The effect of the anhydrous composition on the solubilities of H2O and CO2 in mafic melts varying from MORB to nephelinite was investigated experimentally between 50 and 500MPa at 1200 to 1250°C. In ...all compositions, CO2 is only present as carbonate species in the quenched glasses. The concentrations of dissolved H2O and CO2 have been analyzed by KFT (Karl–Fischer titration) and FTIR (Fourier-transform infrared spectroscopy). The Mid-Infrared (MIR) absorption coefficients for the H2O band at 3500cm−1 are identical within error for all investigated melt compositions and equal to 59.2±4L/(mol∗cm). The absorption coefficients for the carbonate bands vary in the range 306±32 to 360±24L/(mol∗cm) for the 1430cm−1 band and in the range 349±25 to 394±27L/(mol∗cm) for the 1520cm−1 band. However, a simple correlation with the melt composition could not be determined.
Water solubility in mafic to intermediate melts increases slightly with the total alkali content and the effect of composition is more pronounced at higher pressures. At 500MPa, the solubility of H2O in melts coexisting with nearly pure H2O fluids varies from 8.8 to 9.5wt.% H2O. A strong effect of melt composition on the solubility of CO2 is observed at all investigated pressures. For instance, at 500MPa, mafic melts coexisting with nearly pure CO2 fluids can dissolve from around 0.32 to more than 1.30wt.% CO2 as melt composition changes from tholeiite to nephelinite. The compositional effect on the solubility of CO2 in melts coexisting with pure CO2 fluid is best described by non-linear (exponential) correlations with compositional parameters such as the parameter Π proposed by Dixon (1997; American Mineralogist, 82: 368–378) or structural parameters (e.g., nonbridging oxygen per tetrahedrally coordinated cation). The obtained relationships are used to propose empirically derived equations of the form ln(CO2)=1.150·lnP+6.71·Π*−1.345, where CO2 is the solubility of CO2 in silicate melts in wt.% (at 1200 to 1250°C), P is pressure in MPa and Π* is a compositional parameter (Π*=Ca2++0.8K++0.7Na++0.4Mg2++0.4Fe2+)/(Si4++Al3+) with cations expressed as cation fractions in melt.
•New H2O–CO2 solubility experiments for mafic melts at 50–500MPa were performed.•New absorption coefficients for H2O at 3500cm−1 and CO32− at 1430cm−1 and 1520cm−1 were determined.•Effect of melt composition on solubilities of H2O and CO2 was investigated.•H2O solubility in mafic to intermediate melts increases with K+Na and SiO2 in melt.•CO2 solubility in mafic melts is exponential function of complex compositional parameter Π*.
The study was designed to assess the usefulness of routine electrocardiography (ECG) as well as transthoracic echocardiography (TTE) in screening top level endurance athletes. An additional goal was ...to attempt to identify factors determining occurrence of adaptive and abnormal changes in ECG and TTE. The retrospective analysis included basic medical data, ECG and TTE results of 262 athletes (123 rowers, 32 canoeists and 107 cyclists), members of the Polish National Team. The athletes were divided into two age groups: young (≤ 18 years; n = 177) and elite (> 18 years; n = 85). ECG and TTE measurements were analysed according to the International Recommendations from 2017 and 2015, respectively. Adaptive ECG changes were found in 165 (63%) athletes. Abnormal ECG changes were identified in 10 (3.8%) athletes. 98% of athletes exceeded TTE norms for the general population and 26% exceeded norms for athletes. The occurrence of both adaptive ECG findings and abnormalities in the TTE (in norms for athletes) was strongly associated with the years of training, hours of training per week and the age of the athlete. Male gender and the years of training were independent predictors of the ECG and TTE findings. Abnormal ECG changes were not related to the time of sport. Among 10 athletes with ECG changes, only 3 had changes in TTE and no relationship was found between abnormal finding in ECG and TTE (p = 0.45). ECG and TTE screening complement each other in identifying endurance athletes requiring treatment or verification. Unlike abnormal ECG changes, adaptive ECG changes and TTE abnormalities are strongly related to the training duration, which reflects physiological adaptation of the heart to physical exertion in high endurance athletes.
Alzheimer’s disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell ...(iPSC)-derived neurons carrying the familial AD
APP
V717I
mutation after cell injection into the mouse forebrain.
APP
V717I
mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aβ
42
production, elevated phospho-tau, and impaired neurite outgrowth in APP
V717I
neurons. Two months after transplantation, APP
V717I
and control neural cells showed robust engraftment but at 12 months post-injection, APP
V717I
grafts were smaller and demonstrated impaired neurite outgrowth compared to controls, while plaque and tangle pathology were not seen. Single-nucleus RNA-sequencing of micro-dissected grafts, performed 2 months after cell injection, identified significantly altered transcriptome signatures in APP
V717I
iPSC-derived neurons pointing towards dysregulated synaptic function and axon guidance. Interestingly, APP
V717I
neurons showed an increased expression of genes, many of which are also upregulated in postmortem neurons of AD patients including the transmembrane protein LINGO2. Downregulation of LINGO2 in cultured APP
V717I
neurons rescued neurite outgrowth deficits and reversed key AD-associated transcriptional changes related but not limited to synaptic function, apoptosis and cellular senescence. These results provide important insights into transcriptional dysregulation in xenografted APP
V717I
neurons linked to synaptic function, and they indicate that LINGO2 may represent a potential therapeutic target in AD.
Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to ...neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, which we further characterized by single nucleus RNA sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.
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•Postmortem and iPSC-derived FTD neurons upregulate inflammatory genes, including SPP1•FTD neurons show mitochondrial phenotypes partially rescued by SPP1 knockdown•Grafted FTD neurons show impaired cell survival and elevate reactive gliosis•Knockdown of SPP1 in FTD neurons improves engraftment and reactive gliosis
Hargus and colleagues demonstrate that iPSC-derived FTD neurons and human postmortem FTD neurons show phenotypes related to mitochondrial function and neuroinflammation, including an upregulation of osteopontin. Transplanted FTD neurons show impaired survival and elicit an increased microglial response, which is partially rescued by downregulation of osteopontin in transplanted cells.
Summary
Esophageal atresia (EA) is a congenital defect of the esophagus involving the interruption of the esophagus with or without connection to the trachea (tracheoesophageal fistula TEF). EA/TEF ...may occur as an isolated anomaly, may be part of a complex of congenital defects (syndromic), or may develop within the context of a known syndrome or association. The molecular mechanisms underlying the development of EA are poorly understood. It is supposed that a combination of multigenic factors and epigenetic modification of genes play a role in its etiology.
The aim of our work was to assess the human gene expression microarray study in esophageal tissue samples. Total RNA was extracted from 26 lower pouches of esophageal tissue collected during thoracoscopic EA repair in neonates with the isolated (IEA) and the syndromic form (SEA).
We identified 787 downregulated and 841 upregulated transcripts between SEA and controls, and about 817 downregulated and 765 upregulated probes between IEA and controls. Fifty percent of these genes showed differential expression specific for either IEA or SEA. Functional pathway analysis revealed substantial enrichment for Wnt and Sonic hedgehog, as well as cytokine and chemokine signaling pathways. Moreover, we performed reverse transcription polymerase chain reaction study in a group of SHH and Wnt pathways genes with differential expression in microarray profiling to confirm the microarray expression results. We verified the altered expression in SFRP2 gene from the Wnt pathway as well as SHH, GLI1, GLI2, and GLI3 from the Sonic hedgehog pathway. The results suggest an important role of these pathways and genes for EA/TEF etiology.
The aim of this study was to determine the relationship between the degree of cardiorespiratory fitness and the function of the right ventricle (RV). 117 rowers, age 17.5±1.5 years. All subjects ...underwent cardiopulmonary exercise. Standard echocardiography and 2D speckle tracking echocardiography with evaluation of longitudinal strain in each segment of the RV (basal - RVLS-B; mid - RVLS-M, apical - RVLS-A) and global RV free-wall strain (RVLS-G) were performed. RVLS-B values were lower compared to the RVLS-M (-25.8±4.4 vs -29.3±3.5; p<0.001) and RVLS-A values (-25.8±4.4 vs -26.2±3.4; p=0.85). Correlations between VO
max and RVLS were observed in men: RVLS-G strain (r = 0.43; p <0.001); RVLS-B (r = 0.30; p = 0.02); RVLS-M (r = 0.38; p = 0.02). A similar relationship was not observed in the group of women. The strongest predictors corresponding to a change in global and basal strain were VO
max and training time: RVLS-G (VO
max: β = 0.18, p = 0.003; training time: β = -0.39; p = 0.02) and RVLS-B (VO
max: β = 0.23; p = 0.0001 training time: β = -1.16; p = 0.0001). The global and regional reduction of RV systolic function positively correlates with the level of fitness, and this relationship is observed already in young athletes. The character of the relationship between RV deformation parameters and the variables that determine the physical performance depend on gender. The dependencies apply to the proximal fragment of the RV inflow tract, which may be a response to the type of flow during exercise in endurance athletes.
The Ministry of Health in Poland recommends electrocardiogram (ECG)-based cardiovascular screening in athletes, but so far there has been a lack of guidelines on preparticipation assessment. We ...compared different criteria of ECG screening assessment in a group of top-level athletes.
The aims were to evaluate the prevalence of ECG changes in athletes that necessitate further cardiological work-up according to three criteria in various age groups as well as to identify factors determining the occurrence of changes related and unrelated to the training.
262 high-dynamic, high-static Polish athletes (rowers, cyclists, canoeists) were divided into two age categories: young (≤ 18 years of age; n = 177, mean age 16.9 ± 0.8; 15-18 years) and elite (> 18 years of age; n = 85, mean age 22.9 ± 3.4; 19-34 years). All sports persons had a 12-lead ECG performed and evaluated according to 2010 European Society of Cardiology (ESC) recommendations, 2012 Seattle criteria, and 2014 Refined criteria.
The Refined criteria reduced (p < 0.001) the number of training-unrelated ECG findings to 8.0% vs. 12.6% (Seattle criteria) and 30.5% (ESC recommendations). All three criteria revealed more training-related changes in the group of older athletes (76.5% vs. 55.9%, p = 0.001). Predictors that significantly (p < 0.005) affected the occurrence of adaptive changes were the age of the athlete, training duration (in years), and male gender.
1. The ESC criteria identified a group of athletes that was unacceptably large, as for the screening test, requiring verification with other methods (every fourth athlete). 2. The use of the Refined criteria helps to significantly reduce the frequency and necessity for additional tests. 3. The dependence of adaptive changes on training duration and athletes' age confirms the benign nature of those ECG findings.
Background The first reports on the differences in glycosylation, which may negatively affect the antibody function, came from the studies on rheumatoid arthritis (RA), and specifically, the ...occurrence of glycoform G0 (no galactose) 1. The increase of agalactosylated IgG in patients with other diseases (juvenile arthritis, Crohn’s disease) 2 was also found. It is known, that the percentage of IgG agalactosyled N-glycans in RA increases with the disease progress, and returns to normal in the remission phase; both features were confirmed in the previous studies conducted in our laboratory 3. Objectives The aim of this study was to evaluate agalactosylation factor (AF) in patients with PsA during biological treatment at Rheumatology Clinic, Medical University in Wroclaw. Patients were treated with adalimumab in combination with MTX, NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) or cyclosporine under permission of the Commission of Bioethics (Medical University, Wroclaw, Poland). The patients between 26-61 years old (mean 48) were diagnosed by the criteria recommended by CASPAR group. Methods Immunoglobulin G was isolated from the serum samples using a column of Sephadex G-25 and DE52 anion exchange resin. The galactosylation of serum IgG was determined using an ELISA-plate test, with two lectins Ricinus communis (RCA-I) and Griffonia simplicifolia (GSL-II), separately. The IgG control was prepared from the pooled serum samples of 5 healthy persons. Triplet wells on a microplate were used for one sample. The ELISA- plate test was performed as previously described 3. Results The relative binding of GSL –II and RCA –I was expressed as the absorbance given by tested sample, divided by the absorbance of the control sample; the ratio of relative GSL –II/RCA –I binding was termed as agalactosylation factor (AF) 3. We determined AF for IgG samples and a control sample. The AF of control was set to 1.0; we have previously 3 confirmed the AFs of IgG of healthy individuals are close to 1. The AF value for 5 patients decreased during therapy and this correlated with a concomitant decrease of initially elevated clinical parameters and with general improvement of patients’ health. The AF value of Bor was comparatively less elevated at the beginning of treatment and insensibly increased. Conclusions The studies have shown higher AF in PsA patients compared to control (healthy people). During therapy with adalimumab decrease of AF was observed, which meant increase of galactosylation of IgG. We plan to perform tests on a larger group of patients. References Parekh, R.B. et al., Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG, Nature, 316; 452-457; 1985; Rademacher, T.W., Williams, P., Dwek, R.A., Agalactosyl glycoforms of IgG autobodies are pathogenic, Proc. Natl. Acad. Sci. USA, 91, 6123-6127, 1994; Pasek, M. et al., Galactosylation of IgG from rheumatoid arthritis (RA) patients – changes during therapy, Glycoconj. J., 23, 463-471, 2006; Disclosure of Interest None Declared
Dipentyl pyridinedicarboxylates (denoted hereafter as L) with different positions of the ester groups were synthesized and used for copper(II) extraction from chloride solutions containing up to 10 ...mol·L-1 Cl-. The effect of decanol addition on copper extraction was studied. A molecular modeling technique was used to estimate the structures of extractants, copper complexes, and associates with alcohol. It was found that the ability of pyridinecarboxylates to extract copper depends on the aqueous phase composition and the position of the ester groups in the pyridine ring. All the investigated compounds except dipentyl pyridine-2,6-dicarboxylate extract copper(II) by formation of CuCl2L2 complexes. Dipentyl pyridine-2,6-dicarboxylate forms another type of complex, probably CuCl2L. However, this compound is not suitable for copper extraction as its copper complex precipitates. Dipentyl pyridine-3,5-dicarboxylate was found to be the most suitable extractant among the various compounds listed. Finally it is shown that the possibilities to modify the extraction ability of pyridinecarboxylates with a hydrophobic alcohol such as decanol are relatively weak. Some enhancement was, however, observed when 20% of decanol was added to the organic phase containing dipentyl pyridine-3,5-dicarboxylate.
