TICK INNATE IMMUNITY

Ticks are blood feeding parasites transmitting a wide variety of pathogens to their vertebrate hosts. The vector competence of ticks is tightly linked with their immune system. Despite its importance, our knowledge of tick innate immunity is still inadequate and the limited number of sufficiently characterized immune molecules and cellular reactions are dispersed across numerous tick species. The phagocytosis of microbes by tick hemocytes seems to be coupled with a primitive complement-like system, which possibly involves self/nonself recognition by fibrinogen-related lectins and the action of thioester-containing proteins. Ticks do not seem to possess a pro-phenoloxidase system leading to melanization and also coagulation of tick hemolymph has not been experimentally proven. They are capable of defending themselves against microbial infection with a variety of antimicrobial peptides comprising lysozymes, defensins and molecules not found in other invertebrates. Virtually nothing is known about the signaling cascades involved in the regulation of tick antimicrobial immune responses. Midgut immunity is apparently the decisive factor of tick vector competence. The gut content is a hostile environment for ingested microbes, which is mainly due to the antimicrobial activity of hemoglobin fragments generated by the digestion of the host blood as well as other antimicrobial peptides. Reactive oxygen species possibly also play an important role in the tick-pathogen interaction. The recent release of the Ixodes scapularis genome and the feasibility of RNA interference in ticks promise imminent and substantial progress in tick innate immunity research.

Inferring Contagion in Regulatory Networks

Several gene regulatory network models containing concepts of directionality at the edges have been proposed. However, only a few reports have an interpretable definition of directionality. Here, differently from the standard causality concept defined by Pearl, we introduce the concept of contagion in order to infer directionality at the edges, i.e., asymmetries in gene expression dependences of regulatory networks. Moreover, we present a bootstrap algorithm in order to test the contagion concept. This technique was applied in simulated data and, also, in an actual large sample of biological data. Literature review has confirmed some genes identified by contagion as actually belonging to the TP53 pathway.

Somatostatin modulates G-CSF-induced but not interleukin-3-induced proliferative responses in myeloid 32D cells via activation of somatostatin receptor subtype 2

Somatostatin, originally identified as a peptide involved in neurotransmission, functions as an inhibitor of multiple cellular responses, including hormonal secretion and proliferation. Somatostatin acts through activation of G-protein-coupled receptors of which five subtypes have been identified. We have recently established that human CD34/c-kit expressing hematopoietic progenitors and acute myeloid leukemia (AML) cells exclusively express SSTR2. A major mechanism implicated in the antiproliferative action of somatostatin involves activation of the SH2 domain-containing protein tyrosine phosphatase SHP-1. While 0.1-1 x 10(-9) M of somatostatin, or its synthetic stable analog octreotide, can inhibit G-CSF-induced proliferation of AML cells, little or no effects are seen on GM-CSF- or IL-3-induced responses.
MATERIALS AND METHODS: To study the mechanisms underlying the antiproliferative responses of myeloblasts to somatostatin, clones of the IL-3-dependent murine cell line 32D that stably express SSTR2 and G-CSF receptors were generated. RESULTS: Similar to AML cells, octreotide inhibited G-CSF-induced but not IL-3-induced proliferative responses of 32D[G-CSF-R/SSTR2] cells. Somatostatin induced SHP-1 activity and inhibited G-CSF-induced, but not IL-3-induced, activation of the signal transducer and activator of transcription proteins STAT3 and STAT5.
CONCLUSION: Based on these data and previous results, we propose a model in which recruitment and activation of the tyrosine phosphatase SHP-1 by SSTR2 is involved in the selective negative action of somatostatin on G-CSF-R signaling.

The COMPASS subunit Spp1 links histone methylation to initiation of meiotic recombination

During meiosis, combinatorial associations of genetic traits arise from homologous recombination between parental chromosomes. Histone H3 lysine 4 trimethylation marks meiotic recombination hotspots in yeast and mammals, but how this ubiquitous chromatin modification relates to the initiation of double-strand breaks (DSBs) dependent on Spo11 remains unknown. Here, we show that the tethering of a PHD-containing protein, Spp1 (a component of the COMPASS complex), to recombinationally cold regions is sufficient to induce DSB formation. Furthermore, we found that Spp1 physically interacts with Mer2, a key protein of the differentiated chromosomal axis required for DSB formation. Thus, by interacting with H3K4me3 and Mer2, Spp1 promotes recruitment of potential meiotic DSB sites to the chromosomal axis, allowing Spo11 cleavage at nearby nucleosome-depleted regions.

