192 research outputs found

    Pandemic Vibrio cholerae shuts down site-specific recombination to retain an interbacterial defence mechanism

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    Vibrio cholerae is an aquatic microbe that can be divided into three subtypes: harmless environmental strains, localised pathogenic strains, and pandemic strains causing global cholera outbreaks. Each type has a contact-dependent type VI secretion system (T6SS) that kills neighbouring competitors by translocating unique toxic effector proteins. Pandemic isolates possess identical effectors, indicating that T6SS effectors may affect pandemicity. Here, we show that one of the T6SS gene clusters (Aux3) exists in two states: a mobile, prophage-like element in a small subset of environmental strains, and a truncated Aux3 unique to and conserved in pandemic isolates. Environmental Aux3 can be readily excised from and integrated into the genome via site-specific recombination, whereas pandemic Aux3 recombination is reduced. Our data suggest that environmental Aux3 acquisition conferred increased competitive fitness to pre-pandemic V. cholerae, leading to grounding of the element in the chromosome and propagation throughout the pandemic clade

    Type VI secretion system mutations reduced competitive fitness of classical Vibrio cholerae biotype

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    The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains to microbial attack by non-pandemic strains and subsequently caused 6th pandemic strains to become vulnerable to El Tor biotype V. cholerae intraspecific competition. The chronology of these T6SS-debilitating mutations agrees with the decline of 6th pandemic classical strains and the emergence of 7th pandemic El Tor V. cholerae

    Angiosarcoma of the breast: a new therapeutic approach?

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    Introduction Angiosarcomas are highly malignant endothelial cell tumors with poor prognosis. These can be due to breast cancer itself or to subsequent therapeutic modalities. No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Presentation of the case We report the case of a 76-year-old woman who developed an exuberant and aggressive post radiation angiosarcoma of the breast and discuss different aspects of therapy for this disease. A total left mastectomy was performed, followed by a right mastectomy. The lesions into the chest wall, and multiple abdominal skin nodules were treated with local Electrochemotherapy (ECT) with intravenous bleomicin. Discussion No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Electrochemotherapy (ECT) is an efficient palliative treatment of cutaneous and subcutaneous tumor nodules. It consists of the combination of a cytotoxic drug and electroporation, using appropriate electrical parameters; destabilization of the membrane is reversible, ensuring a high survival of permeabilized cells and the delivery of non-permeant molecules inside the cell. Conclusion Due to the rarity of the disease, prospective studies concerning adjuvant or neoadjuvant therapy are limited and no evidence-based guidelines exist. The response to chemotherapy seems to be poor. Treatment with ECT in addition to systemic chemotherapy achieves a complete response in all the lesions and improving patient body image perception

    Straightforward, Metal-free, and Stereoselective Synthesis of 9-Oxo- and 10-Hydroxy-2(E)-decenoic acids, Important Components of Honeybee (Apis mellifera) secretions

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    10-Hydroxy-2E-decenoic (10-HDA) and 9-oxo-2E-decenoic (9-ODA) acids, two components identified in honeybee secretions, have both received considerable recent interest due to their involvement in caste switch and maintenance. Herein we report for the first time a metal-free, gram scale, and stereoselective synthesis of these honeybee secretion components by TEMPO catalyzed oxidation of readily available alcohols and subsequent Doebner–Knoevenagel reactions between the resulting aldehydes and malonic acid. Mechanistic investigations undertaken highlighted the crucial role of the Doebner–Knoevenagel reaction in the high yielding and selective preparation of the α,β-unsaturated acids 10-HDA and 9-ODA. The combination of inexpensive and environmentally friendly reagents with simple synthetic procedures renders this approach a valuable green strategy for the gram scale preparation of these biologically relevant natural molecules

    The T.O.S.C.A. Project: Research, Education and Care

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    Despite recent and exponential improvements in diagnostic- therapeutic pathways, an existing “GAP” has been revealed between the “real world care” and the “optimal care” of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF “metabolic pathophysiological model” and to improve the quality of care of HF patients through research and continuing medical education

    Live Imaging of Innate Immune Cell Sensing of Transformed Cells in Zebrafish Larvae: Parallels between Tumor Initiation and Wound Inflammation

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    Live imaging and genetic studies of the initial interactions between leukocytes and transformed cells in zebrafish larvae indicate an attractant role for H2O2 and suggest that blocking these early interactions reduces expansion of transformed cell clones

    Incidence of breast cancer in Italy: mastectomies and quadrantectomies performed between 2000 and 2005.

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    Objectives. We aimed to determine the incidence of women's breast cancer in Italy without using statistical approximations. Methods. We analyzed the national hospitalizations database at the Ministry of Health to calculate the number of major surgeries in Italian women (mastectomies and quadrantectomies) due to breast cancer between 2000 and 2005, overall and by age groups (<44, 4564, 6574 and 75 years old). Results. Over the six years examined, an overall number of 100,745 mastectomies and 168,147 quadrantectomies were performed. A total of 41,608 major surgeries due to breast cancer were performed in the year 2000 and this number rose to 47,200 in 2005, with a 13.4% increase over six years. Conclusion. by analyzing the hospitalizations database concerning major breast surgery, incidence of breast cancer in Italy was found to be 26.5% higher than the official estimations which have been computed using statistical models (namely 47,200 vs. 37,300 cases in year 2005)
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