Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21cip1 signaling

The maintenance of T cell memory is critical for the development of rapid recall responses to pathogens, but may also have the undesired side effect of clonal expansion of T effector memory (T(EM)) cells in chronic autoimmune diseases. The mechanisms by which lineage differentiation of T cells is controlled have been investigated, but are not completely understood. Our previous work demonstrated a role of the voltage-gated potassium channel Kv1.3 in effector T cell function in autoimmune disease. In the present study, we have identified a mechanism by which Kv1.3 regulates the conversion of T central memory cells (T(CM)) into T(EM). Using a lentiviral-dominant negative approach, we show that loss of function of Kv1.3 mediates reversion of T(EM) into T(CM), via a delay in cell cycle progression at the G2/M stage. The inhibition of Kv1.3 signaling caused an up-regulation of SMAD3 phosphorylation and induction of nuclear p21(cip1) with resulting suppression of Cdk1 and cyclin B1. These data highlight a novel role for Kv1.3 in T cell differentiation and memory responses, and provide further support for the therapeutic potential of Kv1.3 specific channel blockers in T(EM)-mediated autoimmune diseases.     

维吾尔族2 型糖尿病患者糖尿病肾病相关因素分析

目的:探讨维吾尔族2型糖尿病肾病(DN)发病的相关临来因素。方法:分析292例维吾尔族2型糖尿病患者的临床资科。结果:维吾尔族2型糖尿病患者糖尿病肾病(DN)发病率为43.49%(127/292)。DN患者的病程、SBP、TC、TG、FBG、HbAIC、LDL-C、BUN和Cr均显著高于NDN患者(P<0.05);但DBP、HDL-C、BMI之间无统计学差异(P>0.05)。Logistic归分析结果显示,DM病程、患病年龄、SBP、FBP、TC、TG、LDL-C、HbA1c、BUN、Cr是DN的危险因素(OR值>1)。结论:维吾尔族2型糖尿病患者的DM病程、患病年龄、SBP、FBP、TC、TG、LDL-C、HbA1c、BUN、Cr等参数与糖尿病肾病并发率之间有相关性。     

Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+ double-positive cell

BMP2/4 signaling is required for embryogenesis and involved in thymus morphogenesis and T-lineage differentiation. In vitro experiments have shown that treatment of thymus explants with exogenous BMP4 negatively regulated differentiation of early thymocyte progenitors and the transition from CD4−CD8− (DN) to CD4+CD8+ (DP). Here we show that in vivo BMP2/4 signaling is required for fetal thymocyte progenitor homeostasis and expansion, but negatively regulates differentiation from DN to DP cell. Unexpectedly, conditional deletion of BMPRIA from fetal thymocytes (using the Cre-loxP system and directing excision to hematopoietic lineage cells with the Vav promoter) demonstrated that physiological levels of BMP2/4 signaling directly to thymocytes through BMPRIA are required for normal differentiation and expansion of early fetal DN thymocytes. In contrast, the arrest in early thymocyte progenitor differentiation caused by exogenous BMP4 treatment of thymus explants is induced in part by direct signaling to thymocytes through BMPRIA, and in part by indirect signaling through non-hematopoietic cells. Analysis of the transition from fetal DN to DP cell, both by ex vivo analysis of conditional BMPRIA-deficient thymocytes and by treatment of thymus explants with the BMP4-inhibitor Noggin demonstrated that BMP2/4 signaling is a negative regulator at this stage. We showed that at this stage of fetal T-cell development BMP2/4 signals directly to thymocytes through BMPRIA.     

Antioxidative potential of antidiabetic agents: A possible protective mechanism against vascular complications in diabetic patients

Many vascular complications are related to exposure of tissues to elevated levels of glucose, a condition that promotes oxidative stress. The primary goal of antidiabetic medication is for normalization of blood glucose. However, antidiabetic medications may have antioxidant effects that go beyond their hypoglycemic influences. Therefore, antidiabetic drugs may be doubly beneficial in preventing diabetic complications. Vascular dysfunction due to uncontrolled diabetes is a serious complication of the disease and one which has a severe impact on quality of life. Readjustment of the oxidative balance in subjects with diabetes, and the positive effects thereof is a topic of intense interest at present. In the current review, we highlight the antioxidant effects of antidiabetic medications which may prevent or delay the onset of vascular dysfunction.     

Life cycle assessment of district heat distribution in suburban areas using PEX pipes insulated with expanded polystyrene

Goal, Scope and Background

Combined heat and power (CHP) is a strategy aimed at reducing the impact of the energy sector on the climate by more efficient use of the energy content of the fuel. The implementation of CHP requires the utilisation of the heat produced. Space heating by means of district heating is one possible use for such heat. In countries such as Sweden, where district heating is already extensively used, many multiapartment buildings are connected to district heating. For increased use, the distribution systems will have to expand into suburbs with single family homes. However, the environmental impact and cost of the district heat distribution system increase when the pipe networks are extended into such areas. This is due to the production and installation of longer pipe networks and increased heat losses from the system. Attempts have been made to find new types of pipe constructions in order to lower the costs of connecting single family homes to district heating. These should be evaluated from an environmental perspective. The EPSPEX system is a distribution system intended for suburban areas. This system consists of cross-linked polyethylene (PEX) pipes in insulating blocks of expanded polystyrene (EPS). This paper presents a life cycle assessment of the EPSPEX district heat distribution system. In a second scenario, sub-stations were added. The results indicate areas that require improvement and provide a basis for comparison with other types of district heat distribution systems.

Methods

Production, network construction and use of the district heat system were studied by means of life cycle methodology, employing specific data for the EPSPEX system and generic data for upstream impacts of the materials used. The system constructed in Vråen, Värnamo, Sweden, in 2002 was studied. The district heating used in Vråen is mainly based on biofuels. The functional unit was the use of one metre of an EPSPEX district heating system over a period of one year. The expected system life was 30 years. The results were characterised as global warming potential, acidification potential, eutrophication potential and the use of finite resources, as well as weighted by EPS 2000, ExternE and EcoIndicator 99. No external review was performed, but a reference group of district heating experts familiar with the practice has reviewed the study.

Results

Heat losses are clearly the main environmental impact in all characterisations and weightings (71–92% of the total impact), despite the fact that the heat production studied was mainly based on biomass combustion, generally perceived to be environmentally friendly. Of the system components, the production of EPS insulation blocks had the largest environmental impact.

Discussion

This impact, however, is compensated for by the fact that the need to produce less heat leads to a lower level of emissions. Several characterisation methods revealed that the production and combustion of diesel for excavating the pipe trench has a significant environmental impact. The jointing brass swaged coupling used for the PEX fluid pipes has a surprisingly high impact in terms of acidification and EPS 2000, considering the small amount of brass in the system.

Conclusions

The life cycle environmental impact is dominated by the heat production needed to compensate for heat losses from the system, despite the fact that the EPSPEX system is relatively well insulated compared to a conventional district heating system. It is possible to shut down the heating circuit and only use the hot tap water circuit during the summer months; this reduces the heat losses and is an advantageous feature of the system. The second largest environmental impact of the EPSPEX system arises from the production of the EPS insulation blocks. A decrease in nitrogen oxide emissions, especially those caused by the excavation and filling of pipe trenches, would be beneficial. A rough comparison has been made with available literature data for conventional DN25 twin pipes. The results indicate that the environmental impact of the EPSPEX system is probably lower. However, the pipes are not identical, as the water delivery capacity of the conventional pipe is slightly lower.

Recommendations and Perspectives

In Sweden, new types of pipes are being developed for district heating in suburban areas, and there is a need for an environmental comparison between such new alternatives and previous results for conventional polyurethane insulated steel pipes. This study reveals that biofuels, although perceived to be environmentally friendly, must be used with caution in order to ensure a satisfactory environmental performance. Heat loss from district heating should be minimized also when biofuels are used. The most immediate way to reduce such environmental impact is to increase the insulation. The environmental trade-off between lower heat losses achieved by the use of more insulation and the production of greater amounts of insulation material should be further studied.

     

基于转录组分析铜绿假单胞菌DN1降解荧蒽特性

[背景]铜绿假单胞菌DN1是一株从石油污染土壤中分离筛选到的具有广谱降解功能的菌株。[目的]深入了解荧蒽胁迫条件下铜绿假单胞菌DN1降解污染物过程中重要的降解相关基因信息。[方法]通过高通量测序技术对铜绿假单胞菌DN1进行转录组测序,对其所有的转录本进行KEGG (kyoto encyclopedia of genes and genomes)分类和Pathway注释、GO (gene ontology)分类和富集分析。[结果]转录组测序显示:与对照组相比,荧蒽诱导组检测到6 189个基因,其中1 919个基因上调表达,1 603个基因下调表达。KEGG注释分析显示差异上调表达基因匹配到了112个KEGG代谢途径,注释到"代谢途径"的1 408个基因(约占总差异基因的73.4%)中有317个基因参与了碳氢化合物代谢及含有苯环结构的异源生物质的生物降解,占"代谢途径"的16.53%,暗示了菌株DN1降解荧蒽可能与这些途径有密切关系。另外,主要代谢途径中的差异表达基因主要集中在ABC转运系统、氨基酸生物合成、双组分系统及碳代谢,这些途径大多数参与了底物的识别转运、信号转导及基因表达调控。[结论]进一步拓展了铜绿假单胞菌DN1在荧蒽胁迫条件下的代谢途径和逆境反应,也为微生物修复环境污染物研究夯实了理论基础。     

好氧反硝化菌的分离鉴定及特性研究

从土壤中分离到1株能以硝酸钠为氮源进行好氧反硝化作用的细菌,命名为Rhodococcussp.DN,分离菌株革兰氏染色为阳性,球状或杆状,菌落颜色为橙红色。该细菌能以乙酰胺为惟一碳源和氮源,能进行氨化和硝化作用并产生亚硝酸。部分长度的16S rDNA序列分析表明,所分离的细菌与Rhodococcus ruber的16S rDNA序列具有99%相似性。     

A review of the anti-inflammatory properties of antidiabetic agents providing protective effects against vascular complications in diabetes

The global prevalence of Type 2 diabetes mellitus and its associated complications are growing rapidly. Although the role of hyperglycemia is well recognized in the pathophysiology of diabetic complications, its exact underlying mechanisms are not fully understood. In this regard, accumulating evidence suggests that the role of inflammation appears pivotal, with studies showing that most diabetic complications are associated with an inflammatory response. Several classes of antidiabetic agents have been introduced for controlling glycemia, with evidence that these pharmacological agents may have modulatory effects on inflammation beyond their glucose-lowering activity. Here we review the latest evidence on the anti-inflammatory effects of commonly used antidiabetic medications and discuss the relevance of these effects on preventing diabetic complications.     

Association of RAGE gene polymorphisms with type 2 diabetes mellitus,diabetic retinopathy and diabetic nephropathy

A meta-analysis was performed to assess the associations of the receptor for advanced glycation end products (RAGE) gene polymorphisms [Gly82Ser (rs2070600), 1704 G/T (rs184003), 429 T/C (rs1800625)] with type 2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and diabetic nephropathy (DN). A comprehensive research was conducted to identify all case-control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Peters test. Twenty-nine articles were included. Overall, after excluding articles deviating from Hardy–Weinberg equilibrium in controls and sensitive analysis, no significant association was found between RAGE gene polymorphisms (Gly82Ser, 1704 G/T, 429 T/C) and any of T2DM, DR and DN risk, respectively. Subgroup analysis stratified by ethnicity (Asian and Caucasian) also found no significant association between the above-mentioned three polymorphisms and T2DM risk, respectively. This meta-analysis suggested that there might be no association of RAGE gene polymorphisms (Gly82Ser, 1704 G/T, 429 T/C) with T2DM, DR and DN risk.