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Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in Cypriot population.
Inability to correctly repair DNA damage is known to play a role in the development of breast cancer. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been identified, which modify the DNA repair capacity, which in turn may affect the risk of developing breast cancer. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 62 SNPs in 29 genes in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. Five SNPs were associated with breast cancer. SNPs rs13312840 and rs769416 in the NBS1 gene were associated with a decrease in breast cancer risk (OR TT vs. TC/CC = 0.58; 95% CI, 0.37-0.92; P = 0.019 and OR GG vs. GT/TT = 0.23, 95% CI 0.06-0.85, P = 0.017, respectively). The variant allele of MRE11A rs556477 was also associated with a reduced risk of developing the disease (OR AA vs. AG/GG = 0.76; 95% CI, 0.64-0.91; P = 0.0022). MUS81 rs545500 and PBOV1 rs6927706 SNPs were associated with an increased risk of developing breast cancer (OR GG vs. GC/CC = 1.21, 95% CI, 1.02-1.45; P = 0.031; OR AA vs. AG/GG = 1.53, 95% CI, 1.07-2.18; P = 0.019, respectively). Finally, haplotype-based tests identified significant associations between specific haplotypes in MRE11A and NBS1 genes and breast cancer risk. Further large-scale studies are needed to confirm these results
Regeneration of Giant Salvinia from Apical and Axillary Buds following Desiccation or Physical Damage
Can a new giant salvinia infestation occur even if most of
the mat is destroyed except for the protected buds? From
this study, we are able to conclude that buds can produce
new growth under certain stressful conditions. They must be
greater than 0.2 cm in length and they must possess greater
than 30% moisture content to survive
Risk Factors for Bloodstream Infections Among an Urban Population with Skin and Soft Tissue Infections: A Retrospective Unmatched Case-Control Study
Introduction: The prevalence of acute bacterial skin and skin structure infections (ABSSSIs) continues to increase. Bloodstream infection (BSI) is a severe secondary complication of ABSSSI. The objective of this study was to determine clinical and sociodemographic risk factors for BSI in patients with acute bacterial skin and skin structure infections (ABSSSIs) and to determine if sociodemographic factors impact severity at presentation. Methods This was a retrospective unmatched (1:1) case-control study. Predictors of BSI and severe infection were sought through multivariable logistic regression analyses. Cases and controls were collected from two major medical centers located in downtown Detroit, Michigan: the Detroit Medical Center and the Henry Ford Health System. The population of interest included adult patients with community-onset (CO) ABSSSI treated at a participating hospital between January 2010 and December 2015. Cases were defined as those developing BSI within 48 h of admission with CO-ABSSSI as the primary source, while controls were those with CO-ABSSSI without BSI. Results A total of 392 patients (196 cases, 196 controls) were included. Independent predictors of BSI were male gender (aOR 1.85: 95% CI 1.11, 3.66), acute renal failure (aOR 2.08: 95% CI 1.18, 3.66), intravenous drug use (aOR 4.38, 95% CI 2.22, 8.62), and prior hospitalization (aOR 2.41, 95% CI 1.24, 4.93). African American race (aOR 2.18, 95% CI 1.38, 3.4), leukocytosis (aOR 2.24, 95% CI 1.41, 3.55), and prior hospitalization (aOR 2.07, 95% CI 1.19, 3.00) were significantly associated with infection severity. Conclusion Both clinical and sociodemographic factors were associated with BSI and severe infection underscoring the importance of social determinants of health in outcomes among underserved populations
Improving Phrap-Based Assembly of the Rat Using “Reliable” Overlaps
The assembly methods used for whole-genome shotgun (WGS) data have a major impact on the quality of resulting draft genomes. We present a novel algorithm to generate a set of “reliable” overlaps based on identifying repeat k-mers. To demonstrate the benefits of using reliable overlaps, we have created a version of the Phrap assembly program that uses only overlaps from a specific list. We call this version PhrapUMD. Integrating PhrapUMD and our “reliable-overlap” algorithm with the Baylor College of Medicine assembler, Atlas, we assemble the BACs from the Rattus norvegicus genome project. Starting with the same data as the Nov. 2002 Atlas assembly, we compare our results and the Atlas assembly to the 4.3 Mb of rat sequence in the 21 BACs that have been finished. Our version of the draft assembly of the 21 BACs increases the coverage of finished sequence from 93.4% to 96.3%, while simultaneously reducing the base error rate from 4.5 to 1.1 errors per 10,000 bases. There are a number of ways of assessing the relative merits of assemblies when the finished sequence is available. If one views the overall quality of an assembly as proportional to the inverse of the product of the error rate and sequence missed, then the assembly presented here is seven times better. The UMD Overlapper with options for reliable overlaps is available from the authors at http://www.genome.umd.edu. We also provide the changes to the Phrap source code enabling it to use only the reliable overlaps
Fate of the Josephson effect in thin-film superconductors
The dc Josephson effect refers to the dissipationless electrical current --
the supercurrent -- that can be sustained across a weak link connecting two
bulk superconductors. This effect is a probe of the fundamental nature of the
superconducting state. Here, we analyze the case of two superconducting thin
films connected by a point contact. Remarkably, the Josephson effect is absent
at nonzero temperature, and the resistance across the contact is nonzero.
Moreover, the point contact resistance is found to vary with temperature in a
nearly activated fashion, with a UNIVERSAL energy barrier determined only by
the superfluid stiffness characterizing the films, an angle characterizing the
geometry, and whether or not the Coulomb interaction between Cooper pairs is
screened. This behavior reflects the subtle nature of the superconductivity in
two-dimensional thin films, and should be testable in detail by future
experiments.Comment: 16 + 8 pages. 1 figure, 1 tabl
A unified hyperbolic formulation for viscous fluids and elastoplastic solids
We discuss a unified flow theory which in a single system of hyperbolic
partial differential equations (PDEs) can describe the two main branches of
continuum mechanics, fluid dynamics, and solid dynamics. The fundamental
difference from the classical continuum models, such as the Navier-Stokes for
example, is that the finite length scale of the continuum particles is not
ignored but kept in the model in order to semi-explicitly describe the essence
of any flows, that is the process of continuum particles rearrangements. To
allow the continuum particle rearrangements, we admit the deformability of
particle which is described by the distortion field. The ability of media to
flow is characterized by the strain dissipation time which is a characteristic
time necessary for a continuum particle to rearrange with one of its
neighboring particles. It is shown that the continuum particle length scale is
intimately connected with the dissipation time. The governing equations are
represented by a system of first order hyperbolic PDEs with source terms
modeling the dissipation due to particle rearrangements. Numerical examples
justifying the reliability of the proposed approach are demonstrated.Comment: 6 figure
A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer
Background
Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms.
Methods
People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases) and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined.
Discussion
Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification of people who were most likely to have bowel cancer or conditions that may lead to bowel cancer, and who should, therefore, be referred most urgently to secondary car
Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair
Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer
Evaluation of the diagnostic accuracy of prototype rapid tests for human African trypanosomiasis
Peer reviewedPublisher PD
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