Many plants release airborne volatile compounds in response to wounding due to pathogenic assault. These compounds serve as plant defenses and are involved in plant signaling. Here, we study the ...effects of pectin methylesterase (PME)-generated methanol release from wounded plants ("emitters") on the defensive reactions of neighboring "receiver" plants. Plant leaf wounding resulted in the synthesis of PME and a spike in methanol released into the air. Gaseous methanol or vapors from wounded PME-transgenic plants induced resistance to the bacterial pathogen Ralstonia solanacearum in the leaves of non-wounded neighboring "receiver" plants. In experiments with different volatile organic compounds, gaseous methanol was the only airborne factor that could induce antibacterial resistance in neighboring plants. In an effort to understand the mechanisms by which methanol stimulates the antibacterial resistance of "receiver" plants, we constructed forward and reverse suppression subtractive hybridization cDNA libraries from Nicotiana benthamiana plants exposed to methanol. We identified multiple methanol-inducible genes (MIGs), most of which are involved in defense or cell-to-cell trafficking. We then isolated the most affected genes for further analysis: β-1,3-glucanase (BG), a previously unidentified gene (MIG-21), and non-cell-autonomous pathway protein (NCAPP). Experiments with Tobacco mosaic virus (TMV) and a vector encoding two tandem copies of green fluorescent protein as a tracer of cell-to-cell movement showed the increased gating capacity of plasmodesmata in the presence of BG, MIG-21, and NCAPP. The increased gating capacity is accompanied by enhanced TMV reproduction in the "receivers". Overall, our data indicate that methanol emitted by a wounded plant acts as a signal that enhances antibacterial resistance and facilitates viral spread in neighboring plants.
The current study investigated the features of cross-cultural recognition of four basic emotions "joy-neutral (calm state)-sad-anger" in the spontaneous and acting speech of Indian and Russian ...children aged 8-12 years across Russian and Tamil languages. The research tasks were to examine the ability of Russian and Indian experts to recognize the state of Russian and Indian children by their speech, determine the acoustic features of correctly recognized speech samples, and specify the influence of the expert's language on the cross-cultural recognition of the emotional states of children. The study includes a perceptual auditory study by listeners and instrumental spectrographic analysis of child speech. Different accuracy and agreement between Russian and Indian experts were shown in recognizing the emotional states of Indian and Russian children by their speech, with more accurate recognition of the emotional state of children in their native language, in acting speech vs spontaneous speech. Both groups of experts recognize the state of anger via acting speech with the high agreement. The difference between the groups of experts was in the definition of joy, sadness, and neutral states depending on the test material with a different agreement. Speech signals with emphasized differences in acoustic patterns were more accurately classified by experts as belonging to emotions of different activation. The data showed that, despite the universality of basic emotions, on the one hand, the cultural environment affects their expression and perception, on the other hand, there are universal non-linguistic acoustic features of the voice that allow us to identify emotions via speech.
SDF-1α/CXCR4 signaling plays a key role in leukemia/bone marrow microenvironment interactions. We previously reported that bone marrow–derived stromal cells inhibit chemotherapy-induced apoptosis in ...acute myeloid leukemia (AML). Here we demonstrate that the CXCR4 inhibitor AMD3465 antagonized stromal-derived factor 1α (SDF-1α)–induced and stroma-induced chemotaxis and inhibited SDF-1α–induced activation of prosurvival signaling pathways in leukemic cells. Further, CXCR4 inhibition partially abrogated the protective effects of stromal cells on chemotherapy-induced apoptosis in AML cells. Fetal liver tyrosine kinase-3 (FLT3) gene mutations activate CXCR4 signaling, and coculture with stromal cells significantly diminished antileukemia effects of FLT3 inhibitors in cells with mutated FLT3. Notably, CXCR4 inhibition increased the sensitivity of FLT3-mutated leukemic cells to the apoptogenic effects of the FLT3 inhibitor sorafenib. In vivo studies demonstrated that AMD3465, alone or in combination with granulocyte colony-stimulating factor, induced mobilization of AML cells and progenitor cells into circulation and enhanced antileukemic effects of chemotherapy and sorafenib, resulting in markedly reduced leukemia burden and prolonged survival of the animals. These findings indicate that SDF-1α/CXCR4 interactions contribute to the resistance of leukemic cells to signal transduction inhibitor– and chemotherapy-induced apoptosis in systems mimicking the physiologic microenvironment. Disruption of these interactions with CXCR4 inhibitors represents a novel strategy of sensitizing leukemic cells by targeting their protective bone marrow microenvironment.
The goal of the study is to investigate a correlation between different levels of speech organization, indicating the physiological processes of maturation of the vocal tract structures and brain ...regions associated with speech and language, and basic electroencephalogram (EEG) rhythms, reflecting the age-related dynamics of maturation of brain structures in children aged 4-11 years. The complex method of analysis, including EEG registration, clinical and spectral analysis of EEG; dichotic listening, identifying the profile of functional lateral asymmetry (PFLA), and phonemic hearing of the child; recording, linguistic, and acoustic analysis of child speech; and identification of speech characteristics reflecting the formation of its different levels, was used. Two complementary experimental series were conducted: the correlation between EEG parameters, speech features, dichotic listening, the PFLA, and phonemic hearing of the child in the age dynamics of 4-11 years (first); the specificity of EEG patterns in children at different stages of reading skills formation (second). The result of this study showed the correlation between acoustic and linguistic features of child speech and brain activity. The analysis of EEG and acoustic features of child speech revealed the correlation between pitch and pitch range values in spontaneous speech and theta-rhythm intensity in EEG. High values of pitch and its variation in younger children (4-6 years) are related to the intensity of theta rhythm in the EEG pattern, as this rhythm is most expressed in younger children. It was revealed that the alpha rhythm is asymmetrically localized in children with clear pronunciation of words (which determines the intelligibility of their speech) that is typical for 6.5- to 11-year-old children. The formation of reading skills in a child is associated with a change in the characteristics of the alpha rhythm-from irregular, unstable, low frequency, and low amplitude in children at the beginning of reading skills mastering to medium and low amplitude, regular, asymmetrically localized in children reading words and phrases. The specifics of the relation between brain activity and different levels of speech formation at different child's age periods are discussed.
Lipopolysaccharide (LPS) is one of the main constituents of the cell wall of gram-negative bacteria. As an endotoxin, LPS induces neuroinflammation, which is associated with the blood-brain barrier ...impairment. Lactate is a metabolite with some significant physiological functions within the neurovascular unit/blood-brain barrier (BBB). Accumulation of extracellular and cerebrospinal fluid lactate is a specific feature of bacterial meningitis. However, the role of lactate production, transport, and sensing by lactate receptors GPR81 in the pathogenesis of bacterial neuroinflammation is still unknown.
In this study, we analyzed effects of LPS on the expression of GPR81 and MCT-1 and proliferation of cerebral endothelial cells in the BBB model in vitro. We used molecular profiling methods to measure the expression of GPR81, MCT-1, IL-1β, and Ki67 in the cerebral endothelium after treatment with different concentrations of LPS followed by measuring the level of extracellular lactate, transendothelial electric resistance, and permeability of the endothelial cell layer.
Our findings showed that exposure to LPS results in neuroinflammatory changes associated with decreased expression of GPR81 and MCT-1 in endothelial cells, as well as overproduction of IL-1β and elevation of lactate concentrations in the extracellular space in a dose-dependent manner. LPS treatment reduced JAM tight junction protein expression in cerebral endothelial cells and altered BBB structural integrity in vitro.
The impairment of lactate reception and transport might contribute to the alterations of BBB structural and functional integrity caused by LPS-mediated neuroinflammation.
Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a ...humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells.
We describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells.
We conclude that PMT is active in suppression of cell proliferation and tumor growth.
The Great Altai region, located at the boundary of Russia, Mongolia, China, and Kazakhstan, belongs to the system of the Central Asian Orogenic Belt. It has undergone a long complex geological and ...metallogenic history. Extremely rich resources of base, precious, and rare metals (Fe, Cu, Pb, Zn, Ag, Au, Li, Cs, Ta, Nb, REE, etc.) maintain developed mining and metallurgical industry, especially in East Kazakhstan, which is the key metallogenic province. The East Kazakhstan province comprises the Rudny Altai, Kalba-Narym, West-Kalba, and Zharma-Saur metallogenic belts, each having its typical mineralization profiles and deposits. The reconstructed geodynamic and metallogenic history of the Great Altai province, along with the revealed relationships between tectonic settings and mineralization patterns, allowed us to formulate a number of geodynamic, structural, lithostratigraphic, magmatic, mineralogical, and geochemical criteria for exploration and appraisal of mineral potential in Eastern Kazakhstan. Geodynamic criteria are based on the origin of different mineralization types in certain geodynamic settings during the Late Paleozoic–Early Mesozoic orogenic cycle. Structural criteria mean that the location of base-metal deposits in Rudny Altai, gold deposits in the West Kalba belt, rare and base metals in the Kalba-Narym and Zharma-Saur zones is controlled by faults of different sizes. Lithostratigraphic criteria consist of the relation of orebodies with certain types of sedimentary or volcanic-sedimentary rocks. Magmatic criteria are due to the relation between mineralization types and igneous lithologies. Mineralogical and geochemical criteria include typical minerals and elements that can serve as tracers of mineralization. The joint use of all these criteria will open new avenues in prospecting and exploration at a more advanced level.
This paper represents the results of a study of the chemical composition of salt lakes within the Burabay rock mass in eastern Kazakhstan. We sampled water and bottom deposits, geochemically analyzed ...the composition of the salt lakes, and performed aerial photography of the lakes to geometrize them. We studied the linkage between the rare-metal mineralization of granites of the Burabay rock mass and the salt lakes within the territory. Based on the obtained data, we identified the prospects of the survey area for rare metals. The surveys included 15 water samples and 15 bottom-deposit samples. To identify the source of salt in the lake water and deposits, the chemical composition of Burabay rocks was analyzed and seven samples of coarse-grained and porphyritic granites were selected. It was established that the water and bottom deposits accumulated elevated concentrations of valuable components (i.e., Sr, Rb, and U); this fact may be considered as an argument for conducting special surveys of small lakes in the region. The results obtained can be used for conducting further explorations and mining operations in the survey area in order to revive the rare-metal industry in the region, which will allow the development of new high-tech production and the creation of new jobs in this sphere.
Detecting and understanding emotions are critical for our daily activities. As emotion recognition (ER) systems develop, we start looking at more difficult cases than just acted adult audio–visual ...speech. In this work, we investigate the automatic classification of the audio–visual emotional speech of children, which presents several challenges including the lack of publicly available annotated datasets and the low performance of the state-of-the art audio–visual ER systems. In this paper, we present a new corpus of children’s audio–visual emotional speech that we collected. Then, we propose a neural network solution that improves the utilization of the temporal relationships between audio and video modalities in the cross-modal fusion for children’s audio–visual emotion recognition. We select a state-of-the-art neural network architecture as a baseline and present several modifications focused on a deeper learning of the cross-modal temporal relationships using attention. By conducting experiments with our proposed approach and the selected baseline model, we observe a relative improvement in performance by 2%. Finally, we conclude that focusing more on the cross-modal temporal relationships may be beneficial for building ER systems for child–machine communications and environments where qualified professionals work with children.
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