Medicine and Health Sciences Commons^™

Retinal Microvasculature In Relation To Central Hemodynamics In A Flemish Population, Fang-Fei Wei, Lutgarde Thijs, Cai-Guo Yu, Jesus D. Melgarejo, Zhen-Yu Zhang, Gladys E. Maestre

School of Medicine Publications

Arterial stiffness and wave reflection predict cardiovascular mortality and morbidity and are associated with renal microvascular disease. We hypothesized that the retinal microvascular traits might be associated with central hemodynamic properties. In 735 randomly recruited Flemish (mean age, 50.3 years; 47.1% women), we derived central pulse pressure and carotid-femoral pulse wave velocity by applanation tonometry and calculated forward (Pf) and backward (Pb) pulse waves, using an automated pressure-based wave separation algorithm. We measured central retinal arteriolar (CRAE) and venular equivalent and their ratio, using IVAN software (Vasculomatic ala Nicola, version 1.1). Mean values for pulse wave velocity (n=554), Pf and …

Wrap-Around Services To Older Adults With Dementia: Collaboration, Education, And Prevention As A Model For Integration Of Primary Care And Neurobehavioral Health, Gladys E. Maestre, Francisco Fernandez

School of Medicine Publications

Background: Medical care in the Rio Grande Valley (RGV) is fragmented and difficult to navigate, especially for older adults with cognitive decline and dementia. The communities are eager to have a new healthcare delivery system that integrate community-based aging services to provide integrated, team collaborative better health care in our communities. The University of Texas RGV School of Medicine, in collaboration with its affiliates in the regional healthcare systems, is a partner providing comprehensive care across the life-cycle bridging science, social services and patient care. Our interprofessional team collaborative emphasizes safe, appropriate, and effective neurobehavioral care, employing evidence-based medicine in …

A Triphenylethylene Nonsteroidal Serm Attenuates Cervical Cancer Growth, Neeraj Chauhan, Diane M. Maher, Murali M. Yallapu, Bilal B. Hafeez, Man M. Singh, Subhash C. Chauhan, Meena Jaggi

School of Medicine Publications

Selective estrogen receptor modulator drug molecules of triphenylethylene family have gained considerable attention as anti-cancer agents. Despite recent advances in screening and development of HPV vaccines, cervical cancer remains one of the deadliest malignancies as advanced stage metastatic disease is mostly untreatable, thus warrants newer therapeutic strategies. Ormeloxifene (ORM) is a well-known SERM of triphenylethylene family that has been approved for human use, thus represents an ideal molecule for repurposing. In this study, we for the first time have demonstrated the anti-cancerous properties of ormeloxifene in cervical cancer. Ormeloxifene efficiently attenuated tumorigenic and metastatic properties of cervical cancer cells via …

Expression Of Integrin And Tgfbi In Human Retinal Pericytes, Andrew T C Tsin, Brenda Su, Laura Valdez, Edgar Serrato

School of Medicine Publications

Purpose: The aim for this study is to investigate the expression of integrin α3, β1 and TGF-β induced protein (TGFBI) and the secretion of TGFBI by primary culture of human retinal pericytes (pHRP). Evidence suggests that chronic diabetes associate with HRP apoptosis leading to the development of diabetic retinopathy.

Methods: pHRP (Cell Systems) were cultured in complete media (15mM glucose) in a humidified, 5% CO2, 37°C condition. Cells were seeded at passage 6 to 8 into a 24 well-plate with coverslips or P10 dishes. Cells (85% confluence) media were then replaced by DMEM media with euglycemic glucose (5.5mM) or hyperglycemic …

Gen-Z Ambassadors: Students Supporting Persons With Alzheimer’S Disease And Their Caregivers In The Rio Grande Valley, Sofia G. Homes, Samantha R. Woo, Ashley G. Caldera, Sergio N. Gonzalez-Eymard, Rosa V. Pirela, Francisco Fernandez, Gladys E. Maestre

School of Medicine Publications

Background: Youth participation in policy, research, education and community development initiatives is a right embedded in the United Nations Convention on the Rights of the Child (UNCRC, General Assembly, 1989). However, avenues for youth participation in health promotion and care remains limited. Our Ambassadors program prepares high-school students on the Texas-Mexico border to understand and empathize with persons with Alzheimer’s disease (PwAD) and to empower their family and caregivers, consummating the UNCRC in the service of transformative community change actions.

