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Showing papers by "Feng Zhang published in 2005"


Journal ArticleDOI
TL;DR: In this paper, the authors adapted the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons.
Abstract: Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.

4,411 citations


Journal ArticleDOI
03 Aug 2005-JAMA
TL;DR: Findings replicate the Dutch data for a separate racial group and show that prenatal exposure to famine increases risk of schizophrenia in later life.
Abstract: ContextSchizophrenia is a common major mental disorder. Intrauterine nutritional deficiency may increase the risk of schizophrenia. The main evidence comes from studies of the 1944-1945 Dutch Hunger Winter when a sharp and time-limited decline in food intake occurred. The most exposed cohort conceived during the famine showed a 2-fold increased risk of schizophrenia.ObjectiveTo determine whether those who endured a massive 1959-1961 famine in China experienced similar results.Design, Setting, and ParticipantsThe risk of schizophrenia was examined in the Wuhu region of Anhui, one of the most affected provinces. Rates were compared among those born before, during, and after the famine years. Wuhu and its surrounding 6 counties are served by a single psychiatric hospital. All psychiatric case records for the years 1971 through 2001 were examined, and clinical and sociodemographic information on patients with schizophrenia was extracted by researchers who were blinded to the nature of exposure. Data on number of births and deaths in the famine years were available, and cumulative mortality was estimated from later demographic surveys.Main Outcome MeasuresEvidence of famine was verified, and unadjusted and mortality-adjusted relative risks of schizophrenia were calculated.ResultsThe birth rates (per 1000) in Anhui decreased approximately 80% during the famine years from 28.28 in 1958 and 20.97 in 1959 to 8.61 in 1960 and 11.06 in 1961. Among births that occurred during the famine years, the adjusted risk of developing schizophrenia in later life increased significantly, from 0.84% in 1959 to 2.15% in 1960 and 1.81% in 1961. The mortality-adjusted relative risk was 2.30 (95% confidence interval, 1.99-2.65) for those born in 1960 and 1.93 (95% confidence interval, 1.68-2.23) for those born in 1961.ConclusionOur findings replicate the Dutch data for a separate racial group and show that prenatal exposure to famine increases risk of schizophrenia in later life.

727 citations


Journal ArticleDOI
TL;DR: The present study examines two polymorphisms in linkage disequilibrium in the BDNF gene, which have been variously reported as associated with schizophrenia and BP, and concludes that, although the val66met polymorphism has been reported to alter gene function, the risk may depend upon the haplotypic background on which the val/met variant is carried.
Abstract: Schizophrenia is a severe psychiatric disease with a strong genetic component. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar (BP) disorders. The present study has examined two polymorphisms in linkage disequilibrium in the BDNF gene, which have been variously reported as associated with schizophrenia and BP. In our study, 321 probands with a primary diagnosis of schizophrenia or schizoaffective disorder, and 263 with a diagnosis of bipolar affective disorder, were examined together with 350 controls drawn from the same geographical region of Scotland. The val66met single-nucleotide polymorphism (SNP) showed significant (P = 0.005) association for valine (allele G) with schizophrenia but not bipolar disorder. Haplotype analysis of val/met SNP and a dinucleotide repeat polymorphism in the putative promoter region revealed highly significant (P < 1 x 10(-8)) under-representation of the methionine or met-1 haplotype in the schizophrenic but not the BP population. We conclude that, although the val66met polymorphism has been reported to alter gene function, the risk may depend upon the haplotypic background on which the val/met variant is carried.

276 citations


Journal ArticleDOI
TL;DR: The results indicate that the Hmong populations had experienced more contact with the northern East Asians, a finding consistent with historical evidence.
Abstract: Hmong-Mien (H-M) is a major language family in East Asia, and its speakers distribute primarily in southern China and Southeast Asia. To date, genetic studies on H-M speaking populations are virtually absent in the literature. In this report, we present the results of an analysis of genetic variations in the mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS1) region and diagnostic variants in the coding regions in 537 individuals sampled from 17 H-M populations across East Asia. The analysis showed that the haplogroups that are predominant in southern East Asia, including B, R9, N9a, and M7, account for 63% (ranging from 45% to 90%) of mtDNAs in H-M populations. Furthermore, analysis of molecular variance (AMOVA), phylogenetic tree analysis, and principal component (PC) analysis demonstrate closer relatedness between H-M and other southern East Asians, suggesting a general southern origin of maternal lineages in the H-M populations. The estimated ages of the mtDNA lineages that are specific to H-M coincide with those based on archeological cultures that have been associated with H-M. Analysis of genetic distance and phylogenetic tree indicated some extent of difference between the Hmong and the Mien populations. Together with the higher frequency of north-dominating lineages observed in the Hmong people, our results indicate that the Hmong populations had experienced more contact with the northern East Asians, a finding consistent with historical evidence. Moreover, our data defined some new (sub-)haplogroups (A6, B4e, B4f, C5, F1a1, F1a1a, and R9c), which will direct further efforts to improve the phylogeny of East Asian mtDNAs.

