Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5

An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.     

Silk genes support the single origin of orb webs

The orb web is a spectacular evolutionary innovation that enables spiders to catch flying prey. This elegant, geometric structure is woven with silk fibers that are renowned for their superior mechanical properties. We used silk gland expression libraries to address a long-standing controversy concerning the evolution of the orb-web architecture. Contrary to the view that the orb-web design evolved multiple times, we found that the distribution and phylogeny of silk proteins support a single, ancient origin of the orb web at least 136 million years ago. Furthermore, we substantially expanded the repository of silk sequences that can be used for the synthesis of high-performance biomaterials.     

Effect of adrenalectomy on cholecystokinin-8-induced Fos-like immunoreactivity in myenteric neurons and the dorsal vagal complex in rats

OBJECTIVE: To investigate the effect of adrenalectomy on cholecystokinin-8 (CCK-8)-induced Fos-like immunoreactivity (Fos-LI) in the myenteric neurons of the dorsal vagal complex (DVC) in rats. ANIMALS: 16 male Sprague Dawley rats. PROCEDURES: Rats were allocated to 1 of 2 groups and underwent adrenalectomy or a sham adrenalectomy procedure. Rats were challenged with a supraphysiologic dose of CCK-8 (40 microg/kg) or physiologic saline (0.9% NaCl) solution (0.5 mL) administered IP; after 90 minutes, rats were euthanized, and Fos-LI was quantified in the DVC (at the levels of the area postrema, nucleus tractus solitarii, and dorsal motor nucleus of the vagus) and the myenteric neurons of the duodenum and jejunum by use of a diaminobenzidine reaction enhanced with nickel. The Fos-LI-positive cells were counted by use of an automated system and manually in the DVC and intestinal samples, respectively. Counts of Fos-LI in the different hindbrain levels and myenteric neurons were compared between the adrenalectomy--and shamtreated groups and between the CCK-8- and saline solution-treated groups. RESULTS: After adrenalectomy, CCK-8-induced Fos-LI was attenuated only in the myenteric neurons of the duodenum. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that the adrenal gland has a role in the activation of myenteric neurons by CCK-8 in rats.     

Age-dependent seroprevalence of antibodies against a Helicobacter pylori-like organism and Helicobacter pylori in commercially reared swine

OBJECTIVE: To determine the prevalence of antibodies against a swine-origin Helicobacter pylori-like organism (HPLO) and H pylori in conventionally reared swine. ANIMALS: 640 conventionally reared swine of various ages from 16 high-health farms in Canada, 20 sows from Ohio, and 35 gnotobiotic swine. PROCEDURES: Blood was collected from the cranial vena cava. Sera were collected and tested via ELISA for antibodies against antigen prepared from a swine-origin HPLO and human H pylori strain 26695. RESULTS: Antibodies reactive with a swine HPLO, H pylori, or both were detected in 483 of 640 swine from all 16 farms in western Canada. Seroprevalence varied with age and was low (5.6%) in suckling ( 4 weeks old to adulthood. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that colonization by a swine-origin HPLO, H pylori, or both and resultant seroconversion, like that of H pylori infection in humans, were common in commercial swine operations. Furthermore, data indicated that gastric infection was acquired at an early age. The relationships to gastric colonization by HPLOs and clinical manifestations of disease such as gastritis and gastroesophageal ulceration remain to be determined.     

Theileria orientalis MPSP types in Australian cattle herds associated with outbreaks of clinical disease and their association with clinical pathology findings

Between September 2010 and November 2011, 350 EDTA blood samples were received from 73 Australian cattle herds, as cases suspected to be infected with Theileria orientalis. Beef cattle were predominantly affected, with Angus and Angus-crossbred cattle representing 48% of smear positive samples examined. DNA extracts were tested in conventional polymerase chain reaction (PCR) assays for genes encoding the p32, Ikeda, Chitose and Buffeli major piroplasm surface proteins (MPSP). PCR findings were compared with results of clinical pathology examinations of stained blood smears for parasitaemia and packed cell volume (PCV). PCR testing was much more sensitive than clinical pathology examinations in detecting T. orientalis infections, and concurrent testing of neat and diluted extracts gave significantly more PCR positive results than testing of neat extract alone. Significant associations and correlations were shown between PCR results of p32 and Ikeda assays with PCV levels indicative of anaemia, and with the level of parasitaemia estimated by smears. A high proportion of samples had concurrent Ikeda and Chitose infection, and significantly more clinical cases of theileriosis were associated with the Ikeda MPSP type as the sole infection, compared with sole infection with types Chitose or Buffeli. The findings indicate Ikeda type organisms were significantly associated with clinical parameters of theileriosis in cattle herds in eastern Australia, and that this type is most likely to be responsible for outbreaks of theileriosis experienced in affected Australian herds. In New South Wales, 11 of 14 regulatory districts yielded Ikeda positive samples, with five (Mid-Coast, Cumberland, Central North, Hume and Lachlan) containing 234/307 (76%) of the Ikeda positive samples.     

Kinase dysfunction and kinase inhibitors

With recent advances in molecular biology, abnormalities in cancer cells that contribute to dysregulation of cell survival and proliferation are being characterized with greater precision. Through this process, key abnormalities in cancer cells involving proteins that regulate signal transduction, migration, mitosis and other critical processes have been identified. Such abnormalities often involve a class of proteins called kinases that act to phosphorylate other proteins in the cell, resulting in activation of these proteins in the absence of appropriate stimulation/regulation. Given their role in tumour biology, substantial effort has been directed at blocking the function of these proteins. Several approaches have been used, including monoclonal antibodies and small molecule inhibitors. While antibodies are primarily directed at cell surface proteins, small molecule inhibitors, also known as kinase inhibitors, target proteins throughout the cell. A variety of kinase inhibitors have been approved for the treatment of human cancers. In some instances, these inhibitors have exhibited significant clinical efficacy, and it is likely that their biological activity will be further enhanced as combination regimens with standard treatment modalities are explored. The use of kinase inhibitors in dogs and cats is relatively recent, although two inhibitors, toceranib (Palladia; Pfizer Animal Health, Madison, NJ, USA) and masitinib (Kinavet; Catalent Pharma Solutions, Somerset, NJ, USA) have been approved by the Federal Drug Administration (USA) for use in dogs. This article reviews the biology of protein kinase dysfunction in human and animal cancers, and the application of specific kinase inhibitors to veterinary cancer patients.     

An impediment to consumer choice: Overfished species are sold as Pacific red snapper

Concern over the collapse of many wild-caught fisheries has led to a recent focus on seafood-certification and consumer-driven support of sustainable seafood. However, such conservation strategies depend critically on the accurate labeling of seafood species in marketplaces. Pacific rockfish, a group of >60 species in the genus Sebastes, are often marketed as Pacific red snapper, but little is known about the number and identity of rockfish species sold under this name. We used a molecular approach to identify species sold as Pacific red snapper by grocery chains, local fish markets, and sushi restaurants in California and Washington. Using genetic data from two mitochondrial markers (cytochrome-b and control region), we identified seven species of rockfish (Sebastes spp.), tilapia (Oreochromis spp.), and one true red snapper (Lutjanus campechanus) in our samples. Among samples identified as rockfish, 56% were identified as species listed as overfished by the National Marine Fisheries Service within the past three years. By effectively permitting all species of rockfish to be sold under a common vernacular name, state and federal agencies compromise the ability of consumers to make informed choices when buying seafood.