MedWorm: Biomedical Science

A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: A phase II double-blind, randomized placebo-controlled study.

Clinical and Investigative Medicine — Thu, 09 Feb 2012 11:54:09 +0100

Conclusion: PG2 might be an effective and safe treatment for relieving CRF among advanced cancer patients. PMID: 22309959 [PubMed - in process] (Source: Clinical and Investigative Medicine)

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The Value of P wave dispersion in predicting reperfusion and infarct related artery patency in acute anterior myocardial infarction.

Clinical and Investigative Medicine — Thu, 09 Feb 2012 11:54:09 +0100

Conclusion: PWD values, which were higher than 51 ms and 51.6 ms in patients who received fibrinolytic therapy, can serve as a marker of failed reperfusion and occluded IRA. PWD values, in combination with other reperfusion parameters, can contribute to the identification of rescue PCI candidates. PMID: 22309960 [PubMed - in process] (Source: Clinical and Investigative Medicine)

Lower plasma soluble TWEAK concentration in patients with newly diagnosed hypertension.

Clinical and Investigative Medicine — Thu, 09 Feb 2012 11:54:09 +0100

Conclusion: Young patients with yet untreated primary hypertension have lower circulating serum sTWEAK level compared with healthy controls. Further research for possible associations among serum sTWEAK, endothelial dysfunction and other measures of atherosclerosis may be of benefit in order to better understand the pathophysiology of hypertension and to establish more effective treatment options. PMID: 22309961 [PubMed - in process] (Source: Clinical and Investigative Medicine)

Characterization of management and outcomes of patients with acromegaly in Vancouver over 30 years.

Clinical and Investigative Medicine — Thu, 09 Feb 2012 11:54:09 +0100

Conclusion: Based on the size of population studied, this study showed a prevalence of acromegaly of 29 per million. The cure rate was low following surgery but with adjuvant medical treatment disease control was achieved in most individuals. PMID: 22309962 [PubMed - in process] (Source: Clinical and Investigative Medicine)

Increased expression of CD55 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma.

Clinical and Investigative Medicine — Thu, 09 Feb 2012 11:54:09 +0100

Conclusion: The data from this study suggest, for the first time, that CD55 is frequently expressed in nasopharyngeal carcinoma and its expression is associated with decreased patient survival; therefore, CD55 expression may be a potential unfavorable prognostic factor for patients with nasopharyngeal carcinoma. PMID: 22309963 [PubMed - in process] (Source: Clinical and Investigative Medicine)

Comparing health behaviours of internal medicine residents and medical students: An observational study.

Clinical and Investigative Medicine — Thu, 09 Feb 2012 11:54:09 +0100

Conclusion: Medical residents at our institution appear less active and consume fewer servings of fruits and vegetables than undergraduate medical students. These differences are associated with higher BMI, waist circumference and cardiovascular risk. PMID: 22309964 [PubMed - in process] (Source: Clinical and Investigative Medicine)

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Celebrating 25 years of Biomedical Chromatography. A report on the Royal Society of Chemistry, Separation Science Group Meeting, held at the Wellcome Centre, London, 25-26 November 2011.

Biomedical Chromatography : BMC — Thu, 09 Feb 2012 11:49:08 +0100

Authors: Mills GA, Flanagan RJ PMID: 22307750 [PubMed - in process] (Source: Biomedical Chromatography : BMC)

Overexpressing human membrane proteins in stably transfected and clonal human embryonic kidney 293S cells

Nature Protocols — Thu, 09 Feb 2012 05:00:00 +0100

Authors: Sarika Chaudhary, John E Pak, Franz Gruswitz, Vinay Sharma & Robert M Stroud X-ray crystal structures of human membrane proteins, although potentially of extremely great impact, are highly underrepresented relative to those of prokaryotic membrane proteins. One key reason for this is that human membrane proteins can be difficult to express at a level, and at a quality, (Source: Nature Protocols)

Single-molecule pull-down for studying protein interactions

Nature Protocols — Thu, 09 Feb 2012 05:00:00 +0100

Authors: Ankur Jain, Ruijie Liu, Yang K Xiang & Taekjip Ha This protocol describes a single-molecule pull-down (SiMPull) assay for analyzing physiological protein complexes. The assay combines the conventional pull-down assay with single-molecule total internal reflection fluorescence (TIRF) microscopy and allows the probing of single macromolecular complexes directly from cell or tissue extracts. In this method, (Source: Nature Protocols)

Synthesis of N-methylated cyclic peptides

Nature Protocols — Thu, 09 Feb 2012 05:00:00 +0100

Authors: Jayanta Chatterjee, Burkhardt Laufer & Horst Kessler This protocol presents a detailed description of the synthesis of N-methylated cyclic peptides. N-methylation is a powerful technique to modulate the physicochemical properties of peptides by introducing one or more methyl groups into the peptidic amide bonds. Together with peptide cyclization, this procedure (Source: Nature Protocols)

Whole-mount three-dimensional imaging of internally localized immunostained cells within mouse embryos

Nature Protocols — Thu, 09 Feb 2012 05:00:00 +0100

We describe a three-dimensional (3D) confocal imaging technique to characterize and enumerate rare, newly emerging hematopoietic cells located within the vasculature of whole-mount preparations of mouse embryos. However, the methodology is broadly applicable for examining the development and 3D architecture of other tissues. Previously, direct (Source: Nature Protocols)

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Proteomic profiling of acute coronary thrombosis reveals a local decrease of PEDF in acute myocardial infarction

Clinical Science — Thu, 09 Feb 2012 05:00:00 +0100

Conclusion: Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture. (Source: Clinical Science)

New target for Alzheimer's drugs

EurekAlert! - Social and Behavioral Science — Wed, 08 Feb 2012 05:00:00 +0100

(University of California - Riverside) UC Riverside biomedical scientists have identified a new link between a protein (beta-arrestin) and short-term memory that could open new doors for the therapeutic treatment of neurological disorders, particularly Alzheimer's disease. They show that if beta-arrestin is removed from neurons, short-term memory loss is prevented. But beta-arrestin is also required for normal learning/memory. The researchers argue that a fine balance needs to be established, one that could be achieved by pharmaceutical drugs in the future. (Source: EurekAlert! - Social and Behavioral Science)

Identification of helix capping and β-turn motifs from NMR chemical shifts.

Journal of Bimolecular NMR — Wed, 08 Feb 2012 05:00:00 +0100

We present an empirical method for identification of distinct structural motifs in proteins on the basis of experimentally determined backbone and (13)C(β) chemical shifts. Elements identified include the N-terminal and C-terminal helix capping motifs and five types of β-turns: I, II, I', II' and VIII. Using a database of proteins of known structure, the NMR chemical shifts, together with the PDB-extracted amino acid preference of the helix capping and β-turn motifs are used as input data for training an artificial neural network algorithm, which outputs the statistical probability of finding each motif at any given position in the protein. The trained neural networks, contained in the MICS (motif identification from chemical shifts) program, also provide a confidence level for each of ...

Estimating side-chain order in methyl-protonated, perdeuterated proteins via multiple-quantum relaxation violated coherence transfer NMR spectroscopy.

Journal of Bimolecular NMR — Wed, 08 Feb 2012 05:00:00 +0100

We describe a relaxation violated coherence transfer approach where the relaxation of multiple-quantum (1)H-(13)C methyl coherences during the relaxation delay period is quantified. The NMR experiment and the associated fitting procedure that models the time-dependence of the signal build-up, are applicable to the characterization of side-chain order in [(13)CH(3)]-methyl-labeled, highly deuterated protein systems up to ~100 kDa in molecular weight. The feasibility of extracting reliable measures of side-chain order is experimentally verified on methyl-protonated, perdeuterated samples of an 8.5-kDa ubiquitin at 10°C and an 82-kDa Malate Synthase G at 37°C. PMID: 22314703 [PubMed - as supplied by publisher] (Source: Journal of Bimolecular NMR)

N-terminal Dbl domain of the RhoGEF, Kalirin.

Journal of Bimolecular NMR — Wed, 08 Feb 2012 05:00:00 +0100

Authors: Gorbatyuk VY, Schiller MR, Gorbatyuk OI, Barwinski M, Hoch JC PMID: 22314704 [PubMed - as supplied by publisher] (Source: Journal of Bimolecular NMR)

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Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction.

Journal of Bimolecular NMR — Wed, 08 Feb 2012 05:00:00 +0100

Authors: Lehtivarjo J, Tuppurainen K, Hassinen T, Laatikainen R, Peräkylä M Abstract While chemical shifts are invaluable for obtaining structural information from proteins, they also offer one of the rare ways to obtain information about protein dynamics. A necessary tool in transforming chemical shifts into structural and dynamic information is chemical shift prediction. In our previous work we developed a method for 4D prediction of protein (1)H chemical shifts in which molecular motions, the 4th dimension, were modeled using molecular dynamics (MD) simulations. Although the approach clearly improved the prediction, the X-ray structures and single NMR conformers used in the model cannot be considered fully realistic models of protein in solution. In this work, NMR ensembles (N...

Determination of enantiomeric excess by chiral liquid chromatography without enantiomerically pure starting standards.

Biomedical Chromatography : BMC — Tue, 07 Feb 2012 05:00:00 +0100

Authors: Sánchez FG, Navas Díaz A, Sánchez Torreño E, Aguilar A, Medina Lama I, Algarra M Abstract A facile approach for the enantiomeric excess determination of enantiomeric mixtures without the necessity of pure enantiomer standards is presented. Promethazine and trimeprazine commercial nonracemic mixtures were used as cases study to probe the validity of the method. Chromatographic resolutions obtained with a chiral column AGP in reverse phase mode were 1.32-1.16 (promethazine) and 1.20-0.93 (trimeprazine) for the three detectors (circular dichroism, photometric and fluorimetric) in series. Results obtained showed that enantiomeric excess was 10.4, 8.71 and 8.58% for promethazine and 1.60, 1.23 and 1.80% for trimeprazine (medium values of 9.23 ± 1.01% and 1.54 ± 0....

The comparative research on constituents of Radix Aconiti and its processing by HPLC quadrupole TOF-MS.

Biomedical Chromatography : BMC — Tue, 07 Feb 2012 05:00:00 +0100

Authors: Wu J, Hong B, Wang J, Wang X, Niu S, Zhao C Abstract Based upon the regulations stipulated by the State Food and Drug Administration of China, only the processed, detoxified tubers and roots of Aconitum are allowed to be administered orally, used in clinical decoctions and adopted as raw materials for pharmaceutical manufacturing, so the processing principle of preparation of Radix Aconiti is important for ensuring the Radix Aconiti praeparata quality. A simple approach was described for HPLC-Q-TOF-MS screening and identification of many of the aconitine alkaloids present in unprocessed Radix Aconiti and Radix Aconiti praeparata. To compare their fingerprints, the processing principle of preparation of Radix Aconiti was developed. Twenty-nine compounds and 26 compounds wer...

Simultaneous determination of atractylenolide II and atractylenolide III by liquid chromatography-tandem mass spectrometry in rat plasma and its application in a pharmacokinetic study after oral administration of Atractylodes Macrocephala Rhizoma extract.

Biomedical Chromatography : BMC — Tue, 07 Feb 2012 05:00:00 +0100

In this study, a sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of AII and AIII in rat plasma using loliolide as internal standard (IS). After protein precipitation with ethyl acetate, the analytes were injected into an LC-MS/MS system for quantification. Chromatography was performed using a C(18) column, eluting with water and acetonitrile (45:55, v/v) at 0.2 mL/min. All analytes including IS were monitored under positive ionization conditions by multiple reaction monitoring with an electrospray ionization source. The validated method was successfully applied to the pharmacokinetic study of AII and AIII in rat plasma after oral administration of AMR extract. The results provid...

