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Prevalence And Risk Factors Of Major Depressive Disorder In Hiv/Aids As Seen In Semi-Urban Entebbe District, Uganda, Eugene Kinyanda, Susan Hoskins, Juliet Nakku, Saira Nawaz, Vikram Patel

Dartmouth Scholarship

Background:

Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda.

Methods:

A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda.

Results:

Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. …

Cd2ap Regulates Sumoylation Of Cin85 In Podocytes, Irini Tossidou, Rainer Niedenthal, Malte Klaus, Beina Teng, Kirstin Worthmann, Benjamin King, Kevin Peterson

Dartmouth Scholarship

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

Rice Consumption Contributes To Arsenic Exposure In Us Women, Diane Gilbert-Diamond, Kathryn L. Cottingham, Joann F. Gruber, Tracy Punshon, Vicki Sayarath, A. Jay Gandolfi, Emily R. Baker, Brian P. Jackson, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n …

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …

Effects Of Prenatal Food And Micronutrient Supplementation On Child Growth From Birth To 54 Months Of Age: A Randomized Trial In Bangladesh, Ashraful Islam Khan, Iqbal Kabir, Eva-Charlotte Ekström, Kajsa Åsling-Monemi, Dewan Shamsul Alam, Edward A. Frongillo Jr., Md Yunus, Shams Arifeen, Lars-Åke Persson

Faculty Publications

Background: There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations (MMS) on their offspring's growth. We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth. The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0-54 months and a combination of these interventions would further improve these outcomes.

Methods: In the large, randomized MINIMat trial (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436 pregnant women were enrolled …

Changes In Spirituality Partly Explain Health-Related Quality Of Life Outcomes After Mindfulness-Based Stress Reduction., Jeffrey M Greeson, Daniel M Webber, Moria J Smoski, Jeffrey G Brantley, Andrew G Ekblad, Edward C Suarez, Ruth Quillian Wolever

College of Science & Mathematics Departmental Research

Mindfulness-Based Stress Reduction is a secular behavioral medicine program that has roots in meditative spiritual practices. Thus, spirituality may partly explain Mindfulness-Based Stress Reduction outcomes. Participants (N = 279; M (SD) age = 45(12); 75% women) completed an online survey before and after an 8-week Mindfulness-Based Stress Reduction program. Structural equation modeling was used to test the hypothesis that, following Mindfulness-Based Stress Reduction, the relationship between enhanced mindfulness and improved health-related quality of life is mediated by increased daily spiritual experiences. Changes in both spirituality and mindfulness were significantly related to improvement in mental health. Although the initial mediation hypothesis …

Widespread Regulation Of Mirna Biogenesis At The Dicer Step By The Cold-Inducible Rna-Binding Protein, Rbm3, Julie Pilotte, Esther E. Dupont-Versteegden, Peter W. Vanderklish

Physical Therapy Faculty Publications

MicroRNAs (miRNAs) play critical roles in diverse cellular events through their effects on translation. Emerging data suggest that modulation of miRNA biogenesis at post-transcriptional steps by RNA-binding proteins is a key point of regulatory control over the expression of some miRNAs and the cellular processes they influence. However, the extent and conditions under which the miRNA pathway is amenable to regulation at posttranscriptional steps are poorly understood. Here we show that RBM3, a cold-inducible, developmentally regulated RNA-binding protein and putative protooncogene, is an essential regulator of miRNA biogenesis. Utilizing miRNA array, Northern blot, and PCR methods, we observed that over …

Switches, Excitable Responses And Oscillations In The Ring1b/Bmi1 Ubiquitination System., Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots …

Probiotic Bacterial Strains Differentially Modulate Macrophage Cytokine Production In A Strain-Dependent And Cell Subset-Specific Manner., N. Habil, W. Al-Murrani, J. Beal, A. D. Foey

School of Biomedical Sciences

Gut mucosal macrophages play a pivotal role in driving mucosal immune responses, resulting in either activation of inflammatory immune responses to pathogenic challenge or tolerance to beneficial luminal contents such as food and commensal bacteria. Macrophage responses elicited are dependent on tissue environment and the resulting cell subset, where homeostatic macrophages resemble the M2 macrophage subset and inflammatory macrophages resemble M1s. Probiotics can modulate macrophage function with outcome dependent on subset present. Using a THP-1 monocyte cell line-derived model of CD14high/low M1 and M2 macrophages, the aim of this study was to investigate the immunomodulatory effects of a panel of …

Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg

Dartmouth Scholarship

Fold recognition techniques take advantage of the limited number of overall structural organizations, and have become increasingly effective at identifying the fold of a given target sequence. However, in the absence of sufficient sequence identity, it remains difficult for fold recognition methods to always select the correct model. While a native-like model is often among a pool of highly ranked models, it is not necessarily the highest-ranked one, and the model rankings depend sensitively on the scoring function used. Structure elucidation methods can then be employed to decide among the models based on relatively rapid biochemical/biophysical experiments.

A Brief Overview Of Adolescent Developmental Problems In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

Several adolescent developmental problems in Hong Kong are briefly reviewed in this paper. First, rising adolescent substance abuse trends are described. Second, Internet use problems and Internet addiction among young people are examined. Third, worrying trends in adolescent sexuality are identified. Fourth, phenomena on bullying among young people are reviewed. Finally, phenomena related to adolescent materialistic orientation are focused upon. With reference to these adolescent developmental problems, possible solutions are briefly discussed particularly with reference to the ecological perspective. It is argued that the related scientific literature provides useful pointers for designing the curriculum in the extension phase of the …

Effect Of Protein Kinase C Delta (Pkc-Δ) Inhibition On The Transcriptome Of Normal And Systemic Sclerosis Human Dermal Fibroblasts In Vitro., Peter J Wermuth, Sankar Addya, Sergio A Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Previous studies demonstrated that protein kinase C- δ (PKC-δ) inhibition with the selective inhibitor, rottlerin, resulted in potent downregulation of type I collagen expression and production in normal human dermal fibroblasts and abrogated the exaggerated type I collagen production and expression in fibroblasts cultured from affected skin from patients with the fibrosing disorder systemic sclerosis (SSc). To elucidate the mechanisms involved in the ability of PKC-δ to regulate collagen production in fibroblasts, we examined the effects of PKC-δ inhibition on the transcriptome of normal and SSc human dermal fibroblasts. Normal and SSc human dermal fibroblasts were incubated with rottlerin (5 …

Nanoparticulate Formulations Of Mithramycin Analogs For Enhanced Cytotoxicity, Daniel Scott, Jürgen Rohr, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH …

An Automated Internet Application To Help Patients With Bipolar Disorder Track Social Rhythm Stabilization., Daniel Z Lieberman, Susan Swayze, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

This column describes a pilot study of a fully automated, Internet-based program that provides a key element of interpersonal and social rhythm therapy, a form of psychotherapy shown to be effective in the treatment of bipolar disorder when combined with mood-stabilizing medication. Participants (N=64) recorded the time they completed activities of daily living and their mood at the time of each entry. After 90 days they demonstrated a 31% increase in social rhythm stability and a small, though statistically significant, decrease in symptoms of abnormal mood. Internet-based programs can enhance access to a best practice in the management of bipolar …

An Engineered Approach To Stem Cell Culture: Automating The Decision Process For Real-Time Adaptive Subculture Of Stem Cells, Dai Fei Elmer Ker, Lee E. Weiss, Silvina N. Junkers, Mei Chen, Zhaozheng Yin, Mike F. Sandbothe, Seungil Huh, Sungeun Eom, Ryoma Bise, Elvira Osuna-Highley, Takeo Kanade, Phil Gordon Campbell

Computer Science Faculty Research & Creative Works

Current cell culture practices are dependent upon human operators and remain laborious and highly subjective, resulting in large variations and inconsistent outcomes, especially when using visual assessments of cell confluency to determine the appropriate time to subculture cells. Although efforts to automate cell culture with robotic systems are underway, the majority of such systems still require human intervention to determine when to subculture. Thus, it is necessary to accurately and objectively determine the appropriate time for cell passaging. Optimal stem cell culturing that maintains cell pluripotency while maximizing cell yields will be especially important for efficient, cost-effective stem cell-based therapies. …

Differential Il-21 Signaling In Apcs Leads To Disparate Th17 Differentiation In Diabetes-Susceptible Nod And Diabetes-Resistant Nod.Idd3 Mice., Sue M. Liu, David H. Lee, Jenna M. Sullivan, Denise Chung, Anneli Jäger, Bennett O V. Shum, Nora E. Sarvetnick, Ana C. Anderson, Vijay K. Kuchroo

Journal Articles: Regenerative Medicine

Type 1 diabetes (T1D) is an autoimmune disease that shows familial aggregation in humans and likely has genetic determinants. Disease linkage studies have revealed many susceptibility loci for T1D in mice and humans. The mouse T1D susceptibility locus insulin-dependent diabetes susceptibility 3 (Idd3), which has a homologous genetic interval in humans, encodes cytokine genes Il2 and Il21 and regulates diabetes and other autoimmune diseases; however, the cellular and molecular mechanisms of this regulation are still being elucidated. Here we show that T cells from NOD mice produce more Il21 and less Il2 and exhibit enhanced Th17 cell generation compared with …

The Raf/Mek/Extracellular Signal-Regulated Kinase 1/2 Pathway Can Mediate Growth Inhibitory And Differentiation Signaling Via Androgen Receptor Downregulation In Prostate Cancer Cells., Seung-Keun Hong, Jin-Hwan Kim, Ming-Fong Lin, Jong-In Park

Journal Articles: Biochemistry & Molecular Biology

Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase …

Combined Fluorescence And Reflectance Spectroscopy For In Vivo Quantification Of Cancer Biomarkers In Low- And High-Grade Glioma Surgery, Pablo A. ValdéS, Anthony Kim, Keith D. Paulsen, Frederic Leblond, Olga M. Conde, Brent T. Harris, David W. Roberts

Dartmouth Scholarship

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin …

Chromosome Missegregation In Human Cells Arises Through Specific Types Of Kinetochore–Microtubule Attachment Errors, Sarah L. Thompson, Duane A. Compton

Dartmouth Scholarship

Most solid tumors are aneuploid, and many missegregate chromosomes at high rates in a phenomenon called chromosomal instability (CIN). CIN reflects the erosion of mitotic fidelity, and it correlates with poor patient prognosis and drug resistance. The most common mechanism causing CIN is the persistence of improper kinetochore–microtubule attachments called merotely. Chromosomes with merotelic kinetochores often manifest as lagging chromosomes in anaphase, suggesting that lagging chromosomes fail to segregate properly. However, it remains unknown whether the lagging chromosomes observed in anaphase segregate to the correct or incorrect daughter cell. To address this question, we tracked the segregation of a single …

Innate And Adaptive Immunity To The Nematode Strongyloides Stercoralis In A Mouse Model., Sandra Bonne-Annee, Jessica A. Hess, David Abraham

Department of Microbiology and Immunology Faculty Papers

Mice have been used to the study the mechanisms of protective innate and adaptive immunity to larval Strongyloides stercoralis. During primary infection, neutrophils and eosinophils are attracted by parasite components and kill the larvae by release of granule products. Eosinophils also function as antigen-presenting cells for the induction of a Th2 response. B cells produce both IgM and IgG that collaborate with neutrophils to kill worms in the adaptive immune response. Vaccine studies have identified a recombinant diagnostic antigen that induced high levels of immunity to infection with S. stercoralis in mice. These studies demonstrate that there are redundancies in …

Abca12-Mediated Lipid Transport And Snap29-Dependent Trafficking Of Lamellar Granules Are Crucial For Epidermal Morphogenesis In A Zebrafish Model Of Ichthyosis., Qiaoli Li, Michael Frank, Masashi Akiyama, Shiu-Ying Ho, Hiroshi Shimizu, Christine Thisse, Bernard Thisse, Eli Sprecher, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5-6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and …

Pathobiological Implications Of Muc16 Expression In Pancreatic Cancer., Dhanya Haridas, Subhankar Chakraborty, Moorthy P. Ponnusamy, Imayavaramban Lakshmanan, Satyanarayana Rachagani, Eric Cruz, Sushil Kumar, Srustidhar Das, Subodh M. Lele, Judy M. Anderson, Uwe A. Wittel, Michael A. Hollingsworth, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 …

Characterization Of Street Food Consumption In Palermo: Possible Effects On Health, Silvio Buscemi, Annamaria Barile, Vincenza Maniaci, John A. Batsis

Dartmouth Scholarship

Background: Street Food (SF) consists of out-of-home food consumption and has old, historical roots with complex social-economic and cultural implications. Despite the emergence of modern fast food, traditional SF persists worldwide, but the relationship of SF consumption with overall health, well-being, and obesity is unknown.

Methods: This is an observational, cross-sectional study. The study was performed in Palermo, the largest town of Sicily, Italy. Two groups were identified: consumers of SF (n = 687) and conventional restaurant food (RES) consumers (n = 315). Study subjects answered a questionnaire concerning their health conditions, nutritional preferences, frequency of consumption of SF and …

Human Rna Polymerase Ii-Association Factor 1 (Hpaf1/Pd2) Regulates Histone Methylation And Chromatin Remodeling In Pancreatic Cancer., Parama Dey, Moorthy P. Ponnusamy, Shonali Deb, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri-methylation at histone H3 lysine 4 residues in …

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Proliferating Cell Nuclear Antigen Is Required For Loading Of The Smcx/Kmd5c Histone Demethylase Onto Chromatin., Zhihui Liang, Marc Diamond, Johanna A Smith, Matthias Schnell, René Daniel

Department of Medicine Faculty Papers

UNLABELLED: ABSTRACT:

BACKGROUND: Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking.

RESULTS: In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction. We identified a PCNA-interaction protein motif (PIP box) in the …

Microarray-Based Cancer Prediction Using Single Genes., Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Although numerous methods of using microarray data analysis for cancer classification have been proposed, most utilize many genes to achieve accurate classification. This can hamper interpretability of the models and ease of translation to other assay platforms. We explored the use of single genes to construct classification models. We first identified the genes with the most powerful univariate class discrimination ability and then constructed simple classification rules for class prediction using the single genes.

RESULTS: We applied our model development algorithm to eleven cancer gene expression datasets and compared classification accuracy to that for standard methods including Diagonal Linear …

Regional Gray Matter Correlates Of Perceived Emotional Intelligence, Nancy S. Koven, Robert M. Roth, Matthew A. Garlinghouse, Laura A. Flashman, Andrew J. Saykin

Dartmouth Scholarship

Coping with stressful life events requires a degree of skill in the ability to attend to, comprehend, label, communicate and regulate emotions. Individuals vary in the extent to which these skills are developed, with the term ‘alexithymia’ often applied in the clinical and personality literature to those individuals most compromised in these skills. Although a frontal lobe model of alexithymia is emerging, it is unclear whether such a model satisfactorily reflects brain-related patterns associated with perceived emotional intelligence at the facet level. To determine whether these trait meta-mood facets (ability to attend to, have clarity of and repair emotions) have …