When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests ...reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Within the framework of the Landauer-Buttiker formalism, the conductivity of one- and two-barrier graphene structures is calculated. The conditions for formation of the maximum value of the ...conductivity depending on the energy of ultrarelativistic quasielectrons as well as on the parameters of these structures (the values of Fermi velocity in different regions and the potential barriers height) are analyzed. It is believed that there is an electrostatic barrier and also the Fermi velocity barrier due to the fact that this quantity may aсquire different values in the barrier and out-of-barrier regions of the considered structures. The obtained expression for the transmission rates accounts for the π phase change of the transmitted wave function (which was not taken into consideration in the known formulae for the transmission rates of some papers). Consideration of this phase change leads to some new important features which characterize the transmission process in the graphene structures. We are the first to show that the effect of the supertunnelling manifests itself in graphene and it is observed both in the dependences of the transmission rates and of the conductivity on the quasielectron energy. This effect consists in the fact that, under certain conditions, the transmission through the structure is perfect (transmission rates T = 1) for the arbitrary angle of incidence of quasielectrons on the barrier. The expression іs given that determines the specified conditions for the supertunneling. The analysis of the transmission dependence on the problem parameters is also provided.
•All-angled perfect tunneling can be observed in the graphene-based single barrier resonant-tunneling structure.•This type of tunneling significantly affects the conductivity of the given structure.•The analogous effect manifests itself also in the graphene based double barrier resonant-tunneling structure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Speckle tracking echocardiography (STE) has been utilized to evaluate independent spatial alterations in the diabetic heart, but the progressive manifestation of regional and segmental cardiac ...dysfunction in the type 2 diabetic (T2DM) heart remains understudied. Therefore, the objective of this study was to elucidate if machine learning could be utilized to reliably describe patterns of the progressive regional and segmental dysfunction that are associated with the development of cardiac contractile dysfunction in the T2DM heart. Non-invasive conventional echocardiography and STE datasets were utilized to segregate mice into two pre-determined groups, wild-type and Db/Db, at 5, 12, 20, and 25 weeks. A support vector machine model, which classifies data using a single line, or hyperplane, that best separates each class, and a ReliefF algorithm, which ranks features by how well each feature lends to the classification of data, were used to identify and rank cardiac regions, segments, and features by their ability to identify cardiac dysfunction. STE features more accurately segregated animals as diabetic or non-diabetic when compared with conventional echocardiography, and the ReliefF algorithm efficiently ranked STE features by their ability to identify cardiac dysfunction. The Septal region, and the AntSeptum segment, best identified cardiac dysfunction at 5, 20, and 25 weeks, with the AntSeptum also containing the greatest number of features which differed between diabetic and non-diabetic mice. Cardiac dysfunction manifests in a spatial and temporal fashion, and is defined by patterns of regional and segmental dysfunction in the T2DM heart which are identifiable using machine learning methodologies. Further, machine learning identified the Septal region and AntSeptum segment as locales of interest for therapeutic interventions aimed at ameliorating cardiac dysfunction in T2DM, suggesting that machine learning may provide a more thorough approach to managing contractile data with the intention of identifying experimental and therapeutic targets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AM CVn binaries are hydrogen deficient compact binaries with an orbital period in the 5–65 min range and are predicted to be strong sources of persistent gravitational wave radiation. Using Gaia Data ...Release 2, we present the parallaxes and proper motions of 41 out of the 56 known systems. Compared to the parallax determined using the HST Fine Guidance Sensor we find that the archetype star, AM CVn, is significantly closer than previously thought. This resolves the high luminosity and mass accretion rate which models had difficulty in explaining. Using Pan-STARRS1 data we determine the absolute magnitude of the AM CVn stars. There is some evidence that donor stars have a higher mass and radius than expected for white dwarfs or that the donors are not white dwarfs. Using the distances to the known AM CVn stars we find strong evidence that a large population of AM CVn stars has yet to be discovered. As this value sets the background to the gravitational wave signal of LISA this is of wide interest. We determine the mass transfer rate for 15 AM CVn stars and find that the majority has a rate significantly greater than expected from standard models. This is further evidence that the donor star has a greater size than expected.
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Context.
Milky Way dwarf satellites are unique objects that encode the early structure formation and therefore represent a window into the high redshift Universe. So far, their study has been ...conducted using electromagnetic waves only. The future Laser Interferometer Space Antenna (LISA) has the potential to reveal Milky Way satellites through gravitational waves emitted by double white dwarf (DWD) binaries.
Aims.
We investigate gravitational wave signals that will be detectable by LISA as a possible tool for the identification and characterisation of the Milky Way satellites.
Methods.
We used the binary population synthesis technique to model the population of DWDs in dwarf satellites and we assessed the impact on the number of LISA detections when making changes to the total stellar mass, distance, star formation history, and metallicity of satellites. We calibrated predictions for the known Milky Way satellites on their observed properties.
Results.
We find that DWDs emitting at frequencies ≳3 mHz can be detected in Milky Way satellites at large galactocentric distances. The number of these high frequency DWDs per satellite primarily depends on its mass, distance, age, and star formation history, and only mildly depends on the other assumptions regarding their evolution such as metallicity. We find that dwarf galaxies with
M
⋆
> 10
6
M
⊙
can host detectable LISA sources; the number of detections scales linearly with the satellite’s mass. We forecast that out of the known satellites, Sagittarius, Fornax, Sculptor, and the Magellanic Clouds can be detected with LISA.
Conclusions.
As an all-sky survey that does not suffer from contamination and dust extinction, LISA will provide observations of the Milky Way and dwarf satellites galaxies, which will be valuable for Galactic archaeology and near-field cosmology.
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Binary interaction can cause stellar envelopes to be stripped, which significantly reduces the radius of the star. The orbit of a binary composed of a stripped star and a compact object can therefore ...be so tight that the gravitational radiation the system produces reaches frequencies accessible to the Laser Interferometer Space Antenna (LISA). Two such stripped stars in tight orbits with white dwarfs are known so far (ZTF J2130+4420 and CD−30°11223), but many more are expected to exist. These binaries provide important constraints for binary evolution models and may be used as LISA verification sources. We develop a Monte Carlo code that uses detailed evolutionary models to simulate the Galactic population of stripped stars in tight orbits with either neutron star or white dwarf companions. We predict 0-100 stripped star + white dwarf binaries and 0-4 stripped star + neutron star binaries with a signal-to-noise ratio >5 after 10 yr of observations with LISA. More than 90% of these binaries are expected to show large radial velocity shifts of 200 km s − 1 , which are spectroscopically detectable. Photometric variability due to tidal deformation of the stripped star is also expected and has been observed in ZTF J2130+4420 and CD−30°11223. In addition, the stripped star + neutron star binaries are expected to be X-ray bright with LX 1033-1036 erg s − 1 . Our results show that stripped star binaries are promising multimessenger sources for the upcoming electromagnetic and gravitational wave facilities.
We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We ...investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia. Furthermore, neuronal cells carrying NRXN1-alpha deletion were identified as immature by single cell RNA-seq analysis, displayed significant depression in calcium signaling activity and presented impaired maturation action potential profile in neurons investigated with electrophysiology. Our observations propose NRXN1-alpha plays an important role for the efficient establishment of neural stem cells, in neuronal differentiation and in maturation of functional excitatory neuronal cells.
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•Disease modeling of autism in iPS derived neural stem cells carrying bi-allelic NRXN1-alpha deletion.•Single cell analysis accurately resolves genes and cell identities.•Deletion of NRXN1-alpha skews neural stem cells towards radial glia-like cells with preference for generating astroglia.•Deletion of NRXN1-alpha depresses calcium-signaling activity and impairs maturation in excitatory neurons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The evolvement of duplicated gene loci in allopolyploid plants has become the subject of intensive studies. Most duplicated genes remain active in neoallopolyploids contributing either to a ...favourable effect of an extra gene dosage or to the build-up of positive inter-genomic interactions when genes or regulation factors on homoeologous chromosomes are divergent. However, in a small number of loci (about 10%), genes of only one genome are active, while the homoeoalleles on the other genome(s) are either eliminated or partially or completely suppressed by genetic or epigenetic means. For several traits, the retention of controlling genes is not random, favouring one genome over the other(s). Such genomic asymmetry is manifested in allopolyploid wheat by the control of various morphological and agronomical traits, in the production of rRNA and storage proteins, and in interaction with pathogens. It is suggested that the process of cytological diploidization leading to exclusive intra-genomic meiotic pairing and, consequently, to complete avoidance of inter-genomic recombination, has two contrasting effects. Firstly, it provides a means for the fixation of positive heterotic inter-genomic interactions and also maintains genomic asymmetry resulting from loss or silencing of genes. The possible mechanisms and evolutionary advantages of genomic asymmetry are discussed.
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The neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule in the brain and in pancreatic islets. Here, we demonstrate that GABA regulates cytokine secretion from human ...peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. In anti-CD3 stimulated PBMCs, GABA (100nM) inhibited release of 47 cytokines in cells from patients with type 1 diabetes (T1D), but only 16 cytokines in cells from nondiabetic (ND) individuals. CD4+ T cells from ND individuals were grouped into responder or non-responder T cells according to effects of GABA (100nM, 500nM) on the cell proliferation. In the responder T cells, GABA decreased proliferation, and inhibited secretion of 37 cytokines in a concentration-dependent manner. In the non-responder T cells, GABA modulated release of 8 cytokines. GABA concentrations in plasma from T1D patients and ND individuals were correlated with 10 cytokines where 7 were increased in plasma of T1D patients. GABA inhibited secretion of 5 of these cytokines from both T1D PBMCs and ND responder T cells. The results identify GABA as a potent regulator of both Th1- and Th2-type cytokine secretion from human PBMCs and CD4+ T cells where GABA generally decreases the secretion.
•GABA regulates cytokine secretion in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) and CD4+ T cells.•GABA inhibits secretion of 47 cytokines in PBMCs from type 1 diabetes patients.•GABA regulates secretion of pro- and anti-inflammatory cytokines in a concentration-dependent manner.
GABA is a signal molecule in the brain, blood and pancreatic islets where it is secreted by the insulin-producing β cells. GABA has many roles in human islets including optimizing function and survival of β cells. Bhandage et al. now show that GABA is a potent regulator of secretion of both pro- and anti-inflammatory cytokines in stimulated immune cells. In type 1 diabetes the β-cell mass is diminished and thus the protective effect of GABA in the islets although not in blood. Targeting GABA signaling in diabetes mellitus is likely to be a part of the solution when curing diabetes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The features of the repair and construction work during the overhaul of buildings are reflected in the development of organizational and technological design documents, which include calendar plans. ...Organizational and technological models represent the basis for the development and calculation of calendar plans, as well as for determining resource requirements. They for prevention works, the order of their implementation, the nature of the relationship between individual works, reflecting the specifics of the selected technology for the production of work and the features of the simulated object. The scheduling of overhaul works is carried out on the basis of the developed methodology, which allows obtaining rational organizational and technological solutions with a low level of certainty of the initial information. To evaluate the final set of alternative options for calendar plans and choose the best option in accordance with the described methodology, it is recommended to use quasi metric methods. This allows us to lay the foundation for the rhythmic and coordinated work of all units involved in overhaul at the stage of scheduling, as well as to keep track of the possibility of ensuring timely completion of the planned work.
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