PBP4: A New Perspective on Staphylococcus aureus β-Lactam Resistance.

β-lactam antibiotics are excellent drugs for treatment of staphylococcal infections, due to their superior efficacy and safety compared to other drugs. Effectiveness of β-lactams is severely compromised due to resistance, which is widespread among clinical strains of Staphylococcus aureus. β-lactams inhibit bacterial cells by binding to penicillin binding proteins (PBPs), which perform the penultimate steps of bacterial cell wall synthesis. Among PBPs of S. aureus, PBP2a has received the most attention for the past several decades due to its preeminent role in conferring both high-level and broad-spectrum resistance to the entire class of β-lactam drugs. Studies on PBP2a have thus unraveled incredible details of its mechanism of action. We have recently identified that an uncanonical, low molecular weight PBP of S. aureus, PBP4, can also provide high-level and broad-spectrum resistance to the entire class of β-lactam drugs at a level similar to that of PBP2a. The role of PBP4 has typically been considered not so important for β-lactam resistance of S. aureus, and as a result its mode of action remains largely unknown. In this article, we review our current knowledge of PBP4 mediating β-lactam resistance in S. aureus

Anti-EGFR therapy: strategies in head and neck squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that activates downstream signaling pathways, including the Ras-MEK-Erk and PI3K-AKT pathways, leading to cell proliferation, resistance to apoptosis, angiogenesis and the ability to metastasize. EGFR overexpression is a significant finding in cancer, particularly in head and neck cancer, where it is also associated with a poor prognosis. In recent years, several molecules have been designed to inhibit EGFR activation. Among the many available anti-EGFR drugs, only cetuximab was approved for the treatment of head and neck cancers. However, no predictive biomarkers of cetuximab response are currently known. In the present review, we provide an updated assessment of EGFR biology and its clinical impact in head and neck cancers. A special emphasis is placed on novel patents of EGFR-inhibitors that are anticipated to diversify the anti-EGFR therapies available to treat head and neck cancers. In particular, we outline a new class of irreversible multi-target inhibitors (e.g. afatinib, icotinib, CUDC-101), which may significantly contribute to new head and neck cancer therapies.The authors would like to acknowledge Dr. Laura Mussel white for critical revision of the manuscript. André L. Carvalho and Rui M. Reis have a National Counsel of Technological and Scientific Development (CNPq) scholarship. A.C.C, has a FAPESP (2013/13834-7) scholarship.info:eu-repo/semantics/publishedVersio

Modelagem matemática da secagem de bagaço de laranja associado ao método convectivo e radiação infravermelha

Sem informaçãoMathematical modeling enables dimensioning of dryers, optimization of drying conditions and the evaluation of process performance. The aim of this research was to describe the behavior of orange bagasse drying using Page's and Fick's second law models, and to assess activation energy (using Arrhenius equation), moisture content, water activity and bulk density of product at the end of the process. The drying experimental assays were performed in 2011 with convective air temperature between 36 and 64 degrees C and infrared radiation application time in the range from 23 to 277 s in accordance with the experimental central composite rotatable design. Analysis of variance and F-test were applied to results. At the end of the drying process, moisture content was about 0.09 to 0.87 db and water activity was between 0.25 and 0.87. Bulk density did not vary under studied conditions. Empirical Page's model demonstrated better representation of experimental data than the Fick's model for spheres. Activation energy values were about 18.491; 14.975 and 11.421 kJ mol(-1) for infrared application times of 60; 150 e 244 s, respectively.Mathematical modeling enables dimensioning of dryers, optimization of drying conditions and the evaluation of process performance. The aim of this research was to describe the behavior of orange bagasse drying using Page's and Fick's second law models, an191211781184Sem informaçãoSem informaçãosem informaçãoA modelagem matemática permite o dimensionamento de secadores, otimização das condições de secagem e avaliação do desempenho do processo. O objetivo deste trabalho foi descrever o comportamento da secagem de bagaço de laranja utilizando-se os modelos de

AÇÃO COMUNICATIVA E AÇÃO DIALÓGICA: CONTRIBUIÇÕES PARA UMA EDUCAÇÃO LIBERTADORA

O presente trabalho tem por objetivo apresentar as idéias deHabermas e Paulo Freire, demonstrando a convergência de ambas no que serefere à emancipação dos sujeitos na sociedade e na educação. Primeiramente,abordar-se-á a construção da Teoria da Ação Comunicativa de Habermas.Em seguida, serão trazidos alguns elementos do pensamento de Paulo Freire.Por fim, far-se-á uma justaposição das idéias de ambos os autores

Ion-exchange resin as a new tool for characterisation of coordination compounds and MOFs by NMR spectroscopy

1H and 13C NMR spectroscopy is used to investigate the organic constituents of metal complexes, MOFs and coordination compounds synthesised under solvothermal and precipitation conditions. The elucidation of the ligands in paramagnetic compounds bearing Cu2+(d9), Gd3+ (f7), Eu3+ (f6), Fe3+(d5), ions after treatment with a cationic exchange resin is possible. We prove the efficiency of two post-synthesis linker modifications on diamagnetic IRMOF-3 Zn2+ (d10) with ethyl isocyanate and benzyl bromide

