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The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be extracted by Cdc48 for endosome and Golgi associated proteasomal degradation (EGAD), while others will undergo ESCRT dependent vacuolar degradation. Some substrates are degraded by both, EGAD- or ESCRT pathways. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thereby preserves cellular membrane protein and lipid composition. At the Golgi, the Dsc ubiquitin ligase complex targets proteins with shorter transmembrane domains for proteasomal or lysosomal degradation. This quality control at the sorting center of cells restricts the uncontrolled spreading of orphaned proteins. [ABSTRACT FROM AUTHOR]

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Purpose of the Review: The role of multimodality imaging in the evaluation of patients with aortic regurgitation is summarized in this review. Recent Findings: The etiology (mechanism) of the aortic regurgitation and the severity of aortic regurgitation and hemodynamic consequences are key in the decision making of patients with severe aortic regurgitation. While echocardiography remains as the leading technique to assess all these parameters, other imaging techniques have become essential for the accurate assessment of aortic regurgitation severity and the timing of aortic intervention. The anatomic suitability of transcatheter aortic valve implantation in inoperable patients with severe aortic regurgitation is usually assessed with computed tomography. Summary: Aortic regurgitation is a prevalent disease with various pathophysiological mechanisms that need a personalized treatment. The evaluation of the mechanism and severity of aortic regurgitation can be initially performed with echocardiography. Three-dimensional techniques, including echocardiography, have become very relevant for accurate assessment of the regurgitation severity and its hemodynamic consequences. Assessment of myocardial tissue characteristics with cardiac magnetic resonance is key in the risk stratification of patients and in the timing of aortic intervention. Computed tomography is important in the assessment of aortic dimensions and selection of patients for transcatheter aortic valve implantation. [ABSTRACT FROM AUTHOR]

Climate change is causing problems for agriculture, but the effect of combined abiotic stresses on crop nutritional quality is not clear. Here we studied the effect of 10 combinations of climatic conditions (temperature, CO2, O3 and drought) under controlled growth chamber conditions on the grain yield, protein, and mineral content of 3 wheat varieties. Results show that wheat plants under O3 exposure alone concentrated + 15 to + 31% more grain N, Fe, Mg, Mn P and Zn, reduced K by − 5%, and C did not change. Ozone in the presence of elevated CO2 and higher temperature enhanced the content of Fe, Mn, P and Zn by 2–18%. Water-limited chronic O3 exposure resulted in + 9 to + 46% higher concentrations of all the minerals, except K. The effect of climate abiotic factors could increase the ability of wheat to meet adult daily dietary requirements by + 6% to + 12% for protein, Zn and Fe, but decrease those of Mg, Mn and P by − 3% to − 6%, and K by − 62%. The role of wheat in future nutrition security is discussed. [ABSTRACT FROM AUTHOR]

When cultivating the kelp Saccharina latissima, knowledge on the availability of seeding material for the production is essential. Applying a spore seeding approach requires spores from the reproductive organs of the fertile sporophytes (sori). As sori are generally not present during the time of seeding in late summer, the production of spores (sporogenesis) can be artificially induced by removing the meristematic part of the sporophyte and keeping the sporophyte under short day, temperate, and nutrient-replete conditions. Only limited information is available on the effect of light intensities including darkness on the sporogenesis of S. latissima. This study examined the natural pattern of sporogenesis in S. latissima from Middelfart, Denmark, and the effect of four different light regimes (0, 20, 60, or 120 μmol photons m−2 s−1) on the artificial induction of sporogenesis in S. latissima. Natural reproductivity and availability of spores in Denmark peaked in early winter, with 86% of the population being reproductive in November. Reproductive material was available from October until late spring, but with a variable spore release from 11 × 103 to 1.2 × 106 spores cm−2 sori. The artificial induction of sporogenesis was optimal in darkness with > 90% of sporophytes developing sori after 49 days, with an average spore release density of 1.15 ± 0.38 × 106 spores cm−2 sori. The results confirmed that S. latissima in Denmark follows the general pattern of reproduction of S. latissima in North Atlantic regions and demonstrated for the first time that sporogenesis in S. latissima can be efficiently induced in darkness. [ABSTRACT FROM AUTHOR]

Aims: Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to pre-existing preload are often disregarded. To determine volume-related changes in the pulmonary-right ventricle (RV) unit and the preload dependence of its components, we analysed pulmonary haemodynamics and right ventricular performance, taking advantage of the plasma volume removal associated to haemodialysis (HD). Methods and results: Fifty-three stable patients on chronic HD with LVEF > 50% and without heart failure were recruited (mean age 63.0 ± 12.4 years; 31.2% women; hypertension in 89% and diabetes in 53%) and evaluated just before and after HD (mean ultrafiltration volume 2.4 ± 0.7 l). SPAP from both times were available in 39 patients. After HD, SPAP decreased (42.2 ± 12.6 to 33.7 ± 11.6 mmHg, p < 0.001) without modification of non-invasive pulmonary vascular resistance (1.75 ± 0.44 to 1.75 ± 0.40 eWU, p = 0.94). Age and drop in the E/eʹ ratio were the variables associated with greater reduction in PASP (p = 0.022 and p = 0.049, respectively). A significant reduction of right chamber sizes was observed, along with a diminution in measures of RV contractility, excluding RV longitudinal strain. Functional tricuspid regurgitation (FTR) diminution was observed in 26% of patients, occurring in every case with more than mild FTR. On multivariate analyses, left atrial size was the only predictor of pulmonary hypertension (defined as SPAP > 40 mmHg) (OR 1.29 (1.07–1.56), p = 0.006). Conclusion: Rapid volemic changes may affect FTR grading, RV size and contractility, with RV longitudinal strain being less variable than conventional parameters. SPAP decreases after HD, and this reduction is related to age and greater diminution of the E/eʹ ratio. [ABSTRACT FROM AUTHOR]

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0–8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01–1.47], p = 0.041 and HR 1.04 [95% CI 1.01–1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients. [ABSTRACT FROM AUTHOR]

The eukaryotic ascomycete genus Fusarium comprises many species capable of producing secondary metabolites important for agriculture, health, and biotechnology. Filamentous fungi share common physiological features, but even within Fusarium, there are significant differences that affect the success of biotechnological methods used to unravel biosynthetic pathways. The aim of this review is to describe the different methods that have successfully been used throughout the genus Fusarium to identify the products of novel biosynthetic pathways. The results are presented in tables to give the reader an overview and thereby enable the selection of the most appropriate method to the problem, regarding both species and target products. Significant work has gone into characterization of the underlying molecular genetics of secondary metabolites, but still, the products of only 25–30% of predicted gene clusters have been identified. In this review, we highlight existing knowledge and encourage the development of new techniques and strategies to provide access to the many unknown polyketide and non-ribosomal peptide products that await discovery in Fusarium. [ABSTRACT FROM AUTHOR]

Current methods for assessment of cellular uptake of cell-penetrating peptides (CPPs) often rely on detection of fluorophore-labeled CPPs. However, introduction of the fluorescent probe often confers changed physicochemical properties, so that the fluorophore-CPP conjugate may exhibit cytotoxic effects and membrane damage not exerted by the native CPP. In the present study, introduction of fluorine probes was investigated as an alternative to fluorophore labeling of a CPP, since this only confers minor changes to its overall physicochemical properties. The high sensitivity of 19F NMR spectroscopy and the absence of background signals from naturally occurring fluorine enabled detection of internalized CPP. Also, degradation of fluorine-labeled peptides during exposure to Caco-2 cells could be followed by using 19F NMR spectroscopy. In total, five fluorinated analogues of the model CPP penetratin were synthesized by using commercially available fluorinated amino acids as labels, including one analogue also carrying an N-terminal fluorophore. The apparent cellular uptake was considerably higher for the fluorophore-penetratin conjugate indicating that the fluorophore moiety promoted uptake of the peptide. The use of 19F NMR spectroscopy enabled monitoring of the fate of the CPPs over time by establishing molar balances, and by verifying CPP integrity upon uptake. Thus, the NMR-based method offers several advantages over currently widespread methods relying on fluorescence detection. The present findings provide guidelines for improved labeling strategies for CPPs, thereby expanding the repertoire of analytical techniques available for studying degradation and uptake of CPPs. [ABSTRACT FROM AUTHOR]

Sansalvamide is a cyclic pentadepsipeptide produced by Fusarium solani and has shown promising results as potential anti-cancer drug. The biosynthetic pathway has until now remained unidentified, but here we used an Agrobacterium tumefaciens-mediated transformation (ATMT) approach to generate knockout mutants of two candidate non-ribosomal peptide synthetases ( NRPS29 and NRPS30). Comparative studies of secondary metabolites in the two deletion mutants and wild type confirmed the absence of sansalvamide in the NRPS30 deletion mutant, implicating this synthetase in the biosynthetic pathway for sansalvamide. Sansalvamide is structurally related to the cyclic hexadepsipeptide destruxin, which both contain an α-hydroxyisocaproic acid (HICA) unit. A gene cluster responsible for destruxin production has previously been identified in Metarhizium robertsii together with a hypothetical biosynthetic pathway. Using comparative bioinformatic analyses of the catalytic domains in the destruxin and sansalvamide NRPSs, we were able to propose a model for sansalvamide biosynthesis. Orthologues of the gene clusters were also identified in species from several other genera including Acremonium chrysogenum and Trichoderma virens, which suggests that the ability to produce compounds related to destruxin and sansalvamide is widespread. [ABSTRACT FROM AUTHOR]

Late summer harvest of cultivated Saccharina latissima, prior to seasonally determined negative length growth, is considered advantageous in North Atlantic waters to optimize biomass yields. We hypothesized that seasonal increase in tissue protein and pigments over autumn and early winter would counterbalance the loss of biomass, and increase the absolute harvestable amount of protein and pigments. The hypothesis was tested in a land-based, factorial-designed, pilot-scale experiment using whole algae individuals exposed to naturally relevant high or low availability of nutrients and light. The experiment was conducted during fall/early winter in Grenaa, Denmark, in outdoor tanks, exposed to ambient light and temperature variations. With high nutrient availability, the absolute harvestable amounts of nitrogen, fucoxanthin, and chlorophyll a increased by 50.1-60.1, 21.7-53.7, and 47.0-73.5 %, respectively, despite a loss of biomass of 16.2-18.7 %. Under low nutrient availability, there was a net loss of biomass (8.1-9.5 %), tissue nitrogen (10.7-44.1 %), and fucoxanthin (7.1-17.2 %), and a minor increase in chlorophyll a (2.5-22.8 %). Nutrient availability had a significant negative impact on the biomass growth, but a positive control on the tissue concentration of nitrogen, chlorophyll a, and fucoxanthin. Our results, from a land-based experiment, indicate that early winter harvest of S. latissima biomass grown under high nutrient availability in Denmark, fulfills a higher degree of nutrient bioremediation, and has an improved biomass quality in regards of increased concentrations of pigments and nitrogen rich compounds. [ABSTRACT FROM AUTHOR]

The projected future climate will affect the global agricultural production negatively, however, to keep abreast of the expected increase in global population, the agricultural production must increase. Therefore, to safeguard the future crop yield and quality, the adaptive potential of crops to environmental change needs to be explored in order to select the most productive genotypes. Presently, it is unknown whether cereal crops like spring barley can adapt to climate stressors over relatively few generations. To evaluate if strong selection pressures could change the performance of barley to environmental stress, we conducted a selection experiment over five plant generations (G0-G4) in three scenarios, where atmospheric [CO] and temperature were increased as single factors and in combination. The treatments represented the expected environmental characteristics in Northern Europe around year 2075 [700 ppm CO, 22/17 °C (day/night)] as well as a control mimicking present day conditions (390 ppm CO, 19/12 °C). Two different barley accessions, a modern cultivar and an old landrace, were evaluated in terms of yield and biomass production. In all treatments representing future environmental scenarios, the G4-generation of selected plants did not improve its reproductive output compared to the G0-generation, as G4 produced less seeds and had a lower yield than unselected plants. These results indicate that barley might not respond positively to rapid and strong selection by elevated [CO] and temperature, contrary to previous results from oilseed rape. The two barley accessions analyzed presented almost the same response pattern in a given treatment, though the modern cultivar had the highest yield in the climate scenarios, while the landrace was superior in yield under present day climate conditions. [ABSTRACT FROM AUTHOR]

Climate change scenarios predict simultaneously increase in temperature, altered precipitation patterns and elevated atmospheric CO concentration, which will affect key ecosystem processes and plant growth and species interactions. In a large-scale experiment, we investigated the effects of in situ exposure to elevated atmospheric CO concentration, increased temperature and prolonged drought periods on the plant biomass in a dry heathland (Brandbjerg, Denmark). Results after 3 years showed that drought reduced the growth of the two dominant species Deschampsia flexuosa and Calluna vulgaris. However, both species recovered quickly after rewetting and the drought had no significant effect on annual aboveground biomass production. We did not observe any effects of increased temperature. Elevated CO stimulated the biomass production for D. flexuosa in one out of three years but did not influence the standing biomass for either D. flexuosa or the ecosystem as more litter was produced. Treatment combinations showed little interactions on the measured parameters and in particular elevated CO did not counterbalance the drought effect on plant growth, as we had anticipated. The plant community did not show any significant responses to the imposed climate changes and we conclude that the two heathland species, on a short time scale, will be relatively resistant to the changes in climatic conditions. [ABSTRACT FROM AUTHOR]

Temperate terrestrial ecosystems are currently exposed to increased atmospheric CO2 and progressive climatic changes with increased temperature and periodical drought. We here present results from a field experiment, where the effects of these three main climate change related factors are investigated solely and in all combinations at a temperate heathland. Significant responses were found in the top soils below the two dominant species ( Calluna vulgaris and Deschampsia flexuosa). During winter incubation, microbial immobilization of N and ammonification rate decreased in response to warming in Deschampsia soil, and microbial immobilization of N and P decreased in warmed Calluna soil. Warming tended to increase microbial N and P in Calluna but not in Deschampsia soil in fall, and more microbial C was accumulated under drought in Calluna soil. The effects of warming were often counteracted or erased when combined with CO2 and drought. Below Deschampsia, the net nitrification rate decreased in response to drought and, while phosphorus availability and microbial P immobilization decreased, but nitrification increased in response to elevated CO2. Furthermore, leaf litter decomposition of both species decreased in response to drought. These complex changes in availability and release of nutrients from soil organic matter turnover and mineralization in response to elevated CO2 and climate change may influence the future plant carbon sequestration and species composition at temperate heathlands. [ABSTRACT FROM AUTHOR]

In this paper examples are given of the importance of flow separation for fluid patterns at moderate Reynolds numbers—both in the stationary and in the time-dependent domain. In the case of circular hydraulic jumps, it has been shown recently that it is possible to generalise the Prandtl–Kármán–Pohlhausen approach to stationary boundary layers with free surfaces going through separation, and thus obtain a quantitative theory of the simplest type of hydraulic jump, where a single separation vortex is present outside the jump. A second type of jump, where an additional roller appears at the surface, cannot be captured by this approach and has not been given an adequate theoretical description. Such a model is needed to describe “polygonal” hydraulic jumps, which occur by spontaneous symmetry breaking of the latter state. Time-dependent separation is of importance in the formation of sand ripples under oscillatory flow, where the separation vortices become very strong. In this case no simple theory exists for the determination of the location and strengths of separation vortices over a wavy bottom of arbitrary profile. We have, however, recently suggested an amplitude equation describing the long-time evolution of the sand ripple pattern, which has the surprising features that it breaks the local sand conservation and has long-range interaction, features that can be underpinned by experiments. Very similar vortex dynamics takes place around oscillating structures such as wings and fins. Here, we present results for the vortex patterns behind a flapping foil in a flowing soap film, which shows the interaction and competition between the vortices shed from the round leading edge (like the von Kármán vortex street) and those created at the sharp trailing edge. [ABSTRACT FROM AUTHOR]

