Effect of actinomycin D onTrypanosoma cruzi

Summary Viable metacyclic forms ofT. cruzi, Y strain, treated with an adequate dose of actinomycin D (50 g Act-D/ml/10⁷ parasites/ml for 72 h at 28° C) showed the following properties: 1) they lost their ability to replicate in culture medium, in blood and in tissues of normal mice and were no longer able to incorporate tritiated thymidine; 2) they could no penetrate into Vero cells and could not replicate inside normal macrophages; 3) they retained their immunogenicity and the ability to protect mice against a virulent infection; 4) they did not induce histological lesions as described in chronic experimental Chagas' disease.     

Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex

SUMO-1 (for small ubiquitin-related modifier) belongs to the ubiquitin (Ub) and ubiquitin-like (Ubl) protein family. SUMO conjugation occurs on specific lysine residues within protein targets, regulating pathways involved in differentiation, apoptosis, the cell cycle and responses to stress by altering protein function through changes in activity or cellular localization or by protecting substrates from ubiquitination. Ub/Ubl conjugation occurs in sequential steps and requires the concerted action of E2 conjugating proteins and E3 ligases. In addition to being a SUMO E3, the nucleoporin Nup358/RanBP2 localizes SUMO-conjugated RanGAP1 to the cytoplasmic face of the nuclear pore complex by means of interactions in a complex that also includes Ubc9, the SUMO E2 conjugating protein. Here we describe the 3.0-A crystal structure of a four-protein complex of Ubc9, a Nup358/RanBP2 E3 ligase domain (IR1-M) and SUMO-1 conjugated to the carboxy-terminal domain of RanGAP1. Structural insights, combined with biochemical and kinetic data obtained with additional substrates, support a model in which Nup358/RanBP2 acts as an E3 by binding both SUMO and Ubc9 to position the SUMO-E2-thioester in an optimal orientation to enhance conjugation.     

A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size

Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ. We found neuroepithelial expression of the genes during prenatal neurogenesis and protein localization to the spindle poles of mitotic cells, suggesting that a centrosomal mechanism controls neuron number in the developing mammalian brain.     

Flashing phenomenon in blood platelets stained with fluorescent basic drugs

Zusammenfassung Nach Behandlung von Blutplättchen mit Mepacrin, Acridin-Orange und Daunomycin, die sich selektiv in den 5-Hydroxytryptamin- (5HT)-Speicher-organellen anreichern, werden letztere im Fluoreszenzmikroskop sichtbar. Unter violett-blauer Bestrahlung zeigen die einzelnen Plättchen mehrere sukzessive, blitzartige Zunahmen der Fluoreszenz-Intensität, wobei sie während einiger Sekunden vollständig ausgeleuchtet erscheinen. Die Blitze sind wahrscheinlich durch Freisetzung der fluoreszierenden Stoffe aus je einer 5HT-Speicherorganelle bedingt.

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Acknowledgment. We thank DrsH. R. Baumgartner andH. Steffen, Research Department, F. Hoffmann-La Roche & Co. Ltd, Basel, for advice in performing and interpreting the experiments.     

Anti-muscarinic activity of a family of C11N5 compounds isolated fromAgelas sponges

In a search for potential target sites for C₁₁N₅ compounds obtained from marine sponges of the genusAgelas we evaluated their interaction with muscarinic acetylcholine receptors from rat brain membranes. In competition experiments with³H-QNB these compounds displayed the following rank order of potency: sceptrin>oroidindibromosceptrinclathrodin. Sceptrin (50 M) was shown to be a competitive inhibitor of³H-QNB binding as revealed by Scatchard analysis. The results demonstrate the ability of these compounds to interact with multiple target molecules in the micromolar range.     

Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans

Snake venom α-neurotoxins potently inhibit rodent nicotinic acetylcholine receptors (nAChRs), but their activity on human receptors and their role in human paralysis from snakebite remain unclear. We demonstrate that two short-chain α-neurotoxins (SαNTx) functionally inhibit human muscle-type nAChR, but are markedly more reversible than against rat receptors. In contrast, two long-chain α-neurotoxins (LαNTx) show no species differences in potency or reversibility. Mutant studies identified two key residues accounting for this. Proteomic and clinical data suggest that paralysis in human snakebites is not associated with SαNTx, but with LαNTx, such as in cobras. Neuromuscular blockade produced by both subclasses of α-neurotoxins was reversed by antivenom in rat nerve–muscle preparations, supporting its effectiveness in human post-synaptic paralysis.     

Metazoan endoparasites of 18 anuran species from the mesophytic semideciduous Atlantic Forest in southern Brazil

Brazil has the richest anuran biodiversity in the world and many species have not yet been studied for parasites. One hundred and forty frogs belonging to 18 species (Rhinella schneideri, Dendropsophus aff. minutus, Dendropsophus nanus, Hypsiboas albopunctatus, Hypsiboas punctatus, Hypsiboas raniceps, Phyllomedusa tetraploidea, Pseudis platensis, Scinax fuscovarius, Trachycephalus typhonius, Leptodactylus chaquensis, Leptodactylus fuscus, Leptodactylus aff. latrans, Leptodactylus mystacinus, Leptodactylus podicipinus, Physalaemus cuvieri, Physalaemus nattereri and Elachistocleis bicolor) collected in aquatic habitats in forest remnants and surrounding agricultural landscapes in southern Brazil were examined for endoparasites. Twenty-four species of endoparasites were identified among 21 adult and three larval individuals: one species of Monogenea, Polystoma lopezromani; eight species of Digenea, Catadiscus marinholutzi, Catadiscus propinquus, Choledocystus simulans, Gordoderina sp., Neohaematoloechus neivai, Rauschiella lenti, Rauschiella linguatula, Rauschiella repandum; one species of Cestoda, Ophiotaenia sp.; one species of Acanthocephala, Centrorhyncus sp.; 12 species of Nematoda, Aplectana sp., Aplectana travassosi, Cosmocerca podicipinus, Raillietnema sp., Schrankiana formolusa, Falcaustra mascula, Oxyascaris oxyascaris, Ochoterenella digiticauda, Physaloptera sp., Brevimulticecum sp., Rhabdias sp., Parapharyngodon hylidae; and one species of Annelida, Dero (Allodero) lutzi. The endoparasite fauna found is constituted by generalist species. Two new records of occurrence in Brazil and 33 new host records are reported.     

Potential geographic distribution niche modeling based on bioclimatic variables of three species of Temnomastax Rehn and Rehn, 1942 (Orthoptera: Eumastacidae)

Predictive modeling of geographic distribution based on ecological niche has become an important tool in ecology. It uses previous information about distribution of species and environmental variations associated with this distribution, restricting to the models the closest prediction of the ecological niche. The eumastacid grasshoppers are distributed mainly in the Neotropical region, and Temnomastacinae is the subfamily with the largest geographic distribution. Little is known about the biology of Eumastacidae, the only data available reporting the association between some grasshopper species and plants of several families. In the Cerrado only Temnomastax is recorded, which has a wide distribution in the central region of Brazil. The aim of this work was to determine the potential geographic distribution of three species of Temnomastax occurring in the Cerrado biome. We used 446 records of occurrence obtained in specialised literature, inventories, museums and photographs, from the following species: Temnomastax hamus, Temnomastax ricardoi and Temnomastax tigris. The niche modeling was generated with the bioclimatic model DOMAIN through DIVA-GIS. The potential geographic distribution of T. hamus is the largest among all Temnomastax species. Temnomastax ricardoi has its potential distribution in the central-north of Mato Grosso do Sul, in regions surrounding the type locality, while T. tigris. exhibits a restricted potential distribution along the carbonate arc of the Corumbá Formation, which outcrops in the region of Serra da Bodoquena and Corumbá, entering the eastern portion of Bolivia.     

双层地下室底层结构顶板空气冲击波压力研究

高层建筑多层地下室内人防结构顶板核爆荷载的合理确定是目前人防结构设计中急特解决的问题,应用模爆试验和空气动力学数值分析手段对问题进行研究,得到了典型工程双层地下室底层结构顶板爆炸压力分布规律。     

Lats基因敲除小鼠胚胎玻璃化冷冻的研究

用冷冻麦管、细胞冷冻管分别采用一步法和二步法对Lats基因敲除小鼠胚胎进行玻璃化冷冻 ,胚胎解冻后 ,囊胚发育率分别为 90 %、90 1%、89 2 %和 91 4 % ;移植后着床率分别为 :5 0 0 %、4 7 1%、4 3 4 %和 4 6 5 % ,差异不显著 ;并且与对照组相比差异也不显著。因此 ,玻璃化冷冻可以作为Lats鼠保种方法之一