Simultaneous determination of lactate and pyruvate in human sweat using reversed-phase high-performance liquid chromatography: a noninvasive approach.

Biomedical Chromatography : BMC — Tue, 07 Feb 2012 05:00:00 +0100

Authors: Biagi S, Ghimenti S, Onor M, Bramanti E Abstract The simultaneous determination of lactate and pyruvate in sweat has been performed using reversed phase high-performance liquid chromatography (RP-HPLC) with UV detection at 220 nm. The calibration curves were linear in the investigated range 0.3 - 350 mm of lactate, 0.003- 1 mm of pyruvate. The sensitivity was good with a limit of detection of 0.03 mm for lactate and 0.001 mm for pyruvate. Recoveries evaluated for the entire procedure were 102 ± 0.1 and 96 ± 0.1for lactate and pyruvate, respectively. The method was successfully applied to analysis of sweat in 8 athletes at rest (pilocarpine sweating) and during physical exercise. Copyright © 2012 John Wiley & Sons, Ltd. PMID: 22311625 [PubMed - ...

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Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0834 and its metabolite in human plasma using semi-automated 96-well protein precipitation.

Biomedical Chromatography : BMC — Tue, 07 Feb 2012 05:00:00 +0100

Authors: Shin YG, Jones SA, Murakami SC, Liu L, Wong H, Buonarati MH, Hop CE Abstract A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0834 and its amide hydrolysis metabolite (M1) in human plasma to support clinical development. The method consisted of semi-automated 96-well protein precipitation extraction for sample preparation and LC-MS/MS analysis in positive ion mode using TurboIonSpray® for analysis. D6-GDC-0834 and D6-M1 metabolite were used as internal standards. A linear regression (weighted 1/concentration(2) ) was used to fit calibration curves over the concentration range of 1 - 500 ng/mL for both GDC-0834 and M1 metabolite. The accuracy (percentage bias) at the lower limit of quantitation ...

Norton Zinder, pioneering molecular geneticist, dies at 83

The Rockefeller University Newswire — Mon, 06 Feb 2012 22:03:03 +0100

Zinder was a geneticist and microbiologist whose research on the genetics of bacteria and on the properties of bacteriophages provided important information on the mechanisms of heredity. He died February 3 after a long illness. More » (Source: The Rockefeller University Newswire)

Staging Neuropsychiatric Disorders

Springer Biomedical Sciences titles — Mon, 06 Feb 2012 18:35:15 +0100

Implications for Etiopathogenesis and TreatmentBook chapters are authored by participants in the International Meeting on Staging Neuropsychiatric Disorders: Implications for Etiopathogenesis and Treatment, held in Mojácar (Almería) Spain from 14-18 October 2009. Chapters are organized into four sections on themes encompassed by Staging Neuropsychiatric Disorders: 1) Clinical Staging in the Pathophysiology of Psychotic and Affective ... (Source: Springer Biomedical Sciences titles)

NPs — heart hormones that regulate brown fat?

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

Thermogenesis in brown adipose tissue (BAT) is well characterized as being under the control of the sympathetic nervous system. The energy-burning capacity of BAT makes it an attractive target for anti-obesity therapies. However, previous attempts to manipulate BAT’s sympathetic activation have lacked specificity. In this issue of the JCI, Bordicchia et al. provide new data indicating that cardiac natriuretic peptides (NPs) are also able to activate thermogenic machinery in adipose tissue. Their findings suggest a novel strategy to increase energy dissipation in adipose tissue, independent of adrenergic receptors. (Source: Journal of Clinical Investigation)

Unraveling the mystery of the hygiene hypothesis through Helicobacter pylori infection

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

Epidemiological studies have revealed an inverse association between Helicobacter pylori infection and the incidence of allergic asthma. This association is consistent with the hygiene hypothesis, which posits that exposure to microbes early in life prevents the later development of allergic diseases, and has been reproduced in mouse models of asthma. In this issue of the JCI, Oertli and colleagues report that H. pylori infection in neonates elicits tolerogenic DCs that produce IL-18, which drive the generation of Tregs that subsequently protect the mice from allergic asthma. This finding strengthens the intriguing link between pathogen exposure and allergic disease. (Source: Journal of Clinical Investigation)

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DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori–specific tolerance. DC depletion result...

DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

Dysregulation of the G1/S transition in the cell cycle contributes to tumor development. The oncogenic transcription factors c-Jun and c-Myc are indispensable regulators at this transition, and their aberrant expression is associated with many malignancies. Degradation of c-Jun/c-Myc is a critical process for the G1/S transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 β (GSK3β). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this GSK3β modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation–regulated kinase DYRK2 functions as a priming kinase of c-Jun and c-Myc. Knockdown of DYRK2 in human cancer cells shortened the G...

ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1–/– mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormaliti...

Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of “brown adipocytes” within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional “brown-like” adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induce...

Anti-ganglioside antibody internalization attenuates motor nerve terminal injury in a mouse model of acute motor axonal neuropathy

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

In the Guillain-Barré syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor nerve terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were traffi...

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Essential role of gastric gland mucin in preventing gastric cancer in mice

Journal of Clinical Investigation — Mon, 06 Feb 2012 18:32:05 +0100

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt–/– mice to better understand its role in vivo. A4gnt–/– mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori...

New MSc course focuses on developing strategic thinkers who can apply economic know-how to business

Imperial College News — Mon, 06 Feb 2012 05:00:00 +0100

New MSc in Economics and Strategy for Business launched at Imperial College Business School (Source: Imperial College News)

Developing strategic thinkers who can apply economic know-how to business today, is the focus of new Master’s programme

Imperial College News — Mon, 06 Feb 2012 05:00:00 +0100

New MSc in Economics and Strategy for Business launched at Imperial College Business School (Source: Imperial College News)

Restoration of adipose function in obese, glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein {beta} upregulation

Clinical Science — Mon, 06 Feb 2012 05:00:00 +0100

Obese adipose tissue (AT) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The current study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and adipose tissue macrophages (ATM). In addition, a pilot randomised placebo controlled trial using the peroxisome proliferator-activated receptor (PPAR) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=32) were randomised to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum infla...

Cancer dynamics for identical twin brothers

Theoretical Biology and Medical Modelling — Mon, 06 Feb 2012 05:00:00 +0100

In this paper, a new mathematical model is developed to represent the interaction between healthy and cancer cells in the human body, focusing on the role of environmental factors and quality of life in the progression of cancer. We have investigated the dynamic effects of inputs on cancer growth, and provide an explanation of how cancer has variable behavior patterns throughout the lives of different patients. The behavior of the system with input and its trajectory patterns are investigated using trajectory patterns and stability analysis. The analysis suggests that a proper treatment method should change the dynamics of the cancer instead of only reducing the population of cancer cells and treatment burden. (Source: Theoretical Biology and Medical Modelling)

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Dysmorphometrics: the modelling of morphological abnormalities

Theoretical Biology and Medical Modelling — Mon, 06 Feb 2012 05:00:00 +0100

Conclusion: The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice and research. (Source: Theoretical Biology and Medical Modelling)

Sensory Perception

Springer Biomedical Sciences titles — Sun, 05 Feb 2012 17:44:57 +0100

Mind and MatterSensory perception: mind and matter brings together the neurosciences with psychology and philosophy thereby meeting the demand of an interdisciplinary discourse between those fields of interest in order to understand the many facets of sensory perception and their relation to brain functions and cognition. It gives an interdisciplinary insight into the understanding of neurobiology and ... (Source: Springer Biomedical Sciences titles)

Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency.

Aging — Sat, 04 Feb 2012 05:00:00 +0100

Authors: Ohmine S, Squillace KA, Hartjes KA, Deeds MC, Armstrong AS, Thatava T, Sakuma T, Terzic A, Kudva Y, Ikeda Y Abstract Nuclear reprogramming enables patient-specific derivation of induced pluripotent stem (iPS) cells from adult tissue. Yet, iPS generation from patients with type 2 diabetes (T2D) has not been demonstrated. Here, we report reproducible iPS derivation of epidermal keratinocytes (HK) from elderly T2D patients. Transduced with human OCT4, SOX2, KLF4 and c-MYC stemness factors under serum-free and feeder-free conditions, reprogrammed cells underwent dedifferentiation with mitochondrial restructuring, induction of endogenous pluripotency genes - including NANOG, LIN28, and TERT, and down-regulation of cytoskeletal, MHC class I- and apoptosis-related genes. Notably,...

Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo.

Biomechanics and Modeling in Mechanobiology — Sat, 04 Feb 2012 05:00:00 +0100

Authors: Kowalski WJ, Teslovich NC, Dur O, Keller BB, Pekkan K Abstract In the early embryo, a series of symmetric, paired vessels, the aortic arches, surround the foregut and distribute cardiac output to the growing embryo and fetus. During embryonic development, the arch vessels undergo large-scale asymmetric morphogenesis to form species-specific adult great vessel patterns. These transformations occur within a dynamic biomechanical environment, which can play an important role in the development of normal arch configurations or the aberrant arch morphologies associated with congenital cardiac defects. Arrested migration and rotation of the embryonic outflow tract during late stages of cardiac looping has been shown to produce both outflow tract and several arch abnormalities. H...

A power-law rheology-based finite element model for single cell deformation.

Biomechanics and Modeling in Mechanobiology — Sat, 04 Feb 2012 05:00:00 +0100

Authors: Zhou EH, Xu F, Quek ST, Lim CT Abstract Physical forces can elicit complex time- and space-dependent deformations in living cells. These deformations at the subcellular level are difficult to measure but can be estimated using computational approaches such as finite element (FE) simulation. Existing FE models predominantly treat cells as spring-dashpot viscoelastic materials, while broad experimental data are now lending support to the power-law rheology (PLR) model. Here, we developed a large deformation FE model that incorporated PLR and experimentally verified this model by performing micropipette aspiration on fibroblasts under various mechanical loadings. With a single set of rheological properties, this model recapitulated the diverse micropipette aspiration data obt...

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Calcific nodule morphogenesis by heart valve interstitial cells is strain dependent.

Biomechanics and Modeling in Mechanobiology — Sat, 04 Feb 2012 05:00:00 +0100

Authors: Fisher CI, Chen J, Merryman WD Abstract Calcific aortic valve disease (CAVD) results in impaired function through the inability of valves to fully open and close, but the causes of this pathology are unknown. Stiffening of the aorta is associated with CAVD and results in exposing the aortic valves to greater mechanical strain. Transforming growth factor β1 (TGF-β1) is enriched in diseased valves and has been shown to combine with strain to synergistically alter aortic valve interstitial cell (AVIC) phenotypes. Therefore, we investigated the role of strain and TGF-β1 on the calcification of AVICs. Following TGF-β1 pretreatment, strain induced intact monolayers to aggregate and calcify. Using a wound assay, we confirmed that TGF-β1 increases tension in the monolayer in ...

