Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis.

While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease.

Prostate brachytherapy training with simulated ultrasound and fluoroscopy images.

In this paper, a novel computer-based virtual training system for prostate brachytherapy is presented. This system incorporates, in a novel way, prior methodologies of ultrasound image synthesis and haptic transrectal ultrasound (TRUS) transducer interaction in a complete simulator that allows a trainee to maneuver the needle and the TRUS, to see the resulting patient-specific images and feel the interaction forces. The simulated TRUS images reflect the volumetric tissue deformation and comprise validated appearance models for the needle and implanted seeds.

Characterizing multistationarity regimes in biochemical reaction networks.

Switch like responses appear as common strategies in the regulation of cellular systems. Here we present a method to characterize bistable regimes in biochemical reaction networks that can be of use to both direct and reverse engineering of biological switches. In the design of a synthetic biological switch, it is important to study the capability for bistability of the underlying biochemical network structure.

Maternal high-fat diet in mice programs emotional behavior in adulthood.

The maternal environment has a significant role in the normal development of the fetus and may have long-term impact on brain development including critical central pathways such as the gamma-aminobutyric acid (GABA), serotonergic and the neurotrophin systems. For example, maternal malnutrition plays an important role in programming many aspects of physiology and behavior including predisposition to mental-health related disorders such as anxiety. Here we investigated the effects of maternal high-fat diet or control diet for nine weeks (prior to gestation, gestation and lactation) on the adult offspring with respect to anxiety related behaviors as well as exploration and conditioned fear response.

Analysis of the subunit stoichiometries in viral entry.

Virions of the Human Immunodeficiency Virus (HIV) infect cells by first attaching with their surface spikes to the CD4 receptor on target cells. This leads to conformational changes in the viral spikes, enabling the virus to engage a coreceptor, commonly CCR5 or CXCR4, and consecutively to insert the fusion peptide into the cellular membrane. Finally, the viral and the cellular membranes fuse.

Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously.

Spontaneous termination of atrial fibrillation: study of the effect of atrial geometry in a biophysical model.

We studied the mechanisms of spontaneous termination of atrial fibrillation in a biophysical model of human atria, during the eight seconds preceding termination. The earliest detectable changes in the cycle length and the number of wavefronts occurred about three seconds prior to termination. We compared the mechanisms involved in the right and left atrium and investigated the effects of atrial geometry on the termination processes.

Optimization of antitachycardia pacing protocols applied to atrial fibrillation: insights from a biophysical model.

We present a model-based systematic study of antitachycardia pacing protocols applied to atrial fibrillation, focusing on the ability to achieve and maintain capture during pacing, as a function of both pacing site and period. We observed that pacing sites located away from anatomical obstacles led to faster and more robust capture. Moreover, after comparing burst and ramp pacing, our results indicate that in order to get capture it is necessary to pace at a fixed optimal period over a sufficient long time.

Visual proteomics of the human pathogen Leptospira interrogans.

Systems biology conceptualizes biological systems as dynamic networks of interacting elements, whereby functionally important properties are thought to emerge from the structure of such networks. Owing to the ubiquitous role of complexes of interacting proteins in biological systems, their subunit composition and temporal and spatial arrangement within the cell are of particular interest. 'Visual proteomics' attempts to localize individual macromolecular complexes inside of intact cells by template matching reference structures into cryo-electron tomograms.

Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin.

Background: Plasma hepcidin appears to be a major regulator of iron absorption and homeostasis, but there are few data in humans.

Objectives: With the use of iron stable isotopes, we aimed to determine whether circulating hepcidin predicts dietary iron bioavailability, to quantify the amount of absorbed iron after oral iron loading, and to measure the plasma hepcidin response.

Design: In the first study, young women (n = 98) with an iron status varying from iron deficiency anemia to iron sufficiency (women with serum ferritin concentrations 25-40 microg/L were not included) were given stable isotope-labeled test meals (n = 196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after which plasma hepcidin and iron bioavailability were measured.

Structural and functional insights into nucleocytoplasmic transport.

The cell nucleus is surrounded by a double membrane system, the nuclear envelope (NE), with the outer nuclear membrane being continuous with the endoplasmic reticulum. Nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes, forming aqueous channels that allow free diffusion of small molecules but that also mediate the energy-dependent transport of large macromolecules. The NPC represents the largest known molecular complex and is composed of about 30 different proteins, termed nucleoporins (Nups).

Error-related EEG potentials generated during simulated brain-computer interaction.

Brain-computer interfaces (BCIs) are prone to errors in the recognition of subject's intent. An elegant approach to improve the accuracy of BCIs consists in a verification procedure directly based on the presence of error-related potentials (ErrP) in the electroencephalogram (EEG) recorded right after the occurrence of an error. Several studies show the presence of ErrP in typical choice reaction tasks.

Correlation of spirometry and symptom scores in childhood asthma and the usefulness of curvature assessment in expiratory flow-volume curves.

Background: Spirometry, and in particular forced expiratory volume in the first second (FEV(1)), are standard tools for objective evaluation of asthma. However, FEV(1) does not correlate with symptom scores, and hence its value in the assessment of childhood asthma may be limited. Therefore, some clinicians subjectively assess the presence of curvature in the maximum expiratory flow-volume (MEFV) curves obtained from spirometry, where concave patterns are observable despite normal FEV(1) values.

An analysis of the evolution of the written description requirement vis-à-vis DNA and biotechnological inventions.

The Federal Circuit uses particular patent doctrines as policy levers to control the nature of the nation's patent output. Most recently, the court has looked to the narrow implementation of the written description doctrine to limit the scope of biotechnology patents in general and DNA patents in particular. Recent case-law now indicates a slow evolution within the Federal Circuit to loosen this control and broaden the scope of DNA patents.

Inducible and neuron-specific gene expression in the adult mouse brain with the rtTA2S-M2 system.

To achieve inducible and reversible gene expression in the adult mouse brain, we exploited an improved version of the tetracycline-controlled transactivator-based system (rtTA2(S)-M2, rtTA2 hereafter) and combined it with the forebrain-specific CaMKIIalpha promoter. Several independent lines of transgenic mice carrying the CaMKIIalpha promoter-rtTA2 gene were generated and examined for anatomical profile, doxycycline (dox)-dependence, time course, and reversibility of gene expression using several lacZ reporter lines. In two independent rtTA2-expressing lines, dox-treatment in the diet induced lacZ reporter expression in neurons of several forebrain structures including cortex, striatum, hippocampus, amygdala, and olfactory bulb.

Model polymer release system study of PAH bioaccessibility: the relationship between "rapid" release and bioaccessibility.

This paper examines bacterial uptake of polycyclic aromatic hydrocarbons (PAHs) entrained within model polymer release systems (MPRSs) whose release kinetics, particularly for operationally defined "slow" release, are similarto PAH release kinetics from sediments and soils. We find that biodegradation is not restricted to the fraction "rapidly" released, f1, as quantified by an empirical biphasic exponential fitting parameter. Though our results indicate that f1 does not predict bioaccessibility (defined by a recent paper calling for a standard definition of same), we analyze the causes of the reported limitation of biodegradation to rapidly released PAHs and we find that, for the MPRSs, there are very strong correlations between an ad hoc bioaccessibility and a wide range of fitting parameters from various kinetic expressions used to phenomenologically characterize release.

Mesolimbic dopaminergic pathways in fear conditioning.

One of the most common paradigms used to study the biological basis of emotion, as well as of learning and memory, is Pavlovian fear conditioning. In the acquisition phase of a fear conditioning experiment, an emotionally neutral conditioned stimulus (CS)--which can either be a discrete stimulus, such as a tone, or a contextual stimulus, such as a specific environment--is paired with an aversive unconditioned stimulus (US), for example a foot shock. As a result, the CS elicits conditioned fear responses when subsequently presented alone during the expression phase of the experiment.

Early deprivation under specific conditions leads to reduced interest in reward in adulthood in Wistar rats.

Early life adversity can lead to increased vulnerability to psychiatric disease including depression, with symptoms of depressed mood, impaired coping with negative events, anhedonia, reduced appetite, and elevated stress hormone activity. In rats, postnatal manipulation studies have focused on behavioural and endocrine anxiety effects, and have demonstrated that mild pup stimulation in the form of early handling (EH) is chronically anxiolytic relative to no stimulation in the form of non-handling (NH). Furthermore, apparently severe manipulations in the form of 3-4 h daily litter-dam separation (maternal separation) or pup-litter-dam separation (early deprivation, ED) are either without effect or even EH-like, relative to NH.

High light field confinement for fluorescent correlation spectroscopy using a solid immersion lens.

In this paper we present recent single molecule detection experiment using a solid immersion lens (SIL) for fluorescent correlation spectroscopy measurements. We compared the performance of the SIL in combination with an air objective (40x, numerical aperture (NA)=1.15) with a water immersion objective (40x, NA=0.

Behavioural and cardiovascular responses during latent inhibition of conditioned fear: measurement by telemetry and conditioned freezing.

This study assessed freezing behaviour and cardiovascular responses during the expression of latent inhibition of conditioned fear. Animals that were either repeatedly preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (non-preexposed; NPE) subsequently experienced three presentations of the tone paired with footshock. Animals were tested 24 h later in the context of the footshock chamber, and on the following day, in the presence of the tone CS.

Dosimetric analysis of the carousel setup for the exposure of rats at 1.62 GHz.

The so-called carousel setup has been widely utilized for testing the hypotheses of adverse health effects on the central nervous system (CNS) due to mobile phone exposures in the frequency bands 800-900 MHz. The objectives of this article were to analyze the suitability of the setup for the upper mobile frequency range, i.e.

Hippocampal modulation of sensorimotor processes.

While the hippocampus makes unique contributions to memory, it has also long been associated with sensorimotor processes, i.e. innate processes involving control of motor responses to sensory stimuli.

Dopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition.

The functions and interactions of cortical and subcortical dopamine systems are of interest because alterations in these systems have been implicated in neuropsychiatric diseases, such as schizophrenia. It has been proposed that prefrontal dopamine transmission may oppose dopamine transmission in subcortical sites, such as the nucleus accumbens. Accordingly, reduced prefrontal dopamine transmission would be expected to enhance or induce behavioral effects that have been associated with stimulation of accumbal dopamine receptors.