The Other Side of Through: Young Breast Cancer Survivors’ Spectrum of Sexual and Reproductive Health Needs

The long-term reproductive health impact of cancer treatments is a concern for premenopausal women with a history of breast cancer. This study examined the unmet sexual and reproductive health needs of breast cancer survivors, as well as concordances and discordances in needs by childbearing status and race. We interviewed 17 women diagnosed with breast cancer between the ages of 18 and 45 years and living in North Carolina. To analyze these data, we used the Sort and Sift, Think and Shift© method, a multidimensional qualitative analysis approach. We learned that breast cancer survivors (a) received limited reproductive health information, (b) desired realistic expectations of conceiving postcancer, (c) struggled with adjusting to their altered physical appearance, and (d) had menopause symptoms that led to sexual health and quality of life issues. Breast cancer survivors are in need of and desire more education and resources to address their sexual and reproductive health concerns

NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity

Background: NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation for this. Objective: We sought to clarify the role of NLRP1 in asthma pathogenesis. Methods: Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level. Results: We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activation in the context of N-terminal destabilization, but decreases NLRP1 activation on dipeptidyl peptidase 9 inhibition. In vitro studies demonstrate that M1184V increases binding to dipeptidyl peptidase 9, which can account for its inhibitory role in this context. In addition, in vivo data from a mouse model of airway inflammation reveal a protective role for NLRP1 inflammasome activation reducing eosinophilia in this setting. Conclusions: Linking our in vitro and in vivo results, we found that the NLRP1 variant M1184V reduces inflammasome activation in the context of dipeptidyl peptidase 9 inhibition and could thereby increase asthma severity. Our studies may have implications for the treatment of asthma in patients carrying this variant of NLRP1

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

Distinct host tropism protein signatures to identify possible zoonotic influenza a viruses

10.1371/journal.pone.0150173PLoS ONE112e015017

Predicting host tropism of influenza A virus proteins using random forest

10.1186/1755-8794-7-S3-S1BMC Medical Genomics7352

Predicting zoonotic risk of influenza a viruses from host tropism protein signature using random forest

10.3390/ijms18061135International Journal of Molecular Sciences186A113

Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis

Genome-wide association studies (GWAS) hold tremendous promise to improve our understanding of human biology. Recent GWAS have revealed over 75 loci associated with erythroid traits, including the 4q27 locus that is associated with red blood cell size (mean corpuscular volume). The close linkage disequilibrium block at this locus harbors the CCNA2 gene that encodes cyclin A2. CCNA2 mRNA is highly expressed in human and murine erythroid progenitor cells and regulated by the essential erythroid transcription factor GATA1. To understand the role of cyclin A2 in erythropoiesis, we have reduced expression of this gene using short hairpin RNAs in a primary murine erythroid culture system. We demonstrate that cyclin A2 levels affect erythroid cell size by regulating the passage through cytokinesis during the final cell division of terminal erythropoiesis. Our study provides new insight into cell cycle regulation during terminal erythropoiesis and more generally illustrates the value of functional GWAS follow-up to gain mechanistic insight into hematopoiesis