Janus kinase mutations in mice lacking PU.1 and Spi-B drive B cell leukemia through reactive oxygen species-induced DNA damage

Precursor B cell acute lymphoblastic leukemia (B-ALL) is caused by genetic lesions in developing B cells that function as drivers for the accumulation of additional mutations in an evolutionary selection process. We investigated secondary drivers of leukemogenesis in a mouse model of B-ALL driven by PU.1/Spi-B deletion (Mb1-CreΔPB). Whole-exome-sequencing analysis revealed recurrent mutations in Jak3 (encoding Janus kinase 3), Jak1, and Ikzf3 (encoding Aiolos). Mutations with a high variant-allele frequency (VAF) were dominated by C¡T transition mutations that were compatible with activation-induced cytidine deaminase, whereas the majority of mutations, with a low VAF, were dominated by C¡A transversions associated with 8-oxoguanine DNA damage caused by reactive oxygen species (ROS). The Janus kinase (JAK) inhibitor ruxolitinib delayed leukemia onset, reduced ROS and ROS-induced gene expression signatures, and altered ROS-induced mutational signatures. These results reveal that JAK mutations can alter the course of leukemia clonal evolution through ROS-induced DNA damage

Projeto Orla: análise dos equipamentos de esporte e lazer da praia de Atalaia em Aracaju/SE

Rede Cede

Is urinary density an adequate predictor of urinary osmolality?

Urinary density (UD) has been routinely used for decades as a surrogate marker for urine osmolality (U-osm). We asked if UD can accurately estimate U-osm both in healthy subjects and in different clinical scenarios of kidney disease. UD was assessed by refractometry. U-osm was measured by freezing point depression in spot urines obtained from healthy volunteers (N = 97) and in 319 inpatients with acute kidney injury (N = 95), primary glomerulophaties (N = 118) or chronic kidney disease (N = 106). UD and U-osm correlated in all groups (p < 0.05). However, a wide range of U-osm values was associated with each UD value. When UD was <= 1.010, 28.4% of samples had U-osm above 350 mOsm/kg. Conversely, in 61.6% of samples with UD above 1.020, U-osm was below 600 mOsm/kg. As expected, U-osm exhibited a strong relationship with serum creatinine (S-creat), whereas a much weaker correlation was found between UD and Screat. We found that UD is not a substitute for U-osm. Although UD was significantly correlated with U-osm, the wide dispersion makes it impossible to use UD as a dependable clinical estimate of U-osm. Evaluation of the renal concentrating ability should be based on direct determination of U-osm1

Mutation profling of cancer drivers in Brazilian colorectal cancer

The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%), TP53 (56.0%), KRAS (52.7%), PIK3CA (15.4%) and FBXW7 (10.9%) genes. Overall, genes in the MAPK/ERK, PIK3/AKT, NOTCH and receptor tyrosine kinase signaling pathways were mutated in 68.0%, 23.1%, 16.5%, and 15.3% of patients, respectively. MSI was found in 13.3% of tumors, most of which were proximal (52.4%, P< 0.001) and had a high mutation burden. European genetic ancestry was predominant (median of 83.1%), followed by Native American (4.1%), Asian (3.4%) and African (3.2%). NF1 and BRAF mutations were associated with African ancestry, while TP53 and PIK3CA mutations were inversely correlated with Native American ancestry. Our study suggests that Brazilian CRC patients exhibit a mutation profile similar to other populations and identify the most frequently mutated genes, which could be useful in future target therapies and molecular cancer screening strategies.We are thankful to Barretos Cancer Hospital. This work was supported by the Brazilian Federal Agency for the Support and Evaluation of Graduate Education (CAPES, Brazil), the National Council for Scientifc and Technological Development (CNPq, Brazil), and the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer, Brazil)

Unveiling the anticancer potential of the ethanolic extract from Trichoderma asperelloides

The discovery of new therapeutic alternatives for cancer treatment is essential for improving efficacy and specificity, overcoming resistance, and enabling a more personalized approach for each patient. We investigated the antitumor activity of the crude ethanolic extract of the fungus Trichoderma asperelloides (ExtTa) and its interaction with chemotherapeutic drugs. It was observed, by MTT cytotoxicity assay, that ExtTa significantly reduced cell viability in breast adenocarcinoma, glioblastoma, lung carcinoma, melanoma, colorectal carcinoma, and sarcomas cell lines. The highest efficacy and selectivity of ExtTa were found against glioblastoma T98G and colorectal HCT116 cell lines. ExtTa is approximately four times more cytotoxic to those tumor cells than to non-cancer cell lines. A synergistic effect between ExtTa and doxorubicin was found in the treatment of osteosarcoma Saos-2 cells, as well as with 5-fluorouracil in the treatment of HCT116 colorectal carcinoma cells using CompuSyn software. Our data unravel the presence of bioactive compounds with cytotoxic effects against cancer cells present in T. asperelloides ethanolic crude extract, with the potential for developing novel anticancer agents