Mobilizing Science for Climate Change, Agriculture and Food Security: Engaging the Southeast Asian Media

In the context of agriculture and food security, science innovations on mitigating and adapting to climate change are available, but these are not well shared with next users and end users (especially farmers) and the public due to inadequate coverage by the mainstream media, a powerful partner in communication and engagement. The urgent need for media practitioners to have an accurate, science-based understanding of climate change and enhance their skills on environmental reporting gave CCAFS-SEA the impetus to conduct a series of inter-Center media seminar-workshops for key Southeast Asian media practitioners in collaboration with NARS and national media partners. Overall, the media seminar-workshop series was participated in by 149 media professionals and 39 government information officers in SEA. The journalists came from print, broadcast (radio-TV) and web-based media outlets. This initiative was a critical first step in implementing CCAFS-SEA’s regional engagement and communication plan, pursued as a CGIAR inter-Center activity in collaboration with NARS and national media partners. The content of the two-day seminar-workshops focused on two major areas: science innovations in climate change, agriculture and food security and communicating climate change. Complementing the plenary sessions was a story ideas marketplace which primarily served as a venue for dialogue among participants and resource persons on possible stories to be developed and released in their respective media outlets. A half-day field tour exposed participants to climate change and agriculture R4D either by a CGIAR Center or a NARS partner and/or climate smart agriculture practices of a farming community. One of the outcomes of the SEA media workshop series in the Philippines is the forging of partnership with a private company, Metro-Pacific Investments Corporation (MPIC), which provided volunteer funding a proposal of the Philippine Agriculture Journalists, Inc. and the Department of Agriculture (DA) to replicate the initiative in strategic regions in the Philippines. This is an unprecedented public-private-civil society partnership in communicating climate change, agriculture and food security in the Philippines. With six media seminar-workshops completed in Cambodia, Lao PDR, Vietnam and the Philippines, the next step for CCAFS-SEA would be to move the engagement process further with partners in the region

Enhanced Manhattan-based Clustering using Fuzzy C-Means Algorithm for High Dimensional Datasets

The problem of mining a high dimensional data includes a high computational cost, a high dimensional dataset composed of thousands of attribute and or instances. The efficiency of an algorithm, specifically, its speed is oftentimes sacrificed when this kind of dataset is supplied to the algorithm. Fuzzy C-Means algorithm is one which suffers from this problem. This clustering algorithm requires high computational resources as it processes whether low or high dimensional data. Netflix data rating, small round blue cell tumors (SRBCTs) and Colon Cancer (52,308, and 2,000 of attributes and 1500, 83 and 62 of instances respectively) dataset were identified as a high dimensional dataset. As such, the Manhattan distance measure employing the trigonometric function was used to enhance the fuzzy c-means algorithm. Results show an increase on the efficiency of processing large amount of data using the Netflix ,Colon cancer and SRCBT an (39,296, 38,952 and 85,774 milliseconds to complete the different clusters, respectively) average of 54,674 milliseconds while Manhattan distance measure took an average of (36,858, 36,501 and 82,86 milliseconds, respectively)  52,703 milliseconds for the entire dataset to cluster. On the other hand, the enhanced Manhattan distance measure took (33,216, 32,368 and 81,125 milliseconds, respectively) 48,903 seconds on clustering the datasets. Given the said result, the enhanced Manhattan distance measure is 11% more efficient compared to Euclidean distance measure and 7% more efficient than the Manhattan distance measure respectively

Design of the Front End Electronics for the Infrared Camera of JEM-EUSO, and manufacturing and verification of the prototype model

