Neotropical Copestylum (Diptera,Syrphidae) breeding in Agavaceae and Cactaceae including seven new species

We studied 42 species of saprophagous, Neotropical Copestylum (Diptera, Syrphidae) reared from decaying Cactaceae and Agavaceae. Thirty‐three species were reared during fieldwork in Bolivia, Costa Rica, Ecuador, Mexico, Peru, and Trinidad from 1998–2007. Nine species came from museum and private collections. Seven were new species. We describe these new species and the third stage larva and/or puparium and breeding sites of 40 species. Not described are two apparent species related to Copestylum apicale (Loew, 1866) reared from Cactaceae. Resolution of their status was beyond the scope of this paper but reference is made to their distinctive larval morphology. Based on early stage characters all reared species can be placed in ten species groups, all but three of which have been recognized previously on the basis of adult characters. A high level of congruence was found between adult and larval characters in terms of these species groups. Eight of the groups appear to be related closely and may represent a monophyletic lineage within Copestylum that has diversified in xeric habitats. Early stage morphology varied within and amongst groups but two trends in functional morphology are recognizable. One trend is towards feeding in watery decay and the other towards feeding in firmer decay. The latter trend is characterized by species that scoop food and use grinding mills in their head skeletons to break it up. They also have armoured thoraces with varying arrangements of sclerotized spicules or stiffened setae for gripping and protection during tunnelling, a short anal segment, and a short posterior breathing tube for protecting the openings. The former trend is characterized by species with opposite and contrasting features. They filter food and have well‐developed pre‐oral setal filters but they lack grinding mills or only have poorly developed grinding mills. They have reduced thoracic armature, elongate anal segments, and posterior breathing tubes which facilitates simultaneous feeding and respiration. Comparison with 23 Copestylum species reared from bromeliads (Bromeliaceae) suggests a common pattern of diversification in that species groups with the largest body sizes are more specialized.     

BR-TRG-Ⅰ型体腔热灌注治疗系统安全性评估的动物实验

目的探讨应用BR-TRG-I型体腔热灌注治疗系统进行持续循环腹腔热灌注治疗（continuous circulatory hyperthermic intraperitoneal perfusion treatment,CCHIP）对实验动物的生命体征、肝肾功能及内脏器官病理形态的影响。方法选用家猪作为实验动物,应用BR-TRG-I型体腔热灌注治疗系统建立CCHIP动物模型,分别用44℃、45℃的设定温度进行CCHIP。在CCHIP期间记录实验动物的生命体征变化;CCHIP前及治疗后1d、3d、7d和14d抽取外周血液保存备检;CCHIP结束后即刻及2周后处死动物,观察内脏器官的大体形态学改变,切取肝、肾、小肠等器官进行病理检查。结果44℃CCHIP持续1.5h对猪的生命体征、肝肾功能无明显影响,肝、肾、小肠等脏器损伤较轻,2周后恢复正常;45℃CCHIP持续1.5h对猪的生命体征影响严重,肝肾功能损害持续2周尚不能恢复正常,肝、肾、小肠等脏器病理损伤明显。结论44℃温度CCHIP1.5h安全可行,可以作为CCHIP的安全温度;45℃温度CCHIP1.5h可对实验动物肝肾功能造成严重损害,不适合作为CCHIP的治疗温度。     

High-yield bacterial expression and structural characterization of recombinant human insulin-like growth factor binding protein-2

The diverse biological activities of the insulin-like growth factors (IGF-1 and IGF-2) are mediated by the IGF-1 receptor (IGF-1R). These actions are modulated by a family of six IGF-binding proteins (IGFBP-1-6; 22-31 kDa) that via high affinity binding to the IGFs (K_D ∼ 300-700 pM) both protect the IGFs in the circulation and attenuate IGF action by blocking their receptor access. In recent years, IGFBPs have been implicated in a variety of cancers. However, the structural basis of their interaction with IGFs and/or other proteins is not completely understood. A critical challenge in the structural characterization of full-length IGFBPs has been the difficulty in expressing these proteins at levels suitable for NMR/X-ray crystallography analysis. Here we describe the high-yield expression of full-length recombinant human IGFBP-2 (rhIGFBP-2) in Escherichia coli. Using a single step purification protocol, rhIGFBP-2 was obtained with >95% purity and structurally characterized using NMR spectroscopy. The protein was found to exist as a monomer at the high concentrations required for structural studies and to exist in a single conformation exhibiting a unique intra-molecular disulfide-bonding pattern. The protein retained full biologic activity. This study represents the first high-yield expression of wild-type recombinant human IGFBP-2 in E. coli and first structural characterization of a full-length IGFBP.     

生物软件在序列分析过程中的运用

介绍了组合使用BLAST、FASTA/BLASTScan3.2,或用多序列比对软件,从数据库中快速提取大数量目标序列,最后用MEGA4快捷编辑整理大数量序列的方法。还介绍了一种生成核酸序列与其氨基酸序列相似性百分率整合表格的方法。简述了对引物设计的基本认识并介绍了多重引物兼容性筛选软件;对构建系统发育树的认识并引出分子进化树构建软件MEGA4的使用和PAUP 4.0常用建树命令模块。期望这些方法和软件的使用能解决生物序列分析过程的常见问题。     

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.     

Cardiotoxicity of the cancer therapeutic agent imatinib mesylate

Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. Here we report ten individuals who developed severe congestive heart failure while on imatinib and we show that imatinib-treated mice develop left ventricular contractile dysfunction. Transmission electron micrographs from humans and mice treated with imatinib show mitochondrial abnormalities and accumulation of membrane whorls in both vacuoles and the sarco- (endo-) plasmic reticulum, findings suggestive of a toxic myopathy. With imatinib treatment, cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death. Retroviral gene transfer of an imatinib-resistant mutant of c-Abl, alleviation of ER stress or inhibition of Jun amino-terminal kinases, which are activated as a consequence of ER stress, largely rescues cardiomyocytes from imatinib-induced death. Thus, cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib.