Mild and efficient oxidation of Hantzsch 1,4-dihydropyridines with sodium periodate catalyzed by a new polystyrene-bound Mn(TPP)Cl

Mild and efficient oxidation of Hantzsch 1,4-dihydropyridines with sodium periodate catalyzed by Mn(TTP)Cl supported on polystyrene-bound imidazole is reported. This heterogeneous catalyst is of great stability and reusability in the oxidation of 1,4-dihydropyridines with sodium periodate without significant loss of its catalytic activity.     

Anti-Ulcerogenic Effect of Methanolic Extracts from Enicosanthellum pulchrum (King) Heusden against Ethanol-Induced Acute Gastric Lesion in Animal Models

A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2–7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4–7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.     

TNF receptor-associated factor 5 limits the induction of Th2 immune responses

The TNF receptor-associated factor (TRAF) family of molecules acts as adapter proteins for signaling pathways initiated by several members of the TNF receptor (TNFR) superfamily. TRAF5(-/-) animals are viable and have normal development of the immune system despite interacting with several TNFR family members. A clear role for TRAF5 has yet to emerge. OX40 (CD134) interacts with TRAF5, suggesting that this pathway could be involved in regulating T cell differentiation into Th1 or Th2 cells. In tissue culture, OX40 stimulation of TRAF5(-/-) T cells resulted in a pronounced Th2 phenotype with elevated levels of IL-4 and IL-5. Similarly, in vivo immunization with protein in adjuvant in the presence of an agonist anti-OX40 Ab resulted in enhanced Th2 development in TRAF5(-/-) mice. Additionally, lung inflammation induced by T cells, which is critically controlled by OX40, was more pronounced in TRAF5(-/-) mice, characterized by higher levels of Th2 cytokines. These results suggest that TRAF5 can limit the induction of Th2 responses, and that TRAF5 can play a role in modulating responses driven by OX40 costimulation.     

Tailoring translational strength using Kozak sequence variants improves bispecific antibody assembly and reduces product-related impurities in CHO cells

Optimal production of bispecific antibodies (bsAb) requires efficient and tailored co-expression and assembly of two distinct heavy and two distinct light chains. Here, we describe a novel technology to modulate the translational strength of antibody chains via Kozak sequence variants to produce bsAb in a single cell line. In this study, we designed and screened a large Kozak sequence library to identify 10 independent variants that can modulate protein expression levels from approximately 0.2 to 1.3-fold compared with the wild-type sequence in transient transfection. We used a combination of several of these variants, covering a wide range of translational strength, to develop stable single cell Chinese hamster ovary bispecific cell lines and compared the results with those obtained from the wild-type sequence. A significant increase in bispecific antibody assembly with a concomitant reduction in the level of product-related impurities was observed. Our findings suggest that for production of bsAb it can be advantageous to modify translational strength for selected protein chains to improve overall yield and product quality. By extension, tuning of translational strength can also be applied to improving the production of a wide variety of heterologous proteins.     

桑蓟马在桑树中空间分布的研究

桑蓟马Pseudodendrothrips mori是桑树的一种主要害虫。它的寄生直接影响供桑叶的质量和产量。我们通过泰勒幂法则和Morisita的散度指标对桑树蓟马在植株和桑园内的空间分布进行检验,结果显示:P.mori种群在植株内和桑园里的分布都存在局部化。桑树中蓟马的分布在树内显示出幼虫蓟马位于低层(从上面叶子起5-10层),但成虫更喜欢上层(从上面叶子起1-5层)。同一植株叶子的不同方向上蓟马密度没有出现明显变化。桑园内蓟马主要分布在桑园东部、南部和北部的植株上,中部,西部植株上的蓟马密度较低。P.mori的成虫和幼虫在叶子上的分布呈现明显聚集化。     

Biology of Anagrus atomus (Hymenoptera: Mymaridae), an egg parasitoid of the grape leafhopper Arboridia kermanshah (Homoptera: Cicadellidae)

Biology, morphology and oviposition behavior of Anagrus atomus (Linnaeus), an egg parasitoid of the grape leafhopper Arboridia kermanshah Dlabola in Isfahan, Iran, were investigated. Adults were smaller than those so far reported from other regions. Females continuously drummed on plant surfaces with their antennae to search for host eggs. Parasitoid eggs hatched 2–3 days after oviposition, and A. atomus had two larval instars. First instar larvae were sacciform and immobile. Second instar larvae appeared 4 days after oviposition and were very active, and doubled their body length. The prepupal and pupal stages lasted for 1 and 5–6 days, respectively. Adult emergence began 16 days after oviposition, and peaked on day 17.     

