Medicine and Health Sciences Commons^™

Nmda Receptor Internalization Down-Regulates Nmda Receptor-Mediated Synaptic Responses Through The Inhibition Of Remaining (Non-Internalized) Surface Nmda Receptors, Xian-Min Yu, Xiao-Qian Fang, Xing-Hong Jiang

School of Medicine Publications

Cell-surface protein endocytosis is critically involved in the regulation of organismal homeostasis, immune responses, development and neurotransmission [1,2,3,4]. Mechanisms underlying the endocytosis of cell surface proteins have been extensively investigated. However, until very recently no study has reported how non-internalized cell surface proteins may behave following endocytosis of same type of proteins. Here, we highlight findings that regulated NMDA receptor (NMDAR) internalization not only reduces the amount of NMDARs expressed on neuronal surface but also through activating PKD1 pathway phosphorylates and down-regulates remaining (non-internalized) surface NMDARs. This down-regulation of remaining surface NMDARs plays a critical role in the modulation of …

Physical Activity And Fto Genotype By Physical Activity Interactive Influences On Obesity, Joon Young Kim, Jacob T. Demenna, Sobha Puppala, Geetha Chittoor, Jennifer Schneider, Ravindranath Duggirala, Lawrence J. Mandarino, Gabriel Q. Shaibi, Dawn K. Coletta

School of Medicine Publications

Background: Although the effect of the fat mass and obesity-associated (FTO) gene on adiposity is well established, there is a lack of evidence whether physical activity (PA) modifies the effect of FTO variants on obesity in Latino populations. Therefore, the purpose of this study was to examine PA influences and interactive effects between FTO variants and PA on measures of adiposity in Latinos.

Results: After controlling for age and sex, participants who did not engage in regular PA exhibited higher BMI, fat mass, HC, and WC with statistical significance (P < 0.001). Although significant associations between the three FTO genotypes and adiposity measures were found, none of the FTO genotype by PA interaction assessments revealed nominally significant associations. However, several of such interactive influences exhibited considerable trend towards association.

Conclusions: These data suggest that adiposity measures are associated with …

Filtering Genetic Variants And Placing Informative Priors Based On Putative Biological Function, Stefanie Friedrichs, Dörthe Malzahn, Elizabeth W. Pugh, Marcio Almeida, Xiao Qing Liu, Julia N. Bailey

School of Medicine Publications

High-density genetic marker data, especially sequence data, imply an immense multiple testing burden. This can be ameliorated by filtering genetic variants, exploiting or accounting for correlations between variants, jointly testing variants, and by incorporating informative priors. Priors can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. Based on Genetic Analysis Workshop (GAW) 19 data, this article discusses diversity and usefulness of functional variant scores provided, for example, by PolyPhen2, SIFT, or RegulomeDB annotations. Incorporating functional scores into variant filters or weights and adjusting the significance level for …

Curcumin Nanoformulation For Cervical Cancer Treatment, Mohd S. Zaman, Neeraj Chauhan, Murali M. Yallapu, Rishi K. Gara, Diane M. Maher, Sonam Kumari, Mohammed Sikander, Sheema Khan, Nadeem Zafar, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based …

Type 2 Diabetes As A Risk Factor For Dementia In Women Compared With Men: A Pooled Analysis Of 2.3 Million People Comprising More Than 100,000 Cases Of Dementia, Saion Chatterjee, Sanne A. Peters, Mark Woodward, Silvia Mejia-Arango, G. David Batty, Nigel Beckett, Alexa Beiser, Amy R. Borenstein, Paul K. Crane, Mary Haan

School of Medicine Publications

Objective: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia.

Research design and methods: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and …

A Large Genome-Wide Association Study Of Age-Related Macular Degeneration Highlights Contributions Of Rare And Common Variants, Lars G. Fritsche, Wilmar Igl, Jessica N. Cooke Bailey, Felix Grassmann, Sebanti Sengupta, Jennifer L. Bragg-Gresham, Kathryn P. Burdon, Scott J. Hebbring, Matthew P. Johnson, John Blangero

School of Medicine Publications

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10–8) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9 (difference-P = 4.1×10–10). Very rare coding variants (frequency < 0.1%) in CFH, CFI, and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate …

Genome-Wide Linkage On Chromosome 10q26 For A Dimensional Scale Of Major Depression, Emma E. M. Knowles, Jack W. Kent Jr., D. Reese Mckay, Emma Sprooten, Samuel R. Mathias, Joanne E. Curran, Melanie A. Carless, Marcio A.A. De Almeida, Harald H. H. Goring, Thomas D. Dyer, Rene L. Olvera, Peter T. Fox, Ravindranath Duggirala, Laura Almasy, John Blangero, David C. Glahn

School of Medicine Publications

Major depressive disorder (MDD) is a common and potentially life-threatening mood disorder. Identifying genetic markers for depression might provide reliable indicators of depression risk, which would, in turn, substantially improve detection, enabling earlier and more effective treatment. The aim of this study was to identify rare variants for depression, modeled as a continuous trait, using linkage and post-hoc association analysis. The sample comprised 1221 Mexican–American individuals from extended pedigrees. A single dimensional scale of MDD was derived using confirmatory factor analysis applied to all items from the Past Major Depressive Episode section of the Mini-International Neuropsychiatric Interview. Scores on this …

Genetic Influences On Schizophrenia And Subcortical Brain Volumes: Large-Scale Proof-Of-Concept And Roadmap For Future Studies, Barbara Franke, Jason L. Stein, Stephan Ripke, Verneri Anttila, Derrek P. Hibar, Kimm J. E. Van Hulzen, Alejandro Arias-Vasquez, Jordan W. Smoller, Thomas E. Nichols, Anderson M. Winkler

School of Medicine Publications

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current …

Genome-Wide Meta-Analysis Uncovers Novel Loci Influencing Circulating Leptin Levels, Tuomas O. Kilpeläinen, Jayne F.Martin Carli, Alicja A. Skowronski, Qi Sun, Jennifer Kriebel, Mary F. Feitosa, Åsa K. Hedman, Alexander W. Drong, James E. Hayes, John Blangero

School of Medicine Publications

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci …

New Loci For Body Fat Percentage Reveal Link Between Adiposity And Cardiometabolic Disease Risk, Yingchang Lu, Felix R. Day, Stefan Gustafsson, Martin L. Buchkovich, Jianbo Na, Veronique Bataille, Diana L. Cousminer, Zari Dastani, Joanne E. Curran, John Blangero

School of Medicine Publications

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed …

Analysis Of Slc16a11 Variants In 12,811 American Indians: Genotype-Obesity Interaction For Type 2 Diabetes And An Association With Rnasek Expression, Michael Traurig, Robert L. Hanson, Alejandra Marinelarena, Sayuko Kobes, Paolo Piaggi, Shelley A. Cole, Joanne E. Curran, John Blangero, Harald H. H. Goring, Satish Kumar

School of Medicine Publications

Genetic variants in SLC16A11 were recently reported to be associated with type 2 diabetes in Mexican and other Latin American populations. The diabetes risk haplotype had a frequency of 50% in Native Americans from Mexico but was rare in Europeans and Africans. In the current study, we analyzed SLC16A11 in 12,811 North American Indians and found that the diabetes risk haplotype, tagged by the rs75493593 A allele, was nominally associated with type 2 diabetes (P = 0.001, odds ratio 1.11). However, there was a strong interaction with BMI (P = 5.1 × 10(-7)) such that the diabetes association was stronger …

Phenotypic Features Of Circulating Leukocytes From Non-Human Primates Naturally Infected With Trypanosoma Cruzi Resemble The Major Immunological Findings Observed In Human Chagas Disease, Renato Sathler-Avelar, Danielle Marquete Vitelli-Avelar, Armanda Moreira Mattoso-Barbosa, Marcelo Perdigão-De-Oliveira, Ronaldo Peres Costa, Silvana Maria Elói-Santos, Matheus De Souza Gomes, Laurence Rodrigues Do Amaral, Jane F. Vandeberg, John L. Vandeberg

School of Medicine Publications

Background: Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.

Methods and findings: Our data established that …

The Common Genetic Influence Over Processing Speed And White Matter Microstructure: Evidence From The Old Order Amish And Human Connectome Projects, Peter Kochunov, Paul M. Thompson, Anderson M. Winkler, Mary Morrissey, Mao Fu, Thomas R. Coyle, Xiaoming Du, Florian Muellerklein, Anya Savransky, Christopher Gaudiot

School of Medicine Publications

Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior.

Genome- And Epigenome-Wide Association Study Of Hypertriglyceridemic Waist In Mexican American Families, Manju Mamtani, Hemant Kulkarni, Thomas D. Dyer, Harald H. H. Goring, Jennifer L. Neary, Shelley A. Cole, Jack W. Kent Jr., Satish Kumar, David C. Glahn, Michael C. Mahaney, Anthony G. Comuzzie, Laura Almasy, Joanne E. Curran, Ravindranath Duggirala, John Blangero, Melanie A. Carless

School of Medicine Publications

Background: There is growing interest in the hypertriglyceridemic waist (HTGW) phenotype, defined as high waist circumference (≥95 cm in males and ≥80 cm in females) combined with high serum triglyceride concentration (≥2.0 mmol/L in males and ≥1.5 mmol/L in females) as a marker of type 2 diabetes (T2D) and cardiovascular disease. However, the prevalence of this phenotype in high-risk populations, its association with T2D, and the genetic or epigenetic influences on HTGW are not well explored. Using data from large, extended families of Mexican Americans (a high-risk minority population in the USA) we aimed to: (1) estimate the prevalence of …

The Cit's Use In Older Adults In Maracaibo (Venezuela), Carmen Paz, Nelly Garcia, Jenniffer Fernandez, Gladys E. Maestre

School of Medicine Publications

The article describes the possibilities of access to CITs by older adults at a healthcare center of Maracaibo. The analytical resources are taken from the convergence understood as a symbolic field of the meaning of construction in everyday life and appropriation of technology by older adults. The information was collected from 44 subjects, 34 women and 10 men aged between 50 and 85 years old. It is concluded emphasizing the value that older adults give to the use of CITs when interacting with family and friends.

Association Of Urinary Phthalates With Self-Reported Eye Affliction/Retinopathy In Individuals With Diabetes: National Health And Nutrition Examination Survey, 2001-2010, Manju Mamtani, Joanne E. Curran, John Blangero, Hemant Kulkarni

School of Medicine Publications

Background. An epidemiological association between exposure to phthalates and type 2 diabetes (T2D) is known. However, the potential role of environmental phthalates in the complications of T2D is unknown. Methods. Using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2010, we studied the association of 12 urinary phthalate metabolites with self-reported eye affliction/retinopathy in 1,004 participants with diabetes. Data from retinal imaging was used to validate this outcome. Independence of the phthalates→T2D association was studied by adjusting for age, sex, race, marital status, educational attainment, poverty income ratio, physical activity, glycated hemoglobin levels, total serum cholesterol, serum high-density …

The Quantitative-Mfg Test: A Linear Mixed Effect Model To Detect Maternal-Offspring Gene Interactions, Michelle M. Clark, John Blangero, Thomas D. Dyer, Eric M. Sobel, Janet S. Sinsheimer

School of Medicine Publications

Maternal-offspring gene interactions, aka maternal-fetal genotype (MFG) incompatibilities, are neglected in complex diseases and quantitative trait studies. They are implicated in birth to adult onset diseases but there are limited ways to investigate their influence on quantitative traits. We present the Quantitative-MFG (QMFG) test, a linear mixed model where maternal and offspring genotypes are fixed effects and residual correlations between family members are random effects. The QMFG handles families of any size, common or general scenarios of MFG incompatibility, and additional covariates. We develop likelihood ratio tests (LRTs) and rapid score tests and show they provide correct inference. In addition, …

Metabolic Control In Patients With Type 2 Diabetes Mellitus In A Public Hospital In Peru: A Cross-Sectional Study In A Low-Middle Income Country, Irma Huayanay, Felix Guerra-Castañon, Maria Lazo-Porras, Ana Castaneda-Guarderas, Nimmy Josephine Thomas, Ana-Lucia Garcia-Guarniz, Augusto A. Valdivia Bustamante, German Malaga

School of Medicine Publications

Objective

The objective of this study was to assess patients’ achievement of ADA (American Diabetes Association) guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM) outpatient clinic in a low-middle income country (LMIC) setting.

