Tim50 maintains the permeability barrier of the mitochondrial inner membrane

Transport of metabolites across the mitochondrial inner membrane is highly selective, thereby maintaining the electrochemical proton gradient that functions as the main driving force for cellular adenosine triphosphate synthesis. Mitochondria import many preproteins via the presequence translocase of the inner membrane. However, the reconstituted Tim23 protein constitutes a pore remaining mainly in its open form, a state that would be deleterious in organello. We found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation. Thus, the hydrophilic cis domain of Tim50 maintains the permeability barrier of mitochondria by closing the translocation pore in a presequence-regulated manner.     

Selective and efficient platinum(0)-carbene complexes as hydrosilylation catalysts

The hydrosilylation reaction enables the production of silicon polymers. Platinum-carbene complexes are reported that catalyze the hydrosilylation reaction of alkenes with remarkable efficiency and exquisite selectivity and avoid the formation of platinum colloids. By-products, typically encountered with previous catalytic systems, are suppressed with these platinum derivatives.     

Signatures of adaptation to obligate biotrophy in the Hyaloperonospora arabidopsidis genome

Many oomycete and fungal plant pathogens are obligate biotrophs, which extract nutrients only from living plant tissue and cannot grow apart from their hosts. Although these pathogens cause substantial crop losses, little is known about the molecular basis or evolution of obligate biotrophy. Here, we report the genome sequence of the oomycete Hyaloperonospora arabidopsidis (Hpa), an obligate biotroph and natural pathogen of Arabidopsis thaliana. In comparison with genomes of related, hemibiotrophic Phytophthora species, the Hpa genome exhibits dramatic reductions in genes encoding (i) RXLR effectors and other secreted pathogenicity proteins, (ii) enzymes for assimilation of inorganic nitrogen and sulfur, and (iii) proteins associated with zoospore formation and motility. These attributes comprise a genomic signature of evolution toward obligate biotrophy.     

Diazaquinomycins E–G,Novel Diaza-Anthracene Analogs from a Marine-Derived Streptomyces sp.

As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC₅₀ values against OVCAR5 of 9.0 and 8.8 μM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites.     

植物促生菌及其促生机理 (续)

3 植物促生菌的促生长机理 3.1 产生嗜铁素 铁是生命的基本物质.不论是动、植物还是微生物,均需含铁蛋白来参与呼吸等一系列生理活动.尽管地球表面矿物含铁丰富,但土壤中能够直接为植物和微生物利用的铁却不多.土壤中铁主要以三价铁(Fe3+)状态存在,在pH值为7.4时其溶解度为10-18mol/L,此浓度下的铁一般无法满足土壤微生物繁衍和植物生长发育的需要.然而,某些细菌和植物分泌一种专门结合铁的小分子蛋白(siderophores)可从土壤中收集铁,这种物质被称之为嗜铁素.铁一旦与嗜铁素相结合则形成可溶性铁-嗜铁素复合体,并可通过植物和微生物细胞膜的特殊通道进入生物体内.氧化铁在体内还原后被释放并参与生物代谢活动.产生嗜铁素被认为是植物促生菌最主要的直接和间接促进植物生长的有效途径之一.植物促生菌产生的嗜铁素一般都具有高度的铁亲合性和专一性,含有各种能鳌合铁的结构基团(如邻二苯酚结构、羧基结构和乙二胺结构等)来摄取土壤中的铁,这种嗜铁素具有极强的吸收铁的能力,可在铁有效性极低时收集土壤中微量的移动性铁,从而使土壤中可用的铁降低至更为缺乏的程度.     

Optimizing interfacial features to regulate neural progenitor cells using polyelectrolyte multilayers and brain derived neurotrophic factor

The development of biomaterials with controllable interfacial features which have the capability to instruct cellular behavior are required to produce functional scaffolds for the treatment of spinal cord injury (SCI). Here, poly-?-caprolactone surfaces were biofunctionalized via layer-by-layer (LbL) deposition. The polyelectrolytes employed in this LbL technique were heparin and poly-L-lysine (PLL), the latter being chosen to improve cell adhesion and the subsequent cellular function of in vitrocultured neural progenitor cells. Material characterization results confirmed the deposition of well structured multilayers. Cell culture studies revealed significant differences in the cellular response to these adhesive/nonadhesive (PLL/heparin) polyelectrolyte multilayer (PEM)surfaces, with neurite outgrowth being significantly promoted on the PLL terminating layers. In addition, brain derived neurotrophic factor (BDNF) was adsorbed onto the LbL surfaces. This combined chemical and biological effect was then characterized in terms of neurite length along with the full length/truncated isoform 1 tyrosine kinase receptor (TrkB-FL/TrkB-T1) and growth associated protein-43 mRNA levels. Here, the authors report the differential effect of adsorbed and soluble BDNF of different concentrations. Adsorbed BDNF promoted neurite outgrowth and led to elevated, sustained TrkB mRNA levels. These findings highlight the potential of PEM biofunctionalized surfaces with integrated chemical and neurotrophin supportive cues to overcome SCI inhibitory environments and to promote regeneration.     