SOCS proteins in development and disease

Cytokine and growth factor signaling mediates essential roles in the differentiation, proliferation, survival and function of a number of cell lineages. This is achieved via specific receptors located on the surface of target cells, with ligand binding activating key intracellular signal transduction cascades to mediate the requisite cellular outcome. Effective resolution of receptor signaling is also essential, with excessive signaling having the potential for pathological consequences. The Suppressor of cytokine signaling (SOCS) family of proteins represent one important mechanism to extinguish cytokine and growth factor receptor signaling. There are 8 SOCS proteins in mammals; SOCS1-7 and the alternatively named Cytokine-inducible SH2-containing protein (CISH). SOCS1-3 and CISH are predominantly associated with the regulation of cytokine receptor signaling, while SOCS4-7 are more commonly involved in the control of Receptor tyrosine kinase (RTK) signaling. Individual SOCS proteins are typically induced by specific cytokines and growth factors, thereby generating a negative feedback loop. As a consequence of their regulatory properties, SOCS proteins have important functions in development and homeostasis, with increasing recognition of their role in disease, particularly their tumor suppressor and anti-inflammatory functions. This review provides a synthesis of our current understanding of the SOCS family, with an emphasis on their immune and hematopoietic roles.

Evidence for conformational changes in the yeast deoxyhypusine hydroxylase Lia1 upon iron displacement from its active site

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

Morfologia e anatomia da semente de Esenbeckia grandiflora Mart. (Rutaceae)

Foram descritos e ilustrados aspectos morfo-anatômicos das sementes de Esenbeckia grandiflora Mart., visando o conhecimento dos tegumentos, endosperma e embrião. As sementes são de elipsóides a piramidais, marrom-escuras, anátropas, mesotestais, sem tégmem, exariladas e exalbuminosas. O embrião é axial, reto, total, branco, com cotilédones carnosos de reserva lipo-protéica, eixo hipocótilo-radícula curto e plúmula reduzida.

Morfologia e anatomia da semente de Dictyoloma vandellianum Adr. Juss.(Rutaceae)

Foram descritos e ilustrados aspectos morfo-anatômicos das sementes de Dictyoloma vandellianum Adr. Juss., visando o conhecimento dos tegumentos, endosperma e embrião. As sementes são reniformes, aladas, acobreadas, mesotestais, exariladas e albuminosas (reserva protéica). O embrião é axial, curvo, dominante, com cotilédones carnosos de reserva protéica, eixo hipocótilo-radícula longo e plúmula reduzida.

Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsion model in rats

In previous studies, it was shown that lipid microemulsions resembling LDL (LDE) but not containing protein, acquire apolipoprotein E when injected into the bloodstream and bind to LDL receptors (LDLR) using this protein as ligand. Aiming to evaluate the effects of apolipoprotein (apo) B-100 on the catabolism of these microemulsions, LDE with incorporated apo B-100 (LDE-apoB) and native LDL, all labeled with radioactive lipids were studied after intraarterial injection into Wistar rats. Plasma decay curves of the labels were determined in samples collected over 10 h and tissue uptake was assayed from organs excised from the animals sacrificed 24 h after injection. LDE-apo B had a fractional clearance rate (FCR) similar to native LDL (0.40 and 0.33, respectively) but both had FCR pronouncedly smaller than LDE (0.56, P<0.01). Liver was the main uptake site for LDE, LDE-apoB, and native LDL, but LDE-apoB and native LDL had lower hepatic uptake rates than LDE. Pre-treatment of the rats with 17 alpha-ethinylestradiol, known to upregulate LDLR, accelerated the removal from plasma of both LDE and LDE-apoB, but the effect was greater upon LDE than LDE-apoB. These differences in metabolic behavior documented in vivo can be interpreted by the lower affinity of LDLR for apo B-100 than for apo E, demonstrated in in vitro studies. Therefore, our study shows in vivo that, in comparison with apo E, apo B is a less efficient ligand to remove lipid particles such as microemulsions or lipoproteins from the intravascular compartment. (C) 1999 Elsevier B.V. B.V. All rights reserved.

