A directed enolization strategy enables by-product-free construction of contiguous stereocentres en route to complex amino acids.

Homochiral α-amino acids are widely used in pharmaceutical design as key subunits in chiral catalyst synthesis or as building blocks in synthetic biology. Many synthetic methods have been developed to access rare or unnatural variants by controlling the installation of the α-stereocentre. By contrast, and despite their importance, α-amino acids possessing β-stereocentres are much harder to synthesize. Here we demonstrate an iridium-catalysed protocol that allows the direct upconversion of simple alkenes and glycine derivatives to give β-substituted α-amino acids with exceptional levels of regio- and stereocontrol. Our method exploits the native directing ability of a glycine-derived N-H unit to facilitate Ir-catalysed enolization of the adjacent carbonyl. The resulting stereodefined enolate cross-couples with a styrene or α-olefin to install two contiguous stereocentres. The process offers very high levels of regio- and stereocontrol and occurs with complete atom economy. In broader terms, our reaction design offers a unique directing-group-controlled strategy for the direct stereocontrolled α-alkylation of carbonyl compounds, and provides a powerful approach for the synthesis of challenging contiguous stereocentres

Interdisciplinary research: putting the methods under the microscope

BACKGROUND: While the desirability of interdisciplinary inquiry has been widely acknowledged, indeed has become 'the mantra of science policy', the methods of interdisciplinary collaboration are opaque to outsiders and generally remain undescribed. DISCUSSION: Many have analysed interdisciplinarity, especially in relation to the creation of new disciplines and institutions. These analyses are briefly outlined. Still, there currently persists a silence about the methods of interdisciplinary collaboration itself, and the core of this paper proposes a template for such methods. SUMMARY: Breaking this silence – by making the methods of interdisciplinary projects transparent – could further invigorate interdisciplinary research

Genoviz Software Development Kit: Java tool kit for building genomics visualization applications

<p>Abstract</p> <p>Background</p> <p>Visualization software can expose previously undiscovered patterns in genomic data and advance biological science.</p> <p>Results</p> <p>The Genoviz Software Development Kit (SDK) is an open source, Java-based framework designed for rapid assembly of visualization software applications for genomics. The Genoviz SDK framework provides a mechanism for incorporating adaptive, dynamic zooming into applications, a desirable feature of genome viewers. Visualization capabilities of the Genoviz SDK include automated layout of features along genetic or genomic axes; support for user interactions with graphical elements (Glyphs) in a map; a variety of Glyph sub-classes that promote experimentation with new ways of representing data in graphical formats; and support for adaptive, semantic zooming, whereby objects change their appearance depending on zoom level and zooming rate adapts to the current scale. Freely available demonstration and production quality applications, including the Integrated Genome Browser, illustrate Genoviz SDK capabilities.</p> <p>Conclusion</p> <p>Separation between graphics components and genomic data models makes it easy for developers to add visualization capability to pre-existing applications or build new applications using third-party data models. Source code, documentation, sample applications, and tutorials are available at <url>http://genoviz.sourceforge.net/</url>.</p

The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats

In all likelihood, it is only a matter of time before our public health system will face a major biological threat, whether intentionally dispersed or originating from a known or newly emerging infectious disease. It is necessary not only to increase our reactive “biodefense,” but also to be proactive and increase our preparedness. To achieve this goal, it is essential that the scientific and public health communities fully embrace the genomic revolution, and that novel bioinformatic and computing tools necessary to make great strides in our understanding of these novel and emerging threats be developed. Genomics has graduated from a specialized field of science to a research tool that soon will be routine in research laboratories and clinical settings. Because the technology is becoming more affordable, genomics can and should be used proactively to build our preparedness and responsiveness to biological threats. All pieces, including major continued funding, advances in next-generation sequencing technologies, bioinformatics infrastructures, and open access to data and metadata, are being set in place for genomics to play a central role in our public health system

Atom and step economical synthesis of acyclic quaternary centers via iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes

Quaternary benzylic centers are accessed with high atom and step economy by Ir-catalyzed alkene hydroarylation. These studies provide unique examples of the use of non-polarized 1,1-disubstituted alkenes in branch selective Murai-type hydro(hetero)arylations. Detailed mechanistic studies have been undertaken, and these indicate that the first irreversible step is the demanding alkene carbometallation process. Structure-reactivity studies show that the efficiency of this is critically dependent on key structural features of the ligand. Computational studies have been undertaken to rationalize this experimental data, showing how more sterically demanding ligands reduce the reaction barrier via predistortion of the reacting intermediate. The key insight disclosed here will underpin the ongoing development of increasingly sophisticated branch selective Murai hydroarylations

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

PORTAL: Pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Major surgical procedures facilitate systemic endotoxinemia and formation of free radicals with subsequent inflammatory changes that can influence the postoperative course. Experimental data suggest that preoperative supraphysiological doses of melatonin, a potent immuno-modulator and antioxidant, would decrease postoperative infectious and non-infectious complications induced by major abdominal surgery.</p> <p>Methods/Design</p> <p>A randomized controlled double blind single center clinical trial with two study arms comprising a total of 40 patients has been designed to assess the effects of a single preoperative dose of melatonin before major liver resection. Primary endpoints include the determination of safety and tolerance of the regimen as well as clinical parameters reflecting pathophysiological functions of the liver. Furthermore, data on clinical outcome (infectious and non-infectious complications) will be collected as secondary endpoints to allow a power calculation for a randomized clinical trial aiming at clinical efficacy.</p> <p>Discussion</p> <p>Based on experimental data, this ongoing clinical trial represents an advanced element of the research chain from bench to bedside in order to reach the highest level of evidence-based clinical facts to determine if melatonin can improve the general outcome after liver resection.</p> <p>Trial Registration</p> <p>EudraCT200600530815</p

Accuracy in Copy Number Calling by qPCR and PRT: A Matter of DNA

The possible implication of copy number variation (CNV) in the genetic susceptibility to human disease needs to be assessed using robust methods that can be applied at a population scale. In this report, we analyze the performance of the two major techniques, quantitative PCR (qPCR) and paralog ratio test (PRT), and investigate the influence of input DNA amount and template integrity on the reliability of both methods. Analysis of three genes (PRELID1, SYNPO and DEFB4) in a large sample set showed that both methods are prone to false copy number assignments if sufficient attention is not paid to DNA concentration and quality. Accurate normalization of samples is essential for reproducible qPCR because it avoids the effect of differential amplification efficiencies between target and control assays, whereas PRT is generally more sensitive to template degradation due to the fact that longer amplicons are usually needed to optimize sensitivity and specificity of paralog sequence PCR. The use of normalized, high quality genomic DNA yields comparable results with both methods