Subtropical coral-reef associated sedimentary facies characterized by molluscs (Northern Bay of Safaga, Red Sea, Egypt)

Summary The shallow marine subtropical Northern Bay of Safaga is composed of a complex pattern of sedimentary facies that are generally rich in molluscs. Thirteen divertaken bulk-samples from various sites (reef slopes, sand between coral patches, muddy sand, mud, sandy seagrass, muddy seagrass, mangrove channel) at water depths ranging from shallow subtidal to 40m were investigated with regard to their mollusc fauna >1mm, which was separated into fragments and whole individuals. Fragments make up more than 88% of the total mollusc remains of the samples, and their proportions correspond to characteristics of the sedimentary facies. The whole individuals were differentiated into 622 taxa. The most common taxon,Rissoina cerithiiformis, represented more than 5% of the total mollusc content in the samples. The main part of the fauna consists of micromolluscs, including both small adults and juveniles. Based on the results of cluster-, correspondence-, and factor analyses the fauna was grouped into several associations, each characterizing a sedimentary facies: (1) “Rhinoclavis sordidula—Corbula erythraeensis-Pseudominolia nedyma association” characterizes mud. (2) “Microcirce sp.—Leptomyaria sp. association” characterizes muddy sand. (3)”Smaragdia spp.-Perrinia stellata—Anachis exilis—assemblage” characterizes sandy seagrass. (4) “Crenella striatissima—Rastafaria calypso—Cardiates-assemblage” characterizes muddy seagrass. (5) “Glycymeris spp.-Parvicardium sueziensis-Diala spp.-assemblage” characterizes sand between coral patches. (6) “Rissoina spp.-Triphoridae —Ostreoidea-assemblage” characterizes reef slopes. (7) “Potamides conicus—Siphonaria sp. 2—assemblage” characterizes the mangrove. The seagrass fauna is related to those of sand between coral patches and reef slopes with respect to gastropod assemblages, numbers of taxa and diversity indices, and to the muddy sand fauna on the basis of bivalve assemblages and feeding strategies of bivalves. The mangrove assemblage is related to those of sand between coral patches and the reef slope with respect to taxonomic composition and feeding strategies of bivalves, but has a strong relationship to those of the fine-grained sediments when considering diversity indices. Reef slope assemblages are closely related to that of sand between coral patches in all respects, except life habits of bivalves, which distincly separates the reef slope facies from all others.     

The use of digital signal processors (DSPs) in real-time processing of multi-parametric bioelectronic signals.

In many cases of bioanalytical measurement, calculation of large amounts of data, analysis of complex signal waveforms or signal speed can overwhelm the performance of microcontrollers, analog electronic circuits or even PCs. One method to obtain results in real time is to apply a digital signal processor (DSP) for the analysis or processing of measurement data. In this paper we show how DSP-supported multiplying and accumulating (MAC) operations, such as time/frequency transformation, pattern recognition by correlation, convolution or filter algorithms, can optimize the processing of bioanalytical data. Discrete integral calculations are applied to the acquisition of impedance values as part of multi-parametric sensor chips, to pH monitoring using light-addressable potentiometric sensors (LAPS) and to the analysis of rapidly changing signal shapes, such as action potentials of cultured neuronal networks, as examples of DSP capability.     

High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle.

The regulation of intracellular pH during intense muscle contractions occurs via a number of different transport systems [e.g., monocarboxylate transporters (MCTs)] and via intracellular buffering (beta m(in vitro)). The aim of this study was to investigate the effects of an acute bout of high-intensity exercise on both MCT relative abundance and beta m(in vitro) in humans. Six active women volunteered for this study. Biopsies of the vastus lateralis were obtained at rest and immediately after 45 s of exercise at 200% of maximum O2 uptake. Beta m(in vitro) was determined by titration, and MCT relative abundance was determined in membrane preparations by Western blots. High-intensity exercise was associated with a significant decrease in both MCT1 (-24%) and MCT4 (-26%) and a decrease in beta m(in vitro) (-11%; 135 +/- 3 to 120 +/- 2 micromol H+ x g dry muscle(-1) x pH(-1); P < 0.05). These changes were consistently observed in all subjects, and there was a significant correlation between changes in MCT1 and MCT4 relative abundance (R2 = 0.92; P < 0.05). In conclusion, a single bout of high-intensity exercise decreased both MCT relative abundance in membrane preparations and beta m(in vitro). Until the time course of these changes has been established, researchers should consider the possibility that observed training-induced changes in MCT and beta m(in vitro) may be influenced by the acute effects of the last exercise bout, if the biopsy is taken soon after the completion of the training program. The implications that these findings have for lactate (and H+) transport following acute, exhaustive exercise warrant further investigation.     

Butyrylcholinesterase Predicts Cardiac Mortality in Young Patients with Acute Coronary Syndrome

Background

The incidence of acute coronary syndrome (ACS) in young people (≤65 years) is continuously rising. While prognostic factors in ACS are well-investigated less attention has been paid to their age-dependent prognostic value and their particular relevance in younger patients. The aim of our study was to assess the age-dependent prognostic impact of butyrylcholinesterase (BChE).