Measurements of variation in the diameter of tree stems provide a rapid response, high resolution tool for detecting changes in water tension inside the xylem. Water movement inside the xylem is caused by changes in the water tension and theoretically, the sap flow rate should be directly proportional to the water tension gradient and, therefore, also linearly linked to the xylem diameter variations. The coefficient of proportionality describes the water conductivity and elasticity of the conducting tissue. Xylem diameter variation measurements could thus provide an alternative approach for estimating sap flow rates, but currently we lack means for calibration. On the other hand, xylem diameter variation measurements could also be used as a tool for studying xylem structure and function. If we knew both the water tension in the xylem and the sap flow rate, xylem conductivity and/or elasticity could be calculated from the slope of their relationship. In this study we measured diurnal xylem diameter variation simultaneously with sap flow rates (Granier-type thermal method) in six deciduous species ( Acer rubrum L., Alnus glutinosa Miller, Betula lenta L., Fagus Sylvatica L. Quercus rubra L., and Tilia vulgaris L.) for 7–91 day periods during summers 2003, 2005 and 2006 and analyzed the relationship between these two measurements. We found that in all species xylem diameter variations and sap flow rate were linearly related in daily scale (daily average R 2 = 0.61–0.87) but there was a significant variation in the daily slopes of the linear regressions. The largest variance in the slopes, however, was found between species, which is encouraging for finding a species specific calibration method for measuring sap flow rates using xylem diameter variations. At a daily timescale, xylem diameter variation and sap flow rate were related to each other via a hysteresis loop. The slopes during the morning and afternoon did not differ statistically significantly from each other, indicating no overall change in the conductivity. Because of the variance in the daily slopes, we tested three different data averaging methods to obtain calibration coefficients. The performance of the averaging methods depended on the source of variance in the data set and none of them performed best for all species. The best estimates of instantaneous sap flow rates were also given by different averaging methods than the best estimates of total daily water use. Using the linear relationship of sap flow rate and xylem diameter variations we calculated the conductance and specific conductivity of the soil–xylem–atmosphere water pathway. The conductance were of the order of magnitude 10−5 kg s−1 MPa−1 for all species, which compares well with measured water fluxes from broadleaved forests. Interestingly, because of the large sap wood area the conductance of Betula was approximately 10 times larger than in other species. [ABSTRACT FROM AUTHOR]

Lysosome-related organelles have versatile functions, including protein and lipid degradation, signal transduction and protein secretion. The molecular elucidation of rare congenital diseases affecting endosomal-lysosomal biogenesis has given insights into physiological functions of the innate and adaptive immune system. Here, we describe a previously unknown human primary immunodeficiency disorder and provide evidence that the endosomal adaptor protein p14, previously characterized as confining mitogen-activated protein kinase (MAPK) signaling to late endosomes, is crucial for the function of neutrophils, B cells, cytotoxic T cells and melanocytes. Combining genetic linkage studies and transcriptional profiling analysis, we identified a homozygous point mutation in the 3′ untranslated region (UTR) of p14 (also known as MAPBPIP), resulting in decreased protein expression. In p14-deficient cells, the distribution of late endosomes was severely perturbed, suggesting a previously unknown role for p14 in endosomal biogenesis. These findings have implications for understanding endosomal membrane dynamics, compartmentalization of cell signal cascades, and their role in immunity. [ABSTRACT FROM AUTHOR]

This paper presents an account of the progress of the integration between the Danish and Swedish parts of the Öresund Region within the world of science, with emphasis on biotech. The paper is based on data from the database Science Citation Index Expanded. The amount of co-authorships produced by agents from each side of the region is analysed for a 12-year period (1994-2005) and used as an indicator to show how the integration is proceeding. Each of the co-authorships is examined to shed light on the nature of the interactions, thereby identifying the agents most involved in collaboration. Furthermore, the development in co-authorships within the region is compared to the development in co-authorships between the Öresund Region and four selected reference areas. Our findings indicate that there has been a substantial increase in both the number of co-authorships overall and within biotech solely. The rise in co-authorships between the two parts is proceeding at a faster pace than the rise in coauthorships between the Öresund Region and the reference areas. The overall results of this paper indicate a growing integration of the biotech sector in the Öresund Region. [ABSTRACT FROM AUTHOR]

Cell surface receptors are used to transmit extracellular information. The activation of cell surface receptors initiates signal transduction and receptor endocytosis. Signal transduction and the endosomal transport of activated receptors require precise regulation. New concepts for the integration of endocytosis and signaling arise from recent findings that suggest bidirectional interplay of these two processes. This review discusses the following questions: (i) do activated cell surface receptors modify the endosomal system to promote internalization and endosomal traffic, and (ii) do internalized cell surface receptors use specifically localized signaling complexes to generate specific biological signals? [ABSTRACT FROM AUTHOR]

T cell hybridomas were raised against the glycopeptide S72 (Core-1) containing the tumor-associated disaccharide βGal (1–3) αGalNAc (Core-1) O-linked to serine at position 72 in the mouse hemoglobin derived decapeptide Hb (67–76). All hybridomas recognized the glycopeptide S72 (Core-1). Two of the selected hybridomas responded, however, much better to the S72 (Tn) glycopeptide containing the monosaccharide αGalNAc O-linked to serine. In addition, one hybridoma cross-responded to the glycopeptide T72 (Core-1) having a threonine at position 72 instead of a serine. No cross-responses were found to other glycopeptides consisting of the same hemoglobin peptide with different glycans attached or to the unglycosylated peptides. The T cell receptor Vα and Vβ usage was clearly diverse. The CDR3α regions demonstrated moreover a predominance of small polar amino acid side chains, and three hybridomas contained a common sequence motif. All the sequenced CDR3β regions contained furthermore a conserved proline-glycine motif. In conclusion, immunization with the disaccharide containing glycopeptides S72 (Core-1) created a heterogeneous population of glycopeptide specific T cells with the ability of cross-responding toward related glycopeptides. [ABSTRACT FROM AUTHOR]

We study flow phenomena in relativistic heavy-ion collisions, both in transverse and radial direction, in comparison to experimental data. The collective dynamics of the nucleus-nucleus collision is described within a transport model of the coupled channel BUU type (CBUU). This recently developed version includes all nucleonic resonances up to 1.95 GeV in mass and mean-field potentials both of the Skyrme and momentum dependent MDYI type. We find that heavy resonances play an important role in the description of transverse flow above 1 AGeV incident energy. For radial flow we analyse reaction times and equilibration and extract the parameters T and β for temperature and collective flow velocity within different prescriptions. Furthermore, we apply a coalescence model for fragment production and check the mass dependence of the flow signals. [ABSTRACT FROM AUTHOR]

The effect of calcium infusion was studied in patients with renal tubular acidosis (RTA) and secondary hyperparathyroidism. Both developed after jejunoileal bypass operation (JIB) for morbid obesity. In three of four cases the acidification defect was abolished, probably due to a decrease of serum parathyroid hormone. As we found RTA in 9% (95% confidence limits 2-21%) of our patients, screening for acidosis is recommended in obesity patients after malabsorptive operations. RTA can be verified through an ammonium loading test. Before deciding on reestablishing bowel continuity due to RTA, we suggest that patients be evaluated for secondary hyperparathyroidism and vitamin D deficiency by measurement of serum calcium, parathyroid hormone and vitamin 1.25(OH)D, and any calcium and vitamin D deficiency be corrected. An intravenous calcium loading test can predict the outcome of oral calcium and vitamin D supplementation. If RTA can be abolished through correction of calcium homeostasis, reoperation may be avoided. Before deciding on re-establishing bowel continuity in JIB patients with RTA, we therefore suggest that patients be evaluated for secondary hyperparathyroidism and any calcium deficiency be corrected. [ABSTRACT FROM AUTHOR]

Twelve patients having received an end-to-side jejunoileal bypass operation for morbid obesity 6-10 years previously were studied over three periods of 2 weeks each. The first period was used for baseline observations without any treatment. For the second period patients were randomly assigned to equimolar (75 mmol/day) oral calcium supplements administered either as a slow-release or as a bolus calcium preparation. During the third period these treatments were crossed over. The calcium preparations used caused equal reductions in frequency of bowel movements. Both preparations increased serum calcium and serum phosphate, but significance ( p < 0.05) was reached only during supplementation with the slow-release preparation. Despite the intended raising of serum calcium levels, none of the preparations influenced the 24-hour urine oxalate to creatinine ratio or the urine stone index. There are several other reasons for supplying extra calcium after intestinal bypass procedures, but our data do not support the concept of preventing renal stone formation by means of calcium supplementation. [ABSTRACT FROM AUTHOR]

We investigate the production of pions in heavyion collisions in the energy range of 1-2 GeV/A. The dynamics of the nucleus-nucleus collisions is described by a set of coupled transport equations of the Boltzmann-Uehling-Uhlenbeck type for baryons and mesons. Besides the N(938) and the Δ(1232) we also take into account nucleon resonances up to masses of 1.95 GeV/c as well as π-, η- and ρ-mesons. We study in detail the influence of the higher baryonic resonances and the 2 π-production channels ( NN→NNππ) on the pion spectra in comparison to π data from Ar+ KCl collisions at 1.8 GeV/A and π -data for Au+Au at 1.0GeV/A. We, furthermore, present a detailed comparison of differential pion angular distributions with the BEVALAC data for Ar+ KCl at 1.8 GeV/A. The general agreement obtained indicates that the overall reaction dynamics is well described by our novel transport approach. [ABSTRACT FROM AUTHOR]

We calculate the quasifree photoproduction of pions and eta mesons on nuclei fromC toPb. Assuming that for the quasifree process the cross sections for π/η photoproduction on a nucleon in medium are - besides a lowering due to Pauli blocking - identical to those on a free nucleon, we use these as an input. The produced mesons or resonances then propagate through the nucleus where they can undergo several scattering and absorption processes. This final state interaction, which leads to a lowering of the initial meson yield up to 70%, we simulate in a coupled channel Boltzmann-Uehling-Uhlenbeck transport model. It allows us to study in detail the influence of Fermi motion, Pauli blocking and of the additional decay channels for nucleon resonances in medium on the photoproduction cross section. The calculated total and differential cross sections are compared to experimental data and the influence of the different medium effects on the cross sections is discussed in detail. [ABSTRACT FROM AUTHOR]

In a case of collagenous colitis, cholestyramine treatment resulted in symptomatic and histological normalization. After discontinuation of cholestyramine, collagenous colitis relapsed. At this time fecal cytotoxic activity was demonstrated in McCoy cell lines. Symptoms, histologic changes, and cytotoxicity disappeared when cholestyramine treatment was reinstituted. We hypothesize that a bacterial toxin is responsible for the development of collagenous colitis. [ABSTRACT FROM AUTHOR]

