[Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis].

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion: Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

Expressed sequence tag-PCR markers for identification of alien barley chromosome 2H in wheat.

We developed EST-PCR markers specific to barley chromosome 2H, for the purpose of effectively tracing alien chromosomes or chromosome parts in the wheat genetic background. The target alien chromosome 2H confers high resistance to pre-harvest sprouting, which is a worldwide natural disaster in wheat. A total of 120 primer pairs were selected by combining the wheat group 2 chromosomes of the EST database and the genome sequences of the new model plant Brachypodium distachyon. Seventy-seven of 120 primer pairs were polymorphic and 31 of 120 primer pairs were monomorphic between a set of wheat-barley chromosome 2H disomic addition/substitution lines and their parents by agarose gel electrophoresis and polyacrylamide gel electrophoresis. Thirty of 77 polymorphic primer pairs including primer pair P120 derived from the basi gene were chromosome 2H-specific. These markers are expected to be valuable in screening of wheat-barley chromosome 2H recombination lines and pre-harvest sprouting resistant varieties.

Development of EST-PCR markers for Thinopyrum intermedium chromosome 2Ai#2 and their application in characterization of novel wheat-grass recombinants.

A series of expressed sequence tags-derived polymerase chain reaction (EST-PCR) markers specific to chromosome 2Ai#2 from Thinopyrum intermedium were developed in this study using a new integrative approach. The target alien chromosome confers high resistance to barley yellow dwarf virus (BYDV), which is a severe virus disease in wheat. To generate markers evenly distributed on 2Ai#2, a total of 105 primer pairs were designed based on mapped ESTs from 8 bins of wheat chromosome 2B with intron-prediction by aligning ESTs with genomic sequences of the new model plant Brachypodium distachyon. Eight and seven polymorphic markers on the short arm and the long arm of chromosome 2Ai#2, respectively, were obtained with a polymorphism rate of 14.3%. These chromosome 2Ai#2-specific EST-PCR markers were then used in tracing and exploring the structural variation of the alien chromosome in the population derived from the immature embryo culture of the cross between N452, a 2Ai#2(2D) substitution line, and common wheat CB037. Two centric fusion of translocations involving 2Ai#2 short or long arm with wheat chromosome 2D and some new genetic stocks including telosomes with the alien chromosome short or long arm were identified in the SC(3) generations, which provided basic materials to further study the mechanism of the BYDV resistance. BYDV tests in two field seasons suggest that the BYDV resistance was mainly conferred by the short arm, gene interaction on both arms of the alien chromosome was discussed.

Heterogeneity of GABAA receptor in goldfish retina.

The possibility of GABAA receptor heterogeneity in goldfish retina was studied with immunocytochemical and biochemical approaches: 1) immunoblotted membrane particulates of goldfish retina with mAb 62-3G1; 2) immunoprecipitation of the detergent-solubilized membrane proteins with mAb 62-3G1 followed by the receptor binding assay; 3) photoaffinity labeling of the membrane particulates with 3H-flunitrazepam (FNZ) and visualization of the labeled receptors by SDS-PAGE and fluorography; 4) dry autoradiography of 3H-muscimol and 3H-FNZ binding sites on frozen sections. Immunoblots showed that 62-3G1 reacted with 55-57.5 kDa M(r) polypeptides, similar to the muscimol-binding subunit of the receptor complex in bovine brain; while 3H-FNZ photoaffinity labeled the 52.5 kDa and 41-43 kDa M(r) polypeptides. Immunoprecipitated receptors bound only 3H-muscimol, not 3H-FNZ. An attempt to precipitate the 3H-FNZ photolabeled polypeptides failed. Dry autoradiography showed 3H-FNZ binding only in the inner plexiform layer (IPL); the binding was enhanced with gamma-aminobutyric acid (GABA) and blocked by clonazepam. In contrast, 3H-muscimol was bound in both the outer plexiform layer (OPL) and IPL, similar to that observed with 62-3G1 immunocytochemistry. We suggest that there are two subtypes of GABAA receptor in the goldfish retina: 1) GABAA receptors that are not linked to a benzodiazepine (BZD) receptor are located in the OPL and at amacrine-to-amacrine and amacrine-to-ganglion cell synapses in the IPL and are recognized by 62-3G1; 2) GABAA receptors that are linked to a BZD receptor are located only in the IPL, largely at amacrine-to-bipolar cell synapses and are not recognized by mAb 62-3G1.

