Comparisons of plankton at 59 degrees N and 37 degrees N during two Lagrangian drift experiments in the North Atlantic in June and July 1996

Data are summarised for two Lagrangian experiments in the North Atlantic in early summer 1996. At 59 degreesN 20 degreesW, plankton dynamics was studied in an SF, tracer release experiment within a mesoscale eddy over a 9-day period. At 37 degreesN 20 degreesW, a second experiment followed a drifting buoy for 7 days. The data obtained in these two experiments have been averaged for 3 depth strata; the euphotic zone, the surface mixed layer (SML), and the seasonal thermocline immediately beneath the surface mixed layer. At 59 degreesN, the euphotic zone was only marginally deeper than the SML, but at 37 degreesN the SML was ca 30 m and the euphotic depth was ca 110 m. At 37 degreesN, nutrient concentrations in the SML were low but significant new production occurred in the thermocline because of light penetration into the nutricline. The particulate organic carbon (POC) concentration of the SML at 59 degreesN was 13-15 mu mol C kg(-1), but at 37 degreesN POC concentrations were 4 mu mol C kg(-1). These POC measurements include biota and detritus. As a way of investigating latitudinal differences in the plankton communities, estimates have been made of the carbon and nitrogen content of phytoplankton, bacterioplankton, microzooplankton and mesozooplankton. At both 59 degreesN and 37 degreesN, phytoplankton was the largest component, accounting for ca 50% of the planktonic biomass in the SML. At 59 degreesN, microzooplankton was 16% of the planktonic carbon, but at 37 degreesN this reduced to 8% of the total. Mesozooplankton was a relatively constant proportion (ca 20%) of the planktonic carbon in the SML at both 59 degreesN and 37 degreesN. Bacterioplankton was 14% of the biomass at 59 degreesN, increasing to 24% in the microbial loop-dominated system at 37 degreesN. Mean carbon fixation rate in the oligotrophic southern station was 24% of that at the north, with more carbon fixation below the SML at 37 degreesN than at 59 degreesN. Respiration rates showed little variation with latitude, and the rates at 37 degreesN were 80% of those at 59 degreesN. Nitrate and ammonium uptake rates were very low in the oligotrophic conditions in the SML at 37 degreesN, but nitrate uptake in the euphotic zone was comparable to that at 59 degreesN. Ammonium uptake by phytoplankton was also significantly greater at 37 degreesN, in both the euphotic zone and thermocline, but uptake in the SML was only 20% of that in the SML at 59 degreesN. (C) 2001 Elsevier Science Ltd. All rights reserved.

Application of semiquantitative proteomics techniques to the Maillard reaction

Proteomic tools-in particular, mass spectrometry (MS)-have advanced significantly in recent years, and the identification of proteins within complex mixtures is now a routine procedure. Quantitative methods of analysis are less well advanced and continue to develop. These include the use of stable isotope ratio approaches, isotopically labeled peptide standards, and nonlabeling methods. This paper summarizes the use of MS as a proteomics tool to identify and semiquantify proteins and their modified forms by using examples of relevance to the Maillard reaction. Finally, some challenges for the future are presented.

Proteomic method for the quantification of methionine sulfoxide

Glycoxidation and lipoxidation reactions contribute to the chemical modification of proteins during the Maillard reaction. Reactive oxygen species, produced during the oxidation of sugars and lipids in these processes, irreversibly oxidize proteins. Methionine is particularly susceptible to oxidation, yielding the oxidation product methionine sulfoxide (MetSO). Here we describe a method for the analysis of MetSO using proteomic techniques. Using these techniques, we measured MetSO formation on the model protein RNase during aerobic incubations with glucose and arachidonate. We also evaluated the susceptibility of MetSO to reduction by NaBH4, a commonly used reductant in the analysis of Maillard reaction products.

Fasciola hepatica: time-dependent disruption of spermatogenesis following in vivo treatment with triclabendazole

Sheep infected with the Cullompton isolate of Fasciola hepatica were treated with triclabendazole at a concentration of 10 mg/kg at 12 weeks post-infection. Adult flukes were recovered from the liver and, where present, from the gall bladder at 48, 72 and 96 h post-treatment (pt). Gross changes to the spermatogenic cells of the testis were examined by histology and ultrastructural alterations were visualised via transmission electron microscopy. Disruption was progressive in nature, with the testis tubules becoming shrunken, vacuolated and gradually more denuded of cellular content over the 96-h time period. From 48 h pt, the number of primary and secondary spermatogonia decreased and multinucleate spermatogonial cells were frequent. Later, developmental stages were uncommon, giving rise to much empty space within the tubules. By 72 h pt, the tubules contained many apoptotic and degraded cells and had an extremely disorganised appearance. At 96 h pt, the tubules were almost completely empty, with the exception of the remains of degraded spermatogenic cells. These results indicate that triclabendazole severely disrupts spermatogenesis in the liver fluke from 48 h pt in vivo.

Oxaliplatin/capecitabine versus oxaliplatin/infusional 5-FU in advanced colorectal cancer: The MRC COIN Trial.

Background:

COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC).


Methods:

Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment.


Results:

In total, 64% of 2397 patients received OxCap(±cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (±cetuximab) was associated with more mucositis and infection whereas OxCap(±cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50–80?ml?min-1 on OxCap(±cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function.


Conclusions:

Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50–80?ml?min-1 on both regimens require close toxicity monitoring.

Who makes prescribing decisions in hospital inpatients?:An observational study

Errors involving drug prescriptions are a key target for patient safety initiatives. Recent studies have focused on error rates across different grades of doctors in order to target interventions. However, many prescriptions are not instigated by the doctor who writes them. It is important to clarify how often this occurs in order to interpret these studies and create interventions. This study aimed to provisionally quantify and describe prescriptions where the identity of the decision maker and prescription writer differed.

Geographic atrophy in retinal angiomatous proliferation

Purpose: To describe the occurrence of geographic atrophy in patients with retinal angiomatous proliferation (RAP). Methods: Demographics, visual acuity, color fundus photographs, fluorescein and indocyanine green angiograms, and fundus autofluorescence and near-infrared autofluorescence images were reviewed in 53 patients (66 eyes) with RAP. Results: Of 53 treatment-naive eyes, 19 (36%) had atrophy at baseline. Of 66 eyes, 57 (86%) developed de novo atrophy or enlargement of preexisting areas of atrophy during the follow-up (median, 17 months; range, 3-53 months) after treatment. Areas of atrophy were observed at the site of the RAP (58 of 66 eyes, 88%) of a previously existing pigment epithelial detachment (18 of 44 eyes; 41%) and elsewhere (43 of 66 eyes, 65%). At presentation, RAP was found to be frequently associated with increased autofluorescence at the fovea because of cystoid macular edema (36 of 53 eyes, 68%) and reduced autofluorescence because of hard exudation (38 of 53 eyes, 72%) and intraretinal hemorrhages (32 of 53 eyes, 60%). Background reticular (39%) and homogeneous (36%) autofluorescence were most commonly observed. Conclusion: Geographic atrophy occurs frequently in patients with RAP after treatment. This information, if confirmed in other cohorts, would be valuable for the counseling of patients with this disease and for the understanding of the pathogenesis of this condition and its progression after treatment. Copyright © 2011 Lippincott Williams &Wilkins.

Effects of modified low-density lipoproteins on human retinal pericyte survival

According to a current paradigm cardiovascular diseases can be initiated by exposure of vascular cells to qualitatively modified low-density lipoproteins (LDL). Capillary leakage, an early feature of diabetic retinopathy, results in the exposure of retinal pericytes to modified LDL, including glycated (G-LDL) and heavily oxidized glycated LDL (HOG-LDL). We demonstrate here that modified LDL inhibits the proliferation and survival of cultured human retinal pericytes. Modified LDL also induced DNA fragmentation in bovine retinal pericytes. Overall, HOG-LDL produced a significantly higher extent of cytotoxicity and apoptosis in retinal pericytes. These results indicate that exposure of pericytes to HOG-LDL could be implicated in the development of diabetic retinopathy.

Glycation does not alter LDL-induced secretion of tissue plasminogen activator and plasminogen activator inhibitor-1 from human aortic endothelial cells

Diabetes may induce both quantitative and qualitative changes in lipoproteins, especially low-density lipoprotein (LDL). Effects of LDL glycation on endothelial cell secretion of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) have not been fully elucidated. Human aortic endothelial cell (HAEC) tPA and PAI-1 production were determined after incubation with LDL (50 to 500 microg/mL protein, 24 h) from three sources: (1) nondiabetic LDL (N-LDL) modified in vitro to form six preparations: native, nonmodified (N); glycated (G); minimally oxidized (MO); minimally oxidized and glycated (MOG); heavily oxidized (HO); and heavily oxidized and glycated (HOG); (2) in vivo glycated and relatively nonglycated LDL subfractions from type 1 diabetic patients; (3) LDL from type 1 diabetic patients and matched controls, which was subfractionated using density gradient ultracentrifugation. In experiments using LDL modified in vitro, the rate of tPA release by HAECs incubated with N-LDL (83 +/- 4 ng/mg cell protein/24 h) did not differ significantly from those incubated with G-LDL (73 +/- 7), MO-LDL (74 +/- 13), or MOG-LDL (66 +/- 15) and was not influenced by LDL concentration. The rate of PAI-1 release was similar in HAECs incubated with N-LDL (5.7 +/- 0.6 mug/mg cell protein/24 h), G-LDL (5.7 +/- 0.7), MO-LDL (5.5 +/- 0.8), or MOG-LDL (5.7 +/- 0.9) and was not influenced by LDL concentration. In contrast, tPA release was significantly decreased in cells incubated with LDL (10 microg/mL) modified extensively by oxidation, and averaged 45.2 +/- 5.0 and 43.7 +/- 9.9 ng/mg/24 h for HO-LDL and HOG-LDL, respectively, and was further decreased with increasing concentrations of the heavily oxidized LDL preparations. PAI-1 release was not significantly decreased relative to N-LDL in cells incubated with low concentrations (5 to 50 microg/mL) of HO-LDL and HOG-LDL, but was decreased to 3.2 +/- 0.5 and 3.1 +/- 0.7 microg/mg/24 h for HO-LDL and HOG-LDL at 200 microg/mL, respectively. Results using in vivo glycated versus nonglycated LDL showed that tPA and PAI-1 release did not differ between subfractions. Release of tPA averaged 5.11 +/- 0.6 and 5.12 +/- 0.7 ng/mg/24 h, whereas release of PAI-1 averaged 666 +/- 27 ng/mg/24 h and 705 +/- 30 ng/mg/24 h for nonglycated and glycated LDL subfractions, respectively. Using LDL of different density subclasses, tPA and PAI-1 release in response to LDL from diabetic patients compared with control subjects did not differ when HAECs were incubated with LDLs of increasing density isolated from each subject pair. We conclude that oxidation of LDL, but not glycation, may contribute to the altered fibrinolysis observed in diabetes.

The superluminous supernova PS1-11ap: bridging the gap between low and high redshift

We present optical photometric and spectroscopic coverage of the superluminous supernova (SLSN) PS1-11ap, discovered with the Pan-STARRS1 Medium Deep Survey at z = 0.524. This intrinsically blue transient rose slowly to reach a peak magnitude of Mu = −21.4 mag and bolometric luminosity of 8 × 1043 erg s−1 before settling on to a relatively shallow gradient of decline. The observed decline is significantly slower than those of the SLSNe-Ic which have been the focus of much recent attention. Spectroscopic similarities with the lower redshift SN2007bi and a decline rate similar to 56Co decay time-scale initially indicated that this transient could be a candidate for a pair instability supernova (PISN) explosion. Overall the transient appears quite similar to SN2007bi and the lower redshift object PTF12dam. The extensive data set, from 30 d before peak to 230 d after, allows a detailed and quantitative comparison with published models of PISN explosions. We find that the PS1-11ap data do not match these model explosion parameters well, supporting the recent claim that these SNe are not pair instability explosions. We show that PS1-11ap has many features in common with the faster declining SLSNe-Ic, and the light-curve evolution can also be quantitatively explained by the magnetar spin-down model. At a redshift of z = 0.524, the observer-frame optical coverage provides comprehensive rest-frame UV data and allows us to compare it with the SLSNe recently found at high redshifts between z = 2 and 4. While these high-z explosions are still plausible PISN candidates, they match the photometric evolution of PS1-11ap and hence could be counterparts to this lower redshift transient.