115 citations


Journal ArticleDOI
TL;DR: In this paper, the dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia, and a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied.
Abstract: The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms (SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 (SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.

62 citations


Journal ArticleDOI
TL;DR: It is shown here that rearrangements induced by reversed Ac ends transposition can join the coding and regulatory sequences of two linked paralogous genes to generate a series of chimeric genes, some of which are functional.
Abstract: The maize Activator/Dissociation (Ac/Ds) elements are members of the hAT (hobo, Ac, and Tam3) superfamily of type II (DNA) transposons that transpose through a “cut-and-paste” mechanism. Previously, we reported that a pair of Ac ends in reversed orientation is capable of undergoing alternative transposition reactions that can generate large-scale chromosomal rearrangements, including deletions and inversions. We show here that rearrangements induced by reversed Ac ends transposition can join the coding and regulatory sequences of two linked paralogous genes to generate a series of chimeric genes, some of which are functional. To our knowledge, this is the first report demonstrating that alternative transposition reactions can recombine gene segments, leading to the creation of new genes.

55 citations


Journal ArticleDOI
TL;DR: Results indicated that either decrease of Ang II or blockage of AT1 receptor in the PVN normalized the enhanced CSAR evoked by epicardial application of BK in rats with CHF, and that increased expression of AT 1 receptor inThe PVN contributed to theEnhanced CSAR in the CHF state.
Abstract: Our previous studies have shown that the cardiac sympathetic afferent reflex (CSAR) was enhanced in the chronic heart failure in dogs and rats. Exogenous angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated this reflex which was mediated by AT1 receptor. The aim of the present study was to determine if the abnormal endogenous Ang II and AT1 receptor in the PVN were responsible for the enhanced CSAR in rats with coronary ligation-induced chronic heart failure (CHF). Under urethane and alpha-chloralose anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded in sino-aortic denervated and cervical vagotomized CHF and sham-operated rats. The effects of bilateral microinjection of AT1 receptor antagonist losartan and angiotensin converting enzyme inhibitor captopril on the CSAR evoked by epicardial application of bradykinin (BK, 0.04 and 0.4 microg) were determined respectively. Both AT1 receptor mRNA and AT1 receptor protein in the PVN were measured. Bilateral microinjection of either captopril (10 nmol) or losartan (50 nmol) into the PVN inhibited the enhanced CSAR evoked by BK in rats with CHF, but had no significant effects in sham-operated rats. AT1 receptor protein in the PVN significantly increased in CHF rats compared with sham-operated rats. These results indicated that either decrease of Ang II or blockage of AT1 receptor in the PVN normalized the enhanced CSAR evoked by epicardial application of BK in rats with CHF, and that increased expression of AT1 receptor in the PVN contributed to the enhanced CSAR in the CHF state.

48 citations


Journal ArticleDOI
TL;DR: The red pericarp color specified by P1-rw1077 suggests that the p1- and p2-encoded proteins are functionally equivalent as regulatory factors in the flavonoid biosynthesis pathway.
Abstract: The maize (Zea mays) p1 (for pericarp color1) gene encodes an R2R3 Myb-like transcription factor that regulates the flavonoid biosynthetic pathway in floral organs, most notably kernel pericarp and cob. Alleles of the p1 gene condition distinct tissue-specific pigmentation patterns; to elucidate the molecular basis of these allele-specific expression patterns, we characterized two novel P1-rw (for red pericarp/white cob) alleles, P1-rw1077 and P1-rw751∷Ac. Structural analysis of P1-rw1077 indicated that this allele was generated by recombination between p1 and the tightly linked paralogous gene, p2. In the resulting gene, the p1 coding sequence was replaced by the p2 coding sequence, whereas the flanking p1 regulatory sequences remained largely preserved. The red pericarp color specified by P1-rw1077 suggests that the p1- and p2-encoded proteins are functionally equivalent as regulatory factors in the flavonoid biosynthesis pathway. Sequence analysis shows that the P1-rw1077 allele lacks a 386-bp sequence in a distal enhancer region 5 kb upstream of the transcription start site. An independently derived P1-rw allele contains an Ac insertion into the same sequence, indicating that this site likely contains cob glume–specific regulatory elements.

44 citations


Journal ArticleDOI
TL;DR: Association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups.
Abstract: We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; χ2 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (χ2 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.

41 citations


Journal ArticleDOI
TL;DR: Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment, and can provide potent protection against cold I/R injury.
Abstract: CONCLUSION: HO-1 overexpression can provide potent protection against cold I/R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism.

31 citations


Journal ArticleDOI
TL;DR: It is concluded that both tempol and tiron significantly reduce reperfusion-induced arrhythmias in rats, and this protective action is independent of hemodynamic effects.

Journal ArticleDOI
TL;DR: The data suggested that there existed the statistical relationship between the infection of HPV16 and the expression of CD44v6 in ESCCs and that HPV16 may be involved in invasion and metastasis of ESCC.
Abstract: The esophageal squamous cell carcinoma (ESCC) has high incidence in Shaanxi Province of China. More and more researches indicated that human papillomavirus type 16 (HPV16) might play an important role in carcinogenesis of ESCC but the relationship between HPV16 and CD44v6, nm23H1 has not been elucidated. HPV16 was detected by amplifying HPV16 E6 gene through polymerase chain reaction (PCR) method and the expression of CD44v6, nm23H1 in 40 ESCCs and fifteen normal esophageal mucosa (NEM) from Shaanxi Province was examined by Streptavidin-Peroxidase (SP) method using monoclonal antibody specific to CD44v6 and nm23H1. The positive rates of HPV16 E6 gene, CD44v6 and nm23H1 were 60% (24/40), 65% (26/40) and 45% (18/40) respectively in ESCCs and 26.67% (4/15), 33.33% (5/15) and 86.67% (13/15) respectively in NEMs. There exited statistical difference for HPV16, CD44v6 and nm23H1 between NEMs and ESCCs respectively (p 0.05). The expression rates of CD44v6 and nm23H1 were statistically different between grade I and II (p = 0.004, 0.016) respectively and between grade I and grade III (p = 0.014, 0.020), but not statistically different between grade II and III (p = 0.792, 0.943) respectively. Our data firstly suggested that there existed the statistical relationship between the infection of HPV16 and the expression of CD44v6 in ESCCs and that HPV16 may be involved in invasion and metastasis of ESCC.

Journal ArticleDOI
TL;DR: According to X-ray diffraction analysis, at least two phases exist in HfN x O y film, and Xray photoelectron spectroscopy results are in good agreement with these analysis.

Journal ArticleDOI
TL;DR: In order to improve the blood compatibility and security of mechanical heart valves, ion beam technology was used to modify the surface properties of the materials.
Abstract: Heart valve diseases threaten human health. One reliable way to save lives of such patients is to replace the pathologically changed heart valves by artificial ones. Over 2 million patients have received LTI-carbon heart valve’s implantation. However, the thrombosis after the implantation is one of the difficulties that need to be solved. In order to improve the blood compatibility and security of mechanical heart valves, ion beam technology was used to modify the surface properties of the materials. The investigation results have been summarized in this paper.

Journal ArticleDOI
TL;DR: The clinical description, pedigree, dark adaptation and elctroretinogram studies indicate that the patients have an autosomal dominant form of CSNB, and the ERG data reveal that affected persons have severely diminished b‐wave responses to dim light, but normal a‐wave and subnormal b‐ wave responses to maximum light stimuli.
Abstract: A pedigree of congenital stationary night blindness (CSNB) is described in a large Chinese family. The clinical description, pedigree, dark adaptation and elctroretinogram (ERG) studies indicate that the patients have an autosomal dominant form (ad) of CSNB. The disorder has been transmitted through at least 12 generations with over 40 affected individuals identified. The ERG data reveal that affected persons have severely diminished b‐wave responses to dim light, but normal a‐wave and subnormal b‐wave responses to maximum light stimuli. The dark adaptation curves of three patients show a monophase curve, typical for night blindness. We have excluded the five previously known mutations in the three genes (RHO, PDE6B and GNAT1) associated with adCSNB, and linkage studies have excluded tight linkage between the disease locus and markers associated with these three genes. Thus, this family has adCSNB caused by a different gene from the previously identified RHO, PDE6B, and GNAT1.

01 Jan 2005
TL;DR: The fl avonoids from Ginkgo biloba leaf inhibited the proliferation of BGC823 cells in a dosedependent manner.
Abstract: AIM: To extract the fl avonoids from Ginkgo biloba leaf, and to investigate its inhibitroy effects on the proliferation of human gastric cancer cell line BGC823 cultured in vitro . METHODS: Ethanol (700 mL/L) was used to extract the flavonoids from the leaf of Ginkgo biloba . Three wavelength spectrophotometry was used to determine the content of fl avonoids in the extracts. Human gastric cancer cells BGC823 cultured in vitro were treated with different concentrations of the fl avonoids, and then the proliferation of the cells was detected by MTT assay and fl ow cytometry. RESULTS: The content of flavonoids in the extracts was 140 mg/g. The fl avonoids from Ginkgo biloba leaf inhibited the proliferation of BGC823 cells in a dosedependent manner. The rate of cells in S phase was notably increased as compared with that in the controls (42.17±0.50% vs 32.13±0.45%, P = 0.001), and the apoptotic rate of the cells was also increased (4.10±0.03% vs 2.21±0.01%, P = 0.002).