Methods

Retrospective cohort study including 624 patients with ACS. Patients were stratified by age into equal groups (n = 208) corresponding to “young patients” (45–64 years), "middle-aged patients” (65–84 years) and “old patients” (85–100 years). Cox regression hazard analysis was used to assess the influence of BChE on survival.

Results

After a mean follow-up time of 4.0 (interquartile range [IQR] 2.0–6.4) years, 154 patients (24.7%) died due to a cardiac cause. In the overall cohort, BChE was indirectly associated with cardiac mortality-free survival (adjusted hazard ratio (HR): 0.70 (95% confidence interval [CI] 0.53–0.93, p = 0.01). The primary-analysis of BChE by age strata showed the strongest effect in the age group 45–64 years with an adjusted HR per 1-SD of 0.28 (95% CI 0.12–0.64, p = 0.003), a weaker association with mortality in middle aged (65–84 years: adjusted HR per 1-SD 0.66 [95% CI: 0.41–1.06], p = 0.087), and no association in older patients (85–100 years: adjusted HR per 1-SD 0.89 [95% CI: 0.58–1.38], p = 0.613).

Conclusion

BChE is a strong predictor for cardiac mortality specifically in younger patients with ACS aged between 45 and 64 years. No significant association of BChE with cardiac-mortality was detected in other age classes.     

MR Angiography Follow-Up 10 Years after Cryptogenic Nonperimesencephalic Subarachnoid Hemorrhage

ObjectivesLong-term magnetic resonance angiography (MRA) follow-up studies regarding cryptogenic nonperimesencephalic subarachnoid hemorrhage (nSAH) are scarce. This single-centre study identified all patients with angiographically verified cryptogenic nSAH from 1998 to 2007: The two main objectives were to prospectively assess the incidence of de novo aneurysm with 3.0-MRI years after cryptogenic nSAH in patients without evidence for further hemorrhage, and retrospectively assess patient demographics and outcome.MethodsFrom prospectively maintained report databases all patients with angiographically verified cryptogenic nSAH were identified. 21 of 29 patients received high-resolution 3T-MRI including time-of-flight and contrast-enhanced angiography, 10.2 ± 2.8 years after cryptogenic nSAH. MRA follow-up imaging was compared with initial digital subtraction angiography (DSA) and CT/MRA. Post-hemorrhage images were related to current MRI with reference to persistent lesions resulting from delayed cerebral ischemia (DCI) and post-hemorrhagic siderosis. Patient-based objectives were retrospectively abstracted from clinical databases.Results29 patients were identified with cryptogenic nSAH, 17 (59%) were male. Mean age at time of hemorrhage was 52.9 ± 14.4 years (range 4 – 74 years). 21 persons were available for long-term follow-up. In these, there were 213.5 person years of MRI-follow-up. No de novo aneurysm was detected. Mean modified Rankin Scale (mRS) during discharge was 1.28. Post-hemorrhage radiographic vasospasm was found in three patients (10.3%); DCI-related lesions occurred in one patient (3.4%). Five patients (17.2%) needed temporary external ventricular drainage; long-term CSF shunt dependency was necessary only in one patient (3.4%). Initial DSA retrospectively showed a 2 x 2 mm aneurysm of the right distal ICA in one patient, which remained stable. Post-hemorrhage siderosis was detected 8.1 years after the initial bleeding in one patient (4.8%).ConclusionPatients with cryptogenic nSAH have favourable outcomes and do not exhibit higher risks for de novo aneurysms. Therefore the need for long-term follow up after cryptogenic nSAH is questionable.     

Proteomics of Skin Proteins in Psoriasis: From Discovery and Verification in a Mouse Model to Confirmation in Humans