Oxygen limitation and tissue metabolic potential of the African fish Barbus neumayeri : roles of native habitat and acclimatization

Background  

Oxygen availability in aquatic habitats is a major environmental factor influencing the ecology, behaviour, and physiology of fishes. This study evaluates the contribution of source population and hypoxic acclimatization of the African fish, Barbus neumayeri, in determining growth and tissue metabolic enzyme activities. Individuals were collected from two sites differing dramatically in concentration of dissolved oxygen (DO), Rwembaita Swamp (annual average DO 1.35 mgO₂ L^-1) and Inlet Stream West (annual average DO 5.58 mgO₂ L^-1) in Kibale National Park, Uganda, and reciprocally transplanted using a cage experiment in the field, allowing us to maintain individuals under natural conditions of oxygen, food availability, and flow. Fish were maintained under these conditions for four weeks and sampled for growth rate and the activities of phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS), and cytochrome c oxidase (CCO) in four tissues, liver, heart, brain, and skeletal muscle.     

Effect of immunosuppressive doses of cyclosporine on pancreatic beta cell function in pigs

OBJECTIVE: To evaluate whether immunosuppressive doses of cyclosporine (CsA) have an adverse effect on the liver, kidney, and pancreatic beta cells of pigs. ANIMALS: 8 juvenile 8-week-old Landrace X Large White crossbred pigs. PROCEDURE: CsA (100 to 140 mg/kg) was administered orally to euglycemic pigs to reach whole blood trough concentrations of approximately 1500 ng/mL. To determine pancreatic beta cell function, plasma C-peptide and insulin concentrations were measured in response to i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Effects on liver and kidney were determined by monitoring serum measurements of liver function and serum creatinine concentrations, respectively. RESULTS: Plasma concentrations of C-peptide were significantly lower in euglycemic CsA-treated pigs, compared with control pigs, following i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Furthermore, the glucose clearance rate was decreased in euglycemic CsA-treated pigs, compared with control pigs. Serum creatinine concentrations and 4 of 7 serum measurements of liver function were not adversely affected by CsA administration. Serum concentrations of bilirubin and albumin were significantly increased, and serum alanine aminotransferase activity was significantly decreased in CsA-treated pigs, compared with control pigs. Histologic evaluation of liver and kidney sections revealed no pathologic findings in CsA-treated or control pigs. CONCLUSIONS AND CLINICAL RELEVANCE: In our study, immunosuppressive doses of CsA caused an impairment of porcine pancreatic beta cell function, but did not have toxic effects on the kidney. However, on the basis of changes in serum bilirubin and albumin concentrations and alanine aminotransferase activity, subclinical toxic effects on the liver did occur when immunosuppressive doses of CsA were administered.     

Comparison of hematologic and biochemical values for blood samples obtained via jugular venipuncture and via vascular access ports in cats

OBJECTIVE: To determine whether hematologic and serum biochemical values for blood samples obtained from cats via vascular access ports (VAP) are comparable to those for samples obtained by direct venipuncture. DESIGN: Prospective study. ANIMALS: 14 healthy cats. PROCEDURE: A VAP was surgically implanted in a jugular vein in each cat. Blood samples were obtained from the VAP and by direct venipuncture of the contralateral jugular vein 10 weeks after VAP placement. Results of hematologic and serum biochemical analyses were compared by use of a paired t-test. The Pvalue to reject the null hypothesis was adjusted to account for multiple comparisons by using the Bonferroni procedure in which the nominal P-to-reject value is divided by the number of comparisons (0.05/24 = 0.002). RESULTS: Paired samples (VAP and venipuncture) obtained 10 weeks after VAP placement were evaluated for each cat. Of the 24 measured analytes, only potassium, total protein, and albumin concentrations differed significantly (P< 0.001 for all 3) between VAP and venipuncture samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that samples obtained from VAP are suitable for routine hematologic monitoring of feline cancer patients. Sample hemolysis may account for a slight increase in potassium, total protein, and albumin concentrations obtained from VAP samples. However, the values of variables most critical for monitoring of patients receiving chemotherapy (ie, mature neutrophil and platelet counts) are comparable. If proper techniques are used, VAP may be used for administration of chemotherapy as well as for blood collection in cats undergoing cancer treatment.