Humanity\u27s Best Friend: A Dog-Centric Approach to Addressing Global Challenges

No other animal has a closer mutualistic relationship with humans than the dog (Canis familiaris). Domesticated from the Eurasian grey wolf (Canis lupus), dogs have evolved alongside humans over millennia in a relationship that has transformed dogs and the environments in which humans and dogs have co-inhabited. The story of the dog is the story of recent humanity, in all its biological and cultural complexity. By exploring human-dog-environment interactions throughout time and space, it is possible not only to understand vital elements of global history, but also to critically assess our present-day relationship with the natural world, and to begin to mitigate future global challenges. In this paper, co-authored by researchers from across the natural and social sciences, arts and humanities, we argue that a dog-centric approach provides a new model for future academic enquiry and engagement with both the public and the global environmental agenda

The History of Farm Foxes Undermines the Animal Domestication Syndrome

The Russian Farm-Fox Experiment is the best known experimental study in animal domestication. By subjecting a population of foxes to selection for tameness alone, Dimitry Belyaev generated foxes that possessed a suite of characteristics that mimicked those found across domesticated species. This \u27domestication syndrome\u27 has been a central focus of research into the biological pathways modified during domestication. Here, we chart the origins of Belyaev\u27s foxes in eastern Canada and critically assess the appearance of domestication syndrome traits across animal domesticates. Our results suggest that both the conclusions of the Farm-Fox Experiment and the ubiquity of domestication syndrome have been overstated. To understand the process of domestication requires a more comprehensive approach focused on essential adaptations to human-modified environments

The role of family functioning and self-esteem in the quality of life of adolescents referred for psychiatric services: a 3-year follow-up.

PurposeTo investigate, in adolescents referred for psychiatric services, the associations of initial self-esteem and family functioning with level and change of quality of life (QoL) over a 3-year period, over and above the effect of their emotional problems.MethodsOf 1648 eligible 13-18 years old patients attending the child and adolescent psychiatric clinic (CAP) at least once, 717 (54.8% females) were enrolled at baseline (a response rate of 43.5%). Self- and parent reports on the McMaster Family Assessment Device were obtained. Adolescents reported self-esteem on the Rosenberg Scale, and emotional problems on the Symptom Check List-5. Adolescents completed the Inventory of Life Quality in Children and Adolescents (ILC). After 3 years, 570 adolescents again completed the ILC, and for 418 adolescents parent information was available. The longitudinal analysis sample of 418 adolescents was representative of the baseline sample for age, gender, emotional problems, and QoL. We used modified growth-model analysis, adjusted for SES, age, gender and time of contact with CAP, where residual variances for ILC at baseline and follow-up were fixed to 0.ResultsA poorer family functioning at baseline, reported by parents, was significantly associated with worsening QoL during the 3 years follow-up period (p = 0.001).ConclusionsParents have important knowledge about their families that may reflect long-term influences on QoL development in adolescent psychiatric patients. Health care providers and policy makers should optimize treatment outcomes by addressing family functioning in adolescents with emotional problems

Aggregation Limits Surface Expression of Homomeric GluA3 Receptors

AMPA receptors are glutamate-gated cation channels assembled from GluA1-4 subunits and have properties that are strongly dependent on the subunit composition. The subunits have different propensities to form homomeric or various heteromeric receptors expressed on cell surface, but the underlying mechanisms are still poorly understood. Here, we examined the biochemical basis for the poor ability of GluA3 subunits to form homomeric receptors, linked previously to two amino acid residues, Y454 and R461, in its ligand-binding domain (LBD). Surface expression of GluA3 was improved by co-assembly with GluA2 but not with stargazin, a trafficking chaperone and modulator of AMPA receptors. The secretion efficiency of GluA2 and GluA3 LBDs paralleled the transport difference between the respective full-length receptors and was similarly dependent on Y454/R461, but not on LBD stability. In comparison to GluA2, GluA3 homomeric receptors showed a strong and Y454/R461-dependent tendency to aggregate both in the macroscopic scale measured as lower solubility in nonionic detergent and in the microscopic scale evident as the preponderance of hydrodynamically large structures in density gradient centrifugation and native gel electrophoresis. We conclude that the impaired surface expression of homomeric GluA3 receptors is caused by nonproductive assembly and aggregation to which LBD residues Y454 and R461 strongly contribute. This aggregation inhibits the entry of newly synthesized GluA3 receptors to the secretory pathway

Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ

The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS. The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992-2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed. Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82-1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60-0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53-1.37 for left-sided versus right-sided RT). The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.Peer reviewe

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted