Use of a candidate gene array to delineate gene expression patterns in cattle selected for resistance or susceptibility to intestinal nematodes

In the present study, we use microarray technology to investigate the expression patterns of 381 genes with known association to host immune responses. Hybridization targets were derived from previously characterized bovine cDNAs. A total of 576 reporters (473 sequence-validated cDNAs and 77 controls) were spotted onto glass slides in two sets of four replicates. Two color, comparative hybridizations across both mesenteric lymph node (MLN) and small intestine mucosa (SIM) RNA samples were done between animals with previously demonstrated phenotypic differences based on natural exposure to gastro- intestinal (GI) nematodes over a 6-month exposure period. A total of 138 significant hybridization differences were detected by mixed model analysis of variance. A subset of these significant differences was validated by quantitative, real-time RT-PCR to assay transcript levels for 18 genes. These results confirmed that in the SIM, susceptible animals showed significantly higher levels in the genes encoding IGHG1, CD3E, ACTB, IRF1, CCL5 and C3, while in the MLN of resistant animals, higher levels of expression were confirmed for PTPRC, CD1D and ITGA4. Combined, the results indicate that immune responses against GI nematode infections involve multiple response pathways. Higher levels of expression for IgE receptor, integrins, complement, monocyte/macrophage and tissue factors are related to resistance. In contrast, higher levels of expression for immunoglobulin chains and TCRs are related to susceptibility. Identification of these genes provides a framework to better understand the genetic variation underlying parasite resistance

In Praise of Twisted Embeddings

Our main result in this work is the extension of the Ring-LWE problem in lattice-based cryptography to include algebraic lattices, realized through twisted embeddings. We define the class of problems Twisted Ring-LWE, which replaces the canonical embedding by an extended form. We prove that our generalization for Ring-LWE is secure by providing a security reduction from Ring-LWE to Twisted Ring-LWE in both search and decision forms. It is also shown that the addition of a new parameter, the torsion factor defining the twisted embedding, does not affect the asymptotic approximation factors in the worst-case to average-case reductions. Thus, Twisted Ring-LWE maintains the consolidated hardness guarantee of Ring-LWE and increases the existing scope of algebraic lattices that can be considered for cryptographic applications. Additionally, we expand on the results of Ducas and Durmus (Public-Key Cryptography, 2012) on spherical Gaussian distributions to the proposed class of lattices under certain restrictions. Thus, sampling from a spherical Gaussian distribution can be done directly in the respective number field, while maintaining its shape and standard deviation when seen in $\mathbb{R}^n$ via twisted embeddings

Caspase-8 mediates inflammation and disease in rodent malaria

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFalpha and IL-1beta and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease

Validation of reference genes for expression analysis in the salivary gland and the intestine of Rhodnius prolixus (Hemiptera, Reduviidae) under different experimental conditions by quantitative real-time PCR

<p>Abstract</p> <p>Background</p> <p><it>Rhodnius prolixus </it>is a blood-feeding insect that can transmit <it>Trypanosoma cruzi </it>and <it>Trypanosoma rangeli </it>to vertebrate hosts. Recently, genomic resources for invertebrate vectors of human pathogens have increased significantly, and <it>R. prolixus </it>has been one of the main species studied among the triatomines. However, the paucity of information on many of the fundamental molecular aspects of this species limits the use of the available genomic information. The present study aimed to facilitate gene expression studies by identifying the most suitable reference genes for the normalization of mRNA expression data from qPCR.</p> <p>Results</p> <p>The expression stability of five candidate reference genes (<it>18S </it>rRNA, <it>GAPDH</it>, β-actin, α-tubulin and ribosomal protein <it>L26</it>) was evaluated by qPCR in two tissues (salivary gland and intestine) and under different physiological conditions: before and after blood feeding and after infection with <it>T. cruzi </it>or <it>T. rangeli</it>. The results were analyzed with three software programs: geNorm, NormFinder and BestKeeper. All of the evaluated candidate genes proved to be acceptable as reference genes, but some were found to be more appropriate depending on the experimental conditions. <it>18S</it>, <it>GAPDH </it>and α-tubulin showed acceptable stability for studies in all of the tissues and experimental conditions evaluated. β-actin, one of the most widely used reference genes, was confirmed to be one of the most suitable reference genes in studies with salivary glands, but it had the lowest expression stability in the intestine after insect blood feeding. <it>L26 </it>was identified as the poorest reference gene in the studies performed.</p> <p>Conclusions</p> <p>The expression stability of the genes varies in different tissue samples and under different experimental conditions. The results provided by three statistical packages emphasize the suitability of all five of the tested reference genes in both the crop and the salivary glands with a few exceptions. The results emphasise the importance of validating reference genes for qRT-PCR analysis in <it>R. prolixus </it>studies.</p