The use of sample positioning to control defect creation by oxygen plasma in isotopically labelled bilayer graphene membranes

Monolayer and isotopically labelled bilayer graphene membranes were prepared on grids for transmission electron microscopy (TEM). In order to create defects in the graphene layers in a controlled way, we studied the sensitivity of the individual graphene layers to the oxygen plasma treatment. We tested samples with different configurations by varying the order of the transfer of layers and changing the orientation of the samples with respect to the plasma chamber. Using Raman spectroscopy, HRTEM and X-ray photoelectron spectroscopy, we demonstrated defect formation and determined the quantity and chemical composition of the defects. By keeping the sample structure and the setup of the experiment unchanged, the significant role of the sample orientation with respect to the chamber was demonstrated. The effect was accounted for by the variation of the accessibility of the sample surface for the reactive species. Therefore, this effect can be used to control the degree of damage in each layer, resulting in differing numbers of defects present on each side of the sample.

Monolayer and isotopically labelled bilayer graphene membranes were prepared on grids for transmission electron microscopy (TEM).     

Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain

Acid-sensing ion channels (ASICs) are Na⁺-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons co-released with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer''s disease.     

Crosstalk between gut microbiota and antidiabetic drug action

Type 2 diabetes(T2 D) is a disorder characterized by chronic inflated blood glucose levels(hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2 D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin, α-glucosidase inhibitors, glucagon-like peptide-1 agonists,peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2 D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2 D,and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria,responsible for losing weight and suppressing inflammation.     

Ca2+ entry following P2X receptor activation induces IP3 receptor-mediated Ca2+ release in myocytes from small renal arteries

BACKGROUND AND PURPOSE

P2X receptors mediate sympathetic control and autoregulation of the renal circulation triggering contraction of renal vascular smooth muscle cells (RVSMCs) via an elevation of intracellular Ca²⁺ concentration ([Ca²⁺]_i). Although it is well-appreciated that the myocyte Ca²⁺ signalling system is composed of microdomains, little is known about the structure of the [Ca²⁺]_i responses induced by P2X receptor stimulation in vascular myocytes.

EXPERIMENTAL APPROACHES

Using confocal microscopy, perforated-patch electrical recordings, immuno-/organelle-specific staining, flash photolysis and RT-PCR analysis we explored, at the subcellular level, the Ca²⁺ signalling system engaged in RVSMCs on stimulation of P2X receptors with the selective agonist αβ-methylene ATP (αβ-meATP).

KEY RESULTS

RT-PCR analysis of single RVSMCs showed the presence of genes encoding inositol 1,4,5-trisphosphate receptor type 1(IP₃R1) and ryanodine receptor type 2 (RyR2). The amplitude of the [Ca²⁺]_i transients depended on αβ-meATP concentration. Depolarization induced by 10 µmol·L⁻¹αβ-meATP triggered an abrupt Ca²⁺ release from sub-plasmalemmal (‘junctional’) sarcoplasmic reticulum enriched with IP₃Rs but poor in RyRs. Depletion of calcium stores, block of voltage-gated Ca²⁺ channels (VGCCs) or IP₃Rs suppressed the sub-plasmalemmal [Ca²⁺]_i upstroke significantly more than block of RyRs. The effect of calcium store depletion or IP₃R inhibition on the sub-plasmalemmal [Ca²⁺]_i upstroke was attenuated following block of VGCCs.

CONCLUSIONS AND IMPLICATIONS

Depolarization of RVSMCs following P2X receptor activation induces IP₃R-mediated Ca²⁺ release from sub-plasmalemmal (‘junctional’) sarcoplasmic reticulum, which is activated mainly by Ca²⁺ influx through VGCCs. This mechanism provides convergence of signalling pathways engaged in electromechanical and pharmacomechanical coupling in renal vascular myocytes.     

Angiolipoma of the female breast: clinicomorphological correlation of 52 cases

The authors analyzed 52 cases of female breast angiolipoma (AL). Age distribution was 25 to 80 years of age (56.81 ± 12.78). Most cases showed vascularity below 50%, and 14 cases had vascularity >50%. Cellular and low-vascularity ALs had different clinical and radiological presentations. The mean size was 7.00 ± 3.62 mm for cellular ALs and 19.61 ± 7.58 mm for low-vascularity ALs. In any paucicellular area, the authors could identify a cluster of at least 3 interconnected vessels. The endothelium was mostly flat with uniform, hyperchromatic nuclei, and mitoses and nucleoli were absent. Fibrin thrombi in proliferating capillaries were noted in 96% of cases. Low-vascularity AL can be reliably distinguished on needle core biopsy from other lipomatous and vascular tumors of the breast. Tortuosity and proliferation of capillaries with at least 3 interconnected capillary channels in 1 focus with associated fibrin thrombi constitute a very strong clue for the diagnosis of AL on a breast needle core biopsy. Definite diagnosis of cellular AL is not always feasible because of rare cases with mitotic activity and cellular atypia. Excision is often recommended for cellular AL.     

Walker 256 tumor growth in rats with hereditary defect of vasopressin synthesis

Stable deceleration of Walker 256 tumor growth was detected in Brattleboro rats with vasopressin synthesis defect in comparison with normal WAG rats. In contrast to continuous tumor growth typical of rats, the growth of this tumor in Brattleboro rats was negligible and was observed during the first 15–18 days after transplantation, after which the tumor regressed and disappeared. The effect was age-dependent and was more pronounced in old animals. Repeated injection of Walker 256 cells does not lead to tumor development, which attested to direct involvement of the immune system in the detected phenomenon. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 9, pp. 316–318, September, 2006     

Saturation‐recovery metabolic‐exchange rate imaging with hyperpolarized [1‐13C] pyruvate using spectral‐spatial excitation

Within the last decade hyperpolarized [1‐¹³C] pyruvate chemical‐shift imaging has demonstrated impressive potential for metabolic MR imaging for a wide range of applications in oncology, cardiology, and neurology. In this work, a highly efficient pulse sequence is described for time‐resolved, multislice chemical shift imaging of the injected substrate and obtained downstream metabolites. Using spectral‐spatial excitation in combination with single‐shot spiral data acquisition, the overall encoding is evenly distributed between excitation and signal reception, allowing the encoding of one full two‐dimensional metabolite image per excitation. The signal‐to‐noise ratio can be flexibly adjusted and optimized using lower flip angles for the pyruvate substrate and larger ones for the downstream metabolites. Selectively adjusting the excitation of the down‐stream metabolites to 90° leads to a so‐called “saturation‐recovery” scheme with the detected signal content being determined by forward conversion of the available pyruvate. In case of repetitive excitations, the polarization is preserved using smaller flip angles for pyruvate. Metabolic exchange rates are determined spatially resolved from the metabolite images using a simplified two‐site exchange model. This novel contrast is an important step toward more quantitative metabolic imaging. Goal of this work was to derive, analyze, and implement this “saturation‐recovery metabolic exchange rate imaging” and demonstrate its capabilities in four rats bearing subcutaneous tumors. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

New Materials Based on Polyvinylpyrrolidone-Containing Copolymers with Ferromagnetic Fillers

The article investigates the peculiarities of the effect of ferromagnetic fillers (FMFs) of various natures (Ni, Co, Fe, FeCo, SmCo₅) on the formation of the structure and properties of 2-hydroxyethylmethacrylate (HEMA) with polyvinylpyrrolidone (PVP) copolymers. The composites were characterized using FTIR-spectroscopy, SEM, DMTA, magnetometry of vibrating samples, specific electrical resistivity studies, and mechanical and thermophysical studies. The formation of a grafted spatially crosslinked copolymer (pHEMA-gr-PVP) was confirmed and it was established that the FMF introduction of only 10 wt.% into the copolymer formulation increased the degree of crosslinking of the polymer network by three times. The surface hardness of composites increased by 20–25%. However, the water content decreased by 16–18% and lay within 42–43 wt.%, which is a relatively high number. The heat resistance of dry composites was characterized by Vicat softening temperature, which was 39–42 °C higher compared to the unfilled material. It was established that the obtained composites were characterized by a coercive force of 200 kA × m⁻¹ and induction of a magnetic field at the poles of 4–5 mT and 10–15 mT, respectively. The introduction of FMF particles into pHEMA-gr-PVP copolymers, which, in the dry state, are dielectrics, provides them with electrical conductivity, which was evaluated by the specific volume resistance. Depending on the FMF nature and content, as well as their orientation in the magnetic field, the resistance of filled materials could be regulated within 10²–10⁶ Ohm·m. Therefore, the modification of HEMA with PVP copolymers by ferromagnetic fillers of various natures provides the possibility of obtaining materials with unique predicted properties and expands the fields of their use, for instance as magnetic sorbents for various applications, as well as the possibilities associated with their being electrically conductive materials that can respond by changing of electrical conductivity, depending on various factors.     

Thyroid stimulating hormone levels and BRAFV600E mutation contribute to pathophysiology of papillary thyroid carcinoma: Relation to outcomes?

AimsThe aim of this study was to evaluate the relation between the level of thyroid stimulating hormone (TSH) and progression of papillary thyroid carcinoma (PTC) with or without BRAF^V600E mutation.MethodsThe medical records and laboratory data of 547 patients with PTC and 94 patients with follicular adenoma (FA) were collected. The relationship between hormones levels and such end-points as extrathyroid extension (ETE), lymphovascular invasion (LVI) and lymph node metastasis (LNM) was assessed. In addition, age, gender, BRAF^V600E mutation status, histological type and Hashimoto’s thyroiditis (HT) were considered.Key findingsMost of the patients with PTC had hormones levels within the normal range, however, serum TSH concentration was significantly higher in PTC comparing with FA (P = 0.022). High levels of TSH in PTC were more frequent among women rather than men (P = 0.03) due to the gender differences in coexisting HT rate (P = 0.003). In contrast, LNM rate was higher in men (P = 0.0014). Coexisting HT significantly decreased the risk of ETE (OR = 0.67; 95%CI 0.44–1.00; P = 0.05) and LNM (OR = 0.59; 95%CI 0.37?0.94; P = 0.028) among males with PTC. However, there was no significant relationship between HT and PTC-related ETE and LNM in females. BRAF^V600E mutation was associated with presence of lymphocytic infiltration (P < 0.001) but not with HT (P = 0.08) and violation of thyroid function.ConclusionThe present study showed the lack of significant relationship between TSH levels and PTC aggressiveness (LNM, TNM stage, BRAF^V600E mutation). Higher TSH levels were found in patients with coexisting HT that was associated with female sex and multifocality of PTC.