MedWorm: Biomedical Science

Same Kinds of Circadian Rhythms Control Cyanobacteria Division and Human Sleep

NIGMS - Results — Fri, 19 Mar 2010 21:12:54 +0100

(Source: NIGMS - Results)

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Heritable Individuality May Lie Not in Genes But in Gene-Controlling Regions

NIGMS - Results — Fri, 19 Mar 2010 19:50:21 +0100

(Source: NIGMS - Results)

Notes to Contributors

Metabolism - Clinical and Experimental — Fri, 19 Mar 2010 17:18:58 +0100

(Source: Metabolism - Clinical and Experimental)

Editorial Board

Metabolism - Clinical and Experimental — Fri, 19 Mar 2010 17:18:58 +0100

(Source: Metabolism - Clinical and Experimental)

Metabolism - Clinical and Experimental — Fri, 19 Mar 2010 17:18:58 +0100

(Source: Metabolism - Clinical and Experimental)

Masthead

Metabolism - Clinical and Experimental — Fri, 19 Mar 2010 17:18:55 +0100

(Source: Metabolism - Clinical and Experimental)

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Microarray Methods for Drug Discovery

Springer Biomedical Sciences titles — Fri, 19 Mar 2010 17:18:41 +0100

series:Methods in Molecular BiologyWhile the utilization of microarrays for gene expression studies has been widely published, Microarray Methods for Drug Discovery describes the use of this technology for a multitude of other vital applications. Covering the field of drug discovery through its various aspects, including high throughput screening, target identification, drug metabolism and toxicity screening as well as clinical ... (Source: Springer Biomedical Sciences titles)

Science signaling podcast: 16 march 2010.

Science Signaling — Fri, 19 Mar 2010 05:24:03 +0100

Authors: Bennett V, Vanhook AM This is a conversation with Vann Bennett about a Research Article published in the 16 March 2010 issue of Science Signaling. PMID: 20234001 [PubMed - in process] (Source: Science Signaling)

Cholinergic augmentation of insulin release requires ankyrin-B.

Science Signaling — Fri, 19 Mar 2010 05:24:03 +0100

Authors: Healy JA, Nilsson KR, Hohmeier HE, Berglund J, Davis J, Hoffman J, Kohler M, Li LS, Berggren PO, Newgard CB, Bennett V Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca(2+)) release. Ankyrin-B binds to the IP(3)R and is enriched in pancreatic beta cells. We found that ankyrin-B-deficient islets displayed impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular Ca(2+) release, and reduced the abundance of IP(3)R. Ankyrin-B-haploinsufficient mice exhibited hyperglycemia after oral ingestion but not after intraperitoneal injection of glucose, consistent with impaired parasympathetic potentiation ...

Inferring signaling pathway topologies from multiple perturbation measurements of specific biochemical species.

Science Signaling — Fri, 19 Mar 2010 05:24:03 +0100

Authors: Xu TR, Vyshemirsky V, Gormand A, von Kriegsheim A, Girolami M, Baillie GS, Ketley D, Dunlop AJ, Milligan G, Houslay MD, Kolch W The specification of biological decisions by signaling pathways is encoded by the interplay between activation dynamics and network topologies. Although we can describe complex networks, we cannot easily determine which topology the cell actually uses to transduce a specific signal. Experimental testing of all plausible topologies is infeasible because of the combinatorially large number of experiments required to explore the complete hypothesis space. Here, we demonstrate that Bayesian inference-based modeling provides an approach to explore and constrain this hypothesis space, permitting the rational ranking of pathway models. Our approach can use m...

A Loss-of-Function Screen Reveals Ras- and Raf-Independent MEK-ERK Signaling During Chlamydia trachomatis Infection.

Science Signaling — Fri, 19 Mar 2010 05:24:03 +0100

Authors: Gurumurthy RK, Mäurer AP, Machuy N, Hess S, Pleissner KP, Schuchhardt J, Rudel T, Meyer TF Chlamydiae are obligate intracellular bacterial pathogens that have a major effect on human health. Because of their intimate association with their host, chlamydiae depend on various host cell functions for their survival. Here, we present an RNA-interference-based screen in human epithelial cells that identified 59 host factors that either positively or negatively influenced the replication of Chlamydia trachomatis (Ctr). Two factors, K-Ras and Raf-1, which are members of the canonical Ras-Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway, were identified as central components of signaling networ...

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RNA Interference

Springer Biomedical Sciences titles — Fri, 19 Mar 2010 00:11:36 +0100

From Biology to Clinical Applicationsseries:Methods in Molecular BiologyFrom the early days when RNA interference was a strange artifact in worms to the 2006 Noble Prize received by Fire and Mello and the current clinical trials, the field of RNA interference has grown at a breakneck pace. In RNA Interference: From Biology to Clinical Applications, expert contributors provide an overview of the most current science and protocols that span the biological ... (Source: Springer Biomedical Sciences titles)

Drug Delivery

Springer Biomedical Sciences titles — Fri, 19 Mar 2010 00:07:57 +0100

series:Handbook of Experimental PharmacologyIn the view of most experts pharmacology is on drugs, targets, and actions. In the context the drug as a rule is seen as an active pharmaceutical ingredient and not as a complex mixture of chemical entities of a well defined structure. Today, we are becoming more and more aware of the fact that delivery of the active compound to the target site is a key. The present volume gives a topical ... (Source: Springer Biomedical Sciences titles)

PCS-based structure determination of protein-protein complexes.

Journal of Bimolecular NMR — Fri, 19 Mar 2010 00:00:00 +0100

Authors: Saio T, Yokochi M, Kumeta H, Inagaki F A simple and fast nuclear magnetic resonance method for docking proteins using pseudo-contact shift (PCS) and (1)H(N)/(15)N chemical shift perturbation is presented. PCS is induced by a paramagnetic lanthanide ion that is attached to a target protein using a lanthanide binding peptide tag anchored at two points. PCS provides long-range (~40 A) distance and angular restraints between the lanthanide ion and the observed nuclei, while the (1)H(N)/(15)N chemical shift perturbation data provide loose contact-surface information. The usefulness of this method was demonstrated through the structure determination of the p62 PB1-PB1 complex, which forms a front-to-back 20 kDa homo-oligomer. As p62 PB1 does not intrinsically bind metal ions, the la...

A model for arterial adaptation combining microstructural collagen remodeling and 3D tissue growth.

Biomechanics and Modeling in Mechanobiology — Fri, 19 Mar 2010 00:00:00 +0100

Authors: Machyshyn IM, Bovendeerd PH, van de Ven AA, Rongen PM, van de Vosse FN Long-term adaptation of soft tissues is realized through growth and remodeling (G&R). Mathematical models are powerful tools in testing hypotheses on G&R and supporting the design and interpretation of experiments. Most theoretical G&R studies concentrate on description of either growth or remodeling. Our model combines concepts of remodeling of collagen recruitment stretch and orientation suggested by other authors with a novel model of general 3D growth. We translate a growth-induced volume change into a change in shape due to the interaction of the growing tissue with its environment. Our G&R model is implemented in a finite element package in 3D, but applied to two rotationally symmetric...

Scientists go into battle to disarm superbug

Imperial College News — Fri, 19 Mar 2010 00:00:00 +0100

Imperial researchers talk about tackling Clostridium difficile in video interviews - News Release (Source: Imperial College News)

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Evolutionary optimization of peptide substrates for proteases that exhibit rapid hydrolysis kinetics

Biotechnology and Bioengineering — Fri, 19 Mar 2010 00:00:00 +0100

Protease cleavage site recognition motifs can be identified using protease substrate discovery methodologies, but typically exhibit non-optimal specificity and activity. To enable evolutionary optimization of substrate cleavage kinetics, a two-color cellular library of peptide substrates (CLiPS) methodology was developed. Two-color CLiPS was applied to identify peptide substrates for the tobacco etch virus (TEV) protease from a random pentapeptide library, which were then optimized by screening of a focused, extended substrate library. Quantitative library screening yielded seven amino acid substrates exhibiting rapid hydrolysis by TEV protease and high sequence similarity to the native seven-amino-acid substrate, with a strong consensus of EXLY[Phi]QG. Comparison of hydrolysis rates for a...

Effects of Oral Glucocorticoid Therapy on CD4+CD25+CD127- and CD4+CD25high T Cell Levels in Asthmatic Patients

Inflammation — Thu, 18 Mar 2010 19:32:20 +0100

Abstract Our purpose was to evaluate the effects of short-term oral glucocorticoid (GC) treatment on frequencies of T cells with putative regulatory phenotype (namely, CD4+CD25+CD127- and CD4+CD25high) in patients with asthma exacerbations. In addition, we sought to determine frequencies of above T cell subsets in adult asthmatic patients in relation to disease severity and different treatment regimens. The analysis was performed in 62 patients with different stages of asthma and ten healthy controls. Polychromatic flow cytometry was applied to delineate T cells with CD4+CD25+CD127- and CD4+CD25high phenotype. Exhaled nitric oxide analysis was used to assess allergic airway inflammation. Levels of neither CD4+CD25+CD127- nor CD4+CD25high T cells were significantly altered ...

Blinking Bacteria

NIGMS Computing Life — Thu, 18 Mar 2010 18:00:00 +0100

Systems biologists have built a synchronized oscillator--a big step toward developing a blink-based sensor with environmental and drug delivery applications. (Source: NIGMS Computing Life)

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

Histochemistry and Cell Biology — Thu, 18 Mar 2010 15:24:42 +0100

Abstract The implication of dendritic cells (DCs) in the peripheral spreading of prions has increased in the last few years. It has been recently described that DCs can transmit prions to primary neurons from the central nervous system. In order to improve the understanding of the earliest steps of prion peripheral neuroinvasion, we studied, using an in vitro model, the effect of exposing primary peripheral neurons to scrapie-infected lymphoid cells. Thanks to this system, there is evidence that bone marrow dendritic cells (BMDCs) are in connection with neurites of peripheral neurons via cytoplasmic extensions. BMDCs are competent to internalize prions independently from the expression of cellular prion protein (PrPC) and have the capacity to transmit detergent-insoluble, r...

Qi-Shao-Shuang-Gan, a Combination of Astragalus membranaceus Saponins with Paeonia lactiflora Glycosides, Ameliorates Polymicrobial Sepsis Induced by Cecal Ligation and Puncture in Mice

Inflammation — Thu, 18 Mar 2010 14:16:12 +0100

Abstract The present study was performed to investigate the anti-septic effects of Qi-Shao-Shuang-Gan (QSSG), a combination of Astragalus membranaceus saponins (SAM) and Paeonia lactiflora glycosides (GPL), in septic mice induced by cecal ligation and puncture. QSSG was shown to elevate the survival rate of mice, decrease infiltration of polymorphonuclear leukocytes into livers and lungs, lower serum levels of myeloperoxidase, nitric oxide, and lactate dehydrogenase, and decrease mRNA expressions of inducible nitric oxide synthase and interleukin-1β in livers. It also restored the impaired expressions of protein C (PC) mRNA in mouse livers and expressions of thrombomodulin and endothelial PC receptor mRNA in endothelial cells. Neither SAM nor GPL alone could significantly i...

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Tissue stretch induces nuclear remodeling in connective tissue fibroblasts

Histochemistry and Cell Biology — Thu, 18 Mar 2010 14:13:49 +0100

Abstract Studies in cultured cells have shown that nuclear shape is an important factor influencing nuclear function, and that mechanical forces applied to the cell can directly affect nuclear shape. In a previous study, we demonstrated that stretching of whole mouse subcutaneous tissue causes dynamic cytoskeletal remodeling with perinuclear redistribution of α-actin in fibroblasts within the tissue. We have further shown that the nuclei of these fibroblasts have deep invaginations containing α-actin. In the current study, we hypothesized that tissue stretch would cause nuclear remodeling with a reduced amount of nuclear invagination, measurable as a change in nuclear concavity. Subcutaneous areolar connective tissue samples were excised from 28 mice and randomized to ei...

Human LPLUNC1 is a secreted product of goblet cells and minor glands of the respiratory and upper aerodigestive tracts

Histochemistry and Cell Biology — Thu, 18 Mar 2010 14:13:48 +0100

Abstract Long PLUNC1 (LPLUNC1, C20orf114) is a member of a family of poorly described proteins (PLUNCS) expressed in the upper respiratory tract and oral cavity, which may function in host defence. Although it is one of the most highly expressed genes in the upper airways and has been identified in sputum and nasal secretions by proteomic studies, localisation of LPLUNC1 protein has not yet been described. We developed affinity purified antibodies and localised the protein in tissues of the human respiratory tract, oro- and nasopharynx. We have complemented these studies with analysis of LPLUNC1 expression in primary human lung cell cultures and used Western blotting to study the protein in cell culture secretions and in BAL. LPLUNC1 is a product of a population of goblet ...

Multigenerational interstitial growth of biological tissues.

Biomechanics and Modeling in Mechanobiology — Thu, 18 Mar 2010 00:00:00 +0100

This study formulates a theory for multigenerational interstitial growth of biological tissues whereby each generation has a distinct reference configuration determined at the time of its deposition. In this model, the solid matrix of a growing tissue consists of a multiplicity of intermingled porous permeable bodies, each of which represents a generation, all of which are constrained to move together in the current configuration. Each generation's reference configuration has a one-to-one mapping with the master reference configuration, which is typically that of the first generation. This mapping is postulated based on a constitutive assumption with regard to that generations' state of stress at the time of its deposition. For example, the newly deposited generation may be assumed to be i...

A nonlocal constitutive model for trabecular bone softening in compression.

Biomechanics and Modeling in Mechanobiology — Thu, 18 Mar 2010 00:00:00 +0100

Authors: Charlebois M, Jirásek M, Zysset PK Using the three-dimensional morphological data provided by computed tomography, finite element (FE) models can be generated and used to compute the stiffness and strength of whole bones. Three-dimensional constitutive laws capturing the main features of bone mechanical behavior can be developed and implemented into FE software to enable simulations on complex bone structures. For this purpose, a constitutive law is proposed, which captures the compressive behavior of trabecular bone as a porous material with accumulation of irreversible strain and loss of stiffness beyond its yield point and softening beyond its ultimate point. To account for these features, a constitutive law based on damage coupled with hardening anisotropic elastoplas...

Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test

Theoretical Biology and Medical Modelling — Thu, 18 Mar 2010 00:00:00 +0100

Background: The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative. Methods: The SDM was applied to 74 IVGTTs from lean (19), overweight (22), obese (22) and morbidly obese (11) subjects. Estimates from the SDM (KxgI) were compared with the corresponding MM (SI), 1/HOMA-IR index and Euglycemic-Hyperinsulinemic Clamp (M-EHC over 7 subjects) estimates. Results: KxgI was identifiable (CV< 52%) in 73 out of 74 subjects (CV=69% in the 74th subject) and ranged from 1.25E-05 to 4.36E-04 1/(min pM); SI CV was >52% in 36 subjects (u...

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Major new research effort targets key pig diseases

Imperial College News — Thu, 18 Mar 2010 00:00:00 +0100

The project aims to prevent and diagnose costly respiratory diseases in pigs - News Release (Source: Imperial College News)

Increased levels of N{epsilon}-(Carboxymethyl)Lysine in epithelial lining fluid from peripheral airways in patients with chronic obstructive pulmonary disease: a pilot study

Clinical Science — Thu, 18 Mar 2010 00:00:00 +0100

This study was designed to determine the validity of measurement of Nε-(Carboxymethyl)Lysine (CML) levels in ELF for the assessment of small airways inflammation in COPD. Ten non-smokers, 10 current smokers, and 16 COPD patients were included in this study. Concentrations of CML, 8-isoprostane, and interleukin-8 (IL-8) were measured in ELF separately from the central or peripheral airways. CML levels in central airways did not significantly differ, but were markedly higher in peripheral than in central airways in the three groups. However, CML levels in peripheral airways of COPD patients were significantly higher than those in non-smokers and current smokers. In COPD patients, CML level in peripheral airways was significantly correlated with FEV1 (r = -0.82, p = 0.002) and FEV1/FVC...

Theoretical analysis of the mechanisms of a gender differentiation in the propensity for orthostatic intolerance after spaceflight

Theoretical Biology and Medical Modelling — Thu, 18 Mar 2010 00:00:00 +0100

Conclusions: The analysis demonstrated that a 15% lowering of the longitudinal center of gravity in the anatomic structure of the model was all that was necessary to prevent the physiologic compensatory mechanisms from overcoming the propensity for reentry orthostasis leading to syncope. (Source: Theoretical Biology and Medical Modelling)

Just Found

NIGMS Findings — Wed, 17 Mar 2010 17:00:00 +0100

Read about scientists who study the body’s response to anesthetics, why some dogs have curly hair, how Facebook can help scientists study how the flu spreads, and more. Read more. (Source: NIGMS Findings)

The Right Fit

NIGMS Findings — Wed, 17 Mar 2010 17:00:00 +0100

Julie Johnson studies genes and medications that influence blood pressure. Her work may help doctors figure out the best drug and dosage for each patient, leading to safer, more effective medicines for everyone. Read more. (Source: NIGMS Findings)

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Mountains and Mouse Genes

NIGMS Findings — Wed, 17 Mar 2010 17:00:00 +0100

Passionate about rock climbing and biostatistics, Gary Churchill studies mice at the Jackson Laboratory in Maine to learn how genes work together to influence human disease. Read more. (Source: NIGMS Findings)

HHMI’s Gilliam Fellowships Aim to Increase Diversity in Sciences

NIGMS - Results — Wed, 17 Mar 2010 16:28:29 +0100

Former IMSD scholar Lisandro Maya-Ramos was named a 2010 Gilliam fellow by the Howard Hughes Medical Institute. The fellowship provides graduate school support annually for up to 5 years to help move recipients toward careers in science research and teaching. (Source: NIGMS - Results)

Keystone Symposia Awarded $1.37 Million, 5-Year NIH Grant to Fund Ongoing Diversity Efforts

NIGMS - What's New — Wed, 17 Mar 2010 16:28:28 +0100

NIGMS Awards 5-Year MARC Ancillary Training Activities Grant to Keystone Symposia on Molecular and Cellular Biology. (Source: NIGMS - What's New)

New partnership with Sainsbury’s to help reduce its carbon footprint

Imperial College News — Wed, 17 Mar 2010 00:00:00 +0100

Innovative research and engineering solutions for making business more energy efficient - News (Source: Imperial College News)

A comparative analysis of oncofetal fibronectin and tenascin-C incorporation in tumour vessels using human recombinant SIP format antibodies

Histochemistry and Cell Biology — Tue, 16 Mar 2010 14:49:23 +0100

In conclusion, tumours differ in the pattern of Fn or Tn-C isoform positivity in the vessel wall, potentially representing a tumour type specific endothelial cell–tumour cell–stromal cell interaction. Carcinoma cells themselves are involved in vascular Tn-C matrix organization. Up to antigen distribution, Fn and Tn-C domain antibodies may serve as vehicles for antiangiogenetic and antifibrotic agents; oncFn/oncTn-C based targeting should be adapted individually. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00418-010-0685-yAuthors Alexander Berndt, University Hospital Jena Institute of Pathology Ziegelmühlenweg 1 07743 Jena GermanyRobert Köllner, University Hospital Jena Institute of Pathology Ziegelmühlenweg 1 07743 Jena GermanyPetra Richter, University ...

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Effects of dissolucytotic gold ions on recovering brain lesions

Histochemistry and Cell Biology — Tue, 16 Mar 2010 14:49:22 +0100

Abstract Recent experimental research has shown that metallic gold releases charged gold atoms when placed intracerebrally and that the liberated gold ions affect inflammation in the brain. The observations suggest that metallic gold can be used as a safe suppressor of inflammation in the central nervous system. Content Type Journal ArticleCategory ReviewDOI 10.1007/s00418-010-0681-2Authors Gorm Danscher, University of Aarhus Department of Anatomy and Neurobiology 8000 Aarhus C DenmarkAgnete Larsen, University of Aarhus Department of Anatomy and Neurobiology 8000 Aarhus C Denmark Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

Narrow carbonyl resonances in proton-diluted proteins facilitate NMR assignments in the solid-state.

Journal of Bimolecular NMR — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Linser R, Fink U, Reif B HNCO/HNCACO type correlation experiments are an alternative for assignment of backbone resonances in extensively deuterated proteins in the solid-state, given the fact that line widths on the order of 14-17 Hz are achieved in the carbonyl dimension without the need of high power decoupling. The achieved resolution demonstrates that MAS solid-state NMR on extensively deuterated proteins is able to compete with solution-state NMR spectroscopy if proteins are investigated with correlation times tau (c) that exceed 25 ns. PMID: 20232230 [PubMed - as supplied by publisher] (Source: Journal of Bimolecular NMR)

SAGA: rapid automatic mainchain NMR assignment for large proteins.

Journal of Bimolecular NMR — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Crippen GM, Rousaki A, Revington M, Zhang Y, Zuiderweg ER Here we describe a new algorithm for automatically determining the mainchain sequential assignment of NMR spectra for proteins. Using only the customary triple resonance experiments, assignments can be quickly found for not only small proteins having rather complete data, but also for large proteins, even when only half the residues can be assigned. The result of the calculation is not the single best assignment according to some criterion, but rather a large number of satisfactory assignments that are summarized in such a way as to help the user identify portions of the sequence that are assigned with confidence, vs. other portions where the assignment has some correlated alternatives. Thus very imperfect initial data ...

Computer model predicts how materials meet in the middle

Imperial College News — Tue, 16 Mar 2010 00:00:00 +0100

Watch a video of Imperial researchers explaining how they are predicting the structure of interfaces in materials, and why this is important - News (Source: Imperial College News)

University research contributes £45 billion a year to the UK economy, according to new impact study

Imperial College News — Tue, 16 Mar 2010 00:00:00 +0100

Research from Imperial College Business School demonstrates the value of public spending on research in higher education - News Release (Source: Imperial College News)

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The Loss of a Single Gene Confers Mice With the Ability to Regenerate Tissue

NIGMS - Results — Mon, 15 Mar 2010 21:28:40 +0100

(Source: NIGMS - Results)

Complete List of Currently Approved NDA and ANDA Application Submissions

What's New at CBER — Mon, 15 Mar 2010 16:18:00 +0100

Information updated through February 28, 2010 (Source: What's New at CBER)

Complete List of Currently Approved Premarket Approvals (PMAs)

What's New at CBER — Mon, 15 Mar 2010 16:16:00 +0100

Information updated through February 28, 2010 (Source: What's New at CBER)

Complete List of Substantially Equivalent 510(k) Device Applications

What's New at CBER — Mon, 15 Mar 2010 16:15:00 +0100

Information updated through February 28, 2010 (Source: What's New at CBER)

Urine suPAR Levels Compared with Plasma suPAR Levels as Predictors of Post-consultation Mortality Risk Among Individuals Assumed to be TB-negative: A Prospective Cohort Study

Inflammation — Mon, 15 Mar 2010 05:32:55 +0100

Abstract Plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator (suPAR) have been shown to carry prognostic information in various infectious and inflammatory diseases. The present study aimed to compare the prognostic value of urine suPAR (U-suPAR) to that of plasma suPAR (P-suPAR), thereby exploring the possibility of replacing the blood sample with an easy obtainable urine sample. We enrolled 1,007 adults, older than 15 years of age, with a negative TB diagnosis between April 2004 and December 2006. Levels of U-suPAR and P-suPAR were available in 863 individuals. U-suPAR was measured using a commercial ELISA (suPARnostic®). We found that U-suPAR carried significant prognostic information on mortality for HIV-infected subjects with an a...

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Propagation of kinetic uncertainties through a canonical topology of the TLR4 signaling network in different regions of biochemical reaction space

Theoretical Biology and Medical Modelling — Mon, 15 Mar 2010 00:00:00 +0100

Conclusions: Overall, our in silico study suggests that biologically relevant and non-intuitive aspects on the general behavior of a complex biomolecular network can be elucidated only when taking into account a wide spectrum of dynamical regimes attainable by the system. Most importantly, this strategy provides the means for a suitable assessment of the inherent variational constraints imposed by the structure of the system when systematically probing its parameter space. (Source: Theoretical Biology and Medical Modelling)

Developmental regulation of TRPC3 ion channel expression in the mouse cochlea

Histochemistry and Cell Biology — Sun, 14 Mar 2010 11:27:48 +0100

Abstract Canonical transient receptor potential type 3 (TRPC3) ion channels assemble from TRPC3 subunits and exhibit multiple activation mechanisms. TRPC3 has been proposed to contribute to Ca2+ entry supporting Ca2+ homeostasis in cochlear hair cells and to be activated by G protein-coupled receptor (GPCR) signaling in spiral ganglion neurons. The present study was designed to determine the spatiotemporal profile of TRPC3 expression during mouse cochlear ontogeny. TRPC3 immunofluorescence of cryosectioned cochleae was performed using E16–adult tissue. We found that prior to birth, TRPC3 expression was strongest in epithelial cells that form the cochlear partition. In the early postnatal period, to the onset of hearing (~P12), immunofluorescence was strongest in the hair ...

Differential expression of stem cell markers in human follicular bulge and interfollicular epidermal compartments

Histochemistry and Cell Biology — Sun, 14 Mar 2010 11:27:47 +0100

In this study, we whole mounted single human scalp hair follicles and examined their profiles using in situ immunohistochemistry and multicolor immunofluorescence in search of markers to distinguish between stem cells residing in the interfollicular epidermis (IFE) and bulge. Our study revealed that expression of several biomarkers localized uniquely to the basal IFE (CD34 and CD117), bulge region (CD200), or both (CK15, CD49f, and CD29). In addition, we found that both basal IFE and bulge stem cells did not express CD71 or CD24 suggesting their potential utility as negative selection markers. Dermal papilla but not basal IFE or bulge stem cells expressed CD90, making it a potential positive selection marker for dermal hair follicle stem cells. The markers tested in this study may en...

Prenatal Exposure to Inflammation Induced by Zymosan Results in Activation of Intrarenal Renin-Angiotensin System in Adult Offspring Rats

Inflammation — Sun, 14 Mar 2010 11:26:22 +0100

In conclusion, prenatal exposure to zymosan resulted in the activation of intrarenal renin-Ang system in adult offspring rats. Content Type Journal ArticleDOI 10.1007/s10753-010-9199-yAuthors Xue-Qin Hao, Third Military Medical University Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy Chongqing 400038 ChinaHai-Gang Zhang, Third Military Medical University Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy Chongqing 400038 ChinaShu-Hui Li, Third Military Medical University Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy Chongqing 400038 ChinaYi Jia, Third Military Medical University Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy Chongqing 400038 ChinaYa ...

Precise structural determination of weakly binding peptides by utilizing dihedral angle constraints.

Journal of Bimolecular NMR — Sun, 14 Mar 2010 00:00:00 +0100

Authors: Mizukoshi Y, Nagasu M, Shimada I, Takahashi H Structural determination of target-bound conformations of peptides is of primary importance for the optimization of peptide ligands and peptide-mimetic design. In the structural determination of weakly binding ligands, transferred nuclear Overhauser effect (TrNOE) methods have been widely used. However, not many distance constraints can be obtained from small peptide ligands by TrNOE, especially for peptides bound to a target molecule in an extended conformation. Therefore, for precise structural determination of weakly binding peptides, additional structural constraints are required. Here, we present a strategy to systematically introduce dihedral angle constraints obtained from multiple transferred cross-correlated relaxation exp...

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Multi-scale simulation of L-selectin-PSGL-1-dependent homotypic leukocyte binding and rupture.

Biomechanics and Modeling in Mechanobiology — Sun, 14 Mar 2010 00:00:00 +0100

Authors: Gupta VK, Sraj IA, Konstantopoulos K, Eggleton CD L-selectin-PSGL-1-mediated polymorphonuclear (PMN) leukocyte homotypic interactions potentiate the extent of PMN recruitment to endothelial sites of inflammation. Cell-cell adhesion is a complex phenomenon involving the interplay of bond kinetics and hydrodynamics. As a first step, a 3-D computational model based on the Immersed Boundary Method is developed to simulate adhesion-detachment of two PMN cells in quiescent conditions. Our simulations predict that the total number of bonds formed is dictated by the number of available receptors (PSGL-1) when ligands (L-selectin) are in excess, while the excess amount of ligands influences the rate of bond formation. Increasing equilibrium bond length results in a higher number of rec...

A biochemical/biophysical 3D FE intervertebral disc model.

Biomechanics and Modeling in Mechanobiology — Sat, 13 Mar 2010 00:00:00 +0100

Authors: Schroeder Y, Huyghe JM, van Donkelaar CC, Ito K Present research focuses on different strategies to preserve the degenerated disc. To assure long-term success of novel approaches, favorable mechanical conditions in the disc tissue are essential. To evaluate these, a model is required that can determine internal mechanical conditions which cannot be directly measured as a function of assessable biophysical characteristics. Therefore, the objective is to evaluate if constitutive and material laws acquired on isolated samples of nucleus and annulus tissue can be used directly in a whole-organ 3D FE model to describe intervertebral disc behavior. The 3D osmo-poro-visco-hyper-elastic disc (OVED) model describes disc behavior as a function of annulus and nucleus tissue biochemical c...

Whole Genome Sequencing of Family of Four Reveals New Genetic Power

NIGMS - Results — Fri, 12 Mar 2010 21:32:49 +0100

(Source: NIGMS - Results)

Molecular Image of System That Moves Electrons Between Proteins in Cells

NIGMS - Results — Fri, 12 Mar 2010 21:29:50 +0100

(Source: NIGMS - Results)

Title page/Editorial Board

Medical Hypotheses — Fri, 12 Mar 2010 16:15:27 +0100

(Source: Medical Hypotheses)

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Effects of curvature and cell-cell interaction on cell adhesion in microvessels.

Biomechanics and Modeling in Mechanobiology — Fri, 12 Mar 2010 00:00:00 +0100

In this study, the fluid dynamics was carried out by the lattice Boltzmann method (LBM), and the cell dynamics was governed by the Newton's law of translation and rotation. The adhesive dynamics model involved the effect of receptor-ligand bonds between circulating cells and endothelial cells (ECs). It is found that the curved vessel would increase the simultaneous bond number, and the probability of cell adhesion is increased consequently. The interaction between traveling cells would also affect the cell adhesion significantly. For two-cell case, the simultaneous bond number of the rear cell is increased significantly, and the curvature of microvessel further enhances the probability of cell adhesion. PMID: 20224897 [PubMed - as supplied by publisher] (Source: Biomechanics and Modeli...

Core-specific adaptive regulatory T cells in different outcomes of hepatitis C

Clinical Science — Fri, 12 Mar 2010 00:00:00 +0100

Conclusions: We identified functionally active HCV core-specific Tregs in patients with chronic hepatitis C, which share their epitopes with conventional T cells and require the continued presence of antigen to maintain their functional differentiation. Thus, HCV core-specific Tregs may contribute to the immunoregulatory balance in chronic hepatitis C. (Source: Clinical Science)

PINing for Things Past.

Science Signaling — Thu, 11 Mar 2010 17:46:02 +0100

Authors: Sacktor TC Long-term memories are thought to be maintained by persistent changes in the strength of synaptic connections among neurons, but how such changes can persist for days to years has been one of the fundamental enigmas of neuroscience. Recently, however, one mechanism that is dependent on the persistent increased activity of an enzyme has been shown to be necessary for the persistence of long-term memory. The transient inhibition of the brain-specific, constitutively active protein kinase C isoform PKMzeta erases memories that are even months old. This finding raises a number of issues; chief among them is the question, how can PKMzeta maintain memories for months when its half-life is probably much shorter? New data suggest how the high abundance of PKMzeta can be mai...

Pin1 and PKM{zeta} Sequentially Control Dendritic Protein Synthesis.

Science Signaling — Thu, 11 Mar 2010 17:46:02 +0100

Authors: Westmark PR, Westmark CJ, Wang S, Levenson J, O'Riordan KJ, Burger C, Malter JS Some forms of learning and memory and their electrophysiologic correlate, long-term potentiation (LTP), require dendritic translation. We demonstrate that Pin1 (protein interacting with NIMA 1), a peptidyl-prolyl isomerase, is present in dendritic spines and shafts and inhibits protein synthesis induced by glutamatergic signaling. Pin1 suppression increased dendritic translation, possibly through eukaryotic translation initiation factor 4E (eIF4E) and eIF4E binding proteins 1 and 2 (4E-BP1/2). Consistent with increased protein synthesis, hippocampal slices from Pin(-/-) mice had normal early LTP (E-LTP) but significantly enhanced late LTP (L-LTP) compared to wild-type controls. Protein kinase C zet...

Stress-Activated Cap'n'collar Transcription Factors in Aging and Human Disease.

Science Signaling — Thu, 11 Mar 2010 17:46:02 +0100

Authors: Sykiotis GP, Bohmann D Cap'n'collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3; the Caenorhabditis elegans SKN-1; and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory sy...

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Scientists pinpoint source of recurrent yeast infections in autoimmune syndrome

The Rockefeller University Newswire — Thu, 11 Mar 2010 14:15:00 +0100

It turns out that the immune system can create its own infections. Scientists now report that the immune-fighting proteins that keep yeast in check in healthy immune systems are under siege in patients with a rare autoimmune disorder known as APS-1. By pinpointing the cause of candidiasis in these patients, the finding paves the way for treating these fungal infections with drugs that are already out in the market. (Source: The Rockefeller University Newswire)

Preventive Effects of Valnemulin on Lipopolysaccharide-Induced Acute Lung Injury in Mice

Inflammation — Thu, 11 Mar 2010 02:45:02 +0100

In this study, we established a mouse model of lipopolysaccharide (LPS)-induced inflammatory lung injury and investigated the effect of valnemulin (100 mg/kg) on acute lung injury (ALI) 8 h after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels, and superoxidase dismutase (SOD) activity, and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, cytokine mRNA expression, and histological change. We found that the pre-administration of valnemulin significantly decreases the W/D ratio of lungs, protein concentrations, and the number of total cells, neutrophils, macrophages, and leukomonocytes, and histologic analysis indicates that valnemulin significantly attenuates tiss...

New Techniques Identify Interactions Between Chromosomes That Drive Human Cell Division

NIGMS - Results — Wed, 10 Mar 2010 20:29:30 +0100

(Source: NIGMS - Results)

The Neurochemical Basis of Autism

Springer Biomedical Sciences titles — Wed, 10 Mar 2010 17:46:40 +0100

From Molecules to MinicolumnsThe recent perceived rise in autism worldwide has spurned a dramatic increase in autism research, but few studies have focused on determining the neurochemical basis of the disorder. The Neurochemical Basis of Autism: From Molecules to Minicolumns is a uniquely vital and interdisciplinary text that presents the latest findings and newest ideas regarding the physiological, neuropathological, ... (Source: Springer Biomedical Sciences titles)

Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat cochlea

Histochemistry and Cell Biology — Wed, 10 Mar 2010 16:14:07 +0100

This study reports the changes in expression of NTPDase5 and NTPDase6 in the developing rat cochlea. These two intracellular members of the E-NTPDase family can be released in a soluble form and show preference for nucleoside 5′-diphosphates, such as UDP and GDP. Here, we demonstrate differential spatial and temporal patterns for NTPDase5 and NTPDase6 expression during cochlear development, which are indicative of both cytosolic and extracellular action via pyrimidines. NTPDase5 is noted during the early postnatal period in developing sensory hair cells and supporting Deiters’ cells of the organ of Corti, and primary auditory neurons located in the spiral ganglion. In contrast, NTPDase6 is confined to the embryonic and early postnatal hair cell bundles. NTPDase6 immunolocalisatio...

