The macrophage scavenger receptor class A (SR-A) participates in the innate immune and inflammatory responses. This study examined the role of macrophage SR-A in myocardial ischemia/reperfusion (I/R) injury and hypoxia/reoxygenation (H/R)-induced cell damage. SR-A-/- and WT mice were subjected to ischemia (45min) followed by reperfusion for up to 7days. SR-A-/- mice showed smaller myocardial infarct size and better cardiac function than did WT I/R mice. SR-A deficiency attenuated I/R-induced myocardial apoptosis by preventing p53-mediated Bak-1 apoptotic signaling. The levels of microRNA-125b in SR-A-/- heart were significantly greater than in WT myocardium. SR-A is predominantly expressed on macrophages. To investigate the role of SR-A macrophages in H/R-induced injury, we isolated peritoneal macrophages from SR-A deficient (SR-A-/-) and wild type (WT) mice. Macrophages were subjected to hypoxia followed by reoxygenation. H/R markedly increased NF-κB binding activity as well as KC and MCP-1 production in WT macrophages but not in SR-A-/- macrophages. H/R induced caspase-3/7 and -8 activities and cell death in WT macrophages, but not in SR-A-/- macrophages. The levels of miR-125b in SR-A-/- macrophages were significantly higher than in WT macrophages. Transfection of WT macrophages with miR-125b mimics attenuated H/R-induced caspase-3/7 and -8 activities and H/R-decreased viability, and prevented H/R-increased p-53, Bak-1 and Bax expression. The data suggest that SR-A deficiency attenuates myocardial I/R injury by targeting p53-mediated apoptotic signaling. SR-A-/- macrophages contain high levels of miR-125b which may play a role in the protective effect of SR-A deficiency on myocardial I/R injury and H/R-induced cell damage.

The macrophage scavenger receptor class A (SR-A) participates in the innate immune and inflammatory responses. This study examined the role of macrophage SR-A in myocardial ischemia/reperfusion (I/R) injury and hypoxia/reoxygenation (H/R)-induced cell damage. SR-A-/- and WT mice were subjected to ischemia (45min) followed by reperfusion for up to 7days. SR-A-/- mice showed smaller myocardial infarct size and better cardiac function than did WT I/R mice. SR-A deficiency attenuated I/R-induced myocardial apoptosis by preventing p53-mediated Bak-1 apoptotic signaling. The levels of microRNA-125b in SR-A-/- heart were significantly greater than in WT myocardium. SR-A is predominantly expressed on macrophages. To investigate the role of SR-A macrophages in H/R-induced injury, we isolated peritoneal macrophages from SR-A deficient (SR-A-/-) and wild type (WT) mice. Macrophages were subjected to hypoxia followed by reoxygenation. H/R markedly increased NF-κB binding activity as well as KC and MCP-1 production in WT macrophages but not in SR-A-/- macrophages. H/R induced caspase-3/7 and -8 activities and cell death in WT macrophages, but not in SR-A-/- macrophages. The levels of miR-125b in SR-A-/- macrophages were significantly higher than in WT macrophages. Transfection of WT macrophages with miR-125b mimics attenuated H/R-induced caspase-3/7 and -8 activities and H/R-decreased viability, and prevented H/R-increased p-53, Bak-1 and Bax expression. The data suggest that SR-A deficiency attenuates myocardial I/R injury by targeting p53-mediated apoptotic signaling. SR-A-/- macrophages contain high levels of miR-125b which may play a role in the protective effect of SR-A deficiency on myocardial I/R injury and H/R-induced cell damage.

