compounds, creatine, leucine and valine. ApcMin/+ mouse tumours showed negative choline and valine gradients, but a positive glycine gradient. 5-Hydroxymethylcytosine showed a positive gradient in the tumours. The linear gradients we found along the length of the mouse small intestine and in tumours contrast with previous reports of discrete concentration changes in the duodenum, jejunum and ileum. To our knowledge, this is also the first report of a systematic measurement of global levels of DNA cytosine modification in wild-type and ApcMin/+ mouse small intestine

Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions.

Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufficient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription.The authors acknowledge all the members of Murrell, Rinn, Odom and Gergely laboratory as well as Massimiliano di Pietro, Klaas Mulder, Anna Git, Jason Carroll in Cambridge and Laurence Hurst (University of Bath) for reading and providing helpful comments on the manuscript. We also thank the Genomics, Microscopy and Bioinformatics core facilities at the Cambridge Institute for support, Christina Ernst for thumbnail image design, Ezgi Hacisuleyman for the design of the negative control vector, Cole Trapnell and David Hendrickson for providing us with lincExpress vector, Arjun Raj with the RNA FISH and Alaisdair Russell with the lentiviral work. This research was supported by The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. The authors have no conflicting financial interests.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1040

The modern pollen-vegetation relationship of a tropical forest-savannah mosaic landscape, Ghana, West Africa

Transitions between forest and savannah vegetation types in fossil pollen records are often poorly understood due to over-production by taxa such as Poaceae and a lack of modern pollen-vegetation studies. Here, modern pollen assemblages from within a forest-savannah transition in West Africa are presented and compared, their characteristic taxa discussed, and implications for the fossil record considered. Fifteen artificial pollen traps were deployed for 1 year, to collect pollen rain from three vegetation plots within the forest-savannah transition in Ghana. High percentages of Poaceae and Melastomataceae/Combretaceae were recorded in all three plots. Erythrophleum suaveolens characterised the forest plot, Manilkara obovata the transition plot and Terminalia the savannah plot. The results indicate that Poaceae pollen influx rates provide the best representation of the forest-savannah gradient, and that a Poaceae abundance of >40% should be considered as indicative of savannah-type vegetation in the fossil record

Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer.

Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers-either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions. Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array. Firstly, we performed SNP and gene-level analyses of protein-altering variants on the array to identify novel associations the following ADRs, which were grouped into four phenotypes based on symptoms of diarrhea, mucositis, and neutropenia and hand-and-foot syndrome. Secondly, we performed detailed analyses of the HLA region on the same phenotypes after imputing the HLA alleles and amino acids. No protein-altering variants, or sets of protein-altering variants collapsed into genes, were associated with the main outcomes after Bonferroni correction. We found evidence that the HLA region was enriched for associations with Hand-and-Foot syndrome (p = 0.023), but no specific SNPs or HLA alleles were significant after Bonferroni correction. Larger studies will be required to characterize the genetic contribution to ADRs to 5FU. Future studies that focus on the HLA region are likely to be fruitful