Transdisciplinary research in support of land and water management in China and Southeast Asia : evaluation of four research projects

Unidad de excelencia María de Maeztu MdM-2015-0552Transdisciplinary research (TDR) aims at identifying implementable solutions to difficult sustainability problems and at fostering social learning. It requires a wellmanaged collaboration among multidisciplinary scientists and multisectoral stakeholders. Performing TDR is challenging, particularly for foreign researchers working in countries with different institutional and socio-cultural conditions. There is a need to synthesize and share experience among researchers as well as practitioners regarding how TDR can be conducted under specific contexts. In this paper, we aim to evaluate and synthesize our unique experience in conducting TDR projects in Asia. We applied guiding principles of TDR to conduct a formative evaluation of four consortium projects on sustainable land and water management in China, the Philippines, and Vietnam. In all projects, local political conditions restricted the set of stakeholders that could be involved in the research processes. The set of involved stakeholders was also affected by the fact that stakeholders in most cases only participate if they belong to the personal network of the project leaders. Language barriers hampered effective communication between foreign researchers and stakeholders in all projects and thus knowledge integration. The TDR approach and its specific methods were adapted to respond to the specific cultural, social, and political conditions in the research areas, also with the aim to promote trust and interest of the stakeholders throughout the project. Additionally, various measures were implemented to promote collaboration among disciplinary scientists. Based on lessons learned, we provide specific recommendations for the design and implementation of TDR projects in particular in Asia

PeRL:A circum-Arctic Permafrost Region Pond and Lake database

Ponds and lakes are abundant in Arctic permafrost lowlands. They play an important role in Arctic wetland ecosystems by regulating carbon, water, and energy fluxes and providing freshwater habitats. However, ponds, i.e., waterbodies with surface areas smaller than 1. 0 × 104ĝ€m2, have not been inventoried on global and regional scales. The Permafrost Region Pond and Lake (PeRL) database presents the results of a circum-Arctic effort to map ponds and lakes from modern (2002-2013) high-resolution aerial and satellite imagery with a resolution of 5ĝ€m or better. The database also includes historical imagery from 1948 to 1965 with a resolution of 6ĝ€m or better. PeRL includes 69 maps covering a wide range of environmental conditions from tundra to boreal regions and from continuous to discontinuous permafrost zones. Waterbody maps are linked to regional permafrost landscape maps which provide information on permafrost extent, ground ice volume, geology, and lithology. This paper describes waterbody classification and accuracy, and presents statistics of waterbody distribution for each site. Maps of permafrost landscapes in Alaska, Canada, and Russia are used to extrapolate waterbody statistics from the site level to regional landscape units. PeRL presents pond and lake estimates for a total area of 1. 4 × 106ĝ€km2 across the Arctic, about 17ĝ€% of the Arctic lowland ( < ĝ€300ĝ€mĝ€a.s.l.) land surface area. PeRL waterbodies with sizes of 1. 0 × 106ĝ€m2 down to 1. 0 × 102ĝ€m2 contributed up to 21ĝ€% to the total water fraction. Waterbody density ranged from 1. 0 × 10 to 9. 4 × 101ĝ€kmĝ'2. Ponds are the dominant waterbody type by number in all landscapes representing 45-99ĝ€% of the total waterbody number. The implementation of PeRL size distributions in land surface models will greatly improve the investigation and projection of surface inundation and carbon fluxes in permafrost lowlands. Waterbody maps, study area boundaries, and maps of regional permafrost landscapes including detailed metadata are available at https://doi.pangaea.de/10.1594/PANGAEA.868349

Use of a mixed tissue RNA design for performance assessments on multiple microarray formats

The comparability and reliability of data generated using microarray technology would be enhanced by use of a common set of standards that allow accuracy, reproducibility and dynamic range assessments on multiple formats. We designed and tested a complex biological reagent for performance measurements on three commercial oligonucleotide array formats that differ in probe design and signal measurement methodology. The reagent is a set of two mixtures with different proportions of RNA for each of four rat tissues (brain, liver, kidney and testes). The design provides four known ratio measurements of >200 reference probes, which were chosen for their tissue-selectivity, dynamic range coverage and alignment to the same exemplar transcript sequence across all three platforms. The data generated from testing three biological replicates of the reagent at eight laboratories on three array formats provides a benchmark set for both laboratory and data processing performance assessments. Close agreement with target ratios adjusted for sample complexity was achieved on all platforms and low variance was observed among platforms, replicates and sites. The mixed tissue design produces a reagent with known gene expression changes within a complex sample and can serve as a paradigm for performance standards for microarrays that target other species

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation

Background. Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Methods. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. Results. Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. Conclusions. Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratificatio

Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Background Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. Findings The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74–1·88] and non-European (1·42 [1·34–1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56–9·72) in European ancestry and 4·83 (3·45–6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79–0·81] vs 0·76 [0·75–0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. Interpretation A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtyp

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants