Chemical potential oscillations from a single nodal pocket in the underdoped high-Tc superconductor YBa2Cu3O6+x

The mystery of the normal state in the underdoped cuprates has deepened with the use of newer and complementary experimental probes. While photoemission studies have revealed solely `Fermi arcs' centered on nodal points in the Brillouin zone at which holes aggregate upon doping, more recent quantum oscillation experiments have been interpreted in terms of an ambipolar Fermi surface, that includes sections containing electron carriers located at the antinodal region. To address the question of whether an ambipolar Fermi surface truly exists, here we utilize measurements of the second harmonic quantum oscillations, which reveal that the amplitude of these oscillations arises mainly from oscillations in the chemical potential, providing crucial information on the nature of the Fermi surface in underdoped YBa2Cu3O6+x. In particular, the detailed relationship between the second harmonic amplitude and the fundamental amplitude of the quantum oscillations leads us to the conclusion that there exists only a single underlying quasi-two dimensional Fermi surface pocket giving rise to the multiple frequency components observed via the effects of warping, bilayer splitting and magnetic breakdown. A range of studies suggest that the pocket is most likely associated with states near the nodal region of the Brillouin zone of underdoped YBa2Cu3O6+x at high magnetic fields.Comment: 7 pages, 4 figure

Preliminary investigation of the associations between psychological flexibility, symptoms, and daily functioning in people with chronic abdominal pain

Objective: Acceptance and Commitment Therapy, based in the psychological flexibility model, may benefit people with chronic abdominal pain. The current study preliminarily investigates associations between psychological flexibility processes and daily general, social, and emotional functioning in chronic abdominal pain. Methods: An online survey comprising measures of psychological flexibility processes and daily functioning was distributed through social media. Subjects: 89 participants with chronic abdominal pain were included in the analyses. Results: All investigated psychological flexibility processes significantly correlated with pain interference, work and social adjustment, and depression, in the expected directions (|r|=.35-.68). Only pain acceptance significantly correlated with gastrointestinal symptoms, r=-.25. After adjusting for pain in the analyses, pain acceptance remained significantly associated with all outcomes, |β|=.28 to .56, but depression. After adjusting for pain and pain acceptance, only cognitive fusion remained significantly associated with anxiety, β=-.27, and depression, β=.43. When contrasting GI-specific anxiety with psychological flexibility processes, pain acceptance was uniquely associated with pain-related interference and work and social adjustment, and cognitive fusion and committed action were uniquely associated with depression. Conclusions: Psychological flexibility processes were positively associated with daily functioning in people with chronic abdominal pain. Acceptance and Commitment Therapy may provide benefit for these people. Further studies with experimental designs are needed to examine the utility of ACT for people with abdominal pain

Thiol-Based Redox Switches in Eukaryotic Proteins

Abstract For many years, oxidative thiol modifications in cytosolic proteins were largely disregarded as in vitro artifacts, and considered unlikely to play significant roles within the reducing environment of the cell. Recent developments in in vivo thiol trapping technology combined with mass spectrometric analysis have now provided convincing evidence that thiol-based redox switches are used as molecular tools in many proteins to regulate their activity in response to reactive oxygen and nitrogen species. Reversible oxidative thiol modifications have been found to modulate the function of proteins involved in many different pathways, starting from gene transcription, translation and protein folding, to metabolism, signal transduction, and ultimately apoptosis. This review will focus on three well-characterized eukaryotic proteins that use thiol-based redox switches to influence gene transcription, metabolism, and signal transduction. The transcription factor Yap1p is a good illustration of how oxidative modifications affect the function of a protein without changing its activity. We use glyeraldehyde-3-phosphate dehydrogenase to demonstrate how thiol modification of an active site cysteine re-routes metabolic pathways and converts a metabolic enzyme into a pro-apoptotic factor. Finally, we introduce the redox-sensitive protein tyrosine phosphatase PTP1B to illustrate that reversibility is one of the fundamental aspects of redox-regulation. Antioxid. Redox Signal. 11, 997-1014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78110/1/ars.2008.2285.pd

Computing and visually analyzing mutual information in molecular co-evolution

<p>Abstract</p> <p>Background</p> <p>Selective pressure in molecular evolution leads to uneven distributions of amino acids and nucleotides. In fact one observes correlations among such constituents due to a large number of biophysical mechanisms (folding properties, electrostatics, ...). To quantify these correlations the mutual information -after proper normalization - has proven most effective. The challenge is to navigate the large amount of data, which in a study for a typical protein cannot simply be plotted.</p> <p>Results</p> <p>To visually analyze mutual information we developed a matrix visualization tool that allows different views on the mutual information matrix: filtering, sorting, and weighting are among them. The user can interactively navigate a huge matrix in real-time and search e.g., for patterns and unusual high or low values. A computation of the mutual information matrix for a sequence alignment in FASTA-format is possible. The respective stand-alone program computes in addition proper normalizations for a null model of neutral evolution and maps the mutual information to <it>Z</it>-scores with respect to the null model.</p> <p>Conclusions</p> <p>The new tool allows to compute and visually analyze sequence data for possible co-evolutionary signals. The tool has already been successfully employed in evolutionary studies on HIV1 protease and acetylcholinesterase. The functionality of the tool was defined by users using the tool in real-world research. The software can also be used for visual analysis of other matrix-like data, such as information obtained by DNA microarray experiments. The package is platform-independently implemented in <monospace>Java</monospace> and free for academic use under a GPL license.</p

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Using the Prevalence of Individual Species of Intestinal Nematode Worms to Estimate the Combined Prevalence of Any Species

Mixed infections with roundworm, whipworm and hookworm are common, but survey reports often give only the separate prevalence of each type. However, the combined prevalence is important to estimate accurately the number of individuals who would benefit from control programmes and to make decisions about the frequency of treatment. Previous work suggests that mixed infections involving hookworm occur randomly, but that roundworm and whipworm infections are found together more frequently than would be expected by chance. We used 63 data sets from community surveys that reported both the proportions infected with individual types of worms and the combined proportion infected with any worm. We then calculated the proportion that would be infected with any type of worm if infections had occurred randomly and compared it with the observed combined proportion infected. We found a strong correlation between the observed and predicted combined proportions infected. A small downward correction of the predicted proportion infected by dividing by a factor of 1.06 brought it to a value that nearly equalled the observed proportion infected almost all the time. This simple model could be applied to published survey data to estimate accurately the number of individuals that would benefit from mass deworming

Recovery index, attentiveness and state of memory after xenon or isoflurane anaesthesia: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Performance of patients immediately after anaesthesia is an area of special interest and so a clinical trial was conducted to compare Xenon with Isoflurane anaesthesia. In order to assess the early cognitive recovery the syndrome short test (SST) according to Erzigkeit (Geromed GmbH) was applied.</p> <p>Methods</p> <p>ASA I and II patients undergoing long and short surgical interventions were randomised to receive either general anaesthesia with Xenon or Isoflurane. The primary endpoint was the validated SST which covering memory disturbances and attentiveness. The test was used on the day prior to intervention, one and three hours post extubation. The secondary endpoint was the recovery index (RI) measured after the end of the inhalation of Xenon or Isoflurane. In addition the Aldrete score was evaluated up to 180 min. On the first post-operative day the patients rated the quality of the anaesthetic using a scoring system from 1-6.</p> <p>Results</p> <p>The demographics of the groups were similar. The sum score of the SST delivered a clear trend one hour post extubation and a statistically significant superiority for Xenon three hours post extubation (p < 0.01). The RI likewise revealed a statistically significant superiority of Xenon 5 minutes post extubation (p < 0.01). The Aldrete score was significantly higher for 45 min. The scoring system results were also better after Xenon anaesthesia (p < 0.001).</p> <p>Conclusions</p> <p>The results show that recovery from anaesthesia and the early return of post-operative cognitive functions are significantly better after Xenon anaesthesia compared to Isoflurane. The results of the RI for Xenon are similar with the previously published results.</p> <p>Trial Registration</p> <p>The trial was registered with the number ISRCTN01110844 <url>http://www.controlled-trials.com/isrctn/pf/01110844</url>.</p

Reduced Reactivation from Dormancy but Maintained Lineage Choice of Human Mesenchymal Stem Cells with Donor Age

Mesenchymal stem cells (MSC) are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5–80 years) were characterized regarding colony-forming unit-fibroblast (CFU-F) numbers, single cell cloning efficiency (SSCE), osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP) activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. Conclusion: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals

Expansion and Harvesting of hMSC-TERT

The expansion of human mesenchymal stem cells as suspension culture by means of spinner flasks and microcarriers, compared to the cultivation in tissue culture flasks, offers the advantage of reducing the requirements of large incubator capacities as well as reducing the handling effort during cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of hMSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d-1. The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin-accutase mix was most effective. After spinner expansion and harvesting the cells were successfully differentiated to adipocytes