Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimers disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimers disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker

Engineering handbook

2005 handbook for the faculty of Engineerin

Universal Level dynamics of Complex Systems

. We study the evolution of the distribution of eigenvalues of a $N\times N$ matrix subject to a random perturbation drawn from (i) a generalized Gaussian ensemble (ii) a non-Gaussian ensemble with a measure variable under the change of basis. It turns out that, in the case (i), a redefinition of the parameter governing the evolution leads to a Fokker-Planck equation similar to the one obtained when the perturbation is taken from a standard Gaussian ensemble (with invariant measure). This equivalence can therefore help us to obtain the correlations for various physically-significant cases modeled by generalized Gaussian ensembles by using the already known correlations for standard Gaussian ensembles. For large $N$-values, our results for both cases (i) and (ii) are similar to those obtained for Wigner-Dyson gas as well as for the perturbation taken from a standard Gaussian ensemble. This seems to suggest the independence of evolution, in thermodynamic limit, from the nature of perturbation involved as well as the initial conditions and therefore universality of dynamics of the eigenvalues of complex systems.Comment: 11 Pages, Latex Fil

The impact of the level and distribution of methyl-esters of pectins on TLR2-1 dependent anti-inflammatory responses

Pectins have anti-inflammatory effects via Toll-like receptor (TLR) inhibition in a degree of methyl-esterification-(DM)-dependent manner. However, pectins also vary in distribution of methyl-esters over the galactumnic-acid (GalA) backbone (Degree of Blockiness - DB) and impact of this on anti-inflammatory capacity is unknown. Pectins mainly inhibit TLR2-1 but magnitude depends on both DM and DB. Low DM pectins (DM18/19) with both low (DB86) and high DB (DB94) strongly inhibit TLR2-1. However, pectins with intermediate DM (DM43/ DM49) and high DB (DB60), but not with low DB (DB33), inhibit TLR2-1 as strongly as low DM. High DM pectins (DM84/88) with DB71 and DB91 do not inhibit TLR2-1 strongly. Pectin-binding to TLR2 was confirmed by capture-ELISA. In human macrophages, low DM and intermediate DM pectins with high DB inhibited TLR2-1 induced IL-6 secretion. Both high number and blockwise distribution of non-esterified GalA in pectins are responsible for the anti-inflammatory effects via inhibition of TLR2-1

A Survey of Women in Academia and the role of a Multidisciplinary Professional Society

The Society of Women Engineers (SWE) is a global professional society of over 30,000 members with a mission to “Stimulate women to achieve full potential in careers as engineers and leaders, expand the image of the engineering profession as a positive force in improving the quality of life, and demonstrate the value of diversity”1. SWE is an organization that is deeply rooted in industry. The founding members were employed by firms that are a result of the industrial revolution, and thus the focus of its membership is on those that work for industry, consultants, and often themselves. This focus has unintentionally left a large population of its membership, the academic population, underrepresented and misunderstood. Early discussion at the board level in the mid 2000’s indicated a willingness for a paradigm shift. However, the representation of academics on the board and other leadership roles has been lacking. This can be attributed to the lower numbers of this group relative to the whole, as well as the requirements of tenure that do not support the time and dedication to such an endeavor. A small but influential group of members, including a former board member, and a few involved at various levels of the society have been working toward increasing opportunities for women in academia (WIA). Some of the initiatives have been the societal support of the WIA committee, the addition of professional development opportunities targeting women in academic careers, providing recognition and awards, and aiding in networking opportunities. These all lead toward career advancement, making SWE more attractive to women engineers in the academe. To further our understanding of available opportunities and those opportunities that will make membership and active participation more attractive to members in academia, a survey was developed. Information gathered by the survey include demographics, perceived needs, and potential contributions the individual could make in furthering the creation of professional development opportunities for this population. This work is intended to share the results of this survey, using descriptive statistics, further developing our understanding of this underserved population within SWE

Impaired trophoblast invasion and increased numbers of immune cells at day 18 of pregnancy in the mesometrial triangle of type 1 diabetic rats

AbstractIntroductionType 1 diabetes (T1D) is associated with adverse pregnancy outcome, usually attributed to hyperglycemia. Recently, we showed that pregnancy outcome in normoglycemic T1D rats was characterized by decreased fetal and placental weight, suggesting impaired placental development. In the present study, we tested the hypothesis that trophoblast invasion and spiral artery (SA) remodeling is impaired in T1D rats ant that this is associated with aberrant local presence of NK cells and macrophages in the mesometrial triangle (MT).MethodsPlacentae with MT from pregnant biobreeding diabetes-prone (BBDP; T1D model) rats, control biobreeding diabetes-resistant (BBDR) and Wistar-rats were dissected at day 18 of gestation and stained for trophoblast invasion, SA remodeling, uNK cells and macrophages.ResultsInterstitial trophoblast invasion and SA remodeling was impaired in BBDP-rats vs. control rats, coinciding with increased presence of NK cells and an increased iNOS+/CD206+ ratio of macrophages.DiscussionDecreased fetal and placental weight in BBDP-rats was associated with diminished interstitial trophoblast invasion and less optimal SA remodeling, increased numbers of NK cells and increased iNOS+/CD206+ macrophage ratio in the MT of BBDP-rats.ConclusionsThe impaired trophoblast invasion and SA remodeling may be due to an aberrant local immune-response and may result in damage to the fetal placenta and insufficient supply of nutrients towards the fetus with eventually decreased fetal weight as a consequence

Decidual memory T‐cell subsets and memory T‐cell stimulatory cytokines in early‐ and late‐onset preeclampsia

Problem: Preeclampsia is a major cause of fetal and maternal mortality and morbidity. Disturbed fetal-maternal immune tolerance, and therewith memory T cells, might be involved in its etiology. This study aims to give insight into memory T-cell populations and its associated cytokines in the decidual layers in early-onset preeclampsia (EO-PE) and late-onset preeclampsia (LO-PE). Method of Study: Lymphocytes were isolated from the decidua parietalis and basalis from EO-PE (n = 6), LO-PE (n = 8) and healthy (n = 15) pregnancies. CD4+ and CD8+ central- (CCR7+), effector- (CCR7−), tissue resident- (CD103+), and regulatory- (Foxp3+) memory cell (CD45RO+) populations and their activation status (CD69+) were analyzed using flow cytometry. qRT-PCR analysis was performed on decidua parietalis and basalis biopsies to detect mRNA expression of interferon-gamma, interleukin-1B, IL2, IL6, IL7, IL8, IL10, IL15, and IL23. Results: CD4+ central-memory (CM) cell proportions were lower in the decidua parietalis in LO-PE (P <.0001) and EO-PE (P <.01) compared to healthy pregnancies. CD8+ memory (P <.05) and CD8+ CM (P <.01) cell proportions were also lower in the decidua parietalis in EO-PE compared to healthy pregnancies. This was accompanied by higher IL15 (P <.05) and IL23 (P <.05) and lower IL7 (P <.05) mRNA expression in decidua basalis biopsies from EO-PE compared to healthy pregnancies, analyzed by qPCR. Conclusion: In conclusion, decidual memory T-cell proportions, their activation status, and associated cytokines are altered in preeclampsia and might therefore be involved in fetal-maternal immune tolerance and the pathophysiology of preeclampsia

Microbiota Induced Changes in the Immune Response in Pregnant Mice

Pregnancy is associated with adaptations of the immune response and with changes in the gutmicrobiota. We hypothesized the gut microbiota are involved in inducing (part of) the immunological adaptations during pregnancy. To test this hypothesis, we collected feces from pregnant conventional mice before and during pregnancy (days 7, 14, and 18) and microbiota were measured using 16S RNA sequencing. At day 18, mice were sacrificed and splenic (various Th cell populations) and blood immune cells (monocyte subsets) were measured by flow cytometry. The data were compared with splenic and blood immune cell populations from pregnant (day 18) germfree mice and non-pregnant conventional and germfree mice. Finally, the abundances of the individual gut bacteria in the microbiota of each conventional pregnant mouse were correlated to the parameters of the immune response of the same mouse. The microbiota of conventional mice were significantly different at the end of pregnancy (day 18) as compared with pre-pregnancy (Permanova, p <0.05). The Shannon index was decreased and the Firmicutes/Bacteroidetes ratio was increased (Friedman followed by Dunn's test, p <0.05), while abundances of various species (such as Allobaculum stercoricanis, Barnesiella intestihominis, and Roseburia faecis) were significantly different at day 18 compared with pre-pregnancy. In pregnant conventional mice, the percentage of Th1 cells was decreased, while the percentages of Treg cells and Th2 cells were or tended to be increased vs. non-pregnant mice. In germfree mice, only the percentage of Th1 cells was decreased in pregnant vs. non-pregnant mice, with no effect of pregnancy on Treg and Th2 cells. The percentages of monocyte subsets were affected by pregnancy similarly in conventional and germfree mice. However, the activation status of monocytes (expression of CD80 and MHCII) was affected by pregnancy mainly in conventional mice, and not in germfree mice. Correlation (Spearman's coefficient) of pregnancy affected microbiota with pregnancy affected immune cells, i.e., immune cells that were only affected differently in conventional mice and germfree mice, showed 4 clusters of bacteria and 4 clusters of immune cells, some of these clusters were correlated with each other. For instance, the microbiota in cluster 1 and 2 (in which there were various short chain fatty acid producing microbiota) are positively correlated with immune cells in cluster B, containing Treg cells and Th2 cells. Microbiota and immune cells are affected by pregnancy in mice. The different immunological adaptations to pregnancy between conventional and germfree mice, such as the increase in Treg and tendency to an increase in Th2 cells in conventional pregnant mice only, may suggest that the microbiota may play a role in adapting the maternal immune response to pregnancy