[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
Q Wang
Publications and source records attributed to Q Wang.
Stabilization of Si60 cage structure.
A comprehensive search for the stable geometries of bare Si60 and Si60 supported on a C60 fullerene was carried out using first principles calculations based on density functional theory. In contrast to previous theoretical studies and in agreement with recent experiments, we show that Si60 and C(60)@Si(60) clusters are unstable in the fullerenelike cage structure. However, Si60 cage can be stabilized by including within it, as endohedral units, small magic clusters such as Al12X (X=Si, Ge, Sn, Pb) and Ba@Si(20).
Journal Article↗
The Ribosomal Database Project (RDP-II): previewing a new autoaligner that allows regular updates and the new prokaryotic taxonomy.
The Ribosomal Database Project-II (RDP-II) pro-vides data, tools and services related to ribosomal RNA sequences to the research community. Through its website (http://rdp.cme.msu.edu), RDP-II offers aligned and annotated rRNA sequence data, analysis services, and phylogenetic inferences (trees) derived from these data. RDP-II release 8.1 contains 16 277 prokaryotic, 5201 eukaryotic, and 1503 mitochondrial small subunit rRNA sequences in aligned and annotated format. The current public beta release of 9.0 debuts a new regularly updated alignment of over 50 000 annotated (eu)bacterial sequences. New analysis services include a sequence search and selection tool (Hierarchy Browser) and a phylogenetic tree building and visualization tool (Phylip Interface). A new interactive tutorial guides users through the basics of rRNA sequence analysis. Other services include probe checking, phylogenetic placement of user sequences, screening of users' sequences for chimeric rRNA sequences, automated alignment, production of similarity matrices, and services to plan and analyze terminal restriction fragment polymorphism (T-RFLP) experiments. The RDP-II email address for questions or comments is rdpstaff@msu.edu.
Animals↗
Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats.
Tau hyperphosphorylation leads to formation of paired helical filament/neurofibrillary tangles, the hallmark lesion seen in Alzheimer's disease (AD) brain. An imbalanced regulation in protein kinases and protein phosphatases in the affected neurons is proposed to be a reasonable causative factor to the disease process. To verify the hypothesis, we have injected in the present study calyculin A, a potent and specific inhibitor of protein phosphatase (PP) 2A and PP1, into rat hippocampus bilaterally, thus reproduced an Alzheimer's-like deficiency in dephosphorylation system. It was found that calyculin A-injected rats developed lesions in spatial memory retention in Morris water maze test. At mean time, tau was hyperphosphorylated at Ser396/Ser404 (PHF-1) and Ser-262/Ser-356 (12E8) sites determined both by immunohistochemistry and Western blot. It is implicated that (1) PP2A and PP1 participate in the in vivo regulation of tau phosphorylation, and down-regulation of the two phosphatases will result in tau hyperphosphorylation; (2) hyperphosphorylation of tau at PHF-1 and 12E8 sites might be crucial to affect spatial memory in AD.
Animals↗
KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death.
Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies which cause syncope and sudden death. LQT1, due to mutations of KCNQ1 (KVLQT1), is the most common form. This study describes the genotype-phenotype characteristics in 10 families with mutations of KCNQ1, including 5 novel mutations. One hundred and two families with a history of lethal cardiac events, 55 LQTS, 9 Brugada syndrome, 18 idiopathic ventricular fibrillation (IVF), and 20 acquired LQTS, were studied by single-strand conformational polymorphism (SSCP) and DNA sequence analyzes. Families found to have KCNQ1 mutations were phenotyped using ECG parameters and cardiac event history, and genotype-phenotype correlation was performed. No mutations were found in Brugada syndrome, IVF, or acquired LQTS families. Ten out of 55 LQTS families had KCNQ1 mutations and 62 carriers were identified. Mutations included G269S in domain S5; W305X, G314C, Y315C, and D317N in the pore region; A341E and Q357R in domain S6; and 1338insC, G568A and T587M mutations in the C-terminus. W305X, G314C, Q357R, 1338insC, and G568A, appeared to be novel mutations. Gene carriers were 26 +/- 19 years (32 females). Baseline QTc was 0.47 +/- 0.03 s (range 0.40-0.57 s) and 40% had normal to borderline QTc (< or = 0.46 s). Typical LQT1 T wave patterns were present in at least one affected member of each family, and in 73% of all affected members. A history of cardiac events was present in 19/62 (31%), 18 with syncope, 2 with aborted cardiac arrest (ACA) and six with sudden death (SD). Two out of 6 SDs (33%) occurred as the first symptom. No difference in phenotype was evident in pore vs. non-pore mutations. KCNQ1 mutations were limited to LQTS families. All five novel mutations produced a typical LQT1 phenotype. Findings emphasize (1) reduced penetrance of QTc and symptoms, resulting in diagnostic challenges, (2) the problem of sudden death as the first symptom (33% of those who died), and (3) genetic testing is important for identification of gene carriers with reduced penetrance, in order to provide treatment and to prevent lethal cardiac arrhythmias and sudden death.
