Grassland productivity limited by multiple nutrients

Terrestrial ecosystem productivity is widely accepted to be nutrient limited1. Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)2,3, the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized4,​5,​6,​7,​8. However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+μ), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+μ co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.

Plant species’ origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands

Exotic species dominate many communities; however the functional significance of species’ biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.

Collaborative data exploration interfaces - From participatory sensing to participatory sensemaking

As technological capabilities for capturing, aggregating, and processing large quantities of data continue to improve, the question becomes how to effectively utilise these resources. Whenever automatic methods fail, it is necessary to rely on human background knowledge, intuition, and deliberation. This creates demand for data exploration interfaces that support the analytical process, allowing users to absorb and derive knowledge from data. Such interfaces have historically been designed for experts. However, existing research has shown promise in involving a broader range of users that act as citizen scientists, placing high demands in terms of usability. Visualisation is one of the most effective analytical tools for humans to process abstract information. Our research focuses on the development of interfaces to support collaborative, community-led inquiry into data, which we refer to as Participatory Data Analytics. The development of data exploration interfaces to support independent investigations by local communities around topics of their interest presents a unique set of challenges, which we discuss in this paper. We present our preliminary work towards suitable high-level abstractions and interaction concepts to allow users to construct and tailor visualisations to their own needs.

Hyaluronic acid enhances the mechanical properties of tissue-engineered cartilage constructs

There is a need for materials that are well suited for cartilage tissue engineering. Hydrogels have emerged as promising biomaterials for cartilage repair, since, like cartilage, they have high water content, and they allow cells to be encapsulated within the material in a genuinely three-dimensional microenvironment. In this study, we investigated the mechanical properties of tissue-engineered cartilage constructs using in vitro culture models incorporating human chondrocytes from osteoarthritis patients. We evaluated hydrogels formed from mixtures of photocrosslinkable gelatin-methacrylamide (Gel-MA) and varying concentrations (0–2%) of hyaluronic acid methacrylate (HA-MA). Initially, only small differences in the stiffness of each hydrogel existed. After 4 weeks of culture, and to a greater extent 8 weeks of culture, HA-MA had striking and concentration dependent impact on the changes in mechanical properties. For example, the initial compressive moduli of cell-laden constructs with 0 and 1% HA-MA were 29 and 41 kPa, respectively. After 8 weeks of culture, the moduli of these constructs had increased to 66 and 147 kPa respectively, representing a net improvement of 69 kPa for gels with 1% HA-MA. Similarly the equilibrium modulus, dynamic modulus, failure strength and failure strain were all improved in constructs containing HA-MA. Differences in mechanical properties did not correlate with glycosaminoglycan content, which did not vary greatly between groups, yet there were clear differences in aggrecan intensity and distribution as assessed using immunostaining. Based on the functional development with time in culture using human chondrocytes, mixtures of Gel-MA and HA-MA are promising candidates for cartilage tissue-engineering applications.

Interleukin 10 polymorphisms in ankylosing spondylitis

Genetic polymorphisms of the IL10 promoter region have been implicated in many autoimmune diseases, including seronegative spondyloarthropathies. We studied three SNPs (IL10-1087,-824, and -597) and two microsafellites(IL10R and IL10G) lying within the promoter region of IL10 for association with susceptibility to and clinical manifestations of ankylosing spondylitis (AS), a common form of spondyloarthritis. Four hundred and sixty-eight individuals from 182 Finnish families affected with AS were studied. No association between individual IL10 promoter region polymorphisms or marker haplotype was observed with susceptibility to AS, but weak association was noted between the IL10-597 and -824 SNPs and age of disease onset (P= 0.01 for each SNP). The IL10.G4 allele was associated with BASFI (corrected for disease duration) (P= 0.03). We conclude that IL10 promoter polymorphisms have no significant effect on susceptibility to AS, but may play a minor role in determining age of disease onset and disease severity. © 2003 Nature Publishing Group All rights reserved.

Developing the ASEAN regional road safety strategy

In 2011, more than 75,000 people died in road crashes in the ten member countries of the Association of South East Asian Nations (ASEAN) and many times this number sustained long term injuries. Improving road safety outcomes in ASEAN is not only important for the welfare and economic benefit of these countries, but given that a significant proportion of the world’s population lives in ASEAN, it will strongly influence whether the aims of the United Nations Decade of Action for Road Safety and the Sustainable Development Goals are reached. For this reason, the Asian Development Bank, funded by the Japan Fund for Poverty Reduction, has funded a package of action to improve road safety in ASEAN, including the development of a regional road safety strategy. The diversity of the member nations of ASEAN poses significant challenges for the development of the strategy. For example, the road fatality rates per 100,000 population in Malaysia and Thailand are about 5 times greater than in Singapore. In addition, the importance of particular road safety issues varies across the ASEAN countries and for countries which are undergoing rapid motorization, the order of importance may change over the life of the strategy. The development of the ASEAN Regional Road Safety Strategy has adopted the five pillars of road safety of the UN Decade of Action but focused on those aspects which are most relevant at the regional level and where a regional approach will support and facilitate actions taken by individual countries.

ASEAN and ADB implementing new approaches to building road safety capacity

Following the Association of Southeast Asian Nations (ASEAN) senior transport officials meeting in May 2011, the Secretariat requested the Asian Development Bank (ADB) to provide assistance to improve road safety in ASEAN. In response, ADB, funded by the Japan Fund for Poverty Reduction, has begun an innovative approach to capacity building that has already been adapted and replicated in other sub-regions. This paper will discuss the model central to the project. The Road Safety Capacity Building for ASEAN Project commenced in May 2013. Each country has appointed a National Focal Point (NFP) to identify and coordinate information. A team of International Experts were appointed to develop materials and present a comprehensive train the trainer program focused on five key areas. Thirty eight senior Government officers from across ASEAN attended a two week program at ADB headquarters in Manila and will arrange and deliver specific training and associated activities to other colleagues within their country. ADB has appointed a National Consultant to work in partnership with the trainees on a range of activities including development of “pipeline project proposals” for funding consideration investors and donors. As part of the project, a draft ASEAN Regional Road Safety Strategy document has been prepared and consultation will further refine its directions and contents. The project will reach its conclusion in 2015 and a follow up phase three project is being considered.

A large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3' untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P<2.3×10(-5)) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. SIGNIFICANCE Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk.

Generalizability of established prostate cancer risk variants in men of African ancestry

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function

Proximal tubule epithelial cells (PTEC) of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC) as the model system. We demonstrate that PTEC express three inhibitory molecules: (i) cell surface PD-L1 that induces MoDC expression of PD-L1; (ii) intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii) soluble HLA-G (sHLA-G) that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

Applying the principles of interpretive field research: An example of an IS case study on shared services

All sound research commence with the selection of a research paradigm. The chosen research paradigm is significant in shaping the researcher’s perspectives of the world and it is a vital step in any study’s’ research design. There are different paradigms that IS researchers can choose from; amongst which the interpretive paradigm is growing in acceptance.. Though interpretive research has emerged as an important strand in Information Systems (IS), guidelines on how to conduct interpretive research and how to evaluate them have been scarce. Klein and Myers presented seven principles with examples for each from three case examples. While these principles are much valued, there is a lack of support for novice researchers on how to embed these principles in an overall research design, which could help with the aid of a detailed example that has done so. Thus, this paper aims to address this gap, and presents how Klein and Myers’s principles were applied within an example study that investigated shared services in the Malaysian Higher Education context. The example study adopted the interpretive paradigm as the most suited approach that fitted their research questions and goals. More details about the selection and adoption of the Klein and Myers’s guidelines in the context of the shared services research case study are presented in the paper.

Challenges in developing a new regional road safety strategy for ASEAN

In 2011, more than 75,000 people died in road crashes in the ten member countries of the Association of South East Asian Nations (ASEAN) and many times this number sustained long term injuries. Improving road safety outcomes in ASEAN is not only important for the welfare and economic benefit of these countries, but given that a significant proportion of the world's population lives in ASEAN, it will strongly influence whether the aims of the United Nations Decade of Action for Road Safety and the Sustainable Development Goals are reached. Following the ASEAN Senior Transport Officials Meeting in May 2011, the Secretariat requested the Asian Development Bank (ADB) to provide assistance to improve road safety in ASEAN. In response, ADB, funded by the Japan Fund for Poverty Reduction, has funded a package of action to improve road safety in ASEAN, including the development of a new regional road safety strategy. The diversity of the member nations of ASEAN poses significant challenges for the development of the strategy. For example, the road fatality rates per 100,000 population in Malaysia and Thailand are about 5 times greater than in Singapore. In addition, the importance of particular road safety issues varies across the ASEAN countries and for countries which are undergoing rapid motorization, the order of importance may change over the life of the strategy. The development of the ASEAN Regional Road Safety Strategy has adopted the five pillars of road safety of the UN Decade of Action but focused on those aspects which are most relevant at the regional level and where a regional approach will support and facilitate actions taken by individual countries. A draft ASEAN Regional Road Safety Strategy document has been prepared and consultation will further refine its directions and contents. The paper will describe the processes undertaken to identify issues and solutions, the measurement of road safety maturity and behavioural risk factors, and the overall structure and themes of the strategy.

Statistical analysis of spectral data: A methodology for designing an intelligent monitoring system for the diabetic foot

Early detection of (pre-)signs of ulceration on a diabetic foot is valuable for clinical practice. Hyperspectral imaging is a promising technique for detection and classification of such (pre-)signs. However, the number of the spectral bands should be limited to avoid overfitting, which is critical for pixel classification with hyperspectral image data. The goal was to design a detector/classifier based on spectral imaging (SI) with a small number of optical bandpass filters. The performance and stability of the design were also investigated. The selection of the bandpass filters boils down to a feature selection problem. A dataset was built, containing reflectance spectra of 227 skin spots from 64 patients, measured with a spectrometer. Each skin spot was annotated manually by clinicians as "healthy" or a specific (pre-)sign of ulceration. Statistical analysis on the data set showed the number of required filters is between 3 and 7, depending on additional constraints on the filter set. The stability analysis revealed that shot noise was the most critical factor affecting the classification performance. It indicated that this impact could be avoided in future SI systems with a camera sensor whose saturation level is higher than 106, or by postimage processing.