Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation

Experimental violation of a Bell's inequality in time with weak measurement

The violation of J. Bell's inequality with two entangled and spatially separated quantum two- level systems (TLS) is often considered as the most prominent demonstration that nature does not obey ?local realism?. Under different but related assumptions of "macrorealism", plausible for macroscopic systems, Leggett and Garg derived a similar inequality for a single degree of freedom undergoing coherent oscillations and being measured at successive times. Such a "Bell's inequality in time", which should be violated by a quantum TLS, is tested here. In this work, the TLS is a superconducting quantum circuit whose Rabi oscillations are continuously driven while it is continuously and weakly measured. The time correlations present at the detector output agree with quantum-mechanical predictions and violate the inequality by 5 standard deviations.Comment: 26 pages including 10 figures, preprint forma

Mathematical Modelling as a Proof of Concept for MPNs as a Human Inflammation Model for Cancer Development

<p><b>Left:</b> Typical development in stem cells (top panel A) and mature cells (bottom panel B). Healthy hematopoietic cells (full blue curves) dominate in the early phase where the number of malignant cells (stipulated red curves) are few. The total number of cells is also shown (dotted green curves). When a stem cell mutates without repairing mechanisms, a slowly increasing exponential growth starts. At a certain stage, the malignant cells become dominant, and the healthy hematopoietic cells begin to show a visible decline. Finally, the composition between the cell types results in a takeover by the malignant cells, leading to an exponential decline in hematopoietic cells and ultimately their extinction. The development is driven by an approximately exponential increase in the MPN stem cells, and the development is closely followed by the mature MPN cells. <b>Right:</b> B)The corresponding allele burden (7%, 33% and 67% corresponding to ET, PV, and PMF, respectively) defined as the ratio of MPN mature cells to the total number of mature cells.</p

Why do dogs (Canis familiaris) select the empty container in an observational learning task?

Many argue that dogs show unique susceptibility to human communicative signals that make them suitable for being engaged in complex co-operation with humans. It has also been revealed that socially provided information is particularly effective in influencing the behaviour of dogs even when the human’s action demonstration conveys inefficient or mistaken solution of task. It is unclear, however, how the communicative nature of the demonstration context and the presence of the human demonstrator affect the dogs’ object-choice behaviour in observational learning situations. In order to unfold the effects of these factors, 76 adult pet dogs could observe a communicative or a non-communicative demonstration in which the human retrieved a tennis ball from under an opaque container while manipulating another distant and obviously empty (transparent) one. Subjects were then allowed to choose either in the presence of the demonstrator or after she left the room. Results showed a significant main effect of the demonstration context (presence or absence of the human’s communicative signals), and we also found some evidence for the response-modifying effect of the presence of the human demonstrator during the dogs’ choice. That is, dogs predominantly chose the baited container, but if the demonstration context was communicative and the human was present during the dogs’ choice, subjects’ tendency to select the baited container has been reduced. In agreement with the studies showing sensitivity to human’s communicative signals in dogs, these findings point to a special form of social influence in observational learning situations when it comes to learning about causally opaque and less efficient (compared to what comes natural to the dog) action demonstrations

Characterizations of how species mediate ecosystem properties require more comprehensive functional effect descriptors

The importance of individual species in mediating ecosystem process and functioning is generally accepted, but categorical descriptors that summarize species-specific contributions to ecosystems tend to reference a limited number of biological traits and underestimate the importance of how organisms interact with their environment. Here, we show how three functionally contrasting sediment-dwelling marine invertebrates affect fluid and particle transport - important processes in mediating nutrient cycling - and use high-resolution reconstructions of burrow geometry to determine the extent and nature of biogenic modification. We find that individual functional effect descriptors fall short of being able to adequately characterize how species mediate the stocks and flows of important ecosystem properties and that, in contrary to common practice and understanding, they are not substitutable with one another because they emphasize different aspects of species activity and behavior. When information derived from these metrics is combined with knowledge of how species behave and modify their environment, however, detailed mechanistic information emerges that increases the likelihood that a species functional standing will be appropriately summarized. Our study provides evidence that more comprehensive functional effect descriptors are required if they are to be of value to those tasked with projecting how altered biodiversity will influence future ecosystems

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease

The effect of acute vs chronic magnesium supplementation on exercise and recovery on resistance exercise, blood pressure and total peripheral resistance on normotensive adults

© 2015 Kass and Poeira; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Magnesium supplementation has previously shown reductions in blood pressure of up to 12 mmHg. A positive relationship between magnesium supplementation and performance gains in resistance exercise has also been seen. However, no previous studies have investigated loading strategies to optimise response. The aim of this study was to assess the effect of oral magnesium supplementation on resistance exercise and vascular response after intense exercise for an acute and chronic loading strategy on a 2-day repeat protocol. Methods: The study was a randomised, double-blind, cross-over design, placebo controlled 2 day repeat measure protocol (n = 13). Intense exercise (40 km time trial) was followed by bench press at 80% 1RM to exhaustion, with blood pressure and total peripheral resistance (TPR) recorded. 300 mg/d elemental magnesium was supplemented for either a 1 (A) or 4 (Chr) week loading strategy. Food diaries were recorded. Results: Dietary magnesium intake was above the Reference Nutrient Intake (RNI) for all groups. Bench press showed a significant increase of 17.7% (p = 0.031) for A on day 1. On day 2 A showed no decrease in performance whilst Chr showed a 32.1% decrease. On day 2 post-exercise systolic blood pressure (SBP) was significantly lower in both A (p = 0.0.47) and Chr (p = 0.016) groups. Diastolic blood pressure (DBP) showed significant decreases on day 2 solely for A (p = 0.047) with no changes in the Chr. TPR reduced for A on days 1 and 2 (p = 0.031) with Chr showing an increase on day 1 (p = 0.008) and no change on day 2. Conclusion: There was no cumulative effect of Chr supplementation compared to A. A group showed improvement for bench press concurring with previous research which was not seen in Chr. On day 2 A showed a small non-significant increase but not a decrement as expected with Chr showing a decrease. DBP showed reductions in both Chr and A loading, agreeing with previous literature. This is suggestive of a different mechanism for BP reduction than for muscular strength. TPR showed greater reductions with A than Chr, which would not be expected as both interventions had reductions in BP, which is associated with TPR.Peer reviewedFinal Published versio

Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications

<p>Abstract</p> <p>Background</p> <p>The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where selective pressure is applied to a partially genetically engineered strain to confer a desirable phenotype. The exact genetic modification or resulting genotype that leads to the improved phenotype is often not identified or understood to enable further metabolic engineering.</p> <p>Results</p> <p>In this work we performed whole genome high-throughput sequencing and annotation can be used to identify single nucleotide polymorphisms (SNPs) between <it>Saccharomyces cerevisiae </it>strains S288c and CEN.PK113-7D. The yeast strain S288c was the first eukaryote sequenced, serving as the reference genome for the <it>Saccharomyces </it>Genome Database, while CEN.PK113-7D is a preferred laboratory strain for industrial biotechnology research. A total of 13,787 high-quality SNPs were detected between both strains (reference strain: S288c). Considering only metabolic genes (782 of 5,596 annotated genes), a total of 219 metabolism specific SNPs are distributed across 158 metabolic genes, with 85 of the SNPs being nonsynonymous (e.g., encoding amino acid modifications). Amongst metabolic SNPs detected, there was pathway enrichment in the galactose uptake pathway (<it>GAL1</it>, <it>GAL10</it>) and ergosterol biosynthetic pathway (<it>ERG8</it>, <it>ERG9</it>). Physiological characterization confirmed a strong deficiency in galactose uptake and metabolism in S288c compared to CEN.PK113-7D, and similarly, ergosterol content in CEN.PK113-7D was significantly higher in both glucose and galactose supplemented cultivations compared to S288c. Furthermore, DNA microarray profiling of S288c and CEN.PK113-7D in both glucose and galactose batch cultures did not provide a clear hypothesis for major phenotypes observed, suggesting that genotype to phenotype correlations are manifested post-transcriptionally or post-translationally either through protein concentration and/or function.</p> <p>Conclusions</p> <p>With an intensifying need for microbial cell factories that produce a wide array of target compounds, whole genome high-throughput sequencing and annotation for SNP detection can aid in better reducing and defining the metabolic landscape. This work demonstrates direct correlations between genotype and phenotype that provides clear and high-probability of success metabolic engineering targets. The genome sequence, annotation, and a SNP viewer of CEN.PK113-7D are deposited at <url>http://www.sysbio.se/cenpk</url>.</p

Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing a New Population from the Southern Edge of Their Distribution

Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is the most threatened small cetacean on the Atlantic coast of South America. Four Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro (FMA I), São Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA III), and Argentina (FMA IV). Further genetic studies distinguished additional populations within these FMAs. We analyzed the population structure, phylogeography, and demographic history in the southernmost portion of the species range. From the analysis of mitochondrial DNA control region sequences, 5 novel haplotypes were found, totalizing 60 haplotypes for the entire distribution range. The haplotype network did not show an apparent phylogeographical signal for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and Necochea (NC)+Claromecó (CL)+Río Negro (RN). The low levels of genetic variability, the relative constant size over time, and the low levels of gene flow may indicate that MH has been colonized by a few maternal lineages and became isolated from geographically close populations. The apparent increase in NC+CL+RN size would be consistent with the higher genetic variability found, since genetic diversity is generally higher in older and expanding populations. Additionally, RN may have experienced a recent split from CL and NC; current high levels of gene flow may be occurring between the latter ones. FMA IV would comprise four franciscana dolphin populations: Samborombón West+Samborombón South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and MH. Results achieved in this study need to be taken into account in order to ensure the long-term survival of the species.Fil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Tunez, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján; ArgentinaFil: Dejean, Cristina Beatriz. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas. Sección Antropología Biológica; ArgentinaFil: Failla, Mauricio. Fundación Cethus; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Negri, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Cappozzo, Humberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; Argentin

Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

<p>Abstract</p> <p>Background</p> <p>Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach.</p> <p>Methods</p> <p>Differentiated mouse myotube cultures (C2C12) were exposed to 5 mM creatine monohydrate (CMH) for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional ¹H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH₂oxidation after 24 h pre-incubation with CMH.</p> <p>Results</p> <p>The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the antioxidative defence system. The suggested improvement of the antioxidative defence was confirmed by a reduced intracellular DCFH₂oxidation with increasing concentrations of CMH in the 24 h pre-incubation medium.</p> <p>Conclusions</p> <p>The explorative approach of this study combined with the determination of a decreased intracellular DCFH₂oxidation revealed an additional stimulation of cellular antioxidative mechanisms when myotubes were exposed to CMH. This may contribute to an increased exercise performance mediated by increased ability to cope with training-induced increases in oxidative stress.</p