Suppression of Aβ toxicity by puromycin-sensitive aminopeptidase is independent of its proteolytic activity.

The accumulation of β-amyloid (Aβ) peptide in the brain is one of the pathological hallmarks of Alzheimer's disease and is thought to be of primary aetiological significance. In an unbiased genetic screen, we identified puromycin-sensitive aminopeptidase (PSA) as a potent suppressor of Aβ toxicity in a Drosophila model system. We established that coexpression of Drosophila PSA (dPSA) in the flies' brains improved their lifespan, protected against locomotor deficits, and reduced brain Aβ levels by clearing the Aβ plaque-like deposits. However, confocal microscopy and subcellular fractionation of amyloid-expressing 7PA2 cells demonstrated that PSA localizes to the cytoplasm. Therefore, PSA and Aβ are unlikely to be in the same cellular compartment; moreover, when we artificially placed them in the same compartment in flies, we could not detect a direct epistatic interaction. The consequent hypothesis that PSA's suppression of Aβ toxicity is indirect was supported by the finding that Aβ is not a proteolytic substrate for PSA in vitro. Furthermore, we showed that the enzymatic activity of PSA is not required for rescuing Aβ toxicity in neuronal SH-SY5Y cells. We investigated whether the stimulation of autophagy by PSA was responsible for these protective effects. However PSA's promotion of autophagosome fusion with lysosomes required proteolytic activity and so its effect on autophagy is not identical to its protection against Aβ toxicity

Low-level Laser Therapy to the Mouse Femur Enhances the Fungicidal Response of Neutrophils against Paracoccidioides brasiliensis

Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. the goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. the aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. the number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. the highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. the kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)National Institute of Health (US NIH)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fed Univ Alfenas UNIFAL MG, Inst Biomed Sci, Dept Microbiol & Immunol, Alfenas, MG, BrazilFed Univ Alfenas UNIFAL MG, Inst Biomed Sci, Dept Biochem, Alfenas, MG, BrazilState Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, São Paulo, SP, BrazilMassachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USAHarvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USAMIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USAFed Univ Alfenas UNIFAL MG, Inst Biomed Sci, Dept Pathol & Parasitol, Alfenas, MG, BrazilFed Univ São Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, São Paulo, SP, BrazilCNPq: 486135/2012-8CNPq: 304827/2012-6FAPEMIG: CBB-PPM-00119-14National Institute of Health (US NIH): R01AI050875CAPES: AEX-9765-14-0Web of Scienc

Stopping power and depth dose profile of H+ and He+ ion beams in hydroxyapatite thin films.

Hadron therapy is a promising technique to treat deep-seated tumors. For an accurate treatment planning, the energy deposition in the soft and hard human tissue must be well known. Water has been usually employed as a phantom of soft tissues, but other biomaterials, such as hydroxyapatite (HAp), used as bone substitute, are also relevant as a phantom for hard tissues. The stopping power of HAp for H+ and He+ beams has been studied experimentally and theoretically. The measurements have been done using the Rutherford backscattering technique in an energy range of 450-2000 keV for H+ and of 400-5000 keV for He+ projectiles. The theoretical calculations are based in the dielectric formulation together with the MELF-GOS (Mermin Energy-Loss Function – Generalized Oscillator Strengths) method [1] to describe the target excitation spectrum. A quite good agreement between the experimental data and the theoretical results has been found. The depth dose profile of H+ and He+ ion beams in HAp has been simulated by the SEICS (Simulation of Energetic Ions and Clusters through Solids) code [2], which incorporates the electronic stopping force due to the energy loss by collisions with the target electrons, including fluctuations due to the energy-loss straggling, the multiple elastic scattering with the target nuclei, with their corresponding nuclear energy loss, and the dynamical charge-exchange processes in the projectile charge state. The energy deposition by H+ and He+ as a function of the depth are compared, at several projectile energies, for HAp and liquid water, showing important differences.European Regional Development Fun

CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens

The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also available, together with links to PubMed for relevant CT antigen article

A invenção como ofício: as máquinas de preparo e benefício do café no século XIX

The article studies the Brazilian coffee-growing society from the point of view of the generation of inventions and machine innovations aimed at the preparation and processing of coffee beans in the period between 1860 and 1882. Under the protection of the 1830 Patents Law, the machinistas developed their inventions and submitted them to the National Industry Auxiliary Society (Sociedade Auxiliadora da Indústria Nacional - SAIN) for the concession of industrial privilege and later manufacture and commercialization. It is demonstrated how the coffee machinery developed by these inventors-entrepreneurs in Brazil brought to the slave-labour coffee plantation the technological update of agricultural machines existing in the industrial countries and how that has propitiated an improvement in the quality of large-scale coffee bean processing. This fact has made possible not only the consolidation of the country as the largest exporter in the international market, but has also has allowed for changes in the productive structure of the slave-labour plantations.Aborda-se a sociedade cafeeira brasileira sob o aspecto da geração de invenções e inovações de máquinas destinadas ao preparo e benefício do café no período de 1860 a 1882. Sob a proteção da Lei de Patentes de 1830, os machinistas desenvolviam seus inventos, que eram examinados pela Sociedade Auxiliadora da Indústria Nacional (SAIN) para concessão do privilégio industrial e posterior fabricação e comercialização. Demonstra-se como as máquinas de café desenvolvidas por estes inventores-empresários no Brasil trouxeram para a fazenda cafeeira escravista a atualização tecnológica de máquinas agrícolas existentes nos países industriais e propiciaram uma melhoria de qualidade do benefício em grandes quantidades de café. Tal fato tornou possível não só a consolidação do país como maior exportador no mercado internacional, mas permitiu alterações na estrutura produtiva das fazendas escravistas

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors