Gene × Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study

BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 – 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer

Maxwell-Chern-Simons Vortices and Holographic Superconductors

We investigate probe limit vortex solutions of a charged scalar field in Einstein-Maxwell theory in 3+1 dimensions, for an asymptotically AdS Schwarzschild black hole metric with the addition of an axionic coupling to the Maxwell field. We show that the inclusion of such a term, together with a suitable potential for the axion field, can induce an effective Chern-Simons term on the 2+1 dimensional boundary. We obtain numerical solutions of the equations of motion and find Maxwell-Chern-Simons like magnetic vortex configurations, where the magnetic field profile varies with the size of the effective Chern-Simons coupling. The axion field has a non-trivial profile inside the AdS bulk but does not condense at spatial infinity.Comment: 17 pages, 5 figures, version accepted for publication in JHE

Kank Is an EB1 Interacting Protein that Localises to Muscle-Tendon Attachment Sites in Drosophila

Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role in the regulation of microtubule plus ends. It directly binds to microtubule plus ends and recruits proteins which regulate microtubule dynamics and behaviour. We report the identification of Kank, the sole Drosophila orthologue of human Kank proteins, as an EB1 interactor that predominantly localises to embryonic attachment sites between muscle and tendon cells. Human Kank1 was identified as a tumour suppressor and has documented roles in actin regulation and cell polarity in cultured mammalian cells. We found that Drosophila Kank binds EB1 directly and this interaction is essential for Kank localisation to microtubule plus ends in cultured cells. Kank protein is expressed throughout fly development and increases during embryogenesis. In late embryos, it accumulates to sites of attachment between muscle and epidermal cells. A kank deletion mutant was generated. We found that the mutant is viable and fertile without noticeable defects. Further analysis showed that Kank is dispensable for muscle function in larvae. This is in sharp contrast to C. elegans in which the Kank orthologue VAB-19 is required for development by stabilising attachment structures between muscle and epidermal cells

First analysis of anisotropic flow with Lee--Yang zeroes

We report on the first analysis of directed and elliptic flow with the new method of Lee--Yang zeroes. Experimental data are presented for Ru+Ru reactions at 1.69 AGeV measured with the FOPI detector at SIS/GSI. The results obtained with several methods, based on the event-plane reconstruction, on Lee--Yang zeroes, and on multi-particle cumulants (up to 5th order) applied for the first time at SIS energies, are compared. They show conclusive evidence that azimuthal correlations between nucleons and composite particles at this energy are largely dominated by anisotropic flow.Comment: 5 pages, 3 figures, submitted to Phys. Rev. C Rapid Co

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Rare gallbladder adenomyomatosis presenting as atypical cholecystitis: case report

<p>Abstract</p> <p>Background</p> <p>Gallbladder adenomyomatosis is a benign condition characterized by hyperplastic change in the gallbladder wall and overgrowth of the mucosa because of an unknown cause. Patients with gallbladder adenomyomatosis usually present with abdominal pain. However, we herein describe a case of a patient with gallbladder adenomyomatosis who did not present with abdominal pain, but with only fever.</p> <p>Case presentation</p> <p>A 34-year-old man presented to our hospital with a fever. No abdominal discomfort was declared. His physical examination showed no abnormalities. Ultrasound of the abdomen revealed thickness of the gallbladder. Acute cholecystitis was diagnosed. The fever persisted even after 1 week of antibiotic therapy. Magnetic resonance imaging of the abdomen showed gallbladder adenomyomatosis with intramural Rokitansky-Aschoff sinuses. Exploratory laparotomy with cholecystectomy was performed. The fever recovered and no residual symptoms were reported at the 3-year follow-up.</p> <p>Conclusions</p> <p>Gallbladder adenomyomatosis can present with fever as the only symptom. Although the association between gallbladder adenomyomatosis and malignancy has yet to be elucidated, previous reports have shown a strong association between gallbladder carcinoma and a subtype of gallbladder adenomyomatosis. Surgical intervention remains the first-choice treatment for patients with gallbladder adenomyomatosis.</p

Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Doppler findings in a rare Coronary Artery Fistula

One of the primary forms of congenital anomalies of the coronary arteries is coronary artery fistula (CAF). It is defined as a direct communication between the coronary artery and any surrounding cardiac chamber or vascular structure, which bypasses the myocardial capillary bed. We present a newborn baby with a large coronary artery fistula connecting the left anterior descending (LAD) artery to the left ventricular (LV) apex. Associated cardiac abnormalities were found: a ventricular septal defect (diameter 4 mm), a patent foramen ovale as well as trivial tricuspid and mitral regurgitation. Here we demonstrate the echocardiograms of an extremely rare form of CAF diagnosed within the first days of postnatal life