Primary structure and chromosomal localization of human and mouse rod photoreceptor cGMP-gated cation channel

Journal ArticleWe have determined the primary structures of the human and mouse retinal rod cGMP-gated cation channel by analysis of cDNA clones and amplified DNA. The open reading frames predicted polypeptides of 690 and 683 residues exhibiting 88% sequence similarity. Sequence comparison indicated that the rod channels consist of a variable 90-residue N-terminal region, a short highly charged segment rich in lysine and glutamate, and a 540-residue C-terminal portion that is well conserved in three mammalian species. Significant sequence similarity (59%) of the visual cGMP-gated channel to the olfactory cAMP-gated channel established the existence of a family of cyclic nucleotide-gated ion channel genes. RNA blot analysis revealed transcripts of 3.2 kilobases (kb) in human, mouse, and dog, 3.2, 4.6, and 5.2 kb in bovine, and 3.6 kb in fish. The human channel gene was mapped by polymerase chain reaction of somatic cell hybrid DNAs to chromosome 4 (p14-q13) near the centromere. The mouse channel gene locus (Cncg) was mapped by interspecific backcross haplotype analysis 0.9 centimorgan proximal of the Kit locus on chromosome 5

Dietary Supplements and Sports Performance: Herbals

This is the fourth in a series of six articles to discuss the major classes of dietary supplements (vitamins; minerals; amino acids; herbs or botanicals; metabolites, constituents/extracts, or combinations). The major focus is on efficacy of such dietary supplements to enhance exercise or sport performance

Pion transition form factor from twisted-mass lattice QCD and the hadronic light-by-light π 0 -pole contribution to the muon g − 2

The neutral pion generates the leading pole contribution to the hadronic light-by-light tensor, which is given in terms of the nonperturbative transition form factor $\mathcal{F}_{\pi^0\gamma\gamma}(q_1^2,q_2^2)$. Here we present an ab-initio lattice calculation of this quantity in the continuum and at the physical point using twisted-mass lattice QCD. We report our results for the transition form factor parameterized using a model-independent conformal expansion valid for arbitrary space-like kinematics and compare it with experimental measurements of the single-virtual form factor, the two-photon decay width, and the slope parameter. We then use the transition form factors to compute the pion-pole contribution to the hadronic light-by-light scattering in the muon $g-2$, finding $a_\mu^{\pi^0\text{-pole}} = 56.7(3.2) \times 10^{-11}$.Comment: 21 pages, 17 figures, 4 tables, updated to published versio

Pseudoscalar-pole contributions to the muon g−2g-2 at the physical point

Pseudoscalar-pole diagrams are an important component of estimates of the hadronic light-by-light (HLbL) contribution to the muon g−2. We report on our computation of the transition form factors P→γ∗γ∗ for the neutral pseudoscalar mesons P=π0 and η . The calculation is performed using twisted-mass lattice QCD with physical quark masses. On the lattice, we have access to a broad range of (space-like) photon four-momenta and therefore produce form factor data complementary to the experimentally accessible single-virtual direction, which directly leads to an estimate of the pion- and η -pole components of the muon g−2 . For the pion, our result for the g−2 contribution in the continuum is comparable with previous lattice and data-driven determinations, with combined relative uncertainties below 10% . For the η meson, we report on a preliminary determination from a single lattice spacing

Consumers of natural health products: natural-born pharmacovigilantes?

<p>Abstract</p> <p>Background</p> <p>Natural health products (NHPs), such as herbal medicines and vitamins, are widely available over-the-counter and are often purchased by consumers without advice from a healthcare provider. This study examined how consumers respond when they believe they have experienced NHP-related adverse drug reactions (ADRs) in order to determine how to improve current safety monitoring strategies.</p> <p>Methods</p> <p>Qualitative semi-structured interviews were conducted with twelve consumers who had experienced a self-identified NHP-related ADR. Key emergent themes were identified and coded using content analysis techniques.</p> <p>Results</p> <p>Consumers were generally not comfortable enough with their conventional health care providers to discuss their NHP-related ADRs. Consumers reported being more comfortable discussing NHP-related ADRs with personnel from health food stores, friends or family with whom they had developed trusted relationships. No one reported their suspected ADR to Health Canada and most did not know this was possible.</p> <p>Conclusion</p> <p>Consumers generally did not report their suspected NHP-related ADRs to healthcare providers or to Health Canada. Passive reporting systems for collecting information on NHP-related ADRs cannot be effective if consumers who experience NHP-related ADRs do not report their experiences. Healthcare providers, health food store personnel, manufacturers and other stakeholders also need to take responsibility for reporting ADRs in order to improve current pharmacovigilance of NHPs.</p

Moxibustion for ulcerative colitis: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicine (CAM) is increasingly used for treatment of inflammatory bowel disease (IBD). Acupuncture-type treatments are among the most popular options. Several studies have reported that moxibustion is effective in ulcerative colitis (UC). The objective of this review was to assess the clinical evidence for or against moxibustion as a treatment for UC.</p> <p>Methods</p> <p>We searched the literature using 18 databases from their inception to February 10, 2010, without language restrictions. We included randomized clinical trials (RCTs), in which human patients with UC were treated with moxibustion. Studies were included if they were placebo-controlled or controlled against a drug therapy or no treatment group. The methodological quality of all RCTs was assessed using the Cochrane risk of bias.</p> <p>Results</p> <p>In total, five RCTs were included. All were of low methodological quality. They compared the effects of moxibustion with conventional drug therapy. Three tested moxibustion against sulfasalazine and two against sulfasalazine plus other drugs. A meta-analysis of five RCTs showed favorable effects of moxibustion on the response rate compared to conventional drug therapy (n = 407; risk ratio = 1.24, 95% CI = 1.11 to 1.38; P < 0.0001; heterogeneity: I²= 16%).</p> <p>Conclusions</p> <p>Current evidence is insufficient to show that moxibustion is an effective treatment of UC. Most of included trials had high risk of bias. More rigorous studies seem warranted.</p

The Cis-regulatory Logic of the Mammalian Photoreceptor Transcriptional Network

The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation