A whole-organism screen identifies new regulators of fat storage.

The regulation of energy homeostasis integrates diverse biological processes ranging from behavior to metabolism and is linked fundamentally to numerous disease states. To identify new molecules that can bypass homeostatic compensatory mechanisms of energy balance in intact animals, we screened for small-molecule modulators of Caenorhabditis elegans fat content. We report on several molecules that modulate fat storage without obvious deleterious effects on feeding, growth and reproduction.

Pharmacokinetic Compatibility Study of Lidocaine with EXPAREL in Yucatan Miniature Pigs.

We explored the potential for EXPAREL to interact with lidocaine. Sixty (60) male Yucatan Swine were randomized into 20 groups (N = 3/group). EXPAREL (2 or 4 mg/kg) and/or lidocaine HCl solution 1% or 2% (with epinephrine 1 : 200,000) were injected subcutaneously along a 5 cm virtual incision line.

Comparison of clinical characteristics and performance of pneumonia severity score and CURB-65 among younger adults, elderly and very old subjects.

Background: Age-related alterations in the clinical characteristics and performance of severity scoring systems for community-acquired pneumonia (CAP) are unknown.

Methods: Consecutive patients with CAP presenting to the emergency department were prospectively studied. Patients were classified as younger adults (age 18-64 years), elderly (age 65-84 years) and very old subjects (age ≥85 years).

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts.

Genomic landscape of meningiomas.

Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur.

Effect of Electromechanical Stimulation on the Maturation of Myotubes on Aligned Electrospun Fibers.

Tissue engineering may provide an alternative to cell injection as a therapeutic solution for myocardial infarction. A tissue-engineered muscle patch may offer better host integration and higher functional performance. This study examined the differentiation of skeletal myoblasts on aligned electrospun polyurethane (PU) fibers and in the presence of electromechanical stimulation.

Conformational changes in redox pairs of protein structures.

Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function.

Measuring cultural identity: validation of a modified Cortes, Rogler and Malgady Bicultural Scale in three ethnic groups in New York.

Cultural identity is central to health. Acculturation may be formulated with a bicultural model, assessing in parallel the degree of identification with both the original and the host culture. The Cortes, Rogler and Malgady Bicultural Scale (CRM-BS) is composed of two subscales: "original" culture and "mainstream-United States" (US) culture.

Sustained viral gene delivery through core-shell fibers.

Although viral gene transfer is efficient in achieving transgene expression for tissue engineering, drawbacks of virus dissemination, toxicity and transient gene expression due to immune response have hindered its widespread application. Many tissue engineering studies thus opt to genetically engineer cells in vitro prior to their introduction in vivo. However, it would be attractive to obviate the need for in vitro manipulation by transducing the infiltrating progenitor cells in situ.

Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors.

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy.

Comparison of automated candidate gene prediction systems using genes implicated in type 2 diabetes by genome-wide association studies.

Background: Automated candidate gene prediction systems allow geneticists to hone in on disease genes more rapidly by identifying the most probable candidate genes linked to the disease phenotypes under investigation. Here we assessed the ability of eight different candidate gene prediction systems to predict disease genes in intervals previously associated with type 2 diabetes by benchmarking their performance against genes implicated by recent genome-wide association studies.

Results: Using a search space of 9556 genes, all but one of the systems pruned the genome in favour of genes associated with moderate to highly significant SNPs.

Preferential gene expression in the limbus of the vervet monkey.

Purpose: To elucidate the unique molecular factors and biological processes that are differentially expressed in the limbal stem cell microenvironment by comparing directly to that of its immediate adjacent structures, the cornea and conjunctiva.

Methods: Total RNA was isolated and amplified from the limbus, cornea, and conjunctiva. A gene expression profile of each tissue type was obtained by using microarray technique.

Effects of prenatal exposure to coal-burning pollutants on children's development in China.

Background: Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs), lead, and mercury are released by combustion of coal and other fossil fuels.

Objectives: In the present study we evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age.

Methods: The study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air.

Development and validation of the Chinese version of the Multicultural Quality of Life Index (MQLI-Ch).

This study documents the validation study of the Multicultural Quality of Life Index, Chinese version (MQLI-Ch). This self-rated instrument is composed of ten items that correspond to multiple dimensions of the concept of quality of life. Each item is rated on a scale from 1 to 10, according to the subject's culture-informed understanding of the concept.

The Korean version of the Multicultural Quality of Life Index (MQLI-Kr): development and validation.

Our research team of multilingual and multicultural members designed comprehensive, yet efficient, culture-informed, and self-rated Multicultural Quality of Life Indexes for both English-speaking individuals and for growing immigrant groups in the United States. A Korean version of the Multicultural Quality of Life Index (MQLI-Kr) was developed as part of this multilingual project. The team tested the MQLI-Kr on 130 Koreans (100 psychiatric patients and 30 professionals).

Racial differences in clinical and pathological associations with PhIP-DNA adducts in prostate.

African-American men have a higher dietary intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is the most abundant heterocyclic amine in cooked meats and is carcinogenic in rat prostate through the formation of DNA adducts. To determine the clinical and demographic factors associated with PhIP-DNA adduct levels, the biologically effective dose of PhIP in human prostate, we immunohistochemically measured PhIP-DNA adducts in a study of 162 Caucasian and 102 African-American men who underwent radical prostatectomy for prostate cancer. A strong correlation between PhIP-DNA adduct levels in prostate tumor and adjacent non-tumor cells was observed (rho = 0.

Grilled meat consumption and PhIP-DNA adducts in prostate carcinogenesis.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the major heterocyclic amine generated from cooking meats at high temperatures, and dietary exposures have been shown to induce prostate cancer in rats. PhIP derives its carcinogenic potential through the formation of PhIP-DNA adducts. The purpose of this study was to examine whether self-reported consumption and preparation doneness of grilled meats were associated with PhIP-DNA adduct levels in prostate epithelial cells.

Angiogenic factors stimulate tubular branching morphogenesis of sonic hedgehog-deficient lungs.

Sonic Hedgehog (Shh)-deficient mice have a severe lung branching defect. Recent studies have shown that hedgehog signaling is involved in vascular development and it is possible that the diminished airway branching in Shh-deficient mice is due to abnormal pulmonary vasculature formation. Therefore, we investigated the role of Shh in pulmonary vascular development using Shh/Tie2lacZ compound mice, which exhibit endothelial cell-specific LacZ expression, and Pecam-1 immunohistochemistry.

Analysis of protein sequence and interaction data for candidate disease gene prediction.

Linkage analysis is a successful procedure to associate diseases with specific genomic regions. These regions are often large, containing hundreds of genes, which make experimental methods employed to identify the disease gene arduous and expensive. We present two methods to prioritize candidates for further experimental study: Common Pathway Scanning (CPS) and Common Module Profiling (CMP).

Primary glioblastomas express mesenchymal stem-like properties.

Glioblastoma is the most common and aggressive primary brain cancer. Recent isolation and characterization of brain tumor-initiating cells supports the concept that transformed neural stem cells may seed glioblastoma. We previously identified a wide array of mesenchymal tissue transcripts overexpressed in a broad set of primary glioblastoma (de novo) tumors but not in secondary glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal brain tissues.

PAH-DNA adducts in cord blood and fetal and child development in a Chinese cohort.

Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic pollutants released by fossil fuel combustion. Other pollutants include metals and particulate matter. PAH-DNA adducts, or benzo[a]pyrene (BaP) adducts as their proxy, provide a chemical-specific measure of individual biologically effective doses that have been associated with increased risk of cancer and adverse birth outcomes.

Iroquois genes influence proximo-distal morphogenesis during rat lung development.

Lung development is a highly regulated process directed by mesenchymal-epithelial interactions, which coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. The Iroquois homeobox (Irx) genes have been implicated in the patterning and specification of several Drosophila and vertebrate organs, including the heart. Herein, we investigated whether the Irx genes play a role in lung morphogenesis.

Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung.

Recent investigations have suggested an active role for endothelial cells in organ development, including the lung. Herein, we investigated some of the molecular mechanisms underlying normal pulmonary vascular development and their influence on epithelial branching morphogenesis. Because the lung in utero develops in a relative hypoxic environment, we first investigated the influence of low oxygen on epithelial and vascular branching morphogenesis.

Induction of heme oxygenase-1 expression inhibits platelet-dependent thrombosis.

Heme oxygenase-1 (HO-1) plays a key role in protecting tissue from oxidative stress. Although some studies implicate HO-1 in modulating thrombosis after vascular injury, the impact of HO-1 on the rate of clot formation in vivo is poorly defined. This study examined the potential function of HO-1 in regulating platelet-dependent arterial thrombosis.

Linked linear amplification for simultaneous analysis of the two most common hemochromatosis mutations.

Background: Two mutations in HFE, G845A (amino acid substitution C282Y) and C187G (H63D), are associated with hereditary hemochromatosis. We developed and validated a novel method, linked linear amplification (LLA), for detection of these two mutations.

Methods: Two segments of HFE were amplified by a multiplex LLA reaction that generated biotinylated LLA products.