Structure-function relations in phosphorylcholine-binding mouse myeloma proteins

The binding site interactions between the phosphorylcholine (phosphocholine)-binding mouse myeloma proteins TEPC 15, W3207, McPC 603, MOPC 167, and MOPC 511 and the isotopically substituted hapten phosphoryl-[methyl-13C]choline have been investigated using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy. Each protein exhibits a unique NMR pattern, but extensive similarities in chemical shift parameters upon binding of hapten to immunoglobulin suggest a significant degree of conservation of important hapten-binding site interactions. Moreover, independent binding studies, in conjunction with the NMR data, allow construction of a simple model of the binding sites of these antibodies, analyzed in terms of the relative strength of interaction between hapten and two main subsites. The NMR evidence supports the view that the heavy chains of these proteins dominate in interacting with bound phosphorylcholine; the various subspecificities of these proteins for phosphorylcholine analogues can be accounted for by amino acid changes in the hypervariable regions of the heavy chains

Do current-density nonlinearities cut off the glass transition?

Extended mode coupling theories for dense fluids predict that nonlinear current-density couplings cut off the singular `ideal glass transition', present in the standard mode coupling theory where such couplings are ignored. We suggest here that, rather than allowing for activated processes as sometimes supposed, contributions from current-density couplings are always negligible close to a glass transition. We discuss in schematic terms how activated processes can nonetheless cut off the transition, by causing the memory function to become linear in correlators at late times.Comment: 4 page

Efficacy of carprofen on conception rates in lactating dairy cows after subcutaneous or intrauterine administration at the time of breeding

Manipulation of the reproductive tract can cause inflammatory processes in the endometrium and release of cytokines and prostaglandins. It has been shown that PGF2α has direct negative effects on embryonic survival and development. Treatment with nonsteroidal antiinflammatory drugs (e.g., ibuprofen lysinate, flunixin meglumine) might improve pregnancy rates after embryo transfer in recipient heifers. The primary objective of this study was to evaluate the effect of a nonsteroidal antiinflammatory drug on reproductive performance in lactating dairy cows when administered at the time of first-service artificial insemination (AI) based on the hypothesis that uterine manipulation during AI might be similarly intense compared with embryo transfer in its effect on prostaglandin release. A total of 970 cows (333 primiparous and 637 multiparous) from 17 Holstein dairy farms were enrolled. On the day of first AI, cows were randomly allocated to 1 of 3 treatment groups. Cows of group 1 received 1.4 mg/kg of body weight (BW) of carprofen subcutaneously immediately after AI (SC group). In group 2, 1.4 mg/kg of BW of carprofen was administered into the uterus using a sterile disposable catheter 12 to 24 h after AI (IU group). Animals of group 3 remained as untreated controls. First AI conception rate was similar for the SC group (42.2%) compared with the untreated control group (45.1%). A binary logistic regression model for the odds of conception at first AI revealed a negative effect of an intrauterine administration of carprofen on conception rate (38.3%). Cows allocated to the IU group had a lower likelihood of being pregnant within 200 d in milk than cows in the control group. In summary, subcutaneous treatment with the nonsteroidal antiinflammatory drug carprofen at the time of AI did not influence conception rate, whereas an intrauterine administration of carprofen 12 to 24 h after first AI had a negative effect on first-service conception rate in lactating dairy cows

The utility of B-type natriuretic peptide in predicting postoperative cardiac events and mortality in patients undergoing major emergency non-cardiac surgery

B-type natriuretic peptide (BNP) levels predict cardiovascular risk in several settings. We hypothesized that they would identify individuals at increased risk of complications and mortality following major emergency non-cardiac surgery.Forty patients were studied with a primary end-point of a new post-operative cardiac event, and/or development of significant ECG changes, and/or cardiac death. The main secondary outcome was all cause mortality at 6 months. Preoperative BNP levels were higher in 11 patients who suffered a new postoperative cardiac event (p=0.001) and predicted this outcome with an area under the receiver operating characteristic curve of 0.85 (CI=0.72-0.98,p=0.001). A pre-operative BNP value >170pg.ml-1 has a sensitivity of 82% and a specificity of 79% for the primary end-point. In this small study, pre-operative BNP levels identify patients undergoing major emergency non-cardiac surgery who are at increased risk of early post-operative cardiac events. Larger studies are required to confirm these data.Peer reviewedPreprin

The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

<p>Abstract</p> <p>Introduction</p> <p>Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD), increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive ¹³C-methionine breath test (MeBT) in patients with histologically proven NAFLD.</p> <p>Methods</p> <p>118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system.</p> <p>Results</p> <p>Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative ¹³C-exhalation (expressed as cPDR(%)). cPDR_1.5hwas markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p < 0.001). ¹³C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36). The area under the ROC curve (AUROC) for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1).</p> <p>Conclusion</p> <p>The ¹³C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial) function in non-alcoholic fatty liver disease.</p

Are there localized saddles behind the heterogeneous dynamics of supercooled liquids?

We numerically study the interplay between heterogeneous dynamics and properties of negatively curved regions of the potential energy surface in a model glassy system. We find that the unstable modes of saddles and quasi-saddles undergo a localization transition close to the Mode-Coupling critical temperature. We also find evidence of a positive spatial correlation between clusters of particles having large displacements in the unstable modes and dynamical heterogeneities.Comment: 7 pages, 3 figures, submitted to Europhys. Let