Herein, we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n = 3) were compared with littermate controls (n = 3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average p = 0.0082; cystatin A, human ortholog); slc25a5 (average fold change of 46.2 and an average p = 0.0318); serpinb3b (average fold change of 35.6 and an average p = 0.0345; serpinB1, human ortholog); and kallikrein related peptidase 6 (average fold change of 4.7 and an average p = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, p < 0.0001), KLK6 (9-fold, p = 0.002), stefin A1 (7.3-fold; p < 0.001), and slc25A5 (1.5-fold; p = 0.05) using qRT-PCR on a second cohort of animals (n = 8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; p < 0.05), 29,000-fold (stefinA1; p < 0.01), 322-fold (KLK6; p < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes versus healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3-fold), KLK6 (5.8-fold), and serpinB1 (76-fold; all p < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover, slc25a5, cystatin A, KLK6, and serpinB1 protein were all increased in lesional psoriasis skin compared with normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.One in three individuals in the United States is afflicted with a skin disease, with ∼2–3% of the American population suffering from psoriasis (1–3) a chronic, immune-mediated inflammatory skin disease characterized by well-demarcated areas of “involved” red, raised, and scaly skin adjacent to areas of “uninvolved” normal appearing skin. The underlying cause of psoriasis remains unknown and the specific signals that trigger disease onset have yet to be identified; however, several lines of evidence suggest the involvement of antigen-specific T cells, although the antigens involved remain elusive (4). A combination of human and animal studies have led to the understanding that in patients with a genetically susceptible background, some initiating stimulus, often a stressful event, an injury to the skin, or an infection, leads to a coordinated series of signaling events involving cytokines, resident skin cells, and skin-infiltrating immune cells, that once started, initiates a vicious pro-inflammatory hyperproliferative cycle. Once initiated, this cycle perpetuates sustained inflammatory responses. Intervention at several points in this cycle results in clinical resolution, however, durable remission and/or permanent clearance has not yet been achieved.Current psoriasis therapies are directed toward symptomatic relief and none of them represent a cure for this chronic illness. Current treatments include topical therapies, phototherapy, and systemic administration of immune-suppressants, anti-metabolites, oral retinoids, and biologics targeting immune cells or inflammatory cytokines (5, 6). Many of the most effective therapeutics however, also have the greatest adverse reactions; moreover, psoriasis can become resistant to specific therapies over time. Therefore, an ongoing need for discovery of new biological pathways and targets for psoriasis is obvious.We studied a mouse model of psoriasis using an unbiased proteomics screening approach to identify dysregulated peptides of interest in psoriasiform-inflamed mouse skin and ultimately compared these findings to psoriasis patient skin. We used in-gel label-free protein expression analysis to observe quantitative changes in protein expression. The peptides that were determined to be top-scoring from a statistical perspective and of biological interest were subjected to further analysis and confirmation using a targeted mass spectrometry approach along with qRT-PCR to assess gene expression in a distinct set of animal samples. Further validation of the translational importance of these novel proteins was then conducted in primary keratinocytes expanded from psoriasis skin as well as human skin taken directly from psoriasis patient lesional and nonlesional areas. The results of these experiments confirm the ability of a discovery in-gel label-free expression model to identify proteins that are in the moderate to high abundance range that are significantly different in their distribution between control and genetically modified psoriasiform mouse skin and demonstrate the usefulness of mouse models and proteomic approaches for identifying novel proteins that are differentially regulated in human psoriasis, providing future biomarkers and targets for development of translational approaches to disease improvement.     

Building the Foundation for International Conservation Planning for Breeding Ducks across the U.S. and Canadian Border

We used publically available data on duck breeding distribution and recently compiled geospatial data on upland habitat and environmental conditions to develop a spatially explicit model of breeding duck populations across the entire Prairie Pothole Region (PPR). Our spatial population models were able to identify key areas for duck conservation across the PPR and predict between 62.1 – 79.1% (68.4% avg.) of the variation in duck counts by year from 2002 – 2010. The median difference in observed vs. predicted duck counts at a transect segment level was 4.6 ducks. Our models are the first seamless spatially explicit models of waterfowl abundance across the entire PPR and represent an initial step toward joint conservation planning between Prairie Pothole and Prairie Habitat Joint Ventures. Our work demonstrates that when spatial and temporal variation for highly mobile birds is incorporated into conservation planning it will likely increase the habitat area required to support defined population goals. A major goal of the current North American Waterfowl Management Plan and subsequent action plan is the linking of harvest and habitat management. We contend incorporation of spatial aspects will increase the likelihood of coherent joint harvest and habitat management decisions. Our results show at a minimum, it is possible to produce spatially explicit waterfowl abundance models that when summed across survey strata will produce similar strata level population estimates as the design-based Waterfowl Breeding Pair and Habitat Survey (r² = 0.977). This is important because these design-based population estimates are currently used to set duck harvest regulations and to set duck population and habitat goals for the North American Waterfowl Management Plan. We hope this effort generates discussion on the important linkages between spatial and temporal variation in population size, and distribution relative to habitat quantity and quality when linking habitat and population goals across this important region.     

G-CSF Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease

Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4–40.5 pg/mL vs. 24.6 pg/mL IQR 16.4–34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug-eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents.     

Conformational changes of the histidine ATP-binding cassette transporter studied by double electron–electron resonance spectroscopy

The conformational dynamics of the histidine ABC transporter HisQMP₂ from Salmonella enterica serovar Typhimurium, reconstituted into liposomes, is studied by site-directed spin labeling and double electron–electron resonance spectroscopy in the absence of nucleotides, in the ATP-bound, and in the post-hydrolysis state. The results show that the inter-dimer distances as measured between the Q-loops of HisP₂ in the intact transporter resemble those determined for the maltose transporter in all three states of the hydrolysis cycle. Only in the presence of liganded HisJ the closed conformation of the nucleotide binding sites is achieved revealing the transmembrane communication of the presence of substrate. Two conformational states can be distinguished for the periplasmic moiety of HisQMP₂ as detected by differences in distributions of interspin distances between positions 86 and 96 or 104 and 197. The observed conformational changes are correlated to proposed open, semi-open and closed conformations of the nucleotide binding domains HisP₂. Our results are in line with a rearrangement of transmembrane helices 4 and 4′ of HisQM during the closed to the semi-open transition of HisP₂ driven by the reorientation of the coupled helices 3a and 3b to occur upon hydrolysis.