Arrhythmias, Cardiac↗
Abnormal pancreatic isoamylases in the serum of children with choledochal cyst.
PURPOSE: To investigate the changes of pancreatic isoamylases in the serum of children with choledochal cyst. METHODS: Serum and bile from 20 children with choledochal cyst were studied for total amylase activity and isoamylases. Using electrophoresis, the assay of pancreatic isoamylases was expressed by peak appearance rate (PAR) and ratio of isoenzyme activity (RIA). Serum from 20 healthy children and 12 adults with acute pancreatitis served as a comparison. RESULTS: The total amylase activity in the serum of children with choledochal cyst was slightly higher than that of healthy controls, but dramatically lower than that of acute pancreatitis. The serum of children with choledochal cyst showed 5 pancreatic peaks (PAR: P1, 100 %; P2, 100 %; P3, 100 %; P4, 75 %; P5, 45 %) without any major peak. In healthy controls, only P1 and P2 were present (PAR: P1, 40 %; P2, 100 %) with the latter being a major peak (RIA: 81.8 +/- 25.3 %). These results in children with choledochal cyst differed from those of patients with acute pancreatitis who presented with the less common P4 and no P5 (PAR: P1, 100 %; P2, 100 %; P3, 91.6 %; P4, 8.3 %). The pattern of pancreatic isoenzymes in bile was similar to that in the serum from patients with choledochal cyst. These abnormal pancreatic isoamylases gradually disappeared after operation. CONCLUSIONS: Abnormal pancreatic isoamylases, especially P4 and P5, are found in the serum of patients with choledochal cyst, which would point to a reflux of pancreatic juice into the biliary tract.
Abdominal Pain↗
Novel TBX5 mutations and molecular mechanism for Holt-Oram syndrome.
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3T3 Cells↗
Inactivation of olfactory sensilla of a single morphological type differentially affects the response of Drosophila to odors.
The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe. Our data suggest that BS are required for a normal sensitivity to many odorants with a variety of chemical structures, through a wide range of concentrations. Interestingly, however, in contrast to other odorants tested, the behavioral response of ablated flies to intermediate concentrations of propionic and butyric acids is normal, suggesting the involvement of sensilla unaffected by ectopic reaper expression, probably coeloconic sensilla that respond strongly to these two organic acids. As inactivation of BS causes an underestimation of the concentration of both acids detectable at both the highest and lowest odorants concentrations, our results suggest that concentration coding for these two odorants relies on the integration of signals from different subsets of sensilla, most likely of different morphological types.
Animals↗
Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice.
AIMS/HYPOTHESIS: Glucagon-like peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of glucagon-like peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes. METHODS: The potent glucagon-like peptide-1 analogue Exendin-4 or vehicle (control) was administered (i.p.; 1 nmol/kg) to obese 6-week old db/db mice daily for 14 days ( n=10). RESULTS: By 8 weeks of age, control db/db mice developed hyperglycaemia (fasting: 10.4+/-0.5 mmol/l), hyperinsulinaemia and impaired glucose tolerance. However, Exendin-4 treatment prevented hyperglycaemia (fasting: 6.1+/-1.0 mmol/l, p<0.01), with reduced plasma insulin concentrations ( p<0.001) and improved glucose tolerance ( p<0.05). Peripheral insulin sensitivity was not affected. However, insulin release in vivo and in vitro from the perfused pancreas was improved by Exendin-4, as were pancreatic insulin concentrations (0.54+/-0.02 vs 0.32+/-0.01 micro g/mg protein, p<0.05). These changes occurred in conjunction with increased beta-cell mass (3.01+/-0.31 vs 2.22+/-0.22 mg, p<0.05) and proliferation (BrdU(+) beta-cells: 1.08+/-0.20 vs 0.47+/-0.11%, p<0.05), as well as decreased apoptosis (Tunel (+) beta-cells: 0.37+/-0.06 vs 1.20+/-0.21%). Western blot demonstrated increased expression of Akt1 (by fivefold, p<0.01) and p44 MAP kinase (by sixfold, p<0.01), and decreased activation of caspase-3 (by 30%, p<0.05). CONCLUSION/INTERPRETATION: Our results suggest that Ex4 treatment delays the onset of diabetes in 6-8 week old db/db mice, through a mechanism involving Akt1 and expansion of the functional beta-cell mass.