A Preliminary and Qualitative Metallomics Study of Mercury in the Muscle of Fish from Amazonas, Brazil

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

Stimulation of MMP-1 and CCL2 by NAMPT in PDL cells

Periodontitis is an inflammatory disease caused by pathogenic microorganisms and characterized by the destruction of the periodontium. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), may be a pathomechanistic link between both diseases. The aim of this in vitro study was to examine the regulation of periodontal ligament (PDL) cells by NAMPT and its production under inflammatory and infectious conditions. NAMPT caused a significant upregulation of 9 genes and downregulation of 3 genes, as analyzed by microarray analysis. Eight of these genes could be confirmed by real-time PCR: NAMPT induced a significant upregulation of EGR1, MMP-1, SYT7, ITPKA, CCL2, NTM, IGF2BP3, and NRP1. NAMPT also increased significantly the MMP-1 and CCL2 protein synthesis. NAMPT was significantly induced by interleukin-1β and the periodontal microorganism P. gingivalis. NAMPT may contribute to periodontitis through upregulation of MMP-1 and CCL2 in PDL cells. Increased NAMPT levels, as found in obesity, may therefore represent a mechanism whereby obesity could confer an increased risk of periodontitis. Furthermore, microbial and inflammatory signals may enhance the NAMPT synthesis in PDL cells and thereby contribute to the increased gingival and serum levels of this adipokine, as found in periodontitis. © 2013 Marjan Nokhbehsaim et al.

Associação genômica ampla para características reprodutivas em bovinos da raça Nelore

Pós-graduação em Medicina Veterinária - FCAV

Análise microbiológica e físico-química de material proteico comestível derivado do processamento da gordura oriunda do abate de bovinos

Background: The use of all by-products of bovine slaughter is of high economic importance for the industries of products of animal origin. Among these products, fat has an important role, once fat rendering may generate several different products, such as protein material that may be used in the manufacture of meat products. However, in spite of the importance that the use of all by-products has for the economic balance of the industry, there are no reports on their use in Brazil, or studies that supply data on microbiological and physical-chemical local standards for this protein. Thus, the objective of this study was to evaluate microbiological and physical-chemical characteristics of protein material obtained from fat rendering, as well as to provide support for companies to use fat rendering to generate protein material, adding value to industrialized meat products.Materials, Methods & Results: The experimental production of edible protein obtained of fat rendering was conducted in slaughterhouse with supervision of the Brazilian Ministry of Agriculture, Livestock and Food Supply. Protein material was obtained in a continuous, humid heat system at high temperatures. Fat scraps containing protein were ground and cooked at high temperature (85 degrees C), and placed in a three phase decanter centrifuge. After centrifugation, protein material was ground again and packed. Samples were collected from 15 batches of protein material, and the following microbiological analyses were carried out: counts of aerobic mesophilic and psychrotrophic microorganisms, coliforms at 35 degrees C, Escherichia coli, sulfite-reducing Clostridium, and Staphylococcus aureus, besides presence or absence of Salmonella and Listeria monocytogens. The following physical-chemical analyses were also carried out: protein, total lipid, moisture, ash, carbohydrate, and energy content. Mean counts of mesophiles, psychrotrophs, and coliforms at 35 degrees C were 4.17; 3.69 and 1.87 (log CFU/g), respectively. Levels of protein, total lipids, moisture, ashes and carbohydrates were 27.50; 7.83; 63.88%; 0.24%; and 0.55%, respectively, and energy content was 182.63 kcal/100g.Discussion: Results of microbiological analyses demonstrated that, although low, the final product showed to be contaminated. Contamination that occurred during the second grinding procedure may be an explanation for these bacterial counts. Also, the temperature used for fat fusion was not enough to eliminate thermoduric microorganisms. However, even with the presence of indicator microorganisms in the samples, none was contaminated by E. coli, sulfite-reducing Clostridium, S. aureus, Salmonella or L. monocytogenes. Physical-chemical analyses showed that the product had adequate nutritional quality. Based on these results, it was possible to conclude that protein material obtained in fat rendering showed characteristics that enable the use of this product as raw material for processed meat products. Besides, the present study was the first one to present scientific results in relation to edible by-products obtained in fat rendering, supplying important information for slaughterhouses and meat-processing plants. The study also produced relevant data on the innocuousness of the product, which may be used to guide decision-making of health inspectors.

ROCK1 as a novel prognostic marker in vulvar cancer

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