Comparison of the Role of D1- and D2-Like Receptors in the CA1 Region of the Hippocampus in the Reinstatement Induced by a Subthreshold Dose of Morphine and Forced Swim Stress in Extinguished Morphine-CPP in Rats

Reward-seeking and relapse to drug use are two characteristics of addiction and reports have indicated the role of hippocampal structures in reward learning. To find the best ways of treatment, the understanding of the neurobiological mechanisms of reward and its involved factors is a must. For this reason, in the present study, we aimed to investigate the role of D1- and D2-like dopamine receptors and compared their activities in the CA1 region, focusing on the reinstatement induced by forced swim stress (FSS) or the combination of FSS and a subthreshold dose of morphine in extinguished morphine-CPP in rats. The rats were bilaterally implanted by two separate cannulas into the CA1 region. The animals received different doses of SCH23390 or sulpiride (0.5, 2, and 4 µg/0.5 µl vehicle/side) into the CA1 region on the reinstatement day and were tested for FSS-induced reinstatement or the combination of FSS and a subthreshold dose of morphine in separate groups. Our findings indicated that the D1- and D2-like receptor antagonists attenuated the reinstatement induced by the combination of FSS and the subthreshold dose of morphine. The behavioral results were more prominent in the groups of animals that received SCH23390 as compared to sulpiride. The data may suggest a role for the dopamine receptors in the CA1 region in relapse to drugs of abuse, which may be induced by exposure to a stressor.     

Bilayered,non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction

Classically skin defects are covered by split thickness skin grafts or by means of local or regional skin flaps. In the presented case series for the first time a bilayered, non-crossed-linked collagen matrix has been used in an off-label fashion in order to reconstruct facial skin defects following different types of skin cancer resection. The material is of porcine origin and consists of a spongy and a compact layer. The ratio of the two layers is 1:3 in favour of the spongy layer. The aim of the study was to investigate the potential of this matrix for skin regeneration as an alternative to the standard techniques of skin grafts or flaps. Six patients between 39 and 83 years old were included in the study based on a therapeutic trial. The collagen matrix was used in seven defects involving the nose, eyelid, forehead- and posterior scalp regions, and ranging from 1,2 to 6 cm in diameter. Two different head and neck surgeons at two different institutions performed the operations. Each used a different technique in covering the wound following surgery, i.e. with and without a latex-based sheet under the pressure dressing. In three cases cylindrical biopsies were taken after 14 days. In all cases the biomaterial application was performed without any complication and no adverse effects were observed. Clinically, the collagen matrix contributed to a tension-free skin regeneration, independent of the wound dressing used. The newly regenerated skin showed strong similarity to the adjacent normal tissue both in quality and colour. Histological analysis indicated that the spongy layer replaced the defective connective tissue, by providing stepwise integration into the surrounding implantation bed, while the compact layer was infiltrated by mononuclear cells and contributed to its epithelialization by means of a ?conductive“process from the surrounding epithelial cells. The clinical and histological data demonstrate that the collagen bilayered matrix used in this series contributes to a ?Guided-Integrative-Regeneration-Process“, which still needs to be further understood. The biomimetic nature of this material seems to contribute to physiological matrix remodelling, which probably involves other matricellular proteins essential for soft tissue regeneration. A deeper understanding of the mechanism, involved in the tissue integration of this material and its contribution to soft tissue regeneration based on the direct and indirect effect of matricellular proteins could open new therapeutic avenues for biomaterial-based soft tissue regeneration as an alternative to traditional flap-based plastic surgery.     

Localization of 3′, 5′-cyclic nucleotide phosphodiesterase activity in isolated thyroid cells and intact thyroid tissue

Summary Cytochemical localization of 3,5-cyclic nucleotide phosphodiesterase (cPDEase) has been investigated by light and electron microscopy in dissociated bovine thyroid cells and in intact bovine thyroid tissue. By light microscopy in isolated thyroid cells reaction product deposition associated with cPDEase activity was localized at the level of the plasma membrane. In intact cryostat cut thyroid tissue, the activity was primarily observed in the cytoplasm and to a lesser extent at the level of the plasma membrane. By electron microscopy, cPDEase activity in isolated cells was found on the plasma membrane and was also encountered on the inner surface of membrane bound vacuoles, presumably pinocytic in origin. In intact tissue, cPDEase activity appeared mostly localized on the apical and lateral plasma membranes and was also present on the outer surface of the endoplasmic reticulum (ER).Even though cPDEase and 5-AMPase did share the same plasma membrane localization, the inhibitory response to theophylline and stimulation with Imidazole permitted the dissociation of their respective activities. 5-AMPase failed to respond to either theophylline or Imidazole suggesting absence of cross reactivity between 5-AMP and cyclic AMP. Thyrotropin (TSH) had no effect on cPDEase activity.We conclude that: (1) regardless of the nature of the material used, the cytomembranes of thyroid cells possess cPDEase activity; and that (2) the variability in distribution as well as in staining intensity recorded by light and electron microscopy between isolated thyroid cells and cryostat cut thyroid tissue is probably inherent to the methodology used.This paper was presented, in part, at the 60th Annual Meeting of the International Academy of Pathology, Montreal, Canada, March 1971 and was initiated in the Department of Pathology, Rhode Island Hospital, Providence, R.I., supported from a Grant-in-Aid of the American Cancer Society, Rhode Island Division, Inc. and the Brown-Hazen Fund.