Animals↗
Kinetic equation for gluons in the background gauge of QCD.
We derive the quantum kinetic equation for a pure gluon plasma, applying the background field and closed-time-path method. The derivation is more general and transparent than earlier works. A term in the equation is found which, as in the classical case, corresponds to the color charge precession for partons moving in the gauge field.
Journal Article↗
Novel genes expressed in subsets of chemosensory sensilla on the front legs of male Drosophila melanogaster.
Detection of courtship-activating female pheromones by contact chemoreceptors on the front legs of male Drosophila melanogaster is thought to play an important role in triggering courtship behavior. However, the chemosensory organs, cells, and molecules responsible are not known. We have isolated two genes, CheA29a and CheB42a, expressed in nonneuronal auxiliary cells within two nested subsets of chemosensory sensilla on the front legs of sexually mature, adult males. The proteins encoded by the CheA29a and CheB42a genes have no sequence similarity to each other or any other known protein, but they belong to two novel families of proteins encoded by the D. melanogaster genome. Members of the two families are predicted to have a single transmembrane domain at their amino terminus, probably to serve as a signal peptide, suggesting that they are soluble and secreted. Finally, in addition to CheA29a and CheB42a, other genes within each family are expressed preferentially in appendages where chemosensory organs are concentrated, in several cases in a male-specific manner. Our data suggest that CheA29a and CheB42a and other members of these two protein families are involved in male-specific chemical senses, perhaps pheromone response.
Amino Acid Sequence↗
Microvascular permeability of rat cerebral pia mater by using image computer analysis.
UNLABELLED: Microcirculation viviperception and fluorescent tracer techniques were used and digital image analysis applied for quantitative measurement of fluorescein sodium (FiNa) permeability in microvessels of the cerebral pia mater. The diffusion permeation equations of FiNa within the blood vessels and through the vessel walls into the perivascular tissue of normal rats and ischemic rats were established with two vessels as study object, thus the permeation speed equations under different ischemic conditions were deduced. Based on analysis of the results, we deduced the relation between the permeability and the intersection angle of two vessels. RESULT: logarithm model showed a good fit of the experiment data. The permeation equation showed logarithmic distribution and then tended towards stability. FiNa could pass through microvessel walls with the highest speed in the one-hour ischemic rat group, and the permeation speed of FiNa in rats receiving reperfusion after twelve hours of ischemia was much faster than that in normal rats. CONCLUSION: the method can be useful for quantitative analysis of cerebral pia mater microvascular permeability
Algorithms↗
Abrogation of bleomycin-induced lung fibrosis by nitric oxide synthase inhibitor, aminoguanidine in mice.
