Conformations Of Peptides Containing 1-Aminocyclohexane-Carboxylic Acid (Acc6) - Crystal-Structures Of 2 Model Peptides

The crystal structures of two peptides containing 1-aminocyclohexanecarboxylic acid (Acc6) are described. Boc-Aib-Acc6-NHMe · H2O adopts a β-turn conformation in the solid state, stabilized by an intramolecular 4 → 1 hydrogen bond between the Boc CO and methylamide NH groups. The backbone conformational angles (φAib = – 50.3°, ψAib = – 45.8°; φAcc6 = – 68.4°, ψAcc6 = – 15°) lie in between the values expected for ideal Type I or III β-turns. In Boc-Aib-Acc6-OMe, the Aib residue adopts a partially extended conformation (φAib = – 62.2°, ψAib = 143°) while the Acc6residue maintains a helical conformation (φAcc6 = 48°, ψAcc6= 42.6°). 1H n.m.r. studies in CDCl3 and (CD3)2SO suggest that Boc-Aib-Acc6-NHMe maintains the β-turn conformation in solution.

High Rydberg state carbon recombination lines toward Cassiopeia A: 332 MHz VLA observations and comparison with H I and molecular lines

We present observations of the C270alpha carbon recombination line, 21 cm neutral hydrogen line and (CO)-C-12 (J = 1 --> 0) molecular line toward Cas A. A comparison of the distribution of recombination line optical depths over the face of Cas A with that of H I optical depths and molecular line emission favors the association of C270alpha regions with H I rather than molecular clouds. The association makes it possible to self-consistently determine several physical parameters of the clouds by combining the recombination line and 21 cm H I measurements.

平顶猴TRIM5α基因变异影响其抗HIV-1功能

目的:解释平顶猴成为唯一能够被HIV-1感染的旧大陆猴以及在被SIV感染时出现较其他旧大陆猴严重临床症状的原因.方法:参考人TRIM5α基因的结构和序列合成引物,以平顶猴DNA 为模板,分别扩增其TRIM5α基因编码序列的所有外显子.利用生物学软件分析获得的编码序列,分析在已经明确与TRIM5α抗病毒功能密切相关的几个位点上是否发生可能影响其功能的突变.结果:在平顶猴基因组上CypA基因融合到TRIM5α基因第八外显子的下游,融合方式与在鹰猴中发现的CypA与TRIM5α的融合方式完全不同.恒河猴TRIM5α基因具有限制HIV-1复制的功能,第332位脯氨酸对其抗病毒功能非常重要,但在平顶猴的TRIM5α上,该氨基酸突变成谷氨酰胺;第335位以后8个氨基酸对恒河猴TRIM5α抗病毒功能也有重要影响,但在平顶猴的TRIM5α上,与其对应的氨基酸片段不仅缺失了两个氨基酸,还有两个氨基酸发生突变,附近区域还有另外两个发生突变.在平顶猴TRIM5α基因的Coiled-Coil结构域插入了13个氨基酸,但没有影响到编码框.结论:在平顶猴的基因组上CypA与TRIM5α的融合以及平顶猴TRIM5α基因抗病毒功能关键位点上的氨基酸突变可能影响其抗病毒功能,是其成为唯一能够被HIV-1感染的旧大陆猴以及在被SIV感染时出现较其他旧大陆猴严重临床症状的重要原因.

杀伤血管内皮生长因子受体1阳性细胞的靶向毒素

白喉毒素(diphtheria toxin DT) 是棒状白喉杆菌被茁噬菌体感染后分泌的一种外毒素. 它可以阻断真核细胞的蛋白质合成,杀死细胞. 血管内皮生长因子(VEGF) 的R82A,K84A,H86A突变体可以和肿瘤血管上高表达的VEGF受体1 (VEGFR-1) 特异性结合. 首先从白喉杆菌中提取基因组DNA,扩增出白喉毒素C区、T区基因. 并运用点突变技术,制成VEGF的R82A,K84A,H86A突变体. 利用这个可以和肿瘤血管上特异性受体相结合的VEGF的突变体,代替白喉毒素上的受体结合区,制成了针对VEGFR-1的靶向融合毒素——DT391-mVEGF. 以去除了受体结合区的DT391为阴性对照,细胞实验表明,融合毒素对VEGFR-1阳性的肿瘤细胞有特异性杀伤作用.

Microstructures and mechanical properties of as-cast Mg–5Al–0.4Mn–xNd (x=0, 1, 2 and 4) alloys

Mg-5Al-0.4Mn-xNd (x=0, 1, 2 and 4wt.%) alloys were prepared by metal mould casting method. The microstructures and mechanical properties were investigated. The results demonstrated that Al11Nd3 phase was formed and mainly aggregated along the grain boundaries with the addition of Nd. Meanwhile, the grain sizes were greatly reduced with the increasing Nd content.

The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis.

The PITSLRE protein kinases are parts of the large family of p34cdc2-related kinases. During apoptosis induced by some stimuli, specific PITSLRE isoforms are cleaved by caspase to produce a protein that contains the C-terminal kinase domain of the PITSLRE proteins (p110C). The p110C induces apoptosis when it is ectopically expressed in Chinese hamster ovary cells. In our study, similar induction of this p110C was observed during anoikis in NIH3T3 cells. To investigate the molecular mechanism of apoptosis mediated by p110C, we used the yeast two-hybrid system to screen a human fetal liver cDNA library and identified p21-activated kinase 1 (PAK1) as an interacting partner of p110C. The association of p110C with PAK1 was further confirmed by in vitro binding assay, in vivo coimmunoprecipitation, and confocal microscope analysis. The interaction of p110C with PAK1 occurred within the residues 210-332 of PAK1. Neither association between p58PITSLRE or p110PITSLRE and PAK1 nor association between p110C and PAK2 or PAK3 was observed. Anoikis was increased and PAK1 activity was inhibited when NIH3T3 cells were transfected with p110C. Furthermore, the binding of p110C with PAK1 and inhibition of PAK1 activity were also observed during anoikis. Taken together, these data suggested that PAK1 might participate in the apoptotic pathway mediated by p110C.

Inteligencia motora-1 : programa para el crecimiento motor, afectivo y cognitivo : 2õ ciclo de educación infantil.

Programa de inteligencia motora paralelo al currículum de educación infantil, que pretende trabajar el movimiento de manera que favorezca la autonomía personal, la aceptación y conocimiento de sí mismo, el respeto hacia el propio cuerpo y la confianza en sí mismo. Se trata de que los niños conozcan su cuerpo y desarrollen sus posibilidades de movimiento, de comunicación y expresión a través del mismo. Este cuaderno abarca el bloque de contenidos de identidad y autonomía personal referidos sobre todo al conocimiento corporal: esquema corporal, lateralidad, estructuración espacial, estructuración temporal y ritmo.

Immunolocalization of aquaporins 1, 2 and 7 in rete testis, efferent ducts, epididymis and vas deferens of adult dog

The transepithelial movement of water into the male reproductive tract is an essential process for normal male fertility. Protein water channels, referred to as aquaporins (AQPs), are involved in increasing the osmotic permeability of membranes. This study has examined the expression of AQP1, AQP2, and AQP7 in epithelial cells in adult dog efferent ducts, epididymis, and vas deferens. Samples of dog male reproductive tract comprising fragments of the testis, initial segment, caput, corpus and cauda epididymidis, and vas deferens were investigated by immunohistochemistry and Western blotting procedures to show the localization and distribution of the AQPs. AQP1 was noted in rete testis, in efferent ducts, and in vessels in the intertubular space, suggesting that AQP1 participated in the absorption of the large amount of testicular fluid occurring characteristically in the efferent ducts. AQP2 expression was found in the rete testis, efferent ducts and epididymis, whereas AQP7 was expressed in the epithelium of the proximal regions of the epididymis and in the vas deferens. This is the first time that AQP2 and AQP7 have been observed in these regions of mammalian excurrent ducts, but their functional role in the dog male reproductive tract remains unknown. Investigations of AQP biology could be relevant for clinical studies of the male reproductive tract and to technologies for assisted procreation.

Remodeling of rat ventral prostate after castration involves heparanase-1

Androgen deprivation causes the rat ventral prostate to reduce to 10% of its original size by 21 days after castration. The regressive changes result from the loss of epithelial cells by apoptosis and marked reorganization of the stroma. We have investigated whether these changes are accompanied by variations in heparanase expression. The ventral prostate of castrated rats was collected and processed for the quantification of heparan sulfate (HS), for the measurement of heparanase expression and its localization by reverse transcription/polymerase chain reaction, Western blotting, and immunohistochemistry, and for transmission electron microscopy (TEM). Absolute HS content decreased significantly as early as day 7 after surgery. Heparanase mRNA peaked 7 days after castration. The heparanase proenzyme (65 kDa) and the active form (50 kDa) were identified and peaked on day 7 after castration; this coincided with maximum HS-degrading activity. Heparanase was located to the basolateral surface of epithelial cells and in the adjacent stroma. After castration, staining for heparanase was reduced in the epithelium and increased in the stroma. TEM revealed that the peak of heparanase expression at day 7 after castration was associated with extensive changes in the basement membrane of the epithelium, endothelium and smooth muscle cells involving cell shrinkage and/or deletion by apoptosis. These results suggest that heparanase expression increases after castration and correlates with a decreased amount of HS. This variation in heparanase expression is involved in tissue remodeling and in the control of the regressive pattern after 1 week of androgen deprivation.

AN INVESTIGATION OF THE ELECTRONIC-STRUCTURE OF THE ANTITUMOR DRUG ELLIPTICINE AND ITS DERIVATIVES .1. GEOMETRICAL AM1 STUDY

Ellipticine and its derivatives are a class of molecules that show antitumor and cytotoxic activity with a multimodal mechanism of action. In this paper we report a preliminary Austin Method One (AM1) study of ellipticine and some molecules derived from it. We have observed a relationship between charge density distribution and biological selectivity. A mechanism that could improve cytotoxic activity is proposed.

Immunohistochemical and molecular expression of laminin-332 gamma-2 chain in canine mammary tumors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)