Leishmanicidal activity of amphotericin B encapsulated in PLGA–DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice

The major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin B (D-AMB), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. For this, AMB nanoencapsulated in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles (Nano-D-AMB) has been developed, and its efficacy was evaluated in the treatment of experimental cutaneous leishmaniasis in C57BL/6 mice, to test if our nano-drug delivery system could favor the reduction of the dose frequency required to achieve the same therapeutic level of free D-AMB, and so, an extended dosing interval. Magnetic citrate-coated maghemite nanoparticles were added to this nanosystem (Nano-D-AMB-MG) aiming to increase controlled release of AMB by magnetohyperthermia. Female mice (N = 6/group) were infected intradermally in the right footpad with promastigotes of Leishmania amazonensis in the metacyclic phase, receiving the following intraperitoneal treatments: 1% PBS for 10 consecutive days; D-AMB at 2 mg/kg/day for 10 days (totalizing 20 mg/kg/animal); Nano-D-AMB and Nano-D-AMB-MG at 6 mg/kg on the 1st, 4th and 7th days and at 2 mg/kg on the 10th day, also totalizing 20 mg/kg/animal by treatment end. The Nano-D-AMB-MG group was submitted to an AC magnetic field, allowing the induction of magnetohyperthermia. The evaluations were through paw diameter measurements; parasite number and cell viability were investigated by limiting dilution assay. D-AMB-coated PLGA–DMSA nanoparticles showed the same efficacy as free D-AMB to reduce paw diameter; however, the Nano-D-AMB treatment also promoted a significantly greater reduction in parasite number and cell viability compared with free D-AMB. The nano-drug AMB delivery system appeared more effective than free D-AMB therapy to reduce the dose frequency required to achieve the same therapeutic level. It thus favors a longer interval between doses, as expected with development of a new nano drug delivery system, and may be useful in the treatment of many different pathologies, from cancer to neurodegenerative diseases.     

Abscisic acid mediates hydrogen peroxide production in peanut induced by water stress

Peanut plants exposed to water stress induced by polyethylene glycol (PEG) accumulated abscisic acid (ABA) and hydrogen peroxide (H₂O₂), the increase being significant at 12 and 24 h after addition, respectively. To address the question whether the increase in H₂O₂ production was related to ABA accumulation, the peanut leaves were pretreated with ABA biosynthesis inhibitor (sodium tungstate) and then exposed to water stress. Under these conditions, a decrease of ABA and H₂O₂ content were found after 12 h. The addition of 100 μM ABA restored H₂O₂ content reaching values similar to those under water stress at 12 h. We concluded that ABA accumulation is the first signal that triggers the H₂O₂ generation in peanut during first 12 h but its subsequent production is partially ABA-independent.     

Population Composition and Ectoparasite Prevalence on Bats (Sturnira ludovici; Phyllostomidae) in Forest Fragments and Coffee Plantations of Central Veracruz,Mexico

Studies comparing the abundance of frugivorous bats in shade‐coffee plantations and forest fragments report contradictory results, and have not taken into account the landscape context in which coffee plantations are immersed. Variables of population composition such as abundance, sex proportion, and reproductive condition, together with biological tags (i.e., bat fly prevalence), can provide information about spatiotemporal dynamics of habitats used by bats. In the central part of Veracruz, Mexico, we compared population variables and ectoparasite prevalence of the highland yellow‐shouldered bat (Sturnira ludovici) in two landscapes, one dominated by shade‐coffee plantations and another by forest fragments. Comparing these attributes between these two landscapes will increase our knowledge about the role of this agro‐ecosystem in the conservation of this species, which is an important seed disperser of cloud forest vegetation. Total abundance and proportion of females was greater in forest fragments than in coffee plantations, whereas the percentage of reproductive females and bat fly prevalence was similar between landscapes. Our results show that landscapes with forest fragments harbor the greatest abundance of S. ludovici, but shade‐coffee plantations also are utilized by S. ludovici and likely adjacent forest remnants provide enough food resources for this species and other frugivores. Moreover, this study provides more evidence documenting the importance of preserving the last cloud forest fragments in the central region of Veracruz, Mexico, and suggests that using shade‐coffee plantations to connect forest fragments may be an effective way of maintaining populations of S. ludovici and likely other volant frugivores.     

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.     

Rice bran enzymatic extract restores endothelial function and vascular contractility in obese rats by reducing vascular inflammation and oxidative stress

BackgroundRice bran enzymatic extract (RBEE) used in this study has shown beneficial activities against dyslipidemia, hyperinsulinemia and hypertension. Our aim was to investigate the effects of a diet supplemented with RBEE in vascular impairment developed in obese Zucker rats and to evaluate the main mechanisms mediating this action.Methods and resultsObese Zucker rats were fed a 1% and 5% RBEE-supplemented diet (O1% and O5%). Obese and their lean littermates fed a standard diet were used as controls (OC and LC, respectively). Vascular function was evaluated in aortic rings in organ baths. The role of nitric oxide (NO) was investigated by using NO synthase (NOS) inhibitors. Aortic expression of endothelial NOS (eNOS), inducible NOS (iNOS), tumor necrosis factor (TNF)-α and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and superoxide production in arterial wall were determined. Endothelial dysfunction and vascular hyperreactivity to phenylephrine in obese rats were ameliorated by RBEE treatment, particularly with 1% RBEE. Up-regulation of eNOS protein expression in RBEE-treated aortas should contribute to this activity. RBEE attenuated vascular inflammation by reducing aortic iNOS and TNF-α expression. Aortas from RBEE-treated groups showed a significant decrease of superoxide production and down-regulation of NADPH oxidase subunits.ConclusionRBEE treatment restored endothelial function and vascular contractility in obese Zucker rats through a reduction of vascular inflammation and oxidative stress. These results show the nutraceutical potential of RBEE to prevent obesity-related vascular complications.     

Heating and microwave assisted SPPS of C-terminal acid peptides on trityl resin: the truth behind the yield

Despite correct purity of crude peptides prepared on trityl resin by Fmoc/tBu microwave assisted solid phase peptide synthesis, surprisingly, lower yields than those expected were obtained while preparing C-terminal acid peptides. This could be explained by cyclization/cleavage through diketopiperazine formation during the second amino acid deprotection and third amino acid coupling. However, we provide here evidence that this is not the case and that this yield loss was due to high temperature promoted hydrolysis of the 2-chlorotrityl ester, yielding premature cleavage of the C-terminal acid peptides.     

Which are, what is their status and what can we expect from ecosystem services provided by Spanish rivers and riparian areas?

By applying the framework proposed by Millennium Ecosystem Assessment, we analysed the current state and trends of 20 ecosystem services provided by Spanish rivers and riparian areas using 139 indicators. We compared the obtained results with the Europe and UK assessment. It is the first document that attempts to analyse the importance of services provided by Spanish rivers and riparian areas, and it forms part of the evaluation carried out for the Spanish Millennium Ecosystem Assessment. Among the provisioning services, freshwater, hydropower energy and genetic resources were classified as high importance, and water regulation and self-purification capacity, and natural hazard mitigation are among the regulating services, with landscape-aesthetic values and recreation and ecotourism featuring among the cultural services. About 61 % of the assessed ecosystem services are currently declining or degrading, but are higher than the percentage calculated for Europe (45 %) or for the UK (53 %). All regulating services are degrading, especially water regulation, natural hazard mitigation, soil formation and fertility and biological control, and the cultural services related to rural populations. Likewise, the biodiversity of Spanish aquatic ecosystems is decreasing rapidly. Land use changes and overexploitation of biological and mineral raw materials have been the main direct drivers of change in Spanish rivers and riparian zones, and relate directly to increase urbanised areas and irrigated agriculture. Finally, we draw some considerations on alternative models for aquatic ecosystems management which maintain aquatic ecosystem services and their biodiversity.     

The SH2 Domain Interaction Landscape

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Highlights? The recognition specificity of 70 SH2 domains is probed ? Recognition specificity diverges faster than sequence ? PepspotDB is a database of protein interactions mediated by SH2 domains