The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations

PIK3CA, one of the two most frequently mutated oncogenes in human tumors, codes for p110alpha, the catalytic subunit of a phosphatidylinositol 3-kinase, isoform alpha (PI3Kalpha, p110alpha/p85). Here, we report a 3.0 angstrom resolution structure of a complex between p110alpha and a polypeptide containing the p110alpha-binding domains of p85alpha, a protein required for its enzymatic activity. The structure shows that many of the mutations occur at residues lying at the interfaces between p110alpha and p85alpha or between the kinase domain of p110alpha and other domains within the catalytic subunit. Disruptions of these interactions are likely to affect the regulation of kinase activity by p85 or the catalytic activity of the enzyme, respectively. In addition to providing new insights about the structure of PI3Kalpha, these results suggest specific mechanisms for the effect of oncogenic mutations in p110alpha and p85alpha.     

Long-distance signaling in nodulation directed by a CLAVATA1-like receptor kinase

Proliferation of legume nodule primordia is controlled by shoot-root signaling known as autoregulation of nodulation (AON). Mutants defective in AON show supernodulation and increased numbers of lateral roots. Here, we demonstrate that AON in soybean is controlled by the receptor-like protein kinase GmNARK (Glycine max nodule autoregulation receptor kinase), similar to Arabidopsis CLAVATA1 (CLV1). Whereas CLV1 functions in a protein complex controlling stem cell proliferation by short-distance signaling in shoot apices, GmNARK expression in the leaf has a major role in long-distance communication with nodule and lateral root primordia.     

Differential antigen processing by dendritic cell subsets in vivo

Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.     

Emerging arthropod-borne diseases of companion animals in Europe

Vector-borne diseases are caused by parasites, bacteria or viruses transmitted by the bite of hematophagous arthropods (mainly ticks and mosquitoes). The past few years have seen the emergence of new diseases, or re-emergence of existing ones, usually with changes in their epidemiology (i.e. geographical distribution, prevalence, and pathogenicity). The frequency of some vector-borne diseases of pets is increasing in Europe, i.e. canine babesiosis, granulocytic anaplasmosis, canine monocytic ehrlichiosis, thrombocytic anaplasmosis, and leishmaniosis. Except for the last, these diseases are transmitted by ticks. Both the distribution and abundance of the three main tick species, Rhipicephalus sanguineus, Dermacentor reticulatus and Ixodes ricinus are changing. The conditions for such changes involve primarily human factors, such as travel with pets, changes in human habitats, social and leisure activities, but climate changes also have a direct impact on arthropod vectors (abundance, geographical distribution, and vectorial capacity). Besides the most known diseases, attention should be kept on tick-borne encephalitis, which seems to be increasing in western Europe, as well as flea-borne diseases like the flea-transmitted rickettsiosis. Here, after consideration of the main reasons for changes in tick vector ecology, an overview of each “emerging” vector-borne diseases of pets is presented.     

Effects of graded doses of propofol for anesthesia induction on cardiovascular parameters and intraocular pressures in normal dogs

ObjectiveTo determine the effects of graded doses of propofol on cardiovascular parameters and intraocular pressures (IOP) in normal dogs.Study designProspective, randomized, modified Latin square, cross-over experimental study.AnimalsEleven adult random-source dogs weighing 20.2 ± 5.7 kg.MethodsThere were three treatment groups: propofol 8 mg kg^?1 intravenous (IV) until loss of jaw tone (Group P), propofol until loss of jaw tone +20% (Group P20), and propofol until loss of jaw tone +50% (Group P50). Atracurium 0.1 mg kg^?1 IV was administered in all treatments immediately after the propofol. All dogs received the three treatments in a randomized order, with at least a one week interval between treatments. Direct arterial blood pressure and IOP by applanation tonometry were obtained at baseline, after 5 minutes of pre-oxygenation (before induction), before, and after intubation. Blood gas samples were obtained at baseline, after pre-oxygenation, and before intubation.ResultsThere was no significant difference in IOP readings at any time point among groups. The IOP was significantly higher before intubation versus before induction in all three groups. There was a significantly smaller change in systolic, mean (MAP), and diastolic (DAP) arterial pressures in the P50 group compared with the P group after intubation. There was a significantly smaller change in MAP and DAP in the P50 group compared with the P20 group after intubation. The increase in CO₂ from before induction to before intubation was significantly greater in the P50 group than in the P or P20 groups.Conclusions and clinical relevanceGraded doses of propofol did not affect the increase in IOP observed with propofol induction in normal dogs. Higher doses of propofol are of no apparent additional benefit in animals who cannot tolerate an abrupt increase in IOP but may be of benefit in dogs who cannot tolerate an abrupt increase in blood pressure accompanying orotracheal intubation.     

