Chapman University: Celebrating the Past, Shaping the Future

In celebration of Chapman University’s 150 years of educational excellence this book looks back over the decades at our school’s rich history and the many people that have enriched the campus.https://digitalcommons.chapman.edu/chapman_150th_anniversary_publications/1000/thumbnail.jp

Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium

Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT) Dictyostelium and mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss of chdC caused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning during Dictyostelium multicellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states

Religious education in the experience of young people from mixed-faith families

On the basis of recent ethnographic study at the University of Warwick of the religious identity formation of young people in ‘mixed-faith’ families, this article focuses on their (and their parents’) experiences and perceptions of religious education (RE) and of religious nurture in the community. The young people’s experience of RE differed between primary and secondary school and only a few were engaged in supplementary classes. We highlight the complementarity between school and home in young people’s religious learning and draw out implications for RE

Porcine iGb3s gene silencing provides minimal benefit for clinical xenotransplantation

Background The Galα(1,3)Gal epitope (α-GAL), created by α-1,3-glycosyltransferase-1 (GGTA1), is a major xenoantigen causing hyperacute rejection in pig-to-primate and pig-to-human xenotransplantation. In response, GGTA1 gene-deleted pigs have been generated. However, it is unclear whether there is a residual small amount of α-Gal epitope expressed in GGTA1−/− pigs. Isoglobotrihexosylceramide synthase (iGb3s), another member of the glycosyltransferase family, catalyzes the synthesis of isoglobo-series glycosphingolipids with an α-GAL-terminal disaccharide (iGb3), creating the possibility that iGb3s may be a source of α-GAL epitopes in GGTA1−/− animals. The objective of this study was to examine the impact of silencing the iGb3s gene (A3GalT2) on pig-to-primate and pig-to-human immune cross-reactivity by creating and comparing GGTA1−/− pigs to GGTA1−/−- and A3GalT2−/−-double-knockout pigs. Methods We used the CRISPR/Cas 9 system to target the GGTA1 and A3GalT2 genes in pigs. Both GGTA1 and A3GalT2 genes are functionally inactive in humans and baboons. CRISPR-treated cells used directly for somatic cell nuclear transfer produced single- and double-gene-knockout piglets in a single pregnancy. Once grown to maturity, the glycosphingolipid profile (including iGb3) was assayed in renal tissue by normal-phase liquid chromatography. In addition, peripheral blood mononuclear cells (PBMCs) were subjected to (i) comparative cross-match cytotoxicity analysis against human and baboon serum and (ii) IB4 staining for α-GAL/iGb3. Results Silencing of the iGb3s gene significantly modulated the renal glycosphingolipid profile and iGb3 was not detected. Moreover, the human and baboon serum PBMC cytotoxicity and α-GAL/iGb3 staining were unchanged by iGb3s silencing. Conclusions Our data suggest that iGb3s is not a contributor to antibody-mediated rejection in pig-to-primate or pig-to-human xenotransplantation. Although iGb3s gene silencing significantly changed the renal glycosphingolipid profile, the effect on Galα3Gal levels, antibody binding, and cytotoxic profiles of baboon and human sera on porcine PBMCs was neutral

Using Automated Health Plan Data to Assess Infection Risk from Coronary Artery Bypass Surgery

We determined if infection indicators were sufficiently consistent across health plans to allow comparison of hospitals’ risks of infection after coronary artery bypass surgery. Three managed care organizations accounted for 90% of managed care in eastern Massachusetts, from October 1996 through March 1999. We searched automated inpatient and outpatient claims and outpatient pharmacy dispensing files for indicator codes suggestive of postoperative surgical site infection. We reviewed full text medical records of patients with indicator codes to confirm infection status. We compared the hospital-specific proportions of cases with an indicator code, adjusting for health plan, age, sex, and chronic disease score. A total of 536 (27%) of 1,953 patients had infection indicators. Infection was confirmed in 79 (53%) of 149 reviewed records with adequate documentation. The proportion of patients with an indicator of infection varied significantly (p<0.001) between hospitals (19% to 36%) and health plans (22% to 33%). The difference between hospitals persisted after adjustment for health plan and patients’ age and sex. Similar relationships were observed when postoperative antibiotic information was ignored. Automated claims and pharmacy data from different health plans can be used together to allow inexpensive, routine monitoring of indicators of postoperative infection, with the goal of identifying institutions that can be further evaluated to determine if risks for infection can be reduced