The innate immune response is involved in the pathophysiology of cerebral ischemia-reperfusion (I/R) injury. Recent evidence suggests that scavenger receptors have a role in the induction of innate immunity. In this study, we examined the role of scavenger receptor A (SR-A) in focal cerebral I/R injury. Both SR-A-/- mice (n=10) and age-matched wild-type (WT) mice (n=9) were subjected to focal cerebral ischemia (60 minutes), followed by reperfusion (for 24 hours). Infarct size was determined by TTC (triphenyltetrazolium chloride) staining. The morphology of neurons in the brain sections was examined by Nissl's staining. Activation of intracellular signaling was analyzed by western blot. Cerebral infarct size in SR-A -/- mice was significantly reduced by 63.9% compared with WT mice after cerebral I/R. In SR-A -/- mice, there was less neuronal damage in the hippocampus compared with WT mice. Levels of FasL, Fas, FADD, caspase-3 activity, and terminal deoynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling-positive apoptotic cells were significantly increased in WT mice after cerebral I/R, but not in SR-A -/- mice. Cerebral I/R increased nuclear factor-B activation in WT mice, but not in SR-A -/- mice. These data suggest that SR-A has a central role in cerebral I/R injury and that suppression of SR-A may be a useful approach for ameliorating brain injury in stroke patients.

No description available.

Coral-based climate studies commonly use elemental ratios and stable isotopes of coral skeletons to address seawater temperature and hydrologic balance issues in the tropical surface oceans. Replication, or cross-checking, a standard technique used to assess the fidelity of proxy records in paleoclimatology has not been widely applied in coral-based climate studies, primarily because of the time and cost associated with generating multiple records from a single reef site. Modern and paleoclimate reconstructions based on a single proxy-coral record from a site may contain errors if individual corals from the same reef record different geochemical signals. In this study we perform a replication test using elemental ratios and stable isotopes in three Porites corals from New Caledonia. The reef complex offshore Amédée Island, New Caledonia is an ideal site to perform a coral replication test because instrumental sea surface temperatures (SST) and sea surface salinity measurements (SSS) have been made there for over 25 years. In this study, we compare sub-monthly resolved, geochemical variations (Sr/Ca, δ18O and δ13C) in three Porites lutea coral heads, located ~500 m apart, with the instrumental SST and SSS records over the interval 1992-1967. The monthly coral Sr/Ca and δ18O time series are well correlated to each other (r=0.86, p<.0001) and to the monthly instrumental SST record (r= -0.86, p<.0001, coral Sr/Ca to SST; r= -0.77, p<.0001, coral δ18O to SST). The three, sub-monthly resolved, 30-year coral Sr/Ca-SST time series have mean SST values that agree within 0.2o C with the instrumental mean SST value. A similar comparison for the coral δ18O-SST records indicate a maximum difference between predicted and observed mean SST of 0.5˚C. Analysis of the monthly climatological means also indicates that Sr/Ca-SST records closely match the instrumental SST record ±0.4˚C; a similar comparison using the δ18O-SST record yields an average offset of ±0.6˚C between observed and predicted monthly SST. Stacking the three records to form composite Sr/Ca-SST and δ18O-SST records does not appreciably improve the goodness of fit between the proxy and instrumental SST records; hence a coral-based proxy climate record from a single coral accurately reflects the observed record of climate variability at this locality. These results support the concept that high fidelity climate records can be generated using a single coral core.

The purpose of this study is the characterization of the membrane-water interfaces of both sarcoplasmic reticulum membrane (SR) and charged lipid bilayers under varied properties of the surrounding aqueous solution. In this work we studied the electrokinetic properties of liposomes and SR vesicles as well as the interaction of lipophilic ions with these membranes. The study of electrokinetic properties is based on the measurements of electrophoretic mobility of SR membrane vesicles and PC/PG liposomes. Electrophoretic mobility of SR vesicles was measured as a function of ionic strength for six pH values (pH 4.0, 4.7, 5.0, 6.0, 7.5, and 9.0). Electrophoretic mobility of single-layered and multi-layered PC/PG liposomes was measured at neutral pH as a function of ionic strength. For interpretation of electrophoretic mobility studies, SR vesicles (at pH 4, 7, and 9) and multi-layered and single-layered liposome sizes were determined using photoelectron microscopy. The study of the interaction of lipophilic ions with these membranes is based on (1) measurements of their partition coefficients described in terms of an ion partition model based on the Langmuir adsorption model and (2) electrophoretic mobility measurements of SR vesicles and PC liposomes in suspension with varied concentration of lipophilic ions. SR-water and PC-water partition coefficients were measured as a function of concentration for two anions tetraphenylborate (TePB-) and pentabromophenol (PBP-) and two cations (Imipramine+, and Clomipramine+). The anions belong to a class of pesticides and the cations are drugs once prescribed as anti-depressants. Partition into the SR membrane was shown to be significantly greater for all lipophilic ions except TePB-, which only showed this effect at the higher lipophilic ion range of the data. The PC-water partition coefficient was also measured for TePP+. Since the lipid bilayer of SR is not significantly different than that of PC liposomes, we believe the differences in partition are due to excess lipophilic ions being absorbed to the proteins of SR. The electrokinetics of charged PCPG liposomes, and PC liposomes with absorbed lipophilic ions could be understood in terms of the charge being located below their surface and screened by counter-ions inside the polar head-group region. We call this model the "permeable surface model". The assumptions of this model are that (1) the charge exists on a plane at a depth, d, below the surface of the liposome within the lipid head-group region and (2) small ions (Na+, K+, Cl-) are able to penetrate the lipid head-group region with a molar membrane-water partition coefficient of 0.4. Using this model we were able to obtain the depth of sorption of lipophilic ions in PC liposomes. We found values of 0.13 nm for TePB-, 0.5 nm for PBP-, 0.12 nm for Imipramine+, 0.17 nm for Clomipramine and 0.25 nm for TePP+. The depth of lipophilic ions in PC is a valuable quantity for the study of the effect of lipophilic ions on membrane function. For PCPG mobility we found the charged plane due to PG lipids was 0.2 nm for single-layered liposomes and 0.1 nm for multi-layered liposomes. This is consistent with the relative size of PC and PG head groups The dependence of SR mobility on pH was found to be directly correlated with the total charge of the A, P, and N domains of the Ca2+-ATPase as determined by the amino acid residues and their corresponding pKa values in water. We found that detached charged plane model, a new model developed in our group, could be fit to the mobility of SR as a function of ionic strength while other soft particle models failed. The assumptions of this model are that (1) the friction caused by protruding proteins on the surface of SR can be represented by a homogeneous retardation layer of thickness D and softness parameter λRL, and (2) the charge of the APN domain can be represented as a plane of charge embedded in the retardation layer at a distance s from the membrane surface. The best-fit values for λRL, and s were not consistent for different pH value studies. The detached charged plane model was unable to predict the mobility of SR vesicles in the presence of lipophilic ions if we assumed that the lipophilic ions were sorbing to the detached charged plane that represents the native charge of the APN domains of SR. At high lipophilic ion concentration the experimental mobilities consistently were greater in magnitude than the values predicted by the model. We concluded that there is significant absorption of lipophilic ions to the proteins in SR membrane, and that the lipophilic ion sorption sites are not the same as the detached plane of charge that represents the native charge of the APN domain.

This bachelor’s essay aims to discuss breastfeeding and complications related to breastfeeding within archaeological contexts. Why complications have arisen when such a natural act is per- formed and how individuals have tried to manage them. By looking at different methods of recording breastfeeding patterns I aim to broaden the interpretations of breastfeeding in differ- ent time periods and locations. Isotope analysis will be an important part as well as paleopatho- logical analysis of human remains. Information from three completed studies from Öland and Västerhus in Sweden and Quarto Cappello del Prete in Rome will be presented and discussed. In conclusion I suggest that breastfeeding is a complex act surrounded by difficulties such as diseases and cultural norms. There is variation within populations regarding breastfeeding and weaning. People have been struggling as well as fighting for the survival of their children.

Inputs of the major element potassium into the ocean from rivers and on-axis high temperature hydrothermal systems have likely varied on geological timescales. Variable uptake of potassium into lavas altered in low-temperature, off-axis, hydrothermal systems could keep the potassium concentration in seawater within the narrow range (~9.5 to 11 mmol L-1) observed in the Phanerozoic. To test this hypothesis a better understanding of the timing of alteration, and of the role of changing environmental conditions on seawater/basalt reactions is required. The age of 69 samples of the secondary, potassium-rich, phyllosilicate mineral celadonite from lavas in the Troodos ophiolite were determined using Rb-Sr radiometric dating to test whether potassium uptake occurs within a specific time interval. Measurements used tandem quadrupole ICP-MS/MS. Combined with published radiometric ages the dataset revealed regional differences in the duration of celadonite formation in the Troodos ophiolite lavas. In one area, where significant hydrothermal sediments were deposited on the lavas, celadonite formed as much as ~40 Myr after the crust accreted, whereas in an area with rare hydrothermal sediments celadonite formation was largely limited to the first ~20 Myr after crustal accretion. These differences in duration of celadonite formation in the upper oceanic crust are interpreted as reflecting differences in distribution of hydrothermal sediments that act as a source of labile Fe that is needed for celadonite formation. To test if there are significant variations of duration and timing of celadonite formation on various scales in the upper oceanic crust I measured the first in-situ Rb-Sr ages of celadonite in lavas from DSDP and ODP drill cores. These ages show that ~80% of celadonite formed from pervasive fluid flow within the first ~20 Myr after the oceanic crust accreted. All celadonite ages roughly correlate with the cumulative heat flow removed from the oceanic lithosphere in the same time interval. In combination the >100 new celadonite ages presented here provide strong evidence that most celadonite forms in the first ~20 Myr after crustal accretion and environmental conditions could be significant in controlling potassium uptake. To determine whether the potassium sink from seawater into altered seafloor lavas varied over time I compile a dataset of the potassium content of lavas from DSDP and ODP drill cores (0 to 180 Myr age range). Estimates of the average potassium content of individual holes reveal that this varies with age. However, holes of similar age show a similar magnitude of variability to that which occurs over this time. To investigate the source of the variability of potassium in altered lavas I modelled the effects of bottom seawater temperature and pH using PHREEQC. The models indicate that if the fluid is in equilibrium with K-feldspar, Na-beidellite and calcite, an increase in bottom seawater temperature and/or decrease in pH would lead to the potassium concentration in the off-axis fluid to increase significantly. This emphasizes the need for future studies to investigate feedback mechanisms between low-temperature hydrothermal alteration in response to changing environmental conditions. / Graduate / 2022-07-12

Yes / The production of a number of methyl esters such as methyl decanoate (MeDC), methyl salicylate (MeSC), and methyl benzoate (MeBZ) by esterification reactions of several carboxylic acids such as decanoic acid (DeC), salicylic acid (ScA), and benzoic acid (BeZ) with methanol, respectively, through a reactive distillation system (batch or continuous) is cost-intensive and operationally challenging operation. It is difficult to keep the reaction species together in the reaction section due to wide boiling point differences between the reactants. Methanol (in those esterification processes) having the lowest boiling temperature in the reaction mixture can separate easily from carboxylic acid as the distillation progresses, resulting in a severe drop in the reaction conversion ratio of the acid employing batch/continuous distillation system. In order to overcome this type of challenge and to increase the overall reaction conversion, a novel split-reflux conventional batch reactive distillation configuration (sr-BRD) is proposed/studied in detail in this investigation. The optimal performance of BRD/ sr-BRD column is determined in terms of maximum achievable conversion of acids, and highest concentration of the esters produced for each chemical reaction scheme. The results for given separation tasks are compared with those obtained using conventional batch distillation (BRD) process. The optimization results clearly show that the sr-BRD process significantly improves the process efficiency, the conversion ratio of acid, and the product purity of methyl esters compared to that obtained via the BRD process.

No description available.