Characterization of phenylpropanoid pathway genes within European maize (Zea mays L.) inbreds

<p>Abstract</p> <p>Background</p> <p>Forage quality of maize is influenced by both the content and structure of lignins in the cell wall. Biosynthesis of monolignols, constituting the complex structure of lignins, is catalyzed by enzymes in the phenylpropanoid pathway.</p> <p>Results</p> <p>In the present study we have amplified partial genomic fragments of six putative phenylpropanoid pathway genes in a panel of elite European inbred lines of maize (<it>Zea mays </it>L.) contrasting in forage quality traits. Six loci, encoding C4H, 4CL1, 4CL2, C3H, F5H, and CAD, displayed different levels of nucleotide diversity and linkage disequilibrium (LD) possibly reflecting different levels of selection. Associations with forage quality traits were identified for several individual polymorphisms within the <it>4CL1</it>, <it>C3H</it>, and <it>F5H </it>genomic fragments when controlling for both overall population structure and relative kinship. A 1-bp indel in <it>4CL1 </it>was associated with <it>in vitro </it>digestibility of organic matter (IVDOM), a non-synonymous SNP in <it>C3H </it>was associated with IVDOM, and an intron SNP in <it>F5H </it>was associated with neutral detergent fiber. However, the <it>C3H </it>and <it>F5H </it>associations did not remain significant when controlling for multiple testing.</p> <p>Conclusion</p> <p>While the number of lines included in this study limit the power of the association analysis, our results imply that genetic variation for forage quality traits can be mined in phenylpropanoid pathway genes of elite breeding lines of maize.</p

Anaesthesia Monitoring by Recurrence Quantification Analysis of EEG Data

Appropriate monitoring of the depth of anaesthesia is crucial to prevent deleterious effects of insufficient anaesthesia on surgical patients. Since cardiovascular parameters and motor response testing may fail to display awareness during surgery, attempts are made to utilise alterations in brain activity as reliable markers of the anaesthetic state. Here we present a novel, promising approach for anaesthesia monitoring, basing on recurrence quantification analysis (RQA) of EEG recordings. This nonlinear time series analysis technique separates consciousness from unconsciousness during both remifentanil/sevoflurane and remifentanil/propofol anaesthesia with an overall prediction probability of more than 85%, when applied to spontaneous one-channel EEG activity in surgical patients

Polymorphisms in O-methyltransferase genes are associated with stover cell wall digestibility in European maize (Zea mays L.)

<p>Abstract</p> <p>Background</p> <p>OMT (O-methyltransferase) genes are involved in lignin biosynthesis, which relates to stover cell wall digestibility. Reduced lignin content is an important determinant of both forage quality and ethanol conversion efficiency of maize stover.</p> <p>Results</p> <p>Variation in genomic sequences coding for <it>COMT, CCoAOMT1</it>, and <it>CCoAOMT2 </it>was analyzed in relation to stover cell wall digestibility for a panel of 40 European forage maize inbred lines, and re-analyzed for a panel of 34 lines from a published French study. Different methodologies for association analysis were performed and compared. Across association methodologies, a total number of 25, 12, 1, 6 <it>COMT </it>polymorphic sites were significantly associated with DNDF, OMD, NDF, and WSC, respectively. Association analysis for <it>CCoAOMT1 </it>and <it>CCoAOMT2 </it>identified substantially fewer polymorphic sites (3 and 2, respectively) associated with the investigated traits. Our re-analysis on the 34 lines from a published French dataset identified 14 polymorphic sites significantly associated with cell wall digestibility, two of them were consistent with our study. Promising polymorphisms putatively causally associated with variability of cell wall digestibility were inferred from the total number of significantly associated SNPs/Indels.</p> <p>Conclusions</p> <p>Several polymorphic sites for three O-methyltransferase loci were associated with stover cell wall digestibility. All three tested genes seem to be involved in controlling DNDF, in particular <it>COMT</it>. Thus, considerable variation among <it>Bm3 </it>wildtype alleles can be exploited for improving cell-wall digestibility. Target sites for functional markers were identified enabling development of efficient marker-based selection strategies.</p

Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning : a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation

Background: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach. Methods: We analyzed long-term outcomes in a cohort of 1423 AML patients, age >= 50 years, after SCT from HLA-matched siblings, during the years 1997-2005, median follow-up 8.3 years (0.1-17). Results: The 10-year leukemia-free survival (LFS) was 31 % (95CI, 27-35) and 32 % (28-35) after MAC and RIC, respectively (P = 0.57). The 10-year GVHD/relapse-free survival (GRFS), a surrogate for quality of life was 22 % (18-25) and 21 % (18-24), respectively (P = 0.79). The 10-year non-relapse mortality (NRM) was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65-76) and 73 % (67-78) after MAC and RIC, respectively (P = 0.76). Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC. Conclusions: Long-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches.Peer reviewe

There is no age limit for methadone: a retrospective cohort study

BACKGROUND: Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. METHODS: The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized data was taken from the methadone register of Basel-City. For analysis of age distributions, patient samples were split into four age categories from '20-29 years' to '50 years and over'. Cross-sectional comparisons were performed using patient samples of 1996 and 2003. RESULTS: Analysis showed a significant increase in older patients between 1996 and 2003 (p < 0.001). During that period, the percentage of patients aged 50 and over rose almost tenfold, while the proportion of patients aged under 30 dropped significantly from 52.8% to 12.3%. The average methadone dose (p < 0.001) and the 1-year retention rate (p < 0.001) also increased significantly. CONCLUSIONS: Findings point to clear trends in aging of methadone patients in Basel-City which are comparable, although less pronounced, to developments among US methadone populations. Many unanswered questions on medical, psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively. However, older methadone patients, just as any other patients, should be accorded treatment appropriate to their medical condition and needs. Particular attention should be paid to adequate solutions for persons in need of care

Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory Perspective

High-throughput screening (HTS) represents a major cornerstone of drug discovery. The availability of an innovative, relevant and high-quality compound collection to be screened often dictates the final fate of a drug discovery campaign. Given that the chemical space to be sampled in research programs is practically infinite and sparsely populated, significant efforts and resources need to be invested in the generation and maintenance of a competitive compound collection. The European Lead Factory (ELF) project is addressing this challenge by leveraging the diverse experience and know-how of academic groups and small and medium enterprises (SMEs) engaged in synthetic and/or medicinal chemistry. Here, we describe the novelty, diversity, structural complexity, physicochemical characteristics and overall attractiveness of this first batch of ELF compounds for HTS purposes

Dwarf Elliptical Galaxies

Dwarf elliptical (dE) galaxies, with blue absolute magnitudes typically fainter than $M_B = -16$, are the most numerous type of galaxy in the nearby universe. Tremendous advances have been made over the past several years in delineating the properties of both Local Group satellite dE's and the large dE populations of nearby clusters. We review some of these advances, with particular attention to how well currently available data can constrain 1) models for the formation of dE's, 2) the physical and evolutionary connections between different types of galaxies (nucleated and nonnucleated dE's, compact E's, irregulars, and blue compact dwarfs) that overlap in the same portion of the mass-spectrum of galaxies, 3) the contribution of dE's to the galaxy luminosity functions in clusters and the field, 4) the star-forming histories of dE's and their possible contribution to faint galaxy counts, and 5) the clustering properties of dE's. In addressing these issues, we highlight the extent to which selection effects temper these constraints, and outline areas where new data would be particularly valuable.Comment: 63p, uuencoded compressed postscript, 2/8 figs included, A&A Review in press, request paper copies from [email protected], STScI 86