Seroprevalence of foot and mouth disease and peste des petits ruminants in small ruminants in Zambia on the border to Tanzania : Searching for common traits among seropositive herds

Foot and mouth disease (FMD) and peste des petits ruminants (PPR) are highly contagious viral diseases affecting sheep and goats all over the world. Small ruminants are often owned by poor small-scale farmers in the developing world, and several studies have identified them to be among the most important livestock species for the poor. Controlling, or even eradicating, FMD and PPR is important for alleviating poverty. More than half of Zambia’s population was living below the national poverty line in 2015. FMD is today considered to be endemic in Zambia, the most recent outbreak was in March 2018. No clinical cases of PPR have been found within the country so far but PPR is highly present in Zambia’s bordering countries in the north and Zambia is therefore under constant risk of the incursion of PPR. This study was carried out in the districts Nakonde and Mbala in northeastern Zambia on the border to Tanzania. The purpose was to investigate the seroprevalence of FMD and PPR in sheep and goats and to identify possible associations between animal characteristics, management of herds or trade and seropositivity. Serum samples were collected from 480 small ruminants from 160 herds in 40 randomly selected villages. Details on species, breed, origin, sex, age and history of disease were noted for each sampled individual. The owner of each herd was also questioned about management of the herd and trade. Serum samples were analyzed for presence of antibodies to foot-and-mouth-disease virus and peste-des-petits ruminants virus. Potential risk factors were analyzed with Fisher’s Exact Test to see if there were any significant correlations with seropositivity for FMD or PPR. The results showed that the dominating species in the villages was goat, and the dominating gender was female. The majority of the sampled animals were born at the farm where they were sampled, only two were bought from another country. The herd size varied between two and 34 animals. The majority of the farmers let their herds graze freely in the dry season and had them tethered during the rainy season. Seventy-one percent of the herds met other herds of sheep and/or goats on at least a weekly basis, and the proportion that met cattle as often was only 21%. Four percent of the herds met wild ruminants on at least a weekly basis. Most farmers never bought goats or sheep from other countries. The true herd seroprevalence in the Nakonde and Mbala districts was approximately 3.2 percent (95% CI 1.1; 7.4) for FMD and 0.03 percent (95% CI 0;3) for PPR. No risk factors for FMD or PPR seropositivity could be identified. The study design was considered to have good external and internal validity. The low seroprevalences of both FMD and PPR, relatively to what was expected, are most likely representative of the true seroprevalences in the target population. This study found serological evidence of PPR in a goat in Zambia, but this result needs to be confirmed with other methods since there is a high risk of the result being falsely positive. It could be interesting to do further research on whether there are any protective factors keeping the small ruminants from encountering FMDV and PPRV in this area since the seroprevalence was lower than expected for both diseases

A structure of persuasion in Galatians: epistolary and rhetorical appeal in an aural setting

The purpose of this paper is to ponder the reception of the Letter to the Galatians in an aural setting. How did the first recipients react, what can we expect that they remembered after having listened to the letter? Are there structural elements in the letter that would have aided the aural reception of the letter? In four readings, the investigation traces textual indicators of interaction and emotion, compares their locations with epistolary and rhetorical structure-analysis and identifies a structure of persuasion. The focus on listeners is motivated by the supposition that illiteracy was the rule rather than the exception among those to whom the letter to the Galatians was sent. The different readings reveal a structure of persuasion with a realistic prospect to succeed as a mnemonic device in an aural setting on a macro-structural level. Situational passages (1:6-10; 3:1-5; 4:8-20; 5:2-12 and 6:12-13), together with recurring affirmations of Christ and Paul as embodiments of faithfulness and commitment in suffering, imprint on the aural memory of the first listeners a concern for an imitatio Christi crucifixi

Unfolding times for proteins in a force clamp

The escape process from the native valley for proteins subjected to a constant stretching force is examined using a model for a Beta-barrel. For a wide range of forces, the unfolding dynamics can be treated as one-dimensional diffusion, parametrized in terms of the end-to-end distance. In particular, the escape times can be evaluated as first passage times for a Brownian particle moving on the protein free-energy landscape, using the Smoluchowski equation. At strong forces, the unfolding process can be viewed as a diffusive drift away from the native state, while at weak forces thermal activation is the relevant mechanism. An escape-time analysis within this approach reveals a crossover from an exponential to an inverse Gaussian escape-time distribution upon passing from weak to strong forces. Moreover, a single expression valid at weak and strong forces can be devised both for the average unfolding time as well as for the corresponding variance. The analysis offers a possible explanation of recent experimental findings for ddFLN4 and ubiquitin.Comment: 6 pages, 4 figures, submitted for pubblication to Physical Review Letter

Noninvasive diagnostic methods for perceptual and motor disabilities in children with cerebral palsy

The field of neuroorthopedics centers on chronic diseases demanding close clinical monitoring. We shall use several examples to show how the various noninvasive diagnostic instruments can be used to obtain insight into the central nervous system as well as into the musculoskeletal system and its morphology. The choice of the most appropriate method depends on the problem; that is, whether the method is to be applied for clinical use or for basic research. In this report we introduce various technical examination methods that are being used successfully in the fields of pediatrics, orthopedics, and neurology. The major examination instrument in pediatric diagnostics is sonography, which is being used in this report as a research instrument for the biomechanics of the musculoskeletal system, but which also gives insight into neurofunctional sequences. In orthopedics, pedography is used for diagnosing deformities of the feet. In neuroorthopedics for children pedography acts as a functional monitor for apraxia and thus allows, for example, a classification of the degree of neurological malfunctions in the lower extremities. The 3D bodyscan is used to minimize x-raying in patients with neurogenic scoliosis. This report introduces examples of the application of MRI and fMRI for basic research. The biometric measuring methods introduced provide precise data in the areas of diagnostics and monitoring and are highly valuable for further neuroorthopedic basic research. In future we expect the ever-evolving technical measuring methods to enable a deeper understanding of the primary neurological causes of and the implications for patients with cerebral palsy and other neuroorthopedic conditions. This may allow the development of new forms of therapy not necessarily predictable today

A geometry-based generic predictor for catalytic and allosteric sites

An important aspect of understanding protein allostery, and of artificial effector design, is the characterization and prediction of substrate- and effector-binding sites. To find binding sites in allosteric enzymes, many of which are oligomeric with allosteric sites at domain interfaces, we devise a local centrality measure for residue interaction graphs, which behaves well for both small/monomeric and large/multimeric proteins. The measure is purely structure based and has a clear geometrical interpretation and no free parameters. It is not biased towards typically catalytic residues, a property that is crucial when looking for non-catalytic effector sites, which are potent drug targets.Norwegian Research Council/FUGE IIacceptedVersio

Coherent Conformational Degrees of Freedom as a Structural Basis for Allosteric Communication

Conformational changes in allosteric regulation can to a large extent be described as motion along one or a few coherent degrees of freedom. The states involved are inherent to the protein, in the sense that they are visited by the protein also in the absence of effector ligands. Previously, we developed the measure binding leverage to find sites where ligand binding can shift the conformational equilibrium of a protein. Binding leverage is calculated for a set of motion vectors representing independent conformational degrees of freedom. In this paper, to analyze allosteric communication between binding sites, we introduce the concept of leverage coupling, based on the assumption that only pairs of sites that couple to the same conformational degrees of freedom can be allosterically connected. We demonstrate how leverage coupling can be used to analyze allosteric communication in a range of enzymes (regulated by both ligand binding and post-translational modifications) and huge molecular machines such as chaperones. Leverage coupling can be calculated for any protein structure to analyze both biological and latent catalytic and regulatory sites

