Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha.

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is involved in the coordinate induction of changes in gene expression in the liver that enable a homeostatic response to alterations in metabolic state, environmental cues, and nutrient availability. In exploring the specific pathways under PGC-1alpha regulation in the liver, we have made the surprising observation that this coactivator can induce the expression of CYP11A1 and CYP17A1, key rate-limiting enzymes involved in the initial steps of steroidogenesis. Both of these enzymes function to produce C(19)-steroids, converting cholesterol into pregnenolone, and then to dehydroepiandrosterone (DHEA).

A sensitive, noise-resistant method for identifying focal demyelination and remyelination in patients with multiple sclerosis via voxel-wise changes in magnetization transfer ratio.

Magnetization transfer imaging (MTI) provides a reliable and histopathologically validated means for identifying important tissue changes in multiple sclerosis (MS), including demyelination and remyelination. However, most approaches to date have been based on a priori regions of interest (ROIs) and have been relatively insensitive to small focal changes or competing processes. More recent techniques have sought to address this through a voxel-wise approach, but have been limited in their detection capabilities by the amount of noise in standard MTR images.

Signal abnormalities on 1.5 and 3 Tesla brain MRI in multiple sclerosis patients and healthy controls. A morphological and spatial quantitative comparison study.

Previous studies in patients with multiple sclerosis (MS) revealed increased lesion count and volume on 3 T compared to 1.5 T. Morphological and spatial lesion characteristics between 1.

Hip-muscle activation during the lunge, single-leg squat, and step-up-and-over exercises.

Context: Functional exercises are often used in strengthening programs after lower extremity injury. Activation levels of the stabilizing hip muscles have not been documented.

Objective: To document the progression of hip-muscle activation levels during 3 lower extremity functional exercises.

Extent of cerebellum, subcortical and cortical atrophy in patients with MS: a case-control study.

Cortical and subcortical atrophy occurs in multiple sclerosis (MS) and relates to clinical outcomes. FreeSurfer, a voxel-based automated software for brain reconstruction was used to investigate the extent of subcortical and cortical atrophy in 71 MS and 17 clinically isolated syndrome (CIS) patients, and 38 normal controls (NC), and to relate group differences to disease type and severity. Segmentation was performed on 3D SPGR T1-weighted MRI 1.

Amazon heart: an exploration of the role of challenge events in personal growth after breast cancer.

High-profile events where in response to the experience of breast cancer women take on adventure activities to raise awareness and/or funds for breast cancer are increasing. These activities offer physical and psychological challenges within a peer support group setting. We investigated the experiences of 21 breast cancer survivors who participated in a 7-day breast cancer awareness motorcycle ride.

Fluoroalkyl alpha side chain containing 3,4-diamino-cyclobutenediones as potent and orally bioavailable CXCR2-CXCR1 dual antagonists.

A series of potent and orally bioavailable 3,4-diaminocyclobutenediones with various fluoroalkyl groups as alpha side chain were prepared and found to show significant improvements in the binding affinities towards both CXCR2 and CXCR1 receptors.

Gray matter atrophy and disability progression in patients with early relapsing-remitting multiple sclerosis: a 5-year longitudinal study.

We assessed the relationship between gray matter (GM) and white matter (WM) atrophy and clinical status in early relapsing-remitting multiple sclerosis (MS) patients over 5 years. A group of 181 patients who participated in the ASA (Avonex-Steroid-Azathioprine) study and had complete clinical and MRI assessments over 2 and 5 years was investigated. One hundred seventy (170) patients completed the 12-month follow-up, 147 the 24-month, 98 the 36-month, 65 the 48-month and 47 the 60-month.

Gender-related differences in MS: a study of conventional and nonconventional MRI measures.

Background: Studies showed gender-associated differences in multiple sclerosis (MS) disease evolution and in the evolution of conventional magnetic resonance imaging (MRI) findings.

Objective: The aim of this study was to investigate gender differences according to a number of conventional and nonconventional MRI measures in patients with MS.

Methods: We examined 763 consecutive patients with MS [499 (19.

Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke.

The perfusion/diffusion 'mismatch model' in acute ischemic stroke provides the potential to more accurately understand the consequences of thrombolytic therapy on an individual patient basis. Few methods exist to quantify mismatch extent (ischemic penumbra) and none have shown a robust ability to predict infarcted tissue outcome. Hidden Markov random field (HMRF) approaches have been used successfully in many other applications.

Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis.

Objective: To investigate differences in lesions and surrounding normal appearing white matter (NAWM) by perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in patients with acute and chronic ischemic stroke and multiple sclerosis (MS).

Methods: Study subjects included 45 MS patients, 22 patients with acute ischemic stroke and 20 patients with chronic ischemic stroke. All subjects underwent T2-weighted imaging (WI), flair attenuated inversion recovery (FLAIR), DWI and dynamic contrast enhanced PWI.

Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.

Background: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles.

Methodology/principal Findings: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM) anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified.

Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis.

Disease-modifying agents (DMAs), including interferon beta (IFNbeta) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent anti-inflammatory agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy.

Cortical atrophy and personality in multiple sclerosis.

Although the cognitive disorder of multiple sclerosis (MS) is well characterized, little is known about personality changes that may occur in this disease. There are reliable personality tests available for research in neurological disease, based on the well-known Five Factor Model. Preliminary research suggests that cognitively impaired MS patients exhibit elevation in Neuroticism, and diminution in Extraversion, Agreeableness, and Conscientiousness, as do patients with Alzheimer's disease.

Genetic analyses reveal independent domestication origins of Eurasian reindeer.

Although there is little doubt that the domestication of mammals was instrumental for the modernization of human societies, even basic features of the path towards domestication remain largely unresolved for many species. Reindeer are considered to be in the early phase of domestication with wild and domestic herds still coexisting widely across Eurasia. This provides a unique model system for understanding how the early domestication process may have taken place.

Ocular findings in patients with orbitozygomatic complex fractures: a retrospective study.

Purpose: To evaluate the incidence of ocular injuries and clinical ocular signs in patients with orbitozygomatic fractures of varying severity, presenting to a regional oral and maxillofacial surgery service.

Patients And Methods: This is a retrospective study of patients presenting to Limerick Regional Hospital (Limerick, Ireland) with orbitozygomatic fractures from January 1998 to December 2004. Patients with panfacial fractures and those with isolated zygomatic arch fractures were excluded.

Sampling and modeling for the quantification of adventitious genetically modified presence in maize.

The coexistence of genetically modified (GM) and non-GM crops is an important economic and political issue in the European Union. We examined the GM content in non-GM maize crops in Spain in 2005. Both the standing crop and the harvest were tested, and the %GM DNA was quantified by real-time polymerase chain reaction.

The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome.

Magnetic resonance imaging (MRI) is the most important paraclinical measure for assessing and monitoring the pathologic changes implicated in the onset and progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1-weighted gadolinium (Gd) enhanced and spin-echo T2-weighted imaging, only provide an incomplete picture of the degree of inflammation and underlying neurodegenerative changes in this disease. Two- and three-dimensional fluid-attenuated inversion recovery and double inversion recovery sequences allow better identification of cortical, periventricular and infratentorial lesions.

Regional specificity of magnetization transfer imaging in multiple sclerosis.

Background: The goal of this study was to develop and validate a method for generation of regional magnetization transfer ratio (MTR). We also studied the topography of MTR changes in multiple sclerosis (MS) and in normal controls (NC), and preliminarily examined the clinical usefulness of this method.

Methods: We examined 45 patients with MS (relapsing remitting [RR] = 28 and secondary progressive[SP] = 17] and 19 NC.

Synthesis and structure-activity relationships of heteroaryl substituted-3,4-diamino-3-cyclobut-3-ene-1,2-dione CXCR2/CXCR1 receptor antagonists.

Comprehensive SAR studies were undertaken in the 3,4-diaminocyclobut-3-ene-1,2-dione class of CXCR2/CXCR1 receptor antagonists to explore the role of the heterocycle on chemokine receptor binding affinities, functional activity, as well as oral exposure in rat. The nature of the heterocycle as well as the requisite substitution pattern around the heterocycle was shown to have a dramatic effect on the overall biological profile of this class of compounds. The furyl class, particularly the 4-halo adducts, was found to possess superior binding affinities for both the CXCR2 and CXCR1 receptors, functional activity, as well as oral exposure in rat versus other heterocyclic derivatives.

Addressing the need for access to culturally and linguistically appropriate HIV/AIDS prevention for Latinos.

This article reports a comprehensive national needs assessment of Latinos' access to HIV/AIDS prevention and education services in 14 cities throughout the United States and Puerto Rico. Interviews and focus groups were conducted with Latinos who were HIV-positive and at risk for HIV infection. The study explored risk behaviors, access to health care services, and exposure to HIV prevention messages.

Comparison of three different methods for measurement of cervical cord atrophy in multiple sclerosis.

Background And Purpose: Evidence is mounting that spinal cord atrophy significantly correlates with disability in patients with multiple sclerosis (MS). The purpose of this work was to validate 3 different measures for the measurement of cervical cord atrophy on high-resolution MR imaging in patients with MS and in normal control subjects (NCs). We also wanted to evaluate the relationship between cervical cord atrophy and clinical disability in the presence of other conventional and nonconventional brain MR imaging metrics by using a unique additive variance regression model.

Gabapentin suppresses spasticity in the spinal cord-injured rat.

Unlabelled: Spasticity poses a major detrimental impact on the quality of life in a significant number of people with spinal cord injury (SCI). Recent observations in our laboratory suggest that spinal transection at the sacral S(2) level induces a significant increase in glutamatergic input to sacrocaudal motoneurons during the time spasticity is present in the tail muscles. The present study examined the efficacy of gabapentin, an agent that has been shown to reduce glutamate release, in managing spasticity within the tail musculature.

Structure-guided discovery of cyclin-dependent kinase inhibitors.

CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules.