Формирование изображения нарушителя в радиолучевых системах охраны

В статье рассмотрены вопросы улучшения информационных характеристик двухпозиционных радио- лучевых технических систем охраны. В качестве первого приближения сигналообразования использована лучевая модель формирования интерференционной картины ЭМ-волны. Разработан метод формирования двумерного изображения нарушителя в виде теневого силуэта. Получено обратное преобразование Кирхгофа, связывающее функцию пропускания объекта с распределением комплексной амплитуды ЭМ-волны в плоскости приема.У статті розглянуті питання поліпшення інформаційних характеристик двопозиційних радіопроменевих технічних систем охорони. Як перше наближення сигналостворення використана променева модель формування інтерференційної картини ЕМ-хвилі. Розроблено метод формування двовимірного зображення порушника у вигляді тіньового силуету. Отримано зворотне перетворення Кірхгофа, що зв’язує функцію пропускання об’єкта з розподілом комплексної амплітуди ЕМ-хвилі в площині прийому.The article deals with the issues of improving information characteristics of two-position radio-beam technical protection systems. The beam model of forming EM wav interference pattern is used as the first approximation of signal forming. The method of forming the intruder’s two-dimensional image as a shadow silhouette has been developed. The author has drawn the Kirchhoff inversion connecting the object’s transmission function with the distribution of the EM wave complex amplitude in the reception plane

Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

During cell migration or differentiation, cell surface receptors are simultaneously exposed to different ligands. However, it is often unclear how these extracellular signals are integrated. Neogenin (NEO1) acts as an attractive guidance receptor when the Netrin-1 (NET1) ligand binds, but it mediates repulsion via repulsive guidance molecule (RGM) ligands. Here, we show that signal integration occurs through the formation of a ternary NEO1-NET1-RGM complex, which triggers reciprocal silencing of downstream signaling. Our NEO1-NET1-RGM structures reveal a “trimer-of-trimers” super-assembly, which exists in the cell membrane. Super-assembly formation results in inhibition of RGMA-NEO1-mediated growth cone collapse and RGMA- or NET1-NEO1-mediated neuron migration, by preventing formation of signaling-compatible RGM-NEO1 complexes and NET1-induced NEO1 ectodomain clustering. These results illustrate how simultaneous binding of ligands with opposing functions, to a single receptor, does not lead to competition for binding, but to formation of a super-complex that diminishes their functional outputs

Development, wiring and function of dopamine neuron subtypes

The midbrain dopamine (mDA) system is composed of molecularly and functionally distinct neuron subtypes that mediate specific behaviours and are linked to various brain diseases. Considerable progress has been made in identifying mDA neuron subtypes, and recent work has begun to unveil how these neuronal subtypes develop and organize into functional brain structures. This progress is important for further understanding the disparate physiological functions of mDA neurons and their selective vulnerability in disease, and will ultimately accelerate therapy development. This Review discusses recent advances in our understanding of molecularly defined mDA neuron subtypes and their circuits, ranging from early developmental events, such as neuron migration and axon guidance, to their wiring and function, and future implications for therapeutic strategies

The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections

Mical is a reduction-oxidation (redox) enzyme that functions as an unusual F-actin disassembly factor during Drosophila development. Although three Molecule interacting with CasL (MICAL) proteins exist in vertebrate species, their mechanism of action remains poorly defined and their role in vivo unknown. Here, we report that vertebrate MICAL-1 regulates the targeting of secretory vesicles containing immunoglobulin superfamily cell adhesion molecules (IgCAMs) to the neuronal growth cone membrane through its ability to control the actin cytoskeleton using redox chemistry, thereby maintaining appropriate IgCAM cell surface levels. This precise regulation of IgCAMs by MICAL-1 is essential for the lamina-specific targeting of mossy fibre axons onto CA3 pyramidal neurons in the developing mouse hippocampus in vivo. These findings reveal the first in vivo role for a vertebrate MICAL protein, expand the repertoire of cellular functions controlled through MICAL-mediated effects on the cytoskeleton, and provide insights into the poorly characterized mechanisms underlying neuronal protein cell surface expression and lamina-specific axonal targeting

The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections

Mical is a reduction-oxidation (redox) enzyme that functions as an unusual F-actin disassembly factor during Drosophila development. Although three Molecule interacting with CasL (MICAL) proteins exist in vertebrate species, their mechanism of action remains poorly defined and their role in vivo unknown. Here, we report that vertebrate MICAL-1 regulates the targeting of secretory vesicles containing immunoglobulin superfamily cell adhesion molecules (IgCAMs) to the neuronal growth cone membrane through its ability to control the actin cytoskeleton using redox chemistry, thereby maintaining appropriate IgCAM cell surface levels. This precise regulation of IgCAMs by MICAL-1 is essential for the lamina-specific targeting of mossy fibre axons onto CA3 pyramidal neurons in the developing mouse hippocampus in vivo. These findings reveal the first in vivo role for a vertebrate MICAL protein, expand the repertoire of cellular functions controlled through MICAL-mediated effects on the cytoskeleton, and provide insights into the poorly characterized mechanisms underlying neuronal protein cell surface expression and lamina-specific axonal targeting

An image-based miRNA screen identifies miRNA-135s as regulators of CNS axon growth and regeneration by targeting krüppel-like factor 4

