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We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

Recent evidence demonstrates genomic and morphological continuity in the Arctic ancestral lineage of dogs. Here, we use the Siberian Husky to investigate the genomic legacy of the northeast Eurasian Arctic lineage and model the deep population history using genome-wide single nucleotide polymorphisms. Utilizing ancient dog-calibrated molecular clocks, we found that at least two distinct lineages of Arctic dogs existed in ancient Eurasia at the end of the Pleistocene. This pushes back the origin of sled dogs in the northeast Siberian Arctic with humans likely intentionally selecting dogs to perform different functions and keeping breeding populations that overlap in time and space relatively reproductively isolated. In modern Siberian Huskies, we found significant population structure based on how they are used by humans, recent European breed introgression in about half of the dogs that participate in races, moderate levels of inbreeding, and fewer potentially harmful variants in populations under strong selection for form and function (show, sled show, and racing populations of Siberian Huskies). As the struggle to preserve unique evolutionary lineages while maintaining genetic health intensifies across pedigreed dogs, understanding the genomic history to guide policies and best practices for breed management is crucial to sustain these ancient lineages and their unique evolutionary identity. [ABSTRACT FROM AUTHOR]

The retinal degenerative disease, progressive retinal atrophy (PRA) is a major reason of vision impairment in canine population. Canine PRA signifies an inherently dissimilar category of retinal dystrophies which has solid resemblances to human retinis pigmentosa. Even though much is known about the biology of PRA, the knowledge about the intricate connection among genetic loci, genes and pathways associated to this disease in dogs are still remain unknown. Therefore, we have performed a genome wide association study (GWAS) to identify susceptibility single nucleotide polymorphisms (SNPs) of PRA. The GWAS was performed using a case–control based association analysis method on PRA dataset of 129 dogs and 135,553 markers. Further, the gene-set and pathway analysis were conducted in this study. A total of 1,114 markers associations with PRA trait at p < 0.01 were extracted and mapped to 640 unique genes, and then selected significant (p < 0.05) enriched 35 gene ontology (GO) terms and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contain these genes. In particular, apoptosis process, homophilic cell adhesion, calcium ion binding, and endoplasmic reticulum GO terms as well as pathways related to focal adhesion, cyclic guanosine monophosphate)-protein kinase G signaling, and axon guidance were more likely associated to the PRA disease in dogs. These data could provide new insight for further research on identification of potential genes and causative pathways for PRA in dogs.

Background: Recent research using serum high sensitivity C-reactive protein (hs-CRP) has evidenced existence of low grade systemic inflammation in asthmatics whose correlation with various clinical indices is not fully studied. Objective: To investigate the relationship between systemic inflammation and various clinical and treatment characteristics of asthma. Materials and Methods: Forty asthmatics (22 steroid inhaling and 18 steroid naïve) and 40 healthy subjects matched for age and sex were examined cross-sectionally. Along with clinical assessment, serum hs-CRP levels were measured for all subjects using latex enhanced immunoturbidometry method. Results: Serum hs CRP levels were significantly higher in steroid naïve asthmatics when compared to normal subjects (0.93 ± 1.18 vs 0.24 ± 0.31 mg/dL, respectively; Mann-Whitney U test, P < 0.001). This association persisted after adjusting for age, gender, body mass index (BMI), and socioeconomic status (adjusted odds ratio 10.47; 95% CI 1.88-58.3; P < 0.01). Steroid inhaling asthmatics had serum hs-CRP levels comparable with control group (0.17 ± 0.18 vs 0.24 ± 0.31 mg/dL respectively, P > 0.05). Among the clinical and treatment related variables, duration of inhaled steroids usage alone correlated significantly with serum hs-CRP levels (Pearson correlation coefficient r = 0.449, P < 0.05), which was independent of age, BMI, duration of illness, and frequency of emergency visits. Conclusion: This study confirms the existence of low grade systemic inflammation in asthma which is effectively controlled by inhaled steroids. Such an effect of inhaled steroids appears to be more pronounced in recent users than that of long-term users, possibly due to lower adherence rate among the latter.

Arabidopsis roots are important organs for gravity sensing and gravitropic response. Long-term exposure of Arabidopsis to three-dimensional (3D) clinorotation was found to result in increased expression of WRKY46. In this study, the response of wrky46 mutants, constructed by T-DNA insertion, to simulated microgravity and gravistimulation by reorientation was studied. Microgravity conditions were simulated using a 3D clinostat, which simulates weightlessness. Morphological changes, such as root coiling, waving, and multidirectional growth patterns, were observed in the wild type (WT) seedlings after only 4 days of 3D clinorotation treatment, while in the wrky46 mutant seedlings, the changes observed were minimal compared with those of WT seedlings. Polar auxin transport played an important role in the observed morphological changes. Therefore, expression of the polar auxin transport genes AUX1, PIN2, -3, -4, and -7, and ARG1 was analyzed. Their expression was found to be higher in wrky46 seedlings than in WT seedlings under 3D clinorotation. Gravistimulation by reorientation was achieved by horizontally reorienting the seedlings. Root tip bending to 90[degrees] was observed in all WT seedlings within 18-20 h, whereas in mutant seedlings, bending of the root tip to a right angle took more than 20 h. AXR expression is known to directly correlate with root tip bending. The expression of AXR1, -2, -3, -4 was found to be higher in WT seedlings relative to mutant seedlings under gravistimulation by reorientation. However, their expression was relatively low in both WT and wrky46 plants under 3D clinorotation. These results suggest that WRKY46 plays an important role in the root gravitropic response, and in the reduction of polar auxin transport that is necessary for decreasing the effect of gravity due to clinorotation. Key words: Arabidopsis, 3D clinorotation, gravistimulation by reorientation, WRKY, wrky46 mutant. Les racines d'Arabidopsis sont des organes importants pour la detection de la gravite et la reponse geotropique. Une exposition a long terme d'Arabidopsis a une clinorotation en 3D s'est averee resulter en une augmentation de l'expression de WKRY46. Dans cette etude, la reponse de mutants wkry46, construits au moyen d'une insertion par un ADN-T, a une microgravite simulee et a une gravistimulation par reorientation a ete etudiee. Les conditions de microgravite ont ete simulees a l'aide d'un clinostat qui simule l'apesanteur. Des changements morphologiques comme l'enracinement en vrille, l'ondulation et les patrons de croissance multidirectionnelle ont ete observes chez les pousses sauvages apres seulement 4 jours de traitement en clinorotation en 3D, alors que chez les pousses des mutants wrky46, les changements observes etaient minimes comparativement aux pousses sauvages. Le transport polaire de l'auxine jouait un role important dans les changements morphologiques observes. Ainsi, l'expression des genes de transport de l'auxine AUX1, PIN2, -3, -4 et -7, et ARG1 a ete analysee. Leur expression s'est revelee plus elevee chez les pousses wrky46 que chez les pousses sauvages soumises a la clinorotation en 3D. La gravistimulation par reorientation a ete obtenue en reorientant les pousses de maniere horizontale. Une flexion de l'apex des racines a 90[degrees] etait observee chez toutes les pousses sauvages en moins de 18-20 h, alors que chez les pousses des mutants, la flexion de l'apex des racines a angle droit necessitait plus de 20 h. L'expression de AXR est connue pour etre en correlation directe avec la flexion de l'apex des racines. L'expression de AXR1, -2, -3 et -4 etait plus elevee chez les pousses sauvages relativement aux pousses mutantes placees en condition de gravistimulation par reorientation. Cependant, leur expression etait relativement faible tant chez les plants sauvages que les plants mutants en condition de clinorotation en 3D. Ces resultats suggerent que WRKY46 joue un role important dans la reponse geotropique des racines et dans la reduction du transport polaire de l'auxine, necessaire a la diminution de l'effet de la gravite causee par la clinorotation. [Traduit par la Redaction] Mots-cles : Arabidopsis, clinorotation en 3D, gravistimulation par reorientation, WRKY, mutant wrky46., Introduction Plants adapt their growth in response to environmental stress. A change in gravity is a stressful condition for plants, and they respond to it via changes not only at [...]

We review the recently developed models for load fluctuations in the displacement controlled mode and displacement jumps in the load controlled mode of indentation. To do this, we devise a method for calculating plastic contribution to load drops and displacement jumps by setting-up a system of coupled nonlinear time evolution equations for the mobile and forest dislocation densities by including relevant dislocation mechanisms. These equations are then coupled to the equation defining constant displacement rate or load rate. The model for the displacement controlled mode using a spherical indenter predicts all the generic features of nanoindentation such as the elastic branch followed by several force drops of decreasing magnitudes and residual indentation depth after unloading. The stress corresponding to the elastic force maximum is close to the yield stress of an ideal solid. The predicted numbers for all the quantities match experiments on single crystals of Au using a spherical indenter. We extend the approach to model the load controlled nanoindentation experiments that employ a Berkovich indenter. We first identify the dislocation mechanisms contributing to different regions of the F − z curve as a first step for obtaining a good fit to a given experimental F − z curve. This is done by studying the influence of the parameters associated with various dislocation mechanisms on the model F − z curves. The study also demonstrates that the model predicts all the generic features of nanoindentation such as the existence of an initial elastic branch followed by several displacement jumps of decreasing magnitudes and residual plasticity after unloading for a range of model parameter values. Furthermore, an optimized set of parameter values can be easily determined that give a good fit to the experimental load–displacement curves for Al single crystals of ( 110 ) and ( 133 ) orientations. Our model also predicts the indentation size effect in a region where the displacement jumps disappear. The good agreement of the results of the models with experiments supports our view that the present approach can be used as an alternate method to simulations. The approach also provides insights into several open questions.