Periodicity and frequency coding in human auditory cortex

Understanding the neural coding of pitch and frequency is fundamental to the understanding of speech comprehension, music perception and the segregation of concurrent sound sources. Neuroimaging has made important contributions to defining the pattern of frequency sensitivity in humans. However, the precise way in which pitch sensitivity relates to these frequency-dependent regions remains unclear. Single-frequency tones also cannot be used to test this hypothesis as their pitch always equals their frequency. Here, temporal pitch (periodicity) and frequency coding were dissociated using stimuli that were bandpassed in different frequency spectra (centre frequencies 800 and 4500 Hz), yet were matched in their pitch characteristics. Cortical responses to both pitch-evoking stimuli typically occurred within a region that was also responsive to low frequencies. Its location extended across both primary and nonprimary auditory cortex. An additional control experiment demonstrated that this pitch-related effect was not simply caused by the generation of combination tones. Our findings support recent neurophysiological evidence for a cortical representation of pitch at the lateral border of the primary auditory cortex, while revealing new evidence that additional auditory fields are also likely to play a role in pitch coding

Copy number signatures and mutational processes in ovarian carcinoma.

The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.NIHR, Ovarian Cancer Action, Cancer Research UK Cambridge Centre, Cambridge Experimental Cancer Medicine Centr

Changes in landscape and vegetation of coastal dunes in northwest Europe: a review

In coastal dunes, landscape changes are a rule, rather than an exception. This paper gives an overview of changes in landscape and vegetation with a focus on the past century. The history of dunes is characterised by phases of sand drift, alternated with geomorphological stability. The historical development of dune woodland during these stable phases has been documented for sites all over Europe. Vegetation reconstructions of historical open dune habitats however is very difficult due to limited preservation of fossil remains. People have drastically altered coastal dune landscapes through centuries of exploitation and more recently development of the coast. Historical land use has generally pushed vegetation back into a semi-natural state. During roughly the past century a tendency of increasing fixation and succession is observed on coastal dunes throughout northwest Europe. Six causes of change are discussed. 1) Changes in land use, mainly abandonment of agricultural practices, have led to the development of late successional stages such as scrub and woodland. 2) Crashing rabbit populations due to myxomatosis in the 1950s caused vigorous grass growth and probably stimulated scrub development. 3) A general tendency of landscape fixation is observed due to both natural and anthropogenic factors. 4) Eutrophication, mainly due to atmospheric nitrogen deposition is clearly linked to grass encroachment on acidic but also on some calcareous dunes. 5) The impact of climate change on vegetation is still unclear but probably lengthening of growing season and maybe enhanced CO2 concentrations have led to an acceleration of succession. 6) A general anthropogenisation of the landscape occurs with rapid spread of non-native species as an important consequence. The reconstruction of a natural reference landscape is considered largely unattainable because of irreversible changes and the long tradition of human impact, in many cases since the development of the dunes. Two contradictory elements need reconciliation. First, the general acceleration of succession and scrub and woodland development in particular is partly caused by a decreased anthropogenic interference in the landscape and deserves more appreciation. Second, most biodiversity values are largely linked to open, early succession dune habitats and are threatened by the same tendency. Apart from internal nature management, in which grazing plays an important part, re-mobilisation of stable, senescent dunes is an important challenge for dune management

Recent development of monoamine oxidase inhibitors

The monoamine oxidases (MAO-A and MAO-B) are flavoenzymes located in the outer mitochondrial membrane responsible for the oxidative deamination of many endogenous and exogenous monoamines. Recognition of the importance of monoamine oxidases as targets for drug intervention for the treatment of a variety of conditions, such as schizophrenia, Alzheimer's disease, Parkinson's disease and other psychiatric and neurological disorders, has produced an enormous interest in the development of molecules that act as inhibitors on these enzymes. This review mainly focuses on the numerous monoamine oxidase inhibitor (MAO-I)-related patents published from August 2002 to June 2005. In this paper recent developments of monoamine oxidase inhibitors are reported, ordering all patents by molecular structure. A structure-activity relationship (SAR) study that reports on known MAO inhibitors is also outlined before a discussion on new associations with other drugs of classical MAO inhibitors and their new target