Intragenic antimicrobial peptides (IAPs) from human proteins with potent antimicrobial and anti-inflammatory activity

Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected using the software Kamal, synthesized by solid phase chemistry, and had their interactions with model phospholipid vesicles investigated by differential scanning calorimetry and circular dichroism. Their antimicrobial activity against bacteria, yeasts and filamentous fungi was determined, along with their cytotoxicity towards erythrocytes. Our data demonstrates that Hs IAPs are capable to bind model membranes while attaining α-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1μM. Hs02, a novel sixteen residue long internal peptide (KWAVRIIRKFIKGFISNH2) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-α in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-α in LPSprimed cells at the lowest assayed concentration, 0.1 μM. A three-dimensional solution structure of Hs02 bound to DPC micelles was determined by Nuclear Magnetic Resonance. Our work exemplifies how the human genome can be mined for molecules with biotechnological potential in human health and demonstrates that IAPs are actual alternatives to antimicrobial peptides as pharmaceutical agents or in their many other putative applications

Desafíos para la recolección de sangre y el análisis bioquímico en un gran estudio multicéntrico con adolescentes en las escuelas: lecciones del ERICA en Brasil

The Study of Cardiovascular Risk in Adolescents (ERICA) is a pioneering study that aimed to assess the prevalence of cardiovascular risk factors, including metabolic syndrome components in Brazilian adolescents. This study aims to describe the methodological aspects related to blood collection as well as to report pertaining results of the preparation, transport, storage, and exams in ERICA. Exams in ERICA were performed in a single laboratory and blood samples were collected in schools in a standardized manner. Logistics involved air transportation of samples to the reference laboratory with controlled temperature since sample collection. The serum was stored in local biorepositories in four centers to be used in future analyses. During the study, 284,247 exams were performed and rate of participation in exams was 56.2%, thus involving 40,732 adolescents. From the total, 92.6% of the samples reached the reference laboratory maintaining the temperature between 0-10°C. No clinical significant changes in results due to temperature changes were identified. External quality control recorded satisfactory results in 98.7% of the evaluations. Four biorepositories with samples of 7,785 adolescents were created. Thus, we can consider that the logistics adopted in ERICA was fairly successful and description of this as well as the difficulties experienced in Brazil can inform and facilitate the planning of future studies, especially in developing countries.O Estudo de Riscos de Cardiovasculares em Adolescentes (ERICA) é um estudo pioneiro que tem como objetivo avaliar a prevalência de fatores de risco cardiovascular, incluindo componentes da síndrome metabólica, entre adolescentes brasileiros. Este artigo tem como objetivo descrever os aspectos metodológicos relacionados com a coleta de sangue, assim como informar os resultados da preparação, transporte, armazenamento e exames no ERICA. Os exames foram realizados em um único laboratório e as amostras de sangue foram coletadas de forma padronizada. A logística envolveu o transporte aéreo das amostra até o laboratório de referência, com a temperatura controlada desde a coleta do sangue. O soro foi armazenado em biorrepositores locais em quatro centros e se serão utilizados em análises futuras. Durante o estudo foram realizados 284.247 exames e a taxa de participação foi de 56,2%, representando 40.732 adolescentes. Do total, 92,6% das amostras chegaram ao laboratório de referência mantendo a temperatura entre 0-10°C. Não foram identificadas alterações clínicas significativas nos resultados devido a mudanças de temperatura. O controle de qualidade externo registrou resultados satisfatórios em 98,7% das avaliações. Foram criados quatro biorrepositores com amostras de 7.785 adolescentes. Assim, podemos considerar que a logística adotada no ERICA foi bastante exitosa e sua descrição, tal como as dificuldades experimentadas no Brasil, podem informar e facilitar o planejamento de futuros estudos, especialmente nos países em desenvolvimento.El Estudio de Riesgos Cardiovasculares en Adolescentes (ERICA) es un estudio pionero que tiene como objetivo evaluar la prevalencia de factores de riesgo cardiovascular, incluyendo componentes del síndrome metabólico en adolescentes brasileños. Este estudio tiene como objetivo describir los aspectos metodológicos relacionados con la recolección de sangre, así como informar sobre los resultados de la preparación, transporte, almacenamiento y exámenes en el ERICA. Los exámenes en ERICA se realizaron en un solo laboratorio y se recogieron muestras de sangre en las escuelas de manera estandarizada. La logística involucró el transporte aéreo de muestras al laboratorio de referencia con temperatura controlada desde la recolección de muestras. El suero fue almacenado en biorepositories locales en cuatro centros que se utilizarán en análises futuros. Durante el estudio se realizaron 284.247 exámenes y la tasa de participación fue de 56,2%, lo que involucró a 40.732 adolescentes. Del total, el 92,6% de las muestras alcanzaron el laboratorio de referencia manteniendo la temperatura entre 0-10°C. No se identificaron cambios clínicos significativos en los resultados debido a cambios de temperatura. El control de calidad externo registró resultados satisfactorios en el 98,7% de las evaluaciones. Se crearon cuatro biorrepositores con muestras de 7.785 adolescentes. Así, podemos considerar que la logística adoptada en el ERICA fue bastante exitosa y su descripción así como las dificultades experimentadas en Brasil pueden informar y facilitar la planificación de futuros estudios, especialmente en los países en desarrollo

Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages

Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of Leishmania and severe side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-β, TNF-α and IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-β release. The effect of PSN-1 on IL-12 and TNF-α secretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications

Cinerascetins, new peptides from Hypsiboas cinerascens : MALDI LIFT-TOF-MS/MS de novo sequence and imaging analysis

The continuous search for antimicrobial candidates pushes the pursuit of compounds in the most diverse organisms. Amphibians are known as a prolific source of antibacterial peptides. Based on the rich biodiversity of the Amazon region the unexplored green-tree frog (Hypsiboas cinerascens) was studied for its skin secretion peptide content. Chromatographic separations and established tandem mass spectrometry (MS/MS) methods were used for sequencing the primary structures of the purified compounds. De novo sequencing lead to the identification of five new peptides related to hylaseptin P1, displaying an aminated C-terminal. Sequencing of the complementary deoxyribonucleic acid (cDNA) analysis allowed the disambiguation of isobaric amino-acids for C-01. Matrix assisted laser desorption ionization (MALDI) was carried out, demonstrating the in situ co-occurrence of the identified peptides in the dorsal skin. The major peptide C-01 was synthesized and assayed against a selection of microorganisms displaying minimal inhibitory concentrations (MICs) ranging from 4 to 16 µM

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good