Impact of glycolysis inhibitor (2-DG) and oxidation and phosphorylation uncoupler (2,4-DNP) on brain metabolites

Deviations in brain metabolism are the result of longterm pathological processes, which finally are manifested as symptoms of Parkinson’s or Alzheimer’s diseases or multiple sclerosis and other neuropathologies, as for example diabetic neuropathy. A deficiency of available energy for brain cells under neurodegenerative diseases is either developed due to age-dependent underexpression of genes that encode glycolytic enzymes or induced due to the uncoupling of oxidation and phosphorylation that could be mediated by inflammatory cytokines. Since the activity of many enzymes is under the control of adenosine triphosphate (ATP) or cofactors, such as nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), energy deficiency can cause metabolic changes in brain tissue. Some clinical studies using proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) revealed metabolic changes in brain tissue in patients with neurodegenerative diseases. However, data from different authors are quite contradictory, probably because of the complex genesis of metabolic disorders. In the present study, we tested the hypothesis of multidirectional changes in metabolism under the impact of the oxidation and phosphorylation uncoupler 2,4-dinitrophenol (2,4-DNP) and under the impact of 2-deoxy-Dglucose (2-DG), blocking the access of glucose to the brain cells. 1H NMR spectroscopy showed that 2-DG leads to the predominance of excitatory (glutamine + glutamate) neurotransmitters over inhibitory ones (gamma-aminobutyric acid), and 2,4 DNP causes opposite effects. The biochemical mechanisms of the observed changes require a special study, but it can be noted that the ATP deficiency caused by inhibition of glycolysis and the ATP deficiency caused by the uncouplers are accompanied by differently directed changes in the intensity of the tricarboxylic acid cycle. These changes in the intensity of the Krebs cycle are correlated with differently directed changes in the balance of the exciting and inhibitory neurotransmitters. The obtained results show that 1H NMR spectroscopy can be an effective method of differentiated lifetime assessment of the available energy deficit caused by a general suppression of energy exchange in nerve cells or oxidation and phosphorylation uncoupling

A Testis-Specific Chaperone and the Chromatin Remodeler ISWI Mediate Repackaging of the Paternal Genome

During spermatogenesis, the paternal genome is repackaged into a non-nucleosomal, highly compacted chromatin structure. Bioinformatic analysis revealed that Drosophila sperm chromatin proteins are characterized by a motif related to the high-mobility group (HMG) box, which we termed male-specific transcript (MST)-HMG box. MST77F is a MST-HMG-box protein that forms an essential component of sperm chromatin. The deposition of MST77F onto the paternal genome requires the chaperone function of tNAP, a testis-specific NAP protein. MST77F, in turn, enables the stable incorporation of MST35Ba and MST35Bb into sperm chromatin. Following MST-HMG-box protein deposition, the ATP-dependent chromatin remodeler ISWI mediates the appropriate organization of sperm chromatin. Conversely, at fertilization, maternal ISWI targets the paternal genome and drives its repackaging into de-condensed nucleosomal chromatin. Failure of this transition in ISWI mutant embryos is followed by mitotic defects, aneuploidy, and haploid embryonic divisions. Thus, ISWI enables bi-directional transitions between two fundamentally different forms of chromatin

Brain metabolites in ISIAH and Wistar rats

Hypertension is one of the most common human diseases. This disease leads to serious disturbances such as myocardial infarction and stroke. Due to the development of nuclear magnetic resonance spectroscopy (NMRS), a decrease in neuron viability in different parts of the brain in humans with hypertension has been shown. Translation of NMRS tools to the clinic requires the accumulation of empirical data about neurometabolic changes in a strictly controlled experiment. It is particularly interesting to compare the metabolic parameters of laboratory animals with normal and high blood pressure kept in standard conditions on exactly the same diet. In this study, cortex and hypothalamus metabolites of ISIAH and Wistar male rats at the age of 8–9 weeks were examined. Cortex and hypothalamus metabolites were measured in animals under isoflurane anesthesia using proton magnetic resonance spectroscopy (1Н MRS). Processing of primary data using Partial least squares Discriminant Analysis (PLS-DA) allowed us to identify the main discriminating axis (Y1), its variations reflecting the predominance of excitatory neurometabolites (glutamine and glutamate) over inhibitory ones (GABA and glycine). In the cortex, the values of the Y1-axis were lower in ISIAH than in Wistar rats. This fact indicates a decrease in cortical excitability in hypertensive animals. By contrast, in the hypothalamus, the values of the Y1-axis were higher in ISIAH than in Wistar rats and the predominance of excitatory neurometabolites positively correlated with the level of mean blood pressure, which agrees well with the view of caudal hypothalamic activation in hypertensive animal models

Study of the neuronal response to olfactory stimuli in control and LPS-stimulated mice by functional magnetic resonance imaging

Olfactory perception plays the key role in the inter­action of animals with biotic factors of the species-specific econiche. Identification of odorants informs nocturnal animals about social environment, presence of predators, or infected food. Olfactory efficiency depends on physiological conditions; in particular, odor sensitivity can be changed by infection. This work considers use of fMRI in the study of the influence of innate immunity activation on neuronal response during perception and differentiation of socially significant (2.5-dimethylpyrazine, 2-heptanon) and socially insignificant (1-hexanol and isoprene) olfactory stimuli by CD-1 mice. We stimulated innate immunity by intraperitoneal injection of bacterial lipopolysaccharide (LPS) at the dose 500 µg/kg three hours before tomography. Urethane anesthesia was used during MRI trail. Odor stimulation was done with a lab-made metering unit for supplying standard doses of volatile organic compounds. The supply of olfactory stimuli induced activation of neurons in the primary perceptual center and the centers of secondary processing of olfactory information. Olfactory stimulus type affected neuronal response rate in an olfactory bulb but did not affect response parameters in other brain regions studied. This increase in neuronal activity is likely to be of adaptive significance as a mechanism supporting olfactory sensitivity increase, which plays the key role in the identification of potential sources of infection

The Atmospheric Chemistry Suite (ACS) of Three Spectrometers for the ExoMars 2016 Trace Gas Orbiter

The Atmospheric Chemistry Suite (ACS) package is an element of the Russian contribution to the ESA-Roscosmos ExoMars 2016 Trace Gas Orbiter (TGO) mission. ACS consists of three separate infrared spectrometers, sharing common mechanical, electrical, and thermal interfaces. This ensemble of spectrometers has been designed and developed in response to the Trace Gas Orbiter mission objectives that specifically address the requirement of high sensitivity instruments to enable the unambiguous detection of trace gases of potential geophysical or biological interest. For this reason, ACS embarks a set of instruments achieving simultaneously very high accuracy (ppt level), very high resolving power (>10,000) and large spectral coverage (0.7 to 17 μm—the visible to thermal infrared range). The near-infrared (NIR) channel is a versatile spectrometer covering the 0.7–1.6 μm spectral range with a resolving power of ∼20,000. NIR employs the combination of an echelle grating with an AOTF (Acousto-Optical Tunable Filter) as diffraction order selector. This channel will be mainly operated in solar occultation and nadir, and can also perform limb observations. The scientific goals of NIR are the measurements of water vapor, aerosols, and dayside or night side airglows. The mid-infrared (MIR) channel is a cross-dispersion echelle instrument dedicated to solar occultation measurements in the 2.2–4.4 μm range. MIR achieves a resolving power of >50,000. It has been designed to accomplish the most sensitive measurements ever of the trace gases present in the Martian atmosphere. The thermal-infrared channel (TIRVIM) is a 2-inch double pendulum Fourier-transform spectrometer encompassing the spectral range of 1.7–17 μm with apodized resolution varying from 0.2 to 1.3 cm−1. TIRVIM is primarily dedicated to profiling temperature from the surface up to ∼60 km and to monitor aerosol abundance in nadir. TIRVIM also has a limb and solar occultation capability. The technical concept of the instrument, its accommodation on the spacecraft, the optical designs as well as some of the calibrations, and the expected performances for its three channels are described

Reproductive effects of the tumor necrosis factor (TNF) deficiency in mice

TNF is a multifunctional cytokine that, at physiological concentrations, maintains the balance between apoptosis and survival of male germ cells and, at higher concentrations, has adverse effects on various stages of the reproductive process. Although ant-cytokine therapies have been used in millions of patients, the consequences of cytokine deficiency for reproductive functions are poorly understood and need attention. In this work, we have studied behavioral interactions between males and females, spermatogenesis, male fertility, and embryonic developmental characteristics of the progeny in TNFα knockout mice (TNF-/-). We have demonstrated that TNF is involved in the regulation of sexual behavior, spermatogenesis, pre- and postimplantation development. Complete TNF deficiency led to decreased reproductive efficiency: a lower number of viable embryos were observed in TNF-/- mice than in wild-type mice. The decrease in fertility was caused by preimplantation embryo loss in TNF-/- mice. Preimplantation loss in females might be caused by asospermia in TNF-/- males. Additionally, the sensitivity of reproductive functions to female stimuli was different between TNF-/- mice and wild-type mice, while interactions with females increased the concentrations of sper­matozoids in both TNF-/- and wild-type mice. Still higher levels were observed in knockout animals, which led to increase in the number of immature spermatozoids in epididymides

Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German

The Outer Tracker Detector of the HERA-B Experiment Part I: Detector

The HERA-B Outer Tracker is a large system of planar drift chambers with about 113000 read-out channels. Its inner part has been designed to be exposed to a particle flux of up to 2.10^5 cm^-2 s^-1, thus coping with conditions similar to those expected for future hadron collider experiments. 13 superlayers, each consisting of two individual chambers, have been assembled and installed in the experiment. The stereo layers inside each chamber are composed of honeycomb drift tube modules with 5 and 10 mm diameter cells. Chamber aging is prevented by coating the cathode foils with thin layers of copper and gold, together with a proper drift gas choice. Longitudinal wire segmentation is used to limit the occupancy in the most irradiated detector regions to about 20 %. The production of 978 modules was distributed among six different laboratories and took 15 months. For all materials in the fiducial region of the detector good compromises of stability versus thickness were found. A closed-loop gas system supplies the Ar/CF4/CO2 gas mixture to all chambers. The successful operation of the HERA-B Outer Tracker shows that a large tracker can be efficiently built and safely operated under huge radiation load at a hadron collider.Comment: 28 pages, 14 figure