Fine-scale climate change: modelling spatial variation in biologically meaningful rates of warming

The existence of fine‐grain climate heterogeneity has prompted suggestions that species may be able to survive future climate change in pockets of suitable microclimate, termed ‘microrefugia’. However, evidence for microrefugia is hindered by lack of understanding of how rates of warming vary across a landscape. Here, we present a model that is applied to provide fine‐grained, multidecadal estimates of temperature change based on the underlying physical processes that influence microclimate. Weather station and remotely derived environmental data were used to construct physical variables that capture the effects of terrain, sea surface temperatures, altitude and surface albedo on local temperatures, which were then calibrated statistically to derive gridded estimates of temperature. We apply the model to the Lizard Peninsula, United Kingdom, to provide accurate (mean error = 1.21 °C; RMS error = 1.63 °C) hourly estimates of temperature at a resolution of 100 m for the period 1977–2014. We show that rates of warming vary across a landscape primarily due to long‐term trends in weather conditions. Total warming varied from 0.87 to 1.16 °C, with the slowest rates of warming evident on north‐east‐facing slopes. This variation contributed to substantial spatial heterogeneity in trends in bioclimatic variables: for example, the change in the length of the frost‐free season varied from +11 to −54 days and the increase in annual growing degree‐days from 51 to 267 °C days. Spatial variation in warming was caused primarily by a decrease in daytime cloud cover with a resulting increase in received solar radiation, and secondarily by a decrease in the strength of westerly winds, which has amplified the effects on temperature of solar radiation on west‐facing slopes. We emphasize the importance of multidecadal trends in weather conditions in determining spatial variation in rates of warming, suggesting that locations experiencing least warming may not remain consistent under future climate change

Setting up a platform for plant-based influenza virus vaccine production in South Africa

Background During a global influenza pandemic, the vaccine requirements of developing countries can surpass their supply capabilities, if these exist at all, compelling them to rely on developed countries for stocks that may not be available in time. There is thus a need for developing countries in general to produce their own pandemic and possibly seasonal influenza vaccines. Here we describe the development of a plant-based platform for producing influenza vaccines locally, in South Africa. Plant-produced influenza vaccine candidates are quicker to develop and potentially cheaper than egg-produced influenza vaccines, and their production can be rapidly upscaled. In this study, we investigated the feasibility of producing a vaccine to the highly pathogenic avian influenza A subtype H5N1 virus, the most generally virulent influenza virus identified to date. Two variants of the haemagglutinin (HA) surface glycoprotein gene were synthesised for optimum expression in plants: these were the full-length HA gene (H5) and a truncated form lacking the transmembrane domain (H5tr). The genes were cloned into a panel of Agrobacterium tumefaciens binary plant expression vectors in order to test HA accumulation in different cell compartments. The constructs were transiently expressed in tobacco by means of agroinfiltration. Stable transgenic tobacco plants were also generated to provide seed for stable storage of the material as a pre-pandemic strategy. Results For both transient and transgenic expression systems the highest accumulation of full-length H5 protein occurred in the apoplastic spaces, while the highest accumulation of H5tr was in the endoplasmic reticulum. The H5 proteins were produced at relatively high concentrations in both systems. Following partial purification, haemagglutination and haemagglutination inhibition tests indicated that the conformation of the plant-produced HA variants was correct and the proteins were functional. The immunisation of chickens and mice with the candidate vaccines elicited HA-specific antibody responses. Conclusions We managed, after synthesis of two versions of a single gene, to produce by transient and transgenic expression in plants, two variants of a highly pathogenic avian influenza virus HA protein which could have vaccine potential. This is a proof of principle of the potential of plant-produced influenza vaccines as a feasible pandemic response strategy for South Africa and other developing countries

Predictive Models of Assistance Dog Training Outcomes Using the Canine Behavioral Assessment and Research Questionnaire and a Standardized Temperament Evaluation

Assistance dogs can greatly improve the lives of people with disabilities. However, a large proportion of dogs bred and trained for this purpose are deemed unable to successfully fulfill the behavioral demands of this role. Often, this determination is not finalized until weeks or even months into training, when the dog is close to 2 years old. Thus, there is an urgent need to develop objective selection protocols that can identify dogs most and least likely to succeed, from early in the training process. We assessed the predictive validity of two candidate measures employed by Canine Companions for Independence (CCI), a national assistance dog organization headquartered in Santa Rosa, CA. For more than a decade, CCI has collected data on their population using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) and a standardized temperament assessment known internally as the In-For-Training (IFT) test, which is conducted at the beginning of professional training. Data from both measures were divided into independent training and test datasets, with the training data used for variable selection and cross-validation. We developed three predictive models in which we predicted success or release from the training program using C-BARQ scores (N = 3,569), IFT scores (N = 5,967), and a combination of scores from both instruments (N = 2,990). All three final models performed significantly better than the null expectation when applied to the test data, with overall accuracies ranging from 64 to 68%. Model predictions were most accurate for dogs predicted to have the lowest probability of success (ranging from 85 to 92% accurate for dogs in the lowest 10% of predicted probabilities), and moderately accurate for identifying the dogs most likely to succeed (ranging from 62 to 72% for dogs in the top 10% of predicted probabilities). Combining C-BARQ and IFT predictors into a single model did not improve overall accuracy, although it did improve accuracy for dogs in the lowest 20% of predicted probabilities. Our results suggest that both types of assessments have the potential to be used as powerful screening tools, thereby allowing more efficient allocation of resources in assistance dog selection and training.Ministry of Food, Agriculture and Fisheries of Denmark (DFFE) [3304-FVFP-09-F-011]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Development of Complement Factor H-Based Immunotherapeutic Molecules in Tobacco Plants Against Multidrug-Resistant Neisseria gonorrhoeae

Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococci possess several mechanisms to evade killing by human complement, including binding of factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized in a head-to-tail manner as a single chain. N. gonorrhoeae binds two regions in FH; domains 6 and 7 and domains 18 through 20. We designed a novel anti-infective immunotherapeutic molecule that fuses domains 18-20 of FH containing a D-to-G mutation in domain 19 at position 1119 (called FH*) with human IgG1 Fc. FH*/Fc retained binding to gonococci but did not lyse human erythrocytes. Expression of FH*/Fc in tobacco plants was undertaken as an alternative, economical production platform. FH*/Fc was expressed in high yields in tobacco plants (300-600 mg/kg biomass). The activities of plant- and CHO-cell produced FH*/Fc against gonococci were similar in vitro and in the mouse vaginal colonization model of gonorrhea. The addition of flexible linkers [e.g., (GGGGS)2 or (GGGGS)3] between FH* and Fc improved the bactericidal efficacy of FH*/Fc 2.7-fold. The linkers also improved PMN-mediated opsonophagocytosis about 11-fold. FH*/Fc with linker also effectively reduced the duration and burden of colonization of two gonococcal strains tested in mice. FH*/Fc lost efficacy: i) in C6(-/-) mice (no terminal complement) and ii) when Fc was mutated to abrogate complement activation, suggesting that an intact complement was necessary for FH*/Fc function in vivo. In summary, plant-produced FH*/Fc represent promising prophylactic or adjunctive immunotherapeutics against multidrug-resistant gonococci

Organic Matter Preservation and Incipient Mineralization of Microtubules in 120 Ma Basaltic Glass

Hollow tubular structures in subaqueously-emplaced basaltic glass may represent trace fossils caused by microbially-mediated glass dissolution. Mineralized structures of similar morphology and spatial distribution in ancient, metamorphosed basaltic rocks have widely been interpreted as ichnofossils, possibly dating to similar to 3.5 Ga or greater. Doubts have been raised, however, regarding the biogenicity of the original hollow tubules and granules in basaltic glass. In particular, although elevated levels of biologically-important elements such as C, S, N, and P as well as organic compounds have been detected in association with these structures, a direct detection of unambiguously biogenic organic molecules has not been accomplished. In this study, we describe the direct detection of proteins associated with tubular textures in basaltic glass using synchrotron X-ray spectromicroscopy. Protein-rich organic matter is shown to be associated with the margins of hollow and partly-mineralized tubules. Furthermore, a variety of tubule-infilling secondary minerals, including Ti-rich oxide phases, were observed filling and preserving the microtextures, demonstrating a mechanism whereby cellular materials may be preserved through geologic time

The Orthologue of Sjögren's Syndrome Nuclear Autoantigen 1 (SSNA1) in Trypanosoma brucei Is an Immunogenic Self-Assembling Molecule

Primary Sjögren's Syndrome (PSS) is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14) is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13) and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle

Predictive Models of Assistance Dog Training Outcomes Using the Canine Behavioral Assessment and Research Questionnaire and a Standardized Temperament Evaluation

Assistance dogs can greatly improve the lives of people with disabilities. However, a large proportion of dogs bred and trained for this purpose are deemed unable to successfully fulfill the behavioral demands of this role. Often, this determination is not finalized until weeks or even months into training, when the dog is close to 2 years old. Thus, there is an urgent need to develop objective selection protocols that can identify dogs most and least likely to succeed, from early in the training process. We assessed the predictive validity of two candidate measures employed by Canine Companions for Independence (CCI), a national assistance dog organization headquartered in Santa Rosa, CA. For more than a decade, CCI has collected data on their population using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) and a standardized temperament assessment known internally as the In-For-Training (IFT) test, which is conducted at the beginning of professional training. Data from both measures were divided into independent training and test datasets, with the training data used for variable selection and cross-validation. We developed three predictive models in which we predicted success or release from the training program using C-BARQ scores (N = 3,569), IFT scores (N = 5,967), and a combination of scores from both instruments (N = 2,990). All three final models performed significantly better than the null expectation when applied to the test data, with overall accuracies ranging from 64 to 68%. Model predictions were most accurate for dogs predicted to have the lowest probability of success (ranging from 85 to 92% accurate for dogs in the lowest 10% of predicted probabilities), and moderately accurate for identifying the dogs most likely to succeed (ranging from 62 to 72% for dogs in the top 10% of predicted probabilities). Combining C-BARQ and IFT predictors into a single model did not improve overall accuracy, although it did improve accuracy for dogs in the lowest 20% of predicted probabilities. Our results suggest that both types of assessments have the potential to be used as powerful screening tools, thereby allowing more efficient allocation of resources in assistance dog selection and training