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Biomedical subjects

W He

Publications and source records attributed to W He.

At least 73 records · Page 4Linked to original sources
PubMed2000

Yeast Sm-like proteins function in mRNA decapping and decay.

One of the main mechanisms of messenger RNA degradation in eukaryotes occurs by deadenylation-dependent decapping which leads to 5'-to-3' decay. A family of Sm-like (Lsm) proteins has been identified, members of which contain the 'Sm' sequence motif, form a complex with U6 small nuclear RNA and are required for pre-mRNA splicing. Here we show that mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead to inhibition of mRNA decapping. In addition, the Lsm1-Lsm7 proteins co-immunoprecipitate with the mRNA decapping enzyme (Dcp1), a decapping activator (Pat1/Mrt1) and with mRNA. This indicates that the Lsm proteins may promote decapping by interactions with the mRNA and the decapping machinery. In addition, the Lsm complex that functions in mRNA decay appears to be distinct from the U6-associated Lsm complex, indicating that Lsm proteins form specific complexes that affect different aspects of mRNA metabolism.

Autoantigens↗
PubMed2000

High-gain wide-band gyrotron traveling wave amplifier with a helically corrugated waveguide

First bandwidth measurements of a novel gyrotron amplifier are presented. The coupling between the second harmonic cyclotron mode of a gyrating electron beam and the radiation field occurred in the region of near infinite phase velocity over a broad bandwidth by using a cylindrical waveguide with a helical corrugation on its internal surface. With a beam energy of 185 keV, the amplifier achieved a maximum output power of 1.1 MW, saturated gain of 37 dB, linear gain of 47 dB, saturated bandwidth of 8.4 to 10.4 GHz ( 21% relative bandwidth), and an efficiency of 29%, in good agreement with theory.

Journal Article↗
PubMed2000

A regulator of G protein signaling interaction surface linked to effector specificity.

Proteins of the regulator of G protein signaling (RGS) family accelerate GTP hydrolysis by the alpha subunits (G(alpha)) of G proteins, leading to rapid recovery of signaling cascades. Many different RGS proteins can accelerate GTP hydrolysis by an individual G(alpha), and GTP hydrolysis rates of different G(alpha)s can be enhanced by the same RGS protein. Consequently, the mechanisms for specificity in RGS regulation and the residues involved remain unclear. Using the evolutionary trace (ET) method, we have identified a cluster of residues in the RGS domain that includes the RGS-G(alpha) binding interface and extends to include additional functionally important residues on the surface. One of these is within helix alpha3, two are in alpha5, and three are in the loop connecting alpha5 and alpha6. A cluster of surface residues on G(alpha) previously identified by ET, and composed predominantly of residues from the switch III region and helix alpha3, is spatially contiguous with the ET-identified residues in the RGS domain. This cluster includes residues proposed to interact with the gamma subunit of G(talpha)'s effector, cGMP phosphodiesterase (PDEgamma). The proximity of these clusters suggests that they form part of an interface between the effector and the RGS-G(alpha) complex. Sequence variations in these residues correlate with PDEgamma effects on GTPase acceleration. Because ET identifies residues important for all members of a protein family, these residues likely form a general site for regulation of G protein-coupled signaling cascades, possibly by means of effector interactions.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Co-expression of Gbeta5 enhances the function of two Ggamma subunit-like domain-containing regulators of G protein signaling proteins.

Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain, which mediates a specific interaction with Gbeta5. The role of such interactions in RGS function is unclear. RGS proteins can accelerate the kinetics of coupling of G protein-coupled receptors to G-protein-gated inwardly rectifying K(+) (GIRK) channels. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK channels in Xenopus oocytes to evaluate the effect of Gbeta5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When Gbeta5 was co-expressed with either RGS7 or RGS9, the acceleration of GIRK channel kinetics was strongly increased over that produced by RGS7 or RGS9 alone. RGS function was not enhanced by co-expression of Gbeta1, and co-expression of Gbeta5 alone had no effect on GIRK channel kinetics. Gbeta5 did not modulate the function either of RGS4, an RGS protein that lacks a GGL domain, or of a functional RGS7 construct in which the GGL domain was omitted. Enhancement of RGS7 function by Gbeta5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein.

Animals↗
PubMed2000

Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1.

Timely deactivation of the alpha-subunit of the rod G-protein transducin (Galphat) is essential for the temporal resolution of rod vision. Regulators of G-protein signalling (RGS) proteins accelerate hydrolysis of GTP by the alpha-subunits of heterotrimeric G proteins in vitro. Several retinal RGS proteins can act in vitro as GTPase accelerating proteins (GAP) for Galphat. Recent reconstitution experiments indicate that one of these, RGS9-1, may account for much of the Galphat GAP activity in rod outer segments (ROS). Here we report that ROS membranes from mice lacking RGS9-1 hydrolyse GTP more slowly than ROS membranes from control mice. The Gbeta5-L protein that forms a complex with RGS9-1 was absent from RGS9-/- retinas, although Gbeta5-L messenger RNA was still present. The flash responses of RGS9-/- rods rose normally, but recovered much more slowly than normal. We conclude that RGS9-1, probably in a complex with Gbeta5-L, is essential for acceleration of hydrolysis of GTP by Galphat and for normal recovery of the photoresponse.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Congenital cataracts: gene mapping.

Congenital cataracts are one of the major causes of induced blindness in children. Gene mapping is an important step in understanding the molecular defects of congenital cataracts. Some congenital cataract genes have been mapped, and more genes will be located and identified in the future. The locations and candidate locations of congenital cataract genes are discussed in this review.

Animals↗
PubMed2000

A new phase consistency criterion and its application in electron crystallography

In this work, we present the principles and potential advantages of a methodology to assess Fourier components in terms of phase consistency. We define a new phase consistency criterion among sets of spatially translated images based upon a novel conception of the spatial shift property of the Fourier transform. The article shows how this criterion can be used in the alignment stage of the 3D reconstruction process with a two-fold objective: Assessment of the frequency components and robustness in the alignment. In that sense, the article shows and analyzes the results obtained from the application of the new index of quality in the context of projection image alignment. We have focussed our attention on the electron crystallography field, by applying such a phase consistency definition over image reflections. The results that have been obtained show that the new phase-consistency definition may complement the traditional SNR-based index of quality (commonly known as IQ) of reflections. As a consequence, the reliability of the alignment may be improved by discarding those reflections judged as non-reliable according to the phase-consistency criterion.

Journal Article↗
PubMed2000

Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells.

Multipotent stem cells that generate both neurons and glia are widespread components of the early neuroepithelium. During CNS development, neurogenesis largely precedes gliogenesis: how is this timing achieved? Using clonal cell culture combined with long-term time-lapse video microscopy, we show that isolated stem cells from the embryonic mouse cerebral cortex exhibit a distinct order of cell-type production: neuroblasts first and glioblasts later. This is accompanied by changes in their capacity to make neurons versus glia and in their response to the mitogen EGF. Hence, multipotent stem cells alter their properties over time and undergo distinct phases of development that play a key role in scheduling production of diverse CNS cells.

Animals↗
PubMed2000

Functions of Lsm proteins in mRNA degradation and splicing.

Recent results have identified a family of Lsm (Like Sm) proteins that are related to the Sm protein family. Seven Lsm proteins form a complex, which interacts with the U6 snRNA and functions in splicing. In addition, a different complex of Lsm proteins interacts with cytoplasmic mRNA and promotes its turnover. These diverse functions of Lsm proteins suggest that they are important modulators of RNA biogenesis and function.

Humans↗
PubMed2000

Spectral behavior and pH dependence of N-hexadecyl-5-iminomethyl-8-hydroxyquinoline.

A new kind of amphiphile derived from 8-hydroxyquinoline, N-hexadecyl-5-iminomethyl-8-hydroxyquinoline (HIHQ) was synthesized and characterized by different physical methods. The influence of pH value on UV-vis absorption, fluorescence spectra were investigated and the surface pressure area isotherms were recorded under different pH subphase. The linear response range between the emission intensity and the concentration of HIHQ was 1-4 x 10(-6) mol L(-1). The strongest emission of HIHQ about 460 nm was obtained at pH 8.2 and the acid-base equilibrium of HIHQ in monolayer and solution was also discussed.

Hydrogen-Ion Concentration↗
PubMed2000

Oral mucosal Langerhans' cells as target, effector and vector in HIV infection.

