Photorepair of Either CPD or 6-4PP DNA Lesions in Basal Keratinocytes Attenuates Ultraviolet-Induced Skin Effects in Nucleotide Excision Repair Deficient Mice.

Ultraviolet (UV) radiation is one of the most genotoxic, universal agents present in the environment. UVB (280-315 nm) radiation directly damages DNA, producing cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs). These photolesions interfere with essential cellular processes by blocking transcription and replication polymerases, and may induce skin inflammation, hyperplasia and cell death eventually contributing to skin aging, effects mediated mainly by keratinocytes. Additionally, these lesions may also induce mutations and thereby cause skin cancer. Photolesions are repaired by the Nucleotide Excision Repair (NER) pathway, responsible for repairing bulky DNA lesions. Both types of photolesions can also be repaired by distinct (CPD- or 6-4PP-) photolyases, enzymes that specifically repair their respective photolesion by directly splitting each dimer through a light-dependent process termed photoreactivation. However, as photolyases are absent in placental mammals, these organisms depend solely on NER for the repair of DNA UV lesions. However, the individual contribution of each UV dimer in the skin effects, as well as the role of keratinocytes has remained elusive. In this study, we show that in NER-deficient mice, the transgenic expression and photorepair of CPD-photolyase in basal keratinocytes completely inhibited UVB-induced epidermal thickness and cell proliferation. On the other hand, photorepair by 6-4PP-photolyase in keratinocytes reduced but did not abrogate these UV-induced effects. The photolyase mediated removal of either CPDs or 6-4PPs from basal keratinocytes in the skin also reduced UVB-induced apoptosis, ICAM-1 expression, and myeloperoxidase activation. These findings indicate that, in NER-deficient rodents, both types of photolesions have causal roles in UVB-induced epidermal cell proliferation, hyperplasia, cell death and inflammation. Furthermore, these findings also support the notion that basal keratinocytes, instead of other skin cells, are the major cellular mediators of these UVB-induced effects.

Baryon Acoustic Oscillations from Integrated Neutral Gas Observations: an instrument to observe the 21cm hydrogen line in the redshift range 0.13 < z < 0.45 - status update.

BINGO (BAO from Integrated Neutral Gas Observations) is a unique radio telescope designed to map the intensity of neutral hydrogen distribution at cosmological distances, making the first detection of Baryon Acoustic Oscillations (BAO) in the frequency band 980 MHz - 1260 MHz, corresponding to a redshift range 0.127 < z < 0.449. BAO is one of the most powerful probes of cosmological parameters and BINGO was designed to detect the BAO signal to a level that makes it possible to put new constraints on the equation of state of dark energy. The telescope will be built in Paraíba, Brazil and consists of two \thicksim 40m mirrors, a feedhorn array of 50 horns, and no moving parts, working as a drift-scan instrument. It will cover a 15 ^{\circ} ∘ declination strip centered at \sim \delta ∼ δ =-15 ^{\circ} ∘ , mapping \sim ∼ 5400 square degrees in the sky. The BINGO consortium is led by University of São Paulo with co-leadership at National Institute for Space Research and Campina Grande Federal University (Brazil). Telescope subsystems have already been fabricated and tested, and the dish and structure fabrication are expected to start in late 2020, as well as the road and terrain preparation.

Characterization and in vitro antitumor activity of polymeric nanoparticles loaded with Uncaria tomentosa extract.

Uncaria tomentosa (UT) extracts have been shown to have promising anti-tumor activity. We hypothesized that its incorporation into nanostructured systems could improve the anticancer properties. Here, poly-e-caprolactone (PCL) and poly-d,l-lactide-co-glycolide (PLGA) were employed to generate nanoparticles loaded with UT extract in a single emulsion solvent evaporation method. The nanoparticles were characterized by particle size, zeta potential, morphology and entrapment efficiency along with stability and release profiles. The nanoparticles presented entrapment efficiencies above 60% and a mean diameter below 300nm. UT-PCL nanoparticles presented higher entrapment efficiency and mean particle size as well as a slow release rate. The UT-PLGA nanoparticles showed higher drug loading. Two prostate cancer cell-lines, LNCaP and DU145 that were derived from metastatic sites, served as model systems to assess cytotoxicity and anti-cancer activity. In vitro, both formulations reduced the viability of DU145 and LNCaP cells. Yet, the UT-PLGA nanoparticles showed higher cytotoxicity towards DU145 cells while the UTPCL against LNCaP cells. The results confirm that the incorporation of UT into nanoparticles could enhance its anti-cancer activities that can offer a viable alternative for the treatment of prostrate canner and highlights the potential of nanostructured systems to provide a promising methodology to enhance the activity of natural extracts.