Primary angiitis of the central nervous system: unusual MR appearance.

The MR findings of a biopsy-proved case of primary angiitis of the central nervous system are described and compared with previously reported cases. Multiple punctate and linear areas of gadopentetate dimeglumine enhancement were present in the brain stem and white matter and appear to correspond to the inflammatory reaction of the small perforating vessels and perivascular tissues seen in the pathologic specimen.

Differential effects of dopamine depletion on the distribution of [3H]SCH 23390 and [3H]spiperone binding sites in the goldfish retina.

The distributions of dopamine D1 and D2 receptors were studied in intact goldfish retina with in vitro autoradiography. Specific [3H]SCH 23390 binding (D1 receptors) was greatest over the outer plexiform layer (OPL)/horizontal cell bodies and less so over the inner nuclear and inner plexiform layers (IPL). Specific [3H]spiperone binding (D2 receptors) appeared in two bands, over the OPL/horizontal cell bodies and the IPL. Depletion of retinal dopamine, by intraocular injections of 6-hydroxydopamine, had no effect on the pattern and density of [3H]SCH 23390 binding; however, specific [3H]spiperone binding over the OPL and IPL was virtually eliminated, suggestive of D2 autoreceptors on dopamine interplexiform cells. These data are consistent with electrophysiological studies indicating the presence of D1 and D2 receptors in both plexiform layers of the goldfish retina.

Dopaminergic control of light-adaptive synaptic plasticity and role in goldfish visual behavior.

Dopamine has been implicated in processes of retinal light and dark adaptation. In goldfish retina, horizontal cell dendrites elaborate neurite processes (spinules) into cone terminals, in a light- and dopamine-dependent manner. However, the functions of retinal dopamine and the horizontal cell spinules in visual behavior are unknown. These issues were addressed in behavioral, electroretinographic, and anatomical studies of normal fish and those with unilateral depletion of retinal dopamine induced by intraocular (i.o.) injections with 6-hydroxydopamine (6-OHDA). Dopamine interplexiform cells (DA-IPC) disappear within 2 weeks after 6-OHDA injection; cell bodies appear at the marginal zone within 6 weeks at which time neurites slowly reinnervate the retina with a sparse plexus over the next 12 months. We found that dopamine depletion increased light sensitivity at photopic but not scotopic backgrounds by 2.5 log units, an effect mimicked by i.o. injections of dopamine D1 and D2 antagonists. The ERG b-wave increment thresholds were the same for control and dopamine depleted eyes, indicating a normal transition from rod to cone systems in the ON pathway. Light-dependent spinule formation was reduced by about 60% in dopamine-depleted retinas, but returned to normal by 3 months and 9 months after injection in the entire retina, even areas not directly innervated with DA-IPC processes. Spinule formation in vivo was inhibited 50% with i.o. injection of SCH 23390 in control retinas as well as throughout 3 month 6-OHDA injected retinas, including DA-IPC free areas. This latter result indicates a volume effect of dopamine, diffusing laterally through the retina over several millimeters, in regulating spinules. We conclude that DA-IPCs regulate sensitivity to background at photopic levels not via the ON pathway, but perhaps the OFF pathway. Goldfish display both increased sensitivity to light and a normal Purkinje shift in the ERG b-wave whether or not horizontal cell spinules are present, indicating that dopamine control of photopic vision in fish is not mediated through light-induced spinule formation of horizontal cell dendrites.

Retinoids bound to interstitial retinol-binding protein during light and dark-adaptation.

High-performance liquid chromatography was used to determine the types and amounts of retinoids bound to interstitial retinol-binding protein (IRBP) during light- and dark-adaptation in frogs. IRBP was separated from CRBP and CRA1BP by ion-exchange chromatography and quantitated by determining the amount of Serva Blue R dye bound to it in stained sodium dodecyl sulfate polyacrylamide gels. The amount of IRBP was not significantly different in light- and dark-adapted eyes (0.15 +/- 0.05 nmol/eye compared with 0.18 +/- 0.08 nmol/eye). In the dark-adapted state, IRBP bound mainly 11-cis retinol and 11-cis retinal in quantities that summed to about 1 mol/mol IRBP. After the onset of light-adaptation, all-trans retinol increased from its very low dark-adapted level, peaked at 0.2 mol/mol IRBP and then declined to the dark-adapted level again. Concomitantly, the total retinoid bound to IRBP fell, mainly because there was a drop in the amount of 11-cis retinal. During dark-adaptation, the amount of 11-cis retinal increased. No significant changes were seen in the amount of 11-cis retinol in light and darkness. These findings support the hypothesis that when rhodopsin is bleached IRBP transports all-trans retinol from the retina to the pigment epithelium and that it delivers 11-cis retinal to the rod outer segments for rhodopsin regeneration.

Patchy environment as a factor of complex plankton dynamics.

We study the role of the diffusive interaction in plankton dynamics in a patchy environment. We use a minimal reaction-diffusion model of the nutrient-plankton-fish food chain to simulate the diffusive interaction between fish-populated and fish-free habitats. We show that such interaction can give rise to spatiotemporal plankton patterns. The plankton dynamics depend on the fish predation rate and can exhibit both regular and chaotic behavior. We show that limit cycle and chaotic attractor coexist in the system. The entire basin of attraction of the limit cycles is found to be riddled with "holes" leading to the competitive chaotic attractors. The chaotic dynamics is typical of a wide range of the fish predation rates.

[Identification of the barley chromosome in wheat by GISH and RFLP].

The barley chromosome in wheat was identified by genomic in situ hybridization (GISH) in which biotin labelled total genomic DNA of barley Betzes was used as probe and the unlabelled total DNA of common wheat Chinese Spring (CS) as blocking DNA. A series of wheat materials were tested as follows: two disomic alien substitution and monosomic alien addition lines, 2n = 43; two monosomic alien substitution lines, 2n = 42; seven disomic alien substitution lines, 2n = 42. RFLP probe psr131 on the short arm of the homologous group 2 was used to analyze the barley chromosome in wheat. The result indicated that there was a same band in barley Betzes and substitution line A5. The chromosome 2A of A5 was substituted by the chromosome 2H of barley. These materials will be useful in transferring the valuable genes in the chromosome 2H to wheat.

[Molecular cytogenetic characterization of a new wheat line YW443 with resistance to barley yellow dwarf virus].

A new wheat line YW443 with BYDV resistance and good traits was developed from the combination of PP9-1/Shan7859¿Fengkang 8. The wheat line YW443 was identified by BYDV resistance analysis, genomic in situ hybridization (GISH), RFLP and RAPD analysis. The results indicated as follows: (1) YW443 was resistant to GPV and GAV strains of BYDV; (2) YW443 is a homozygous wheat-Thinopyrum intermedium translocation line with a pair of BYDV resistance genes; (3) The 7StL segment of Th. intermedium carring BYDV resistance gene was transferred onto the distal end of the wheat chromosome 7D long arm, the line YW443 was 7DS.7DL-7StL translocation; (4) A RAPD marker OPR19(-900) could detect the DNA of Th. intermedium 7StL in L1 and L1 derivatives including translocation lines YW443, YW642 etc. The markers may be used as a selecting marker for the BYDV resistance breeding program.

Isolation and molecular analysis of genes Stpk-V2 and Stpk-V3 homologous to powdery mildew resistance gene Stpk-V in a Dasypyrum villosum accession and its derivatives.

Wheat-Dasypyrum villosum translocated chromosomes T6V#2S•6AL and T6V#4S•6DL are known to confer excellent resistance to wheat powdery mildew (PM). However, it is difficult to distinguish the two sources of PM resistance genes through multi-pathotype testing because to date no virulence for them has been found. To reveal the relationship between the PM resistance genes from the two translocations, the sequence of the Stpk-V gene, a key member of powdery mildew resistance locus Pm21, was used as a reference to isolate homologous genes from a D. villosum accession No.1026 and its derivatives 6V#4(6D) disomic substitution (DS) line RW15 and T6V#4S•6DL translocation line Pm97033. Two genes Stpk-V2 and Stpk-V3 were cloned from No.1026. Sequence alignment showed that Stpk-V2 and Stpk-V3 shared 98.2 % and 96.2 % of their DNA and 99.3 % and 100 % of their amino acids in identity with Stpk-V. Compared with Stpk-V, a 22-bp direct sequence repeat and a miniature inverted-repeat transposable element (MITE) were found in the intron 4 of Stpk-V2 and Stpk-V3, respectively. However, Stpk-V2 was not present in DS line RW15 and translocation line Pm97033 based on the PCR result, indicating that Stpk-V2 did not contribute to the PM resistance of RW15 and Pm97033. In the promoter region, a 78-bp insertion was found not only in Stpk-V2 and Stpk-V3, but also in its orthologous gene Stpk-A of wheat. In addition, there was a 17 bp/8 bp deletion/insertion in the putative promoter of Stpk-V3 in comparison with that of Stpk-V/Stpk-V2. Real-time quantitative RT-PCR analysis indicated that the expression levels of Stpk-V and Stpk-V3 genes in the translocation lines were induced by the pathogen, but Stpk-V had a higher expression level than Stpk-V3 at 12 h after inoculation with Bgt. The diversity of Stpk-V gene will help to explore new resistance genes to PM in D. villosum for wheat breeding.