The mechanism underlying a transition of the oral cavity mucosal epithelium towards susceptibility to opportunistic infections in HIV-seropositive patients was investigated. Phenotypic markers CD1a, HLA-DR, and CD86 of oral mucosal Langerhans' cells (LCs), p17 core protein of human immunodeficiency virus (HIV), and CD45RO of memory T cells were labeled on oral hairy leukoplakia lesional biopsies and clinically normal autologous tissue of HIV-infected patients. HIV p17 protein was detected in association with mucosal LCs, mainly within the lesional epithelium. There were significant correlations between the detection of HIV p17 and the depletion of LCs, and between the depletion of LCs and the presence of hairy leukoplakia lesions. Conjugates of activated LCs and memory T cells were also evident in the submucosal area of lesional biopsies. The findings from this study support the hypothesis that oral mucosal LCs are also the target of HIV infection. Cytopathic changes of LCs caused by productive HIV infection may contribute to selective depletion of LCs, which may impair the mucosal immunologic protection against colonization by microorganisms causing HIV-associated oral mucosal lesions.

AIDS-Related Opportunistic Infections↗
PubMed2000

Finasteride increases anagen hair in men with androgenetic alopecia.

BACKGROUND: The growth of scalp hair is a cyclical process of successive phases of growth (anagen) and rest (telogen). In previous clinical trials in men with androgenetic alopecia, treatment with finasteride increased scalp hair counts in a defined area (i.e. increased hair density). OBJECTIVES: The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle. PATIENTS/METHODS: Two hundred and twelve men, age 18-40 years, with androgenetic alopecia were randomized to receive finasteride 1 mg daily or placebo for 48 weeks. At baseline and at 24 and 48 weeks, macrophotographs were taken to measure total and anagen hair count in a 1-cm(2) target area of the scalp. RESULTS: At baseline, mean total and anagen hair counts in the finasteride group were 200 and 124 hairs, respectively (% anagen = 62%) and the anagen to telogen ratio was 1.74 (geometric mean). In the placebo group, the respective values were 196 and 119 hairs (% anagen = 60%) and 1.57. At week 48, the finasteride group had a net improvement (mean +/- SE) compared with placebo in total and anagen hair counts of 17.3 +/- 2.5 hairs (8.3% +/- 1.4%) and 27.0 +/- 2.9 hairs (26% +/- 3.1%), respectively (P < 0.001). Furthermore, treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47% (P < 0.001). In this study, treatment with finasteride 1 mg day(-1) for 48 weeks increased both total and anagen hair counts, and improved the anagen to telogen ratio. CONCLUSIONS: These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients.

Adolescent↗
PubMed2000

Substrate-bound beta-amyloid peptides inhibit cell adhesion and neurite outgrowth in primary neuronal cultures.

Accumulation of the beta-amyloid protein (Abeta) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism of Abeta toxicity remains unclear. Abeta can bind to the extracellular matrix, a structure that regulates adhesive events such as neurite outgrowth and synaptogenesis. The binding of Abeta to the extracellular matrix suggests that Abeta may disrupt cell-substrate interactions. Therefore, the effect of substrate-bound Abeta on the growth of isolated chick sympathetic and mouse cortical neurons was examined. Abeta1-40 and Abeta1-42 had dose-dependent effects on cell morphology. When tissue culture plates were coated with 0.1-10 ng/well Abeta, neurite outgrowth increased. Higher amounts of Abeta peptides (> or =3 microg/well) inhibited outgrowth. The inhibitory effect was related to aggregation of the peptide, as preincubation of Abeta1-40 for 24 h at 37 degrees C (a process known to increase amyloid fibril formation) was necessary for inhibition of neurite outgrowth. Abeta29-42, but not Abeta1-28, also inhibited neurite outgrowth at high concentrations, demonstrating that the inhibitory domain is located within the hydrophobic C-terminal region. Abeta1-40, Abeta1-42, and Abeta29-42 also inhibited cell-substrate adhesion, indicating that the effect on neurite outgrowth may have been due to inhibition of cell adhesion. The results suggest that accumulation of Abeta may disrupt cell-adhesion mechanisms in vivo.

Amyloid beta-Peptides↗
PubMed2000

Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction.

Protein kinase C (PKC) inhibitors, chelerythrine (Chel, 0.6 mg) and polymyxin B (Poly B, 1.0 mg), and PKC activators, phorbol 12-myristate 13-acetate (PMA, 0.05 mg) and 1-oleoyl-2-acetyl glycerol (OAG, 0.1 mg), were used as probes to investigate the role of PKC in mediation of ischemic preconditioning (IPC) of noncontracting pig latissimus dorsi (LD) muscles against infarction in vivo. These drugs were delivered to each LD muscle flap (8 x 12 cm) by 10 min of local intra-arterial infusion. It was observed that LD muscle flaps sustained 43 +/- 5% infarction when subjected to 4 h of global ischemia and 24 h of reperfusion. IPC with three cycles of 10 min ischemia-reperfusion reduced muscle infarction to 25 +/- 3% (P < 0.05). This anti-infarction effect of IPC was blocked by Chel (42 +/- 7%) and Poly B (37 +/- 2%) and mimicked by PMA (19 +/- 10%) and OAG (14 +/- 5%) treatments (P < 0.05), given 10 min before 4 h of ischemia. In addition, the ATP-sensitive K(+) (K(ATP)) channel antagonist sodium 5-hydroxydecanoate attenuated (P < 0.05) the anti-infarction effect of IPC (37 +/- 2%), PMA (44 +/- 17%), and OAG (46 +/- 9%). IPC, OAG, and Chel treatment alone did not affect mean arterial blood pressure or muscle blood flow assessed by 15-microm radioactive microspheres. Western blot analysis of muscle biopsies obtained before (baseline) and after IPC demonstrated seven cytosol-associated isoforms, with nPKCepsilon alone demonstrating progressive cytosol-to-membrane translocation within 10 min after the final ischemia period of IPC. Using differential fractionation, it was observed that nPKCepsilon translocated to a membrane compartment other than the sarcolemma and/or sarcoplasmic reticulum. Furthermore, IPC and preischemic OAG but not postischemic OAG treatment reduced (P < 0.05) muscle myeloperoxidase activity compared with time-matched ischemic controls during 16 h of reperfusion after 4 h of ischemia. Taken together, these observations indicate that PKC plays a central role in the anti-infarction effect of IPC in pig LD muscles, most likely through a PKC-K(ATP) channel-linked signal-transduction pathway.

Adenosine↗
PubMed2000

Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency.

The thiazolidinedione class of insulin-sensitizing, antidiabetic drugs interacts with peroxisome proliferator-activated receptor gamma (PPAR-gamma). To gain insight into the role of this nuclear receptor in insulin resistance and diabetes, we conducted metabolic studies in the PPAR-gamma gene knockout mouse model. Because homozygous PPAR-gamma-null mice die in development, we studied glucose metabolism in mice heterozygous for the mutation (PPAR-gamma(+/-) mice). We identified no statistically significant differences in body weight, basal glucose, insulin, or FFA levels between the wild-type (WT) and PPAR-gamma(+/-) groups. Nor was there a difference in glucose excursion between the groups of mice during oral glucose tolerance test, but insulin concentrations of the WT group were greater than those of the PPAR-gamma(+/-) group, and insulin-induced increase in glucose disposal rate was significantly increased in PPAR-gamma(+/-) mice. Likewise, the insulin-induced suppression of hepatic glucose production was significantly greater in the PPAR-gamma(+/-) mice than in the WT mice. Taken together, these results indicate that - counterintuitively - although pharmacological activation of PPAR-gamma improves insulin sensitivity, a similar effect is obtained by genetically reducing the expression levels of the receptor.

Animals↗
PubMed2000

[Dynamic features of some biochemical constituents in Gynostemma pentaphyllum under different environments].

With biochemical techniques, the authors preliminarilty examined the dynamics of polyphenols, free amino acids and water-soluble sugars in Gynostemma pentaphyllum collected from different regions and the relationships between them and climate factors. The dynamic patterns of these three types of constituents in stems, blades and shoots under the same environment were different. At different growth phases, stems and blades had different contributions to the constituents. The dynamics of them differed with their environments. Polyphenols, free amino acids and water-soluble sugars might regulate the growth and development of plants. Moreover, they were characterized by plasticity, and the dominant climate factors affecting the dynamics of the constituents varied greatly.

Amino Acids↗
PubMed2000

Factors influencing the expression of Fas and Fas ligand on newborn murine keratinocytes and fibroblasts.

OBJECTIVE: To investigate the expression of Fas, FasL mRNA and proteins on keratinocytes and fibroblasts, and the influence by retinoid acid (RA) and dexamethasone (Dex). METHODS: RNase protection assay and flow cytometry were used. RESULTS: Fas mRNA was expressed on neonatal murine keratinocytes and was up-regulated by all-trans retinoid acid and down-regulated by Dex. RA and Dex also increased the Fas protein expression on keratinocytes. Newborn murine keratinocytes express FasL mRNA, which was up-regulated by RA and Dex, while its protein expression was moderately induced by RA. Newborn murine fibroblasts also expressed Fas and FasL mRNA, which were up-regulated by the RA and Dex. CONCLUSIONS: The results indicated that RA and Dex might regulate apoptosis of keratinocytes and fibroblasts via the Fas-FasL system.

Animals↗