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1.  Does attractiveness influence condom use intentions in heterosexual men? An experimental study 
BMJ Open  2016;6(6):e010883.
Judgements of attractiveness have been shown to influence the character of social interactions. The present study sought to better understand the relationship between perceived attractiveness, perceived sexual health status and condom use intentions in a heterosexual male population.
The study employed an electronic questionnaire to collect all data, during face-to-face sessions.
51 heterosexual, English-speaking men aged between 18 and 69 years.
Outcome measures
Men were asked to rate the attractiveness of 20 women on the basis of facial photographs, to estimate the likelihood that each woman had a sexually transmitted infection (STI) and to indicate their willingness to have sex with or without a condom with each woman.
The more attractive a woman was judged to be on average, the more likely participants would be willing to have sex with her (p<0.0001) and the less likely they were to intend to use a condom during sex (p<0.0001). Multivariate analysis revealed that higher condom use intentions towards a particular woman were associated with lower ratings of her attractiveness (p<0.0005), higher ratings of her STI likelihood (p<0.0001), the participant being in an exclusive relationship (p=0.002), having a less satisfactory sex life (p=0.015), lower age (p=0.001), higher number of sexual partners (p=0.001), higher age at first intercourse (p=0.002), higher rates of condomless sex in the last 12 months (p<0.043) and lower confidence in their ability to assess whether or not a woman had an STI (p=0.001). The more attractive a participant judged himself to be, the more he believed that other men like him would engage in condomless sex (p=0.001) and the less likely he was to intend to use a condom himself (p=0.02).
Male perceptions of attractiveness influence their condom use intentions; such risk biases could profitably be discussed during sex education sessions and in condom use promotion interventions.
PMCID: PMC4916619  PMID: 27315834
STIs; sexual health; condoms
2.  The impact of armed conflict on adolescent transitions: a systematic review of quantitative research on age of sexual debut, first marriage and first birth in young women under the age of 20 years 
BMC Public Health  2016;16:225.
Young women in conflict-affected regions are at risk of a number of adverse outcomes as a result of violence, economic deterioration and the breakdown of community structures and services. This paper presents the findings of a systematic review of quantitative literature reporting how key sexual and reproductive health (SRH) outcomes among young women under the age of 20 years are affected by exposure to armed conflict; namely, sexual debut, first marriage and first birth. Increases in these outcomes among young women are all associated with potential negative public health consequences. It also examines and documents possible causal pathways for any changes seen.
To fit with our inclusion criteria, all reviewed studies included outcomes for comparable populations not exposed to conflict either temporally or spatially. A total of 19 studies with results from 21 countries or territories met our inclusion criteria; seven presented findings on marriage, four on fertility and eight on both of these outcomes. Only one study reporting on sexual debut met our criteria.
Findings show clear evidence of both declines and increases in marriage and childbirth among young women in a range of conflict-affected settings. Several studies that showed increases in marriage below the age of 20 years reported that such increases were concentrated in the younger teenagers. Trends in fertility were predominantly driven by marriage patterns. Suggested causal pathways for the changes observed could be grouped into three categories: involuntary, gender and psycho-social and economic and material factors.
The review reveals a paucity of literature on the impact of conflict on SRH outcomes of young women. Further quantitative and qualitative studies are needed to explore how conflict influences SRH events in young women over both the short- and longer-term.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-016-2868-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4779256  PMID: 26944879
Young women; Armed conflict; Sexual health; Early marriage; Fertility
3.  Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State 
Stem Cell Reports  2013;1(3):235-247.
Direct reprogramming of adult somatic cells into alternative cell types has been shown for several lineages. We previously showed that GATA4, MEF2C, and TBX5 (GMT) directly reprogrammed nonmyocyte mouse heart cells into induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. However, GMT alone appears insufficient in human fibroblasts, at least in vitro. Here, we show that GMT plus ESRRG and MESP1 induced global cardiac gene-expression and phenotypic shifts in human fibroblasts derived from embryonic stem cells, fetal heart, and neonatal skin. Adding Myocardin and ZFPM2 enhanced reprogramming, including sarcomere formation, calcium transients, and action potentials, although the efficiency remained low. Human iCM reprogramming was epigenetically stable. Furthermore, we found that transforming growth factor β signaling was important for, and improved the efficiency of, human iCM reprogramming. These findings demonstrate that human fibroblasts can be directly reprogrammed toward the cardiac lineage, and lay the foundation for future refinements in vitro and in vivo.
•Human fibroblasts can be directly induced toward a CM-like state by defined factors•Reprogramming of fibroblasts toward a CM state is epigenetically stable•Human and mouse in vitro iCMs display a comparable gene-expression shift•TGF-β signaling is important for human iCM reprogramming
PMCID: PMC3849259  PMID: 24319660
4.  Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects 
BMC Medical Genetics  2012;13:62.
Neural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk.
A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.
Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.
To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.
PMCID: PMC3458983  PMID: 22856873
Neural tube defects; Spina bifida; Folic acid; One-carbon metabolism; Candidate gene
5.  Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes 
PLoS ONE  2011;6(7):e21851.
One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are ∼22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA “master regulators” (miR-22 and miR-125) and one candidate pair of “master co-regulators” (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18–28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p  =  0.045), total homocysteine levels (tHcy) (p  =  0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM.
PMCID: PMC3134459  PMID: 21765920
6.  Extranuclear Apoptosis 
The Journal of Cell Biology  1999;146(4):703-708.
PMCID: PMC2156138  PMID: 10459006
7.  Apoptotic Membrane Blebbing Is Regulated by Myosin Light Chain Phosphorylation  
The Journal of Cell Biology  1998;140(3):627-636.
The evolutionarily conserved execution phase of apoptosis is defined by characteristic changes occurring during the final stages of death; specifically cell shrinkage, dynamic membrane blebbing, condensation of chromatin, and DNA fragmentation. Mechanisms underlying these hallmark features of apoptosis have previously been elusive, largely because the execution phase is a rapid event whose onset is asynchronous across a population of cells. In the present study, a model system is described for using the caspase inhibitor, z-VAD-FMK, to block apoptosis and generate a synchronous population of cells actively extruding and retracting membrane blebs. This model system allowed us to determine signaling mechanisms underlying this characteristic feature of apoptosis. A screen of kinase inhibitors performed on synchronized blebbing cells indicated that only myosin light chain kinase (MLCK) inhibitors decreased blebbing. Immunoprecipitation of myosin II demonstrated that myosin regulatory light chain (MLC) phosphorylation was increased in blebbing cells and that MLC phosphorylation was prevented by inhibitors of MLCK. MLC phosphorylation is also mediated by the small G protein, Rho. C3 transferase inhibited apoptotic membrane blebbing, supporting a role for a Rho family member in this process. Finally, blebbing was also inhibited by disruption of the actin cytoskeleton. Based on these results, a working model is proposed for how actin/myosin II interactions cause cell contraction and membrane blebbing. Our results provide the first evidence that MLC phosphorylation is critical for apoptotic membrane blebbing and also implicate Rho signaling in these active morphological changes. The model system described here should facilitate future studies of MLCK, Rho, and other signal transduction pathways activated during the execution phase of apoptosis.
PMCID: PMC2140178  PMID: 9456322

Results 1-7 (7)