Energy band gap engineering in borate ultraviolet nonlinear optical crystals: ab initio studies.

The development of ultraviolet (UV) nonlinear optical (NLO) crystals demands optical materials with wide energy band gaps. Here we report first-principles studies on the electronic structures in several UV NLO borates with representative structures. Combined with model analysis, we find that the oxygen non-bonding 2p orbitals play an important role on the top of valence bands. The energy band gap can be adjusted by modifying the coordination environment around the oxygen atoms. Under ideal conditions the energy band gaps achieve 9 eV if the non-bonding orbitals are totally eliminated, despite the original values varying from 6.6 to 8.3 eV.

Ab initio studies on the optical effects in the deep ultraviolet nonlinear optical crystals of the KBe2BO3F2 family.

Electronic structures of the deep ultraviolet nonlinear optical crystals of the KBe(2)BO(3)F(2) (KBBF) family, including KBBF, RbBe(2)BO(3)F(2) and CsBe(2)BO(3)F(2), have been investigated based on a plane-wave pseudopotential method. Their linear and nonlinear optical coefficients are also calculated, and are in good agreement with the experimental results. A real-space atom-cutting method is adopted to analyze the respective contributions of the alkali metal cations and anionic groups to optical response. The results show that the contributions of anionic groups to the nonlinear optical anisotropic responses are dominant, but the influence of the A-site alkali metal cations becomes slightly more pronounced with the increase of their radius. Moreover, the birefringence difference among these crystals strongly depends on the volume effect, i.e., the spatial density of the (BO(3))(3-) anionic groups.

The electronic structure of RbTiOPO4 and the effects of the A-site cation substitution in KTiOPO4-family crystals.

The electronic structure of RbTiOPO(4) has been investigated with x-ray photoemission spectroscopy. Detailed photoemission spectra of the element core levels have been recorded under excitation by nonmonochromatic Al Kα radiation (1486.6 eV). The chemical bonding parameters are compared to those reported for complex titanates and phosphates. The band structures of KTiOPO(4), RbTiOPO(4), K(0.535)R(0.465)TiOPO(4) and TlTiOPO(4) have been calculated by ab initio methods and compared to available experimental results. It is found that the band structure of KTP-type phosphate crystals is weakly dependent on the nature of the A-site (A=K, Rb, Tl) element.

Habitat destruction and the extinction debt revisited: the Allee effect.

Habitat destruction, often caused by anthropogenic disturbance, can lead to the extinction of species at an unprecedented rate. It is important, therefore, to consider habitat destruction when assessing population viability. Another factor often ignored in population viability analysis, is the Allee effect that adds to the risk of populations already on the verge of extinction. Understanding the Allee effect on species dynamics and response to habitat destruction has intrinsic value in conservation prioritization. Here, the Allee effect was considered in a multi-species hierarchical competition model. Results showed that species persistence declines dramatically due to the Allee effect, and certain species become more susceptible to habitat destruction than others. Two extinction orders emerged under habitat destruction: either the best competitor becomes extinct first or the best colonizer first. The extinction debt and order, as well as the time lag between habitat destruction and species extinction, were found to be determined by species abundance and the intensity of the Allee effect.

Optical properties of LiGaS(2): an ab initio study and spectroscopic ellipsometry measurement.

Electronic and optical properties of lithium thiogallate crystal, LiGaS(2), have been investigated by both experimental and theoretical methods. The plane-wave pseudopotential method based on DFT theory has been used for band structure calculations. The electronic parameters of Ga 3d orbitals have been corrected by the DFT+U methods to be consistent with those measured with x-ray photoemission spectroscopy. Evolution of optical constants of LiGaS(2) over a wide spectral range was determined by developed first-principles theory and dispersion curves were compared with optical parameters defined by spectroscopic ellipsometry in the photon energy range 1.2-5.0 eV. Good agreement has been achieved between theoretical and experimental results.