MedWorm: Biochemistry

The Journal of Nutritional Biochemistry — Tue, 21 May 2013 15:17:15 +0100

(Source: The Journal of Nutritional Biochemistry)

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Unraveling cellulose microfibrils: A twisted tale

Biopolymers — Tue, 21 May 2013 15:16:24 +0100

Abstract Molecular dynamics (MD) simulations of cellulose microfibrils are pertinent to the paper, textile, and biofuels industries for their unique capacity to characterize dynamic behavior and atomic‐level interactions with solvent molecules and cellulase enzymes. While high‐resolution crystallographic data have established a solid basis for computational analysis of cellulose, previous work has demonstrated a tendency for modeled microfibrils to diverge from the linear experimental structure and adopt a twisted conformation. Here, we investigate the dependence of this twisting behavior on computational approximations, and establish the theoretical basis for its occurrence. We examine the role of solvent, the effect of nonbonded force field parameters (partial charges and van der Waa...

Analyzing the visible conformational substates of the FK506-binding protein FKBP12

BJ Structure — Tue, 21 May 2013 04:00:00 +0100

The 1H-15N 2D NMR correlation spectrum of the widely studied FK506-binding protein FKBP12 contains previously unreported peak doublings for at least 31 residues that arise from a minor conformational state (12% of total) which exchanges with the major conformation with a time constant of 3.0 s at 43oC. The largest differences in chemical shift occur for the 80’s loop that forms critical recognition interactions with many of the protein partners for the FKBP family. The residues exhibiting doubling extend into the adjacent strands of the beta sheet, across the active site to the alpha helix and into the 50’s loop. Each of the seven proline residues adopts a trans peptide linkage in both the major and minor conformations, indicating that this slow transition is not the result o...

What can microscopy teach us on suicide? - Mechawar N.

SafetyLit: All (Unduplicated) — Tue, 21 May 2013 01:15:35 +0100

The fine neuroanatomy of mood disorders and suicide is a relatively recent field of investigation. Together with neuroimaging, molecular biology and biochemistry, histological analyses of post-mortem brain regions implicated in mood regulation allow gainin... (Source: SafetyLit: All (Unduplicated))

Discovery of a novel medicine for the treatment of chronic wounds

EurekAlert! - Medicine and Health — Mon, 20 May 2013 04:00:00 +0100

(Umea University) Every 20 seconds, a limb is lost as a consequence of a diabetic foot ulcer that does not heal. To date, medical solutions that can change this situation are very limited. In his doctoral thesis, Yue Shen from the Industrial Doctoral School and the Department of Medical Biochemistry and Biophysics at Umeå University presented a novel medicine for chronic wound treatment that may completely change the lives of millions of patients. (Source: EurekAlert! - Medicine and Health)

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Improved Lipid Profile in Hyperlipidemic Patients Taking Vaccinium arctostaphylos Fruit Hydroalcoholic Extract: A Randomized Double‐Blind Placebo‐Controlled Clinical Trial

Phytotherapy Research — Mon, 20 May 2013 04:00:00 +0100

Dyslipidemia is a common contributory cause of cardiovascular disease. Vaccinium arctostaphylos L. (Caucasian whortleberry) fruit is rich of anthocyanins. Anthocyanins may exert cardioprotective effects by various mechanisms such as favorably modulating dyslipidemia. Therefore, in this randomized double‐blind placebo‐controlled clinical trial with hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) patients aged 20–60 years, the effects of taking a standardized whortleberry fruit hydroalcoholic extract (one 350 mg capsule every 8 h for 2 months) on fasting blood levels of lipids, creatinine and liver enzymes including SGOT and SGPT were evaluated in 40 patients and compared with the placebo group (n = 40). The extract lowered the blood levels of total choles...

PPIP5K1 Modulates Ligand Competition Between Diphosphoinositol Polyphosphates and PtdIns(3,4,5)P3 for Polyphosphoinositide-Binding Domains.

BJ Signal — Mon, 20 May 2013 04:00:00 +0100

We describe new signalling consequences for PPIP5K1-mediated phosphorylation of InsP6 and 5-InsP7 to 1-InsP7 and InsP8. In NIH-3T3 cells, either hyperosmotic stress or receptor-activation by PDGF promoted translocation of PPIP5K1 from the cytoplasm to the plasma membrane. The PtdIns(3,4,5)P3-binding domain (PBD) in PPIP5K1 recapitulated that translocation. Mutagenesis of PBD to reduce affinity for PtdIns(3,4,5)P3 prevented translocation. Using surface plasmon resonance, we found that PBD association with vesicular PtdIns(3,4,5)P3 was inhibited by InsP6 and diphosphoinositol polyphosphates. However, the inhibition by PPIP5K1 substrates (IC50 values: 5-InsP7 = 5 μM; InsP6 = 7 μM) was substantially more potent than that of the PPIP5K1 products (IC50 values: InsP8 = 32 μM,...

Comparative proteomics and correlated signaling network of kidney in ApoE deficient mouse

Proteomics. Clinical Applications — Sat, 18 May 2013 04:00:00 +0100

Conclusions and clinical relevanceTaken together, we originally identify the proteins with differential expression and propose an apoE correlated molecular network in mice kidney. These findings further provide evidence of the role of apoE in mice kidney and a brand new perspective in the protection and treatment of kidney disease.This article is protected by copyright. All rights reserved (Source: Proteomics. Clinical Applications)

Targeted Glycoprotein Enrichment and Identification in Stromal Cell Secretomes using Azido Sugar Metabolic Labeling

Proteomics. Clinical Applications — Sat, 18 May 2013 04:00:00 +0100

Conclusion and clinical relevanceSugar‐azide metabolic labeling is an effective way to enrich for secreted glycoproteins present in cell line secretomes, even in culture media supplemented with serum. The method has utility for identifying secreted stromal proteins associated with cancer progression and the epithelial‐to‐mesenchymal transition.This article is protected by copyright. All rights reserved (Source: Proteomics. Clinical Applications)

Living Cells Must Use Their Brakes Moderately For Effective Speed Control

Health News from Medical News Today — Fri, 17 May 2013 08:00:00 +0100

How cells regulate their own function by "accelerating and braking" is important basic knowledge when new intelligent medicines are being developed, or when plant cells are tweaked to produce more bioenergy. In a study published by Nature Communications, researchers at Uppsala and Umea universities show a model of how cells' regulatory systems work. All living cells have a regulatory system similar to what can be found in today's smartphones... (Source: Health News from Medical News Today)

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Organocatalytic asymmetric synthesis of [small beta]3-amino acid derivatives

RSC - Organic Biomolecular Chemistry — Fri, 17 May 2013 05:11:19 +0100

Org. Biomol. Chem., 2013, Accepted ManuscriptDOI: 10.1039/C3OB40917A, PerspectiveSun Min Kim, Jung Woon Yang[small beta]3-Amino acid derivatives are an essential resource for pharmaceutical production, medicinal chemistry, and biochemistry. In this review, recent developments of versatile organocatalysis, i.e., H-bonding catalysis (or Bronsted acid catalysis), Lewis...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Serum fibrinogen alpha C‐chain 5.9 kDa fragment as a biomarker for early detection of hepatic fibrosis related to hepatitis C virus

Proteomics. Clinical Applications — Fri, 17 May 2013 04:00:00 +0100

Conclusions and clinical relevanceThe serum FIC 5.9 level may be an early indicator of hepatic fibrosis in HCV‐related chronic liver diseases. This study provides an example of a pipeline from biomarker discovery by proteome analysis to assay optimization and preliminary clinical validation. (Source: Proteomics. Clinical Applications)

Crystal Structures of Human Cholinesterases in Complex with Huprine W and Tacrine: Elements of Specificity for Anti-Alzheimer's Drugs Targeting Acetyl- and Butyrylcholinesterase

BJ Structure — Fri, 17 May 2013 04:00:00 +0100

The multifunctional nature of Alzheimer's disease calls for multi-target directed ligands (MTDLs) able to act on different components of the pathology, like the cholinergic dysfunction and amyloid aggregation. Such MTDLs are usually based on cholinesterase inhibitors (e.g., tacrine or huprine) coupled to another active molecule aimed at a different target. To aid in the design of these MTDLs we report the crystal structures of human acetylcholinesterase (hAChE) in complex with FAS-2 and a hydroxylated derivative of huprine (huprine W), and of human butyrylcholinesterase (hBChE) in complex with tacrine. Huprine W in hAChE and tacrine in hBChE reside in strikingly similar positions highlighting the conservation of key interactions, namely, π-π/cation-π interactions with ...

Convergent Evolution of Chromatin Modification by Structurally Distinct Enzymes: Comparative Enzymology of Histone 3 Lysine 27 Methylation by Human Polycomb Repressive Complex 2 and Viral vSET

BJ Structure — Fri, 17 May 2013 04:00:00 +0100

Histone H3 lysine 27 (H3K27) methylation is an important epigenetic modification that regulates gene transcription. In humans, EZH1 and EZH2 are the only enzymes capable of catalyzing methylation of H3K27. There is great interest in understanding structure-function relationships for EZH2, as genetic alterations in this enzyme are thought to play a causal role in a number of human cancers. EZH2 is challenging to study because it is only active in the context of the multi-subunit Polycomb Repressive Complex 2 (PRC2). vSET is a viral lysine methyltransferase that represents the smallest protein unit capable of catalyzing H3K27 methylation. The crystal structure of this minimal catalytic protein has been solved and researchers have suggested that vSET might prove useful as an EZH2 surrogate fo...

