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Issue 5 2011

 

Raman supplement 2011
Raman supplement 2011
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Raman supplement 2011

24 October 2011 | By

In this Raman supplement: Solid state transformations of APIS during manufacturing by Raman analysis of pharmaceutical molecules and dosage forms; Detection, determination of chemical composition and chemical profiling of counterfeit medicines...

FIGURE 1 siRNA design principles. (A) Highly effective standard siRNAs have a guide strand (in green) with a less thermodynamically stable 5’ than 3’ end (indicated with dashed lines) and position-specific nucleotide preferences (indicated above guide strand). P and OH indicate 5’ phosphate groups and 3’ hydroxyl ends, respectively; blue region indicate seed region. (B) Bi-functional siRNAs targeting a single or (C) two different transcripts. (D) A dual-targeting siRNA where one strand (light green) targets EGFR and the other strand (dark green) targets CCND1
FIGURE 1 siRNA design principles. (A) Highly effective standard siRNAs have a guide strand (in green) with a less thermodynamically stable 5’ than 3’ end (indicated with dashed lines) and position-specific nucleotide preferences (indicated above guide strand). P and OH indicate 5’ phosphate groups and 3’ hydroxyl ends, respectively; blue region indicate seed region. (B) Bi-functional siRNAs targeting a single or (C) two different transcripts. (D) A dual-targeting siRNA where one strand (light green) targets EGFR and the other strand (dark green) targets CCND1
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Unconventional RNA interference – recent approaches to robust RNAi

19 October 2011 | By Marie Lundbæk, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology and Pål Sætrom, Department of Cancer Research and Molecular Medicine & Department of Computer and Information Science, Norwegian University of Science and Technology

RNA interference (RNAi) is now a standard tool in molecular biology. Short interfering RNAs (siRNAs) for knocking down your favourite human gene are only a couple of mouse-clicks away at your favourite reagent supplier’s website. Moreover, in contrast to initial attempts at siRNA design, these siRNAs usually give potent target…

FIGURE 1 Nested HOX gene expression along the anterior to posterior axis. The expression domains of members of the HOXB group are illustrated, superimposed on the spinal cord of an early vertebrate. The combined expression of HOX genes in defined spatial positions is a key determinate of cell and tissue identity
FIGURE 1 Nested HOX gene expression along the anterior to posterior axis. The expression domains of members of the HOXB group are illustrated, superimposed on the spinal cord of an early vertebrate. The combined expression of HOX genes in defined spatial positions is a key determinate of cell and tissue identity
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HOX genes: HOX transcription factors as biomarkers in cancer

19 October 2011 | By Richard Morgan, Postgraduate Medical School, Faculty of Health and Medical Sciences, University of Surrey

The HOX genes are a family of closely related transcription factors that help to define the identity of cells and tissues during embryonic development and which are also frequently deregulated in cancer, where they have been shown to promote cell survival and proliferation. The high level of cancer-associated HOX expression…

FIGURE 1 Structures of active and inactive conformations of the β2 adrenoceptor Structures of the β2 adrenoceptor (light grey) in an inactive conformation with the antagonist carazolol bound (left33), and in an active conformation in complex with Gs (dark grey) and the agonist BI-167107 bound (right41). In both cases, the ligand is represented by black spheres to show the location of the orthosteric binding site within the membrane-spanning region of the protein. T4 lysozyme (black) is inserted in the third intracellular loop between helices 5 and 6 in the inactive structure (bottom left), and fused in the extracellular N-terminus for the active structure (top right), to remove flexibility and to provide polar surfaces for crystallisation. The nanobody (black, bottom right) served to stabilise the open conformation of Gs and also provided crystallisation contacts
FIGURE 1 Structures of active and inactive conformations of the β2 adrenoceptor Structures of the β2 adrenoceptor (light grey) in an inactive conformation with the antagonist carazolol bound (left33), and in an active conformation in complex with Gs (dark grey) and the agonist BI-167107 bound (right41). In both cases, the ligand is represented by black spheres to show the location of the orthosteric binding site within the membrane-spanning region of the protein. T4 lysozyme (black) is inserted in the third intracellular loop between helices 5 and 6 in the inactive structure (bottom left), and fused in the extracellular N-terminus for the active structure (top right), to remove flexibility and to provide polar surfaces for crystallisation. The nanobody (black, bottom right) served to stabilise the open conformation of Gs and also provided crystallisation contacts
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Lead discovery for targeting G protein-coupled receptors

19 October 2011 | By Sandra Siehler and Sandra W. Cowan-Jacob, Novartis Institutes for BioMedical Research

G protein-coupled receptors (GPCRs) control a plethora of key physiological functions in every cell of an organism. GPCRs are therefore involved in many diseases, since altered ligand or receptor levels and genetic or epigenetic modifications can lead to GPCR dysfunction and hence a pathophysiological phenotype. About one third of currently…

FIGURE 2 Outline of a strategy for testing drugs that perturb embryonic development. Undifferentiated hES cells are grown in (a) control conditions and (b) in the presence of a drug, and then assessed by a high content assay to determine the effect of a drug on cells (by examining the number of cells, expression of markers associated with the differentiated and undifferentiated state, colony number and size). Cells from both conditions are then induced to differentiate to specific cell types to assess the effect of drug treatment on the differentiation ability of hES cells. For example, low number of neurons upon drug treatment may indicate neurotoxic effects of the drug
FIGURE 2 Outline of a strategy for testing drugs that perturb embryonic development. Undifferentiated hES cells are grown in (a) control conditions and (b) in the presence of a drug, and then assessed by a high content assay to determine the effect of a drug on cells (by examining the number of cells, expression of markers associated with the differentiated and undifferentiated state, colony number and size). Cells from both conditions are then induced to differentiate to specific cell types to assess the effect of drug treatment on the differentiation ability of hES cells. For example, low number of neurons upon drug treatment may indicate neurotoxic effects of the drug
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Drug screens on human stem cells: From understanding cell biology to predicting drug toxicity

19 October 2011 | By Ivana Barbaric and Peter W. Andrews, Centre for Stem Cell Biology, University of Sheffield

The Canadian physician William Osler said: “The person who takes medicine must recover twice, once from the disease and once from the medicine.” Indeed, all medicines have side effects – some of which may complicate a patient’s treatment, or in extreme cases may even be fatal. Of concern is the…

FIGURE 1 Schematic overview of the MALDI-MSI process as applied to imaging compound and metabolite distributions in a whole body rat sample. From one section of an animal dosed with the unlabelled compound, the substance and metabolite distributions can be acquired
FIGURE 1 Schematic overview of the MALDI-MSI process as applied to imaging compound and metabolite distributions in a whole body rat sample. From one section of an animal dosed with the unlabelled compound, the substance and metabolite distributions can be acquired
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MALDI-mass spectrometry imaging applied to drug discovery and development

19 October 2011 | By Brendan Prideaux, Dieter Staab, Gregory Morandi, Nicole Ehrhard and Markus Stoeckli, Novartis Institutes for BioMedical Research

Since its introduction in the field of biomedical imaging over 10 years ago1, matrixassisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) has played an ever increasing role in drug discovery and development and is now utilised in laboratories of many leading pharmaceutical companies and collaborating academic institutions.

FIGURE 1The b5 ion is generated by CID which terminates at the C-terminus in an oxazolone ring structure. N-terminal nucleophilic attack of the oxazolone ring results in formation of a macrocyclic intermediate that undergoes ring opening at various positions to generate sequence scrambled b5 ions.
FIGURE 1The b5 ion is generated by CID which terminates at the C-terminus in an oxazolone ring structure. N-terminal nucleophilic attack of the oxazolone ring results in formation of a macrocyclic intermediate that undergoes ring opening at various positions to generate sequence scrambled b5 ions.
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The Forgotten Fragments

19 October 2011 | By Ross Chawner and Claire E. Eyers, Michael Barber Centre for Mass Spectrometry, University of Manchester

Identification of protein biomarkers and the evaluation of changes in protein expression following drug treatment rely on both the generation of peptides from cellular proteins, and the acquisition and interpretation of spectra generated by tandem mass spectrometry (MS/MS). Acquisition of MS/MS spectra in a datadependent manner means that a significant…

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Under the Microscope: Steve Turner

19 October 2011 | By Steve Turner, CEO, Protea Biosciences

Helen Difford, Editor, speaks exclusively to Steve Turner, CEO, Protea Biosciences Based in Morgantown, West Virginia, US company Protea has spent the past 10 years developing new technologies to identify, characterise and quantify biomolecules - the products of living cells. With over 100 products, the company provides labs across the…