Simple incentives and group dependence for successful payments for ecosystem services programs: evidence from an experimental game in rural Lao PDR

In this paper, we use a new game-based tool to evaluate the immediate and longer-term behavioral change potential of three different payment for environmental services (PES) delivery mechanisms: direct payments for individual performance, direct payments for group performance and insurance. Results from four rural shifting-cultivation dependent communities in Lao PDR suggest that easily understood group-oriented incentives yield the greatest immediate resource-use reduction and experience less free-riding. Group-based incentives may succeed because they motivate participants to communicate about strategies and coordinate their actions and are perceived as fair. No incentive had a lasting effect after it ceased, but neither did any crowd out the participants’ baseline behavior. Temporary reductions in resource dependence may provide a buffer for development of new livelihoods and longer-term change. Games like the one developed here can help policymakers appropriately target environmental incentive programs to local contexts and teach program participants how incentive schemes work

An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to investigate the unique pathobiology of OPSCC. Herein, bioinformatics analyses of human HPV(+) HNSCCs revealed that all tumors express full-length E6 and identified molecular subtypes based on relative E6 and E7 expression levels. To recapitulate the levels, stoichiometric ratios, and anatomic location of E6/E7 expression, we generated a genetically engineered mouse model whereby balanced expression of E6/E7 is directed to the oropharyngeal epithelium. The addition of a mutant PIK3CAE545K allele leads to the rapid development of pre-malignant lesions marked by immune cell accumulation, and a subset of these lesions progress to OPSCC. This mouse provides a faithful immunocompetent model for testing treatments and investigating mechanisms of immunosuppression

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2

Enzymatic glyceride synthesis in a foam reactor

We report the results of our study on Rhizomucor miehei lipaseâ catalyzed lauric acidâ glycerol esterification in a foam reactor. A satisfactory yield of glyceride synthesis can be achieved with an unusually high initial water content (50% w/w). We found that product formation could be regulated by controlling foaming. Foaming was a function of the air flow rate, reaction temperature, pH value, ionic strength, and substrate molar ratio. Monolaurin and dilaurin, which constituted nearly 80% of the total yield, were the two dominant products in this reaction; trilaurin was also formed at the initial stages of the reaction. A study of pH and ionic strength effects on an independent basis revealed that they affect the interfacial mechanism in different manners. On varying the ratio of lauric acid and glycerol, only a slight change in the degree of conversion was detected and the consumption rate of fatty acid was approximately the same.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141443/1/aocs0643.pd

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians

Cytochrome P450 1B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones. We compared allele, genotype and haplotype frequencies of six single-nucleotide polymorphisms (SNPs) within CYP1B1 among non-Hispanic Caucasians (496 cases and 498 controls) and Hispanic Caucasians (153 cases and 240 controls). In the Hispanic Caucasians, the GG genotype for rs1056836 decreased the risk for prostate cancer (PCa) when compared with the CC genotype [odds ratio (OR) = 0.31, P = 0.04, 95% confidence interval (CI) = 0.10–0.96]. Among non-Hispanic Caucasian men with more aggressive PCa, the prevalence of several SNPs (rs2567206, rs2551188, rs2617266, rs10012 and rs1056836) was significantly associated with the disease status. A common C-G-C-C-G-A haplotype for rs2567206-rs2551188-rs2617266-rs10012-rs1056836-rs1800440 showed an inverse association with PCa risk in Hispanic Caucasians (OR = 0.19, P = 0.04, 95% CI = 0.04–0.95) and with aggressive disease status (i.e. Gleason score ≥7) in non-Hispanic Caucasian cases (OR = 0.64, P = 0.008, 95% CI = 0.47–0.89). In the non-Hispanic Caucasian cases, a second major haplotype T-A-T-G-C-A was positively associated with the high-grade disease status (OR = 1.77, P = 0.002, 95% CI = 1.24–2.53). Our findings suggest that genetic polymorphisms in CYP1B1 may modify the risk for PCa and support the role of CYP1B1 as a candidate gene for PCa

Cervicovaginal immune activation in Zambian women with female genital schistosomiasis

HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), an inflammatory disease caused by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection. Elevated levels of the chemokines MIP-1 alpha (CCL-3), MIP-1 beta (CCL-4), IP-10 (CXCL-10), and IL-8 (CXCL-8) in cervicovaginal lavage (CVL) have been associated with HIV-1 acquisition. We hypothesize that levels of cervicovaginal cytokines may be raised in FGS and could provide a causal mechanism for the association between FGS and HIV-1. In the cross-sectional BILHIV study, specimens were collected from 603 female participants who were aged 18-31 years, sexually active, not pregnant and participated in the HPTN 071 (PopART) HIV-1 prevention trial in Zambia. Participants self-collected urine, and vaginal and cervical swabs, while CVLs were clinically obtained. Microscopy and Schistosoma circulating anodic antigen (CAA) were performed on urine. Genital samples were examined for parasite-specific DNA by PCR. Women with FGS (n=28), defined as a positive Schistosoma PCR from any genital sample were frequency age-matched with 159 FGS negative (defined as negative Schistosoma PCR, urine CAA, urine microscopy, and colposcopy imaging) women. Participants with probable FGS (n=25) (defined as the presence of either urine CAA or microscopy in combination with one of four clinical findings suggestive of FGS on colposcope-obtained photographs) were also included, for a total sample size of 212. The concentrations of 17 soluble cytokines and chemokines were quantified by a multiplex bead-based immunoassay. There was no difference in the concentrations of cytokines or chemokines between participants with and without FGS. An exploratory analysis of those women with a higher FGS burden, defined by >= 2 genital specimens with detectable Schistosoma DNA (n=15) showed, after adjusting for potential confounders, a higher Th2 (IL-4, IL-5, and IL-13) and pro-inflammatory (IL-15) expression pattern in comparison to FGS negative women, with differences unlikely to be due to chance (p=0.037 for IL-4 and p<0.001 for IL-5 after adjusting for multiple testing). FGS may alter the female genital tract immune environment, but larger studies in areas of varying endemicity are needed to evaluate the association with HIV-1 vulnerability.Cancer Signaling networks and Molecular Therapeutic

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Target highlights in CASP13: experimental target structures through the eyes of their authors

The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment