Mediator of DNA Damage Checkpoint 1 (MDC1) Contributes to High NaCl-Induced Activation of the Osmoprotective Transcription Factor TonEBP/OREBP

Background: Hypertonicity, such as induced by high NaCl, increases the activity of the transcription factor TonEBP/OREBP whose target genes increase osmoprotective organic osmolytes and heat shock proteins. Methodology: We used mass spectrometry to analyze proteins that coimmunoprecipitate with TonEBP/OREBP in order to identify ones that might contribute to its high NaCl-induced activation. Principal Findings: We identified 20 unique peptides from Mediator of DNA Damage Checkpoint 1 (MDC1) with high probability. The identification was confirmed by Western analysis. We used small interfering RNA knockdown of MDC1 to characterize its osmotic function. Knocking down MDC1 reduces high NaCl-induced increases in TonEBP/OREBP transcriptional and transactivating activity, but has no significant effect on its nuclear localization. We confirm six previously known phosphorylation sites in MDC1, but do not find evidence that high NaCl increases phosphorylation of MDC1. It is suggestive that MDC1 acts as a DNA damage response protein since hypertonicity reversibly increases DNA breaks, and other DNA damage response proteins, like ATM, also associate with TonEBP/OREBP and contribute to its activation by hypertonicity. Conclusions/Significance: MDC1 associates with TonEBP/OREBP and contributes to high NaCl-induced increase of tha

Long term survival after coronary endarterectomy in patients undergoing combined coronary and valvular surgery – a fifteen year experience

<p>Abstract</p> <p>Background</p> <p>Coronary Endarterectomy (CE) in patients undergoing coronary artery bypass graft (CABG) surgery has been shown to be beneficial in those with diffuse coronary artery disease. There are no published data on its role and benefit in patients undergoing more complex operations. We present our experience with CE in patients undergoing valve surgery with concomitant CABG.</p> <p>Materials and methods</p> <p>Between 1989 and 2003, 237 patients underwent CABG with valve surgery under a single surgeon at our institution. Of these, 41 patients needed CE. Data was retrospectively obtained from hospital records and database. Further follow-up was obtained by telephone interview. All variables were analyzed by univariate analysis for significant factors relating to hospital mortality. Morbidity and long term survival was also studied. There were 29 males and 12 females with a mean age of 67.4 ± 8.1 and body mass index of 26.3 ± 3.3. Their mean euroscore was 7.6 ± 3.2 and the log euro score was 12.2 ± 16.1.</p> <p>Results</p> <p>Thirty-two patients were discharged from the intensive therapy unit within 48 hours after surgery. Average hospital stay was 12.7 ± 10.43 days. Thirty day mortality was 9.8%. Six late deaths occurred during the 14 year follow up. Ten year survival was 57.2% (95% CL 37.8%–86.6%). Three of the survivors had Class II symptoms, with one requiring nitrates. None required further percutaneous or surgical intervention. We compared the result with the available mortality figure from the SCTS database.</p> <p>Conclusion</p> <p>Compared to the SCTS database for these patients, we have observed that CE does not increase the mortality in combined procedures. By accomplishing revascularization in areas deemed ungraftable, we have shown an added survival benefit in this group of patients.</p

Cytogenetic analysis of three sea catfish species (Teleostei, Siluriformes, Ariidae) with the first report of Ag-NOR in this fish family

Despite their ecological and economical importance, fishes of the family Ariidae are still genetically and cytogenetically poorly studied. Among the 133 known species of ariids, only eight have been karyotyped. Cytogenetic analyses performed on Genidens barbus and Sciades herzbergii revealed that both species have 2n = 56 chromosomes and Cathorops aff. mapale has 2n = 52 chromosomes: Genidens barbus has 10 Metacentrics (M), 14 Submetacentrics (SM), 26 Subtelocentrics (ST), and 6 Acrocentrics (A), Sciades herzbergii has 14M, 20SM, 18ST and 4A, whereas Cathorops aff. mapale has 14M, 20SM, and 18ST. The nucleolus organizer regions (NORs) were found in a single chromosome pair on the short arm of a large-sized ST pair in Genidens barbus and on the short arm of a middle-size SM pair in Cathorops aff. mapale. Multiple NORs on the short arms of two large-sized ST pairs were found in Sciades herzbergii. The occurrence of diploid numbers ranging from 2n = 52 through 56 chromosomes and the presence of different karyotypic compositions, besides the number and position of NORs suggest that several numeric and structural chromosome rearrangements were fixed during the evolutionary history of this fish family

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Cytogenetic analysis of five Hypostomus species (Siluriformes, Loricariidae)

In this work, we analyzed the karyotypes of five Hypostomus species. Hypostomus cf. heraldoi, from the Mogi-Guaçu River, had 2n = 72 chromosomes, with a nucleolar organizer region (NOR) in one chromosomal pair. Hypostomus regani, from the Mogi-Guaçu River had 2n = 72 chromosomes with NORs in two chromosomal pairs. Hypostomus sp., from the Mogi-Guaçu River basin, had 2n = 68 chromosomes, with NORs in two chromosomal pairs. Hypostomus aff. agna, from Cavalo Stream, had 2n = 74 chromosomes with NORs in two chromosomal pairs. Hypostomus cf. topavae, from Carrapato Stream, had 2n = 80 chromosomes, with NORs in two chromosomal pairs. Hypostomus species showed marked diversity in the karyotypic formula, which suggested the occurrence of several Robertsonian rearrangements and pericentric inversions during the evolutionary history of this genus. This hypothesis was supported by the occurrence of a large number of uniarmed chromosomes and multiple NORs in a terminal position in most species and may be a derived condition in the Loricariidae

