An evolutionary continuum from nucleated dwarf galaxies to star clusters.

Systematic studies have revealed hundreds of ultra-compact dwarf galaxies (UCDs) in the nearby Universe. With half-light radii r of approximately 10-100 parsecs and stellar masses M≈ 10-10solar masses, UCDs are among the densest known stellar systems. Although similar in appearance to massive globular clusters, the detection of extended stellar envelopes, complex star formation histories, elevated mass-to-light ratio and supermassive black holes suggest that some UCDs are remnant nuclear star clusters of tidally stripped dwarf galaxies, or even ancient compact galaxies.

Embedding routine health checks for adults with intellectual disabilities in primary care: practice nurse perceptions.

Background: Adults with intellectual disabilities (IDs) have consistently poorer health outcomes than the general population. There is evidence that routine health checks in primary care may improve outcomes. We conducted a randomised controlled trial of practice nurse led health checks.

Plasma phospholipids identify antecedent memory impairment in older adults.

Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline.

Expression of Voltage-Gated Sodium Channel Na1.8 in Human Prostate Cancer is Associated with High Histological Grade.

Voltage-gated sodium (Na) channels are required for impulse conductance in excitable tissues. Nas have been linked to human cancers, including prostate. The expression and distribution of Na isoforms (Na1.

Network modeling to identify new mechanisms and therapeutic targets for Parkinson's disease.

Biomolecules in subnetworks are the focus of a new strategy to develop drugs that halt complex diseases. In this article, the authors use genome-wide association study and linkage data derived from Parkinson's disease studies to illustrate how algorithms that use gene and protein interaction databases reveal subnetworks in biological systems that suggest mechanisms for disease progression. Network modeling may help develop testable hypotheses for neurodegenerative diseases and open up new avenues for therapeutic development.

Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent.

Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy.

A SWOT analysis of the physiotherapy profession in Kuwait.

Background And Purpose: Since the end of the Gulf War in 1991, Kuwait has become one of the wealthiest countries in the world and one that has a highly socialized health-care system. This rapid growth and socio-economic development appears to have had a negative impact on the health of its people. As such, the profession of physiotherapy may be in a unique position to address this issue by providing health behaviour interventions and promoting healthy lifestyles.

Delayed rehabilitation with task-specific therapies improves forelimb function after a cervical spinal cord injury.

Purpose: The effect of activity based therapies on restoring forelimb function in rats was evaluated when initiated one month after a cervical spinal cord injury.

Methods: Adult rats received a unilateral over-hemisection of the spinal cord at C4/5, which interrupts the right side of the spinal cord and the dorsal columns bilaterally, resulting in severe impairments in forelimb function with greater impairment on the right side. One month after injury rats were housed in enriched housing and received daily training in reaching, gridwalk, and CatWalk.

Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers.

Hermitamides A and B are lipopeptides isolated from a Papau New Guinea collection of the marine cyanobacterium Lyngbya majuscula. We hypothesized that the hermitamides are ligands for the human voltage-gated sodium channel (hNa(V)) based on their structural similarity to the jamaicamides. Herein, we describe the nonracemic total synthesis of hermitamides A and B and their epimers.

Quantitative analysis of the heteromeric neuronal nicotinic receptors in the rat hippocampus.

The objective of this study was to identify and quantify the heteromeric neuronal nicotinic receptors (nAChRs) in the rat hippocampus. The density of nAChR subtypes was assessed by labeling them with [(3)H]epibatidine ([(3)H]EB) followed by immunoprecipitation with subunit-selective antibodies. Sequential immunoprecipitation assays were used to establish associations between two different subunits, which then allowed the full subunit composition of the receptors to be deduced.

Activity-based therapies to promote forelimb use after a cervical spinal cord injury.

Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion.

Retrograde and anterograde transport of HIV protein gp120 in the nervous system.

Neurodegeneration and gliosis are prominent pathological features of subjects with human immunodeficiency virus (HIV) dementia complex (HAD). In these patients, neurodegeneration occurs in uninfected neurons. In addition, these patients develop sensory neuropathy despite the antiretroviral therapy.

Delayed intervention with transplants and neurotrophic factors supports recovery of forelimb function after cervical spinal cord injury in adult rats.

The adult central nervous system is capable of considerable anatomical reorganization and functional recovery after injury. Functional outcomes, however, vary greatly, depending upon size and location of injury, type and timing of intervention, and type of recovery and plasticity evaluated. The present study was undertaken to assess the recovery of skilled and unskilled forelimb function in adult rats after a C5/C6 spinal cord over-hemisection and delayed intervention with fetal spinal cord transplants and neurotrophins.

Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord.

It is likely that the environment within the injured spinal cord influences the capacity of fetal spinal cord transplants to support axonal growth. We have recently demonstrated that fetal spinal cord transplants and neurotrophin administration support axonal regeneration after spinal cord transection, and that the distance and amount of axonal growth is greater when these treatments are delayed by several weeks after injury. In this study, we sought to determine whether differences in inflammatory mediators exist between the acutely injured spinal cord and the spinal cord after a second injury and re-section, which could provide a more favorable environment for the axonal re-growth.

Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins.

Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level.

Descending modulation of opioid-containing nociceptive neurons in rats with peripheral inflammation and hyperalgesia.

Inflammation and hyperalgesia induce a dramatic up-regulation of opioid messenger RNA and peptide levels in nociceptive neurons of the spinal dorsal horn. Descending axons modulate nociceptive transmission at the spinal level during inflammatory pain, and may play a role in the development of persistent pain. The role of descending bulbospinal pathways in opioid-containing nociceptive neurons was examined.

AP-1-related proteins bind to the enkephalin CRE-2 element in adrenal chromaffin cells.

Chromaffin cells of the adrenal medulla are neural crest-derived neuroendocrine cells that express neuropeptide genes in vivo and in vitro. As such these cells are useful for examining tissue- and cell-specific regulation of the enkephalin gene. We previously demonstrated that the chromatin configuration of the enkephalin gene correlated with its tissue-specific expression in the adrenal medulla and primary chromaffin cell cultures.

Neuropeptide genes: targets of activity-dependent signal transduction.

Neuroendocrine cells respond to hormones and synaptic input by increasing or decreasing their own electrical activity and secretory output, and by changes in the repertoire of expression of neuronal genes. Neuropeptide genes are among those whose transcription rates can be dramatically up-and downregulated when neuronal activity is altered. In the last decade or so, our understanding of neuropeptide gene regulation has evolved from the concept of calcium-dependent coupling of neuropeptide secretion and biosynthesis to the current perspective of neuropeptide genes as the targets of multiple intracellular signaling pathways, entrained by intrinsic electrical activity and by transsynaptic influences.

Identification of a TPA-responsive element mediating preferential transactivation of the galanin gene promoter in chromaffin cells.

The gene encoding the neuropeptide galanin is upregulated by second messenger signal transduction pathways in bovine chromaffin cells. To identify its transcriptional regulatory elements, 5'-flanking sequences of the galanin gene were transiently transfected into primary cultures of bovine chromaffin cells within reporter gene constructs. Multiple regions of the galanin 5' flank seem to be necessary for basal activity.

Adrenal secretion of BAM-22P, a potent opioid peptide, is enhanced in rats with acute cholestasis.

The adrenal gland is known to produce and release endogenous opioids into the circulation. Bovine adrenal medulla docosapeptide (BAM-22P) is a potent opioid agonist, derived from the proenkephalin A gene, which is present in the adrenal medulla. This study was undertaken to determine whether BAM-22P is released into plasma during acute cholestatic liver injury, which increases plasma total opioid activity.

Enkephalin gene transcription in bovine chromaffin cells is regulated by calcium and protein kinase A signal transduction pathways: identification of DNase I-hypersensitive sites.

The bovine enkephalin gene is responsive to multiple signaling pathways in primary chromaffin cell cultures. We examined the effects of activation of the calcium and protein kinase A pathways on accumulation of enkephalin peptide and mRNA, gene transcription, and chromatin structure in the 5' region of the gene. We show here that the increase of enkephalin mRNA and peptide after depolarization of chromaffin cells with KCl or activation of adenylate cyclase with forskolin is preceded by an increase in enkephalin gene transcription.

Tumor-suppressor function of muscarinic acetylcholine receptors is associated with activation of receptor-operated calcium influx.

Several members of the family of guanine nucleotide-binding protein (G protein)-coupled receptors have recently been shown to induce agonist-dependent foci development in NIH 3T3 cells and tumors in nude mice. We selected the five subtypes of the muscarinic acetylcholine receptor family to investigate their role in tumor suppression. When transfected and expressed in CHO-K1 Chinese hamster ovary cells, m1, m3, and m5 muscarinic acetylcholine receptor activation resulted in a morphology change.

Enkephalin biosynthesis is coupled to secretory activity via transcription of the proenkephalin A gene.

The molecular mechanisms regulating neuropeptide and secretory protein biosynthesis in neuroendocrine cells were examined using the prototype neuropeptide and secretory proteins enkephalin and chromogranin A (CGA). Treatment with the secretogogue nicotine results in the calcium-dependent secretion of enkephalin peptides from bovine chromaffin cells in primary culture and a concomitant increase in enkephalin peptide biosynthesis. Both secretion and biosynthesis are also stimulated by cell depolarization with elevated potassium.

Malignant transformation of NIH 3T3 fibroblasts by human c-sis is dependent upon the level of oncogene expression.

High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts.