Patterns of Polymorphism and Demographic History in Natural Populations of Arabidopsis lyrata

Many of the processes affecting genetic diversity act on local populations. However, studies of plant nucleotide diversity have largely ignored local sampling, making it difficult to infer the demographic history of populations and to assess the importance of local adaptation. Arabidopsis lyrata, a self-incompatible, perennial species with a circumpolar distribution, is an excellent model system in which to study the roles of demographic history and local adaptation in patterning genetic variation.We studied nucleotide diversity in six natural populations of Arabidopsis lyrata, using 77 loci sampled from 140 chromosomes. The six populations were highly differentiated, with a median FST of 0.52, and structure analysis revealed no evidence of admixed individuals. Average within-population diversity varied among populations, with the highest diversity found in a German population; this population harbors 3-fold higher levels of silent diversity than worldwide samples of A. thaliana. All A. lyrata populations also yielded positive values of Tajima's D. We estimated a demographic model for these populations, finding evidence of population divergence over the past 19,000 to 47,000 years involving non-equilibrium demographic events that reduced the effective size of most populations. Finally, we used the inferred demographic model to perform an initial test for local adaptation and identified several genes, including the flowering time gene FCA and a disease resistance locus, as candidates for local adaptation events.Our results underscore the importance of population-specific, non-equilibrium demographic processes in patterning diversity within A. lyrata. Moreover, our extensive dataset provides an important resource for future molecular population genetic studies of local adaptation in A. lyrata

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Investigating the neural and cognitive basis of moral luck: It's not what you do but what you know

Moral judgments, we expect, ought not to depend on luck. A person should be blamed only for actions and outcomes that were under the person’s control. Yet often, moral judgments appear to be influenced by luck. A father who leaves his child by the bath, after telling his child to stay put and believing that he will stay put, is judged to be morally blameworthy if the child drowns (an unlucky outcome), but not if his child stays put and doesn’t drown. Previous theories of moral luck suggest that this asymmetry reflects primarily the influence of unlucky outcomes on moral judgments. In the current study, we use behavioral methods and fMRI to test an alternative: these moral judgments largely reflect participants’ judgments of the agent’s beliefs. In “moral luck” scenarios, the unlucky agent also holds a false belief. Here, we show that moral luck depends more on false beliefs than bad outcomes. We also show that participants with false beliefs are judged as having less justified beliefs and are therefore judged as more morally blameworthy. The current study lends support to a rationalist account of moral luck: moral luck asymmetries are driven not by outcome bias primarily, but by mental state assessments we endorse as morally relevant, i.e. whether agents are justified in thinking that they won’t cause harm

Healthcare Communication Barriers and Self-Rated Health in Older Chinese American Immigrants

Older Chinese immigrants are a growing population in the United States who experience multiple healthcare communication barriers such as limited English proficiency and low health literacy. Each of these obstacles has been associated with poor health outcomes but less is known about their effects in combination. This study examined the association between healthcare communication barriers and self-rated health among older Chinese immigrants. Cross-sectional survey data were obtained from 705 Chinese American immigrants ages 50-75 living in San Francisco, California. Communication barriers examined included spoken English proficiency, medical interpreter needs, and health literacy in written health information. The study sample (81% females, mean age = 62) included 67% who spoke English poorly or not at all, 34% who reported needing a medical interpreter, and 37% who reported “often” or “always” needing assistance to read health information. Two-thirds (66%) reported poor self-rated health; many reported having access to racial-concordant (74%) and language-concordant (86%) healthcare services. Both poor spoken English proficiency and low health literacy were associated with poor self-rated health, independent of other significant correlates (unemployment, chronic health conditions, and having a primary doctor who was ethnic Chinese). Results revealed that spoken English proficiency and print health literacy are independent communication barriers that directly associated with the health status among elderly Chinese American immigrants. Access to racial- or language-concordant health care services did not appear to resolve these barriers. These findings underscore the importance of addressing both spoken and written healthcare communication needs among older Chinese American immigrants