Methods

This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c), and lipid profile. Laboratory parameters and blood …

Lipidomic Risk Score Independently And Cost-Effectively Predicts Risk Of Future Type 2 Diabetes: Results From Diverse Cohorts, Manju Mamtani, Hemant Kulkarni, Gerard Wong, Jacquelyn M. Weir, Christopher K. Barlow, Thomas D. Dyer, Laura Almasy, Michael C. Mahaney, Anthony G. Comuzzie, David C. Glahn, Sarah Williams-Blangero, Ravindranath Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications

Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening.

Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The …

Independent Test Assessment Using The Extreme Value Distribution Theory, Marcio Almeida, Lucy Blondell, Juan M. Peralta, Jack W. Kent Jr., Goo Jun, Tanya M. Teslovich, Christian Fuchsberger, Andrew R. Wood, Alisa K. Manning, Thomas D. Dyer, Ravindranath Duggirala, John Blangero

School of Medicine Publications

The new generation of whole genome sequencing platforms offers great possibilities and challenges for dissecting the genetic basis of complex traits. With a very high number of sequence variants, a naïve multiple hypothesis threshold correction hinders the identification of reliable associations by the overreduction of statistical power. In this report, we examine 2 alternative approaches to improve the statistical power of a whole genome association study to detect reliable genetic associations. The approaches were tested using the Genetic Analysis Workshop 19 (GAW19) whole genome sequencing data. The first tested method estimates the real number of effective independent tests actually being …

A New Strategy For Enhancing Imputation Quality Of Rare Variants From Next-Generation Sequencing Data Via Combining Snp And Exome Chip Data, Young Jin Kim, Taesung Park, Gonçalo Abecasis, Marcio A. Almeida, David Altshuler, Jennifer L. Asimit, Gil Atzmon, Mathew Barber, John Blangero, Thomas D. Dyer

School of Medicine Publications

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize …

Serum Bilirubin Concentration Is Modified By Ugt1a1 Haplotypes And Influences Risk Of Type-2 Diabetes In The Norfolk Island Genetic Isolate, M. C. Benton, R. A. Lea, D. Macartney-Coxson, C. Bellis, M. A. Carless, Joanne E. Curran, D. Eccles, G. K. Chambers, John Blangero, L. R. Griffiths

School of Medicine Publications

Background

Located in the Pacific Ocean between Australia and New Zealand, the unique population isolate of Norfolk Island has been shown to exhibit increased prevalence of metabolic disorders (type-2 diabetes, cardiovascular disease) compared to mainland Australia. We investigated this well-established genetic isolate, utilising its unique genomic structure to increase the ability to detect related genetic markers. A pedigree-based genome-wide association study of 16 routinely collected blood-based clinical traits in 382 Norfolk Island individuals was performed.

Results

A striking association peak was located at chromosome 2q37.1 for both total bilirubin and direct bilirubin, with 29 SNPs reaching statistical significance (P …

Transcriptomics In Type 2 Diabetes: Bridging The Gap Between Genotype And Phenotype, Christopher Jenkinson, Harald H. H. Goring, Rector Arya, John Blangero, Ravindranath Duggirala, Ralph A. Defronzo

School of Medicine Publications

Type 2 diabetes (T2D) is a common,multifactorial disease that is influenced by genetic and environmental factors and their interactions. However, common variants identified by genome wide association studies (GWAS) explain only about 10% of the total trait variance for T2D and less than 5% of the variance for obesity, indicating that a large proportion of heritability is still unexplained. The transcriptomic approach described here uses quantitative gene expression and disease-related physiological data (deep phenotyping) to measure the direct correlation between the expression of specific genes and physiological traits. Transcriptomic analysis bridges the gulf between GWAS and physiological studies. Recent GWAS …

Statin Action Favors Normalization Of The Plasma Lipidome In The Atherogenic Mixed Dyslipidemia Of Mets: Potential Relevance To Statin-Associated Dysglycemia, Peter J. Meikle, Gerard Wong, Ricardo Tan, Philippe Giral, Paul Robillard, Alexina Orsoni, Neil Hounslow, Dianna J. Magliano, Jonathan E. Shaw, Joanne E. Curran, John Blangero

School of Medicine Publications

The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride ( ô 41%), remnant cholesterol ( ô 55%), and LDLcholesterol ( ô 39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in …

Multi-Level Block Permutation, Anderson M. Winkler, Matthew A. Webster, Diego Vidaurre, Thomas E. Nichols, Stephen M. Smith