Enhanced Identification of Postoperative Infections among Outpatients

Claims data complement other data sources for identification of surgical site infections following breast surgery and cesarean section

The detection and measurement of interleukin-6 in venous and capillary blood samples, and in sweat collected at rest and during exercise

Purpose: This study aimed to quantify the relationship between venous and capillary blood sampling methods for the measurement of plasma interleukin-6 (IL-6). A parallel study was conducted to determine the possibility of measuring IL-6 in sweat using an enzyme-linked immunosorbent assay (ELISA) and investigate the relationship between plasma- and sweat-derived measures of IL-6. Methods: Twelve male participants were recruited for the measurement of IL-6 at rest and during exercise (study 1). An additional group of five female participants was recruited for the measurement of IL-6 in venous blood versus sweat at rest and following exercise (study 2). In study 1, venous and capillary blood samples were collected at rest and in response to exercise. In study 2, venous and sweat samples were collected following exercise. Results: Mean plasma IL-6 concentration was not different between venous and capillary blood sampling methods either at rest (4.27 ± 5.40 vs. 4.14 ± 4.45 pg ml−1), during (5.40 ± 5.17 vs. 5.58 ± 6.34 pg ml−1), or in response to exercise (6.95 ± 6.37 vs. 6.99 ± 6.74 pg ml−1). There was no IL-6 detectable in sweat either at rest or following exercise. Conclusion: There are no differences in the measurement of plasma IL-6 using either venous or capillary blood sampling methods. Capillary measurement represents a minimally invasive way of measuring IL-6 and detecting changes in IL-6, which are linked to fatigue and overtraining

Speech rhythm: a metaphor?

Is speech rhythmic? In the absence of evidence for a traditional view that languages strive to coordinate either syllables or stress-feet with regular time intervals, we consider the alternative that languages exhibit contrastive rhythm subsisting merely in the alternation of stronger and weaker elements. This is initially plausible, particularly for languages with a steep ‘prominence gradient’, i.e. a large disparity between stronger and weaker elements; but we point out that alternation is poorly achieved even by a ‘stress-timed’ language such as English, and, historically, languages have conspicuously failed to adopt simple phonological remedies that would ensure alternation. Languages seem more concerned to allow ‘syntagmatic contrast’ between successive units and to use durational effects to support linguistic functions than to facilitate rhythm. Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence which would most straightforwardly underpin prominence alternation. We conclude that speech is not incontestibly rhythmic, and may even be antirhythmic. However, its linguistic structure and patterning allow the metaphorical extension of rhythm in varying degrees and in different ways depending on the language, and that it is this analogical process which allows speech to be matched to external rhythms

Hypoxia drives glucose transporter 3 expression through HIF-mediated induction of the long non-coding RNA NICI

Hypoxia inducible transcription factors (HIFs) directly dictate the expression of multiple RNA species including novel and as yet uncharacterized long non-coding transcripts with unknown function. We used pan-genomic HIF-binding and transcriptomic data to identify a novel long non-coding RNA NICI (Non-coding Intergenic Co-Induced transcript) on chromosome 12p13.31 which is regulated by hypoxia via HIF-1 promoter-binding in multiple cell types. CRISPR/Cas9-mediated deletion of the hypoxia-response element revealed co-regulation of NICI and the neighboring protein-coding gene, solute carrier family 2 member 3 (SLC2A3) which encodes the high-affinity glucose transporter 3 (GLUT3). Knock-down or knock-out of NICI attenuated hypoxic induction of SLC2A3 indicating a direct regulatory role of NICI in SLC2A3 expression, which was further evidenced by CRISPR/Cas9-VPR mediated activation of NICI expression. We also demonstrate that regulation of SLC2A3 is mediated through transcriptional activation rather than post-transcriptional mechanisms since knock-out of NICI leads to reduced recruitment of RNA polymerase 2 to the SLC2A3 promoter. Consistent with this we observe NICI-dependent regulation of glucose consumption and cell proliferation. Furthermore, NICI expression is regulated by the VHL tumour suppressor and is highly expressed in clear cell renal cancer, where SLC2A3 expression is associated with patient prognosis, implying an important role for the HIF/NICI/SLC2A3 axis in this malignancy