Choanoflagellates are common members of planktonic communities. Some have complex life histories that involve transitions between multiple cell stages. We have grown the loricate choanoflagellate Diaphanoeca grandis on the bacterium Pantoea sp. and integrated kinetic observations at the culture level and at the single cell level. The life history of D. grandis includes a cell division cycle with a number of recognisable cell stages. Mature, loricate D. grandis were immobile and settled on the bottom substratum. Daughter cells were ejected from the lorica 30 min. after cell division, became motile and glided on the bottom substratum until they assembled a lorica. Single cell kinetics could explain overall growth kinetics in D. grandis cultures. The specific growth rate was 0.72 day−1 during exponential growth while mature D. grandis produced daughter cells at a rate of 0.9 day−1. Daughter cells took about 1.2 h to mature. D. grandis was able to abandon and replace its lorica, an event that delayed daughter cell formation by more than 2 days. The frequency of daughter cell formation varied considerably among individuals and single cell kinetics demonstrated an extensive degree of heterogeneity in D. grandis cultures, also when growth appeared to be balanced. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with diverse clinical presentation and outcome. Bio-clinical prognostic models including oncogene expression and cell-of-origin phenotyping has been developed, however, approximately 30% of all patients still die from their disease, illustrating the need for additional prognostic biomarkers associating oncogenesis and phenotypic subclasses. Hence, we tested if alternative splice variations have biomarker potential. Initial alternative splicing analysis of human exon array from clinical DLBCL samples identified candidate genes. Experimental validation by ddPCR was performed in a DLBCL cohort classified into ABC/GCB subclasses, B-cell associated gene signatures (BAGS: naive, centroblast, centrocyte, memory, and plasmablast), and vincristine resistant gene signatures. Prognostic potential was assessed for aberrantly spliced transcripts. Thus, NOTCH3 was identified as alternatively spliced, with differential exon 16 depletion (−exon 16) between differentiation associated BAGS subtypes. Predicted vincristine resistant patients of the GCB subclass had significantly downregulated NOTCH3 −exon 16 transcript expression and tended to display adverse overall survival for R-CHOP treated patients. In conclusion, we have identified a specific alternatively spliced NOTCH3 event that differentiate molecular subtypes of DLBCL and display prognostic and predictive biomarker potential in GCB DLBCL. [ABSTRACT FROM AUTHOR]

In a dry heathland ecosystem we manipulated temperature (warming), precipitation (drought) and atmospheric concentration of CO2 in a full-factorial experiment in order to investigate changes in below-ground biodiversity as a result of future climate change. We investigated the responses in community diversity of nematodes, enchytraeids, collembolans and oribatid mites at two and eight years of manipulations. We used a structural equation modelling (SEM) approach analyzing the three manipulations, soil moisture and temperature, and seven soil biological and chemical variables. The analysis revealed a persistent and positive effect of elevated CO2 on litter C:N ratio. After two years of treatment, the fungi to bacteria ratio was increased by warming, and the diversities within oribatid mites, collembolans and nematode groups were all affected by elevated CO2 mediated through increased litter C:N ratio. After eight years of treatment, however, the CO2-increased litter C:N ratio did not influence the diversity in any of the four fauna groups. The number of significant correlations between treatments, food source quality, and soil biota diversities was reduced from six to three after two and eight years, respectively. These results suggest a remarkable resilience within the soil biota against global climate change treatments in the long term. [ABSTRACT FROM AUTHOR]

The production of antiprotons in proton-nucleus and deuteron-nucleus collisions is analyzed with respect to one-step nucleon-nucleon ( NN → NNp¯ p) and secondary Δ-nucleon ( ΔN → NNN¯ p) production channels within a phase-space model incorporating the selfenergies of the baryons. It is found that contrary to nucleus-nucleus collisions the Δ induced reaction channels are of minor importance except at very low bombarding energies. The data from KEK are approximately reproduced when accounting for the internal momentum distribution of the deuteron which provides a natural explanation for the large enhancement of the ¯ p cross section in d+A as compared to p+A. [ABSTRACT FROM AUTHOR]

Comments on a research article regarding the effects of cimetidine on body weight. Conflicting evidence on the subject matter from academic publications; Analysis of pertinent topics and relevant issues; Implications on the study of obesity.