During embryonic development, axons extend over long distances to establish functional connections. In contrast, axon regeneration in the adult mammalian CNS is limited in part by a reduced intrinsic capacity for axon growth. Therefore, insight into the intrinsic control of axon growth may provide new avenues for enhancing CNS regeneration. Here, we performed one of the first miRNome-wide functional miRNA screens to identify miRNAs with robust effects on axon growth. High-content screening identified miR-135a and miR-135b as potent stimulators of axon growth and cortical neuron migration in vitro and in vivo in male and female mice. Intriguingly, both of these developmental effects of miR-135s relied in part on silencing of Krüppel-like factor 4 (KLF4), a well known intrinsic inhibitor of axon growth and regeneration. These results prompted us to test the effect of miR-135s on axon regeneration after injury. Our results show that intravitreal application of miR-135s facilitates retinal ganglion cell (RGC) axon regeneration after optic nerve injury in adult mice in part by repressing KLF4. In contrast, depletion of miR-135s further reduced RGC axon regeneration. Together, these data identify a novel neuronal role for miR-135s and the miR-135–KLF4 pathway and highlight the potential of miRNAs as tools for enhancing CNS axon regeneration

An Image-Based miRNA Screen Identifies miRNA-135s As Regulators of CNS Axon Growth and Regeneration by Targeting Krüppel-like Factor 4

During embryonic development, axons extend over long distances to establish functional connections. In contrast, axon regeneration in the adult mammalian CNS is limited in part by a reduced intrinsic capacity for axon growth. Therefore, insight into the intrinsic control of axon growth may provide new avenues for enhancing CNS regeneration. Here, we performed one of the first miRNome-wide functional miRNA screens to identify miRNAs with robust effects on axon growth. High-content screening identified miR-135a and miR-135b as potent stimulators of axon growth and cortical neuron migration in vitro and in vivo in male and female mice. Intriguingly, both of these developmental effects of miR-135s relied in part on silencing of Krüppel-like factor 4 (KLF4), a well known intrinsic inhibitor of axon growth and regeneration. These results prompted us to test the effect of miR-135s on axon regeneration after injury. Our results show that intravitreal application of miR-135s facilitates retinal ganglion cell (RGC) axon regeneration after optic nerve injury in adult mice in part by repressing KLF4. In contrast, depletion of miR-135s further reduced RGC axon regeneration. Together, these data identify a novel neuronal role for miR-135s and the miR-135–KLF4 pathway and highlight the potential of miRNAs as tools for enhancing CNS axon regeneration

miRNA expression profiles in developing and mature hippocampal neurons.

<p>A–C) Heat maps showing average expression levels of miRNAs in hippocampal neurons during differentiation (6 h, 20 h, 48 h, 3 day and 5 days) compared to mature hippocampal neurons (21 days) in a blue (low relative expression) to yellow (high relative expression) scale. The selection criterion was an average expression value of >50. Using the following threshold signal values >400, 100–400 and 50–100, we subdivided the neuronal miRNAs in mature hippocampal neurons in respectively high (A), intermediate (B) and low expressing levels (C). The mean values were calculated from 4 independent experiments. One of the duplicate probes is shown in the figure D) Expression analysis of miRNAs by qPCR. Higher Ct value means low expression level of the miRNA. The expression of let-7c was changed with time, 6 hours versus 8 days. Single factor ANOVA was performed for statistical significance. Error bars represent standard deviation. ***p<0.0001.</p

miRNA expression profiling following NMDA receptor-dependent synaptic plasticity.

<p>A) Heat map showing relative expression levels of miRNAs in mature hippocampal neurons (21 days) that are significantly changed following 5 min of 200 μM glycine treatment and recovered for 30 min (chemical LTP), 5 min of 50 μM NMDA treatment recovered for 30 min and 2 hours (chemical LTD) compared to non-treated neurons in a green (negative fold-change) to red (positive fold-change) scale. To control for the specificity of the treatments, all glycine en NMDA experiments were also performed in the presence of NMDA receptor inhibitor APV. Selection criteria; absolute fold change value greater than or equal to 1.4 with P<0.01 for NMDA P<0.05 for glycine and expression changes are blocked by APV. B–E) Graphs of relative signal (normalized fold changes) of miRNA expression following glycine and NMDA treatment compared to non-treated mature hippocampal neurons. The blue and red lines indicate the two probes used to detect the expression of indicated miRNAs, which were spotted in duplicate on the LNA array.</p

Timing of the stages of neuronal differentiation.

<p>A) Schematic overview of different stages of the development of hippocampal neurons in culture. Developing hippocampal neurons were harvested at seven indicated time points at basal state and following the induction of neuronal activity using different chemical stimulation protocols. Synaptic activity was blocked with the voltage-gated sodium channel blocker tetrodotoxin (TTX, 2 μM, 48 h) or enhanced with the GABAA receptor antagonist bicuculline (Bicuc, 40 μM, 48 h). Bath application of 50 μM NMDA for 5 min induces “chemical” long-term depression (LTD) and activation of synaptic NMDARs with 200 μM glycine for 5 min triggering “chemical” long-term potentiation (LTP) in cultured neurons. B) Representative images of hippocampal neurons in culture, fixed at the indicated times and stained for the nucleus (DAPI), neuron specific tubulin (tubulin-ßIII), axon marker Tau, dendrite specific protein MAP2 and postsynaptic protein PSD-95. Scale bar, 20 μm C) Western blot analysis of extract from hippocampal neurons in culture for 6 hours (stage 2), 20 hours (stage 3), 4 days (stage 4) and 3 weeks (stage 5) using indicated antibodies. D) Quantification of the percentage of MAP2 and GFAP positive cells in hippocampal neurons culture for 6 hours (stage 2), 20 hours (stage 3), 4 days (stage 4) and 3 weeks (stage 5). Note that in hippocampal culture of 3 weeks, ∼50% of cells are GFAP positive. E) Representative images of hippocampal neurons in culture, fixed at 3 weeks and stained for dendrite specific protein MAP2 and glial fibrillary acidic protein (GFAP), a marker for astrocytes.</p