The effects of aminoguanidine (AG), a specific inhibitor of inducible nitric oxide synthase, on the bleomycin (BL)-induced lung fibrosis was evaluated in mice. The animals were placed into five groups: saline (SA)-instilled drinking water (SA+H(2)O), saline-instilled drinking water containing 0.5%AG (SA+0.5%AG), BL-instilled drinking water (BL+H(2)O), BL-instilled drinking water containing 0.2%AG (BL+0.2%AG), and BL-instilled drinking water containing 0.5%AG (BL+0.5%AG). The mice had free access to H(2)O or H(2)O containing AG and lab chow ad lib 2 days prior to intratracheal (IT) instillation of BL (0.07U/mouse/100 microL) or an equivalent volume of sterile isotonic saline. The mice in the SA+0.5%AG group consumed the greatest amount of AG without any ill effects than the mice in any other group. There were no differences in any of the measured biochemical determinants between the SA+H(2)O and SA+0.5%AG control groups. The IT instillation of BL in the BL+H(2)O group caused significant increases in the lipid peroxidation, hydroxyproline content, and prolyl hydroxylase activity of lungs and influx of inflammatory cells in the broncheoalveolar lavage fluid (BALF) as compared to both control groups. The intake of aminoguanidine by mice in the BL+0.5%AG group caused significant reductions in the BL-induced increases in all measured biochemical indices of lung fibrosis without any effects on the influx of inflammatory cells in the BALF. In fact, AG in both BL-treated groups additionally increased the total cell counts in the BALF from mice in the BL+0.2%AG and BL+0.5%AG groups as compared to the BL+H(2)O group. Histopathological evaluation of the lungs revealed that the mice in the BL+0.5%AG group had markedly fewer fibrotic lesions than mice in the BL+H(2)O group. These results demonstrate that aminoguanidine minimizes the BL-induced lung fibrosis at both the biochemical and the morphological level and support our earlier hypothesis that the production of nitric oxide plays a significant role in the pathogenesis lung fibrosis caused by BL.
Animals↗
Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100.
Lymphotactin (Lptn) is a C chemokine that attracts T cells and NK cells. Dendritic cells (DC) are highly efficient, specialized antigen-presenting cells and antigen-pulsed DC has been regarded as promising vaccines in cancer immunotherapy. The aim of our present study is to improve the therapeutic efficacy of DC-based tumor vaccine by increasing the preferential chemotaxis of DC to T cells. In this study, Lptn and/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model. Immunization of C57BL/6 mice with DC adenovirally cotransfected with Lptn and gp100 (Lptn/gp100-DC) could enhance the cytotoxicities of CTL and NK cells, increase the production of IL-2 and interferon-gamma significantly, as compared with immunization with gp100-DC, Lptn-DC, LacZ-DC, DC or PBS counterparts. The Lptn/gp100-DC immunized mice exhibited resistance to tumor challenge most effectively. It was found that the tumor mass of mice vaccinated by Lptn/gp100-DC showed obvious necrosis and inflammatory cell infiltration. In vivo depletion analysis demonstrated that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of Lptn/gp100-DC and CD4(+) T cells were necessary in the induction phase of tumor rejection, while NK cells were less important although they participated in the antitumor response either in the induction phase or in the effector phase. In the murine model with the pre-established subcutaneous B16 melanoma, immunization with Lptn/gp100-DC inhibited the tumor growth most significantly when compared with other counterparts. These findings provide a potential strategy to improve the efficacy of DC-based tumor vaccines.
Animals↗
The detection and recovery of Erysipelothrix spp. in meat and abattoir samples in Western Australia.
AIMS: To investigate the occurrence of Erysipelothrix rhusiopathiae and other Erysipelothrix spp. in abattoir and meat samples in Western Australia. METHODS AND RESULTS: Samples were collected from various parts of pig and sheep carcasses, as well as different sections of slaughtering line, pen soil and effluent. Previously evaluated culture methods were applied for the isolation of Erysipelothrix spp., in conjunction with phenotypic and genotypic detection and identification procedures. Of 109 samples from the two abattoirs, 35 (32.1%) were Erysipelothrix genus-specific PCR-positive. These came from swabs of animal exterior surfaces and joints, slaughtering areas, pig pen soil and abattoir effluent. Four samples (3.7%) from sheep arthritic joints and pig abattoir effluent were also E. rhusiopathiae species-specific PCR-positive. Of 123 carcass washing samples, 12 (9.8%) were genus-specific PCR-positive, and these came from all five kinds of meat samples tested, including beef, lamb, mutton, pork and chicken. Four of them (3.3%) were also species-specific PCR-positive. A total of 25 isolates was recovered from the samples, of which seven were identified as E. rhusiopathiae, seven were consistent with E. tonsillarum, and the remaining 11 were other species of Erysipelothrix. CONCLUSIONS: Erysipelothrix spp. can still be isolated and identified from specimens of animal origin with relative ease, provided that appropriate cultural and molecular procedures are used. Clinical microbiology laboratories may need to improve their diagnostic protocols. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms that E. rhusiopathiae and other species of Erysipelothrix continue to colonize and contaminate farmed animals and animal products. Erysipelothrix infection still poses a potential threat to the economy of the farmed animal industry, as well as being a potential human public health hazard.
Abattoirs↗
Screening of pyruvate-producing yeast and effect of nutritional conditions on pyruvate production.
AIMS: To find a yeast strain that can overproduce pyruvate and to investigate the effect of nutrients on pyruvate production. METHODS AND RESULTS: Trichosporon cutaneum PD70, a yeast strain that can overproduce pyruvate, was isolated from shake-flask cultures of 132 yeast strains. Pyruvate was measured by the HPLC or DNP method (see Materials and methods). Pyruvate production reached approximately 30.0 +/- 1.0 g l(-1) in basal fermentation medium. Different nutrient supplements had great effects on pyruvate production. Some of the conditions that gave the highest yield are described. CONCLUSIONS: Exogenous thiamine supplement caused a decrease in pyruvate yield. Some amino acids, such as L-arginine, L-isoleucine and L-valine, caused a minor increase in pyruvate yield. Soybean peptone was the most suitable nitrogen source for pyruvate production. A glucose concentration of 15% in fermentation medium gave the highest yield (34.6 g l(-1)) and the highest yield against consumed glucose (0.429 g g(-1)). SIGNIFICANCE AND IMPACT OF THE STUDY: Nutrients have significant impacts on pyruvate production. As a pyruvate overproducing yeast strain independent of exogenous vitamins or amino acids, T. cutaneum PD70 provides an advantage for commercial pyruvate production.
Amino Acids↗
The effect of zolpidem on operant behavior and its relation to pharmacokinetics after intravenous and subcutaneous administration: concentration-effect relations.
We characterized the effects of i.v. and s.c. zolpidem (1-8 mg/kg) under a differential reinforcement of low-rate schedule (i.e. DRL 45 s) in 3-hour sessions. Both behavioral and pharmacokinetic-pharmacodynamic analyses were used with the intent to compare the effects of zolpidem with those of benzodiazepines reported previously under the same behavioral paradigm. Zolpidem increased the shorter-response [inter-response times (IRTs)<45 s] rate and decreased the reinforcement rate in a dose- and time-related fashion. The behavioral profiles of zolpidem were mainly similar to those of benzodiazepines, except zolpidem produced far fewer shorter IRT responses. Pharmacokinetically, zolpidem decays biexponentially with distributional and terminal elimination half-lives of 5.2 and 42 min, respectively. The absorption rate constant and absolute bioavailability for s.c. zolpidem were 0.083/min and of 84.1%, respectively. The pharmacodynamic parameters for the reinforcement rate, an index of timing performance, were determined by integration of behavioral and pharmacokinetic profiles in a between-subject design using the effect-linked inhibitory sigmoidal E(max) model. The pharmacokinetic-pharmacodynamic analysis revealed that the potency of zolpidem (concentration required to produce 50% maximal effects, IC(50)) in disrupting the timing performance was 0.129 microg/ml. The pharmacodynamic estimates of zolpidem were compared to our previous results for benzodiazepines.
Animals↗
Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells.
BACKGROUND: The transcription factor encoded by the intestinal Cdx2 homeobox gene and treatment with sodium butyrate (NaB), a byproduct of fibre fermentation by colonic bacteria, exert similar effects on colon cancer cell lines as they both inhibit cell growth and stimulate cell differentiation and apoptosis. AIM: To investigate whether NaB regulates expression of the Cdx2 gene in colon cancer cell lines. METHODS: Human adenocarcinoma cell lines Caco2 and HT29 were grown in the presence or absence of NaB. Cells were analysed for Cdx2 mRNA expression by reverse transcription-polymerase chain reaction, for protein expression by western blotting and electromobility shift assays, and for transcriptional activity of the Cdx2 promoter by transfection with luciferase reporter plasmids. RESULTS: In HT29 and Caco2 cells, NaB stimulated Cdx2 mRNA and protein expression as well as transcriptional activity of the Cdx2 promoter. Stimulation of the activity of the Cdx2 promoter by NaB was dose and time dependent. The Cdx2 promoter contains discrete regions that participate in or inversely that blunt the stimulatory effect exerted by NaB. In addition, NaB stimulated the transcriptional activity of the Cdx2 promoter downregulated by oncogenic ras. CONCLUSION: This study is the first report of an intestine specific transcription factor, Cdx2, stimulated by butyrate. Thus it provides a new mechanism whereby butyrate controls proliferation and differentiation of colon cancer cells.
Adenocarcinoma↗