46 research outputs found
Cellular & Molecular Mechanisms That Contribute to the Early Development of Skeletal Muscle & Systemic Insulin Resistance
Indiana University-Purdue University Indianapolis (IUPUI)Insulin resistance starts years before type 2 diabetes (T2D) diagnosis, even before
recognition of prediabetes. Mice on a high fat diet have a similar early onset of insulin
resistance, yet the mechanism remains unknown. Several studies have demonstrated that
skeletal muscle insulin resistance resulting from obesity or high fat feeding does not stem
from defects in proximal insulin signaling. Our lab discovered that excess plasma
membrane cholesterol impairs insulin action. Excess cholesterol in the plasma membrane
causes a loss of cortical actin filaments that are essential for glucose transporter GLUT4
regulation by insulin. Our cell studies further revealed that increased hexosamine
biosynthesis pathway (HBP) activity increases O-linked N-acetylglucosamine
modification of the transcription factor Sp1, leading to transcription of HMG-CoA
reductase (HMGR), the rate-limiting enzyme in cholesterol biosynthesis. Our central
hypothesis is that cholesterol accumulation mediated by HBP activity is an early
reversible mechanism of high-fat diet-induced insulin resistance. We performed a series
of studies and found that early high-fat feeding-induced insulin resistance is associated
with a buildup of cholesterol in skeletal muscle membranes (SMM). Akin to the
antidiabetic effect of caloric restriction, we found that high-fat diet removal fully
mitigated SMM cholesterol accumulation and insulin resistance. Furthermore, using the
cholesterol-binding agent methyl-β-cyclodextrin (MβCD), studies established causality
between excess SMM cholesterol and insulin resistance. To begin to assess the role of the HBP/Sp1 in contributing to de novo cholesterol biosynthesis, SMM accumulation, and
insulin resistance we treated high-fat fed mice with an Sp1 inhibitor, mithramycin. We
found that mithramycin prevented SMM cholesterol accumulation and insulin resistance.
This series of studies provide evidence that HBP/Sp1-mediated cholesterol accumulation
in SMM is a causal, early and reversible mechanism of whole body insulin resistance
New aspects of cellular cholesterol regulation on blood glucose control- review and perspective on the impact of statin medications on metabolic health
Cholesterol is an essential component of cell membranes, and during the past several years, diabetes researchers have found that membrane cholesterol levels in adipocytes, skeletal muscle fibers and pancreatic beta cells influence insulin action and insulin secretion. Consequently, it is thought that dysregulated cell cholesterol homeostasis could represent a determinant of type 2 diabetes (T2D). Recent clinical findings compellingly add to this notion by finding increased T2D susceptibility in individuals with alterations in a variety of cholesterol metabolism genes. While it remains imperfectly understood how statins influence glucose metabolism, the fact that they display an influence on blood glucose levels and diabetes susceptibility seems to intensify the emerging importance of understanding cellular cholesterol in glucose metabolism. Taking this into account, this review first presents cell system and animal model findings that demonstrate the negative impact of cellular cholesterol accumulation or diminution on insulin action and insulin secretion. With this framework, a description of how changes in cholesterol metabolism genes are associated with T2D susceptibility will be presented. In addition, the connection between statins and T2D risk will be reviewed with expanded information on pitavastatin, a newer statin medication that displays actions favoring metabolic healt
Broadband polarization-entangled source for C+L-band flex-grid quantum networks
The rising demand for transmission capacity in optical networks has motivated
steady interest in expansion beyond the standard C-band (1530-1565 nm) into the
adjacent L-band (1565-1625 nm), for an approximate doubling of capacity in a
single stroke. However, in the context of quantum networking, the ability to
leverage the L-band will require advanced tools for characterization and
management of entanglement resources which have so far been lagging. In this
work, we demonstrate an ultrabroadband two-photon source integrating both C-
and L-band wavelength-selective switches for complete control of spectral
routing and allocation across 7.5 THz in a single setup. Polarization state
tomography of all 150 pairs of 25 GHz-wide channels reveals an average fidelity
of 0.98 and total distillable entanglement greater than 181 kebits/s. This
source is explicitly designed for flex-grid optical networks and can facilitate
optimal utilization of entanglement resources across the full C+L-band.Comment: 5 pages, 4 figure
The Grizzly, March 23, 2017
Immigration Panel Will Allow Students to Express Their Experience with Political Issues • International Perspective: Reflections on Adjusting to Campus Culture in the Fall • Important Housing Lottery Dates and Advice from Residence Life • Tech Support Updates Outdated Login Service • From Taxes to Spaghetti, Nerd Camp Helps Students Navigate the Real World • First-Person Perspective: Student Reflects on Class Trip to Chicago • Opinions: Does U.S. Happiness Affect UC Happiness?; Trappe Beer and Soda or Austin\u27s Beverages? • From Amateur Wrestler to College Professor: Nick Scoville Does it All • Fun in the Sun: Five Ursinus Teams Traveled Cross Country to Compete During Spring Breakhttps://digitalcommons.ursinus.edu/grizzlynews/1663/thumbnail.jp
Outcomes from a single-intervention trial to improve interprofessional practice behaviors at a student-led free clinic
Background
Interprofessional collaboration (IPC) is the practice of two or more healthcare professionals working together and learning from one another to improve health outcomes. IPC is important for quality training, typically improving individual and group level outcomes. Students value the opportunity for leadership and teamwork development when IPC is offered in their curriculum. The Indiana University Student Outreach Clinic (IUSOC) is a student run clinic that provides free primary care services to underserved residents residing in Indianapolis, Indiana. The IUSOC partner leaders identified a need to enhance knowledge about partner roles, scope of practice, and professional training with the hopes of improving quality of care through IPC and utilization of clinic resources.
Methods
A cluster randomized design consisted of education session days and control days. Participants had an equal selection probability. Student partners from ten different disciplines were involved. Two survey instruments were used for data collection: 1) The Interprofessional Socialization and Valuing Scale and 2) The Professional Consciousness Raising Questionnaire. The former measured the attitudes and beliefs that underlie interprofessional socialization, while the latter assessed pre/post student knowledge of the roles and responsibilities of each partner.
Results
The control arm of the study was composed of 167 student participants and the intervention arm had 170 participants. Participants in the intervention arm had greater scores for “ability to work with others”, “value in working with others”, and “comfort in working with others.” The intervention arm also had significantly increased odds of correctly identifying the roles responsibilities of the nursing, law, dental, and global health disciplines.
Conclusions
Results of this study demonstrate that administering a short interprofessional education exercise to healthcare professional students leads to improved IPC through increased interprofessional knowledge about other professions and change in beliefs and values toward the value of interprofessional collaboration among healthcare professionals
Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome
We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet
The Lantern, 2015-2016
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Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism
SummaryWe have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe