Immune responses of cattle vaccinated by various routes with Mycobacterium bovis Bacillus Calmette-Guérin (BCG).

Background: Mycobacterium bovis BCG is the human tuberculosis vaccine and is the oldest vaccine still in use today with over 4 billion people vaccinated since 1921. The BCG vaccine has also been investigated experimentally in cattle and wildlife by various routes including oral and parenteral. Thus far, oral vaccination studies of cattle have involved liquid BCG or liquid BCG incorporated into a lipid matrix.

Pathogen Detection in Early Phases of Experimental Bovine Tuberculosis.

Bovine tuberculosis is caused by , a member of the complex of mycobacterial species that cause tuberculosis in humans and animals. Diagnosis of bovine tuberculosis has relied on examinations of cell-mediated immune responses to proteins using tuberculin skin testing and/or interferon gamma release assays. Even when using these methods, disease detection during the earliest phases of infection has been difficult, allowing a window for cattle-to-cattle transmission to occur within a herd.

Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that causes a fatal neurodegenerative disease in cervids. Cases of CWD are rapidly increasing in North America among wild and farmed cervid populations, and potential for zoonotic transmission is not yet determined. Therefore, in order to manage the disease, it is imperative to devise a system that can detect CWD during its early phases to prevent spread to new captive herds through introduction of CWD-affected animals into otherwise CWD-free herds.

Real-Time Quaking-Induced Conversion Detection of PrP in Fecal Samples From Chronic Wasting Disease Infected White-Tailed Deer Using Bank Vole Substrate.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that is fatal to free-range and captive cervids. CWD has been reported in the United States, Canada, South Korea, Norway, Finland, and Sweden, and the case numbers in both wild and farmed cervids are increasing rapidly. Studies indicate that lateral transmission of cervids likely occurs through the shedding of infectious prions in saliva, feces, urine, and blood into the environment.

Evaluation of Antemortem Diagnostic Techniques in Goats Naturally Infected With Scrapie.

Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Sheep and goats can be infected with scrapie as lambs or kids contact with the placenta or placental fluids, or from ingestion of prions shed in the environment and/or bodily fluids (e.g.

Exploring disease comorbidity in a module-module interaction network.

Understanding disease comorbidity contributes to improved quality of life in patients who are suffering from multiple diseases. Therefore, to better explore comorbid diseases, the clarification of associations between diseases based on biological functions is essential. In our study, we propose a method for identifying disease comorbidity in a module-based network, named the module-module interaction (MMI) network, which represents how biological functions influence each other.

Novel Strain of the Chronic Wasting Disease Agent Isolated From Experimentally Inoculated Elk With LL132 Prion Protein.

Chronic wasting disease (CWD) is a fatal, progressive disease that affects cervid species, including Rocky mountain elk (Cervus elaphus nelsoni). There are 2 allelic variants in the elk prion protein gene: L132 (leucine) and M132 (methionine). Following experimental oral challenge with the CWD agent incubation periods are longest in LL132 elk, intermediate in ML132 elk, and shortest in MM132 elk.

Role of donor genotype in RT-QuIC seeding activity of chronic wasting disease prions using human and bank vole substrates.

Chronic wasting disease is a transmissible spongiform encephalopathy of cervids. This fatal neurodegenerative disease is caused by misfolding of the cellular prion protein (PrPC) to pathogenic conformers (PrPSc), and the pathogenic forms accumulate in the brain and other tissues. Real-time Quaking Induced Conversion (RT-QuIC) can be used for the detection of prions and for prion strain discrimination in a variety of biological tissues from humans and animals.

PAD-Beads enrichment enhances detection of PrP using real-time quaking-induced conversion.

Objective: Scrapie is a transmissible spongiform encephalopathy (TSE) that naturally occurs in sheep and goats. This fatal neurodegenerative disease results from misfolding of the normal cellular prion protein (PrP) to a pathogenic prion protein form (PrP). This pathogenic form, PrP, accumulates in the brain and lymphoid tissues.

Source genotype influence on cross species transmission of transmissible spongiform encephalopathies evaluated by RT-QuIC.

Scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats. This fatal neurodegenerative disease is caused by misfolding of the cellular prion protein to pathogenic β-rich conformers (PrPSc) that accumulate in higher order structures of the brain and other tissues. This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC).

Preparation of lyophilized recombinant prion protein for TSE diagnosis by RT-QuIC.

Objective: Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases, often referred as prion diseases. TSEs result from the misfolding of the cellular prion protein (PrP) into a pathogenic form (PrP) that accumulates in the brain and lymphatic tissue. Amplification based assays such as real-time quaking induced conversion allow us to assess the conversion of PrP to PrP.

Thermodynamic characterization for the denatured state of bovine prion protein and the BSE Associated variant E211K.

Propagation of transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrP, into a misfolded oligomeric form, PrP. The most common hereditary prion disease is a genetic form of Creutzfeldt-Jakob disease in humans, in which a mutation in the prion gene results in a glutamic acid to lysine substitution at position 200 (E200K) in PrP. In cattle, the analogous amino acid substitution is found at residue 211 (E211K) and has been associated with a case of bovine spongiform encephalopathy.

PISTON: Predicting drug indications and side effects using topic modeling and natural language processing.

The process of discovering novel drugs to treat diseases requires a long time and high cost. It is important to understand side effects of drugs as well as their therapeutic effects, because these can seriously damage the patients due to unexpected actions of the derived candidate drugs. In order to overcome these limitations, computational methods for predicting the therapeutic effects and side effects have been proposed.

Pathologic and biochemical characterization of PrP from elk with PRNP polymorphisms at codon 132 after experimental infection with the chronic wasting disease agent.

Background: The Rocky Mountain elk (Cervus elaphus nelsoni) prion protein gene (PRNP) is polymorphic at codon 132, with leucine (L132) and methionine (M132) allelic variants present in the population. In elk experimentally inoculated with the chronic wasting disease (CWD) agent, different incubation periods are associated with PRNP genotype: LL132 elk survive the longest, LM132 elk are intermediate, and MM132 elk the shortest. The purpose of this study was to investigate potential mechanisms underlying variations in incubation period in elk of different prion protein genotypes.

Real-Time Quaking-Induced Conversion Detection of Bovine Spongiform Encephalopathy Prions in a Subclinical Steer.

Bovine spongiform encephalopathy (BSE) belongs to a group of fatal prion diseases that result from the misfolding of the cellular prion protein (PrP) into a pathogenic form (PrP) that accumulates in the brain. assays such as serial protein misfolding amplification and real-time quaking-induced conversion (RT-QuIC) allow assessment of the conversion of PrP to PrP. RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals.

Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy.

Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals.

Discovery of a Unique Extracellular Polysaccharide in Members of the Pathogenic Bacillus That Can Co-form with Spores.

An exopolysaccharide, produced during the late stage of stationary growth phase, was discovered and purified from the culture medium of Bacillus cereus, Bacillus anthracis, and Bacillus thuringiensis when strains were grown in a defined nutrient medium that induces biofilm. Two-dimensional NMR structural characterization of the polysaccharide, named pzX, revealed that it is composed of an unusual three amino-sugar sequence repeat of [-3)XylNAc4OAc(α1-3)GlcNAcA4OAc(α1-3)XylNAc(α1-]n The sugar residue XylNAc had never been described previously in any glycan structure. The XNAC operon that contains the genes for the assembly of pzX is also unique and so far has been identified only in members of the Bacillus cereus sensu lato group.

The Biosynthesis of UDP-D-QuiNAc in Bacillus cereus ATCC 14579.

N-acetylquinovosamine (2-acetamido-2,6-di-deoxy-D-glucose, QuiNAc) is a relatively rare amino sugar residue found in glycans of few pathogenic gram-negative bacteria where it can play a role in infection. However, little is known about QuiNAc-related polysaccharides in gram-positive bacteria. In a routine screen for bacillus glycan grown at defined medium, it was surprising to identify a QuiNAc residue in polysaccharides isolated from this gram-positive bacterium.

Pen and Pal are nucleotide-sugar dehydratases that convert UDP-GlcNAc to UDP-6-deoxy-D-GlcNAc-5,6-ene and then to UDP-4-keto-6-deoxy-L-AltNAc for CMP-pseudaminic acid synthesis in Bacillus thuringiensis.

CMP-pseudaminic acid is a precursor required for the O-glycosylation of flagellin in some pathogenic Gram-negative bacteria, a process known to be critical in bacterial motility and infection. However, little is known about flagellin glycosylation in Gram-positive bacteria. Here, we identified and functionally characterized an operon, named Bti_pse, in Bacillus thuringiensis israelensis ATCC 35646, which encodes seven different enzymes that together convert UDP-GlcNAc to CMP-pseudaminic acid.

The biosynthesis of UDP-d-FucNAc-4N-(2)-oxoglutarate (UDP-Yelosamine) in Bacillus cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp protein that ligates 2-oxoglutarate to UDP-4-amino-sugars.

Surface glycan switching is often observed when micro-organisms transition between different biotic and abiotic niches, including biofilms, although the advantages of this switching to the organism are not well understood. Bacillus cereus grown in a biofilm-inducing medium has been shown to synthesize an unusual cell wall polysaccharide composed of the repeating subunit →6)Gal(α1-2)(2-R-hydroxyglutar-5-ylamido)Fuc2NAc4N(α1-6)GlcNAc(β1→, where galactose is linked to the hydroxyglutarate moiety of FucNAc-4-amido-(2)-hydroxyglutarate. The molecular mechanism involved in attaching 2-hydroxyglutarate to 4-amino-FucNAc has not been determined.

Folding of a tryptophan zipper peptide investigated on the basis of the nuclear Overhauser effect and thermal denaturation.

Short, secondary-structure-containing peptides are suitable models for the study of protein folding due to their relative simplicity. Here, we investigate thermal denaturation of the tryptophan zipper peptide, trpzip4, a peptide that forms a β-hairpin in solution. In order to monitor the thermal denaturation of peptides or small proteins, chemical shift values of H(α) or H(N) may be used.

Methanol strengthens hydrogen bonds and weakens hydrophobic interactions in proteins--a combined molecular dynamics and NMR study.

A combined simulation and experimental study was performed to investigate how methanol affects the structure of a model peptide BBA5. BBA5 forms a stable β-hairpin-α-helix structure in aqueous solutions. Molecular dynamics simulations were performed in water and methanol/water solutions using all-atom explicit models.

Folding determinants of disulfide bond forming protein B explored by solution nuclear magnetic resonance spectroscopy.

The two-stage model for membrane protein folding postulates that individual helices form first and are subsequently packed against each other. To probe the two-stage model, the structures of peptides representing individual transmembrane helices of the disulfide bond forming protein B have been studied in trifluoroethanol solution as well as in detergent micelles using nuclear magnetic resonance (NMR) and circular dichroism spectroscopy. In TFE solution, peptides showed well-defined α-helical structures.