Functionalized azamacrocyclic compounds as Ca2+ sensitive contrast agents for MR imaging

The ability to non-invasively observe changes in Ca2+ concentration is important for neuroscience. We have therefore developed a series of gadolinium chelate complexes based on DO3A (Scheme 1), which is hypothesized to change relaxivity in magnetic resonance experiments dynamically with Ca2+ concentration. Different lengths of the phosphonate side chains are expected to lead to different binding constants of the phosphonate - gadolinium bonds. The latter property can be exploited for fine-tuning the sensitivity of the agent to calcium ion concentration

How to run a brain bank. A report from the Austro-German brain bank

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures

Extracellular-intracellular distribution of glucose and lactate in the rat brain assessed noninvasively by diffusion-weighted 1H nuclear magnetic resonance spectroscopy in vivo

To determine the distribution of cerebral glucose and lactate between the intracellular and the extracellular space of the rat brain in vivo, the diffusion characteristic of glucose and lactate was compared with that of metabolites known to be mainly intracellular (N-acetylaspartate, choline, creatine, glutamate, myo-inositol, and taurine) using a pulsed-field-gradient 1H nuclear magnetic resonance technique. The detection of a glucose signal at large diffusion weighting provided direct experimental evidence of intracellular glucose in the rat brain. At large diffusion weighting, the apparent diffusion coefficient (ADC) of glucose and lactate was similar to that of the intracellular metabolites such as N-acetylaspartate, creatine, and glutamate. At small diffusion weighting, the ADC of glucose and lactate was increased, which was explained by a decreased relative contribution of intracellular glucose to the total signal. The calculated extracellular volume fraction of glucose (0.19 ± 0.05) and lactate (0.17 ± 0.06) was consistent with a substantial fraction of glucose and lactate signals being intracellular. The findings were direct in vivo evidence that the largest concentration gradient of glucose is at the blood-brain barrier and that glucose is evenly distributed in the brain in vivo between the intracellular and extracellular space

Metabolic changes in quinolinic acid-lesioned rat striatum detected noninvasively by in vivo 1H NMR spectroscopy

Intrastriatal injection of quinolinic acid (QA) provides an animal model of Huntington disease. In vivo 1H NMR spectroscopy was used to measure the neurochemical profile non-invasively in seven animals 5 days after unilateral injection of 150 nmol of QA. Concentration changes of 16 metabolites were measured from 22 μl volume at 9.4 T. The increase of glutamine ((+25 ± 14)%, mean ± SD, n = 7) and decrease of glutamate (-12 ± 5)%, N-acetylaspartate (-17 ± 6)%, taurine (-14 ± 6)% and total creatine (-9 ± 3%) were discernible in each individual animal (P < 0.005, paired t-test). Metabolite concentrations in control striata were in excellent agreement with biochemical literature. The change in glutamate plus glutamine was not significant, implying a shift in the glutamate-glutamine interconversion, consistent with a metabolic defect at the level of neuronal-glial metabolic trafficking. The most significant indicator of the lesion, however, were the changes in glutathione ((-19 ± 9)%, P < 0.002)), consistent with oxidative stress. From a comparison with biochemical literature we conclude that high-resolution in vivo 1H NMR spectroscopy accurately reflects the neurochemical changes induced by a relatively modest dose of QA, which permits one to longitudinally follow mitochondrial function, oxidative stress and glial-neuronal metabolic trafficking as well as the effects of treatment in this model of Huntington disease. © 2001 Wiley-Liss, Inc

The Quantum Spin Hall Effect: Theory and Experiment

The search for topologically non-trivial states of matter has become an important goal for condensed matter physics. Recently, a new class of topological insulators has been proposed. These topological insulators have an insulating gap in the bulk, but have topologically protected edge states due to the time reversal symmetry. In two dimensions the helical edge states give rise to the quantum spin Hall (QSH) effect, in the absence of any external magnetic field. Here we review a recent theory which predicts that the QSH state can be realized in HgTe/CdTe semiconductor quantum wells. By varying the thickness of the quantum well, the band structure changes from a normal to an "inverted" type at a critical thickness $d_c$. We present an analytical solution of the helical edge states and explicitly demonstrate their topological stability. We also review the recent experimental observation of the QSH state in HgTe/(Hg,Cd)Te quantum wells. We review both the fabrication of the sample and the experimental setup. For thin quantum wells with well width $d_{QW}< 6.3$ nm, the insulating regime shows the conventional behavior of vanishingly small conductance at low temperature. However, for thicker quantum wells ($d_{QW}> 6.3$ nm), the nominally insulating regime shows a plateau of residual conductance close to $2e^2/h$. The residual conductance is independent of the sample width, indicating that it is caused by edge states. Furthermore, the residual conductance is destroyed by a small external magnetic field. The quantum phase transition at the critical thickness, $d_c= 6.3$ nm, is also independently determined from the occurrence of a magnetic field induced insulator to metal transition.Comment: Invited review article for special issue of JPSJ, 32 pages. For higher resolution figures see official online version when publishe

BioContainers: An open-source and community-driven framework for software standardization

Motivation BioContainers (biocontainers.pro) is an open-source and community-driven framework which provides platform independent executable environments for bioinformatics software. BioContainers allows labs of all sizes to easily install bioinformatics software, maintain multiple versions of the same software and combine tools into powerful analysis pipelines. BioContainers is based on popular open-source projects Docker and rkt frameworks, that allow software to be installed and executed under an isolated and controlled environment. Also, it provides infrastructure and basic guidelines to create, manage and distribute bioinformatics containers with a special focus on omics technologies. These containers can be integrated into more comprehensive bioinformatics pipelines and different architectures (local desktop, cloud environments or HPC clusters). Availability and Implementation The software is freely available at github.com/BioContainers/.publishedVersio

Dairy Consumption and the Incidence of Hyperglycemia and the Metabolic Syndrome: Results from a French prospective study, Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

International audienceOBJECTIVE: In the French Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, cross-sectional analyses have shown that a higher consumption of dairy products and calcium are associated with a lower prevalence of the metabolic syndrome (MetS). We assess the influence of dairy products on 9-year incident MetS and on impaired fasting glycemia and/or type 2 diabetes (IFG/T2D). RESEARCH DESIGN AND METHODS: Men and women who completed a food frequency questionnaire at baseline and after 3 years were studied (n = 3,435). Logistic regression models were used to study associations between the average year 0 and year 3 consumption of milk and dairy products, cheese, dietary calcium density, and incident MetS and IFG/T2D after adjusting for 1) sex, age, alcohol, smoking, physical activity, fat intake and 2) additionally for BMI. Associations between dairy products and continuous variables were studied by repeated-measures ANCOVA, using the same covariates. RESULTS: Dairy products other than cheese, and dietary calcium density, were inversely associated with incident MetS and IFG/T2D; cheese was negatively associated with incident MetS. All three parameters were associated with lower diastolic blood pressure, and with a lower BMI gain. Higher cheese intake and calcium density were associated with a lower increase in waist circumference and lower triglyceride levels. Calcium density was also associated with a lower systolic blood pressure and a lower 9-year increase in plasma triglyceride levels. CONCLUSIONS: A higher consumption of dairy products and calcium was associated with a lower 9-year incidence of MetS and IFG/T2D in a large cohort drawn from the general population

Rapid MR elastography of the liver for subsecond stiffness sampling

PURPOSE: Depicting the stiffness of biological soft tissues, MR elastography (MRE) has a wide range of diagnostic applications. The purpose of this study was to improve the temporal resolution of 2D hepatic MRE in order to provide more rapid feedback on the quality of the wavefield and ensure better temporal sampling of respiration-induced stiffness changes. METHODS: We developed a rapid MRE sequence that uses 2D segmented gradient-echo spiral readout to encode 40 Hz harmonic vibrations and generate stiffness maps within 625 ms. We demonstrate the use of this technique as a rapid test for shear wave amplitudes and overall MRE image quality and as a method for monitoring respiration-induced stiffness changes in the liver in comparison to 3D MRE and ultrasound-based time-harmonic elastography. RESULTS: Subsecond MRE allowed monitoring of increasing shear wave amplitudes in the liver with increasing levels of external stimulation within a single breath-hold. Furthermore, the technique detected respiration-induced changes in liver stiffness with peak values (1.83 ± 0.22 m/s) at end-inspiration, followed by softer values during forced abdominal pressure (1.60 ± 0.22 m/s) and end-expiration (1.49 ± 0.22 m/s). The effects of inspiration and expiration were confirmed by time-harmonic elastography. CONCLUSION: Our results suggest that subsecond MRE of the liver is useful for checking MRE driver settings and monitoring breathing-induced changes in liver stiffness in near real time

A proteomics sample metadata representation for multiomics integration and big data analysis

The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets.publishedVersio

Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems