A Vision for Transdisciplinarity in Future Earth: Perspectives from Young Researchers

Meeting the demand for food, energy, and water as world population increases is a major goal for the food systems of the future. These future challenges, which are complex, multiscalar, and cross-sectoral in nature, require a food systems approach that recognizes the socio-ecological and socio-technical dimensions of food (Ericksen, 2008; Ingram, 2011; Rivera-Ferre, 2012). The United Nations' Future Earth Program aims to provide a new platform for consolidating the knowledge required for societies to transition to global sustainability (Future Earth Transition Team, 2012). In this paper, we explore how Future Earth could become a vehicle for inspiring the production of new research ideas and collaborations for sustainably transforming the future food system. We do this on the basis of a synthesis of views from 28 young (below 40 years old) food system scientists, representing five continents. Their expertise comes from disciplines including food engineering, agronomy, ecology, geography, psychology, public health, food politics, nutritional science, political science, sociology and sustainability science. This paper begins with an outline of the institutional framework of Future Earth and how it might support innovative transdisciplinary research on food systems, and the position of young scientists within this framework. Secondly, we outline the key insights expressed by the young scientists during the Food Futures Conference in Villa Vigoni, Italy, in April 2013, including the core research questions raised during the meeting as well as some of the challenges involved in realizing their research ambitions within their professional spheres

Quantitative phosphoproteomics to unravel the cellular response to chemical stressors with different modes of action

Damage to cellular macromolecules and organelles by chemical exposure evokes activation of various stress response pathways. To what extent different chemical stressors activate common and stressor-specific pathways is largely unknown. Here, we used quantitative phosphoproteomics to compare the signaling events induced by four stressors with different modes of action: the DNA damaging agent: cisplatin (CDDP), the topoisomerase II inhibitor: etoposide (ETO), the pro-oxidant: diethyl maleate (DEM) and the immunosuppressant: cyclosporine A (CsA) administered at an equitoxic dose to mouse embryonic stem cells. We observed major differences between the stressors in the number and identity of responsive phosphosites and the amplitude of phosphorylation. Kinase motif and pathway analyses indicated that the DNA damage response (DDR) activation by CDDP occurs predominantly through the replication-stress-related Atr kinase, whereas ETO triggers the DDR through Atr as well as the DNA double-strand-break-associated Atm kinase. CsA shares with ETO activation of CK2 kinase. Congruent with their known modes of action, CsA-mediated signaling is related to down-regulation of pathways that control hematopoietic differentiation and immunity, whereas oxidative stress is the most prominent initiator of DEM-modulated stress signaling. This study shows that even at equitoxic doses, different stressors induce distinctive and complex phosphorylation signaling cascades.Toxicolog

Extraction of bodily features for gait recognition and gait attractiveness evaluation

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-012-1319-2. Copyright @ 2012 Springer.Although there has been much previous research on which bodily features are most important in gait analysis, the questions of which features should be extracted from gait, and why these features in particular should be extracted, have not been convincingly answered. The primary goal of the study reported here was to take an analytical approach to answering these questions, in the context of identifying the features that are most important for gait recognition and gait attractiveness evaluation. Using precise 3D gait motion data obtained from motion capture, we analyzed the relative motions from different body segments to a root marker (located on the lower back) of 30 males by the fixed root method, and compared them with the original motions without fixing root. Some particular features were obtained by principal component analysis (PCA). The left lower arm, lower legs and hips were identified as important features for gait recognition. For gait attractiveness evaluation, the lower legs were recognized as important features.Dorothy Hodgkin Postgraduate Award and HEFCE

Continuous observations of CO2 and CH4 exchange from East-African rangelands

Semi-arid rangelands in Sub-Saharan Africa (SSA) are an important source of food security and nutrition but are under increased anthropogenic pressure by a growing population. These rangelands are characterized by nutrient poor soils and distinct wet and dry season(s). Due to the soil and climate combination, conventional crop agriculture is rarely feasible without irrigation and mineral fertilizer amendments, which in turn are limited by prohibitively high fertilizer prices and lack of water. Instead, pastoral livestock keeping is a valuable option to use these marginal lands and – under the right management – can be a sustainable form of food production and biodiversity protection given that most of these landscapes have co-evolved with megafauna over millennia. Despite the global role of livestock systems on climate change, there is still limited understanding on the role of SSA rangelands. At the same time, livestock systems emit greenhouse gases (GHG) and can promote global warming. But despite the impact of livestock systems on climate change, our understanding of the role of SSA rangelands is limited. To date, a thorough assessment that includes continuous GHG exchange measurement in combined wildlife-livestock systems on the African continent has not been undertaken. Here we provide the first eddy covariance (EC) measurements of CO2/CH4/H2O fluxes from the ILRI Kapiti Wildlife Conservancy - a benchmark rangeland site in East Africa that is grazed by livestock and wildlife. Our results show continuous ecosystem CO2 uptake from the wet to dry seasons with considerable CO2 emission pulses following precipitation events after long dry periods that turn the landscape into short-term net CO2 emitters. In contrast to CO2, CH4 fluxes are highly variable and depend particularly on wildlife and/or livestock being present in the fetch of the EC tower. In addition to EC measurements and given the need for scaling of our results, we relate CO2 and CH4 fluxes to simple remote sensing measurements of vegetation greenness derived from phenological cameras. Our results show good agreement between the two approaches. Yet, more observations across a climatic gradient and along varying management intensities are needed to reduce existing uncertainties in the effect of SSA rangelands on climate change. To build a complete GHG budget, hot spots of greenhouse gas emissions such as from livestock enclosures or water bodies as well as soil carbon sequestration have yet to be accounted for

Plasma metabolomics in tuberculosis patients with and without concurrent type 2 diabetes at diagnosis and during antibiotic treatment

Tuberculosis (TB) and type 2 diabetes mellitus (DM), a major TB risk factor, are both accompanied by marked alterations in metabolic processes. Dissecting the specific metabolic changes induced by disease through metabolomics has shown potential to improve our understanding of relevant pathophysiological mechanisms of disease, which could lead to improved treatment. Targeted tandem liquid chromatography-mass spectrometry (LC-MS/MS) was used to compare amine and acylcarnitine levels in plasma samples of patients with TB or TB-DM from Indonesia at time of diagnosis and during antibiotic treatment. Partial least squares discrimination analysis (PLS-DA) showed good separation of patient groups. Amine levels were strongly altered in both disease groups compared to healthy controls, including low concentrations of citrulline and ornithine. Several amino acid ratios discriminated TB from controls (phenylalanine/histidine; citrulline/arginine; kynurenine/tryptophan), possibly reflecting changes in indoleamine-pyrrole 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) activity. Choline, glycine, serine, threonine and homoserine levels were lower in TB-DM compared to TB, and, in contrast to other analytes, did not normalize to healthy control levels during antibiotic treatment. Our results not only provide important validation of previous studies but also identify novel biomarkers, and significantly enhance our understanding of metabolic changes in human TB and TB-DM.Analytical BioScience

Developmental defects and male sterility in mice lacking the ubiquitin-like DNA repair gene mHR23B.

mHR23B encodes one of the two mammalian homologs of Saccharomyces cerevisiae RAD23, a ubiquitin-like fusion protein involved in nucleotide excision repair (NER). Part of mHR23B is complexed with the XPC protein, and this heterodimer functions as the main damage detector and initiator of global genome NER. While XPC defects exist in humans and mice, mutations for mHR23A and mHR23B are not known. Here, we present a mouse model for mHR23B. Unlike XPC-deficient cells, mHR23B(-/-) mouse embryonic fibroblasts are not UV sensitive and retain the repair characteristics of wild-type cells. In agreement with the results of in vitro repair studies, this indicates that mHR23A can functionally replace mHR23B in NER. Unexpectedly, mHR23B(-/-) mice show impaired embryonic development and a high rate (90%) of intrauterine or neonatal death. Surviving animals display a variety of abnormalities, including retarded growth, facial dysmorphology, and male sterility. Such abnormalities are not observed in XPC and other NER-deficient mouse mutants and point to a separate function of mHR23B in development. This function may involve regulation of protein stability via the ubiquitin/proteasome pathway and is not or only in part compensated for by mHR23A

Pyruvate dehydrogenase kinase inhibitor dichloroacetate improves host control of Salmonella enterica serovar Typhimurium infection in human macrophages

Global increases in the prevalence of antimicrobial resistance highlight the urgent need for novel strategies to combat infectious diseases. Recent studies suggest that host metabolic pathways play a key role in host control of intracellular bacterial pathogens. In this study we explored the potential of targeting host metabolic pathways for innovative host-directed therapy (HDT) against intracellular bacterial infections. Through gene expression profiling in human macrophages, pyruvate metabolism was identified as potential key pathway involved in Salmonella enterica serovar Typhimurium (Stm) infections. Next, the effect of targeting pyruvate dehydrogenase kinases (PDKs) - which are regulators of the metabolic checkpoint pyruvate dehydrogenase complex (PDC) - on macrophage function and bacterial control was studied. Chemical inhibition of PDKs by dichloroacetate (DCA) induced PDC activation and was accompanied with metabolic rewiring in classically activated macrophages (M1) but not in alternatively activated macrophages (M2), suggesting cell-type specific effects of dichloroacetate on host metabolism. Furthermore, DCA treatment had minor impact on cytokine and chemokine secretion on top of infection, but induced significant ROS production by M1 and M2. DCA markedly and rapidly reduced intracellular survival of Stm, but interestingly not Mycobacterium tuberculosis, in human macrophages in a host-directed manner. In conclusion, DCA represents a promising novel HDT compound targeting pyruvate metabolism for the treatment of Stm infections.Immunogenetics and cellular immunology of bacterial infectious disease

The ‘Self-Regulated Learning Opportunities Questionnaire': a diagnostic instrument for teacher educators' professional development

Many recent studies have stressed the importance of students’ self-regulated learning (SRL) skills for successful learning. Although primary teacher educators are aware of the importance of SRL for their students, they often find it difficult to implement SRL opportunities in their teaching. To support teacher professional development, an SRL model was described in a previous theoretical study. In the present article, this SRL model is elaborated towards the ‘SRL Opportunities Questionnaire’ (SRLOQ) that can be applied by primary teacher educators as a diagnostic instrument for classroom settings. A four-phase research design is applied consisting of scale development, score validation, further validation of the SRLOQ in primary teacher education, and a confirmatory factor analysis. Finally, a single case study is described that illustrates the usefulness of the SRLOQ in classroom practice

Development of a limits of stability protocol for use in transtibial prosthesis users: learning effects and reliability of outcome variables

The aims of this study were to empirically quantify reliability and learning effects of a Limits of Stability protocol for transtibial prosthesis users. Outcome variables from center of pressure and center of mass were tested on: 1) multiple test repetitions within a single test occasion; and 2) between multiple test occasions. Trantibial prosthesis users (n=7) and matched controls (n=7) executed five trials of the Limits of Stability protocol on two occasions per day, on two consecutive days. Inter-trial learning effects and reliability of outcomes extracted via center of mass and center of pressure were evaluated utilizing standard biomechanics laboratory equipment. Reliability was good to excellent except the reaction time variable which was poor (Pooled 95%CI of ICC=0.248-0.484). An inter-trial learning effect was present in directional control for prosthesis users when the first trial was included in analysis (center of mass: 95%CI of r=0.065-0.239; center of pressure: 95%CI of r=0.076-0.249). The use of standard biomechanics lab equipment can produce reliable results for the Limits of Stability protocol. Researchers should be aware of low reliability of reaction time variable in the protocol assessed and should execute at least one practice trial prior to that which is used in subsequent analysis