Introduction
. There is a problem in predicting the efficacy and safety of antipsychotic therapy. Dopamine receptor D1 is one of the targets of antipsychotics. Peripheral blood lymphocytes (PBL) are ...the research object of neurotransmission receptors.
The objective
was to study DRD1 gene expression (mRNA, protein level) in PBL as a possible biomarker of olanzapine and haloperidol therapy prognosis.
Methods and Materials
. Sample: 106 patients diagnosed with schizophrenic spectrum disorder. Study design: prospective longitudinal follow-up with drug administration by randomization. Assessment of mental status and development of Parkinsonism: Positive and Negative Syndrome Scale (PANSS) and Simpson-Agnus Scale (SAS), respectively. PBL was study material. DRD1 mRNA level was determined by real-time PCR. DRD1 protein concentration in PBL was measured by enzyme immunoassay.
Results
. Haloperidol (but not olanzapine) treatment for 28 days, leads to DRD1 protein concentration decrease in PBL in a manner dependent on its initial level. DRD1 mRNA level in PBL remained unchanged during the treatment. Patients with effective therapy by olanzapine had lower DRD1 mRNA levels. Side effects of the therapy (Parkinsonism, weight gain) were not associated with studied DRD1 parameters.
Conclusions
. Haloperidol treatment leads to a decrease of DRD1 protein concentration in PBL, which depends on the initial protein level. Effective olanzapine therapy is associated with reduced DRD1 mRNA level in PBL before the treatment.
Mitophagy is critical for cell homeostasis. Externalization of the inner mitochondrial membrane phospholipid, cardiolipin (CL), to the surface of the outer mitochondrial membrane (OMM) was identified ...as a mitophageal signal recognized by the microtubule-associated protein 1 light chain 3. However, the CL-translocating machinery remains unknown. Here we demonstrate that a hexameric intermembrane space protein, NDPK-D (or NM23-H4), binds CL and facilitates its redistribution to the OMM. We found that mitophagy induced by a protonophoric uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), caused externalization of CL to the surface of mitochondria in murine lung epithelial MLE-12 cells and human cervical adenocarcinoma HeLa cells. RNAi knockdown of endogenous NDPK-D decreased CCCP-induced CL externalization and mitochondrial degradation. A R90D NDPK-D mutant that does not bind CL was inactive in promoting mitophagy. Similarly, rotenone and 6-hydroxydopamine triggered mitophagy in SH-SY5Y cells was also suppressed by knocking down of NDPK-D. In situ proximity ligation assay (PLA) showed that mitophagy-inducing CL-transfer activity of NDPK-D is closely associated with the dynamin-like GTPase OPA1, implicating fission-fusion dynamics in mitophagy regulation.
Pliocardiines (Bivalvia: Vesicomyidae: Pliocardiinae) are a chemosymbiotrophic group of bivalve mollusks that are obligate for reducing environments. These mollusks house endosymbiotic ...thioautotrophic bacteria in their gills, which provide nutrition for the host. The ultrastructure of spermatozoa and the state of the gonads in the pliocardiine bivalve
Calyptogena pacifica
in June 2016 were studied. Material was collected in the Bering Sea on the slopes of the Piip’s Volcano at a depth of 466 m. The condition of the gonads indicated a pre-spawning state. Active processes of spermatogenesis and oogenesis were noted in the gonads. The mature spermatozoon has an elongated bullet-shaped head with an average length of 4 ± 0.2 μm from the tip of the acrosome to the base of the mid-piece. The mid-piece was formed by a complex of four spherical mitochondria with a diameter of approximately 0.7 μm. An electron dense material of a lipid nature was observed in the distal region of the mid-piece of the sperm.
C.
pacifica
mature eggs are approximately 200 μm in diameter. The results are discussed in the context of the available data on the morphology of pliocardiine gametes.
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that are crucial for the regulation of immune responses in cancer. These cells contribute to ...the failure of cancer therapies and are associated with poor clinical outcomes. Despite recent advances in the understanding of PMN-MDSC biology, the mechanisms responsible for the pathological activation of neutrophils are not well defined, and this limits the selective targeting of these cells. Here we report that mouse and human PMN-MDSCs exclusively upregulate fatty acid transport protein 2 (FATP2). Overexpression of FATP2 in PMN-MDSCs was controlled by granulocyte-macrophage colony-stimulating factor, through the activation of the STAT5 transcription factor. Deletion of FATP2 abrogated the suppressive activity of PMN-MDSCs. The main mechanism of FATP2-mediated suppressive activity involved the uptake of arachidonic acid and the synthesis of prostaglandin E
. The selective pharmacological inhibition of FATP2 abrogated the activity of PMN-MDSCs and substantially delayed tumour progression. In combination with checkpoint inhibitors, FATP2 inhibition blocked tumour progression in mice. Thus, FATP2 mediates the acquisition of immunosuppressive activity by PMN-MDSCs and represents a target to inhibit the functions of PMN-MDSCs selectively and to improve the efficiency of cancer therapy.
This work is devoted to study of the diamond based radiation detectors. Experiments were carried out with two types of detectors: based on a thin diamond film and on a composite diamond plate. The ...following types of ionizing radiation has been used in experiments: beta radiation of 90Sr - 90Y, fission fragments and alpha particles of 252Cf, and Kr ions obtained at the particle accelerator. It is shown that the developed thin-film diamond based detector effectively registers heavy charged particles, whereas beta, neutron and gamma radiation does not give a significant contribution to the detector signals. Those type of detectors are proposed for measurement of heavy charged particles linear energy transfer in diamond. The multilayer diamond based detector (detector with a composite diamond plate) showed improved charge collection efficiency values in compare with the detection with a single diamond plate.
We have studied the gamma sensitivity of single-crystal CVD diamond neutron detectors using a
252
Cf neutron source placed in a moderator. It has been shown that a major contribution to the count ...rate of the detectors is made by the gamma rays from the source. We have compared the count rates of a detector with a
10
B boron isotope-based slow-neutron converter and without it. With allowance for the theoretically calculated detection efficiency, the difference between the count rates is consistent with the fraction of slow neutrons measured using a scintillation detector.
In this work we study influence of various factors on stability of ionizing radiation detectors installed in the cosmic ray spectrometer (SCR) based on diamond detectors of ionization radiation ...(DDIR). Diamond detectors for SCR are made of single crystals of synthetic diamond type IIa. Diamond detectors were studied successively in three different experiments. Checking detector stability with ambient temperature increased up to 70 degrees Celsius was the first experiment. At next we change the geometry of detector irradiation by rotating nuclear source around it and measuring changes in detector count rate. And last one experiment was about checking the phenomenon of polarization by prolonged detector irradiation by ionizing radiation of various types and energies. The study revealed the presence of the strong influence of the polarization effect on the work of diamond detectors for registration of ionizing particles with short mean free path (in our experiment they were the alfa-particles of 238Pu). In this work correspondence of the experimental results of the "rotation" the source around the detector with the data obtained by simulation in GEANT-4 was shown.
We comment on phase selection of the scattering amplitude, emphasizing that the elastic overlap function should have a central impact parameter profile at high energies and highlighting the role of ...the reflective scattering mode at the LHC energies. Emerging problems with the use of peripheral impact parameter dependence of the elastic overlap function are explicitly indicated. Their solution is an elimination of the phases connected to peripheral form of the elastic overlap function. Contrary, we adhere to a relative peripheral form of the inelastic overlap function with an additional new feature of a maximum at nonzero value of the impact parameter at the highest energies. Phenomenologically, the dynamics of hadron scattering is motivated by a hadron structure with a hard central core presence.
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