Methods: Our long-term objective is youth participation, defined as practices that involve collaboration between students and various community stakeholders …

Gene Expression Across Mammalian Organ Development, Margarida Cardoso-Moreira, Jean Halbert, Delphine Valloton, Britta Velten, Chunyan Chen, Yi Shao, Angélica Liechti, Kelly Ascenção, Coralie Rummel, John L. Vandeberg

School of Medicine Publications

The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified developmental stage correspondences across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes …

The Role Of T-Cell Protein Tyrosine Phosphatase In Epithelial Carcinogenesis, Liza D. Morales, Anna K. Archbold, Serena Olivarez, Thomas J. Slaga, John Digiovanni, Dae Joon Kim

School of Medicine Publications

T-cell protein tyrosine phosphatase (TC-PTP, encoded by PTPN2) is a non-receptor PTP that is mostly highly expressed in hematopoietic tissues. TC-PTP modulates a variety of physiological functions including cell cycle progression, cell survival and proliferation, and hematopoiesis through tyrosine dephosphorylation of its target substrates, such as EGFR, JAK1, JAK3, STAT1, and STAT3. Studies with whole or tissue-specific loss of TC-PTP function transgenic mice have shown that TC-PTP has crucial roles in the regulation of the immune response, insulin signaling, and oncogenic signaling. More recently, generation of epidermal-specific TC-PTP-deficient mice for use in multistage skin carcinogenesis bioassays demonstrated that TC-PTP …

Investigation Of Precise Molecular Mechanistic Action Of Tobacco-Associated Carcinogen ‘Nnk’ Induced Carcinogenesis: A System Biology Approach, Ad Anukriti, Anupam Dhasmana, Swati Uniyal, Pallavi Somvanshi, Uma Bhardwaj, Meenu Gupta, Shafiul Haque, Mohtashim Lohani, Dhruv Kumar, Janne Ruokolainen, Kavindra Kumar Kesari

School of Medicine Publications

Cancer is the second deadliest disease listed by the WHO. One of the major causes of cancer disease is tobacco and consumption possibly due to its main component, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A plethora of studies have been conducted in the past aiming to decipher the association of NNK with other diseases. However, it is strongly linked with cancer development. Despite these studies, a clear molecular mechanism and the impact of NNK on various system-level networks is not known. In the present study, system biology tools were employed to understand the key regulatory mechanisms and the perturbations that will happen in the …

Transferrin-Bearing Liposomes Entrapping Plumbagin For Targeted Cancer Therapy, Intouch Sakpakdeejaroen, Sukrut Somani, Partha Laskar, Margaret Mullin, Christine Dufès

School of Medicine Publications

The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anticancer properties, is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation, and its rapid elimination in vivo. We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumours after intravenous administration. The objectives of this study were therefore to prepare and …

Physical Activity And Its Association With Depression In The Diabetic Hispanic Population, Sukaina Rizvi, Ali M. Khan

School of Medicine Publications

Introduction Hispanics are the largest ethnic minority group in the United States. The prevalence of depression and co-morbid depression in the Hispanic population is well-recognized. The positive association between physical activity and psychological health improves mood, emotional well-being, and prognostic outcome.

Objectives There are two aspects of our research paper. First, it critically reviews the available literature showing the correlation between physical exercise and depression. Second, it analyzes the association between exercise and depression in uncontrolled diabetic Hispanics using data collected from the local community intervention program.

