Structural studies of human brain-type creatine kinase complexed with the ADP-Mg2+-NO3- -creatine transition-state analogue complex

Creatine kinase is a member of the phosphagen kinase family, which catalyzes the reversible phosphoryl transfer reaction that occurs between ATP and creatine to produce ADP and phosphocreatine. Here, three structural aspects of human-brain-type-creatine-kinase (hBB-CK) were identified by X-ray crystallography: the ligand-free-form at 2.2 Å; the ADP-Mg²⁺, nitrate, and creatine complex (transition-state-analogue complex; TSAC); and the ADP-Mg²⁺-complex at 2.0 Å. The structures of ligand-bound hBB-CK revealed two different monomeric states in a single homodimer. One monomer is a closed form, either bound to TSAC or the ADP-Mg²⁺-complex, and the second monomer is an unliganded open form. These structural studies provide a detailed mechanism indicating that the binding of ADP-Mg²⁺ alone may trigger conformational changes in hBB-CK that were not observed with muscle-type-CK.     

FMRP acts as a key messenger for dopamine modulation in the forebrain

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that controls translational efficiency and regulates synaptic plasticity. Here, we report that FMRP is involved in dopamine (DA) modulation of synaptic potentiation. AMPA glutamate receptor subtype 1 (GluR1) surface expression and phosphorylation in response to D1 receptor stimulation were reduced in cultured Fmr1(-/-) prefrontal cortex (PFC) neurons. Furthermore, D1 receptor signaling was impaired, accompanied by D1 receptor hyperphosphorylation at serine sites and subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in both PFC and striatum of Fmr1(-/-) mice. FMRP interacted with GRK2, and pharmacological inhibition of GRK2 rescued D1 receptor signaling in Fmr1(-/-) neurons. Finally, D1 receptor agonist partially rescued hyperactivity and enhanced the motor function of Fmr1(-/-) mice. Our study has identified FMRP as a key messenger for DA modulation in the forebrain and may provide insights into the cellular and molecular mechanisms underlying fragile X syndrome.     

Plasmid composition and the chpG gene determine the virulence level of Clavibacter capsici natural isolates in pepper

The gram-positive bacterial species Clavibacter capsici causes necrosis and canker in pepper plants. Genomic and functional analyses of C. capsici type strain PF008 have shown that multiple virulence genes exist in its two plasmids. We aimed to identify the key determinants that control the virulence of C. capsici. Pepper leaves inoculated with 54 natural isolates exhibited significant variation in the necrosis. Six isolates showed very low virulence, but their population titres in plants were not significantly different from those of the highly virulent isolates. All six isolates lacked the pCM1_Cc plasmid that carries chpG, which has been shown to be required for virulence and encodes a putative serine protease, but two of them, isolates 1,106 and 1,207, had the intact chpG elsewhere in the genome. Genomic analysis of these two isolates revealed that chpG was located in the pCM2_Cc plasmid, and two highly homologous regions were present next to the chpG locus. The chpG expression in isolate 1,106 was not induced in plants. Introduction of chpG of the PF008 strain into the six low-virulence isolates restored their virulence to that of PF008. Our findings indicate that there are at least three different variant groups of C. capsici and that the plasmid composition and the chpG gene are critical for determining the virulence level. Moreover, our findings also indicate that the virulence level of C. capsici does not directly correlate with bacterial titres in plants.     

须癣毛癣菌致人兔共患体癣3例

报道须癣毛癣菌引起的人兔共患体癣3例.患者皮损均为环状红斑丘疹,上覆鳞屑,炎症明显,伴瘙痒,均与兔子有密切接触史,且兔子均有明显皮损.取患者及兔子的皮屑真菌镜检及培养,鉴定为须癣毛癣菌,经口服及外用抗真菌药物后治愈.     

高血压患者饮食习惯、传统制剂服用现状调查及其影响因素分析

目的:调查高血压患者饮食习惯以及传统制剂服用现状,并分析饮食习惯与高血压患病的关系以及传统制剂服用的影响因素。方法:按照简单随机抽样法,采用自制调查问卷对呼和浩特市3个镇共8个行政村成年常住农村村民进行问卷调查,调查内容包括人口学特征、饮食习惯等内容,并采用多因素logistic回归分析饮食习惯与高血压患病的关系以及高血压患者传统制剂服用的影响因素。结果:呼和浩特市高血压患病率为22.68%。多因素logistic回归结果显示,较高的BMI、高血压家族史、饮酒史、泡菜咸菜、油炸食品、红肉(猪/牛/羊肉)/动物内脏、海产品是高血压独立危险因素(OR=1.257、1.451、1.358、1.317、1.108、1.146、1.373,P<0.05),奶制品、豆制品、新鲜果蔬是高血压保护因素(OR=0.797、0.868、0.903,P<0.05)。高血压患者传统制剂服用率为16.90%。多因素logistic回归结果显示,年龄≥60岁、文化程度高中以下、不了解高血压知识是高血压患者传统制剂服用的危险因素(OR=1.342、1.545、1.142,P<0.05)。结论:呼和浩特市农村成年村民高血压患病率较高,不良饮食习惯(饮食偏咸、油腻等)是高血压独立危险因素,高龄、文化程度低、不了解高血压知识的高血压患者传统制剂服用率较高,应加强农村居民合理膳食、保持均衡饮食习惯的宣传教育以及农村高血压患者用药规范。     

Scalable Water‐Based Production of Highly Conductive 2D Nanosheets with Ultrahigh Volumetric Capacitance and Rate Capability

Highly conductive and ultrathin 2D nanosheets are of importance for the development of portable electronics and electric vehicles. However, scalable production and rational design for highly electronic and ionic conductive 2D nanosheets still remain a challenge. Herein, an industrially adoptable fluid dynamic exfoliation process is reported to produce large quantities of ionic liquid (IL)‐functionalized metallic phase MoS₂ (m‐MoS₂) and defect‐free graphene (Gr) sheets. Hybrid 2D–2D layered films are also fabricated by incorporating Gr sheets into compact m‐MoS₂ films. The incorporated IL functionalities and Gr sheets prevent aggregation and restacking of the m‐MoS₂ sheets, thereby creating efficient and rapid ion and electron pathways in the hybrid films. The hybrid film with a high packing density of 2.02 g cm^?3 has an outstanding volumetric capacitance of 1430.5 F cm^?3 at 1 A g^?1 and an extremely high rate capability of 80% retention at 1000 A g^?1. The flexible supercapacitor assembled using a polymer‐gel electrolyte exhibits excellent resilience to harsh electrochemical and mechanical conditions while maintaining an impressive rate performance and long cycle life. Successful achievement of an ultrahigh volumetric energy density (1.14 W h cm^?3) using an organic electrolyte with a wide cell voltage of ≈3.5 V is demonstrated.     

Distinguishing structural features between Crohn's disease and gastrointestinal luminal tuberculosis using Mueller matrix derived parameters

Recently, the incidence of inflammatory bowel diseases, especially the Crohn's disease (CD) and gastrointestinal luminal tuberculosis (ITB), has grown rapidly worldwide. Currently there is no general gold standard to distinguish between CD and ITB tissues, which both have tuberculosis and surrounding fibrous structures. Mueller matrix imaging technique is suitable for describing the location, density and distribution behavior of such fibrous structures. In this study, we apply the Mueller matrix microscopic imaging to the CD and ITB tissue samples. The 2D Mueller matrix images of the CD and ITB tissue slices are measured using the Mueller matrix microscope developed in our previous study, then the Mueller matrix polar decomposition and Mueller matrix transformation parameters are calculated. To evaluate the distribution features of the fibrous structures surrounding the tuberculosis areas more quantitatively and precisely, we analyze the retardance related Mueller matrix derived parameters, which show clear different distribution behaviors between the CD and ITB tissues, using the Tamura image processing method. It is demonstrated that the Mueller matrix derived parameters can reveal the structural features of tuberculosis areas and be used as quantitative indicators to distinguish between CD and ITB tissues, which may be useful for the clinical diagnosis.      

Excitation energy transfer from phycobiliprotein to chlorophyll d in intact cells of Acaryochloris marina studied by time- and wavelength-resolved fluorescence spectroscopy.

The fluorescence decay spectra and the excitation energy transfer from the phycobiliproteins (PBP) to the chlorophyll-antennae of intact cells of the chlorophyll (Chl) d-dominated cyanobacterium Acaryochloris marina were investigated at 298 and 77 K by time- and wavelength-correlated single photon counting fluorescence spectroscopy. At 298 K it was found that (i) the fluorescence dynamics in A. marina is characterized by two emission peaks located at about 650 and 725 nm, (ii) the intensity of the 650 nm fluorescence depends strongly on the excitation wavelength, being high upon excitation of phycobiliprotein (PBP) at 632 nm but virtually absent upon excitation of chlorophyll at 430 nm, (iii) the 650 nm fluorescence band decayed predominantly with a lifetime of 70 +/- 20 ps, (iv) the 725 nm fluorescence, which was observed independent of the excitation wavelength, can be described by a three-exponential decay kinetics with lifetimes depending on the open or the closed state (F(0) or F(m)) of the reaction centre of Photosystem II (PS II). Based on the results of this study, it is inferred that the excitation energy transfer from phycobiliproteins to Chl d of PS II in A. marina occurs with a time constant of about 70 ps, which is about three times faster than the energy transfer from the phycobilisomes to PS II in the Chl a-containing cyanobacterium Synechococcus 6301. A similar fast PBP to Chl d excitation energy transfer was also observed at 77 K. At 77 K a small long-lived fluorescence decay component with a lifetime of 14 ns was observed in the 640-700 nm spectral range. However, it has a rather featureless spectrum, not typical for Chl a, and was only observed upon excitation at 400 nm but not upon excitation at 632 and 654 nm. Thus, this long-lived fluorescence component cannot be used as an indicator that the primary PS II donor of Acaryochloris marina contains Chl a.     

新疆雪莲的高效液相指纹图谱及液-质联用分析

建立新疆雪莲药材的高效液相指纹图谱。以Luna C18为分析柱,用乙腈-0.1%醋酸梯度洗脱,获得分离度较好的新疆雪莲药材HPLC分析条件。通过10批样品的分析和对照,标示出12个共有峰,相似度分析大于0.92。最后通过HPLC-UV-MS/MS联用分析鉴定出其中7个化学成分。该方法可为新疆雪莲药材指纹图谱和质量分析方法的建立提供参考。