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Nanoaperture Fluorescence Enhancement in the Ultraviolet

Plasmonics — Wed, 10 Mar 2010 15:46:09 +0100

Abstract We study fluorescence excitation and emission enhancement in the ultraviolet regime for molecules confined within sub-wavelength metal apertures. Calculations are performed across a range of excitation wavelengths for individual apertures constructed in gold, silver, and aluminum. As expected, enhancement in the ultraviolet is greatest with aluminum. Using excitation and emission wavelengths appropriate for tryptophan, we find that more than 10× net increase in fluorescence count rate should be obtainable for aluminum apertures of ~75 nm diameter. These results suggest that many applications utilizing native protein fluorescence could become practical, even to the single molecule level. Content Type Journal ArticleDOI 10.1007/s11468-010-9126-yAuthors F...

3D Profile Simulation of Metal Nanostructures Obtained by Closely Packed Nanosphere Lithography

Plasmonics — Wed, 10 Mar 2010 15:46:08 +0100

Abstract Closely packed lithography is a versatile technology to fabricate different kinds of periodically arranged nanostructures on substrate or in solution. Due to its large diversities and versatilities, it is necessary to predict the shape of the nanostructures under various fabrication conditions. This paper gives a full simulation for the profile of metal nanostructures fabricated by closely packed nanosphere lithography. The simulation applies to both hexagonal and quadrangular nanosphere arrangements, and the nanospheres can be in one layer or stacked in two layers, with each layer having a different size. For metal evaporated at any angle onto the nanosphere mask, three-dimensional metal nanostructures on each layer of the nanosphere as well as the substrate are ...

Walnut Extract Inhibits LPS-induced Activation of Bv-2 Microglia via Internalization of TLR4: Possible Involvement of Phospholipase D2

Inflammation — Wed, 10 Mar 2010 15:42:31 +0100

Abstract Walnuts are a rich source of essential fatty acids, including the polyunsaturated fatty acids alpha-linolenic acid and linoleic acid. Essential fatty acids have been shown to modulate a number of cellular processes in the brain, including the activation state of microglia. Microglial activation can result in the generation of cytotoxic intermediates and is associated with a variety of age-related and neurodegenerative conditions. In vitro, microglial activation can be induced with the bacterial cell wall component lipopolysaccharide (LPS). In the present study, we generated a methanolic extract of English walnuts (Juglans regia) and examined the effects of walnut extract exposure on LPS-induced activation in BV-2 microglial cells. When cells were treated with walnu...

The ApoB/ApoA1 Ratio is Associated with Metabolic Syndrome and its Components in a Chinese Population

Inflammation — Wed, 10 Mar 2010 15:42:31 +0100

In this study, we assessed whether the apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) is related to metabolic syndrome (MS) and its components in an urban Chinese population. A total of 709 community residents were enrolled. Metabolic syndrome was defined according to the International Diabetes Federation definition in 2005. The high ApoB/ApoA1 group was defined as the gender-specific upper quartile of the ApoB/ApoA1 ratio. Insulin resistance (IR) was defined as the upper quartile of Homa-IR. The ApoB/ApoA1 ratio was significantly higher in subjects with MS, compared to those without (p < 0.05). After adjusting for age and gender, subjects with MS (odds ratio [OR] = 3.5) or IR (OR = 2.3) were more likely to be in the high ApoB/ApoA1 group. The ApoB/ApoA1 ratio in...

Involvement of Src-Suppressed C Kinase Substrate in Neuronal Death Caused by the Lipopolysaccharide-Induced Reactive Astrogliosis

Inflammation — Wed, 10 Mar 2010 15:42:29 +0100

This study delineates that SSeCKS may be important for host defenses in spinal inflammation and suggests a valuable molecular mechanism by which astrocytes modify neuronal viability during pathological states. Content Type Journal ArticleDOI 10.1007/s10753-010-9194-3Authors Ping Wang, Nantong University Department of Immunology, Medical College Nantong 226001 People’s Republic of ChinaLinlin Sun, Nantong University Department of Immunology, Medical College Nantong 226001 People’s Republic of ChinaAiguo Shen, Nantong University Department of Immunology, Medical College Nantong 226001 People’s Republic of ChinaJunling Yang, Affiliated Hospital of Nantong University Laboratory Center Nantong 226001 People’s Republic of ChinaXiaohong Li, Nantong University The Jiangsu Province ...

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Zileuton Reduces Inflammatory Reaction and Brain Damage Following Permanent Cerebral Ischemia in Rats

Inflammation — Wed, 10 Mar 2010 15:42:28 +0100

Abstract 5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-κB) p65 in rat brain was detected by immunohistochem...

Scientists track variant of gene-regulating protein in embryonic stem cells

The Rockefeller University Newswire — Wed, 10 Mar 2010 13:00:00 +0100

The path to fully developed cells from embryonic stem cells requires that the right genes are turned on and off at the right times. New research from Rockefeller University shows that tiny variations between gene-regulating histone proteins play an important role in determining how and when genes are read. The finding shows that each region of the genome may be even more specialized than previously expected and may open a new avenue of investigation regarding the mysterious causes of the human genetic disease known as ATR-X syndrome. (Source: The Rockefeller University Newswire)

A translational study of circulating cell-free microRNA-1 in acute myocardial infarction

Clinical Science — Wed, 10 Mar 2010 00:00:00 +0100

MicroRNAs (miRNAs) precipitate in many diseases including cardiovascular disease. In contrast to our original thought, miRNAs exist in circulating blood and they are relatively stable due to binding with other materials. The current translational study is to establish a method to determine the absolute amount of a miRNA in blood and to determine the potential applications of circulating cell-free microRNA-1 (miR-1) in acute myocardial infarction (AMI). The results revealed that miR-1 is the most abundant miRNA in the heart and is also a heart and muscle specific miRNA. In a cardiac cell necrosis model induced by Triton-100 in vitro, we found that cardiac miR-1 can be released into cultured medium and is stable at least for 24 h. In a rat model of AMI induced by coronary ligation, we found ...

Model Simulates the Complex Signaling Patterns Involved in Stem Cell and Embryonic Development

NIGMS - Results — Tue, 09 Mar 2010 19:48:10 +0100

(Source: NIGMS - Results)

Protein Competition Over an Enzyme Integrates Signals During Early Embryonic Development

NIGMS - Results — Tue, 09 Mar 2010 19:43:12 +0100

(Source: NIGMS - Results)

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Molecular Diagnostics: Promises and Possibilities(Debnath et al.)

Springer Biomedical Sciences titles — Tue, 09 Mar 2010 16:56:26 +0100

(Source: Springer Biomedical Sciences titles)

Research identifies gene that changes the brains response to stress

The Rockefeller University Newswire — Tue, 09 Mar 2010 16:00:00 +0100

Brains change. They change throughout life, responding to developmental but also environmental cues, like stress. Scientists know of several important proteins that play a role in what brains do with new experience. Now they have identified one, brain-derived neurotrophic factor, which must be present at a certain level to enable the brains adaptive plasticity, particularly in response to stress. (Source: The Rockefeller University Newswire)

Modeling Phase Transitions in the Brain

Springer Biomedical Sciences titles — Tue, 09 Mar 2010 00:19:50 +0100

series:Springer Series in Computational NeuroscienceThe induction of unconsciousness using anesthetic drugs demonstrates that the cerebral cortex can operate in two very different modes: alert and responsive versus unaware and quiescent. But the states of wakefulness and sleep are not single-neuron properties---they emerge as bulk properties of cooperating populations of neurons, with the switchover between states being similar to ... (Source: Springer Biomedical Sciences titles)

The Handbook of Biomarkers(Jain)

Springer Biomedical Sciences titles — Tue, 09 Mar 2010 00:14:19 +0100

(Source: Springer Biomedical Sciences titles)

Diabetes, Insulin and Alzheimer's Disease

Springer Biomedical Sciences titles — Tue, 09 Mar 2010 00:05:52 +0100

series:Research and Perspectives in Alzheimer's DiseaseNeurons share more similarities with insulin-producing pancreatic islet cells than with any other cell type. The root of this similarity may lie in the islet’s evolution from an ancestral insulin-producing neuron. The islet-neuron connection becomes less surprising as we learn more about insulin’s involvement in functions far from its traditional role in mediating glucose uptake in muscle. The ... (Source: Springer Biomedical Sciences titles)

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Immune cells use bungee of death to kill dangerous cells, shows new research

Imperial College News — Tue, 09 Mar 2010 00:00:00 +0100

Natural killer cells use membrane nanotubes to pull in escaping dangerous cells - News Release (Source: Imperial College News)

Wall effects in continuous microfluidic magneto-affinity cell separation

Biotechnology and Bioengineering — Tue, 09 Mar 2010 00:00:00 +0100

We present a theoretical and experimental study that provides a quantitative description of hydrodynamic wall interactions and wall rolling velocity of cells. A transient convection model describes the transport of cells in two-phase microfluidic flow under the influence of an external magnetic field. Transport of cells along the microchannel walls is also considered via an additional equation. Results show the variation of cell flux in the fluid phases and the wall as a function of a dimensionless parameter arising in the equations. Our results suggest that conditions may be optimized to maximize cell separation while minimizing contact with the wall surfaces. Experimentally measured cell rolling velocities on the wall indicate the presence of other near-wall forces in addition to fluid s...

Team Coaxes Plants to Reproduce Asexually, Which Could be Applied in Agriculture

NIGMS - Results — Mon, 08 Mar 2010 20:57:33 +0100

(Source: NIGMS - Results)

Discovery Shows How to Efficiently Turn Carbon Dioxide into Useful Carbon Monoxide With Light

NIGMS - Results — Mon, 08 Mar 2010 20:54:59 +0100

(Source: NIGMS - Results)

Editorial Board and publication information

Journal of Biomechanics — Mon, 08 Mar 2010 17:32:55 +0100

(Source: Journal of Biomechanics)

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Students open up about faith and life in Islam Awareness Week

Imperial College News — Mon, 08 Mar 2010 00:00:00 +0100

A series of talks and social events begins today, to allow staff and students to get to know Imperial Islamic Society - News (Source: Imperial College News)

Imperial celebrates International Women’s Day with a look at women in science

Imperial College News — Mon, 08 Mar 2010 00:00:00 +0100

Two photography exhibitions highlight the work of women in science at Imperial - News (Source: Imperial College News)

The predictive accuracy of secondary chemical shifts is more affected by protein secondary structure than solvent environment.

Journal of Bimolecular NMR — Sat, 06 Mar 2010 00:00:00 +0100

Authors: Tremblay ML, Banks AW, Rainey JK Biomolecular NMR spectroscopy frequently employs estimates of protein secondary structure using secondary chemical shift (Deltadelta) values, measured as the difference between experimental and random coil chemical shifts (RCCS). Most published random coil data have been determined in aqueous conditions, reasonable for non-membrane proteins, but potentially less relevant for membrane proteins. Two new RCCS sets are presented here, determined in dimethyl sulfoxide (DMSO) and chloroform:methanol:water (4:4:1 by volume) at 298 K. A web-based program, CS-CHEMeleon, has been implemented to determine the accuracy of secondary structure assessment by calculating and comparing Deltadelta values for various RCCS datasets. Using CS-CHEMeleon, Deltadelta ...

When a predator avoids infected prey: a model-based theoretical study

Mathematical Medicine and Biology — Fri, 05 Mar 2010 13:45:33 +0100

In this paper we study a predator–prey model with logistic growth in the prey population, where a disease spreads among the prey according to an susceptible-infected-susceptible (SIS) epidemic model. The predators do not consume infected prey. After a review of the literature we formulate the basic mathematical model. For simplicity, we work initially with a model involving the fractions of prey susceptible and infected and then translate the results back to the model with absolute numbers. Both local and global stability results are examined. For the model working with absolute numbers, we find six possible equilibria and three important threshold values determining the behaviour of the system. There is always a unique locally stable equilibrium. We make conjectures concerning the g...

Continuum approximations of individual-based models for epithelial monolayers

Mathematical Medicine and Biology — Fri, 05 Mar 2010 13:45:33 +0100

This work examines a 1D individual-based model (IBM) for a system of tightly adherent cells, such as an epithelial monolayer. Each cell occupies a bounded region, defined by the location of its endpoints, has both elastic and viscous mechanical properties and is subject to drag generated by adhesion to the substrate. Differential-algebraic equations governing the evolution of the system are obtained from energy considerations. This IBM is then approximated by continuum models (systems of partial differential equations) in the limit of a large number of cells, N, when the cell parameters vary slowly in space or are spatially periodic (and so may be heterogeneous, with substantial variation between adjacent cells). For spatially periodic cell properties with significant cell viscosity, the r...

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Analytical solution of the Pennes equation for burn-depth determination from infrared thermographs

Mathematical Medicine and Biology — Fri, 05 Mar 2010 13:45:33 +0100

A serious problem in emergency medicine is the correct evaluation of skin burn depth to make the appropriate choice of treatment. In clinical practice, there is no difficulty in classifying first- and third-degree burns correctly. However, differentiation between the IIa (superficial dermal) and IIb (deep dermal) wounds is problematic even for experienced practitioners. In this work, the use of surface skin temperature for the determination of the depth of second-degree burns is explored. An analytical solution of the 3D Pennes steady-state equation is obtained assuming that the ratio between burn depth and the burn size is small. The inverse problem is posed in a search space consisting of geometrical parameters associated with the burned region. This space is searched to minimize the err...

Chronic disease projections in heterogeneous ageing populations: approximating multi-state models of joint distributions by modelling marginal distributions

Mathematical Medicine and Biology — Fri, 05 Mar 2010 13:45:33 +0100

To quantify the effects of changes in risk factors for chronic diseases on morbidity and mortality, Markov-type multi-state models are used. However, with multiple risk factors and many diseases relating to these risk factors, these models contain a large number of states. In this paper, we present an alternative modelling methodology implemented in the National Institute for Public Health and the Environment chronic disease model. This model includes multiple states based on risk factor levels and disease stages but only keeps track of the marginal probability values. Starting from the multi-state model, differential equations are derived that describe the change of the marginal distribution for each risk factor class and disease stage, taking into account population heterogeneity and com...

DIA/FDA CDER/CBER Computational Science Annual Meeting

What's New at CBER — Fri, 05 Mar 2010 02:55:00 +0100

This meeting will review progress on topics such as data standards, best practices-driven analytical tool development, business processes driving information systems development, and user experience/evaluation of current tools. (Source: What's New at CBER)

Imperial paper voted a “must read” of 2009

Imperial College News — Fri, 05 Mar 2010 00:00:00 +0100

The Lancet journal’s Paper of the Year Award sees Imperial research voted runner-up – News (Source: Imperial College News)

Asteroid killed off the dinosaurs, says international scientific panel

Imperial College News — Fri, 05 Mar 2010 00:00:00 +0100

The Cretaceous–Tertiary mass extinction was caused by an asteroid colliding with Earth - News Release (Source: Imperial College News)

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Analysis of viral clearance unit operations for monoclonal antibodies

Biotechnology and Bioengineering — Fri, 05 Mar 2010 00:00:00 +0100

We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log10 were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses. Biotechnol. Bioeng. Published 2010 Wiley Periodical...

Hizentra

What's New at CBER — Thu, 04 Mar 2010 21:03:00 +0100

(Source: What's New at CBER)

Therapeutic Applications of Cell Microencapsulation

Springer Biomedical Sciences titles — Thu, 04 Mar 2010 17:44:32 +0100

series:Advances in Experimental Medicine and BiologyThe main objective of this book has been to analyze in depth and discuss the different aspects related to the design and elaboration of cell-enclosing microcapsules, even the regulatory features and clinical trials under development. These improvements will lead to progression in this therapeutic approach which may become one day closer to a realistic proposal for clinical application.The ... (Source: Springer Biomedical Sciences titles)

Dr. Susan Haynes on Stem Cells, Developmental Biology and Regenerative Biology at NIGMS

NIGMS Multimedia — Thu, 04 Mar 2010 17:00:00 +0100

(Source: NIGMS Multimedia)

Simulation of bone tissue formation within a porous scaffold under dynamic compression.

Biomechanics and Modeling in Mechanobiology — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Milan JL, Planell JA, Lacroix D A computational model of mechanoregulation is proposed to predict bone tissue formation stimulated mechanically by overall dynamical compression within a porous polymeric scaffold rendered by micro-CT. Dynamic compressions of 0.5-5% at 0.0025-0.025 s(-1) were simulated. A force-controlled dynamic compression was also performed by imposing a ramp of force from 1 to 70 N. The model predicts homogeneous mature bone tissue formation under strain levels of 0.5-1% at strain rates of 0.0025-0.005 s(-1). Under higher levels of strain and strain rates, the scaffold shows heterogeneous mechanical behaviour which leads to the formation of a heterogeneous tissue with a mixture of mature bone and fibrous tissue. A fibrous tissue layer was also predicted unde...

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A computational biomimetic study of cell crawling.

Biomechanics and Modeling in Mechanobiology — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Roy S, Qi HJ Cell locomotion is a result of a series of synchronized chemo-mechanical processes. Previous extensive experimental studies have revealed many chemo-mechanical processes that may contribute to cell locomotion. In parallel, theoretical works have been developed to provide deeper insight. To date, however, direct simulations of cell locomotion on a substrate have not been seen. In this paper, a finite element-based computational model is developed to study amoeboid type of cell crawling phenomenon. Here, a cell is modeled as a 2D fluid-filled elastic vesicle, which establishes its interaction with a rigid substrate through a kinetics-based cellular adhesion model. The cell derives its motion through a differential bond breaking at the trailing edge and bond formatio...

Staying healthier for longer

Imperial College News — Thu, 04 Mar 2010 00:00:00 +0100

Imperial's new research initiative aims to speed-up multidisciplinary collaborations for reducing the gap between our lifespan and health span - News (Source: Imperial College News)

Alkyne–azide click reaction catalyzed by metallic copper under ultrasound

Nature Protocols — Thu, 04 Mar 2010 00:00:00 +0100

Alkyne–azide click reaction catalyzed by metallic copper under ultrasound Nature Protocols 5, 607 (2010). doi:10.1038/nprot.2010.1 Authors: Pedro Cintas, Alessandro Barge, Silvia Tagliapietra, Luisa Boffa & Giancarlo Cravotto (Source: Nature Protocols)

Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons

Nature Protocols — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Ian R Wickersham, Heather A Sullivan & H Sebastian Seung (Source: Nature Protocols)

An efficient and easy-to-use cryopreservation protocol for human ES and iPS cells

Nature Protocols — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Hossein Baharvand, Ghasem Hosseini Salekdeh, Adeleh Taei & Sepideh Mollamohammadi (Source: Nature Protocols)

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Segmental isotopic labeling of multi-domain and fusion proteins by protein trans-splicing in vivo and in vitro

Nature Protocols — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Mikko Muona, A Sesilja Aranko, Vytas Raulinaitis & Hideo Iwaï (Source: Nature Protocols)

Immune Responses to Mitochondria Help Explain Body's Inflammatory Response to Injury

NIGMS - Results — Wed, 03 Mar 2010 21:04:58 +0100

(Source: NIGMS - Results)

Mechanism Whereby Estrogen Feeds Breast Cancer Suggests New Angle for Treatment

NIGMS - Results — Wed, 03 Mar 2010 21:03:04 +0100

(Source: NIGMS - Results)

Fluzone and Fluzone High-Dose

What's New at CBER — Wed, 03 Mar 2010 14:36:00 +0100

(Source: What's New at CBER)

Multicenter Sepsis Study Shows Greater Risk of Death in Pneumonia Patients With Kidney Injury

NIGMS - Results — Tue, 02 Mar 2010 20:40:25 +0100

(Source: NIGMS - Results)

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The Chick Embryo Chorioallantoic Membrane in the Study of Angiogenesis and Metastasis(Ribatti)

Springer Biomedical Sciences titles — Tue, 02 Mar 2010 17:26:28 +0100

The CAM assay in the study of angiogenesis and metastasisThe chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane which serves as a gas exchange surface and its function is supported by a dense capillary network. Because of its extensive vascularization and easy accessibility, the CAM has been broadly used to study the morpho-functional aspects of the angiogenesis process in vivo and to investigate the efficacy and mechanisms of ... (Source: Springer Biomedical Sciences titles)

FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice