Weak Interactions Effect on the P-N Mass Splitting and the Principle of Equivalence

The weak interaction contribution to the proton neutron mass difference is computed using a generalization of Cottingham's formula. When included in the analysis of the Eotvos experiment, this contribution reduces the bound on a possible weak interactions violation to the equivalence principle by one order of magnitude.Comment: LaTex, 12 pages, 2 tables. A shorter version appeared in proceedings of Zacatecas 2001 Workshop on Particles and Fields. References added, typos correcte

Spatial variability in shrub vegetation across dune forms in central Saudi Arabia

In desert dune environments, vegetation may be an indicator of dune stability and rates of sediment transport. As topography and underlying controls of vegetation vary over large spatial areas variations in dune form make scaling up of field research difficult. To mitigate this, and to identify spatial variations in vegetation distributions in a Saudi Arabian sand sea, spectral information from high resolution satellite images was classified to map polygons of shrub vegetation over 360 km2 of well-defined linear dunes, broken linear dunes and dome dune forms. When compared to topographic characteristics of the landscape extracted from a digital elevation model, vegetation densities were often highest on 10 to 20-degree slopes elevated above interdune salt deposits on dune flanks. Spatially this was confined to small areas, and density was not always related to dune form, more to the presence of groundwater which could also encourage vegetation on the tops of some dunes. Field observations identified shrubs of mainly Calligonum genus whose size is related to the amounts of salts, moving sediment and access to the water table that varies within and between dune forms. Shrub vegetation density is likened to surface roughness to better understand sediment movement in this environment

Inhibition of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease

Pharmacokinetics and Pharmacodynamics of Intranasal and Intramuscular Administration of Naloxone in Working Dogs Administered Fentanyl

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field. OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs. ANIMALS: Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg. METHODS: In this randomized, controlled cross-over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after reversal with naloxone. Blood samples for naloxone detection were obtained at 0, 5, 10, 30, 60 and 120 minutes. Pharmacokinetic parameters and sedation scores were compared between IM and IN naloxone groups. RESULTS: There was a significant increase in sedation score from baseline (0.25 [-4 to 1] IM; 0 [-2 to 1] IN) after fentanyl administration (11 [5-12] IM; 9.25 [4-11] IN), followed by a significant reduction at 5 (0.5 [-0.5 to 1.5] IM; 1.25 [-1.5 to 4.5] IN) through 120 minutes (-0.5 [-2 to 1] IM; 0 [-4.5 to 1] IN) after reversal with naloxone. Route of administration had no significant effect on sedation score. Maximum plasma concentration was significantly lower after IN administration (11.7 [2.8-18.8] ng/mL IN, 36.7 [22.1-56.4] ng/mL IM, P \u3c .001) but time to reach maximum plasma concentration was not significantly different from IM administration. CONCLUSION AND CLINICAL IMPORTANCE: Although IM administration resulted in higher naloxone plasma concentrations compared to IN, reversal of sedation was achieved via both routes after administration of therapeutic doses of fentanyl

Assessment of variability of peat physicochemical properties, subsidence and their interactions within Selangor forests

Tropical peat swamp forests are carbon-rich ecosystems both above- and belowground, which play a major role in the climate balance of the earth. The majority of the world's tropical peat forest cover is located in Southeast Asia and is increasingly threatened by anthropogenic disturbances. Despite their importance for biodiversity conservation and climatic balance of the earth, pristine peatlands are almost extinct in many parts of Southeast Asia. Peninsular Malaysia is one such region, where there are no undisturbed peatlands left in the west coast. We studied the largest peat forest area in the west coast of Malaysia, located in the state of Selangor. We evaluated variability of peat subsidence (for 1 year), peat physicochemical properties and macronutrient contents between forest regions and between different depths (not for subsidence) covering the top 50 cm, and the complex interactions between them. We found that there was significant peat subsidence in all the studied regions, however, there was no significant difference in subsidence between different forest regions. Physicochemical properties such as peat moisture, pH and carbon (C) content and all macronutrient contents except phosphorus (P), either varied between regions, or showed significant interactions between region and depth in Selangor peat forests. All the measured peat physicochemical properties varied with depth. Among macronutrients, only nitrogen (N), P and calcium (Ca) showed significant change with depth, while there were no changes with depth for sulphur (S), potassium (K) and magnesium (Mg) contents. These changes in each peat physicochemical property and macronutrient contents correlated with changes in other peat physicochemical properties and nutrient contents; however, there is a need for controlled experiments to further understand these significant interactions. The findings show continued carbon loss in secondary peat swamp forests through subsidence, indicating the long-term impact of selective logging and associated historical drainage. The significant variability of peat physicochemical properties and macronutrient contents with region and depth, also show the need for intensive sampling to characterise large secondary peat swamp forests

Assessment of variability of peat physicochemical properties, subsidence and their interactions within Selangor forests

Tropical peat swamp forests are carbon-rich ecosystems both above- and belowground, which play a major role in the climate balance of the earth. The majority of the world's tropical peat forest cover is located in Southeast Asia and is increasingly threatened by anthropogenic disturbances. Despite their importance for biodiversity conservation and climatic balance of the earth, pristine peatlands are almost extinct in many parts of Southeast Asia. Peninsular Malaysia is one such region, where there are no undisturbed peatlands left in the west coast. We studied the largest peat forest area in the west coast of Malaysia, located in the state of Selangor. We evaluated variability of peat subsidence (for 1 year), peat physicochemical properties and macronutrient contents between forest regions and between different depths (not for subsidence) covering the top 50 cm, and the complex interactions between them. We found that there was significant peat subsidence in all the studied regions, however, there was no significant difference in subsidence between different forest regions. Physicochemical properties such as peat moisture, pH and carbon (C) content and all macronutrient contents except phosphorus (P), either varied between regions, or showed significant interactions between region and depth in Selangor peat forests. All the measured peat physicochemical properties varied with depth. Among macronutrients, only nitrogen (N), P and calcium (Ca) showed significant change with depth, while there were no changes with depth for sulphur (S), potassium (K) and magnesium (Mg) contents. These changes in each peat physicochemical property and macronutrient contents correlated with changes in other peat physicochemical properties and nutrient contents; however, there is a need for controlled experiments to further understand these significant interactions. The findings show continued carbon loss in secondary peat swamp forests through subsidence, indicating the long-term impact of selective logging and associated historical drainage. The significant variability of peat physicochemical properties and macronutrient contents with region and depth, also show the need for intensive sampling to characterise large secondary peat swamp forests

Genetic and Chemical Evaluation of Trypanosoma brucei Oleate Desaturase as a Candidate Drug Target

Background: Trypanosomes can synthesize polyunsaturated fatty acids. Previously, we have shown that they possess stearoyl-CoA desaturase (SCD) and oleate desaturase (OD) to convert stearate (C18) into oleate (C18:1) and linoleate (C18:2), respectively. Here we examine if OD is essential to these parasites. Methodology: Cultured procyclic (insect-stage) form (PCF) and bloodstream-form (BSF) Trypanosoma brucei cells were treated with 12- and 13-thiastearic acid (12-TS and 13-TS), inhibitors of OD, and the expression of the enzyme was knocked down by RNA interference. The phenotype of these cells was studied. Principal Findings: Growth of PCF T. brucei was totally inhibited by 100 mM of 12-TS and 13-TS, with EC50 values of 4062 and 3062 mM, respectively. The BSF was more sensitive, with EC50 values of 763 and 261 mM, respectively. This growth phenotype was due to the inhibitory effect of thiastearates on OD and, to a lesser extent, on SCD. The enzyme inhibition caused a drop in total unsaturated fatty-acid level of the cells, with a slight increase in oleate but a drastic decrease in linoleate level, most probably affecting membrane fluidity. After knocking down OD expression in PCF, the linoleate content was notably reduced, whereas that of oleate drastically increased, maintaining the total unsaturated fatty-acid level unchanged. Interestingly, the growth phenotype of the RNAi-induced cells was similar to that found for thiastearate-treated trypanosomes, with the former cells growing twofold slower than the latter ones, indicating that the linoleate content itsel

Mechanisms of growth inhibition of Phytomonas serpens by the alkaloids tomatine and tomatidine

Phytomonas serpens are flagellates in the family Trypanosomatidae that parasitise the tomato plant (Solanum lycopersicum L.), which results in fruits with low commercial value. The tomato glycoalkaloid tomatine and its aglycone tomatidine inhibit the growth of P. serpens in axenic cultures. Tomatine, like many other saponins, induces permeabilisation of the cell membrane and a loss of cell content, including the cytosolic enzyme pyruvate kinase. In contrast, tomatidine does not cause permeabilisation of membranes, but instead provokes morphological changes, including vacuolisation. Phytomonas treated with tomatidine show an increased accumulation of labelled neutral lipids (BODYPY-palmitic), a notable decrease in the amount of C24-alkylated sterols and an increase in zymosterol content. These results are consistent with the inhibition of 24-sterol methyltransferase (SMT), which is an important enzyme that is responsible for the methylation of sterols at the 24 position. We propose that the main target of tomatidine is the sterols biosynthetic pathway, specifically, inhibition of the 24-SMT. Altogether, the results obtained in the present paper suggest a more general effect of alkaloids in trypanosomatids, which opens potential therapeutic possibilities for the treatment of the diseases caused by these pathogens

The effect of topographic variables and location on native vegetation density in an arid environment of Saudi Arabia

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