Diagnostik av atopisk dermatit hos hund

Antalet hundar som behandlas för allergiska sjukdomar ökar i världen och den vanligast förekommande diagnosen är atopisk dermatit (CAD). Hundar med CAD är överkänsliga mot allergen i sin omgivning såsom kvalster, pollen och mögelsporer. Exponering för allergenet utlöser en immunologisk reaktion som karakteriseras av en överproduktion av IgE och degranulering av mastceller. Det framkallar en inflammation i huden med efterföljande rodnad och klåda. När hunden kliar sig skadar den huden och bäddar för sekundära infektioner. Ofta är det symtomen från de sekundära infektionerna som djurägaren tagit sin hund till veterinären för. Vissa raser är överrepresenterade när det gäller CAD vilket indikerar att det förekommer en genetisk predisposition för sjukdomen. Hundens genetiska predisposition innebär dock inte att hunden nödvändigtvis utvecklar sjukdom. Riskfaktorer t.ex. inomhusvistelse och frekvent badning ökar risken för sjukdom medan bland annat utomhusvistelse och samlevnad med katter och/eller andra hundar är skyddande faktorer. Hunden måste även exponeras för allergenet i tillräcklig mängd för att allergin ska utlösas. Syftet med denna litteraturstudie var att undersöka hur atopisk dermatit på hund diagnostiseras och svårigheter med detta. Inledningsvis presenteras även sjukdomens etiologi och patogenes men tillgängliga behandlingar för tillståndet tas ej upp. Symtom vid CAD är främst rodnad, klåda och hudlesioner vilka inte är patognomona utan kliniskt identiska med flera andra tillstånd exempelvis födoallergi. Veterinären måste därför genomgå ett antal steg för att utesluta eventuella differentialdiagnoser innan diagnosen atopisk dermatit kan ställas. För att bekräfta diagnosen och för att utforma immunoterapi utförs sedan allergitest där specifika allergen som hunden är känslig för identifieras. Allergitesten som används idag är intradermalt test och allergenspecifik IgE-serologi. Svårigheter med diagnostiken av CAD är att symtomen är ospecifika och ibland maskerade av sekundära sjukdomar. Det är svårt att differentiera CAD från födoallergi då de båda ger likartade symtom och dessutom kan förekomma samtidigt. När det gäller allergitesterna kan det vara svårt att välja ut rätt allergen och rätt allergenkoncentration att testa hunden för. Det råder även viss osäkerhet kring resultatens korrelation till kliniska symtom då bland annat höga nivåer av allergenspecifika IgE har påvisats även hos icke atopiska hundar. Ytterligare en aspekt är att det förekommer korsreaktivitet mellan allergen vilket kan ge falskt positiva resultat vid allergitest. Diagnostiken av atopisk dermatit tar tid och kräver kompetens. Den försvåras av ospecifika symtom och något trubbiga diagnostiska verktyg. Det behövs ytterligare forskning på egenskaper som skiljer atopiska individer från friska och förbättring av diagnostiska metoder. Kanske kan forskning på genetiska riskfaktorer möjliggöra genotypning av hundar för att identifiera riskindivider i framtiden.The number of dogs being treated för allergic diseases is increasing and the most common diagnosis is Canine Atopic Dermatitis (CAD). Dogs with CAD are hypersensitive to allergens in their environment such as mites, pollens and moulds. When the dog is exposed to an allergen that it is sensitive for, the allergen will elicit an immunological reaction that is characterized by an overprduction of IgE and degranulation of mast cells. The reaction will cause an inflammation in the skin with subsequent erythema and pruritus. Skin lesions will form when the dog scratches itself and these lesions make way for microorganisms to colonize the skin. It is therefore common that dogs with CAD are secondarily infected with bacteria or yeast and these cause problems that often are the primary reasons for taking the dog to the veterinary clinic. There is an overrepresentation of certain breeds among dogs that are diagnosed with CAD. It suggests that they have a genetic predisposition for developing the disease. Dogs with this genetic predisposition have a higher risk of developing CAD but there is also an environmental factor affecting if they develop the disease or not. Risk factors are for example spending much time indoors and being bathed frequently. Protective factors are being outdoors, living in the countryside and living with other dogs or cats. The dog must also be exposed for an enough amount of allergen to elicit an immunological reaction. The purpose of this litterature study was to investigate how Canine Atopic Dermatitis is diagnosed and what could be the difficulties in doing so. In this study, no attention have been put on how to treat the condition, but a short description of the ethiology and pathogenesis of the diseases is presented in the beginning. The main symtoms from CAD are erythema, pruritus and skin lesions. The diagnostics can be difficult since these symtoms aren’t patognomonic but instead clinically identical to some other diseases such as food allergy. Therefore the veterinarian must undergo certain procedures to exclude other possible conditions before suspecting atopic dermatitis. The veterinarian can then proceed with allergy tests to confirm the diagnosis as well as to identify which allergens the dog is sensitive to for development of further treatment. The allergy tests that are being used today are intradermal test and allergenspecific IgE serology. Difficulties with the diagnostics are that the symtoms are unspecific and not seldom disguised by conditions secondary to atopic dermatitis. It is hard to distinguish CAD from food allergy since they show similar symtoms and also can occur together. Regarding the allergy tests, it may be hard to select the proper allergens to test for and the right concentration of allergens. There is also an uncertainty to whether the results of these test really correlate to the symtoms since for example high levels of allergen specific IgE have been found in healthy dogs as well. Another aspect is the occuring cross reactivity between some groups of allergens. To diagnose CAD is time consuming and demanding. It is difficult due to unspecific symtoms and the somewhat rough diagnostic tools of today. Further research is needed to identify what marks out atopic individuals. Maybe can genetic tests be a tool for identifying risk individuals in the future

Mechanical resistance in unstructured proteins

Single-molecule pulling experiments on unstructured proteins linked to neurodegenerative diseases have measured rupture forces comparable to those for stable folded proteins. To investigate the structural mechanisms of this unexpected force resistance, we perform pulling simulations of the amyloid {\beta}-peptide (A{\beta}) and {\alpha}-synuclein ({\alpha}S), starting from simulated conformational ensembles for the free monomers. For both proteins, the simulations yield a set of rupture events that agree well with the experimental data. By analyzing the conformations right before rupture in each event, we find that the mechanically resistant structures share a common architecture, with similarities to the folds adopted by A{\beta} and {\alpha}S in amyloid fibrils. The disease-linked Arctic mutation of A{\beta} is found to increase the occurrence of highly force-resistant structures. Our study suggests that the high rupture forces observed in A{\beta} and {\alpha}S pulling experiments are caused by structures that might have a key role in amyloid formation.Comment: v3: Added correct journal reference plus minor correction