Computational Approaches to Selected Reaction Monitoring Assay Design

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:02 +0100

Selected reaction monitoring (SRM) is becoming the tool of choice for targeted quantitative proteomics, with applications as diverse as clinical diagnostics and systems biology. Assay design is critical to the success of every SRM experiment. For each protein of interest it is necessary to find a set of peptides that can be monitored as surrogates for that protein. These peptides must satisfy a number of criteria, including uniqueness in the proteome, detectability by mass spectrometry, and suitability of product ion series. Finding peptides that meet all these criteria is time consuming, especially when seeking to quantify multiple proteins in a single run. In response to these challenges, a number of groups have developed freely available tools to assist in the process of SRM assay desig...

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Feature Selection and Machine Learning with Mass Spectrometry Data

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Mass spectrometry has been used in biochemical research for a long time. However, its potential of discovering proteomic biomarkers using protein mass spectra aroused tremendous interest in last few years. In spite of its potential of biomarker discovery, it is recognized that identification of meaningful proteomic features from mass spectra needs careful evaluation. Hence, extracting meaningful feature(s) and discriminating the samples based on these features is still an open area of research. Several research groups are actively involved in making the process as perfect as possible. In this chapter, we provide a review of major contributions toward feature selection and classification of proteomic mass spectra involving MALDI-TOF and SELDI-TOF technology. Moreover, in this updated versio...

Considerations in the Analysis of Hydrogen Exchange Mass Spectrometry Data

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

We describe the fundamental parameters to be considered at each step along the way and how data processing, either by an individual or by software, must approach the analysis. (Source: Springer protocols feed by Protein Science)

Permethylated N-Glycan Analysis with Mass Spectrometry

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Protein glycosylation plays an important role in multiple cell functions, and aberrations of protein glycosylation are associated with various malignancies including cancer. In this chapter, we provide a detailed protocol for MALDI MS analysis of permethylated N-glycans extracted from human serum proteins. The protocol includes procedures for N-glycan purification and in-solution permethylation, structural elucidation of permethylated N-glycans by MALDI-QIT-TOF MS, and construction of indices to quantify levels of certain types of glycosylation, such as fucosylation, which may serve as a potential disease biomarker. (Source: Springer protocols feed by Protein Science)

Mass Spectrometry Methods for Studying Glycosylation in Cancer

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Protein glycosylation is a highly complex and regulated posttranslational modification. In this process several glycosyltransferase families are involved. In cancer this delicate equilibrium is disrupted leading to glycosylation changes on glycoconjugates, namely, glycoproteins. One of the major consequences is the increase of sialylated oligosaccharide chains in glycoproteins. Here we describe an experimental methodology focused in the enrichment and characterization of sialic acid containing glycopeptides by MALDI mass spectrometry and the subsequent data analysis. (Source: Springer protocols feed by Protein Science)

Proteomics Data Exchange and Storage: The Need for Common Standards and Public Repositories

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Both the existence of data standards and public databases or repositories have been key factors behind the development of the existing “omics” approaches. In this book chapter we first review the main existing mass spectrometry (MS)-based proteomics resources: PRIDE, PeptideAtlas, GPMDB, and Tranche. Second, we report on the current status of the different proteomics data standards developed by the Proteomics Standards Initiative (PSI): the formats mzML, mzIdentML, mzQuantML, TraML, and PSI-MI XML are then reviewed. (Source: Springer protocols feed by Protein Science)

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Tools for Protein Posttranslational Modifications Analysis: FAK, a Case Study

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Recent advances in mass spectrometry have resulted in an exponential increase in annotation of posttranslational modifications (PTMs). Just in the Swiss-Prot Knowledgebase, there are 89,931 of a total of 27 characterized PTM types reported experimentally. A single protein can be dynamically modified during its lifetime for regulation of its function. Considering a PTM can occur at different levels and the number of different PTMs described, the number of possibilities for a single protein is unthinkable. Narrowing the study to a single PTM can be rather unmerited considering that most proteins are heavily modified. Currently crosstalk between PTMs is plentifully reported in the literature. The example of amino acids serine and threonine on one hand and lysine on the other hand, as targets ...

Proteomic Strategies to Characterize Signaling Pathways

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Cells respond to external stimuli by transducing signals through a series of intracellular molecules and eliciting an appropriate response. The cascade of events through which the signals are transduced include post-translational modifications such as phosphorylation and ubiquitylation in addition to formation of multi-protein complexes. Improvements in biological mass spectrometry and protein/peptide microarray technology have tremendously improved our ability to probe proteins, protein complexes, and signaling pathways in a high-throughput fashion. Today, a single mass spectrometry-based investigation of a signaling pathway has the potential to uncover the large majority of known signaling intermediates painstakingly characterized over decades in addition to discovering a number of novel...

Simple Proteomics Data Analysis in the Object-Oriented PowerShell

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Scripting languages such as Perl and Python are appreciated for solving simple, everyday tasks in bioinformatics. A more recent, object-oriented command shell and scripting language, Windows PowerShell, has many attractive features: an object-oriented interactive command line, fluent navigation and manipulation of XML files, ability to consume Web services from the command line, consistent syntax and grammar, rich regular expressions, and advanced output formatting. The key difference between classical command shells and scripting languages, such as bash, and object-oriented ones, such as PowerShell, is that in the latter the result of a command is a structured object with inherited properties and methods rather than a simple stream of characters. Conveniently, PowerShell is included in al...

Introduction to Mass Spectrometry-Based Proteomics

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Mass spectrometry has been widely applied to study biomolecules and one rapidly developing field is the global analysis of proteins, proteomics. Understanding and handling mass spectrometry data is a multifaceted task that requires many decisions to be made to get the most comprehensive information from an experiment. Later chapters in this book deal in-depth with various aspects of the process and how different tools can be applied to the many analytical challenges. This introductory chapter is intended as a basic introduction to mass spectrometry (MS)-based proteomics to set the scene for newcomers and give pointers to reference material. (Source: Springer protocols feed by Protein Science)

LC-MS Spectra Processing

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Peak extraction from raw data is the first step in LC-MS data analysis. The quality of this procedure is important since it affects the quality and accuracy of all subsequent analysis such as database searches and peak quantitation. The most important and most accurately measured physical entity provided by mass spectrometers is m/z values which need to be extracted by state of art algorithms and scrutinized thoroughly. The aim of this chapter is to provide a discussion of peak processing methods and furthermore discuss some of the yet unresolved or neglected issues. A few novel concepts are also proposed for analysis and visualization. The final section of this chapter provides a note on possible software for spectra processing. (Source: Springer protocols feed by Protein Science)

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Isotopic Distributions

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Isotopic information determined by mass spectrometry can be used in a wide variety of applications. Broadly speaking these could be classified as “passive” applications, meaning that they use naturally occurring isotopic information, and “active” applications, meaning that the isotopic distributions are manipulated in some way. The classic passive application is the determination of chemical composition by comparing observed isotopic patterns of molecules to theoretically calculated isotopic patterns. Active applications include isotope exchange experiments of a variety of types, as well as isotope labeling in tracing studies and to provide references for quantitation. Regardless of the type of application considered, the problem of theoretical calculation of isotop...

Retention Time Prediction and Protein Identification

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

In bottom-up proteomics, proteins are typically identified by enzymatic digestion into peptides, tandem mass spectrometry and comparison of the tandem mass spectra with those predicted from a sequence database for peptides within measurement uncertainty from the experimentally obtained mass. Although now decreasingly common, isolated proteins or simple protein mixtures can also be identified by measuring only the masses of the peptides resulting from the enzymatic digest, without any further fragmentation. Separation methods such as liquid chromatography and electrophoresis are often used to fractionate complex protein or peptide mixtures prior to analysis by mass spectrometry. Although the primary reason for this is to avoid ion suppression and improve data quality, these separations are ...

Algorithms for Database-Dependent Search of MS/MS Data

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

The frequent used bottom-up strategy for identification of proteins and their associated modifications generate nowadays typically thousands of MS/MS spectra that normally are matched automatically against a protein sequence database. Search engines that take as input MS/MS spectra and a protein sequence database are referred as database-dependent search engines. Many programs both commercial and freely available exist for database-dependent search of MS/MS spectra and most of the programs have excellent user documentation. The aim here is therefore to outline the algorithm strategy behind different search engines rather than providing software user manuals. The process of database-dependent search can be divided into search strategy, peptide scoring, protein scoring, and finally protein i...

Interpretation of Tandem Mass Spectra of Posttranslationally Modified Peptides

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Tandem mass spectrometry provides a sensitive means of analyzing the amino acid sequence of peptides and modified peptides by providing accurate mass measurements of precursor and fragment ions. Modern mass spectrometry instrumentation is capable of rapidly generating many thousands of tandem mass spectra and protein database search engines have been developed to match the experimental data to peptide candidates. In most studies there is a schism between discarding perfectly valid data and including nonsensical peptide identifications—this is currently a major bottleneck in data-analysis and it calls for an understanding of tandem mass spectrometry data. Manual evaluation of the data and perhaps experimental cross-checking of the MS data can save many months of experimental work tryi...

Improving Peptide Identification Using Empirical Scoring Systems

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Peptides and proteins are routinely identified from peptide fragmentation spectra acquired in a mass spectrometer, analyzed by database search engines. The types of fragments that can be formed are known, and it is also well appreciated that certain fragment types are more common or more informative than others. However, most search engines do not use detailed knowledge of peptide fragmentation, but rather consider a limited range of fragments, giving each an equivalent weighting in their scoring system that decides which results are likely to be correct. This chapter discusses efforts to make use of information about the frequency of observation of different fragment ion types in order to produce more sophisticated and sensitive scoring systems and demonstrates how these new scoring syste...

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Methods and Algorithms for Quantitative Proteomics by Mass Spectrometry

Springer protocols feed by Protein Science — Thu, 16 May 2013 22:12:01 +0100

Protein quantitation by mass spectrometry (MS) is attractive since it is possible to obtain both identification and quantitative values of proteins and their posttranslational modifications in a single experiment. In contrast, protein arrays only provide quantitative values of targeted proteins and their modifications. There are an overwhelming number of quantitative MS methods for protein and peptide quantitation. The aim here is to provide an overview of the most common MS methods and algorithms used in quantitative proteomics and discuss the computational algorithms needed to reliably quantitate proteins, peptides, and their posttranslational modifications. One of the main challenges in data analysis of many experimental projects is to pipe together a number of software solutions that a...

Editorial Board

FEBS Letters — Thu, 16 May 2013 22:11:58 +0100

(Source: FEBS Letters)

[News of the Week] Newsmakers

Science: Current Issue — Thu, 16 May 2013 20:10:13 +0100

R. Graham Cooks, a chemist at Purdue University in West Lafayette, Indiana, has been awarded the 2013 Dreyfus Prize in the Chemical Sciences. And biochemist Christian de Duve, who helped reveal the internal organization and operation of cells, died on 4 May. (Source: Science: Current Issue)

Most Complete Database To Date Of Human Phosphatases And Their Substrates

Health News from Medical News Today — Thu, 16 May 2013 07:00:00 +0100

Although we know the tool's general purpose, it can sometimes be difficult to tell if a specific pair of precision tweezers belongs to a surgeon or a master jeweller. It is now easier to solve similar conundrums about a type of protein that allows cells to react to their environment, thanks to scientists at the European Molecular Biology Laboratory (EMBL). Published in Science Signaling, their work offers a valuable resource for other researchers... (Source: Health News from Medical News Today)

Vicious cycle: Obesity sustained by changes in brain biochemistry

EurekAlert! - Medicine and Health — Thu, 16 May 2013 04:00:00 +0100

(Brown University) In a new discovery reported in the Journal of Biological Chemistry, Brown University and Lifespan researchers show that in the brain cells of rats, obesity impedes the production of a hormone that curbs appetite and inspires calorie burning. The root cause appears to be a breakdown in the protein-processing mechanism of the cells. In the lab, the researchers showed they could fix the breakdown with drugs. (Source: EurekAlert! - Medicine and Health)

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How Much A Single Cell Breathes

Health News from Medical News Today — Wed, 15 May 2013 07:00:00 +0100

Scanning electrochemical microscopy decisively optimized How active a living cell is can be seen by its oxygen consumption. The method for determining this consumption has now been significantly improved by chemists in Bochum. The problem up to now was that the measuring electrode altered the oxygen consumption in the cell's environment much more than the cell itself. "We already found that out twelve years ago," says Prof. Dr. Wolfgang Schuhmann from the Department of Analytical Chemistry at the Ruhr-Universitat. "Now we have finally managed to make the measuring electrode an spectator... (Source: Health News from Medical News Today)

Researchers Develop Implant To Regenerate Nerves

Health News from Medical News Today — Wed, 15 May 2013 07:00:00 +0100

Some parts of the body, like the liver, can regenerate themselves after damage. But others, such as our nervous system, are considered either irreparable or slow to recover, leaving thousands with a lifetime of pain, limited mobility, or even paralysis. Now a team of Tel Aviv University researchers, including Dr. Shimon Rochkind of TAU's Sackler Faculty of Medicine and Tel Aviv Sourasky Medical Center and Prof. Zvi Nevo of TAU's Department of Human Molecular Genetics and Biochemistry, has invented a method for repairing damaged peripheral nerves... (Source: Health News from Medical News Today)

Biochemistry: The ylide has landed

Nature AOP — Wed, 15 May 2013 04:00:00 +0100

Nature advance online publication 15 May 2013. doi:10.1038/nature12247 Authors: Bradley J. Landgraf & Squire J. Booker The enzyme co-substrate SAM has long been known to have two chemically distinct roles. A study of the CmoA enzyme suggests that SAM has a third trick up its sleeve — it forms species known as ylides. (Source: Nature AOP)

Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function

Nature AOP — Wed, 15 May 2013 04:00:00 +0100

We describe a new metabolite, carboxy-S-adenosyl-l-methionine (Cx-SAM), its biosynthetic pathway and its role in transfer RNA modification. The structure of CmoA, a member of the SAM-dependent methyltransferase superfamily, revealed a ligand consistent with Cx-SAM in the catalytic site. Mechanistic analyses showed an unprecedented role for prephenate as the carboxyl donor and the involvement of a unique ylide intermediate as the carboxyl acceptor in the CmoA-mediated conversion of SAM to Cx-SAM. A second member of the SAM-dependent methyltransferase superfamily, CmoB, recognizes Cx-SAM and acts as a carboxymethyltransferase to convert 5-hydroxyuridine into 5-oxyacetyl uridine at the wobble position of multiple tRNAs in Gram-negative bacteria, resulting in expanded codon-recognition propert...

Hesperidin Prevents Androgen Deficiency‐induced Bone Loss in Male Mice

Phytotherapy Research — Wed, 15 May 2013 04:00:00 +0100

Abstract The purpose of this study was to examine whether hesperidin inhibits bone loss in androgen‐deficient male mice. Male ddY mice aged 7 weeks underwent either a sham operation or orchidectomy (ORX) and were divided into five groups: a sham‐operated group fed a control diet (Sham) based on AIN‐93G formulation with corn oil instead of soy bean oil, an ORX group fed the control diet (ORX), a group fed the control diet containing 0.5% hesperidin (ORX + H), a group fed the control diet containing 0.7% α‐glucosylhesperidin (ORX + αG), and a group fed the control diet containing 0.013% simvastatin (ORX + St). Four weeks after intervention, ORX mice showed a striking decrease in seminal vesicle weight, which was not affected by the administration of hesperidin, α‐glu...

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Aldose Reductase Inhibitors of Plant Origin

Phytotherapy Research — Wed, 15 May 2013 04:00:00 +0100

Diabetic complications are attributed to hyperglycaemic condition which is in turn associated with the polyol pathway and advanced glycation end products. Aldose reductase (AR) is the principal enzyme of polyol pathway which plays a vital role in the development of diabetic complications. AR inhibitory activity can be screened by both in vitro and in vivo methods. In vitro assays for AR enzyme are further classified on the basis of the source of enzyme such as rat lens, rat kidney, cataracted human eye lens, bovine eyes and human recombinant AR enzymes, whereas the in vivo model is based on the determination of lens galactitol levels. A number of synthetic AR inhibitors (ARIs) including tolrestat and sorbinil have been developed, but all of these suffer from drawbacks such as poor permeati...

Bifidobacterium longum NCC3001 inhibits AH neuron excitability

Neurogastroenterology and Motility — Wed, 15 May 2013 03:10:53 +0100

Conclusions & InferencesThe probiotic B. longum reduces excitability of AH sensory neurons likely via opening of potassium channels and closing of hyperpolarization‐activated cation channels. (Source: Neurogastroenterology and Motility)

Hearing, Vision Loss And Kidney Disease May Be Impacted By Cilia Research

Health News from Medical News Today — Tue, 14 May 2013 08:00:00 +0100

Experiments at Johns Hopkins have unearthed clues about which protein signaling molecules are allowed into hollow, hair-like "antennae," called cilia, that alert cells to critical changes in their environments. Researchers found that the size limit for entry is much greater than previously thought, allowing most of a cell's proteins into cilia. The researchers believe that the specific collection of proteins in each cilium, customized to the needs of each cell type, is determined by whether and how cilia keep proteins inside once they enter - not which ones they allow in initially... (Source: Health News from Medical News Today)

Single-molecule DNA repair in live bacteria [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 14 May 2013 04:00:00 +0100

Cellular DNA damage is reversed by balanced repair pathways that avoid accumulation of toxic intermediates. Despite their importance, the organization of DNA repair pathways and the function of repair enzymes in vivo have remained unclear because of the inability to directly observe individual reactions in living cells. Here, we used... (Source: Proceedings of the National Academy of Sciences)

KedY4 as a new MIO-containing aminomutase [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 14 May 2013 04:00:00 +0100

4-Methylideneimidazole-5-one (MIO)-containing aminomutases catalyze the conversion of l-α-amino acids to β-amino acids with either an (R) or an (S) configuration. l-Phenylalanine and l-tyrosine are the only two natural substrates identified to date. The enediyne chromophore of the chromoprotein antitumor antibiotic kedarcidin (KED) harbors an (R)-2-aza-3-chloro-β-tyrosine moiety reminiscent of the (S)-3-chloro-5-hydroxy-β-tyrosine... (Source: Proceedings of the National Academy of Sciences)

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Structures of a viral DNA-packaging terminase [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 14 May 2013 04:00:00 +0100

Many DNA viruses use powerful molecular motors to cleave concatemeric viral DNA into genome-length units and package them into preformed procapsid powered by ATP hydrolysis. Here we report the structures of the DNA-packaging motor gp2 of bacteriophage Sf6, which reveal a unique clade of RecA-like ATPase domain and an RNase... (Source: Proceedings of the National Academy of Sciences)

SKR study of CDK8/CycC specific compounds [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 14 May 2013 04:00:00 +0100

In contrast with the very well explored concept of structure–activity relationship, similar studies are missing for the dependency between binding kinetics and compound structure of a protein ligand complex, the structure–kinetic relationship. Here, we present a structure–kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The scaffold... (Source: Proceedings of the National Academy of Sciences)

Phosphoproteomics—More than meets the eye

Electrophoresis — Tue, 14 May 2013 04:00:00 +0100

PTMs enable cells to adapt to internal and external stimuli in the milliseconds to seconds time regime. Protein phosphorylation is probably the most important of these modifications as it affects protein structure and interactions, critically influencing the life cycle of a cell. In the last 15 years, new insights into phosphorylation have been provided by highly sensitive MS‐based approaches combined with specific phosphopeptide enrichment strategies. Although so far research has mainly focused on the discovery and characterization of O‐phosphorylation, this review also briefly outlines the current knowledge about N‐phosphorylation depicting its ubiquitous relevance. Further, common pitfalls in sample preparation, LC‐MS analysis, and subsequent data analysis are discussed as well ...

STIM1 negatively regulates Ca2{+} release from the sarcoplasmic reticulum in skeletal myotubes

BJ Signal — Tue, 14 May 2013 04:00:00 +0100

Stromal interaction molecule 1 (STIM1) mediates store-operated Ca2+ entry (SOCE) in skeletal muscle. However, the direct role(s) of STIM1 in skeletal muscle, such as Ca2+ release from the sarcoplasmic reticulum (SR) for muscle contraction, have not been identified. The times required for the maximal expression of endogenous STIM1 or Orai1, or for the appearance of puncta during the differentiation of mouse primary skeletal myoblasts to myotubes, were all different, and the formation of puncta was detected with no stimulus during differentiation, suggesting that, in skeletal muscle, the formation of puncta is a part of the differentiation. Wild-type STIM1 and two STIM1 mutants (Triple mutant, missing Ca2+-sensing residues but possessing the intact C-terminus; and, E136X...

How I now know that unless we know what we don’t know we don’t know what we need to know

The Nutrition Society — Mon, 13 May 2013 11:07:52 +0100

What if we stopped doing experiments altogether, and started thinking? Previous articles have suggested that a systematic approach to building a computational model of a very well-known biochemical pathway rapidly led to the identification of some pretty hefty gaps in the literature. In this case the literature was the biochemistry of butyrate handling, but as another article suggested I had the same experience in a different area of nutrition. Given the sheer volume of papers published on my favourite biochemical entity, I don’t think that the reason for these gaps is lack of funding or lack of experimentation. Likewise I don’t think that there’s anything particular about this super-sub-specialism that causes gaps. I’ve paused several times recently and wondered if there is an ina...

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Researchers Unleash The Watchdog Protein To Slow The Progression Of Parkinson's Disease

Health News from Medical News Today — Mon, 13 May 2013 08:00:00 +0100

Research opens door to new drug therapies for Parkinson's disease McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The Neuro, and Dr. Kalle Gehring in the Department of Biochemistry at the Faculty of Medicine, have discovered the three-dimensional structure of the protein Parkin... (Source: Health News from Medical News Today)

A Highly Selective Refuse Collection

Health News from Medical News Today — Mon, 13 May 2013 07:00:00 +0100

At the University of Geneva (UNIGE), the team led by Professor Jean Gruenberg has long been interested in the movement of lysosomes, the sub-compartments of cells to where endocytic vesicles deliver their waste content and the molecules destined to be destroyed. Within this context, researcher Christin Bissig, along with her international colleagues, carried out a detailed study of the route taken by Alix which is lodged inside the endosomal membrane... (Source: Health News from Medical News Today)

Pressurized capillary electrochromatography with amperometric detection using mixed‐mode monolithic column for rapid analysis of chlorophenols and phenol

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

An on‐line sample preconcentration technique based on a dynamic pH junction in capillary electrophoresis‐amperometric detection for the analysis of biogenic amines in urine

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

Encapsulated Electrodes for Microchip Devices: Microarrays and Platinized Electrodes for Signal Enhancement

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

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Nanostructured CaCO3‐PEI microparticles for phenol sensing in fluidic microsystem

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

Integration of a Graphite/PMMA Composite Electrode into a Poly(methyl methacrylate) (PMMA) Substrate for Electrochemical Detection in Microchips

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

Twenty‐one years of microemulsion electrokinetic chromatography (1991–2012): A powerful analytical tool

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

Electrophoresis 2013, 34, 1273‐1294. DOI: 10.1002/elps.201200494 A powerful method to improve the resolution in MEEKC is the use of additives to the background electrolyte. Migration behaviors of analytes can be easily modified by additives, such as carbon nanotubes, ionic liquids, organic solvents and cyclodextrins. These additives can affect the interaction between microemulsions and analytes. (Source: Electrophoresis)

Editorial Board: Electrophoresis 9‐10'13

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

(Source: Electrophoresis)

Contents: Electrophoresis 9‐10'13

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

(Source: Electrophoresis)

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Sweeping of alprenolol enantiomers with an organic solvent and sulfated β‐cyclodextrin in capillary electrophoresis

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

Sweeping, an on‐line sample concentration technique in CE, is the picking and accumulation of analytes by the pseudostationary phase or complexing additive. In the presence of an electric field, the analytes concentrated at the additive front that initially penetrated the sample zone. Here, we describe the sweeping of cationic alprenolol enantiomers using sulfated β‐CD and organic solvent. The separation solution contained the anionic additive while ACN was in the sample solution. With fused silica capillaries, positive polarity, and solutions buffered at pH 3, the direction of the enantiomers' effective electrophoretic mobility was the same as the electrophoretic mobility (or electrophoretic mobility without additive). When the amount of ACN in the sample was increased (i.e. 60%), th...

Errata

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

(Source: Electrophoresis)

Call for Papers

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

(Source: Electrophoresis)

Meetings Diary

Electrophoresis — Mon, 13 May 2013 04:00:00 +0100

(Source: Electrophoresis)

Proteomics of plaques and novel sources of potential biomarkers for atherosclerosis

Proteomics. Clinical Applications — Mon, 13 May 2013 04:00:00 +0100

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Effects of gamma irradiation and 15 days of subsequent ex vivo storage on the cytosolic red blood cell proteome analyzed by 2D DIGE and Orbitrap MS

Proteomics. Clinical Applications — Mon, 13 May 2013 04:00:00 +0100

Conclusions and clinical relevanceGamma irradiation and subsequent ex vivo storage according to the European CE guidelines were found to affect RBC protein structures. The validated marker proteins can serve as a basis for the development of a screening assay to monitor the quality of irradiated RBC concentrates during ex vivo storage.This article is protected by copyright. All rights reserved (Source: Proteomics. Clinical Applications)

Development of a label‐free LC‐MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy

Proteomics. Clinical Applications — Mon, 13 May 2013 04:00:00 +0100

Steric and electronic interactions controlling the cis/trans isomer equilibrium at X‐Pro tertiary amide motifs in solution

Biopolymers — Sun, 12 May 2013 09:11:00 +0100

ABSTRACT A systematic understanding of the non‐covalent interactions that influence the structures of the cis conformers and the equilibrium between the cis and the trans conformers, of the X‐Pro tertiary amide motifs, is presented based on analyses of 1H‐, 13C‐NMR and FT‐IR absorption spectra of two sets of homologous peptides, X‐Pro‐Aib‐OMe and X‐Pro‐NH‐Me (where X is acetyl, propionyl, isobutyryl and pivaloyl), in solvents of varying polarities. Firstly, this work shows that the cis conformers of any X‐Pro tertiary amide motif, including Piv‐Pro, are accessible in the new motifs X‐Pro‐Aib‐OMe, in solution. These conformers are uniquely observable by FT‐IR spectroscopy at ambient temperatures and by NMR spectroscopy from temperatures as high as 273 K. Th...

Biochemistry: Attacked by Radicals

Editors' Choice — Sun, 12 May 2013 07:11:08 +0100

Some bonds are easy to break, and enzymes can handle these via general acid-base catalysis; other bonds are tougher nuts to crack, hence enzymes call upon more potent chemical weaponry, … [Read more] (Source: Editors' Choice)

Editors' Choice

Science: Current Issue — Sun, 12 May 2013 07:11:07 +0100

Biomedicine: The Benefits of Sequestration | Education: Motivation + Skill = Success | Animal Behavior: A Social Shake-up by Song | Chemistry: Brushing Away Toxicity | Chemistry: Mimicking Rodlike Viruses | Biomedicine: Peptide Prevention | Biochemistry: Attacked by Radicals (Source: Science: Current Issue)

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Geometrical constraints limiting the poly(ADP‐ribose) conformation investigated by molecular dynamics simulation

Biopolymers — Sun, 12 May 2013 04:00:00 +0100

Abstract Poly(ADP‐ribosylation) is a post transductional modification that regulates protein's function. Most of the proteins subjected to this control mechanism belong to machineries involved in DNA damage repair, or DNA interacting proteins. Poly(ADP‐ribose) polymers are long chains of even 100 monomer length that can be branched at several positions but, notwithstanding its importance, nothing is known concerning its structure. In order to understand which are the geometrical parameters that confer to the polymer the structural constraints that determine its interaction with the target proteins, we have performed molecular dynamics of three chains of different length, made by 5, 25 and 30 units, the last one being branched. Analysis of the simulations allowed us to identify the main...

