DTNBP1, a schizophrenia susceptibility gene, affects kinetics of transmitter release

Schizophrenia is one of the most debilitating neuropsychiatric disorders, affecting 0.5–1.0% of the population worldwide. Its pathology, attributed to defects in synaptic transmission, remains elusive. The dystrobrevin-binding protein 1 (DTNBP1) gene, which encodes a coiled-coil protein, dysbindin, is a major susceptibility gene for schizophrenia. Our previous results have demonstrated that the sandy (sdy) mouse harbors a spontaneously occurring deletion in the DTNBP1 gene and expresses no dysbindin protein (Li, W., Q. Zhang, N. Oiso, E.K. Novak, R. Gautam, E.P. O'Brien, C.L. Tinsley, D.J. Blake, R.A. Spritz, N.G. Copeland, et al. 2003. Nat. Genet. 35:84–89). Here, using amperometry, whole-cell patch clamping, and electron microscopy techniques, we discovered specific defects in neurosecretion and vesicular morphology in neuroendocrine cells and hippocampal synapses at the single vesicle level in sdy mice. These defects include larger vesicle size, slower quantal vesicle release, lower release probability, and smaller total population of the readily releasable vesicle pool. These findings suggest that dysbindin functions to regulate exocytosis and vesicle biogenesis in endocrine cells and neurons. Our work also suggests a possible mechanism in the pathogenesis of schizophrenia at the synaptic level

Метод расчета зависимости динамики доходов работников от уровня образования в Республике Беларусь

We report a study of the process e(+)e(-) -&gt; (D*(D) over bar*)(0)pi(0) using e(+)e(-) collision data samples with integrated luminosities of 1092 pb(-1) at root s = 4.23 GeV and 826 pb(-1) at root s = 4.26 GeV collected with the BESIII detector at the BEPCII storage ring. We observe a new neutral structure near the (D*(D) over bar*)(0) mass threshold in the pi(0) recoil mass spectrum, which we denote as Z(c)(4025)(0). Assuming a Breit-Wigner line shape, its pole mass and pole width are determined to be (4025.5(-4.7)(+2.0) +/- 3.1) MeV/c(2) and (23.0 +/- 6.0 +/- 1.0) MeV, respectively. The Born cross sections of e(+)e(-) -&gt; Z(c)(4025)(0)pi(0) -&gt; (D*(D) over bar*)(0)pi(0) are measured to be (61.6 +/- 8.2 +/- 9.0) pb at root s = 4.23 GeV and (43.4 +/- 8.0 +/- 5.4) pb at root s = 4.26 GeV. The first uncertainties are statistical and the second are systematic.Funding: The BESIII Collaboration thanks the staff of BEPCII and the IHEP computing center for their strong support. This work is supported in part by the National Key Basic Research Program of China under Contract No. 2015CB856700; the National Natural Science Foundation of China (NSFC) under Contracts No. 11125525, No. 11235011, No. 11275266, No. 11322544, No. 11335008, and No. 11425524; the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; the CAS Center for Excellence in Particle Physics (CCEPP); the Collaborative Innovation Center for Particles and Interactions (CICPI); the Joint Large-Scale Scientific Facility Funds of the NSFC and the CAS under Contracts No. 11179007, No. U1232201, and No. U1332201; the CAS under Contracts No. KJCX2-YW-N29 and No. KJCX2-YW-N45; the 100 Talents Program of the CAS; INPAC and the Shanghai Key Laboratory for Particle Physics and Cosmology; German Research Foundation DFG under Contract No. Collaborative Research Center CRC-1044; the Istituto Nazionale di Fisica Nucleare, Italy; the Ministry of Development of Turkey under Contract No. DPT2006K-120470; the Russian Foundation for Basic Research under Contract No. 14-07-91152; the U.S. Department of Energy under Contracts No. DE-FG02-04ER41291, No. E-FG02-05ER41374, No. DE-FG02-94ER40823, and No. DESC0010118; the U.S. National Science Foundation; the University of Groningen (RuG) and the Helmholtzzentrum fuer Schwerionenforschung GmbH (GSI), Darmstadt; and the WCU Program of National Research Foundation of Korea under Contract No. R32-2008-000-10155-0.</p

台灣毛豬供給預測模式之研究

一、研究目的：１．比較不同預測模式在毛豬供給預測上的能力。 ２．評估不同預測模式在毛豬供給預測上的優缺點。 二、資料來源：１．台灣省政府農林廳農產物價月報 ２．雜糧與畜產台灣省雜糧發展基金。 ３．中華民國台灣地區品價格月報行政院主計處 ４．台灣省政府農林廳未發表的次級資料。 三、研究方法：本文選擇一些在預測新面有較佳結果的預測模式，用來評估及比較其 在毛豬供給預測上的能力，選出被用來比較的預測模式包括： １．天真模式。 ２．簡單移動平均模式。 ３．雙重移動平圴模式。 ４．單一指數平滑法 ５．雙重指數平滑法。 ６．單一方程式計量模型。 ７．單一變數Box-Jenkins 模式 ８．結構計量模型及時間數列分析。 ９．台灣省政府農林廳毛豬供給頭數預測模式。 四、研究結果：議Theils不等係數U而言，簡單移動平均模式之能力較佳，而單一 指數平滑法次之。以根平均平方百分誤差RMSP而言，單一變數Box-Jenkns模式較 好，結構計量模型與時間數列分析次之，再以偏誤成分Um 而言，單一變數Box-Jenk ins 模式之預測結果較理想

Temporal changes in genetic diversity of msp-1, msp-2, and msp-3 in Plasmodium falciparum isolates from Grande Comore Island after introduction of ACT

Abstract Background Malaria is still one of the serious public health problems in Grande Comore Island, although the number of annual cases has been greatly reduced in recent years. A better understanding of malaria parasite population diversity and transmission dynamics is critical for assessing the effectiveness of malaria control measures. The objective of this study is to investigate temporal changes in genetic diversity of Plasmodium falciparum populations and multiplicity of infection (MOI) in Grande Comore 10 years after introduction of ACT. Methods A total of 232 P. falciparum clinical isolates were collected from the Grande Comore Island during two sampling periods (118 for 2006‒2007 group, and 114 for 2013‒2016 group). Parasite isolates were characterized for genetic diversity and complexity of infection by genotyping polymorphic regions in merozoite surface protein gene 1 (msp-1), msp-2, and msp-3 using nested PCR and DNA sequencing. Results Three msp-1 alleles (K1, MAD20, and RO33), two msp-2 alleles (FC27 and 3D7), and two msp-3 alleles (K1 and 3D7) were detected in parasites of both sampling periods. The RO33 allele of msp-1 (84.8%), 3D7 allele of msp-2 (90.8%), and K1 allele of msp-3 (66.7%) were the predominant allelic types in isolates from 2006–2007 group. In contrast, the RO33 allele of msp-1 (63.4%), FC27 allele of msp-2 (91.1%), and 3D7 allele of msp-3 (53.5%) were the most prevalent among isolates from the 2013–2016 group. Compared with the 2006‒2007 group, polyclonal infection rates of msp-1 (from 76.7 to 29.1%, P < 0.01) and msp-2 (from 62.4 to 28.3%, P < 0.01) allelic types were significantly decreased in those from 2013‒2016 group. Similarly, the MOIs for both msp-1 and msp-2 were higher in P. falciparum isolates in the 2006–2007 group than those in 2013–2016 group (MOI = 3.11 vs 1.63 for msp-1; MOI = 2.75 vs 1.35 for msp-2). DNA sequencing analyses also revealed reduced numbers of distinct sequence variants in the three genes from 2006‒2007 to 2013‒2016: msp-1, from 32 to 23 (about 28% decline); msp-2 from 29 to 21 (about 28% decline), and msp-3 from 11 to 3 (about 72% decline). Conclusions The present data showed dramatic reduction in genetic diversity and MOI among Grande Comore P. falciparum populations over the course of the study, suggesting a trend of decreasing malaria transmission intensity and genetic diversity in Grande Comore Island. These data provide valuable information for surveillance of P. falciparum infection and for assessing the appropriateness of the current malarial control strategies in the endemic area

Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy

Abstract Background Plasmodium falciparum malaria is a significant public health problem in Comoros, and artemisinin combination therapy (ACT) remains the first choice for treating acute uncomplicated P. falciparum. The emergence and spread of artemisinin-resistant P. falciparum in Southeast Asia, associated with mutations in K13-propeller gene, poses a potential threat to ACT efficacy. Detection of mutations in the P. falciparum K13-propeller gene may provide the first-hand information on changes in parasite susceptibility to artemisinin. The objective of this study is to determinate the prevalence of mutant K13-propeller gene among the P. falciparum isolates collected from Grande Comore Island, Union of Comoros, where ACT has been in use since 2004. Methods A total of 207 P. falciparum clinical isolates were collected from the island during March 2006 and October 2007 (n = 118) and March 2013 and December 2014 (n = 89). All isolates were analysed for single nucleotide polymorphisms (SNPs) and haplotypes in the K13-propeller gene using nested PCR and DNA sequencing. Results Only three 2006–2007 samples carried SNPs in the K13-propeller gene, one having a synonymous (G538G) and the other having two non-synonymous (S477Y and D584E) substitutions leading to two mutated haplotypes (2.2 %, 2/95). Three synonymous mutations (R471R, Y500Y, and G538G) (5.9 %, 5/85) and 7 non-synonymous substitutions (21.2 %, 18/85) with nine mutated haplotypes (18.8 %, 16/85) were found in isolates from 2013 to 2014. However, none of the polymorphisms associated with artemisinin-resistance in Southeast Asia was detected from any of the parasites examined. Conclusion This study showed increased K13-propeller gene diversity among P. falciparum populations on the Island over the course of 8 years (2006–2014). Nevertheless, none of the polymorphisms known to be associated with artemisinin resistance in Asia was detected in the parasite populations examined. Our data suggest that P. falciparum populations in Grande Comore are still effectively susceptible to artemisinin. Our results provide insights into P. falciparum populations regarding mutations in the gene associated with artemisinin resistance and will be useful for developing and updating anti-malarial guidance in Comoros

(A) Representative mEPSC traces from WT and hippocampal neurons in the presence of 10 μM bicuculline (Bic) and 1 μM tetrodotoxin (TTX)

(B) Cumulative probability of mEPSC amplitude in WT (gray) and (black) mice. (inset) The quantitative results of amplitude; no difference was found between WT and mice. (C) Cumulative distribution of mEPSC frequency in WT (gray) and (black) mice. Inset shows that the lack of dysbindin notably decreased the mean frequency of mEPSCs. (D) Histograms display quantitative analysis of HHD, RT, and charge of mEPSCs, showing that the lack of dysbindin slows the kinetics and increases the charge of single vesicle release. Data are from 238 spikes (7 cells, WT) and 112 spikes (6 cells, ). (E) Analysis of decay time constant (τ) was performed on averaged mEPSCs obtained from 50 individual events. The decay time was best fitted with a single exponential function. The decay of EPSCs in neurons (black) was slower than that in WT (gray). (F) Averaged evoked EPSC waveforms of WT and cells from 10 traces. (G) Comparison of the amplitude, RT, charge transfer, or decay time constant (τ) of evoked EPSCs between WT (gray) and (black) cells. The lack of dysbindin resulted in reduced amplitude and slower decay time without affecting the amount of release as measured by the charge transfer. Data are from 17 cells (WT) and 16 cells (). *, P < 0.05; ***, P < 0.001. Error bars indicate the mean ± SEM.<p><b>Copyright information:</b></p><p>Taken from ", a schizophrenia susceptibility gene, affects kinetics of transmitter release"</p><p></p><p>The Journal of Cell Biology 2008;181(5):791-801.</p><p>Published online 2 Jun 2008</p><p>PMCID:PMC2396815.</p><p></p