Medicine and Health Sciences Commons^™

Genetic, Maternal And Placental Factors In The Association Between Birth Weight And Physical Fitness: A Longitudinal Twin Study, Robert N. H. Touwaslagar, Marji Gielen, Grans E. S. Tan, Antonius L. M. Mulder, Williem J. M. Gerver, Luc J. Zimmermann, Alfons J. H. M. Houben, Maurice P. Zeegers, Catherine Derom, Robert Vlietinck, Hermine Maes, Coen D. A. Stehouwer, Martine Thomis

Human and Molecular Genetics Publications

Background

Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design

Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10–18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study. Their birth weights had been collected prospectively within the East Flanders Prospective Twin Survey.

Results

We identified linear associations between birth weight and adolescent vertical jump (b = 1.96 cm per kg birth weight, …

Increased Frequency Of Micronuclei In Adults With A History Of Childhood Sexual Abuse: A Discordant Monozygotic Twin Study, Timothy P. York, Jenni Brumelle, Jane Juusola, Kenneth S. Kendler, Lindon J. Eaves, Ananda B. Amstadler, Steven H. Aggen, Kimberly H. Jones, Andrea Ferreira-Gonzalez, Colleen Jackson-Cook

Human and Molecular Genetics Publications

Background

Childhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA.

Methods

Monozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a …

Rapid And Inexpensive Screening Of Genomic Copy Number Variations Using A Novel Quantitative Fluorescent Pcr Method, Martin Stofanko, Joan C. Han, Sarah H. Elsea, Heloísa B. Pena, Higgor Gonçalves-Dornelas, Sérgio Danilo Junho Pena

Human and Molecular Genetics Publications

Detection of human microdeletion and microduplication syndromes poses significant burden on public healthcare systems in developing countries. With genome-wide diagnostic assays frequently inaccessible, targeted low-cost PCR-based approaches are preferred. However, their reproducibility depends on equally efficient amplification using a number of target and control primers. To address this, the recently described technique called Microdeletion/Microduplication Quantitative Fluorescent PCR (MQF-PCR) was shown to reliably detect four human syndromes by quantifying DNA amplification in an internally controlled PCR reaction. Here, we confirm its utility in the detection of eight human microdeletion syndromes, including the more common WAGR, Smith-Magenis, and Potocki-Lupski syndromes with 100% …

Identification Of Genes Potentially Regulated By Human Polynucleotide Phosphorylase (Hpnpaseold-35) Using Melanoma As A Model, Upneet K. Sokhi, Manny D. Bacolod, Santanu Dasgupta, Luni Emdad, Swadesh K. Das

Human and Molecular Genetics Publications

Human Polynucleotide Phosphorylase (hPNPaseold-35 or PNPT1) is an evolutionarily conserved 3′→5′ exoribonuclease implicated in the regulation of numerous physiological processes including maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. To further elucidate the functional implications of hPNPaseold-35 in cellular physiology, we knocked-down and overexpressed hPNPaseold-35 in human melanoma cells and performed gene expression analyses to identify differentially expressed transcripts. Ingenuity Pathway Analysis indicated that knockdown of hPNPaseold-35 resulted in significant …

The Krüppel-Like Factor 2 And Krüppel-Like Factor 4 Genes Interact To Maintain Endothelial Integrity In Mouse Embryonic Vasculogenesis, Aditi R. Chiplunkar, Benjamin C. Curtis, Gabriel L. Eades, Megan S. Kane, Sean J. Fox, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Background Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied.

Results Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single …

Krüppel-Like Factor 2 Is Required For Normal Mouse Cardiac Development, Aditi R. Chiplunkar, Tina K. Lung, Yousef Alhashem, Benjamin A. Koppenhaver, Fadi N. Salloum, Rakesh C. Kukreja, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2−/− embryos die earlier, by E11.5. E9.5 FVB/N KLF2−/− hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

A Twin Study Of Early-Childhood Asthma In Puerto Ricans, Supinda Bunyavanich, Judy L. Silberg, Jessica Lasky-Su, Nathan A. Gillespie, Nancy E. Lange, Glorisa Canino, Juan C. Celedon

Human and Molecular Genetics Publications

Background

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood.

Objective

To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤3 years old.

Methods

678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages …

Targeted Apoptotic Effects Of Thymoquinone And Tamoxifen On Xiap Mediated Akt Regulation In Breast Cancer, Shashi Rajput, B. N. P. Kumar, Siddik Sarkar, Subhasis Das, Belal Azab, Prasanna K. Santhekadur, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Paul B. Fisher, Mahitosh Mandal

Human and Molecular Genetics Publications

X-linked inhibitor of apoptosis protein (XIAP) is constitutively expressed endogenous inhibitor of apoptosis, exhibit its antiapoptotic effect by inactivating key caspases such as caspase-3, caspase-7 and caspase-9 and also play pivotal role in rendering cancer chemoresistance. Our studies showed the coadministration of TQ and TAM resulting in a substantial increase in breast cancer cell apoptosis and marked inhibition of cell growth both in vitro and in vivo. Anti-angiogenic and anti-invasive potential of TQ and TAM was assessed through in vitro studies. This novel combinatorial regimen leads to regulation of multiple cell signaling targets including inactivation of Akt and XIAP degradation. …

Lipopolysaccharide-Induced Neuronal Activation In The Paraventricular And Dorsomedial Hypothalamus Depends On Ambient Temperature, Samuel P. Wanner, Kyoko Yoshida, Vladimir A. Kulchitsky, Andrei I. Ivanov, Kazuyuki Kanosue, Andrej A. Romanovsky

Human and Molecular Genetics Publications

Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS). To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously) either in a thermoneutral (30°C) or cool (24°C) environment. At 30°C, LPS caused fever; at 24°C, the same dose caused profound hypothermia. Both fever and hypothermia were …