A dairy bacterium displays in vitro probiotic properties for the pharyngeal mucosa by antagonizing group A streptococci and modulating the immune response

The probiotic approach represents an alternative strategy in the prevention and treatment of infectious diseases, not only at the intestinal level but also at other sites of the body where the microbiota plays a role in the maintenance of physiological homeostasis. In this context, we evaluated in vitro the potential abilities of probiotic and dairy bacteria in controlling Streptococcus pyogenes infections at the pharyngeal level. Initially, we analyzed bacterial adhesion to FaDu hypopharyngeal carcinoma cells and the ability to antagonize S. pyogenes on FaDu cell layers and HaCat keratinocytes. Due to its promising adhesive and antagonistic features, we studied the dairy strain Lactobacillus helveticus MIMLh5, also through in vitro immunological experiments. First, we performed quantification of several cytokines and measurement of NF-\u3baB activation in FaDu cells. MIMLh5 efficiently reduced the induction of interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-\u3b1), in a dose-dependent manner. After stimulation of cells with IL-1\u3b2, active NF-\u3baB was still markedly lowered. Nevertheless, we observed an increased secretion of IL-6, gamma interferon (IFN-\u3b3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) under these conditions. These effects were associated with the ability of MIMLh5 to enhance the expression of the heat shock protein coding gene hsp70. In addition, MIMLh5 increased the GM-CSF/G-CSF ratio. This is compatible with a switch of the immune response toward a TH1 pathway, as supported by our observation that MIMLh5, once in contact with bone marrow-derived dendritic cells, triggered the secretion of TNF-\u3b1 and IL-2. In conclusion, we propose MIMLh5 as a potential probiotic bacterium for the human pharynx, with promising antagonistic and immunomodulatory properties

Manejo da carga de frutos de macieira da cultivar Gala através da poda de precisão.

A poda de precisão para manejar a carga de frutos é um conceito que visa determinar o número de frutos suficiente para obter uma boa produção, objetivando frutos de melhor qualidade e maior massa e tamanho. Além disso, a poda de precisão objetiva reduzir o tempo dispendido com o raleio de frutos. Este processo engloba três etapas: realização da poda de precisão para deixar uma carga de gemas predefinida na planta; raleio químico para reduzir o número inicial de flores; raleio manual para ajustar o número de frutos ao estimado para a colheita. Reduzindo o número de gemas floríferas da planta precocemente, através da poda, pode-se reduzir a competição entre flor e fruto resultando em maior disponibilidade de fotoassimilados para os frutos remanescentes, com tamanho e qualidade. Para determinar o número apropriado de gemas por planta deve-se levar em consideração a produção e a massa média dos frutos desejadas. É importante trabalhar com um número maior de gemas floríferas do que o necessário, já que podem ocorrer fatores naturais que impossibilitam a formação da gema, como geada, má polinização e pouca viabilidade de flor. Desta forma, o presente trabalho teve por objetivo implementar o sistema de poda de precisão na cultivar Gala, em pomar comercial no município de Vacaria, RS.(Embrapa Uva e Vinho. Documentos, 99

NUP98-fusion transcripts characterize different biological entities within acute myeloid leukemia: A report from the AIEOP-AML group.

In the last years, collaborative studies have joined to link the degree of genetic heterogeneity of acute myeloid leukemia (AML) to clinical outcome,1, 2 allowing risk stratification before therapy and guiding post-induction treatment of children with AML. So far, still half of these patients, whose disease is usually characterized by a grim prognosis, lack a known biomarker offering opportunities of targeted treatment

Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human Caco-2 intestinal cells

Intestinal inflammation is a natural process crucial for the maintenance of gut functioning. However, abnormal or prolonged inflammatory responses may lead to the onset of chronic degenerative diseases, typically treated by means of pharmacological interventions. Dietary strategies for the prevention of inflammation are a safer alternative to pharmacotherapy. Anthocyanins and other polyphenols have been documented to display anti-inflammatory activity. In the present study, three bioactive fractions (anthocyanin, phenolic, and water-soluble fractions) were extracted from a wild blueberry powder. The Caco-2 intestinal model was used to test the immunomodulatory effect of the above fractions. Only the anthocyanin-rich fraction reduced the activation of NF-\u3baB, induced by IL-1\u3b2 in intestinal epithelial Caco-2 cells. Specifically, concentrations of 50 and 100 \u3bcg mL(-1) decreased NF-\u3baB activation by 68.9 and 85.2%, respectively (p 64 0.05). These preliminary results provide further support for the role of food bioactives as potential dietary anti-inflammatory agents

In Vitro Functional and Immunomodulatory Properties of the Lactobacillus helveticus MIMLh5-Streptococcus salivarius ST3 Association That Are Relevant to the Development of a Pharyngeal Probiotic Product

The use of proper bacterial strains as probiotics for the pharyngeal mucosa is a potential prophylactic strategy for upper respiratory tract infections. In this context, we characterized in vitro the functional and immunomodulatory properties of the strains Lactobacillus helveticus MIMLh5 and Streptococcus salivarius ST3 that were selected during previous investigations as promising pharyngeal probiotics. In this study, we demonstrated in vitro that strains MIMLh5 and ST3, alone and in combination, can efficiently adhere to pharyngeal epithelial cells, antagonize Streptococcus pyogenes, and modulate host innate immunity by inducing potentially protective effects. In particular, we found that the strains MIMLh5 and ST3 activate U937 human macrophages by significantly inducing the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-\u3b1). Nonetheless, the induction of the anti-inflammatory interleukin-10 (IL-10) by MIMLh5 or ST3 was never lower than that of TNF-\u3b1, suggesting that these bacteria can potentially exert a regulatory rather than a proinflammatory effect. We also found that the strains MIMLh5 and ST3 induce cyclooxygenase 2 (COX-2) expression and demonstrated that toll-like receptor 2 (TLR-2) participates in the recognition of the strains MIMLh5 and ST3 by U937 cells. Finally, we observed that these microorganisms grow efficiently when cocultured in milk, suggesting that the preparation of a milk-based fermented product containing both MIMLh5 and ST3 can be a practical solution for the administration of these bacteria. In conclusion, we propose the combined use of L. helveticus MIMLh5 and S. salivarius ST3 for the preparation of novel products that display probiotic properties for the pharyngeal mucosa

A Systems Biology Approach to Characterize the Regulatory Networks Leading to Trabectedin Resistance in an In Vitro Model of Myxoid Liposarcoma

Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parental 402-91 cell line to stepwise increases in drug concentration. The aim of this study was to compare mRNAs, miRNAs and proteins profiles of 402-91 and 402-91/ET cells through a systems biology approach. We identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402-91 and 402-91/ET cell lines. Interestingly three miRNAs among those differentially expressed, miR-130a, miR-21 and miR-7, harbored CHOP binding sites in their promoter region. We used computational approaches to integrate the three regulatory layers and to generate a molecular map describing the altered circuits in sensitive and resistant cell lines. By combining transcriptomic and proteomic data, we reconstructed two different networks, i.e. apoptosis and cell cycle regulation, that could play a key role in modulating trabectedin resistance. This approach highlights the central role of genes such as CCDN1, RB1, E2F4, TNF, CDKN1C and ABL1 in both pre- and post-transcriptional regulatory network. The validation of these results in in vivo models might be clinically relevant to stratify myxoid liposarcoma patients with different sensitivity to trabectedin treatment

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Shedding light on typical species: Implications for habitat monitoring

Habitat monitoring in Europe is regulated by Article 17 of the Habitats Directive, which suggests the use of typical species to assess habitat conservation status. Yet, the Directive uses the term “typical” species but does not provide a definition, either for its use in reporting or for its use in impact assessments. To address the issue, an online workshop was organized by the Italian Society for Vegetation Science (SISV) to shed light on the diversity of perspectives regarding the different concepts of typical species, and to discuss the possible im-plications for habitat monitoring. To this aim, we inquired 73 people with a very different degree of expertise in the field of vegetation science by means of a tailored survey composed of six questions. We analysed the data using Pearson's Chi-squared test to verify that the answers diverged from a random distribution and checked the effect of the degree of experience of the surveyees on the results. We found that most of the surveyees agreed on the use of the phytosociological method for habitat monitoring and of the diagnostic and characteristic species to evaluate the structural and functional conservation status of habitats. With this contribution, we shed light on the meaning of “typical” species in the context of habitat monitoring

A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens

The objective of this study was to determine the objective response rate in patients with platinum-sensitive and platinum-resistant recurrent ovarian cancer to treatment with trabectedin (Yondelis®) administered as a 3-h infusion weekly for 3 weeks of a 4-week cycle. We carried out a multicentre Phase II trial of trabectedin in patients with advanced recurrent ovarian cancer. Trabectedin (0.58 mg m−2) was administered via a central line, after premedication with dexamethasone, to 147 patients as a 3-h infusion weekly for 3 weeks followed by 1-week rest. Major eligibility criteria included measurable relapsed advanced ovarian cancer and not more than two prior platinum-containing regimens. Patients were stratified according to the treatment-free interval (TFI) between having either platinum-sensitive (⩾6 months TFI) or platinum-resistant disease (<6 months TFI)/platinum-refractory disease (progression during first line therapy). In the platinum-sensitive cohort, 62 evaluable patients with measurable disease had an overall response rate (ORR) of 29.0% (95% CI: 18.2–41.9%) and median progression-free survival (PFS) was 5.1 months (95% CI: 2.8–6.2). Four patients with measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) criteria had no follow-up scans at the end of treatment. In the platinum-resistant/refractory cohort, 79 patients were evaluable with an ORR of 6.3% (95% CI: 2.1–14.2%). Median PFS was 2.0 months (95% CI: 1.7–3.5 months). Two patients with measurable disease per RECIST criteria had no follow-up scans at the end of treatment. The most frequent (⩾2% of patients) drug-related treatment-emergent grade 3/4 adverse events were reversible liver alanine transferase elevation (10%), neutropaenia (8%), nausea, vomiting, and fatigue (5% each). Trabectedin is an active treatment, with documented responses in patients with platinum sensitive advanced relapsed ovarian cancer, and has a manageable toxicity profile