Allozyme differentiation of two populations of the genus Neoplecostomus Eigenmann & Eigenmann, 1888 (Teleostei, Loricariidae) from the upper Paraná River basin, Brazil

Allozyme electrophoresis was used to examine 12 enzymatic systems in two populations of the genus Neoplecostomus from the Paraná River basin. Samples of Neoplecostomus sp. 1 were collected in Paraitinguinha stream of the Tietê River basin, in the municipality of Salesópolis, São Paulo State, and those of Neoplecostomus sp. 2 from São Domingos stream of the Rio Grande River basin, in the municipality of Muzambinho, Minas Gerais State. The genetic variability of the two populations was estimated by Nei’s expected heterozygosity and was considered lower than average for populations of freshwater fish. The proportion of polymorphic loci was low (only 5.26% for the locus Idh). The low frequency of heterozygosity for both populations revealed a high fixation of alleles for each locus. Homozygote excess was observed in both populations. The values of Nei’s genetic identity and the presence of loci with different allele frequencies in both populations may imply that the two populations belong to different species. The genetic variability between populations was compared to other data for loricariids

Ontogenetic Development of Weberian Ossicles and Hearing Abilities in the African Bullhead Catfish

BACKGROUND: The weberian apparatus of otophysine fishes facilitates sound transmission from the swimbladder to the inner ear to increase hearing sensitivity. It has been of great interest to biologists since the 19(th) century. No studies, however, are available on the development of the weberian ossicles and its effect on the development of hearing in catfishes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the development of the weberian apparatus and auditory sensitivity in the catfish Lophiobagrus cyclurus. Specimens from 11.3 mm to 85.5 mm in standard length were studied. Morphology was assessed using sectioning, histology, and X-ray computed tomography, along with 3D reconstruction. Hearing thresholds were measured utilizing the auditory evoked potentials recording technique. Weberian ossicles and interossicular ligaments were fully developed in all stages investigated except in the smallest size group. In the smallest catfish, the intercalarium and the interossicular ligaments were still missing and the tripus was not yet fully developed. Smallest juveniles revealed lowest auditory sensitivity and were unable to detect frequencies higher than 2 or 3 kHz; sensitivity increased in larger specimens by up to 40 dB, and frequency detection up to 6 kHz. In the size groups capable of perceiving frequencies up to 6 kHz, larger individuals had better hearing abilities at low frequencies (0.05-2 kHz), whereas smaller individuals showed better hearing at the highest frequencies (4-6 kHz). CONCLUSIONS/SIGNIFICANCE: Our data indicate that the ability of otophysine fish to detect sounds at low levels and high frequencies largely depends on the development of the weberian apparatus. A significant increase in auditory sensitivity was observed as soon as all weberian ossicles and interossicular ligaments are present and the chain for transmitting sounds from the swimbladder to the inner ear is complete. This contrasts with findings in another otophysine, the zebrafish, where no threshold changes have been observed

Double parton correlations and constituent quark models: a light front approach to the valence sector

An explicit evaluation of the double parton distribution functions (dPDFs), within a relativistic Light-Front approach to constituent quark models, is presented. dPDFs encode information on the correlations between two partons inside a target and represent the non-perturbative QCD ingredient for the description of double parton scattering in proton-proton collisions, a crucial issue in the search of new Physics at the LHC. Valence dPDFs are evaluated at the low scale of the model and the perturbative scale of the experiments is reached by means of QCD evolution. The present results show that the strong correlation effects present at the scale of the model are still sizable, in the valence region, at the experimental scale. At the low values of x presently studied at the LHC the correlations become less relevant, although they are still important for the spin-dependent contributions to unpolarized proton scattering

Mitral valve surgery for mitral regurgitation caused by Libman-Sacks endocarditis: a report of four cases and a systematic review of the literature

Libman-Sacks endocarditis of the mitral valve was first described by Libman and Sacks in 1924. Currently, the sterile verrucous vegetative lesions seen in Libman-Sacks endocarditis are regarded as a cardiac manifestation of both systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). Although typically mild and asymptomatic, complications of Libman-Sacks endocarditis may include superimposed bacterial endocarditis, thromboembolic events, and severe valvular regurgitation and/or stenosis requiring surgery. In this study we report two cases of mitral valve repair and two cases of mitral valve replacement for mitral regurgitation (MR) caused by Libman-Sacks endocarditis. In addition, we provide a systematic review of the English literature on mitral valve surgery for MR caused by Libman-Sacks endocarditis. This report shows that mitral valve repair is feasible and effective in young patients with relatively stable SLE and/or APS and only localized mitral valve abnormalities caused by Libman-Sacks endocarditis. Both clinical and echocardiographic follow-up after repair show excellent mid- and long-term results