The Japanese Experiment Module (JEM) Extreme Universe Space Observatory (EUSO) will be launched and attached to the Japanese module of the International Space Station (ISS). Its aim is to observe UV photon tracks produced by ultra-high energy cosmic rays developing in the atmosphere and producing extensive air showers. The key element of the instrument is a very wide-field, very fast, large-lense telescope that can detect extreme energy particles with energy above $10^{19}$ eV. The Atmospheric Monitoring System (AMS), comprising, among others, the Infrared Camera (IRCAM), which is the Spanish contribution, plays a fundamental role in the understanding of the atmospheric conditions in the Field of View (FoV) of the telescope. It is used to detect the temperature of clouds and to obtain the cloud coverage and cloud top altitude during the observation period of the JEM-EUSO main instrument. SENER is responsible for the preliminary design of the Front End Electronics (FEE) of the Infrared Camera, based on an uncooled microbolometer, and the manufacturing and verification of the prototype model. This paper describes the flight design drivers and key factors to achieve the target features, namely, detector biasing with electrical noise better than $100 \mu$V from $1$ Hz to $10$ MHz, temperature control of the microbolometer, from $10^{\circ}$C to $40^{\circ}$C with stability better than $10$ mK over $4.8$ hours, low noise high bandwidth amplifier adaptation of the microbolometer output to differential input before analog to digital conversion, housekeeping generation, microbolometer control, and image accumulation for noise reduction

Phenotypic, morphological, and metabolic characterization of vascular-spheres from human vascular mesenchymal stem cells

The ability to form spheroids under non-adherent conditions is a well-known property of human mesenchymal stem cells (hMSCs), in addition to stemness and multilineage differentiation features. In the present study, we tested the ability of hMSCs isolated from the vascular wall (hVW-MSCs) to grow as spheres, and provide a characterization of this 3D model. hVW-MSCs were isolated from femoral arteries through enzymatic digestion. Spheres were obtained using ultra-low attachment and hanging drop methods. Immunophenotype and pluripotent genes (SOX-2, OCT-4, NANOG) were analyzed by immunocytochemistry and real-time PCR, respectively. Spheres histological and ultrastructural architecture were examined. Cell viability and proliferative capacity were measured using LIVE/DEATH assay and ki-67 proliferation marker. Metabolomic profile was obtained with liquid chromatography–mass spectrometry. In 2D, hVW-MSCs were spindle-shaped, expressed mesenchymal antigens, and displayed mesengenic potential. 3D cultures of hVW-MSCs were CD44+, CD105low, CD90low, exhibited a low propensity to enter the cell cycle as indicated by low percentage of ki-67 expression and accumulated intermediate metabolites pointing to slowed metabolism. The 3D model of hVW-MSCs exhibits stemness, dormancy and slow metabolism, typically observed in stem cell niches. This culture strategy can represent an accurate model to investigate hMSCs features for future clinical applications in the vascular field

Germline BRCA1 mutation reprograms breast epithelial cell metabolism towards mitochondrial-dependent biosynthesis : evidence for metformin-based "starvation" strategies in BRCA1 carriers

Altres ajuts: This work was supported by grants from the European Regional Development Fund [FEDER] to JJ and Grant CD12/00672 to SFA), co-founded by theand Departament d'Economia I Coneixement, Catalonia, Spain.Altres ajuts: MSCBS/CD15-00033We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. Targeted metabolomic analysis was performed in isogenic pairs of nontumorigenic human breast epithelial cells in which the knock-in of 185delAG mutation in a single BRCA1 allele leads to genomic instability. Mutant BRCA1 one-hit epithelial cells displayed constitutively enhanced activation of biosynthetic nodes within mitochondria. This metabolic rewiring involved the increased incorporation of glutamine- and glucose-dependent carbon into tricarboxylic acid (TCA) cycle metabolite pools to ultimately generate elevated levels of acetyl-CoA and malonyl-CoA, the major building blocks for lipid biosynthesis. The significant increase of branched-chain amino acids (BCAAs) including the anabolic trigger leucine, which can not only promote protein translation via mTOR but also feed into the TCA cycle via succinyl-CoA, further underscored the anabolic reprogramming of BRCA1 haploinsufficient cells. The anti-diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling. Metformin-induced restriction of mitochondrial biosynthetic capacity was sufficient to impair the tumor-initiating capacity of BRCA1 one-hit cells in mammosphere assays. Metabolic rewiring of the breast epithelium towards increased anabolism might constitute an unanticipated and inherited form of metabolic reprogramming linked to increased risk of oncogenesis in women bearing pathogenic germline BRCA1 mutations. The ability of metformin to constrain the production of mitochondrial-dependent biosynthetic intermediates might open a new avenue for "starvation" chemopreventive strategies in BRCA1 carriers

Electrophilicity of neutral square-planar organosilver(III) compounds

Neutral Ag(III) complexes stabilised with just monodentate ligands are here unambiguously established. In a series of square-planar (CF3)3Ag(L) compounds with hard and soft Group 15 donor ligands, L, the metal center has been found to exhibit substantial acidity favouring apical coordination of an additional ligand under no coordination constraints

Accelerated geroncogenesis in hereditary breast-ovarian cancer syndrome

The geroncogenesis hypothesis postulates that the decline in metabolic cellular health that occurs naturally with aging drives a "field effect" predisposing normal tissues for cancer development. We propose that mutations in the cancer susceptibility genes BRCA1/2 might trigger "accelerated geroncogenesis" in breast and ovarian epithelia. By speeding up the rate at which the metabolic threshold becomes "permissive" with survival and expansion of genomically unstable pre-tumoral epithelial cells, BRCA haploinsufficiency-driven metabolic reprogramming would operate as a bona fide oncogenic event enabling malignant transformation and tumor formation in BRCA carriers. The metabolic facet of BRCA1 one-hit might involve tissue-specific alterations in acetyl-CoA, α-ketoglutarate, NAD +, FAD, or S-adenosylmethionine, critical factors for de/methylation or de/acetylation dynamics in the nuclear epigenome. This in turn might induce faulty epigenetic reprogramming at the "install phase" that directs cell-specific differentiation of breast/ovarian epithelial cells, which can ultimately determine the penetrance of BRCA defects during developmental windows of susceptibility. This model offers a framework to study whether metabolic drugs that prevent or revert metabolic reprogramming induced by BRCA haploinsufficiency might displace the "geroncogenic risk" of BRCA carriers to the age typical for those without the mutation. The identification of the key nodes that directly communicate changes in cellular metabolism to the chromatin in BRCA haploinsufficient cells may allow the epigenetic targeting of genomic instability using exclusively metabolic means. The validation of accelerated geroncogenesis as an inherited "one-hit" metabolic "field effect" might offer new strategies to therapeutically revisit the apparently irreversible genetic-hereditary fate of women with hereditary breast-ovarian cancer syndrome

In silico clinical trials for anti-aging therapies

Altres ajuts: CERCA Programme/Generalitat de CatalunyaAltres ajuts: Fundació Oncolliga Girona (Lliga catalana d'ajuda al malalt de càncer, Girona)Altres ajuts: Obra Social La Caixa Foundation on Collaborative Mathematics awarded to the Centre de Recerca Matemàtica (CRM)Therapeutic strategies targeting the hallmarks of aging can be broadly grouped into four categories, namely systemic (blood) factors, metabolic manipulation (diet regimens and dietary restriction mimetics), suppression of cellular senescence (senolytics), and cellular reprogramming, which likely have common characteristics and mechanisms of action. In evaluating the potential synergism of combining such strategies, however, we should consider the possibility of constraining trade-off phenotypes such as impairment in wound healing and immune response, tissue dysfunction and tumorigenesis. Moreover, we are rapidly learning that the benefit/risk ratio of aging-targeted interventions largely depends on intra- and inter-individual variations of susceptibility to the healthspan-, resilience-, and/or lifespan-promoting effects of the interventions. Here, we exemplify how computationally-generated proxies of the efficacy of a given lifespan/healthspan-promoting approach can predict the impact of baseline epigenetic heterogeneity on the positive outcomes of ketogenic diet and mTOR inhibition as single or combined anti-aging strategies. We therefore propose that stochastic biomathematical modeling and computational simulation platforms should be developed as in silico strategies to accelerate the performance of clinical trials targeting human aging, and to provide personalized approaches and robust biomarkers of healthy aging at the individual-to-population levels