Method A chi-square analysis was conducted to examine whether levels of physical activity …

Targeting Iκappab Kinases For Cancer Therapy, Nikee Awasthee, Vipin Rai, Srinivas Chava, Palanisamy Palanisamy Nallasamy, Ajaikumar B. Kunnumakkara, Anupam Bishayee, Subhash C. Chauhan, Kishore B. Challagundla, Subash C. Gupta

School of Medicine Publications

The inhibitory kappa B kinases (IKKs) and IKK related kinases are crucial regulators of the pro-inflammatory transcription factor, nuclear factor kappa B (NF-κB). The dysregulation in the activities of these kinases has been reported in several cancer types. These kinases are known to regulate survival, proliferation, invasion, angiogenesis, and metastasis of cancer cells. Thus, IKK and IKK related kinases have emerged as an attractive target for the development of cancer therapeutics. Several IKK inhibitors have been developed, few of which have advanced to the clinic. These inhibitors target IKK either directly or indirectly by modulating the activities of other signaling …

Exome Sequencing Of 20,791 Cases Of Type 2 Diabetes And 24,440 Controls, Jason Flannick, Josep M. Mercader, Christian Fuchsberger, Miriam S. Udler, Anubha Mahajan, Jennifer Wessel, Gil Atzmon, John Blangero, Ravindranath Duggirala, Benjamin Glaser

School of Medicine Publications

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10−3) and candidate genes from knockout mice (P = 5.2 × …

Genome-Wide Association Study Identifies 30 Loci Associated With Bipolar Disorder, Eli A. Stahl, Gerome Breen, Andreas J. Forstner, Andrew Mcquillin, Stephan Ripke, Vassily Trubetskoy, Manuel Mattheisen, Yunpeng Wang, Jonathan R. I. Coleman, Ney Alliey-Rodriguez

School of Medicine Publications

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1×10−4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5×10−8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.

Impact Of A Formal Patient Safety And Quality Improvement Curriculum: A Prospective, Controlled Trial, Nausheen Jamal, Sarah N. Bowe, Michael J. Brenner, Karthik Balakrishnan, John P. Bent

School of Medicine Publications

Objective

To assess the impact of implementing a dedicated Patient Safety and Quality Improvement (PSQI) curriculum for otolaryngology residents.

Methods

Residents in two otolaryngology residency programs were recruited to participate in the study. Residents at institution A (intervention group) participated in a formal, newly developed, year-long PSQI curriculum. Residents at institution B (control group) participated in traditional, morbidity, and mortality conference-based PSQI education, with no formal curriculum in place. Curriculum participants completed anonymous surveys to assess learner satisfaction. Validated instruments were administered to assess for changes in resident confidence in the ability to develop PSQI projects, their attitudes toward patient …

Doxycycline Didn’T Cure The Fever! An Interesting Case Of Large Granular Lymphocytic (Lgl) Leukemia With Secondary Hemophagocytic Lymphohistiocytosis (Hlh)., Dayan Ojeda Damas, Ayesha Hamid, Kevin Wu, Michael Lapelusa, Nabeel Sarhill, Henry Kwang

School of Medicine Publications

HLH: A rare association with LGL Leukemia Dayan Ojeda-Damas MD, Ayesha Hamid MD, Kevin Wu MD, Michael Lapelusa MS-3, Nabeel Sarhill MD, Henry Kwang MD University of Texas Rio Grande Valley. Internal Medicine Residency at Valley Baptist Medical Center. Harlingen, TX Introduction Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome characterized by excessive immune activation. It is diagnosed in patients of all ages and is classified as either primary from gene mutations or secondary from various triggers. We present an interesting case of HLH in a patient with large granular lymphocytic leukemia (LGL). Presentation A 53-year-old female with a questionable …

Genetic Analysis Localizes A Novel Locus On Chromosome 4q For The Glaucoma Endophenotype, Cup-To-Disc Ratio: The Jiri Eye Study, Sarah E. Miller, Nicholas B. Blackburn, Suman S. Thapa, Sandra Laston, Satish Kumar, Juan M. Peralta, Janardan Subedi, John Blangero, Sarah Williams-Blangero, Matthew P. Johnson

School of Medicine Publications

Purpose: Glaucoma is a heterogeneous disease influenced by genetic risk factors. However, not all genetic risk factors have been identified. The aim of this project is to localize genetic factors influencing known glaucoma endophenotypes: intraocular pressure (IOP), central corneal thickness (CCT), and vertical cup-to-disc ratio (VCDR).

Methods: This family-based study design utilizes phenotypic and genomic data from a single well-characterized pedigree residing in the Jiri region of Nepal. Measures of IOP, CCT and VCDR were obtained by Goldmann applanation tonometry, OCT, and slit lamp biomicroscopy, respectively. Using a genome-wide genotype data set (~550,000 SNPs), we performed a genome-wide linkage scan …

Heritability Of Fetal Hemoglobin, White Cell Count, And Other Clinical Traits From A Sickle Cell Disease Family Cohort, Erik L. Bao, Caleb A. Lareau, Carlo Brugnara, Isabel Fulcher, Caroline Barau, Stephane Moutereau, Anoosha Habibi, Bouchra Badaoui, Jugurtha Berkenou, Michael Mahaney

School of Medicine Publications

Sickle cell disease (SCD) is the most common monogenic disorder in the world. Notably, there is extensive clinical heterogeneity in SCD that cannot be fully accounted for by known factors, and in particular, the extent to which the phenotypic diversity of SCD can be explained by genetic variation has not been reliably quantified. Here, in a family-based cohort of 449 patients with SCD and 755 relatives, we first show that 5 known modifiers affect 11 adverse outcomes in SCD to varying degrees. We then utilize a restricted maximum likelihood procedure to estimate the heritability of 20 hematologic traits, including fetal …

Novel Pharmacological Therapy In Type 2 Diabetes Mellitus With Established Cardiovascular Disease: Current Evidence, Leonardo Pozo, Fatimah Bello, Andres Suarez, Francisco E. Ochoa-Martinez, Yamely Mendez, Chelsea H. Chang, Salim Surani

School of Medicine Publications

Cardiovascular diseases (CVDs) remain the leading cause of death in the world and in most developed countries. Patients with type 2 diabetes mellitus (T2DM) suffer from both microvascular and macrovascular diseases and therefore have higher rates of morbidity and mortality compared to those without T2DM. If current trends continue, the Center for Disease Control and Prevention estimates that 1 in 3 Americans will have T2DM by year 2050. As a consequence of the controversy surrounding rosiglitazone and the increasing prevalence of diabetes and CVDs, in 2008 the Food and Drug Administration (FDA) established new expectations for the evaluation of new …

Use Of Transcranial Magnetic Stimulation For Depression, Sukaina Rizvi, Ali M. Khan

School of Medicine Publications

Transcranial magnetic stimulation (TMS), a research tool with various effects on brain cells, can depolarize cerebral neurons noninvasively. This method offers temporal and spatial resolution and can be combined with other neurocognitive and neuro-experimental techniques. Prefrontal TMS therapy repeated daily for four to six weeks is a neuromodulation technique approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD) in patients resistant to medications. This technique utilizes electromagnetic induction to excite neuronal cells. Several recent studies have enhanced our understanding of this novel treatment intervention. This report reviews recent studies on the mechanism of …

The Re-Emerging Association Between Tuberculosis And Diabetes: Lessons From Past Centuries, Jose Cadena, Selvalakshmi Rathinavelu, Juan Carlos Lopez Alvarenga, Blanca I. Restrepo

School of Medicine Publications

The association between tuberculosis (TB) and diabetes mellitus (DM) had a common place in the literature up to the first half of the 20th century, but virtually disappeared with the discovery of insulin to treat DM and antibiotics to cure TB. In the late 1990s the literature began to re-emerge with the worldwide increase in type 2 DM, particularly in TB-endemic countries. Today, type 2 DM is the most prevalent comorbidity among TB patients and the World Health Organization considers it a threat to TB control. We summarize the literature on TB and DM up to the 1960s. Then we …

The Concept Of Mania In Traditional Andean Culture, Marucela Juana Uscamayta-Ayvar, Rodolfo Sanchez Garrafa, Javier I. Escobar, Gabriel A. De Erausquin

School of Medicine Publications

No abstract provided.

