Amphetamine Administration into the Ventral Striatum Facilitates Behavioral Interaction with Unconditioned Visual Signals in Rats

Background

Administration of psychomotor stimulants like amphetamine facilitates behavior in the presence of incentive distal stimuli, which have acquired the motivational properties of primary rewards through associative learning. This facilitation appears to be mediated by the mesolimbic dopamine system, which may also be involved in facilitating behavior in the presence of distal stimuli that have not been previously paired with primary rewards. However, it is unclear whether psychomotor stimulants facilitate behavioral interaction with unconditioned distal stimuli.

Principal Findings

We found that noncontingent administration of amphetamine into subregions of the rat ventral striatum, particularly in the vicinity of the medial olfactory tubercle, facilitates lever pressing followed by visual signals that had not been paired with primary rewards. Noncontingent administration of amphetamine failed to facilitate lever pressing when it was followed by either tones or delayed presentation or absence of visual signals, suggesting that visual signals are key for enhanced behavioral interaction. Systemic administration of amphetamine markedly increased locomotor activity, but did not necessarily increase lever pressing rewarded by visual signals, suggesting that lever pressing is not a byproduct of heightened locomotor activity. Lever pressing facilitated by amphetamine was reduced by co-administration of the dopamine receptor antagonists SCH 23390 (D1 selective) or sulpiride (D2 selective).

Conclusions

Our results suggest that amphetamine administration into the ventral striatum, particularly in the vicinity of the medial olfactory tubercle, activates dopaminergic mechanisms that strongly enhance behavioral interaction with unconditioned visual stimuli.     

Isolation of two novel corrinoid proteins from acetate-grown Methanosarcina barkeri.

Two corrinoid proteins with molecular sizes of 480 and 29 kDa are stably methylated by [2-14C]acetate-derived intermediates in cell extracts of aceticlastic Methanosarcina barkeri when methylreductase is inhibited by the addition of bromoethanesulfonic acid. Both 14CH3-proteins have been isolated to near homogeneity and found to be abundant soluble proteins. The larger protein possesses two subunits, of 41.4 and 30.4 kDa, in an equimolar ratio, suggesting an alpha 6 beta 6 conformation with six bound methylated corrinoids per 480-kDa molecule. The 29-kDa protein is a monomer in solution and possesses only one methylated corrinoid. All methyl groups on both proteins are photolabile, but the methylated corrinoid bound to the 29-kDa protein undergoes photolysis at a higher rate than that bound to the 480-kDa protein. The two proteins possess discrete N termini and do not appear to be forms of the same protein in equilibrium. Neither protein has an Fe4S4 cluster, and both have UV-visible spectra most similar to that of a base-on methylated corrinoid. A previously identified methylated protein, designated the unknown A 14CH3-protein, copurifies with the 480-kDa protein and has the same subunit composition. The methyl groups of both isolated 14CH3-proteins are converted to methane in cell extracts. The methylated proteins that accumulate in extracts in the presence of bromoethanesulfonic acid are demethylated by the addition of coenzyme M. Both isolated proteins are abundant novel corrinoid proteins that can methylate and be methylated by intermediates of the methanogenic pathway.     

枯草芽孢杆菌渗透压调节基因proB的克隆和表达

用PCR扩增的方法从耐盐的枯草杆菌中克隆出一个13kb长的DNA片段,经功能检测,证明正向插入片段与大肠杆菌的脯氨酸营养缺陷特性(proB-)能够营养互补。含有该重组质粒的大肠杆菌DH5α在基本培养基上的耐盐能力从2%提高至4%。通过引物步行法测定了该插入片段的核苷酸序列。利用DNAsis软件进行序列分析发现,该片段第122～1235bp核苷酸编码一个由370个氨基酸组成的蛋白质分子,其上游存在非典型的-10区,典型的-35区和核糖体结合位点,起始密码子处有最佳翻译起始效率的侧翼核苷酸序列。将其与Genebank中的已知基因的序列和编码的氨基酸序列进行同源性比较,结果表明该片段与枯草杆菌168的核苷酸序列、氨基酸序列的同源性分别为81%和90%。证明该基因确实是一个proB基因。通过与三十个不同种属微芽生物proB基因的氨基酸序列比较,发现该蛋白存在有可能与形成酶的活性中心和三维结构有密切关系的几个绝对保守的区域。     

