Molecular marker analysis of Lr34 in Canada Western Red Spring wheat cultivars

Trabalho final de mestrado integrado em Medicina (Medicina Interna-Nutrição Clínica), apresentado à Faculdade de Medicina da Universidade de CoimbraO Carcinoma Colorretal é uma neoplasia frequente, particularmente nos Países Ocidentais, tendo-se observado um aumento na sua incidência em Portugal nos últimos 30 anos. Pensa-se que para este aumento tenha contribuído decisivamente a progressiva mudança do estilo de vida, particularmente no que diz respeito à alimentação e atividade física, tendencialmente reduzida. Vários estudos sugerem uma relação direta entre a alimentação e o CCR, ditando o possível papel da alimentação como fator de risco ou fator protetor de CCR. A carne vermelha e processada, bem como o consumo de álcool, estão frequentemente associados ao aumento de risco de CCR. Por outro lado, frutos, vegetais, outros alimentos ricos em fibras e peixe, associam-se a um risco diminuído de CCR. Os mecanismos subjacentes à alimentação não são ainda totalmente conhecidos. Até ao momento foram descritas funções essenciais dos componentes dietéticos na inibição ou progressão da inflamação do cólon, evento fundamental na carcinogénese colorretal e transversal a todas as situações de CCR. Objetivos: Comprovar a relação entre a alimentação e o risco de CCR; identificar quais os alimentos que estão associados a um aumento ou à diminuição do risco da doença; identificar os mecanismos subjacentes ao efeito potenciador ou protetor que os alimentos conferem; identificar através dos quais os alimentos interferem na carcinogénese colorretal; definir quais as estratégias necessárias para otimizar a prevenção primária desta doença. Métodos: Foi efetuada uma revisão pormenorizada com base na literatura recente e disponível na base de dados PubMed e B-on, referente ao possível papel da alimentação no desenvolvimento de Carcinoma Colorretal e os mecanismos pelos quais exerce a sua ação. Conclusões: os resultados dos estudos analisados sugerem que o CCR pode em grande parte percentagem de casos ser prevenido através do recurso à adoção de uma alimentação e estilo de vida saudáveis. As carnes vermelhas e processadas estão associadas a um aumento do risco desenvolver Carcinoma Colorretal, principalmente devido à produção de aminas heterocíclicas, devendo o seu consumo ser reduzido. or outro lado, o peixe produz um efeito oposto, exercendo um efeito protetor, principalmente através da diminuição da produção de mediadores pró-inflamatórios. Também os frutos e vegetais se associam a um risco menor de desenvolver esta neoplasia, devendo o seu consumo ser elevado. As propriedades quimiopreventivas destes alimentos devem-se, sobretudo, à inibição da inflamação no cólon, e também a mecanismos antioxidantes, pró-apoptóticos e de paragem do ciclo celular.Introduction: Colorectal carcinoma is a tumor with high incidence rate, particularly in Western countries, having been noticed an increase in incidence in Portugal in the past 30 years. It is widely accepted that progressive changes in lifestyle, regarding diet and reduced physical activity has decisively contributed to this increase. Several studies suggest a direct relationship between diet and CRC, dictating the possible role of diet as a risk factor or protective factor for CRC. Red and processed meat and alcohol consumption are often associated to increased risk of CRC. On the other hand, fruit, vegetables, other fiber rich foods and fish are associated to decreased risk of CRC. The underlying mechanisms of diet are not yet fully known. Up until now the essential functions of dietary components have been described as to inhibiting or helping to progress inflammations of the colon, the key event in colorectal carcinogenesis and transversal to all situations of CRC. Objectives: Demonstrate the relationship between diet and the risk of Colorectal Carcinoma; identify which food is associated with an increased or decreased risk of disease; identify the mechanisms of diet underlying the potentiating effect; determine necessary strategies to optimize the primary prevention of this disease. Methods: A detailed review was performed, based on the literature available on CRC and the mechanisms by which exerts its action. Conclusions: The results of the studies reviewed suggest that the CCR can be largely prevented by adopting a healthy diet and lifestyle. Red and processed meat are associated with increased risk of CRC, mainly due to the production of heterocyclic amines and its consumption should be reduced. On the other hand, fish produces an opposite effect, exerting a protective effect, mainly by decreasing the production of pro-inflammatory mediators. Fruit and vegetables are also associated with decreased risk of developing the disease, and its consumption should be increased. The chemopreventive properties of these foods are due mainly to the inhibition of colon inflammation, as well as antioxidant, pro-apoptotic and cell cycle arrest mechanisms