Cerebral palsy in adult patients: constraint-induced movement therapy is effective to reverse the nonuse of the affected upper limb / A eficácia da terapia por contensão induzida em pacientes adultos com paralisia cerebral

ABSTRACT Objective To determine if the original protocol of Constraint-Induced Movement Therapy (CIMT), is adequate to reverse the nonuse of the affected upper limb (AUL) in patients with Cerebral Palsy (CP) in adulthood. Method The study included 10 patients diagnosed with CP hemiparesis had attended the adult protocol CIMT, from January/August 2009/2014. Results Average age 24.6 (SD 9.44); MAL average pretreatment How Often (HO) = 0.72 and How Well (HW) = 0.68 and post-treatment HO = 3.77 and HW = 3.60 (p ≤ 0.001) and pretreatment WMFT average = 21.03 and post-treatment average = 18.91 (p = 0.350). Conclusion The constraint-induced movement therapy is effective to reverse the nonuse learn of the AUL in adult patients with CP.

RESUMO Objetivo Determinar se o protocolo original da Terapia por Contensão Induzida (TCI), é adequado para reverter o não uso do membro superior afetado (MSA) em pacientes com Paralisia Cerebral (PC) na fase adulta. Método Foram incluídos no estudo 10 pacientes com diagnóstico de PC hemiparéticos que haviam realizado o protocolo adulto da TCI, no período de janeiro/2009 a agosto/2014. Resultados Média de idade 24,6 (DP 9,44); MAL média pré-tratamento Quantidade (QT) = 0,72 e Qualidade (QL) = 0,68 e no pós-tratamento QT = 3,77 e QL = 3,60 (p ≤ 0,001) e WMFT média pré-tratamento = 21,03 e média pós-tratamento = 18,91 (p = 0,350). Conclusão A terapia por contensão induzida é eficaz para reverter o não uso do MSA em pacientes adultos com PC.

Cerebral palsy in adult patients: constraint-induced movement therapy is effective to reverse the nonuse of the affected upper limb.

OBJECTIVE: To determine if the original protocol of Constraint-Induced Movement Therapy (CIMT), is adequate to reverse the nonuse of the affected upper limb (AUL) in patients with Cerebral Palsy (CP) in adulthood. METHOD: The study included 10 patients diagnosed with CP hemiparesis had attended the adult protocol CIMT, from January/August 2009/2014. RESULTS: Average age 24.6 (SD 9.44); MAL average pretreatment How Often (HO) = 0.72 and How Well (HW) = 0.68 and post-treatment HO = 3.77 and HW = 3.60 (p ≤ 0.001) and pretreatment WMFT average = 21.03 and post-treatment average = 18.91 (p = 0.350). CONCLUSION: The constraint-induced movement therapy is effective to reverse the nonuse learn of the AUL in adult patients with CP.

Electrical detection of dengue biomarker using egg yolk immunoglobulin as the biological recognition element.

Nonstructural protein 1 (NS1) is secreted by dengue virus in the first days of infection and acts as an excellent dengue biomarker. Here, the direct electrical detection of NS1 from dengue type 2 virus has been achieved by the measurement of variations in open circuit potential (OCP) between a reference electrode and a disposable Au electrode containing immobilized anti-NS1 antibodies acting as immunosensor. Egg yolk immunoglobulin (IgY) was utilized for the first time as the biological recognition element alternatively to conventional mammalian antibodies in the detection of dengue virus NS1 protein. NS1 protein was detected in standard samples in a 0.1 to 10 µg.mL(-1) concentration range with (3.2 ± 0.3) mV/µg.mL(-1) of sensitivity and 0.09 µg.mL(-1) of detection limit. Therefore, the proposed system can be extended to detect NS1 in real samples and provide an early diagnosis of dengue.

Isolation, characterization and phylogeny of sponge-associated bacteria with antimicrobial activities from Brazil.

Bacteria associated with marine sponges represent a rich source of bioactive metabolites. The aim of this study was to isolate and characterize bacteria with antimicrobial activities from Brazilian sponges. A total of 158 colony-forming units were isolated from nine sponge species. Among these, 12 isolates presented antimicrobial activities against pathogenic bacteria. Based on comparative sequence analysis of their 16S rRNA genes, the sponge-associated bacterial strains could be subdivided into three phylogenetically different clusters. Five strains were affiliated with Firmicutes (genera Bacillus and Virgibacillus), three with alpha-Proteobacteria (Pseudovibrio sp.) and four with gamma-Proteobacteria (genera Pseudomonas and Stenotrophomonas). The sponge-associated bacterial strains Pseudomonas fluorescens H40 and H41 and Pseudomonas aeruginosa H51 exhibited antimicrobial activity against both Gram-negative and Gram-positive bacteria, including strains such as vancomycin-resistant Enterococcus faecium and multiresistant Klebsiella pneumoniae. Bacillus pumilus Pc31 and Pc32, Pseudovibrio ascidiaceicola Pm31 and Ca31 and Pseudovibrio denitrificans Mm37 strains were more effective against Gram-positive bacteria. These findings suggest that the identified strains may contribute to the search for new sources of antimicrobial substances, an important strategy for developing alternative therapies to treat infections caused by multidrug-resistant bacteria.