Evidence of selection signatures that shape the Persian cat breed

The Persian cat is mainly characterized by an extremely brachycephalic face as part of the standard body conformation. Despite the popularity, world-wide distribution, and economic importance of the Persian cat as a fancy breed, little is known about the genetics of their hallmark morphology, brachycephaly. Over 800 cats from different breeds including Persian, non-Persian breeds (Abyssinian, Cornish Rex, Bengal, La Perm, Norwegian Forest, Maine Coon, Manx, Oriental, and Siamese), and Persian-derived breeds (British Shorthair, Scottish Fold, Selkirk Rex) were genotyped with the Illumina 63 K feline DNA array. The experimental strategy was composed of three main steps: (i) the Persian dataset was screened for runs of homozygosity to find and select highly homozygous regions; (ii) selected Persian homozygous regions were evaluated for the difference of homozygosity between Persians and those considered non-Persian breeds, and, (iii) the Persian homozygous regions most divergent from the non-Persian breeds were investigated by haplotype analysis in the Persian-derived breeds. Four regions with high homozygosity (H > 0.7) were detected, each with an average length of 1 Mb. Three regions can be considered unique to the Persian breed, with a less conservative haplotype pattern in the Persian-derived breeds. Moreover, two genes, CHL1 and CNTN6 known to determine face shape modification in humans, reside in one of the identified regions and therefore are positional candidates for the brachycephalic face in Persians. In total, the homozygous regions contained several neuronal genes that could be involved in the Persian cat behavior and can provide new insights into cat domestication.     

Dissociation of gemcitabine chemosensitization by CHK1 inhibition from cell cycle checkpoint abrogation and aberrant mitotic entry

In order to determine the relative contribution of checkpoint abrogation and subsequent aberrant mitotic entry to gemcitabine chemosensitization by CHK1 inhibition, we established a model utilizing the CDK inhibitors roscovitine or purvalanol A to re-establish cell cycle arrest and prevent aberrant mitotic entry in pancreatic cancer cells treated with gemcitabine and the CHK inhibitor AZD7762. In this study, we report that the extent of aberrant mitotic entry, as determined by flow cytometry for the mitotic marker phospho-Histone H3 (Ser10), did not reflect the relative sensitivities of pancreatic cancer cell lines to gemcitabine chemosensitization by AZD7762. In addition, re-establishing gemcitabine-induced cell cycle arrest either pharmacologically, with roscovitine or purvalanol A, or genetically, with cyclin B1 siRNA, did not inhibit chemosensitization uniformly across the cell lines. Furthermore, we found that AZD7762 augmented high-intensity γH2AX signaling in gemcitabine-treated cells, suggesting the presence of replication stress when CHK1 is inhibited. Finally, the ability of roscovitine to prevent chemosensitization correlated with its ability to inhibit AZD7762-induced high-intensity γH2AX, but not aberrant pHH3, suggesting that the effects of AZD7762 on DNA replication or repair rather than aberrant mitotic entry determine gemcitabine chemosensitization in pancreatic cancer cells.     

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55–0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82–0.95, P = 3.99 × 10^?4), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11–1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63–0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.     

Can Lionel Messi’s brain slow down time passing?

It seems that seeing others in slow-motion by heroes does not belong only to movies. When Lionel Messi plays football, you can hardly see anything from him that other players cannot do. Then why he is not stoppable really? It seems the answer may be that opponents do not have enough time to do what they want; because in Messi’s neural system, time passes slower. In differential equations that model a single neuron, this speed can be generated by multiplying an equal term in all equations. Or maybe interactions between neurons and the structure of neural networks play this role.     

Integrating new practices: a qualitative study of how hospital innovations become routine

Background

Hospital quality improvement efforts absorb substantial time and resources, but many innovations fail to integrate into organizational routines, undermining the potential to sustain the new practices. Despite a well-developed literature on the initial implementation of new practices, we have limited knowledge about the mechanisms by which integration occurs.

Methods

We conducted a qualitative study using a purposive sample of hospitals that participated in the State Action on Avoidable Rehospitalizations (STAAR) initiative, a collaborative to reduce hospital readmissions that encouraged members to adopt new practices. We selected hospitals where risk-standardized readmission rates (RSRR) had improved (n?=?7) or deteriorated (n?=?3) over the course of the first 2 years of the STAAR initiative (2010–2011 to 2011–2012) and interviewed a range of staff at each site (90 total). We recruited hospitals until reaching theoretical saturation. The constant comparative method was used to conduct coding and identification of key themes.

Results

When innovations were successfully integrated, participants consistently reported that a small number of key staff held the innovation in place for as long as a year while more permanent integrating mechanisms began to work. Depending on characteristics of the innovation, one of three categories of integrating mechanisms eventually took over the role of holding new practices in place. Innovations that proved intrinsically rewarding to the staff, by making their jobs easier or more gratifying, became integrated through shifts in attitudes and norms over time. Innovations for which the staff did not perceive benefits to themselves were integrated through revised performance standards if the innovation involved complex tasks and through automation if the innovation involved simple tasks.

Conclusions

Hospitals have an opportunity to promote the integration of new practices by planning for the extended effort required to hold a new practice in place while integration mechanisms take hold. By understanding how integrating mechanisms correspond to innovation characteristics, hospitals may be able to foster integrating mechanisms most likely to work for particular innovations.