An adaptive prefix-assignment technique for symmetry reduction

This paper presents a technique for symmetry reduction that adaptively assigns a prefix of variables in a system of constraints so that the generated prefix-assignments are pairwise nonisomorphic under the action of the symmetry group of the system. The technique is based on McKay's canonical extension framework [J.~Algorithms 26 (1998), no.~2, 306--324]. Among key features of the technique are (i) adaptability---the prefix sequence can be user-prescribed and truncated for compatibility with the group of symmetries; (ii) parallelizability---prefix-assignments can be processed in parallel independently of each other; (iii) versatility---the method is applicable whenever the group of symmetries can be concisely represented as the automorphism group of a vertex-colored graph; and (iv) implementability---the method can be implemented relying on a canonical labeling map for vertex-colored graphs as the only nontrivial subroutine. To demonstrate the practical applicability of our technique, we have prepared an experimental open-source implementation of the technique and carry out a set of experiments that demonstrate ability to reduce symmetry on hard instances. Furthermore, we demonstrate that the implementation effectively parallelizes to compute clusters with multiple nodes via a message-passing interface.Comment: Updated manuscript submitted for revie

Attitudes towards 12-step groups and referral practices in a 12-step naive treatment culture; a survey of addiction professionals in Norway

<p>Abstract</p> <p>Background</p> <p>Addressing substance use disorders effectively requires a long-term approach. Substance abuse treatment is typically of short duration; referring patients to Twelve Step based self-help groups (TSGs) – e.g. Narcotics Anonymous, represents a promising complementary recovery resource. Clinicians' attitudes and referral practices towards the TSGs have mainly been studied in countries with high integration of the 12-step philosophy in their substance abuse services and where the TSGs are widely available, such as the US. In Norway, there are currently 294 weekly TSG meetings (6 per 100,000 inhabitants). This study describes clinicians' attitudes and referral practices to TSGs in Norway where health authorities seek to promote self-help participation, but where the treatment culture is unfamiliar with 12-step fellowships.</p> <p>Methods</p> <p>Data collected by a self-administered questionnaire, adapted from established US and UK instruments. Information covered the attitudes, knowledge and referral practices towards TSGs among addiction treatment professionals in Norway in mid 2008.</p> <p>Results</p> <p>The return rate was 79.7% (n = 291). Participants had moderately positive attitude scores towards TSGs, but referral to these groups among Norwegian addiction professionals was low, as was the level of knowledge about TSGs. More than six out of ten did not refer any patients to TSGs in the previous week. Local variation with more referrals to TSGs in the county with the one established 12-step treatment facility was observed. Respondents' integration of the 12-steps in their own treatment work, higher self-efficacy for making a successful referral, and greater TSG knowledge were associated with referring patients.</p> <p>Conclusion</p> <p>Low referral rates to TSGs point to the need for education and training to raise the awareness and knowledge about it among addiction professionals unfamiliar with these 12-step fellowships. Training should focus on the usefulness of these groups for all types of treatment models regardless of therapeutic orientation. Increased knowledge is expected to lead to higher referral rates, which in turn would maximize the likelihood of positive long-term patient outcomes.</p

MicroRNA Expression Data Reveals a Signature of Kidney Damage following Ischemia Reperfusion Injury

Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury, a common problem worldwide associated with significant morbidity and mortality. We have recently examined the role of microRNAs (miRs) in renal IRI using expression profiling. Here we conducted mathematical analyses to determine if differential expression of miRs can be used to define a biomarker of renal IRI. Principal component analysis (PCA) was combined with spherical geometry to determine whether samples that underwent renal injury as a result of IRI can be distinguished from controls based on alterations in miR expression using our data set consisting of time series measuring 571 miRs. Using PCA, we examined whether changes in miR expression in the kidney following IRI have a distinct direction when compared to controls based on the trajectory of the first three principal components (PCs) for our time series. We then used Monte Carlo methods and spherical geometry to assess the statistical significance of these directions. We hypothesized that if IRI and control samples exhibit distinct directions, then miR expression can be used as a biomarker of injury. Our data reveal that the pattern of miR expression in the kidney following IRI has a distinct direction based on the trajectory of the first three PCs and can be distinguished from changes observed in sham controls. Analyses of samples from immunodeficient mice indicated that the changes in miR expression observed following IRI were lymphocyte independent, and therefore represent a kidney intrinsic response to injury. Together, these data strongly support the notion that IRI results in distinct changes in miR expression that can be used as a biomarker of injury

Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning

The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma. © 2014 Hum et al

Eta Carinae -- Physics of the Inner Ejecta

Eta Carinae's inner ejecta are dominated observationally by the bright Weigelt blobs and their famously rich spectra of nebular emission and absorption lines. They are dense (n_e ~ 10^7 to 10^8 cm^-3), warm (T_e ~ 6000 to 7000 K) and slow moving (~40 km/s) condensations of mostly neutral (H^0) gas. Located within 1000 AU of the central star, they contain heavily CNO-processed material that was ejected from the star about a century ago. Outside the blobs, the inner ejecta include absorption-line clouds with similar conditions, plus emission-line gas that has generally lower densities and a wider range of speeds (reaching a few hundred km/s) compared to the blobs. The blobs appear to contain a negligible amount of dust and have a nearly dust-free view of the central source, but our view across the inner ejecta is severely affected by uncertain amounts of dust having a patchy distribution in the foreground. Emission lines from the inner ejecta are powered by photoionization and fluorescent processes. The variable nature of this emission, occurring in a 5.54 yr event cycle, requires specific changes to the incident flux that hold important clues to the nature of the central object.Comment: This is Chapter 5 in a book entitled: Eta Carinae and the Supernova Impostors, Kris Davidson and Roberta M. Humphreys, editors Springe

The role of P2 receptors in controlling infections by intracellular pathogens

A growing number of studies have demonstrated the importance of ATPe-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have shown that ATPe can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATPe may function as a ‘danger signal–that alerts the immune system to the presence of intracellular pathogens that damage the host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATPe-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens

Impact of Splenectomy on Thrombocytopenia, Chemotherapy, and Survival in Patients with Unresectable Pancreatic Cancer

Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy. From 2001 to 2009, 15 patients with recurrent or unresectable PDAC or PET underwent splenectomy for hypersplenism and thrombocytopenia. The clinical variables of this group of patients were analyzed. The overall survival of patients with PDAC was compared to historical controls. Of the 15 total patients, 13 (87%) had PDAC and 2 (13%) had PET. All tumors were either locally advanced (n = 6, 40%) or metastatic (n = 9, 60%). The platelet counts significantly increased after splenectomy (p &lt; 0.01). All patients were able to resume chemotherapy within a median of 11.5 days (range 6–27). The patients with PDAC had a median survival of 20 months (range 4–67) from the time of diagnosis and 10.6 months (range 0.6–39.8) from the time of splenectomy. Splenectomy for patients with unresectable PDAC or PET who developed hypersplenism and thrombocytopenia that limited the administration of chemotherapy, significantly increased platelet counts, and led to resumption of treatment in all patients. Patients with PDAC had better disease-specific survival as compared to historical controls