Title page/Editorial Board

Medical Hypotheses — Fri, 03 Feb 2012 18:55:56 +0100

(Source: Medical Hypotheses)

p27Kip1 controls cytokinesis via the regulation of citron kinase activation

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

p27Kip1 (p27) acts as a tumor suppressor by inhibiting cyclin–cyclin-dependent kinase (cyclin-CDK) activity. However, mice expressing a form of p27 that is unable to bind or inhibit cyclin-CDK complexes (p27CK–) have increased incidence of tumor development as compared with wild-type and p27–/– mice, revealing an oncogenic role for p27. Here, we identified a phenotype of multinucleation and polyploidy in p27CK– mice not present in p27–/– animals, suggesting a role for p27 in G2/M that is independent of cyclin-CDK regulation. Further analysis revealed that p27CK– expression caused a cytokinesis and abscission defect in mouse embryonic fibroblasts. We identified the Rho effector citron kinase (citron-K) as a p27-interacting prot...

PPAR{gamma} agonists enhance ET-743-induced adipogenic differentiation in a transgenic mouse model of myxoid round cell liposarcoma

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

Myxoid round cell liposarcoma (MRCLS) is a common liposarcoma subtype characterized by a translocation that results in the fusion protein TLS:CHOP as well as by mixed adipocytic histopathology. Both the etiology of MRCLS and the mechanism of action of TLS:CHOP remain poorly understood. It was previously shown that ET-743, an antitumor compound with an unclear mechanism of action, is highly effective in patients with MRCLS. To identify the cellular origin of MRCLS, we engineered a mouse model in which TLS:CHOP was expressed under the control of a mesodermally restricted promoter (Prx1) in a p53-depleted background. This model resembled MRCLS histologically as well as functionally in terms of its specific adipocytic differentiation–based response to ET-743. Specifically, endogenous m...

Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

Infections by viruses are associated with approximately 12% of human cancer. Kaposi’s sarcoma-associated herpesvirus (KSHV) is causally linked to several malignancies commonly found in AIDS patients. The mechanism of KSHV-induced oncogenesis remains elusive, due in part to the lack of an adequate experimental system for cellular transformation of primary cells. Here, we report efficient infection and cellular transformation of primary rat embryonic metanephric mesenchymal precursor cells (MM cells) by KSHV. Cellular transformation occurred at as early as day 4 after infection and in nearly all infected cells. Transformed cells expressed hallmark vascular endothelial, lymphatic endothelial, and mesenchymal markers and efficiently induced tumors in nude mice. KSHV established latent ...

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Heparan sulfate sulfatase SULF2 regulates PDGFR{alpha} signaling and growth in human and mouse malignant glioma

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

In this study, we demonstrated that the extracellular sulfatase, SULF2, an enzyme that regulates multiple HSPG-dependent RTK signaling pathways, was expressed in primary human GBM tumors and cell lines. Knockdown of SULF2 in human GBM cell lines and generation of gliomas from Sulf2–/– tumorigenic neurospheres resulted in decreased growth in vivo in mice. We found a striking SULF2 dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. Interestingly, in a survey of SULF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. Therefore, in a...

Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

Appropriate localization and migration of T cells is a prerequisite for antitumor immune surveillance. Studies using fixed tumor samples from human patients have shown that T cells accumulate more efficiently in the stroma than in tumor islets, but the mechanisms by which this occurs are unknown. By combining immunostaining and real-time imaging in viable slices of human lung tumors, we revealed that the density and the orientation of the stromal extracellular matrix likely play key roles in controlling the migration of T cells. Active T cell motility, dependent on chemokines but not on β1 or β2 integrins, was observed in loose fibronectin and collagen regions, whereas T cells migrated poorly in dense matrix areas. Aligned fibers in perivascular regions and around tumor epi...

Metal artefact reduction in gemstone spectral imaging dual-energy CT with and without metal artefact reduction software

European Radiology — Fri, 03 Feb 2012 17:11:57 +0100

Conclusion Dual-energy CT with GSI-MARs can reduce metal-related artefacts and improve the delineation of the prosthesis and periprosthetic region. We should be cautious when using GSI-MARs because the image quality was affected by the prosthesis composition, energy (in keV) and DFOV. The metallic composition and size should be considered in metallic imaging with GSI-MARs reconstruction. Key Points • Metal-related artefacts can be troublesome on musculoskeletal computed tomography (CT). • Gemstone spectral imaging (GSI) with dual-energy CT (DECT) offers a novel solution • GSI and metallic artefact reduction software (GSI-MAR) can markedly reduce these artefacts. • However image quality is influenced by the prosthesis...

GDx VCC measurements and blue-on-yellow perimetry in ocular hypertension

Lasers in Medical Science — Fri, 03 Feb 2012 17:11:21 +0100

Abstract The aim of this work was to investigate the correlation between scanning laser polarimetry with variable corneal compensation (GDx VCC) parameters and blue-on-yellow perimetry (B/YP) indices in ocular hypertension (OHT). One eye each of 52 patients with OHT (with a normal visual field, a normal optic nerve, and an untreated IOP > 21 mmHg) was chosen. All patients were examined with the Octopus 101 automated perimetry dG2 program using the dynamic/normal strategy (white-on-white perimetry, W/WP), with the dG2 program using the dynamic strategy/BY method (blue-on-yellow perimetry, B/YP), and with GDx VCC. Seven of the 52 OHT patients had both B/YP visual field loss and retinal nerve fiber layer (RNFL) defects with the GDx VCC measurements, and four patients ...

Expression and distribution of creatine transporter and creatine kinase (brain isoform) in developing and mature rat cochlear tissues

Histochemistry and Cell Biology — Fri, 03 Feb 2012 17:11:20 +0100

This study postulates that this CRT is developmentally regulated in the rat cochlea. CRT expression was measured by quantitative real-time RT-PCR and immunohistochemistry in the postnatal (P0–P14) and adult (P22–P56) rat cochlea. The maximum CRT expression was reached at the onset of hearing (P12), and this level was maintained through to adulthood. CRT immunoreactivity was strongest in the sensory inner hair cells, supporting cells and the spiral ganglion neurons. Cochlear distribution of the CK brain isoform (CKB) was also assessed by immunohistochemistry and compared with the distribution of CRT in the developing and adult cochlea. CKB was immunolocalized in the organ of Corti supporting cells, and the lateral wall tissues involved in K+ cycling, including stria vascularis and...

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A pseudokinase debut at the mycobacterial cell wall.

Science Signaling — Fri, 03 Feb 2012 14:18:02 +0100

Authors: Warner DF, Mizrahi V Abstract Mycobacterium tuberculosis, the causative agent of tuberculosis, has a complex cellular envelope that comprises both the cytoplasmic membrane and the outer cell wall. Despite advances in elucidating the structural and biochemical composition of these features, the processes that ensure cell wall homeostasis remain poorly understood. New findings implicate the essential mycobacterial serine-threonine protein kinase (STPK), PknB, in regulating the formation of a regulatory complex that includes the integral membrane protein MviN, which is required for peptidoglycan biosynthesis, and a forkhead-associated (FHA) domain protein, FhaA. A model has emerged in which a peptidoglycan-derived muropeptide signal triggers the PknB-mediated phosphorylation ...

Depletion of extracellular Ca2+ prompts astroglia to moderate synaptic network activity.

Science Signaling — Fri, 03 Feb 2012 14:18:02 +0100

Authors: Rusakov DA Abstract Over the past decade, rapid signal exchange between astroglia and neurons across the interstitial space emerged as an essential element of synaptic circuit functioning in the brain. How and where exactly this exchange occurs in various physiological scenarios and the underlying cellular cascades remain a subject of intense study. The excitatory neurotransmitter glutamate and the inhibitory neurotransmitter γ-aminobutyric acid are thought to be the primary signal carriers that are regularly dispatched by active synapses to engage target receptors and transporters on the surface of astrocytes. New evidence identifies another ubiquitous messenger, extracellular calcium ions (Ca(2+)), which can report neural network activity to astroglia. Astrocytes in the...

A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria.

Science Signaling — Fri, 03 Feb 2012 14:18:02 +0100

Authors: Gee CL, Papavinasasundaram KG, Blair SR, Baer CE, Falick AM, King DS, Griffin JE, Venghatakrishnan H, Zukauskas A, Wei JR, Dhiman RK, Crick DC, Rubin EJ, Sassetti CM, Alber T Abstract Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-responsive Ser-Thr protein kinase (STPK), initiates complex assembly by phosphorylating a kinase-like domain in the essential PG biosynthetic protein, MviN. This domain was structurally diverged from active kinases and did not mediate phosphotransfer. Threonine phosphorylation of the...

Extracellular Ca2+ acts as a mediator of communication from neurons to glia.

Science Signaling — Fri, 03 Feb 2012 14:18:02 +0100

Authors: Torres A, Wang F, Xu Q, Fujita T, Dobrowolski R, Willecke K, Takano T, Nedergaard M Abstract Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca(2+)](e)) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca(2+) buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca(2+)](e) or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca(2+) triggered astrocytic...

Myosin I Links PIP3 Signaling to Remodeling of the Actin Cytoskeleton in Chemotaxis.

Science Signaling — Fri, 03 Feb 2012 14:18:02 +0100

Authors: Chen CL, Wang Y, Sesaki H, Iijima M Abstract Class I myosins participate in various interactions between the cell membrane and the cytoskeleton. Several class I myosins preferentially bind to acidic phospholipids, such as phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], through a tail homology 1 (TH1) domain. Here, we show that the second messenger lipid phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) binds to the TH1 domain of a subset of Dictyostelium class I myosins (ID, IE, and IF) and recruits them to the plasma membrane. The PIP(3)-regulated membrane recruitment of myosin I promoted chemotaxis and induced chemoattractant-stimulated actin polymerization. Similarly, PIP(3) recruited human myosin IF to the plasma membrane upon chemotactic st...

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PAS Kinase Promotes Cell Survival and Growth Through Activation of Rho1.

Science Signaling — Fri, 03 Feb 2012 14:18:02 +0100

Authors: Cardon CM, Beck T, Hall MN, Rutter J Abstract In Saccharomyces cerevisiae, phosphorylation of Ugp1 by either of the yeast PASK family protein kinases (yPASK), Psk1 or Psk2, directs this metabolic enzyme to deliver glucose to the periphery for synthesis of the cell wall. However, we isolated PSK1 and PSK2 in a high-copy suppressor screen of a temperature-sensitive mutant of target of rapamycin 2 (TOR2). Posttranslational activation of yPASK, either by cell integrity stress or by growth on nonfermentative carbon sources, also suppressed the growth defect resulting from tor2 mutation. Although suppression of the tor2 mutant growth phenotype by activation of the kinase activity of yPASK required phosphorylation of the metabolic enzyme Ugp1 on serine 11, this resulted in the fo...

The Neutral-Niche Debate: A Philosophical Perspective.

Acta Biotheoretica — Fri, 03 Feb 2012 05:00:00 +0100

Authors: Wennekes PL, Rosindell J, Etienne RS Abstract Ecological communities around the world are under threat while a consensus theory of community structure remains elusive. In the last decade ecologists have struggled with two seemingly opposing theories: niche-based theory that explains diversity with species' differences and the neutral theory of biodiversity that claims that much of the diversity we observe can be explained without explicitly invoking species' differences. Although ecologists are increasingly attempting to reconcile these two theories, there is still much resistance against the neutral theory of biodiversity. Here we argue that the dispute between the two theories is a classic example of the dichotomy between philosophical perspectives, realism and instrumen...

Influence of Sparkle and Saccades on Tongue Electro-Stimulation-Based Vision Substitution of 2D Vectors.

Acta Biotheoretica — Fri, 03 Feb 2012 05:00:00 +0100

Authors: Chekhchoukh A, Glade N Abstract Vision substitution by electro-stimulation has been studied since the 60s beginning with P. Bach-y-Rita. Camera pictures or movies encoded in gray levels are displayed using an electro-stimulation display device on the surface of a body part, such as the skin or the tongue. Medical-technical devices have been developed on this principle to compensate for sensory-motor disabilities such as blindness or loss of balance, or to guide specific actions, such as surgery. However, the electrical signals of stationary or moving slowly moving objects, displayed on a Tongue display unit (TDU), are quickly lost due to saturation of receptors undergoing electrostimulation. We propose to add random saccades or sparkle to the displayed visual scene to incr...

Black holes: Giving life as well as dealing death

Imperial College News — Fri, 03 Feb 2012 05:00:00 +0100

Astrophysicists have identified a black hole that appears to be helping new stars to form amongst its encircling gas clouds - News (Source: Imperial College News)

Surface of Mars an unlikely place for life after 600 million year drought, say

Imperial College News — Fri, 03 Feb 2012 05:00:00 +0100

New study suggests super-drought made it too hostile for any life survive on the Mars' surface - News Release (Source: Imperial College News)

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Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and blood pressure in severe obesity

Clinical Science — Fri, 03 Feb 2012 05:00:00 +0100

A previous expression profiling of visceral adipose tissue (VAT) revealed that the thymic stromal lymphopoietin (TSLP) gene was less expressed in severely obese men with (n=7) vs. without (n=7) the metabolic syndrome (MS). We hypothesized that TSLP single nucleotide polymorphisms (SNPs) are associated with TSLP gene expression in VAT and with MS phenotypes. Following validation of lower TSLP expression (p=0.003) in VAT of severely obese men and women with (n=70) vs. without (n=60) MS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron-exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expre...

Lasers for the treatment of intraocular tumors

Lasers in Medical Science — Thu, 02 Feb 2012 18:15:44 +0100

Abstract Lasers are used extensively in ophthalmology for a variety of conditions, including many choroidal and retinal tumors. With technologic advances, current therapy attempts not only to maximize survival with globe-salvaging treatment, but also to preserve vision. Each neoplasm has different indications for primary and adjuvant therapy, as well as differing laser treatment protocols. Additionally, there are numerous laser applications available for use, including laser photocoagulation, transpupillary thermotherapy (TTT), and photodynamic therapy (PDT). The current review outlines the basic principles of laser treatment for intraocular tumors, focusing on the indications, treatment protocols, efficacy, and safety, while also presenting the latest advances in intraocu...

Reorganization of Cajal bodies and nucleolar targeting of coilin in motor neurons of type I spinal muscular atrophy

Histochemistry and Cell Biology — Thu, 02 Feb 2012 18:15:41 +0100

In this study, we have analyzed the nuclear reorganization of Cajal bodies, PML bodies and nucleoli in type I SMA motor neurons with homozygous deletion of exons 7 and 8 of the SMN1 gene. Western blot analysis revealed a marked reduction of SMN levels compared to the control sample. Using a neuronal dissociation procedure to perform a careful immunocytochemical and quantitative analysis of nuclear bodies, we demonstrated a severe decrease in the mean number of Cajal bodies per neuron and in the proportion of motor neurons containing these structures in type I SMA. Moreover, most Cajal bodies fail to recruit SMN and spliceosomal snRNPs, but contain the proteasome activator PA28γ, a molecular marker associated with the cellular stress response. Neuronal stress in SMA motor neurons als...

Binding of Escherichia coli to Functionalized Gold Nanoparticles

Plasmonics — Thu, 02 Feb 2012 18:13:33 +0100

Abstract The molecular basis of the diversity of fimbrial lectins dictates the extent of adhesion in different types of Escherichia coli strains to mammalian cells. The mechanism of receptor binding by E. coli in eukaryotic cells differs based on the adhesin domains, patterns in the macromolecular structure and the ligand-binding groove. Current sensor technologies utilize biosensors that are based on the carbohydrate moieties that are involved in pathogen adhesion to host cells. Nanoparticles have been extensively used as carriers for pathogen detection. Gold nanoparticles (Au NPs) of 200 nm size were functionalized with two distinct glycoconjugates mannose (Mn–Au NPs) and Neuαc(α2-3)-Gal-(β1-4)Glc–Paa (Sg–Au NPs) in order to investigate primary and fine sugar...

Increased serum soluble CD147 levels in patients with systemic sclerosis: association with scleroderma renal crisis

Clinical Rheumatology — Thu, 02 Feb 2012 06:55:21 +0100

This study aimed to determine serum soluble CD147 (sCD147) levels and their clinical associations in patients with systemic sclerosis (SSc). Serum sCD147 levels were examined by enzyme-linked immunosorbent assay in 61 SSc patients and 24 healthy individuals. Serum sCD147 levels were significantly elevated in SSc patients compared with healthy individuals (P < 0.001). Among patients with SSc, there were no differences in serum sCD147 levels between limited cutaneous (n = 30) and diffuse cutaneous SSc (n = 31). Patients with SSc who had elevated sCD147 levels had renal crisis more often than those with normal sCD147 levels (13% vs 0%; P < 0.05). Serum sCD147 levels were increased in patients with SSc and associated with the presence of renal crisis. These results s...

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Single-mRNA counting using fluorescent in situ hybridization in budding yeast

Nature Protocols — Thu, 02 Feb 2012 05:00:00 +0100

Authors: Tatjana Trcek, Jeffrey A Chao, Daniel R Larson, Hye Yoon Park, Daniel Zenklusen, Shailesh M Shenoy & Robert H Singer Fluorescent in situ hybridization (FISH) allows the quantification of single mRNAs in budding yeast using fluorescently labeled single-stranded DNA probes, a wide-field epifluorescence microscope and a spot-detection algorithm. Fixed yeast cells are attached to coverslips and hybridized with a mixture of FISH probes, each (Source: Nature Protocols)

Improved biocytin labeling and neuronal 3D reconstruction

Nature Protocols — Thu, 02 Feb 2012 05:00:00 +0100

In this report, we describe a reliable protocol for biocytin labeling of neuronal tissue and diaminobenzidine (DAB)-based processing of brain slices. We describe how to embed tissues in different media and how to subsequently histochemically label the tissues for light or electron microscopic examination. We (Source: Nature Protocols)

A pipeline for the generation of shRNA transgenic mice

Nature Protocols — Thu, 02 Feb 2012 05:00:00 +0100

Authors: Lukas E Dow, Prem K Premsrirut, Johannes Zuber, Christof Fellmann, Katherine McJunkin, Cornelius Miething, Youngkyu Park, Ross A Dickins, Gregory J Hannon & Scott W Lowe RNA interference (RNAi) is an extremely effective tool for studying gene function in almost all metazoan and eukaryotic model systems. RNAi in mice, through the expression of short hairpin RNAs (shRNAs), offers something not easily achieved with traditional genetic approaches—inducible and reversible gene silencing. However, (Source: Nature Protocols)

Expression of high-affinity human antibody fragments in bacteria

Nature Protocols — Thu, 02 Feb 2012 05:00:00 +0100

This article provides an overview of expression and purification (Source: Nature Protocols)

Mathematical modeling of solid cancer growth with angiogenesis

Theoretical Biology and Medical Modelling — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Cancer can be settled in an organ if the following combination matches: better fitness of cancercells, decrease in the effciency of the repairing systems, increase in the capacity of sprouting from existingvascularization, and higher capacity of mounting up new vascularization. However, we show that cancer is rarelyinduced in organs (or tissues) displaying an efficient (numerically and functionally) reparative or regenerativemechanism. (Source: Theoretical Biology and Medical Modelling)

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A molecular diffusion based utility model for Drosophila larval phototaxis

Theoretical Biology and Medical Modelling — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Our model provides new insights into decision making mechanisms in general. From an engineering viewpoint, we propose that the model could be applied to a wider range of decision making practices. (Source: Theoretical Biology and Medical Modelling)

Review of HPLC methods and HPLC methods with mass spectrometric detection for direct determination of aspirin with its metabolite(s) in various biological matrices.

Biomedical Chromatography : BMC — Thu, 02 Feb 2012 05:00:00 +0100

Authors: Mullangi R, Sharma K, Srinivas NR Abstract Aspirin, the most widely used drug in the world, has been known to mankind for over a century. It is not only the pharmacologically active entity, but is also biotransformed into a major metabolite, i.e. salicylic acid, which also exhibits similar pharmacologic/pharmacodynamic properties. Hence it is necessary to quantitate aspirin along with its metabolite(s) in various biological matrices accurately and precisely to correlate with pharmacological/pharmacodynamic activity. This paper provides a comprehensive overview of various bioanalytical methods (HPLC and LC-MS/MS) that have been reported for direct quantitation of aspirin along with its metabolite(s). The review also provides general information on sample collection, sample ...

Comprehensive chemical profiling of Guizhi Fuling capsule by the combined use of gas chromatography-mass spectrometry with a deconvolution software and rapid-resolution liquid chromatography quadrupole time-of-flight tandem mass spectrometry.

Biomedical Chromatography : BMC — Thu, 02 Feb 2012 05:00:00 +0100

In this study, an analytical strategy combining two approaches was established for comprehensive analysis of herbal formulations. Guizhi Fuling capsule (GFC), a drug approved by the FDA to enter phase II clinical trial for treatment of primary dysmenorrhea, was taken as a case for analysis. Gas chromatography-mass spectrometry (GC-MS) with automated mass spectral deconvolution and identification system (AMDIS) led to rapid identification of 48 volatile components including four acetophenones, three fatty acid esters, 13 phenylpropanoids and 19 sesquiterpenes. Most of them were found from Guizhi. The volatile oils of Guizhi have been proved to exhibit many pharmacological activities. This is helpful in understanding the pharmacological mechanism of GFC. Furthermore, AMDIS turned out to be e...

Smart-e-Pants aim to eliminate bed sores

CTV Health — Thu, 02 Feb 2012 01:42:52 +0100

Gem Hebert is not shy about bearing her backside for medical science. She's one of about two dozen Alberta patients helping test a new technology called Smart-e-Pants, a custom electric underwear aiming to prevent bed sores. (Source: CTV Health)

Histone deacetylases 2 and 9 are coexpressed and nuclear localized in human molar odontoblasts in vivo

Histochemistry and Cell Biology — Wed, 01 Feb 2012 17:13:14 +0100

Abstract Histone deacetylases (HDACs) are components of nuclear multiprotein complexes that deacetylate histones and perform important roles in repression of transcription. Using specific rabbit mAbs, we analyzed by immunohistochemistry and confocal immunofluorescence analysis the expression and subcellular localization of HDAC1–4 and HDAC9 in sections of adult human third molars. HDAC2 and HDAC9 were expressed in some pulpal cells and strongly expressed in the majority of mature odontoblasts. In contrast, only weak expression of HDAC1, HDAC3 and HDAC4 was observed. Confocal immunofluorescence analysis together with the DNA stain DRAQ5 revealed that HDAC2 and HDAC9 were coexpressed within the odontoblast nucleus, but localized to distinct subnuclear structures. In contra...

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Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease.

Biomechanics and Modeling in Mechanobiology — Wed, 01 Feb 2012 05:00:00 +0100

This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV. PMID: 22294208 [PubMed - as supplied by publisher] (Source: Biomechanics and Modeling in Mechanobiology)

Children test the air for pollutants in Brighton science project

Imperial College News — Wed, 01 Feb 2012 05:00:00 +0100

Imperial scientists gather air pollution data with the help of Brighton school children - News (Source: Imperial College News)

Med Sci Monit 2012; 18(2):PR1-3 "A69S and R38X ARMS2 and Y402H CFH gene polymorphisms as risk factors for neovascular age-related macular degeneration in Poland – a brief report"