BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Published bimonthly, each issue of Current Opinion in Neurology introduces world renowned guest editors and internationally recognized academics within the neurology field, delivering a widespread selection of expert assessments on the latest developments from the most recent literature. All reviews are supplemented with two indispensable sections References and Recommended Reading and Current World Literature which provide a thorough bibliography of references acquired from the top 100 neurology journals.

Current Opinion in Neurology

https://jcp.bmj.com/content/jclinpath/28/6/514.1.full.pdf

Neuropathology and Applied Neurobiology.

Transcriptome analysis of HIV-infected peripheral blood monocytes: Gene transcripts and networks associated with neurocognitive functioning

Background
Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. The aim of our study was to identify the responsible locus for GEFS+ syndrome in a consanguineous Tunisian family showing three affected members, by carrying out a genome-wide single nucleotide polymorphisms (SNPs) genotyping followed by a whole-exome sequencing. We hypothesized an autosomal recessive (AR) mode of inheritance.

/pdf/a-new-locus-on-chromosome-22q13-31-linked-to-recessive-3mkh4xybly.pdf

A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family

The human immunodeficiency virus type-1 (HIV-1) gp160 (gp120-gp41 complex) trimer envelope (ENV) protein is a potential vaccine candidate for HIV/AIDS. HIV-1 vaccine development has been problematic and charge polarity as well as sequence variation across clades may relate to the difficulties. Further obstacles are caused by sequence variation between blood and brain-derived sequences, since the brain is a separate compartment for HIV-1 infection. We utilize a threedimensional residue measure of solvent exposure, accessible surface area (ASA), which shows that major segments of gp120 and gp41 known structures are solvent exposed across clades. We demonstrate a large percent sequence polarity for solvent exposed residues in gp120 and gp41. The range of sequence polarity varies across clades, blood, and brain from different geographical locations. Regression analysis shows that blood and brain gp120 and gp41 percent sequence polarity range correlate with mean Shannon entropy. These results point to the use of protein modifications to enhance HIV-1 ENV vaccines across multiple clades, blood, and brain. It should be noted that we do not address the issue of protein glycosylation here; however, this is an important issue for vaccine design and development.

Abbreviations
HIV-1 - human immunodeficiency virus type 1, AIDS - acquired immunodeficiency syndrome, ENV - envelope, gp160 - 160,000d glycoprotein, gp120 - 120,000d glycoprotein, gp41 - 41,000d glycoprotein, LANL - Los Alamos National Laboratories, PDB - Protein Data Bank, HVTN - STEP HIV vaccine trial, AA - amino acids, MSA - multiple sequence alignment, ASA - accessible surface area, SNPs- single nucleotide polymorphisms, HAART - Highly Active Antiretroviral Therapy, CCR5 - C-C chemokine receptor type 5, CNS - central nervous system, HIVE - HIV encephalitis, P - polarity, NP - non-polarity, CTL - cytotoxic T lymphocyte, NIAID - National Institute of Allergy and Infectious Diseases.

/pdf/hiv-1-envelope-accessible-surface-and-polarity-clade-blood-1rmqjx5igl.pdf

HIV-1 envelope accessible surface and polarity: clade, blood, and brain.

We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene fragments analyzed, expression of 197 genes was identified with significance (p = 0.005).We examined each gene for its position in the human genome and found a non-stochastic occurrence for only seven genes, on chromosome 22. Six of the seven genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1 domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile across these patient categories. There are several mental disease-related genes including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L) identified here are mental disease-related. We speculate that dysregulation of gene expression may occur through mechanisms involving chromatin damage and remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation of expression of mental disease-related genes on chromosome 22 as well as additional genes on other chromosomes. The involvement of these genes as well as miRNA requires additional investigation since numerous genes appear to be involved.

/pdf/hiv-associated-dementia-and-hiv-encephalitis-ii-genes-on-2kfnm29hn4.pdf

HIV associated dementia and HIV encephalitis II: Genes on chromosome 22 expressed in individually microdissected Globus pallidus neurons (Preliminary analysis).

We analyzed gene expression in neurons from 16 cases divided into four groups, ie, human immunodeficiency virus (HIV)-associated dementia (HAD)/HIV encephalitis (HAD/ HIVE), HAD alone, HIVE alone, and HIV positive alone. We produced the neurons using laser capture microdissection from cryopreserved basal ganglia (specifically globus pallidus). Gene expression in pooled neurons from each case was analyzed on GE CodeLink Microarray chips with 55,000 gene fragments per chip. One-way analysis of variance showed significant changes in expression of 197 genes among the four groups (P , 0.005). The three groups, ie, HAD/HIVE, HAD alone, and HIVE alone, were compared with the HIV-positive group using Fisher's least significant difference test, and associated gene expression changes were assigned to each of the three comparisons. Identified genes were associated with 159 functional categories and many of the genes had more than one function. The functional groups included adhesion, amyloid, apoptosis, channel complex, cell cycle, chaperone, chromatin, cytokine, cytoskeleton, metabolism, mitochondria, multinetwork detection protein, sensory perception, receptor, ribosome, noncoding miRNA, signaling, synapse, transcription factor, homeobox, transport, multidrug resistance, and ubiquitin cycle. Several genes were associated with other neurodegenerative and developmental diseases, including Alzheimer's disease, Huntington's disease, and diGeorge syndrome. Thus, a wide range of dysregulated biochemical processes was reported in neuroanatomically pre- cise neurons. This line of investigation is useful and provides specific information about gene expression dysfunction in NeuroAIDS.

/pdf/gene-expression-for-hiv-associated-dementia-and-hiv-7p9mefavf3.pdf

Pandajarasamme Kangueane

Papers

HIV-1 envelope accessible surface and polarity: clade, blood, and brain.

HIV associated dementia and HIV encephalitis II: Genes on chromosome 22 expressed in individually microdissected Globus pallidus neurons (Preliminary analysis).

Gene expression for HIV-associated dementia and HIV encephalitis in microdissected neurons 1: preliminary analysis