Scientists from the Helmholtz Zentrum München and the Technische Universität München (TUM) under the direction of Professor Michael Sattler have developed a new strategy allowing them to determine the spatial structure of biomolecules in solution based around NMR spectroscopy. The method is flexible and generally applicable to obtaining structural information for signal forwarding pathways in the cell or in the regulation of gene expression. Their work is reported in Angewandte Chemie.

Magnetic resonance (MR) spectroscopy may in the future be able both to pinpoint the precise location of prostate cancer and to determine the tumour's aggressiveness, information that could help guide treatment planning. In Science Translational Medicine (doi: 10.1126/scitranslmed.3000513), Massachusetts General Hospital (MGH) researchers report how spectroscopic analysis of the biochemical makeup of prostate glands accurately identified the location of tissue confirmed to be malignant by conventional pathology.

Press release from Nature News - under embargo for Monday 14 December 1800 London time (GMT) Chemical fingerprints of tissue samples taken from patients during operations could soon help surgeons to decide quickly where to make their incisions. Nature News has reported that two groups are leading efforts to use nuclear magnetic resonance (NMR) spectroscopy to analyse the metabolites in biopsies and relay information back to theatre within minutes.

Understanding the extremely fast atomic mechanisms at work when a protein transitions from one shape to another has been an elusive scientific goal for years, but an essential one for elucidating the full range of protein function. How do proteins transition between distinct shapes without unfolding in the process? Until now, this question has been a hypothetical one, approached by computation only rather than experimentation. In a study in Cell (doi: 10.1016/j.cell.2009.11.022), researchers reveal for the first time computationally and experimentally the molecular pathway that a protein takes to cross the energy barrier. The study reports how folded proteins can efficiently change shape while avoiding unfolding, a critical requirement for any protein in the cell.

Bruker BioSpin has installed the world’s first 1000 MHz ultra-high field NMR AVANCE™ spectrometer at the Centre de Resonance Magnétique Nucléaire à Très Hauts Champs (CRMN) in Lyon, France (a joint research unit of CNRS, Ecole Normale Supérieure de Lyon and Université Lyon 1). The AVANCE 1000 system incorporates a 23.5 Tesla superconducting magnet, and offers exciting research opportunities, both to the CRMN and to other French and European scientists who will access this unique facility.

In structural biology, the only technique available to predict the three-dimensional structure of large complex molecules in solution, such as proteins and DNA, is nuclear magnetic resonance (NMR) spectroscopy. To improve the techniques behind these predictions, the “eNMR” project has launched a new initiative. In September’s Nature Methods (doi: 10.1038/nmeth0909-625) the project issued an invitation to the entire biomolecular NMR community to participate in a large scale test of modern computing algorithms. This community-wide “contest” will potentially improve efficiency, reproducibility and reliability of NMR structure determination. eNMR will be using the Enabling Grids for E-sciencE infrastructure to power their analysis.

With the addition of the new Sadtler HNMR Chemical Shifts database from Bio-Rad, HaveItAll NMR now includes chemical shift data of 20,391 more compounds, each being identified by chemical name, solvent used in the analysis, instrument name, chemical structure, molecular formula and molecular weight.

The NMR Metabolites database from Bio-Rad, with its collection of 1H and 13C NMR spectra, now includes 532 compounds with 1055 spectra from BioMagResBank data, which doubles the number of spectra previously in this collection of proteins, peptides and nucleic acids.

David Carteau, Isabelle Pianet and Dario M. BassaniInstitut des Sciences Moléculaires, CNRS UMR 5255, Université Bordeaux 1, 351 Cours de la Libération, 33405 Talence France. E-mail: d.bassani@ism.u-bordeaux1.fr

Introduction

Memories of summer vacations on the Mediterranean would not be complete without recollections of the refreshing anise-flavoured alcoholic beverages served during the hot afternoons. Though varying in name and composition across cultures (Raki in Turkey, Arak in Lebanon, Ouzo in Greece, Sambuca in Italy and Pastis in France), extracts from star anis (Illicium floridanum) are a common principal ingredient of the plant extracts used in their production. Besides their pungent anis aroma, another well-known trademark of these drinks is their transition from a clear solution to an opalescent milky-white substance when they are diluted with water. This sudden change in physical appearance will not go unnoticed by a scientist, who may summarily assign it to the precipitation or separation of the hydrophobic organic fragrances due to the addition of water. We know this not to be entirely correct,1 however, as it should lead to a rather un-appetising biphasic mixture in which the essential oils would float on top of a large volume of water and alcohol. The truth behind this apparently simple phenomenon is actually much more complex—and very interesting indeed!

Isotopically-labelled non-radioactive peptides function as critical internal standards for protein quantitation experiments in MS and NMR experiments. Thermo Fisher Scientific now offers multiple grates of heavy peptides, enabling researchers to match the precision and cost of the internal standard according the assay development stage. The new HeavyPeptide Aqua Ultimate kit is designed for absolute quantification and the Aqua Quant Pro kit is a more affordable alternative when ultimate precision is not necessary.

Thermo Fisher Scientific Issue: 21/05 RSN: 115 More information via

Agilent Technologies have signed a definitive agreement to acquire Varian, paying $1.5 billion. As well as adding $1 billion in annual sales to Agilent’s existing $5.8 billion, it significantly expands the range of technologies in Agilent’s portfolio. Varian are particularly strong in NMR, imaging and vacuum technologies, but also can offer a number of atomic and molecular spectroscopies.

Bruker BioSpin has announced its first order for an Elexsys E780 263 GHz EPR spectrometer by the Helmholtz-Zentrum in Berlin for applications in solar energy and photovoltaic research. www.bruker-biospin.com

Stéphane Balayssac,a Véronique Gilard,a Marc-André Delsucb and Myriam Malet-Martinoa

aUniversité de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, FrancebInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404 Illkirch, France

Introduction

The capability of nuclear magnetic resonance (NMR) spectroscopy to provide valuable information regarding mixture analysis has created broad applicability in chemistry, biochemistry, biology and medicine. As drugs can be considered to be complex mixtures (composed of many different substances and/or including simultaneously high and very low quantities of compounds), NMR is a good tool for studying such formulations.

Bruker BioSpin has launched the 1 GHz ultra-high field Avance 1000 NMR spectrometer. After many years of development, the company has successfully energised and brought to its full magnetic field of 23.5 Tesla a standard-bore, high homogeneity 1 GHz NMR persistent magnet. The high field strength and high field stability, in combination with a 5 mm triple-resonance CryoProbe, enables 1 GHz NMR applications. The 1 GHz NMR spectra demonstrate the capabilities of this new high-end instrument, which can be beneficial for all UHF high- resolution and solid-state NMR experiments.

Bruker BioSpin Issue: 21/03 RSN: 110

Bruker Biospin have launched two new ultra-high NMR magnets which, when combined with the Avance III spectrometer, will deliver improved sensitivity and resolution, enabling new research applications in structural biology research, membrane protein structure determination and a growing number of materials research applications. The two-story 900 MHz WB US2 expands the range of available shielded UHF wide bore magnets from 850 MHz to 900 MHz and combines the company's Ultrastabilised and Ultrashield technologies. The compact 850 MHz US Plus actively-shielded magnet can be placed in a single story laboratory, lowering the barriers for researchers to operate at this UHF strength. Its compact size and small stray field improve siting flexibility and reduce site preparation costs. This standard bore (54 mm) magnet also benefits from Ultrastabilised and Ultrashield technology for improved protection against external perturbations

Bruker BioSpin Issue: 21/02 RSN: 157

Advanced Chemistry Development has released its ACD/NMR Workbook with NMRSync Technology. Available with ACD/Labs Version 12, the NMR Workbook enables the user to peak pick and make assignments to datasets containing multiple types of NMR spectra for one sample more efficiently. The workbook also has data-basing capabilities that enable the user to store assigned experimental spectra along with their chemical structures, assignments, data tables and other associated data. NMRSync automatically processes and aligns all NMR data associated with a given sample upon import. Following the procedure, it is then possible to synchronise all peak picking and structure assignment, reducing the amount of time it takes to interpret and assign a full NMR dataset.

Advanced Chemistry Development Issue: 21/01 RSN: 119

A bench-top NMR reader for quantifying both the magnetic hyperpolarisation as well as the thermal polorisation of a sample by applying time-domain nuclear magnetic resonance spectroscopy, a technique similar to magnetic resonance imaging, has been introduced by Bruker Biospin. The HyperQuant utilises a permanent magnet combined with an innovative probe design and novel NMR pulse sequences to enable the thermal polarisation of 13C-labelled samples using volumes as low as 1 mL. In this way, hyperpolarisation enhancement factors can be obtained directly on the sample of interest without having to obtain a separate calibration reference. The HyperQuant is an easy-to-use turn-key solution for researchers developing new MRI or NMR applications for ­hyperpolarisation.Bruker BioSpinIssue: 20/05 RSN:

A miniature sensor developed at NIST in the USA can detect nuclear magnetic resonance (NMR) in small samples of fluids flowing through a novel microchip. The prototype chip device, developed in a collaboration between NIST and the University of California, may have wide application as a sensitive chemical analyser, for example in rapid screening to find new drugs.

As described in Proc. Nat. Acad. Sci. (doi: 10.1073/pnas.0711505105), the NMR chip detected magnetic signals from atomic nuclei in tap water flowing through a custom silicon chip that juxtaposes a tiny fluid channel and the NIST sensor. The Berkeley group recently codeveloped this "remote NMR" technique for tracking small volumes of fluid or gas flow inside soft materials such as biological tissue or porous rock, for possible applications in industrial processes and oil exploration.

The chip could be used in NMR spectroscopy, where its small size and high sensitivity make it possible to detect weak magnetic resonance signals from a small sample of atoms in the adjacent microchannel. Detection is most efficient when the sensor and sample are about the same size and located close together, lead author Micah Ledbetter says. Thus, when samples are minute, as in economical screening of many chemicals, a small sensor is crucial, Ledbetter says.

Bipolar disorder, or manic depression, is a debilitating psychiatric condition characterised by alternating mania and depression, and affects about one in every hundred people worldwide. Although it is known that the condition can be treated relatively effectively using the moodstabilising drugs lithium and valproic acid, the reasons why these treatments work are poorly understood.

The authors of a new study, from Imperial College London, the University of Cambridge in the UK and the National Institutes of Mental Health in the USA, hope that their research will enable a better understanding of the condition and of how it can be treated.

The researchers compared postmortem brain tissue samples of people with manic depression with those of age and gender matched controls. The samples were taken from the dorsolateral prefrontal cortex, which controls the processes involved in higher cognitive functioning. The researchers analysed these samples using NMR spectroscopy and found that people with manic depression had different concentrations of chemicals in this area of the brain than those without.

The researchers also used rat models to see the effects of lithium and valproic acid on the metabolite makeup of non-bipolar brain tissue. They found that these drugs caused the opposite chemical changes to those seen in the bipolar brain tissue samples. Chemicals that were increased in the bipolar brain tissue were decreased in rats given the mood stabilising drugs, and vice versa.

The researchers' findings lead them to believe that an upset in the balance of different neurotransmitters known as excitatory and inhibitory neurotransmitters, which are involved in sending signals in the brain, may be central to the disorder. The study also suggests that lithium and valproic acid work by restoring the balance of these neurotransmitters in the brain. The work was published in Molecular Psychiatry (doi: 10.1038/sj.mp.4002130).

Peter A. RinckEuropean Magnetic Resonance Forum (EMRF) Foundation, WTC, BP 255, F-06905 Sophia Antipolis Cedex, France

In 1946, two scientists in the United States, independently of each other, described a physicochemical phenomenon that was based upon the magnetic properties of certain nuclei in the periodic system. This was “nuclear magnetic resonance”, for short “NMR”. The two scientists, Felix Bloch and Edward M. Purcell were awarded the Nobel Prize in Physics in 1952.