Ruthenium(II) and Iridium(III) complexes featuring NHC-Sulfonate chelate

International audienc

Recursive music elucidates neural mechanisms supporting the generation and detection of melodic hierarchies

The ability to generate complex hierarchical structures is a crucial component of human cognition which can be expressed in the musical domain in the form of hierarchical melodic relations. The neural underpinnings of this ability have been investigated by comparing the perception of well-formed melodies with unexpected sequences of tones. However, these contrasts do not target specifically the representation of rules generating hierarchical structure. Here, we present a novel paradigm in which identical melodic sequences are generated in four steps, according to three different rules: The Recursive rule, generating new hierarchical levels at each step; The Iterative rule, adding tones within a fixed hierarchical level without generating new levels; and a control rule that simply repeats the third step. Using fMRI, we compared brain activity across these rules when participants are imagining the fourth step after listening to the third (generation phase), and when participants listened to a fourth step (test sound phase), either well-formed or a violation. We found that, in comparison with Repetition and Iteration, imagining the fourth step using the Recursive rule activated the superior temporal gyrus (STG). During the test sound phase, we found fronto-temporo-parietal activity and hippocampal de-activation when processing violations, but no differences between rules. STG activation during the generation phase suggests that generating new hierarchical levels from previous steps might rely on retrieving appropriate melodic hierarchy schemas. Previous findings highlighting the role of hippocampus and inferior frontal gyrus may reflect processing of unexpected melodic sequences, rather than hierarchy generation per se

Differential functional benefits of ultra highfield MR systems within the language network

Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3T and 7T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernicke's area 5/6 measures indicated a benefit of ultra highfield, in Broca's area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts

The prismatic Sigma 3 (10-10) twin bounday in alpha-Al2O3 investigated by density functional theory and transmission electron microscopy

The microscopic structure of a prismatic $\Sigma 3$ $(10\bar{1}0)$ twin boundary in \aal2o3 is characterized theoretically by ab-initio local-density-functional theory, and experimentally by spatial-resolution electron energy-loss spectroscopy in a scanning transmission electron microscope (STEM), measuring energy-loss near-edge structures (ELNES) of the oxygen $K$-ionization edge. Theoretically, two distinct microscopic variants for this twin interface with low interface energies are derived and analysed. Experimentally, it is demonstrated that the spatial and energetical resolutions of present high-performance STEM instruments are insufficient to discriminate the subtle differences of the two proposed interface variants. It is predicted that for the currently developed next generation of analytical electron microscopes the prismatic twin interface will provide a promising benchmark case to demonstrate the achievement of ELNES with spatial resolution of individual atom columns

CSRP3 mediates polyphenols-induced cardioprotection in hypertension

Berries contain bioactive polyphenols, whose capacity to prevent cardiovascular diseases has been established recently in animal models as well in human clinical trials. However, cellular processes and molecular targets of berries polyphenols remain to be identified. The capacity of a polyphenol-enriched diet (i.e., blueberries, blackberries, raspberries, strawberry tree fruits and Portuguese crowberries berries mixture) to promote animal survival and protect cardiovascular function from salt-induced hypertension was evaluated in a chronic salt-sensitive Dahl rat model. The daily consumption of berries improved survival of Dahl/salt-sensitive rats submitted to high-salt diet and normalized their body weight, renal function and blood pressure. In addition, a prophylactic effect was observed at the level of cardiac hypertrophy and dysfunction, tissue cohesion and cardiomyocyte hypertrophy. Berries also protected the aorta from fibrosis and modulated the expression of aquaporin-1, a channel involved in endothelial water and nitric oxide permeability. Left ventricle proteomics analysis led to the identification of berries and salt metabolites targets, including cystein and glycin-rich protein 3 (CSRP3), a protein involved in myocyte cytoarchitecture. In neonatal rat ventricular cardiomyocytes, CSRP3 was validated as a target of a berries-derived polyphenol metabolite, 4-methylcatechol sulfate, at micromolar concentrations, mimicking physiological conditions of human plasma circulation. Accordingly, siRNA silencing of CSRP3 and 4-methylcatechol sulfate pretreatment reversed cardiomyocyte hypertrophy and CSRP3 overexpression induced by phenylephrine. Our systemic study clearly supports the modulation of CSRP3 by a polyphenol-rich berries diet as an efficient cardioprotective strategy in hypertension-induced heart failure

The Impact of Echo Time Shifts and Temporal Signal Fluctuations on BOLD Sensitivity in Presurgical Planning at 7 T.

OBJECTIVES: Gradients in the static magnetic field caused by tissues with differing magnetic susceptibilities lead to regional variations in the effective echo time, which modifies both image signal and BOLD sensitivity. Local echo time changes are not considered in the most commonly used metric for BOLD sensitivity, temporal signal-to-noise ratio (tSNR), but may be significant, particularly at ultrahigh field close to air cavities (such as the sinuses and ear canals) and near gross brain pathologies and postoperative sites. MATERIALS AND METHODS: We have studied the effect of local variations in echo time and tSNR on BOLD sensitivity in 3 healthy volunteers and 11 patients with tumors, postoperative cavities, and venous malformations at 7 T. Temporal signal-to-noise ratio was estimated from a 5-minute run of resting state echo planar imaging with a nominal echo time of 22 milliseconds. Maps of local echo time were derived from the phase of a multiecho GE scan. One healthy volunteer performed 10 runs of a breath-hold task. The t-map from this experiment served as a criterion standard BOLD sensitivity measure. Two runs of a less demanding breath-hold paradigm were used for patients. RESULTS: In all subjects, a strong reduction in the echo time (from 22 milliseconds to around 11 milliseconds) was found close to the ear canals and sinuses. These regions were characterized by high tSNR but low t-values in breath-hold t-maps. In some patients, regions of particular interest in presurgical planning were affected by reductions in the echo time to approximately 13-15 milliseconds. These included the primary motor cortex, Broca's area, and auditory cortex. These regions were characterized by high tSNR values (70 and above). Breath-hold results were corrupted by strong motion artifacts in all patients. CONCLUSIONS: Criterion standard BOLD sensitivity estimation using hypercapnic experiments is challenging, especially in patient populations. Taking into consideration the tSNR, commonly used for BOLD sensitivity estimation, but ignoring local reductions in the echo time (eg, from 22 to 11 milliseconds), would erroneously suggest functional sensitivity sufficient to map BOLD signal changes. It is therefore important to consider both local variations in the echo time and temporal variations in signal, using the product metric of these two indices for instance. This should ensure a reliable estimation of BOLD sensitivity and to facilitate the identification of potential false-negative results. This is particularly true at high fields, such as 7 T and in patients with large pathologies and postoperative cavities

Bestrophin1: A Gene that Causes Many Diseases

Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that lead to the gradual loss of vision in and around the macular area. There are no treatments for patients suffering from bestrophinopathies, and no measures can be taken to prevent visual deterioration in those who have inherited disease-causing mutations. Bestrophinopathies are caused by mutations in the Bestrophin1 gene (BEST1), a protein found exclusively in the retinal pigment epithelial (RPE) cells of the eye. Mutations in BEST1 affect the function of the RPE leading to the death of overlying retinal cells and subsequent vision loss. The pathogenic mechanisms arising from BEST1 mutations are still not fully understood, and it is not clear how mutations in BEST1 lead to diseases with distinct clinical features. This chapter discusses BEST1, the use of model systems to investigate the effects of mutations and the potential to investigate individual bestrophinopathies using induced pluripotent stem cells

The clinical relevance of distortion correction in presurgical fMRI at 7 T

Presurgical planning with fMRI benefits from increased reliability and the possibility to reduce measurement time introduced by using ultra-high field. Echo-planar imaging suffers, however, from geometric distortions which scale with field strength and potentially give rise to clinically significant displacement of functional activation. We evaluate the effectiveness of a dynamic distortion correction (DDC) method based on unmodified single-echo EPI in the context of simulated presurgical planning fMRI at 7 T and compare it with static distortion correction (SDC). The extent of distortion in EPI and activation shifts are investigated in a group of eleven patients with a range of neuropathologies who performed a motor task. The consequences of neglecting to correct images for susceptibility-induced distortions are assessed in a clinical context. It was possible to generate time series of EPI-based field maps which were free of artifacts in the eloquent brain areas relevant to presurgical fMRI, despite the presence of signal dropouts caused by pathologies and post-operative sites. Distortions of up to 5.1 mm were observed in the primary motor cortex in raw EPI. These were accurately corrected with DDC and slightly less accurately with SDC. The dynamic nature of distortions in UHF clinical fMRI was demonstrated via investigation of temporal variation in voxel shift maps, confirming the potential inadequacy of SDC based on a single reference field map, particularly in the vicinity of pathologies or in the presence of motion. In two patients, the distortion correction was potentially clinically significant in that it might have affected the localization or interpretation of activation and could thereby have influenced the treatment plan. Distortion correction is shown to be effective and clinically relevant in presurgical planning at 7 T