Structural consequences of cutting a binding loop: two circularly permuted variants of streptavidin

Acta Crystallographica Section D — Sat, 11 May 2013 04:00:00 +0100

Circular permutation of streptavidin was carried out in order to investigate the role of a main-chain amide in stabilizing the high-affinity complex of the protein and biotin. Mutant proteins CP49/48 and CP50/49 were constructed to place new N-termini at residues 49 and 50 in a flexible loop involved in stabilizing the biotin complex. Crystal structures of the two mutants show that half of each loop closes over the binding site, as observed in wild-type streptavidin, while the other half adopts the open conformation found in the unliganded state. The structures are consistent with kinetic and thermodynamic data and indicate that the loop plays a role in enthalpic stabilization of the bound state via the Asn49 amide–biotin hydrogen bond. In wild-type streptavidin, the entropic penalties o...

High-resolution powder X-ray data reveal the T6 hexameric form of bovine insulin

Acta Crystallographica Section D — Sat, 11 May 2013 04:00:00 +0100

A series of bovine insulin samples were obtained as 14 polycrystalline precipitates at room temperature in the pH range 5.0–7.6. High-resolution powder X-ray diffraction data were collected to reveal the T6 hexameric insulin form. Sample homogeneity and reproducibility were verified by additional synchrotron measurements using an area detector. Pawley analyses of the powder patterns displayed pH- and radiation-induced anisotropic lattice modifications. The pronounced anisotropic lattice variations observed for T6 insulin were exploited in a 14-data-set Rietveld refinement to obtain an average crystal structure over the pH range investigated. Only the protein atoms of the known structure with PDB code 2a3g were employed in our starting model. A novel approach for refining protein structur...

Structure and functional studies of the ribonuclease binase Glu43Ala/Phe81Ala mutant

Acta Crystallographica Section D — Sat, 11 May 2013 04:00:00 +0100

Ribonuclease from Bacillus intermedius (binase) is a small basic protein with antitumour activity. The three-dimensional structure of the binase mutant form Glu43Ala/Phe81Ala was determined at 1.98 Å resolution and its functional properties, such as the kinetic parameters characterizing the hydrolysis of polyinosinic acid and cytotoxicity towards Kasumi-1 cells, were investigated. In all crystal structures of binase studied previously the characteristic dimer is present, with the active site of one subunit being blocked owing to interactions within the dimer. In contrast to this, the new mutant form is not dimeric in the crystal. The catalytic efficiency of the mutant form is increased 1.7-fold and its cytotoxic properties are enhanced compared with the wild-type enzyme. (Source: Acta C...

Revisiting the Haloarcula marismortui 50S ribosomal subunit model

Acta Crystallographica Section D — Sat, 11 May 2013 04:00:00 +0100

The structure of the large ribosomal subunit from the halophilic archaeon Haloarcula marismortui (Hma) is the only crystal structure of an archaeal ribosomal particle that has been determined to date. However, the first model of the Hma 50S ribosomal subunit contained some gaps: the structures of functionally important mobile lateral protuberances were not visualized. Subsequently, some parts of the P (L12) stalk base were visualized at 3.0 Å resolution [Kavran & Steitz (2007), J. Mol. Biol. 371, 1047–1059]: the RNA-binding domain of r-protein P0 (L10), the C-terminal domain of L11 and helices 43 and 44 of the 23 S rRNA. Here, the 2.4 Å resolution electron-density map of the Hma 50S ribosomal subunit was revisited and approximately two-thirds of the P0 protein, residues 1–58 of t...

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Yellow fluorescent protein phiYFPv (Phialidium): structure and structure-based mutagenesis

Acta Crystallographica Section D — Sat, 11 May 2013 04:00:00 +0100

The yellow fluorescent protein phiYFPv (λemmax ≃ 537 nm) with improved folding has been developed from the spectrally identical wild-type phiYFP found in the marine jellyfish Phialidium. The latter fluorescent protein is one of only two known cases of naturally occurring proteins that exhibit emission spectra in the yellow–orange range (535–555 nm). Here, the crystal structure of phiYFPv has been determined at 2.05 Å resolution. The `yellow' chromophore formed from the sequence triad Thr65-Tyr66-Gly67 adopts the bicyclic structure typical of fluorophores emitting in the green spectral range. It was demonstrated that perfect antiparallel π-stacking of chromophore Tyr66 and the proximal Tyr203, as well as Val205, facing the chromophore phenolic ring are chiefly responsible for...

MINIREVIEW: Thematic Series on Metals in Biology 2013 [Enzymology]

Journal of Biological Chemistry — Fri, 10 May 2013 04:00:00 +0100

One-half of the available protein structures contain metals, explaining their roles as essential trace elements. Metals are also critical in many aspects of nucleic acid biochemistry. This prologue briefly introduces the fifth of the Thematic Series on Metals in Biology, which began in the Journal of Biological Chemistry in 2009. The five minireviews in this 2013 series deal with the molybdenum prosthetic group (a pterin known as Moco); the biosynthesis of the “M-cluster” molybdenum prosthetic group of nitrogenase; the biosynthesis of the nickel-based metallocenter of the enzyme urease; several of the processing, transport, and medical aspects of cobalamins; and the growing roles of heme sensor proteins. (Source: Journal of Biological Chemistry)

MINIREVIEW: B12 Trafficking in Mammals [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 10 May 2013 04:00:00 +0100

The reactivity of the cobalt-carbon bond in cobalamins is the key to their chemical versatility, supporting both methyl transfer and isomerization reactions. During evolution of higher eukaryotes that utilize vitamin B12, the high reactivity of the cofactor coupled with its low abundance pressured development of an efficient system for uptake, assimilation, and delivery of the cofactor to client B12-dependent enzymes. Although most proteins suspected to be involved in B12 trafficking were discovered by 2009, the recent identification of a new protein reveals that the quest for elucidating the intracellular B12 highway is still far from complete. Herein, we review the biochemistry of cobalamin trafficking. (Source: Journal of Biological Chemistry)

Glucan Hydrolase Activity of Fungal SUN Proteins [Microbiology]

Journal of Biological Chemistry — Fri, 10 May 2013 04:00:00 +0100

In yeasts, the family of SUN proteins has been involved in cell wall biogenesis. Here, we report the characterization of SUN proteins in a filamentous fungus, Aspergillus fumigatus. The function of the two A. fumigatus SUN genes was investigated by combining reverse genetics and biochemistry. During conidial swelling and mycelial growth, the expression of AfSUN1 was strongly induced, whereas the expression of AfSUN2 was not detectable. Deletion of AfSUN1 negatively affected hyphal growth and conidiation. A closer examination of the morphological defects revealed swollen hyphae, leaky tips, intrahyphal growth, and double cell wall, suggesting that, like in yeast, AfSun1p is associated with cell wall biogenesis. In contrast to AfSUN1, deletion of AfSUN2 either in the parental strain or in th...

Mass spectrometric peptide analysis of 2DE‐separated mouse spinal cord and rat hippocampus proteins suggests an NGxG motif of importance for in vivo deamidation

Electrophoresis — Fri, 10 May 2013 04:00:00 +0100

Asparagine deamidation is a common nonenzymatic post‐translational modification comprising the conversion of asparaginyl residues to aspartyl and isoaspartyl residues, respectively. As a result an additional negative charge is introduced that can affect the tertiary structure as well as the biological activity of a protein. Since deamidation reduces the protein's pI value, differentially deamidated forms of a protein can be separated in 2D gels. We have analyzed a dataset of 430 protein spots from 2D gels that contained mouse spinal cord proteins and estimated that roughly 10% of the spots in a Coomassie‐stained gel derive from in vivo deamidation at particular asparaginyl residues. Several of the deamidated protein forms, e.g. tropomodulin‐2, V‐type proton ATPase subunit B, and pr...

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Journal of Cellular Biochemistry: Volume 114, Number 7, July, 2013

Journal of Cellular Biochemistry — Fri, 10 May 2013 04:00:00 +0100

Abstract Cover: Immunofluorescence images of MIA PaCa‐2 cells cultured in SCM and SFM. See article by Bose et al., pages 1642–1652. Cover designed by Lucía Sagredo S´nchez. (Source: Journal of Cellular Biochemistry)

Table of Contents: Volume 114, Number 7

Journal of Cellular Biochemistry — Fri, 10 May 2013 04:00:00 +0100

(Source: Journal of Cellular Biochemistry)

Features: Volume 114, Number 7

Journal of Cellular Biochemistry — Fri, 10 May 2013 04:00:00 +0100

(Source: Journal of Cellular Biochemistry)

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AKI: Specific causes and conditions

Nephrology Dialysis Transplantation — Fri, 10 May 2013 04:00:00 +0100

Conclusions: AKI occurs is an important complication after lung and heart transplantation and contributes to increased morbidity and mortality. (Source: Nephrology Dialysis Transplantation)

Ferulic acid in the treatment of post‐diabetes testicular damage: relevance to the down regulation of apoptosis correlates with antioxidant status via modulation of TGF‐β1, IL‐1β and Akt signalling

Cell Biochemistry and Function — Fri, 10 May 2013 04:00:00 +0100

The aim of this study was to investigate the protective effect of ferulic acid at different doses (50 mg kg−1 alternative day and 50 mg kg−1 daily) on the streptozotocin (STZ)‐induced post‐diabetes rat testicular damage. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). Rats treated with ferulic acid were given once a day orally for 10 weeks, starting 3 days after STZ injection. Testis tissue and blood samples were collected for investigating biochemical analysis, antioxidant status, sperm parameters, and histopathological, immunohistochemical and apoptotic studies. Treatment with ferulic acid to diabetic rats significantly improved the body weight, testis weight, serum insulin level, serum testosterone level and sperm parameters (viability...