Fat Soluble Vitamins,Cholesterol, and Fatty Acid Composition of Wild and Farmed Black Mussel (Mytilus galloprovincialis) Consumed in Bulgaria

The most commercially important mollusk species from the Bulgarian Black Sea is the black mussel (Mytilus galloprovincialis). There is limited information about fat soluble vitamins, cholesterol, and fatty acid content of the Bulgarian Black Sea mussel. The aims of the present study are to determine and compare the fat soluble vitamin contents as well as relative daily intake of vitamins, cholesterol, fatty acid content, and lipid quality indices (atherogenic, thrombogenic) in the wild and farmed black mussels. Fat soluble vitamins and cholesterol were analyzed simultaneously using reverse phase high performance liquid chromatography. The fatty acid composition was analyzed by gas chromatography-mass spectrometry. In both mussels, fat soluble vitamins A and E were in high amounts, but they were a better source of vitamin D₃. Cholesterol contents were 67.54 ± 0.50 mg/100 g ww (wild) and 49.88 ± 0.30 mg/100 g ww (farmed). The fatty acid distributions of wild and farmed mussels are: saturated > polyunsaturated > monounsaturated fatty acid. The n3/n6 and polyunsaturated/saturated fatty acid ratios were greater than that recommended by the Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO). A 100-g edible portion of both mussels contained from 0.252 g (wild) to 0.425 g (farmed) of eicosapentaenoic acid (EPA, C20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3).     

Taurine Supplementation of All-plant Protein Diets for Rainbow Trout (Oncorhynchus mykiss)

Abstract.— Taurine has been demonstrated to be conditionally indispensable for several carnivorous fish species. Current trends in trout production include decreasing levels of fish-meal content in feeds, along with faster growing strains of fish. Taurine may be a limiting nutrient in support of elevated planes of growth for rainbow trout. A 9-wk feeding trial was conducted using a factorial treatment design with protein source (fish meal or plant) and taurine supplementation (four levels) as the main effects. The fish-meal diet series included 23% herring meal and contained 1.76% total sulfur amino acids (TSAA). The plant diet series did not contain any animal proteins and substituted protein from soy protein concentrate in place of the herring-meal protein and contained 1.5% TSAA. Taurine was supplemented at 0, 5, 10, and 15 g/kg dry diet to each of the diets in the plant series and the fish-meal series of diets. All diets were formulated to contain 43.8% crude protein and 20% lipid with an estimated physiological fuel value of 4.2 kcal/g. Fifteen fish were stocked in each of 24 tanks with a mean initial weight of approximately 26.8 g per fish. The unsupplemented fish-meal diet contained 2 g/kg taurine, and the unsupplemented plant diet had taurine levels below the detection limit of 0.1 g/kg diet. Taurine supplementation improved growth, feed conversion ratios, protein retention efficiencies, and energy retention efficiencies of fish fed the plant protein diets. No effects of taurine supplementation were observed for these response factors in fish fed the fish-meal series diets. This study demonstrates that taurine supplementation may be necessary for rainbow trout fed plant-protein-based feeds.     

凡纳滨对虾养殖塘叶绿素a与水质因子的多元回归分析

2009年4-9月期间,对上海市奉贤区某凡纳滨对虾养殖场22个养殖池塘水体叶绿素a、水温、pH、溶解氧、透明度、悬浮物(SS)、总有机碳(TOC)、五日生化需氧量(BOD₅)、高锰酸盐指数(COD_Mn)等15项水质因子进行测定。取164组测定数据,进行描述性统计,分析叶绿素a与各项因子的相关性系数。分析结果显示,与叶绿素a呈极显著线性正相关的水质因子为SS、TOC、BOD₅、COD_Mn、TN、TP;呈显著正相关的为DO;而叶绿素a与透明度呈极显著线性负相关,与PO^3-₄-P呈显著线性负相关;与水温、pH、NO^-₂-N、 NO^-₃-N、NH₃-N则未呈现显著相关性。根据多元线性回归选择自变量的原则,选择了TOC、TN、PO^3-₄-P和TP₄项水质因子,建立了叶绿素a与4项水质因子的逐步回归模型:Chl.a =-0.054 5+0.0034 9 TOC+0.015 3 TN-0.418 PO^3-₄-P+0.276 TP(r=0.715 5)。利用偏回归系数检验各水质因子对叶绿素a的影响,结果表明,对叶绿素a影响从大到小依次是TP、TOC、PO^3-₄-P和TN。研究结果对进一步探讨养殖池塘生态系统的变化规律及水环境质量保护提供了依据。