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A common feature of glasses is the “boson peak”, observed as an excess in the heat capacity over the crystal or as an additional peak in the terahertz vibrational spectrum. The microscopic origins of this peak are not well understood; the emergence of locally ordered structures has been put forward as a possible candidate. Here, we show that depolarised Raman scattering in liquids consisting of highly symmetric molecules can be used to isolate the boson peak, allowing its detailed observation from the liquid into the glass. The boson peak in the vibrational spectrum matches the excess heat capacity. As the boson peak intensifies on cooling, wide-angle x-ray scattering shows the simultaneous appearance of a pre-peak due to molecular clusters consisting of circa 20 molecules. Atomistic molecular dynamics simulations indicate that these are caused by over-coordinated molecules. These findings represent an essential step toward our understanding of the physics of vitrification. The ‘boson peak’ refers to an extra peak in the terahertz vibrational spectrum of glasses. It is now shown that for liquids of highly symmetric molecules the boson peak can be singled out by means of depolarized Raman scattering; the peak is linked to the formation of clusters of about 20 molecules.

Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk–benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.

Interest in insulin-like growth factors (IGFs) and their effect on carcinogenesis has increased recently because high serum concentrations of IGF1 are associated with an increased risk of breast, prostate, colorectal, and lung cancers. Physiologically, IGF1 is the major mediator of the effects of the growth hormone; it thus has a strong influence on cell proliferation and differentiation and is a potent inhibitor of apoptosis. The action of IGF1 is predominantly mediated through the IGF1 receptor (IGF1R). IGF1R is involved in several oncogenic transformation processes. The availability of unbound IGF1 for interaction with IGF1R is modulated by IGF-binding proteins (IGFBP1–6). IGFBPs, especially IGFBP3, have independent effects on cell growth, for example, IGFBP3 has proapoptotic activities both dependent on and independent of p53.

The NMR assignment of13C,15N-labeled proteins with the use of triple resonance experiments is limited to molecular weights below ∼ 25,000 Daltons, mainly because of low sensitivity due to rapid transverse nuclear spin relaxation during the evolution and recording periods. For experiments that exclusively correlate the amide proton (1HN), the amide nitrogen (15N), and13C atoms, this size limit has been previously extended by additional labeling with deuterium (2H). The present paper shows that the implementation of transverse relaxation-optimized spectroscopy ([15N,1H]-TROSY) into triple resonance experiments results in several-fold improved sensitivity for2H/13C/15N-labeled proteins and approximately twofold sensitivity gain for13C/15N-labeled proteins. Pulse schemes and spectra recorded with deuterated and protonated proteins are presented for the [15N,1H]-TROSY-HNCA and [15N,1H]-TROSY-HNCO experiments. A theoretical analysis of the HNCA experiment shows that the primary TROSY effect is on the transverse relaxation of15N, which is only little affected by deuteration, and predicts sensitivity enhancements that are in close agreement with the experimental data.

Harnessing the unique catalytic properties of enzymes for abiotic reactions is a prized goal that has inspired a variety of approaches in enzyme design and engineering. Now, the transfer hydrogenation of ketones with silanes has been reported, catalysed by a native carbonic anhydrase.

Breast cancer has become curable for the majority of women in Western Europe and North America. Advances have been made in imaging diagnostics as well as the implementation of nationwide screening programmes. Nowadays, we talk about prevention as well as treatment. Pathology has moved from pure morphology (tumour type, grade and stage) to biological characterisation of the tumour. Treatment has changed considerably through a better understanding of the disease; from a local disease predominated by extensive and mutilating surgical techniques to a point where breast cancer has come into its own as a systemic disease with equal “rights” to local as well as systemic treatment. This paradigm shift has led to a multidisciplinary approach of the understanding and treatment of breast cancer. Molecular classification has changed the understanding of breast cancer and will be the basis for an even more individualised treatment. New (biological) agents will help to further tailor treatment to response or resistance. While systemic treatment has been increased in number and duration surgical/local strategies have been reduced to minimum. Evidence-based medicine has helped to improve and standardise treatment of breast cancer. This review summarises the 10th Biedenkopf meeting that was held to review the advances in breast cancer understanding and treatment.

Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function. Terahertz-frequency underdamped vibrational modes in proteins are thought to be involved in biochemical processes, but their observation in solution is difficult. Here, the authors use femtosecond optical Kerr-effect spectroscopy to experimentally identify these modes during enzyme–ligand binding.