人工栽培条件下三叶木通座果及果实生长特性研究

用栽培三叶木通为试材,研究了其座果及果实生长的特性。结果表明：人工栽培条件下,三叶木通座果（雌花）率可以提高到１３．５％,是野生三叶木通的２ １００％;以先年第１、２次攀援茎第３￣３０节位结果为主;３月底开花,花期３０ｄ左右。花后第２０￣５０ｄ（４月中旬至５月上旬）花序、雌花及幼果（子房）大量脱落,出现明显的脱落高峰。三叶木通果实纵向生长呈双Ｓ曲线布,生长期１５０ｄ左右,可划分成５个时期：受精结实     

Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II

Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC₅₀ value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.     

Interleukin-22 Mediates Early Host Defense against Rhizomucor pusilluscan Pathogens

Background

In recent years, the fungal infectious disease zygomycosis has increased in incidence worldwide, especially among the immunodeficient population. Despite the rates of zygomycosis-related death and deformation being very high, the mechanism(s) by which the fungal pathogens cause these severe manifestations remain unknown.

Methods

Using the associated Rhizomucor variabilis species, which can selectively induce cutaneous zygomycosis in otherwise healthy individuals, we investigated the host mechanisms of infection-related responses, including cytokine and chemokine expression as well as contributions of particular T cell subsets. siRNA specifically targeting IL-22,IL-17 and IFN-γ were used to down-regulate expression of those molecules.

Results

In mouse models of infection, IL-22 was implicated in development of Rhizomucor spp.-induced skin lesions. In cultured human peripheral blood monocytes, R. pusilluscan, which is often found in immunodeficient patients, induced the production of IL-22, while R. variabilis did not. Moreover, Rhizomucor spp.-induced secretion of Il-22 from CCR6⁺CCR4⁺CCR10⁺ cells was down-regulated by knockdown of IL-22 related signaling receptors, RORC and ARH.

Conclusion

Our data strongly suggest that avoidance of IL-22 may be one mechanism by which mucor species produce morbidity and mortality in infected individuals.     

Association study between of Tie2/Angiopoietin-2 and VEGF/KDR pathway gene polymorphisms and vascular malformations

Vascular malformations (VMs) are common congenital and neonatal dysmorphogenesis. VMs mostly occur sporadically with a few exceptions of inheritability. Tie2/angiopoietins-2 (Ang-2) and VEGF/KDR pathways are known to be involved in normal and pathogenic angiogenesis. Our study was aimed to test the contribution of these pathway gene variants to VMs. A total of 8 variants were found among 103 VM patients and 142 healthy controls. These variants comprised rs638203, rs639225, rs80338908 and rs80338909 in Tie2 gene, rs1870377 and rs2305949 in KDR gene, rs79337921 and rs34590960 in ANTXR1 gene. Our results indicated that rs638203 (p = 0.029) and rs639225 (p = 0.018) in Tie2 gene were associated with VM. A further bioinformatics analysis suggested the rs638203-G and rs639225-G might cause an abnormal splicing of Tie2 gene into to a defective protein. Our results identified two novel Tie2 gene polymorphisms with genetic susceptibility to VMs, although future functional validation of the two polymorphisms is warranted in the future.     

结直肠癌组织RPN11与Ki67的表达及其临床病理学意义

目的观察去泛素化酶RPN11和增殖相关核标记物Ki67在结直肠癌组织中的表达,研究其与结直肠癌肿瘤细胞增殖的相关性及与结直肠癌临床病理特征的关系。方法采用免疫组织化学SABC法检测56例结直癌组织及20例癌旁正常组织中的RPN11和Ki67表达,结合临床病理学资料进行统计分析。结果免疫组织化学染色显示:RPN11及Ki67在结直肠癌组织的阳性表达率明显高于正常结直肠组织;RPN11和Ki67的表达均与肿瘤分化程度、TNM分期、转移有关,而与性别、年龄无明显相关;RPN11与Ki67的表达呈正相关。结论RPN11和Ki67可能共同参与结直肠癌肿瘤细胞的增殖调控,并促进结直肠癌的发生发展以及浸润转移。