Advancing Age Alters the Contribution of Calcium Release From Smooth Endoplasmic Reticulum Stores in Superior Cervical Ganglion Cells

In superior cervical ganglion (SCG) neurons calcium-induced calcium release (CICR), mediated by ryanodine receptors (RyRs), contributes to stimulation-evoked intracellular calcium ([Ca2+]i) transients. Hypothesis: The contribution of CICR to electrical field stimulation (EFS)–evoked [Ca2+]i transients in SCG cells declines with senescence and may be partially recovered in the presence of caffeine. We measured EFS-evoked [Ca2+]i transients in isolated fura-2–loaded SCG cells from Fischer-344 rats aged 6, 12, and 24 months with either the RyR antagonist ryanodine to block the contribution of CICR to [Ca2+]i transients or caffeine to sensitize CICR to EFS. EFS-evoked [Ca2+]i transients increased from 6 to 12 months and declined at 24 months and ryanodine decreased [Ca2+]i transients in SCG cells from 6- and 12-month-old animals only. Caffeine significantly increased EFS-evoked [Ca2+]i transients in all age groups. These data suggest that CICR declines with senescence and residual CICR function may be reclaimed in senescent cells with caffeine

Глобализация как фактор радикализации трансформации приоритетов социально-экономического развития в посттранзитивних экономиках

Expression of the for khead transcription factor FOXP1 is essential for early B-cell development, whereas down regulation ofFOXP1at the germinal center (GC) stage is required for GC B-cell function. Aberrantly high FOXP1 expression is frequently observed in diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma, being associated with poor prognosis. Here, by gene expression analysis upon ectopic over expression of FOXP1 in primary

Transcriptional Silencing of the Wnt-Antagonist DKK1 by Promoter Methylation Is Associated with Enhanced Wnt Signaling in Advanced Multiple Myeloma

The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology

Adrenomedullin and tumour microenvironment

Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed

Photoreduction of carbon dioxide with hydrogen using temperature programmed method

The photocatalytic reduction of carbon dioxide with hydrogen was studied by Temperature-Programmed Surface Reaction (TPSR). This process was carried out in a flow reactor that was especially designed and constructed for this purpose. Titanium dioxide (TiO2, Degussa P-25) was used as supports for platinum, ruthenium and nickel catalysts. The experimental results indicated that the activity of photoreduction of CO2 changes as follows: Ru/TiO2> Ni/TiO2>= Pt/TiO2> TiO2

Photoreduction of carbon dioxide with hydrogen using temperature programmed method

The photocatalytic reduction of carbon dioxide with hydrogen was studied by Temperature-Programmed Surface Reaction (TPSR). This process was carried out in a flow reactor that was especially designed and constructed for this purpose. Titanium dioxide (TiO2, Degussa P-25) was used as supports for platinum, ruthenium and nickel catalysts. The experimental results indicated that the activity of photoreduction of CO2 changes as follows: Ru/TiO2> Ni/TiO2>= Pt/TiO2> TiO2

Nuclear magnetic resonance study of magnetic phase segregation in La1-xCaxMnO3

A Mn-55 nuclear magnetic resonance (NMR) study of the La1-xCaxMnO3 system, 0 &lt; x &lt; 1, is reported. For x &lt; 0.3 and x &gt; 0.5 the spin echo spectra contain resonance lines corresponding to both the microscopic ferromagnetic and antiferromagnetic regions. A resonance line near 380 MHz, which is similar to that of the spectrum of the ferromagnetic and metallic compounds (0.2 &lt; x &lt; 0.5) is observed for all x. This indicates the presence of clusters in which the Mn magnetic moments are double exchange coupled in the whole range of doping. Their hyperfine field exhibits a much weaker temperature dependence than that of the lines of the host. This reveals the greater strength of the magnetic coupling within the clusters than in the antiferromagnetic regions and indicates a weak magnetic coupling of the clusters to the host matrix. A comparison with the NMR results on the hole doped nonstoichiometric compounds, LaMnO3+delta is made. The temperature dependence of the line intensities corresponding to the double exchange clusters and to the host matrix is attributed to the evolution of the magnetic phases in the compounds. (C) 2000 American Institute of Physics. [S0021-8979(00)66908-6].</p

A Mn-55 nuclear magnetic resonance study of mixed-valence manganites

The temperature dependence of the Mn-55 nuclear magnetic resonance of some manganese perovskites of the form [La(1-x)A(x)]MnO3 (A = Ca, Sr) for x of 1/3 is reported. The Mn-55 spin-echo spectra were measured in zero field and in an applied magnetic field up to 6 T for polycrystalline samples of [La0.67-yTbyCa0.33]MnO3 (y = 0, 0.1, 0.22), [La0.6Y0.07Ca0.33]MnO3 and [La0.7Sr0.3]MnO3. The single resonance line observed for all compounds, for temperatures between 4.2 K and 293 K, is attributed to a fast carrier motion (&lt;10(-9) s) between the Mn3+ and Mn4+ sites resulting from the double-exchange mechanism. For some of the samples the zero-field nuclear magnetic resonance signal has been detected at temperatures far above the magnetic ordering temperature, providing direct evidence of magnetic correlations whose lifetime is greater than 10(-5) s. The correlations can possibly be related to magnetic polarons.</p