1,955 research outputs found

    Purified human BRCA2 stimulates RAD51-mediated recombination.

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    Mutation of the breast cancer susceptibility gene, BRCA2, leads to breast and ovarian cancers. Mechanistic insight into the functions of human BRCA2 has been limited by the difficulty of isolating this large protein (3,418 amino acids). Here we report the purification of full-length BRCA2 and show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). BRCA2 acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. BRCA2 does not anneal ssDNA complexed with RPA, implying it does not directly function in repair processes that involve ssDNA annealing. Our findings show that BRCA2 is a key mediator of homologous recombination, and they provide a molecular basis for understanding how this DNA repair process is disrupted by BRCA2 mutations, which lead to chromosomal instability and cancer

    Microscale spatial distributions of microbes in marine intertidal sediments and photosynthetic microbial mats

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    Marine sedimentary habitats generally have their highest microbial activity in the top few centimeters. Where light reaches the surface sediments, benthic oxygenic photoautotrophs composed of cyanobacteria and eukaryotic microalgae (such as diatoms) dominate. In situations with a low grazing pressure like intertidal flats, this leads to permanently vertically laminated microbial communities (photosynthetic microbial mats). Although the importance of collecting samples at the scale relevant for microbial activity in sedimentary habitats has been acknowledged, this aspect is still virtually unstudied. The main focus in this thesis concerns, therefore, microscale (μm to mm) spatial distributions of key players in photosynthetic microbial mats, i.e. viruses, prokaryotes and oxygenic photoautotrophs. Initially, two methods were developed; to extract and count viruses from microbial mats, and to discriminate in a non-intrusive manner the different photoautotrophic groups. Application showed strong vertical and horizontal microscale heterogeneity in the distributions of these microbes, both in intertidal sediment (Scotland) and photosynthetic microbial mats (Netherlands). Moreover, I studied the effect mortality agents, such as viruses and fungi, may have on microscale spatial and temporal distributions of key members of the microbial mats and sediment. High viral abundances in the microbial mats indicated that viruses could be a significant structuring factor. Fungi clearly affected the spatial distribution of oxygenic photoautotrophs by degrading benthic cyanobacteria and diatoms in ring-like shapes during summer and autumn. Based on these findings I recommend more research on microscale distributions and underlying mortality processes to improve our understanding of species diversity, succession and biogeochemical cycling in microbial mats

    Toxicidade Pulmonar Aguda Precoce Associada à Amiodarona

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    Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome

    Mathematical thinking: studying the notion of 'transfer'.

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    These analyses form part of a three-year project* looking at mathematical thinking as a socially organised activity. We revisit data from a University Calculus class using tools from two theoretical perspectives, used increasingly in mathematics education research: (1) semiotic mediation and (2) discursive practices. We highlight how different theory-driven analyses taking a sociocultural view of thinking and learning can offer insights into the conceptualisation of the 'transfer' of learning

    Cateterização venosa central guiada por ultrassom --- abordagem ‘‘Syringe-Free’’

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    Background and objectives Central venous catheterization of the internal jugular vein is a commonly performed invasive procedure associated with a significant morbidity and even mortality. Ultrasound-guided methods have shown to significantly improve the success of the technique and are recommended by various scientific societies, including the American Society of Anesthesiologists. The aim of this report is to describe an innovative ultrasound-guided central line placement of the internal jugular vein. Technique The authors describe an innovative ultrasound-guided central line placement of the internal jugular vein based on an oblique approach – the “Syringe-Free” approach. This technique allows immediate progression of the guide wire in the venous lumen, while maintaining a real-time continuous ultrasound image. Conclusions The described method adds to the traditional oblique technique the possibility of achieving a continuous real-time ultrasound-guided venipuncture and a guide wire insertion that does not need removing the probe from the puncture field, while having a single operator performing the whole procedure

    PORTUGUESE ENGAGED RESEARCH AND LEARNING COMMUNITY

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    The current research was performed within the ENtRANCE Erasmus+ project in order to identify how may Portuguese Higher Education Institutions (HEI) provide independent participatory research support in response to concerns experienced by civil society, namely based on EU societal challenges. Even though the Biosense project [1] assumed the creation of the first Science Shop in Portugal, it was only active between 2011 and 2013 and there is still no formal evidence of any other one. Nevertheless, several Portuguese HEIs already provide informal services on behalf of citizens and local civil society.info:eu-repo/semantics/publishedVersio

    A Comparison of Phycocyanins from Three Different Species of Cyanobacteria Employing Resonance-Enhanced Coherent Anti-Stokes Raman Spectroscopy

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    Resonance-enhanced coherent anti-Stokes Raman spectra are recorded for monomers and trimers of phycocyanin from three different cyanobacteria: Westiellopsis prolifica, Mastigocladus laminosus and Spirulina platensis. It is shown that upon aggregation from monomer to trimer the electronic structures of both the α84 and β84 chromophores are changed. The spectra of the trimers originating from S. platensis and M. laminosus are very similar to each other, but distinctly different from the spectrum of W. prolifica

    A report on the use of a single intra-articular administration of autologous platelet therapy in a naturally occurring canine osteoarthritis model : a preliminary study

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    Research Areas : Orthopedics ; RheumatologyBackground: Osteoarthritis (OA) represents a significant burden to societies, as it affects quality of life, performance and poses a large healthcare cost. We aimed to describe the use of a single intra-articular (IA) injection of an autologous platelet therapy in the management of osteoarthritis (OA) in a naturally occurring canine model. Methods: Fifteen police working dogs with bilateral hip OA were treated with 3 ml of platelet concentrate per hip joint, produced with the V-PET kit. Response to treatment was measured by the Canine Brief Pain Inventory (CBPI, divided in pain interference score – PIS, and Pain Severity Score - PSS), Liverpool Osteoarthritis in Dogs (LOAD), Canine Orthopedic Index (COI, divided in four dimensions: function, gait, stiffness and quality of life - QOL) and the Hudson Visual Analogue Scale (HVAS). Seven different time points were considered: T0 (before treatment), T1 (after 15 days), T2, T3, T4, T5 and T6 (after 1, 2, 3, 4 and 5 months respectively). Results from each evaluation moment were compared with T0 with a Paired Samples T-Test, and a p < 0.05 was set. Results: Significant differences were observed at T1 (p < 0.01 for HVAS, PSS, COI, Gait and QOL; p = 0.01 for PIS; p = 0.02 for Function; and p < 0.05 for Stiffness), T2 (p < 0.01 for PSS, PIS and Gait; p = 0.01 for COI; p = 0.02 for HVAS, Function and QOL; and p = 0.04 for Stiffness), T3 (p < 0.01 for HVAS, PSS, PIS, Function and Gait; p = 0.01 for COI; and p = 0.02 for QOL), T4 (p < 0.01 for PSS; p = 0.03 for PIS and Gait), T5 (p < 0.01 for COI, Function and Gait; p = 0.03 for PSS, PIS and Stiffness), T6 (p < 0.01 for PSS, Function and Gait; p = 0.04 for PIS; p < 0.05 for COI) and T7 (p < 0.01 for PSS, Function and Gait; p = 0.01 for COI; and p < 0.05 for PIS). Conclusions: Autologous platelet therapy was used without apparent harm in the subjects. A single administration produced significant improvements, which lasted several months, and therefore warrants further study.info:eu-repo/semantics/publishedVersio
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