BRINGING AGROFORESTRY TECHNOLOGY TO FARMERS IN THE PHILIPPINES: IDENTIFYING CONSTRAINTS TO THE SUCCESS OF EXTENSION ACTIVITIES USING SYSTEMS MODELLING

We present a systems modelling approach to evaluating the success of an agroforestry extension program in Leyte the Philippines. During the program, variables which are intrinsic to farmers’ socio-economic and farming systems were found to have influenced the uptake and acceptance of extension advice. Evaluation of the program therefore depended on identifying the variables and their interdependencies and assessing their relative influence on program outputs. For this purpose, a systems approach which encourages breaking systems into component variables, but also acknowledges the context of problems, assisted construction of models. Using both empirical data collected during program activities and input from stakeholders, Bayesian Belief Network (BBN) modelling was undertaken to predict critical success factors for the four main extension activities, namely recruitment, the effectiveness of written extension materials, development of farmers’ self-efficacy in nursery and silvicultural management and attrition of participating farmers. A key predicted constraint to program recruitment is farmers’ perception of harvest security and whereas this variable can be partly addressed through dissemination of information on harvesting legislation, title security cannot. Differing levels of farmers’ education flow through to differences in predicted reading ability, comprehension of extension literature and possible misconstrual of information. The variable most critical to the development of farmers’ self-efficacy is extended problem-solving support

Bringing Agroforestry Technology to Farmers in the Philippines: Identifying constraints to success using systems modelling

Bayesian Belief Network (BBN) modelling may be applied in rural extension in situations where program outputs are influenced by variables which are sequentially influenced by other variables. For a recently completed agroforestry extension program in Leyte the Philippines, BBN modelling of site factors, establishment practices and risk, predicted widely different program outputs for different levels of extension assistance and farmer inputs. In a situation where very little was known about how farmers would respond to offers of extension assistance, monitoring of the program over a period of three years revealed that extended extension assistance was crucial in determining the likely survival and growth of trees. Extended extension assistance was also important for the elimination of unsuitable sites and the use of appropriate establishment procedures. Where extension support was not available, farmers displayed a poor knowledge of the principles of tree growth, planting trees underneath complete canopies and adjacent to mature coconut palms even though they could have been expected to have extensive local knowledge of raising and growing plants. Approximately one third of planting sites were infertile and eroded and growth of newly planted trees on these sites was poor, often because site preparation and maintenance was minimal. Newly established trees were also found to be at risk from fire, typhoon, and grazing and in situations where plantations were destroyed, farmers became antagonistic towards the program. The implications of the BBN modelling for a hypothetically expanded program are that extended assistance and site inspections are necessary to eliminate planting trees on inappropriate and unsuitable sites and to improve establishment practices and weed control in order to avoid plantations of suppressed and chlorotic trees which fail to meet the expectations of farmers, thus impinging on the success of the program

Pyridoxamine, an Inhibitor of Advanced Glycation Reactions, Also Inhibits Advanced Lipoxidation Reactions: Mechanism of Action of Pyridoxamine

Maillard or browning reactions lead to formation of advanced glycation end products (AGEs) on protein and contribute to the increase in chemical modification of proteins during aging and in diabetes. AGE inhibitors such as aminoguanidine and pyridoxamine (PM) have proven effective in animal model and clinical studies as inhibitors of AGE formation and development of diabetic complications. We report here that PM also inhibits the chemical modification of proteins during lipid peroxidation (lipoxidation) reactions in vitro, and we show that it traps reactive intermediates formed during lipid peroxidation. In reactions of arachidonate with the model protein RNase, PM prevented modification of lysine residues and formation of the advanced lipoxidation end products (ALEs) N(epsilon)-(carboxymethyl)lysine, N(epsilon)-(carboxyethyl)lysine, malondialdehyde-lysine, and 4-hydroxynonenal-lysine. PM also inhibited lysine modification and formation of ALEs during copper-catalyzed oxidation of low density lipoprotein. Hexanoic acid amide and nonanedioic acid monoamide derivatives of PM were identified as major products formed during oxidation of linoleic acid in the presence of PM. We propose a mechanism for formation of these products from the 9- and 13-oxo-decadienoic acid intermediates formed during peroxidation of linoleic acid. PM, as a potent inhibitor of both AGE and ALE formation, may prove useful for limiting the increased chemical modification of tissue proteins and associated pathology in aging and chronic diseases, including both diabetes and atherosclerosis

A microrod-resonator Brillouin laser with 240 Hz absolute linewidth

Wedemonstrate an ultralow-noise microrod-resonator based laser that oscillates on the gain supplied by the stimulated Brillouin scattering optical nonlinearity. Microresonator Brillouin lasers are known to offer an outstanding frequency noise floor, which is limited by fundamental thermal fluctuations. Here, we show experimental evidence that thermal effects also dominate the close-to-carrier frequency fluctuations. The 6mmdiameter microrod resonator used in our experiments has a large optical mode area of∼100 μm2, and hence its 10 ms thermal time constant filters the close-to-carrier optical frequency noise. The result is an absolute laser linewidth of 240 Hz with a corresponding white-frequency noise floor of 0.1 Hz2 Hz−1.We explain the steady-state performance of this laser by measurements of its operation state and of its mode detuning and lineshape. Our results highlight a mechanism for noise that is common to many microresonator devices due to the inherent coupling between intracavity power and mode frequency.Wedemonstrate the ability to reduce this noise through a feedback loop that stabilizes the intracavity power.William Loh, Joe Becker, Daniel C Cole, Aurelien Coillet, Fred N Baynes, Scott B Papp and Scott A Diddam

Characterization of Glycated Proteins by \u3csup\u3e13\u3c/sup\u3eC NMR Spectroscopy

13C NMR spectroscopy has been used to characterize Amadori (ketoamine) adducts formed by reaction of [2-13C]glucose with free amino groups of protein. The spectra of glycated proteins were acquired in phosphate buffer at pH 7.4 and were interpreted by reference to the spectra of model compounds, N alpha-formyl-N epsilon-fructose-lysine and glycated poly-L-lysine (GlcPLL). The anomeric carbon region of the spectrum (approximately 90-105 ppm) of glycated cytochrome c was superimposable on that of N alpha-formyl-N epsilon-fructose-lysine, and contained three peaks characteristic of the alpha- and beta-furanose and beta-pyranose anomers of Amadori adducts to peripheral lysine residues on protein (pK alpha approximately 10.5). The spectrum of GlcPLL yielded six anomeric carbon resonances; the second set of three was displaced about 2 ppm to lower shielding of the first and was assigned to the Amadori adduct at the alpha-amino terminus (pK alpha approximately 7.5). The spectrum of glycated RNase was similar to that of GlcPLL, but contained a third set of three signals attributable to modification of active site lysine 41 (pK alpha approximately 8.8). The assignments for RNase were confirmed by analysis of spectra taken at pH 4 and under denaturing conditions. The spectrum of glycated hemoglobin was comparable to that of GlcPLL, and distinct resonances could be assigned to Amadori adducts at amino-terminal valine and intrachain N epsilon-lysine residues. Chemical analyses were performed to measure the relative extent of alpha- and epsilon-amino group modification in the glycated macromolecules, and the results were compared with estimates based on integration of the NMR spectra

The Advanced Glycation End Product, N\u3csup\u3eE\u3c/sup\u3e-(Carboxymethyl)lysine, Is a Product of Both Lipid Peroxidation and Glycoxidation Reactions

Nepsilon-(Carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML content of low density lipoprotein increased in concert with conjugated dienes but was independent of the presence of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate; only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for protein incubated under the same conditions with glucose. Glyoxal, a known precursor of CML, was also formed during incubation of RNase with arachidonate. These results suggest that lipid peroxidation, as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes

\u3csup\u3e13\u3c/sup\u3eC NMR Investigation of Nonenzymatic Glucosylation of Protein

Nonenzymatic glucosylation of protein is initiated by the reversible condensation of glucose in its open chain form with the amino groups on the protein. The initial product is an aldimine (Schiff base) which cyclizes to the glycosylamine derivative. The aldimine can undergo a slow Amadori rearrangement to yield the relatively stable ketoamine adduct which is structurally analogous to fructose. 13C NMR has been used to characterize these early products of nonenzymatic glucosylation, using RNase A as a model protein. C-1 of the beta-pyranose anomer of the glycosylamine was identified at 88.8 ppm in the spectrum of RNase glucosylated approximately 1:1 with D-[1-13C]glucose. C-1 of the Amadori product was also apparent in this spectrum, resonating as a pair of intense peaks at 52.7 and 53.1 ppm. The anomeric (C-2) resonances of the Amadori adduct were seen in the spectrum of RNase glucosylated approximately 1:1 with [U-13C]glucose. This spectrum was interpreted by comparison to the spectra of reference compounds: D-fructose, fructose-glycine, N alpha-formyl-N epsilon-fructose-lysine, and glucosylated poly-L-lysine. In the protein spectrum, the most intense of the C-2 resonances was that of the beta-fructopyranose anomer at 95.8 ppm. The alpha- and beta-fructofuranose anomers were also observed at 101.7 and 99.2 ppm, respectively. One unidentified signal in the anomeric region was observed in the spectra of poly-L-lysine and RNase, both glucosylated with [U-13C]glucose; no comparable resonances were observed in the spectra of the model compounds

IL-6 Regulation on Skeletal Muscle Mitochondrial Remodeling During Cancer Cachexia in the \u3cem\u3eApc\u3csup\u3eMin/+\u3c/sup\u3e\u3c/em\u3e Mouse

BACKGROUND: Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of proteins regulating mitochondrial biogenesis and dynamics are disrupted in severely cachectic ApcMin/+ mice. It has not been determined if these changes occur at the onset of cachexia and are necessary for the progression of muscle wasting. Exercise and anti-cytokine therapies have proven effective in preventing cachexia development in tumor bearing mice, while their effect on mitochondrial content, biogenesis and dynamics is not well understood. The purposes of this study were to 1) determine IL-6 regulation on mitochondrial remodeling/dysfunction during the progression of cancer cachexia and 2) to determine if exercise training can attenuate mitochondrial dysfunction and the induction of proteolytic pathways during IL-6 induced cancer cachexia. METHODS: ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL)-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts. RESULTS: Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1α and fusion (Mfn1, Mfn2) protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1α and fusion proteins were further suppressed, and fission protein (FIS1) was induced. IL-6 receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1α, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1α and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression induced. Exercise normalized these IL-6 induced effects. C2C12 myotubes administered IL-6 had increased FIS1 protein expression, increased oxidative stress, and reduced PGC-1α gene expression without altered mitochondrial protein expression. CONCLUSIONS: Altered expression of proteins regulating mitochondrial biogenesis and fusion are early events in the initiation of cachexia regulated by IL-6, which precede the loss of muscle mitochondrial content. Furthermore, IL-6 induced mitochondrial remodeling and proteolysis can be rescued with moderate exercise training even in the presence of high circulating IL-6 levels