Minocycline Inhibits Pdgf-Bb-Induced Human Aortic Smooth Muscle Cell Proliferation And Migration By Reversing Mir-221- And -222-Mediated Reck Suppression, Yusuke Higashi, Srinivas Mummidi, Sergiy Sukhanov, Tadashi Yoshida, Makoto Noda, Patrice Delafontaine, Bysani Chandrasekar

School of Medicine Publications

Minocycline, a tetracycline antibiotic, is known to exert vasculoprotective effects independent of its anti-bacterial properties; however the underlying molecular mechanisms are not completely understood. Reversion Inducing Cysteine Rich Protein with Kazal Motifs (RECK) is a cell surface expressed, membrane anchored protein, and its overexpression inhibits cancer cell migration. We hypothesized that minocycline inhibits platelet-derived growth factor (PDGF)-induced human aortic smooth muscle cell (SMC) proliferation and migration via RECK upregulation. Our data show that the BB homodimer of recombinant PDGF (PDGF-BB) induced SMC migration and proliferation, effects significantly blunted by pre-treatment with minocycline. Further investigations revealed that PDGF-BB induced PI3K-dependent AKT …

Use Of Gabapentin In The Treatment Of Substance Use And Psychiatric Disorders: A Systematic Review, Saeed Ahmed, Ramya Bachu, Vijaya P. Kotapati, Mahwish Adnan, Rizwan A. Ahmed, Umer Farooq, Hina Saeed, Ali M. Khan, Aarij Zubair, Iqra Qamar, Gulshan Begum

School of Medicine Publications

Objective: Gabapentin (GBP) is an anticonvulsant medication that is also used to treat restless legs syndrome (RLS) and posttherapeutic neuralgia. GBP is commonly prescribed off-label for psychiatric disorders despite the lack of strong evidence. However, there is growing evidence that GBP may be effective and clinically beneficial in both psychiatric disorders and substance use disorders. This review aimed to perform a systematic analysis of peer-reviewed published literature on the efficacy of GBP in the treatment of psychiatric disorders and substance use disorders.

Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. …

Minocycline Inhibits Pdgf-Bb-Induced Human Aortic Smooth Muscle Cell Proliferation And Migration By Reversing Mir-221- And -222-Mediated Reck Suppression, Yusuke Higashi, Srinivas Mummidi, Sergiy Sukhanov, Tadashi Yoshida, Makoto Noda, Patrice Delafontaine, Bysani Chandrasekar

School of Medicine Publications

Minocycline, a tetracycline antibiotic, is known to exert vasculoprotective effects independent of its anti-bacterial properties; however the underlying molecular mechanisms are not completely understood. Reversion Inducing Cysteine Rich Protein with Kazal Motifs (RECK) is a cell surface expressed, membrane anchored protein, and its overexpression inhibits cancer cell migration. We hypothesized that minocycline inhibits platelet-derived growth factor (PDGF)-induced human aortic smooth muscle cell (SMC) proliferation and migration via RECK upregulation. Our data show that the BB homodimer of recombinant PDGF (PDGF-BB) induced SMC migration and proliferation, effects significantly blunted by pre-treatment with minocycline. Further investigations revealed that PDGF-BB induced PI3K-dependent AKT …

Peptides Identified On Monocyte-Derived Dendritic Cells: A Marker For Clinical Immunogenicity To Fviii Products, Wojciech Jankowski, Yara Park, Joseph Mcgil, Eugene Maraskovsky, Marco Hofmann, Vincent P. Diego, Bernadette W. Luu, Tom E. Howard, Roberta Kellerman, Nigel S. Key, Zuben E. Sauna

School of Medicine Publications

The immunogenicity of protein therapeutics is an important safety and efficacy concern during drug development and regulation. Strategies to identify individuals and subpopulations at risk for an undesirable immune response represent an important unmet need. The major histocompatibility complex (MHC)–associated peptide proteomics (MAPPs) assay directly identifies the presence of peptides derived from a specific protein therapeutic on a donor’s MHC class II (MHC-II) proteins. We applied this technique to address several questions related to the use of factor VIII (FVIII) replacement therapy in the treatment of hemophilia A (HA). Although .12 FVIII therapeutics are marketed, most fall into 3 categories: …

The Emergence Of Population Health In Us Academic Medicine, Marc N. Gourevitch, Lesley H. Curtis, Maureen S. Durkin, Angela Fagerlin, Annetine C. Gelijns, Richard Platt, Belinda M. Reininger, Judith Wylie-Rosett, Katherine Jones, William M. Tierney

School of Medicine Publications

Importance In response to rapidly growing interest in population health, academic medical centers are launching department-level initiatives that focus on this evolving discipline. This trend, with its potential to extend the scope of academic medicine, has not been well characterized.

Objective To describe the emergence of departments of population health at academic medical centers in the United States, including shared areas of focus, opportunities, and challenges.

Design, Setting, and Participants This qualitative study was based on a structured in-person convening of a working group of chairs of population health–oriented departments on November 13 and 14, 2017, complemented by a survey …

An Evaluation Of Whether A Gestational Weight Gain Of 5 To 9 Kg For Obese Women Optimizes Maternal And Neonatal Health Risks, Abaigeal Thompson, James A. Thompson

School of Medicine Publications

Background

Maternal obesity has a wide range of health effects on both the pregnant woman and developing fetus. The clinical significance of these disorders, combined with a dramatically increasing prevalence of obesity among pregnant women has precipitated a major health crisis in the United States. The most commonly used recommendations for gestational weight gain were established by the Institute of Medicine (IOM) in 2009 and have become well known and often adopted. The authors of the IOM report acknowledged that the recommended gestational weight gain of 5 to 9 kg for obese women whose body mass index was greater than …

Analysis Of Serum Changes In Response To A High Fat High Cholesterol Diet Challenge Reveals Metabolic Biomarkers Of Atherosclerosis, Biswapriya B. Misra, Sobha Puppala, Anthony G. Comuzzie, Michael Mahaney, Jane F. Vandeberg, Michael Olivier, Laura A. Cox

School of Medicine Publications

Atherosclerotic plaques are characterized by an accumulation of macrophages, lipids, smooth muscle cells, and fibroblasts, and, in advanced stages, necrotic debris within the arterial walls. Dietary habits such as high fat and high cholesterol (HFHC) consumption are known risk factors for atherosclerosis. However, the key metabolic contributors to diet-induced atherosclerosis are far from established. Herein, we investigate the role of a 2-year HFHC diet challenge in the metabolic changes of development and progression of atherosclerosis. We used a non-human primate (NHP) model (baboons, n = 60) fed a HFHC diet for two years and compared metabolomic profiles in serum from …

Rsk2-Mediated Elk3 Activation Enhances Cell Transformation And Breast Cancer Cell Growth By Regulation Of C-Fos Promoter Activity, Sun-Mi Yoo, Cheol-Jung Lee, Hyun-Jung An, Joo Young Lee, Hye Suk Lee, Han Chang Kang, Sung-Jun Cho, Seung-Min Kim, Juhee Park, Dae Joon Kim, Yong-Yeon Cho

School of Medicine Publications

Ribosomal S6 kinase 2 (RSK2), regulated by Ras/Raf/MEKs/ERKs, transmits upstream activation signals to downstream substrates including kinases and transcription and epigenetic factors. We observed that ELK members, including ELK1, 3, and 4, highly interacted with RSK2. We further observed that the RSK2-ELK3 interaction was mediated by N-terminal kinase and linker domains of RSK2, and the D and C domains of ELK3, resulting in the phosphorylation of ELK3. Importantly, RSK2-mediated ELK3 enhanced c-fos promoter activity. Notably, chemical inhibition of RSK2 signaling using kaempferol (a RSK2 inhibitor) or U0126 (a selective MEK inhibitor) suppressed EGF-induced c-fos promoter activity. Moreover, functional deletion of …

Rediscovering The Value Of Families For Psychiatric Genetics Research, David C. Glahn, Vishwajit Nimgaonkar, Henriette Raventós, Javier Contreras, Andrew M. Mcintosh, Pippa Thomson, Assen Jablensky, Nicholas B. Blackburn, Juan M. Peralta, Joanne E. Curran, Laura Almasy, John Blangero

School of Medicine Publications

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples …