Evidence of coat color variation sheds new light on ancient canids.

International audienceWe have used a paleogenetics approach to investigate the genetic landscape of coat color variation in ancient Eurasian dog and wolf populations. We amplified DNA fragments of two genes controlling coat color, Mc1r (Melanocortin 1 Receptor) and CBD103 (canine-β-defensin), in respectively 15 and 19 ancient canids (dogs and wolf morphotypes) from 14 different archeological sites, throughout Asia and Europe spanning from ca. 12 000 B.P. (end of Upper Palaeolithic) to ca. 4000 B.P. (Bronze Age). We provide evidence of a new variant (R301C) of the Melanocortin 1 receptor (Mc1r) and highlight the presence of the beta-defensin melanistic mutation (CDB103-K locus) on ancient DNA from dog-and wolf-morphotype specimens. We show that the dominant K(B) allele (CBD103), which causes melanism, and R301C (Mc1r), the variant that may cause light hair color, are present as early as the beginning of the Holocene, over 10 000 years ago. These results underline the genetic diversity of prehistoric dogs. This diversity may have partly stemmed not only from the wolf gene pool captured by domestication but also from mutations very likely linked to the relaxation of natural selection pressure occurring in-line with this process

Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome

International audienc

Rapid activation of epithelial-mesenchymal transition drives PARP inhibitor resistance in Brca2-mutant mammary tumours

Tumours defective in the DNA homologous recombination repair pathway can be effectively treated with poly (ADP-ribose) polymerase (PARP) inhibitors; these have proven effective in clinical trials in patients with BRCA gene function-defective cancers. However, resistance observed in both pre-clinical and clinical studies is likely to impact on this treatment strategy. Over-expression of phosphoglycoprotein (P-gp) has been previously suggested as a mechanism of resistance to the PARP inhibitor olaparib in mouse models of Brca1/2-mutant breast cancer. Here, we report that in a Brca2 model treated with olaparib, P-gp upregulation is observed but is not sufficient to confer resistance. Furthermore, resistant/relapsed tumours do not show substantial changes in PK/PD of olaparib, do not downregulate PARP1 or re-establish double stranded DNA break repair by homologous recombination, all previously suggested as mechanisms of resistance. However, resistance is strongly associated with epithelial-mesenchymal transition (EMT) and treatment-naïve tumours given a single dose of olaparib upregulate EMT markers within one hour. Therefore, in this model, olaparib resistance is likely a product of an as-yet unidentified mechanism associated with rapid transition to the mesenchymal phenotype

The International Conference on Penal Abolition (ICOPA)

Drawing on debates observed at the fifteenth edition of the International Conference on Penal Abolition (ICOPA) that took place on Algonquin Territory at the University of Ottawa in June 2014, reflections by ICOPA 15 organizing committee and research group members, and interviews with international conference participants, this qualitative study explores four recurring themes debated within this entity: allyship between reformers and abolitionists; the extent of race analysis in abolitionist conceptualization and strategy, as well as oppressed and privileged positions within ICOPA; the power equilibrium among survivors of state or social harm, activists and academics; and deliberative vitality and decision-making within the organization. The exploration of ICOPA as a loose-knit initiative serves to elicit debate about the challenges of collective praxis in the face of co-optation, multiple oppressions, and unequal power structures shaping radical organizing and contemporary life more broadly.La 15e Conférence internationale sur l’abolitionnisme pénal (ICOPA) s’est tenue sur territoire Algonquin à l’Université d’Ottawa en juin 2014. À partir des débats qui y furent observés, des réflexions de membres du comité organisateur et du groupe de recherche ICOPA 15, ainsi que d’entretiens auprès de participants internationaux, cette étude qualitative met en scène quatre enjeux récurrents qui l’ont traversée : les alliances entre les réformistes et les abolitionnistes; la place de la dimension raciale dans la conceptualisation et la stratégie abolitionniste, de même que la tension entre postures privilégiées et opprimées au sein d’ICOPA; l’équilibre des pouvoirs entre les survivants de torts sociaux ou étatiques, les militants et les universitaires; et la vitalité de la délibération et la prise de décision au sein de l’organisation. L’analyse d’ICOPA en tant que mouvement éclaté cherche à renouveler les débats autour d’une praxis collective consciente des risques de cooptation, des inégalités, et des structures de pouvoir asymétriques qui affectent autant l’organisation radicale elle-même qu’elle façonne l’ensemble des sociétés contemporaines

Association of Heart Rate Variability With Cognitive Performance: The Multi-Ethnic Study of Atherosclerosis

Background Heart rate variability (HRV) is associated with vascular risk factors for dementia, but whether HRV is associated with specific domains of cognitive performance is unclear. Methods and Results In the Multi-Ethnic Study of Atherosclerosis (N=3018; mean age 59.3±9.2 years), we assessed the relationship of 10-second HRV to scores on tests of global cognitive performance (Cognitive Abilities Screening Instrument), processing speed (Digit Symbol Coding), and working memory (Digit Span). HRV was computed as the SD of normal-normal intervals (SDNN) and root mean square of successive differences (RMSSD) at Exam 1 (2000-2002) and Exam 5 (2010-2012). Cognitive tests were administered at Exam 5. We report regression coefficients (β [95% CI]) representing cognitive test score change per 2-fold increase in HRV. After adjustment for age, race/ethnicity, sex, education, apolipoprotein E genotype, and cardiovascular risk factors and incident disease, higher Exam 1 (β=0.37 [0.06, 0.67]) and Exam 5 (β=0.31 [0.04, 0.59]) SDNN were associated with better Cognitive Abilities Screening Instrument performance. Higher Exam 1 (β=0.80 [0.17, 1.43]) and Exam 5 (β=0.63 [0.06, 1.20]) SDNN, and Exam 5 RMSSD (β=0.54 [0.01, 1.08]) were associated with better Digit Symbol Coding performance. Finally, higher Exam 5 SDNN was associated with better Digit Span performance (β=0.17 [0.01, 0.33]). Associations were attenuated after adjustment for resting heart rate. Conclusions Higher HRV is generally associated with better cognitive performance in this multi-ethnic cohort of aging adults, and further study of the relationship of autonomic function to cognition is warranted