Balanced maintenance fluids in PICU are safe and cost effective

Archives of Disease in Childhood — Thu, 09 May 2013 04:00:00 +0100

Conclusions Plasmalyte148–5% Glucose as the standard maintenance fluid for PICU is safe and effective; it has facilitated a reduction in the use of hypotonic fluids meeting Trust obligations under NPSA Safety Alert 22. There have been no documented cases of iatrogenic hyponatraemia in PICU since the adoption of this solution. There has been no change in electrolyte balance in the PICU patient population with the use of the balanced solution. Using a licensed balanced solution has reduced overall expenditure on maintenance fluids in PICU by 40% representing a saving in 1 year of £3200. We advocate the use of this balanced solution for all children in acute hospitals requiring intravenous fluids. (Source: Archives of Disease in Childhood)

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Unleashing the watchdog protein

EurekAlert! - Medicine and Health — Thu, 09 May 2013 04:00:00 +0100

(McGill University) McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -- The Neuro, and Dr. Kalle Gehring in the Department of Biochemistry at the Faculty of Medicine, have discovered the 3-D structure of the protein Parkin. (Source: EurekAlert! - Medicine and Health)

MicroRNA‐182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas

Journal of Cellular Biochemistry — Thu, 09 May 2013 04:00:00 +0100

In this study, we found that microRNA‐182 (miRNA‐182, miR‐182) was upregulated, whereas PDCD4 was downregulated in ovarian cancer tissues and cell lines. Blocking or increase of miR‐182 in ovarian cancer cell lines led to an opposite alteration of endogenous PDCD4 protein level. Using fluorescent reporter assay, we confirmed the direct and negative regulation of PDCD4 by miR‐182, which was dependent on the predicted miR‐182 binding site within PDCD4 3′ untranslated region (3′ UTR). MTT and colony formation assays suggested that miR‐182 blockage suppressed, whereas miR‐182 mimics enhanced viability and colony formation of ovarian cancer cells. These effects may partly be attributed to the cell cycle promotion activity of miR‐182. miR‐182 also contributed to migration...

Increased extracellular matrix and proangiogenic factor transcription in endothelial cells after cocultivation with primary human osteoblasts

Journal of Cellular Biochemistry — Thu, 09 May 2013 04:00:00 +0100

Abstract The most promising strategies in bone engineering have concentrated on providing sufficient vascularization to support the newly forming tissue. In this context, recent research in the field has focused on studying the complex interactions between bone forming and endothelial cells. Our previous work has demonstrated that direct contact cocultivation of human umbilical vein endothelial cells (HUVECs) with primary human osteoblasts (hOBs) induces the osteogenic phenotype and survival of hOBs. In order to investigate the mechanisms that lead to this effect, we performed microarray gene expression profiling on HUVECs following cocultivation with hOBs. Our data reveal profound transcriptomic changes that are dependent on direct cell contact between these cell populations. Pathway anal...

Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma

Journal of Cellular Biochemistry — Thu, 09 May 2013 04:00:00 +0100

In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty‐eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme‐linked immunosorbent assay. The number of CD4+CD25+regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin‐eosin, immunofluorescence staining, periodic‐acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL‐12 and high levels of IL‐13, IL‐4, OVA‐specific IgG...

Ganglioside GM3 inhibits hepatoma cell motility via down‐regulating activity of EGFR and PI3K/AKT signaling pathway

Journal of Cellular Biochemistry — Thu, 09 May 2013 04:00:00 +0100

Abstract Two related sublines derived from murine ascites hepatoma cell lines Hca‐F25, which were selected for their markedly different metastatic potential to lymph nodes, were found to be distinct in their ganglioside patterns. The low metastatic cell line (HcaP) contained a major ganglioside GM3, whereas the high metastatic cell line (HcaF) contained a major ganglioside GM2. Suppression of GM3 by P4 enhanced the mobility and migration of the low metastatic HcaP cells in vitro. Increase in GM3 content in high metastatic HcaF cells by addition of exogenous GM3 inhibited the mobility and migration. These results suggested that the differences in lymphatic metastasis potential between these two cell lines could be attributed to the differences in their ganglioside compositions, and GM3 co...

Non insulin producing cell line, MIA PaCa‐2 is rendered insulin producing in vitro via mesenchymal epithelial transition

Journal of Cellular Biochemistry — Thu, 09 May 2013 04:00:00 +0100

Abstract We used non‐insulin producing pancreatic carcinoma cell line, MIA PaCa‐2 and have modulated its culture conditions by using 1% matrigel as extracellular matrix, N2, B27 growth supplements and serum free conditions. Expression of markers was analyzed using qRT‐PCR, immunofluorescence and in vitro functional assay for insulin and C‐peptide release was assessed using insulin and C‐peptide ELISA, respectively. The cells grown under this altered culture conditions have exhibited a transition in the morphology from mesenchymal to epithelial with extensive piling up of cells. A reduction in doubling time from 40 to 18 h, upregulation of beta islet specific markers like pancreatic duodenal homeobox‐1 (Pdx‐1), C‐peptide, insulin, and disappearance of markers like vimentin...

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Comparison Between the Efficacy of Ginger and Sumatriptan in the Ablative Treatment of the Common Migraine

Phytotherapy Research — Thu, 09 May 2013 04:00:00 +0100

This study aims to evaluate the efficacy of ginger in the ablation of common migraine attack in comparison to sumatriptan therapy. In this double‐blinded randomized clinical trial, 100 patients who had acute migraine without aura were randomly allocated to receive either ginger powder or sumatriptan. Time of headache onset, its severity, time interval from headache beginning to taking drug and patient self‐estimation about response for five subsequent migraine attacks were recorded by patients. Patients, satisfaction from treatment efficacy and their willingness to continue it was also evaluated after 1 month following intervention. Two hours after using either drug, mean headaches severity decreased significantly. Efficacy of ginger powder and sumatriptan was similar. Clinical adver...

Gender depended potentiality of differentiation of human umbilical cord mesenchymal stem cells into oocyte‐Like cells in vitro

Cell Biochemistry and Function — Thu, 09 May 2013 04:00:00 +0100

Activated apoptotic and anti‐survival effects on rat hearts with fructose induced metabolic syndrome

Cell Biochemistry and Function — Thu, 09 May 2013 04:00:00 +0100

Consumption of fructose has been linked to the development of metabolic syndrome, whereas the cardiomyopathic changes and cardiac apoptosis of dietary high‐fructose intake have not yet been clarified. The purpose of this study was to evaluate the effects of high‐fructose on cardiac apoptotic and survival pathways. Thirty‐two Wistar rats were randomly divided into a control group (CON), which received a standard chow diet, and a fructose‐induced metabolic syndrome group (FIMS), which received a 50% fructose‐content diet for 13 weeks. Histopathological analysis, TUNEL assays and Western blotting were performed on the excised hearts from both groups. The blood pressure, glucose, insulin, triglyceride and cholesterol levels were significantly increased in the FIMS group, compared wit...

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Effects of raftilose on serum biochemistry and liver morphology in rats fed with normal or high‐fat diet

Nahrung / Food — Wed, 08 May 2013 04:00:00 +0100

In conclusion, 10% OFS supplementation prevented deleterious effects of FD such as alterations on lipid profile (TAG elevation) and hepatic morphologic changes. OFS decreased ALP activity in animals subjected to ND, which may have contributed to the differences on lipid metabolism. (Source: Nahrung / Food)

Optimization and validation of a capillary electrophoresis laser‐induced fluorescence method for amino acids determination in human plasma: Application to bipolar disorder study

Electrophoresis — Wed, 08 May 2013 04:00:00 +0100

Quantitative and qualitative analysis of amino acids in biofluids offers relevant information in diagnosis of diseases, evaluation of nutritional state, and in elucidating metabolic influences on physiology. A simple, rapid, and robust procedure in terms of sample treatment, separation, and quantitation based on CE‐LIF has been optimized for use in human plasma samples. Time required for derivatization was 15 min and analysis time was 35 min. 4‐Fluoro‐7‐nitro‐2,1,3‐benzoxadiazole (NBD‐F) was the labeling agent used for obtaining fluorescent derivatives. Electrophoretic conditions were: 175 mM borate buffer at pH 10.25 prepared with 12.5 mM β‐cyclodextrin. The voltage applied was +21 kV. Fourteen amino acids could be quantified: l‐proline, l‐phenylalanine, l‐leucine, ...

Automated immobilized metal affinity chromatography system for enrichment of Escherichia coli phosphoproteome

Electrophoresis — Wed, 08 May 2013 04:00:00 +0100

Enrichment of bacterial phosphopeptides is an essential step prior to bottom‐up mass spectrometry‐based analysis of the phosphoproteome, which is fundamental to understanding the role of phosphoproteins in cell signaling and regulation of protein activity. We developed an automated immobilized metal affinity chromatography (IMAC) system to enrich strong cation exchange‐fractionated phosphopeptides from the soluble proteome of Escherichia coli MG1655 grown on minimal medium. Initial demonstration of the system resulted in identification of 75 phosphopeptides covering 52 phosphoproteins. Consistent with previous studies, many of these phosphoproteins are involved in the carbohydrate portion of central metabolism. The automated system utilizes a large capacity IMAC column that can effec...

Identification of an unusually sulfated tetrasaccharide chondroitin/dermatan motif in mouse brain by combining chip‐nanoelectrospray multistage MS2‐MS4 and high resolution MS

Electrophoresis — Wed, 08 May 2013 04:00:00 +0100

Chondroitin sulfate (CS)/dermatan sulfate (DS) are often found in nature as hybrid glycosaminoglycan chains in various proteoglycans. In the recent years, several MS methods were developed for the determination of over‐, regular‐, and undersulfated CS/DS chains. In the present work, the released hybrid CS/DS isolated and purified from mouse brain were digested with chondroitin AC lyase. The depolymerized chains were separated by gel filtration chromatography. Collected tetrasaccharides were analyzed by fully automated (NanoMate robot) chip‐based nanoESI high capacity ion trap multistage MS (MS2–MS4) recently introduced in glycosaminoglycan research by our laboratory. The obtained data were confirmed by high resolution MS screening and MS/MS performed on QTOF instrument. NanoMate‐...

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Pivotal role of P450-P450 interactions in CYP3A4 allostery: the case of {alpha}-Naphthoflavone

BJ Energy — Wed, 08 May 2013 04:00:00 +0100

We investigated the relationship between oligomerization of cytochrome P450 3A4 (CYP3A4) and its response to alpha-naphthoflavone (ANF), a prototypical heterotropic activator. Addition of ANF resulted in over a two-fold increase in the rate of CYP3A4-dependent debenzylation of 7-benzyloxy-4-(trifluoromethyl)coumarin (7-BFC) in human liver microsomes (HLM) but failed to produce activation in BD Supersomes™ or Baculosomes® containing recombinant CYP3A4 and NADPH-cytochrome P450 reductase (CPR). However, incorporation of purified CYP3A4 into Supersomes containing only recombinant CPR reproduced the behavior observed with HLM. The activation in this system was dependent on the surface density of the enzyme. While no activation was detectable at a lipid:P450 (L/P) ratio ≥ 7...

Problem‐solving test: Digestion of a plasmid with restriction endonucleases

Biochemistry and Molecular Biology Education — Wed, 08 May 2013 04:00:00 +0100

Terms to be familiar with before you start to solve the test: plasmid, restriction endonuclease, agarose gel electrophoresis, ethidium bromide staining, autoradiography, Coomassie staining, Southern blotting, linear and circular DNA, superhelical DNA, exonuclease, modification methylase, palindrome, sticky and blunt ends, nicked circular DNA. © 2013 by The International Union of Biochemistry and Molecular Biology, 2013 (Source: Biochemistry and Molecular Biology Education)

Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro

Cell Biochemistry and Function — Wed, 08 May 2013 04:00:00 +0100

In this study, we investigated whether cell death is involved in the calcification on osteoblastic differentiation of human bone marrow mesenchymal stem cells (hMSC) under osteogenic culture in vitro. Apoptosis and necrosis occurred in an osteogenic culture of hMSC, and cell death preceded calcification. The generation of intracellular reactive oxygen species, chromatin condensation and fragmentation, and caspase‐3 activation increased in this culture. A pan‐caspase inhibitor (Z‐VAD‐FMK) and anti‐oxidants (Tiron and n‐acetylcysteine) inhibited osteogenic culture‐induced cell death and calcification. Furthermore, calcification was significantly promoted by the addition of necrotic dead cells or its membrane fraction. Spontaneously dead cells by osteogenic culture and exogenous...

HOX antisense lincRNA HOXA‐AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells

Journal of Cellular Biochemistry — Tue, 07 May 2013 21:10:59 +0100

Abstract HOXA cluster antisense RNA 2 (HOXA‐AS2) is a long non‐coding RNA located between the HOXA3 and HOXA4 genes in the HOXA cluster. Its transcript is expressed in NB4 promyelocytic leukemia cells and human peripheral blood neutrophils, and expression is increased in NB4 cells treated with all trans retinoic acid (ATRA). Knockdown of HOXA‐AS2 expression by transduced shRNA decreases the number of viable cells and increases the proportion of apoptotic cells, measured by annexin V binding and by activity and cleavage of caspases‐3, ‐8, and ‐9. The increase in death of HOXA‐AS2 knockdown cells was accompanied by an elevated TNF‐related apoptosis‐inducing ligand (TRAIL) levels, but ATRA‐induced NB4 cells treated with TRAIL did show an increase in HOXA‐AS2 expression. ...

Bristol professor elected Fellow of the Academy of Medical Sciences

University of Bristol news — Tue, 07 May 2013 09:20:00 +0100

Professor Jeremy Henley, from the School of Biochemistry, has been elected a Fellow of the Academy of Medical Sciences. (Source: University of Bristol news)

Key Process Discovered In Sexual Reproduction

Health News from Medical News Today — Tue, 07 May 2013 07:00:00 +0100

The Research Group headed by molecular biologist Andrea Pichler from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg has made an important discovery in meiosis research. Pichler and her group have identified a new mechanism that plays an important role in meiosis. Meiosis, also called reductional division, is a key process in sexual reproduction. It shuffles parental genetic material and thus guarantees genetic variety... (Source: Health News from Medical News Today)

Structures of HetR:DNA complexes [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

HetR is an essential regulator of heterocyst development in cyanobacteria. Many mutations in HetR render Anabaena incapable of nitrogen fixation. The protein binds to a DNA palindrome upstream of hetP and other genes. We have determined the crystal structures of HetR complexed with palindromic DNA targets, 21, 23, and 29... (Source: Proceedings of the National Academy of Sciences)

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FACT action during chromatin transcription [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

FACT (facilitates chromatin transcription) is a histone chaperone that promotes chromatin recovery during transcription, with additional roles in cell differentiation. Although several models of the action of FACT during transcription have been proposed, they remain to be experimentally evaluated. Here we show that human FACT (hFACT) facilitates transcription through chromatin... (Source: Proceedings of the National Academy of Sciences)

Wor3, a previously undescribed DNA-binding protein [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

Sequence-specific DNA-binding proteins are among the most important classes of gene regulatory proteins, controlling changes in transcription that underlie many aspects of biology. In this work, we identify a transcriptional regulator from the human fungal pathogen Candida albicans that binds DNA specifically but has no detectable homology with any previously... (Source: Proceedings of the National Academy of Sciences)

ATPase drives TA protein targeting [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

The localization of tail-anchored (TA) proteins, whose transmembrane domain resides at the extreme C terminus, presents major challenges to cellular protein targeting machineries. In eukaryotic cells, the highly conserved ATPase, guided entry of tail-anchored protein 3 (Get3), coordinates the delivery of TA proteins to the endoplasmic reticulum. How Get3 uses... (Source: Proceedings of the National Academy of Sciences)

Role of PCNA in DNA recombination [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

Proliferating cell nuclear antigen (PCNA) is required for DNA homologous recombination (HR), but its exact role is unclear. Here, we investigated the loading of PCNA onto a synthetic D-loop (DL) intermediate of HR and the functional interactions of PCNA with Rad51 recombinase and DNA polymerase (Pol) δ, Pol η, and... (Source: Proceedings of the National Academy of Sciences)

TAF1 depletion increases transcriptional burst [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

Transcription factor (TF)IID is a central player in activated transcription initiation. Recent evidence suggests that the role and composition of TFIID are more diverse than previously understood. To investigate the effects of changing the composition of TFIID in a simple system, we depleted TATA box-binding protein–associated factor (TAF)1 from Drosophila... (Source: Proceedings of the National Academy of Sciences)

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Correction for Drake et al., Proteomic analysis of skeletal organic matrix from the stony coral Stylophora pistillata [Correction]

Proceedings of the National Academy of Sciences — Tue, 07 May 2013 04:00:00 +0100

BIOCHEMISTRY, ENVIRONMENTAL SCIENCES Correction for “Proteomic analysis of skeletal organic matrix from the stony coral Stylophora pistillata,” by Jeana L. Drake, Tali Mass, Liti Haramaty, Ehud Zelzion, Debashish Bhattacharya, and Paul G. Falkowski, which appeared in issue 10, March 5, 2013, of Proc Natl Acad Sci USA (110:3788–3793; first published... (Source: Proceedings of the National Academy of Sciences)

Receptor for activated C-kinase 1 (RACK1) interacts with F-box and WD-repeat domain containing-2 (FBW2) to upregulate glial cell missing-1 (GCM1) stability and placental cell migration and invasion

BJ Cell — Tue, 07 May 2013 04:00:00 +0100

In this study, we perform tandem affinity purification coupled with mass spectrometry analysis identifying RACK1 as an FBW2-interacting protein. RACK1 is a multifaceted scaffold protein containing seven WD repeats. We demonstrate that the WD repeats in both RACK1 and FBW2 are required for the interaction of RACK1 and FBW2. Furthermore, RACK1 competes with GCM1 for FBW2 and thereby prevents GCM1 ubiquitination, which is also supported by the observation that GCM1 is destabilized in RACK1-knockdown BeWo placental cells. Importantly, RACK1 knockdown leads to decreased expression of the GCM1 target gene high-temperature requirement protein A4 (HtrA4), which encodes a serine protease crucial for cell migration and invasion. As a result, migration and invasion activities are downregulated in RAC...

Minimal Functional Domains of Paralogues hnRNP L and hnRNP LL Exhibit Mechanistic Differences in Exonic Splicing Repression

BJ Gene — Tue, 07 May 2013 04:00:00 +0100

In this study, we use an MS2-tethering assay to delineate the minimal domains of hnRNP L and hnRNP LL which are required for repressing exon inclusion. We demonstrate that for both proteins, regions outside the RRMs – the N-terminal region, and a linker sequence between RRMs 2 and 3 – are necessary for exon repression, but are only sufficient for repression in the case of hnRNP LL. In addition, both proteins require at least one RRM for maximal repression. Notably, we demonstrate that the region encompassing RRMs 1-2 of hnRNP LL imparts a second silencing activity not observed for hnRNP L. This additional functional component of hnRNP LL is consistent with the fact that the full length hnRNP LL has greater silencing activity than hnRNP L. Thus, our data provide important insi...

Structural Characterization of Amorphous Calcium Carbonate-Binding Protein: Insight into the Mechanism of Amorphous Calcium Carbonate Formation

BJ Structure — Tue, 07 May 2013 04:00:00 +0100

Amorphous calcium carbonate (ACC) plays an important role in biomineralization process for its function as a precursor for calcium carbonate biominerals. However, it is unclear how biomacromolecules regulate the formation of ACC precursor in vivo. Here, we used biochemical experiments coupled with bioinformatics approaches to explore the mechanisms of ACC formation controlled by amorphous calcium calcium-binding protein (ACCBP). Size-exclusion chromatography, chemical cross-linking experiments and negative staining electron microscopy reveal that ACCBP is a decamer composed of two adjacent pentamers. Sequence analyses and fluorescence quenching results indicate that ACCBP contains two Ca2+-binding sites. The results of in vitro crystallization experiments suggest that one Ca2+...

From classrooms to hospitals: when medicine doesn t have all the answers

Scientific American - Official RSS Feed — Mon, 06 May 2013 21:45:00 +0100

I'll start with this: it's great to be back.I've been on hiatus from blogging for the past few months because of the exam I took last week: the medical boards, or Step 1, an eight hour test that covers all of the first two years of medical school to prepare us for the hospital wards. To give you an idea of what it entails, most second-year medical students use a 550-page review book as a scaffold that at the minimum gets memorized. Subjects include anatomy, physiology, pathology, biochemistry, pharmacology, microbiology, immunology, embryology, and others. One physician writer described the first half of medical school like this: "It was like being asked to enter a grocery store and memorize the names of every product in the store , their number and location, every ingredient in every prod...

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UTHSC research teams awarded $3 million

bizjournals.com Health Care:Pharmaceuticals headlines — Mon, 06 May 2013 18:39:55 +0100

Two teams of researchers at the University of Tennessee Health Science Center secured more than $3 million in federal funding for a pair of unrelated studies. Eldon Geisert, a professor of ophthalmology and anatomy and neurobiology, received $1.5 million to study genetic risk factors for glaucoma from the National Eye Institute; Kui Li, an associate professor of microbiology, immunology and biochemistry, was awarded two grants totaling $1.56 million for research related to hepatitis C from the National… (Source: bizjournals.com Health Care:Pharmaceuticals headlines)

In the News

The Rockefeller University Newswire — Mon, 06 May 2013 18:16:53 +0100

Christian de Duve, 95, dies; Nobel-winning biochemist “[Dr. de Duve] discovered the lysosome, a tiny sack filled with enzymes that functions like a garbage disposal, destroying bacteria or parts of the cell that are old or worn out. His … More » (Source: The Rockefeller University Newswire)

Grapes Activate Genes Responsible For Antioxidant Defense In The Heart

Health News from Medical News Today — Mon, 06 May 2013 08:00:00 +0100

A study appearing in the Journal of Nutritional BiochemistryÂ¹ demonstrates that grapes are able to reduce heart failure associated with chronic high blood pressure (hypertension) by increasing the activity of several genes responsible for antioxidant defense in the heart tissue. Grapes are a known natural source of antioxidants and other polyphenols, which researchers believe to be responsible for the beneficial effects observed with grape consumption... (Source: Health News from Medical News Today)

How Form Of Complex Organs Evolves By Natural Selection: 3D Simulation

Health News from Medical News Today — Mon, 06 May 2013 07:00:00 +0100

Researchers at the Institute of Biotechnology at the Helsinki University and the Universitat Autonoma de Barcelona (UAB) have developed the first three-dimensional simulation of the evolution of morphology by integrating the mechanisms of genetic regulation that take place during embryo development. The study, published in Nature, highlights the real complexity of the genetic interactions that lead to adult organisms' phenotypes (physical forms), helps to explain how natural selection influences body form and leads towards much more realistic virtual experiments on evolution... (Source: Health News from Medical News Today)

The TRIPSE: A process‐oriented exam for large undergraduate classes

Biochemistry and Molecular Biology Education — Sat, 04 May 2013 04:00:00 +0100

The TRIPSE (tri‐partite problem solving exercise), a process‐oriented exam that mimics the scientific process, was used previously in small classes (15–25). Provided limited data, students frame explanations and design experimental tests that they later revise with additional information. Our 6‐year experience using it with larger numbers (155–204) in a freshman biology course, suggests that it could provide a means of assessing individual student performance. Students rated the learning value of this experience to be significantly higher than a standard MCQ on a 10‐point scale (TRIPSEs 8.2, CI 8.1/8.4 vs. MCQs 4.9, CI 4.8/5.1, n = 712). Additionally, we tested one cohort (n = 146) with a group TRIPSE (groups of 6), and found that this variant also provided a valuable learning ...

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Teaching arrangements of carbohydrate metabolism in biochemistry curriculum in peking university health science center

Biochemistry and Molecular Biology Education — Sat, 04 May 2013 04:00:00 +0100

Biochemistry occupies a unique place in the medical school curricula, but the teaching of biochemistry presents certain challenges. One of these challenges is facilitating students' interest in and mastery of metabolism. The many pathways and modes of regulation can be overwhelming for students to learn and difficult for professors to teach in an engaging manner. The first chapter of the metabolism section in current Chinese biochemistry textbooks covers carbohydrate metabolism. Medical students usually complain about the difficulty of this subject. Here we discuss how to facilitate learning by rearranging the subjects in this introductory chapter of biochemical metabolism and to lay a solid foundation for future study. The strategy involves reorganizing the order in which subjects are tau...

Websites of note

Biochemistry and Molecular Biology Education — Sat, 04 May 2013 04:00:00 +0100

(Source: Biochemistry and Molecular Biology Education)

Exploring higher-order EGFR oligomerisation and phosphorylation-a combined experimental and theoretical approach

RSC - Mol. BioSyst. latest articles — Fri, 03 May 2013 16:11:30 +0100

Mol. BioSyst., 2013, Advance ArticleDOI: 10.1039/C3MB70073A, PaperNoga Kozer, Dipak Barua, Suzanne Orchard, Eduoard C. Nice, Antony W. Burgess, William S. Hlavacek, Andrew H. A. ClaytonBiophysics, biochemistry and rule-based modelling are combined to reveal a positive correlation between higher-order EGF receptor oligomer formation and phosphorylation.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Inflammatory Macrophage Migration in Experimental Autoimmune Encephalomyelitis

Springer protocols feed by Biochemistry — Fri, 03 May 2013 09:11:58 +0100

We describe a flow cytometric technique to monitor the migration of macrophages during EAE development. (Source: Springer protocols feed by Biochemistry)

Visualizing Chemokine-Dependent T Cell Activation and Migration in Response to Central Nervous System Infection

Springer protocols feed by Biochemistry — Fri, 03 May 2013 09:11:58 +0100

In response to central nervous system (CNS) injury and infection, astrocytes, neurons, and CNS vasculature express several chemokines, including CCL21. Quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemical methods can quantify mRNA and protein expression. However, these methods do not quantify chemokine bioavailability and bioactivity, variables modified by many environmental factors including composition of the extracellular matrix (ECM). Here we illustrate how two-photon microscopy and carboxyfluorescein succinimidyl ester (CFSE or CFDA SE) labeling of T cells coupled with flow cytometry can be used as tools to assess chemokine-mediated regulation of T cell proliferation, activation, and migration. (Source: Springer protocols feed by Biochemistry)

Epigenetic Regulation of Chemokine/Chemokine Receptor Expression

Springer protocols feed by Biochemistry — Fri, 03 May 2013 09:11:58 +0100

Epigenetic regulation of gene expression is an important event for normal cellular homeostasis. Gene expression may be “switched” on or “turned” off via epigenetic means through adjustments in DNA architecture. These structural alterations result from changes to the DNA methylation status in addition to histone posttranslational modifications such as acetylation and methylation. Drugs which can alter the status of these epigenetic markers are currently undergoing clinical trials in a wide variety of diseases, including cancer. (Source: Springer protocols feed by Biochemistry)

Using Fluorescent Chemokine Uptake to Detect Chemokine Receptors by Fluorescent Activated Cell Sorting

Springer protocols feed by Biochemistry — Fri, 03 May 2013 09:11:58 +0100

Fluorescent activated cell sorting (FACS) is a powerful technique that allows rapid quantitative cell-by-cell analysis of the expression of multiple distinct proteins and the isolation of specific cell types from complex cellular mixtures. FACS-based detection of chemokine receptors is typically achieved using chemokine receptor-specific antibodies. However, this approach has some limitations, and, in our experience, many anti-chemokine receptor antibodies have poor signal-to-noise ratios and thus low sensitivity and reliability in FACS. Moreover, antibodies against some chemokine receptors are not commercially available, particularly in nonhuman species, and generating good antibodies against chemokine receptors is challenging and expensive. Here, we describe a simple alternative method o...