The Toxicological Intersection between Allergen and Toxin: A Structural Comparison of the Cat Dander Allergenic Protein Fel d1 and the Slow Loris Brachial Gland Secretion Protein.

Slow lorises are enigmatic animal that represent the only venomous primate lineage. Their defensive secretions have received little attention. In this study we determined the full length sequence of the protein secreted by their unique brachial glands.

Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis.

Most cancer deaths result from metastasis, which is the dissemination of cells from a primary tumor to distant organs. Metastasis involves changes to molecules that are essential for tumor cell adhesion to the extracellular matrix and to endothelial cells. Junctional Adhesion Molecule C (JAM-C) localizes at intercellular junctions as homodimers or more affine heterodimers with JAM-B.

Visual methodologies and participatory action research: Performing women's community-based health promotion in post-Katrina New Orleans.

Recovery from disaster and displacement involves multiple challenges including accompanying survivors, documenting effects, and rethreading community. This paper demonstrates how African-American and Latina community health promoters and white university-based researchers engaged visual methodologies and participatory action research (photoPAR) as resources in cross-community praxis in the wake of Hurricane Katrina and the flooding of New Orleans. Visual techniques, including but not limited to photonarratives, facilitated the health promoters': (1) care for themselves and each other as survivors of and responders to the post-disaster context; (2) critical interrogation of New Orleans' entrenched pre- and post-Katrina structural racism as contributing to the racialised effects of and responses to Katrina; and (3) meaning-making and performances of women's community-based, cross-community health promotion within this post-disaster context.

Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems.

Unlabelled: Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.

Intraspecific venom variation in the medically significant Southern Pacific Rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary implications.

Unlabelled: Due to the extreme variation of venom, which consequently results in drastically variable degrees of neutralization by CroFab antivenom, the management and treatment of envenoming by Crotalus oreganus helleri (the Southern Pacific Rattlesnake), one of the most medically significant snake species in all of North America, has been a clinician's nightmare. This snake has also been the subject of sensational news stories regarding supposed rapid (within the last few decades) evolution of its venom. This research demonstrates for the first time that variable evolutionary selection pressures sculpt the intraspecific molecular diversity of venom components in C.

Atractaspis aterrima toxins: the first insight into the molecular evolution of venom in side-stabbers.

Although snake venoms have been the subject of intense research, primarily because of their tremendous potential as a bioresource for design and development of therapeutic compounds, some specific groups of snakes, such as the genus Atractaspis, have been completely neglected. To date only limited number of toxins, such as sarafotoxins have been well characterized from this lineage. In order to investigate the molecular diversity of venom from Atractaspis aterrima-the slender burrowing asp, we utilized a high-throughput transcriptomic approach completed with an original bioinformatics analysis pipeline.

African American and Latina community health workers engage PhotoPAR as a resource in a post-disaster context: Katrina at 5 years.

This article reports on participatory action and photo elicitation research conducted by community health workers and university-based researchers in post-Katrina New Orleans between August 2007 and 2010. It documents how 11 African American and Latina women community health workers forged ties and developed a model for responding to some of the personal, familial, and community effects of this "unnatural disaster." We identify and analyze two of the health literacies they developed and deployed: (1) intragroup and intergroup empathy skills and (2) capacity to critically analyze structural causes of health inequities.

Novel transcripts in the maxillary venom glands of advanced snakes.

Venom proteins are added to reptile venoms through duplication of a body protein gene, with the duplicate tissue-specifically expressed in the venom gland. Molecular scaffolds are recruited from a wide range of tissues and with a similar level of diversity of ancestral activity. Transcriptome studies have proven an effective and efficient tool for the discovery of novel toxin scaffolds.

Functional and structural diversification of the Anguimorpha lizard venom system.

Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade.

The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms.

Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have included AVIT/colipase/prokineticin, CAP, chitinase, cystatin, defensins, hyaluronidase, Kunitz, lectin, lipocalin, natriuretic peptide, peptidase S1, phospholipase A(2), sphingomyelinase D, and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of invertebrates (e.

A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus.

The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus.

Flavonoids for controlling starch digestion: structural requirements for inhibiting human alpha-amylase.

In this study we investigated the structural requirements for inhibition of human salivary alpha-amylase by flavonoids. Four flavonols and three flavones, out of the 19 flavonoids tested, exhibited IC50 values less than 100 microM against human salivary alpha-amylase activity. Structure-activity relationships of these inhibitors by computational ligand docking showed that the inhibitory activity of flavonols and flavones depends on (i) hydrogen bonds between the hydroxyl groups of the polyphenol ligands and the catalytic residues of the binding site and (ii) formation of a conjugated pi-system that stabilizes the interaction with the active site.

Evolution of an arsenal: structural and functional diversification of the venom system in the advanced snakes (Caenophidia).

Venom is a key innovation underlying the evolution of advanced snakes (Caenophidia). Despite this, very little is known about venom system structural diversification, toxin recruitment event timings, or toxin molecular evolution. A multidisciplinary approach was used to examine the diversification of the venom system and associated toxins across the full range of the approximately 100 million-year-old advanced snake clade with a particular emphasis upon families that have not secondarily evolved a front-fanged venom system ( approximately 80% of the 2500 species).

Structural assessment of single amino acid mutations: application to TP53 function.

Single amino acid substitution is the type of protein alteration most related to human diseases. Current studies seek primarily to distinguish neutral mutations from harmful ones. Very few methods offer an explanation of the final prediction result in terms of the probable structural or functional effect on the protein.

Comparison of measured and calculated dose rates for the Castor HAW 20/28 CG.

In January 2003 neutron and gamma dose rate measurements at a CASTOR HAW 20/28 CG were performed by the Bundesamt für Strahlenschutz at Gorleben. First, commercial dose rate measurement devices were used, then spectral measurements with a Bonner sphere system were made to verify the results. Axial and circumferential dose rate profiles were measured near the cask surface and spectral measurements were performed for some locations.

Modeling the pore structure of voltage-gated sodium channels in closed, open, and fast-inactivated conformation reveals details of site 1 toxin and local anesthetic binding.

In this work molecular modeling was applied to generate homology models of the pore region of the Na(v)1.2 and Na(v)1.8 isoforms of human voltage-gated sodium channels.

A rivet model for channel formation by aerolysin-like pore-forming toxins.

The bacterial toxin aerolysin kills cells by forming heptameric channels, of unknown structure, in the plasma membrane. Using disulfide trapping and cysteine scanning mutagenesis coupled to thiol-specific labeling on lipid bilayers, we identify a loop that lines the channel. This loop has an alternating pattern of charged and uncharged residues, suggesting that the transmembrane region has a beta-barrel configuration, as observed for Staphylococcal alpha-toxin.

Early evolution of the venom system in lizards and snakes.

Among extant reptiles only two lineages are known to have evolved venom delivery systems, the advanced snakes and helodermatid lizards (Gila Monster and Beaded Lizard). Evolution of the venom system is thought to underlie the impressive radiation of the advanced snakes (2,500 of 3,000 snake species). In contrast, the lizard venom system is thought to be restricted to just two species and to have evolved independently from the snake venom system.

Quality control of fibrinogen secretion in the molecular pathogenesis of congenital afibrinogenemia.

Congenital afibrinogenemia is a rare bleeding disorder characterized by the absence in circulation of fibrinogen, a hexamer composed of two sets of three polypeptides (Aalpha, Bbeta and gamma). Each polypeptide is encoded by a distinct gene, FGA, FGB and FGG, all three clustered in a region of 50 kb on 4q31. A subset of afibrinogenemia mutations has been shown to specifically impair fibrinogen secretion, but the underlying molecular mechanisms remained to be elucidated.

Challenges for traditional birth attendants in northern rural Honduras.

Objective: to explore the relationship between community-based parteras, the staff at the Centro Materno Infantil (Mother-Child Centre), and other public health facilities within the district of Morazán in northern rural Honduras during the transition to new models of maternity care.

Design: focus-group discussions with two groups composed of a convenience sample of community parteras. After verbatim translation of the interviews, the transcripts were analysed for content.

iMolTalk: an interactive, internet-based protein structure analysis server.

iMolTalk (http://i.moltalk.org) is a new and interactive web server for protein structure analysis.

The Swiss-Prot variant page and the ModSNP database: a resource for sequence and structure information on human protein variants.

Missense mutation leading to single amino acid polymorphism (SAP) is the type of mutation most frequently related to human diseases. The Swiss-Prot protein knowledgebase records information on such mutations in various sections of a protein entry, namely in the "feature," "comment," and "reference" fields. To facilitate users in obtaining the most relevant information about each human SAP recorded in the knowledgebase, the Swiss-Prot Variant web pages were created to provide a summary of available sequence information, as well as additional structural information on each variant.