The Hybrid Drive: a chronic implant device combining tetrode arrays with silicon probes for layer-resolved ensemble electrophysiology in freely moving mice.

. Understanding the function of brain cortices requires simultaneous investigation at multiple spatial and temporal scales and to link neural activity to an animal's behavior. A major challenge is to measure within- and across-layer information in actively behaving animals, in particular in mice that have become a major species in neuroscience due to an extensive genetic toolkit.

Mouse visual cortex contains a region of enhanced spatial resolution.

The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the "focea," represents a location in space in front of, and slightly above, the mouse.

Vision: Depth perception in climbing mice.

Depth perception helps animals interact with a three-dimensional world. A new study presents a novel paradigm for studying depth perception in naturally climbing mice and links their behavior to binocular disparity signals in primary visual cortical neurons.

Two Distinct Types of Eye-Head Coupling in Freely Moving Mice.

Animals actively interact with their environment to gather sensory information. There is conflicting evidence about how mice use vision to sample their environment. During head restraint, mice make rapid eye movements coupled between the eyes, similar to conjugate saccadic eye movements in humans.

A Head-Mounted Camera System Integrates Detailed Behavioral Monitoring with Multichannel Electrophysiology in Freely Moving Mice.

Breakthroughs in understanding the neural basis of natural behavior require neural recording and intervention to be paired with high-fidelity multimodal behavioral monitoring. An extensive genetic toolkit for neural circuit dissection, and well-developed neural recording technology, make the mouse a powerful model organism for systems neuroscience. However, most methods for high-bandwidth acquisition of behavioral data in mice rely upon fixed-position cameras and other off-animal devices, complicating the monitoring of animals freely engaged in natural behaviors.

Growing Protein Crystals with Distinct Dimensions Using Automated Crystallization Coupled with In Situ Dynamic Light Scattering.

The automated crystallization device is a patented technique especially developed for monitoring protein crystallization experiments with the aim to precisely maneuver the nucleation and crystal growth towards desired sizes of protein crystals. The controlled crystallization is based on sample investigation with in situ Dynamic Light Scattering (DLS) while all visual changes in the droplet are monitored online with the help of a microscope coupled to a CCD camera, thus enabling a full investigation of the protein droplet during all stages of crystallization. The use of in situ DLS measurements throughout the entire experiment allows a precise identification of the highly supersaturated protein solution transitioning to a new phase - the formation of crystal nuclei.

The fine art of integral membrane protein crystallisation.

Integral membrane proteins are among the most fascinating and important biomolecules as they play a vital role in many biological functions. Knowledge of their atomic structures is fundamental to the understanding of their biochemical function and key in many drug discovery programs. However, over the years, structure determination of integral membrane proteins has proven to be far from trivial, hence they are underrepresented in the protein data bank.

Models of Neuronal Stimulus-Response Functions: Elaboration, Estimation, and Evaluation.

Rich, dynamic, and dense sensory stimuli are encoded within the nervous system by the time-varying activity of many individual neurons. A fundamental approach to understanding the nature of the encoded representation is to characterize the function that relates the moment-by-moment firing of a neuron to the recent history of a complex sensory input. This review provides a unifying and critical survey of the techniques that have been brought to bear on this effort thus far-ranging from the classical linear receptive field model to modern approaches incorporating normalization and other nonlinearities.

Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the model organism zebrafish.

Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone and 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol and corticosterone).

Fast and robust estimation of spectro-temporal receptive fields using stochastic approximations.

Background: The receptive field (RF) represents the signal preferences of sensory neurons and is the primary analysis method for understanding sensory coding. While it is essential to estimate a neuron's RF, finding numerical solutions to increasingly complex RF models can become computationally intensive, in particular for high-dimensional stimuli or when many neurons are involved.

New Method: Here we propose an optimization scheme based on stochastic approximations that facilitate this task.

Latest methods of fluorescence-based protein crystal identification.

Successful protein crystallization screening experiments are dependent upon the experimenter being able to identify positive outcomes. The introduction of fluorescence techniques has brought a powerful and versatile tool to the aid of the crystal grower. Trace fluorescent labeling, in which a fluorescent probe is covalently bound to a subpopulation (<0.

Systematic analysis of protein-detergent complexes applying dynamic light scattering to optimize solutions for crystallization trials.

Detergents are widely used for the isolation and solubilization of membrane proteins to support crystallization and structure determination. Detergents are amphiphilic molecules that form micelles once the characteristic critical micelle concentration (CMC) is achieved and can solubilize membrane proteins by the formation of micelles around them. The results are presented of a study of micelle formation observed by in situ dynamic light-scattering (DLS) analyses performed on selected detergent solutions using a newly designed advanced hardware device.

Temporal variability of spectro-temporal receptive fields in the anesthetized auditory cortex.

Temporal variability of neuronal response characteristics during sensory stimulation is a ubiquitous phenomenon that may reflect processes such as stimulus-driven adaptation, top-down modulation or spontaneous fluctuations. It poses a challenge to functional characterization methods such as the receptive field, since these often assume stationarity. We propose a novel method for estimation of sensory neurons' receptive fields that extends the classic static linear receptive field model to the time-varying case.

Ligand-based pharmacophore modeling and virtual screening for the discovery of novel 17β-hydroxysteroid dehydrogenase 2 inhibitors.

17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) catalyzes the inactivation of estradiol into estrone. This enzyme is expressed only in a few tissues, and therefore its inhibition is considered as a treatment option for osteoporosis to ameliorate estrogen deficiency. In this study, ligand-based pharmacophore models for 17β-HSD2 inhibitors were constructed and employed for virtual screening.

Preliminary crystallographic analysis of a cruciferin protein from seeds of Moringa oleifera.

A 55 kDa cruciferin protein has been purified and characterized from seeds of Moringa oleifera plant. Protein blast of N-terminal amino-acid sequence showed 60 % sequence similarity with cruciferin from Brassica napus. The M.

Discriminative learning of receptive fields from responses to non-Gaussian stimulus ensembles.

Analysis of sensory neurons' processing characteristics requires simultaneous measurement of presented stimuli and concurrent spike responses. The functional transformation from high-dimensional stimulus space to the binary space of spike and non-spike responses is commonly described with linear-nonlinear models, whose linear filter component describes the neuron's receptive field. From a machine learning perspective, this corresponds to the binary classification problem of discriminating spike-eliciting from non-spike-eliciting stimulus examples.

Formation of threohydrobupropion from bupropion is dependent on 11β-hydroxysteroid dehydrogenase 1.

Bupropion is widely used for treatment of depression and as a smoking-cessation drug. Despite more than 20 years of therapeutic use, its metabolism is not fully understood. While CYP2B6 is known to form hydroxybupropion, the enzyme(s) generating erythro- and threohydrobupropion have long remained unclear.

Carbonyl reduction of triadimefon by human and rodent 11β-hydroxysteroid dehydrogenase 1.

11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the conversion of inactive 11-oxo glucocorticoids (endogenous cortisone, 11-dehydrocorticosterone and synthetic prednisone) to their potent 11β-hydroxyl forms (cortisol, corticosterone and prednisolone). Besides, 11β-HSD1 accepts several other substrates. Using rodent liver microsomes and the unspecific inhibitor glycyrrhetinic acid, it has been proposed earlier that 11β-HSD1 catalyzes the reversible conversion of the fungicide triadimefon to triadimenol.

Structural optimization of 2,5-thiophene amides as highly potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors for the treatment of osteoporosis.

Inhibition of 17β-HSD2 is an attractive mechanism for the treatment of osteoporosis. We report here the optimization of human 17β-HSD2 inhibitors in the 2,5-thiophene amide class by varying the size of the linker (n equals 0 and 2) between the amide moiety and the phenyl group. While none of the phenethylamides (n = 2) were active, most of the anilides (n = 0) turned out to moderately or strongly inhibit 17β-HSD2.

Structure of the recombinant BPTI/Kunitz-type inhibitor rShPI-1A from the marine invertebrate Stichodactyla helianthus.

The BPTI/Kunitz-type inhibitor family includes several extremely potent serine protease inhibitors. To date, the inhibitory mechanisms have only been studied for mammalian inhibitors. Here, the first crystal structure of a BPTI/Kunitz-type inhibitor from a marine invertebrate (rShPI-1A) is reported to 2.

Single-drop optimization of protein crystallization.

A completely new crystal-growth device has been developed that permits charting a course across the phase diagram to produce crystalline samples optimized for diffraction experiments. The utility of the device is demonstrated for the production of crystals for the traditional X-ray diffraction data-collection experiment, of microcrystals optimal for data-collection experiments at a modern microbeam insertion-device synchrotron beamline and of nanocrystals required for data collection on an X-ray laser beamline.

Species-specific differences in the inhibition of human and zebrafish 11β-hydroxysteroid dehydrogenase 2 by thiram and organotins.

Dithiocarbamates and organotins can inhibit enzymes by interacting with functionally essential sulfhydryl groups. Both classes of chemicals were shown to inhibit human 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts active cortisol into inactive cortisone and has a role in renal and intestinal electrolyte regulation and in the feto-placental barrier to maternal glucocorticoids. In fish, 11β-HSD2 has a dual role by inactivating glucocorticoids and generating the major androgen 11-ketotestosterone.

Monitoring and scoring counter-diffusion protein crystallization experiments in capillaries by in situ dynamic light scattering.

In this paper, we demonstrate the feasibility of using in situ Dynamic Light Scattering (DLS) to monitor counter-diffusion crystallization experiments in capillaries. Firstly, we have validated the quality of the DLS signal in thin capillaries, which is comparable to that obtained in standard quartz cuvettes. Then, we have carried out DLS measurements of a counter-diffusion crystallization experiment of glucose isomerase in capillaries of different diameters (0.

Binding of the plant hormone kinetin in the active site of Mistletoe Lectin I from Viscum album.

The crystal structure of the ribosome inhibiting protein Mistletoe Lectin I (ML-I) derived from the European mistletoe, Viscum album, in complex with kinetin has been refined at 2.7Å resolution. Suitably large crystals of ML-I were obtained applying the counter diffusion method using the Gel Tube R Crystallization Kit (GT-R) on board the Russian Service Module on the international space station ISS within the GCF mission No.

Isolation, purification, crystallization and preliminary crystallographic studies of a chitinase from Crocus vernus.

A chitinase has been isolated and purified from Crocus vernus corms. N-terminal amino-acid sequence analysis of the approximately 30 kDa protein showed 33% identity to narbonin, a seed protein from Vicia narbonensis L. The C.