School of Medicine Publications

Under weak and reasonable assumptions, mainly that data are exchangeable under the null hypothesis, permutation tests can provide exact control of false positives and allow the use of various non-standard statistics. There are, however, various common examples in which global exchangeability can be violated, including paired tests, tests that involve repeated measurements, tests in which subjects are relatives (members of pedigrees) - any dataset with known dependence among observations. In these cases, some permutations, if performed, would create data that would not possess the original dependence structure, and thus, should not be used to construct the reference (null) distribution. To …

Genome-Wide Significant Linkage Of Schizophrenia-Related Neuroanatomical Trait To 12q24, Emma Sprooten, Cota Navin Gupta, Emma Knowles, D. Reese Mckay, Samuel R. Mathias, Joanne E. Curran, Jack W. Kent Jr., Melanie A. Carless, Marcio Almeida, Thomas D. Dyer, Harald H. H. Goring, Rene L. Olvera, Peter T. Fox, Ravi Duggirala, Laura Almasy, John Blangero

School of Medicine Publications

The insula and medial prefrontal cortex (mPFC) share functional, histological, transcriptional and developmental characteristics and they serve higher cognitive functions of theoretical relevance to schizophrenia and related disorders. Meta-analyses and multivariate analysis of structural magnetic resonance imaging (MRI) scans indicate that gray matter density and volume reductions in schizophrenia are the most consistent and pronounced in a network primarily composed of the insula and mPFC. We used source-based morphometry, a multivariate technique optimized for structural MRI, in a large sample of randomly ascertained pedigrees (N = 887) to derive an insula-mPFC component and to investigate its genetic determinants. Firstly, we …

Regulated Internalization Of Nmda Receptors Drives Pkd1-Mediated Suppression Of The Activity Of Residual Cell-Surface Nmda Receptors, Xiaoqian Fang, Haifa Qiao, Bradley R. Groveman, Shuang Feng, Melissa Pflueger, Wen-Kuan Xin, Mohammad K. Ali, Shuang-Xiu Lin, Jindong Xu, Florian Duclot, Mohamed Kabbaj, Wei Wang, Teresa Santiago-Sim

School of Medicine Publications

Background

Constitutive and regulated internalization of cell surface proteins has been extensively investigated. The regulated internalization has been characterized as a principal mechanism for removing cell-surface receptors from the plasma membrane, and signaling to downstream targets of receptors. However, so far it is still not known whether the functional properties of remaining (non-internalized) receptor/channels may be regulated by internalization of the same class of receptor/channels. The N-methyl-D-aspartate receptor (NMDAR) is a principal subtype of glutamate-gated ion channel and plays key roles in neuronal plasticity and memory functions. NMDARs are well-known to undergo two types of regulated internalization – homologous and …

Long-Term Neural And Physiological Phenotyping Of A Single Human, Russell A. Poldrack, Timothy O. Laumann, Oluwasanmi Koyejo, Brenda Gregory, Ashleigh Hover, Mei-Yen Chen, Krzysztof J. Gorgolewski, Joanne E. Curran, Harald Hh Goring, John Blangero

School of Medicine Publications

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for …

Impact Of Specialized Nursery Care For Late Preterm Infants On Nicu Admission Rate And Length Of Stay, Laura Hunt, Gene Hallford, Candace Robledo, Edgardo Szyld, Clara Song

School of Medicine Publications

Objective To compare neonatal intensive care unit (NICU) admission rates and length of stay (LOS) of late preterm infants (LPIs) born before and after opening a specialized care nursery (SCN) at our academic, pediatric tertiary care center with 4,500 total deliveries annually

Study Design Retrospective chart review of inborn LPIs (350/7–366/7 weeks) who were asymptomatic or minimally symptomatic at birth and delivered 7 months before the opening of the SCN (pre-SCN) or 7 months subsequently (post-SCN). Infants were excluded for major congenital anomalies or other conditions requiring immediate NICU admission. The pre-SCN options for care were standard couplet care or …

A Global Perspective On The Influence Of Environmental Exposures On The Nervous System, Desire Tshala-Katumbay, Jean-Claude Mwanza, Diane S. Rohlman, Gladys E. Maestre, Reinaldo B. Oria

School of Medicine Publications

Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, …