Maternal hyperleptinemia is associated with male offspring’s altered vascular function and structure in mice

Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Lepr db/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under astandard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post-natal environments to contribute to altered vascular function in offspring of diabetic pregnancie

The Solar Orbiter magnetometer

The magnetometer instrument on the Solar Orbiter mission is designed to measure the magnetic field local to the spacecraft continuously for the entire mission duration. The need to characterise not only the background magnetic field but also its variations on scales from far above to well below the proton gyroscale result in challenging requirements on stability, precision, and noise, as well as magnetic and operational limitations on both the spacecraft and other instruments. The challenging vibration and thermal environment has led to significant development of the mechanical sensor design. The overall instrument design, performance, data products, and operational strategy are described

The Role of Neutrophil Proteins on the Amyloid Beta-RAGE Axis

We would like to thank Dr. Arthur Owora, previously a Research Biostatistician of the Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, for his assistance on the statistical analysis performed in this study. We thank Dr. Sixia Chen of the Department of Biostatistics and Epidemiogy, University of Oklahoma Health Sciences Center, for his additional input on the statistical analysis. We thank the Laboratory for Molecular Biology and Cytometry Research at the University of Oklahoma Health Sciences Center for the use of the Core Facility which allowed us to perform the MALDI-TOF MS and MS/MS experiments. GM-0111 was provided as a gift by Dr. Justin Savage, GlycoMira Therapeutics, Inc.We previously showed an elevated expression of the neutrophil protein, cationic antimicrobial protein of 37kDa (CAP37), in brains of patients with Alzheimer’s disease (AD), suggesting that CAP37 could be involved in AD pathogenesis. The first step in determining how CAP37 might contribute to AD pathogenesis was to identify the receptor through which it induces cell responses. To identify a putative receptor, we performed GAMMA analysis to determine genes that positively correlated with CAP37 in terms of expression. Positive correlations with ligands for the receptor for advanced glycation end products (RAGE) were observed. Additionally, CAP37 expression positively correlated with two other neutrophil proteins, neutrophil elastase and cathepsin G. Enzyme-linked immunosorbent assays (ELISAs) demonstrated an interaction between CAP37, neutrophil elastase, and cathepsin G with RAGE. Amyloid beta 1–42 (Aβ1–42), a known RAGE ligand, accumulates in AD brains and interacts with RAGE, contributing to Aβ1–42 neurotoxicity. We questioned whether the binding of CAP37, neutrophil elastase and/or cathepsin G to RAGE could interfere with Aβ1–42 binding to RAGE. Using ELISAs, we determined that CAP37 and neutrophil elastase inhibited binding of Aβ1–42 to RAGE, and this effect was reversed by protease inhibitors in the case of neutrophil elastase. Since neutrophil elastase and cathepsin G have enzymatic activity, mass spectrometry was performed to determine the proteolytic activity of all three neutrophil proteins on Aβ1–42. All three neutrophil proteins bound to Aβ1–42 with different affinities and cleaved Aβ1–42 with different kinetics and substrate specificities. We posit that these neutrophil proteins could modulate neurotoxicity in AD by cleaving Aβ1–42 and influencing the Aβ1–42 –RAGE interaction. Further studies will be required to determine the biological significance of these effects and their relevance in neurodegenerative diseases such as AD. Our findings identify a novel area of study that underscores the importance of neutrophils and neutrophil proteins in neuroinflammatory diseases such as AD.Yeshttp://www.plosone.org/static/editorial#pee

Rank one subspaces of bimodules over maximal abelian selfadjoint algebras

Spaces of operators that are left and right modules over maximal abelian selfadjoint algebras (masa bimodules For short) are natural generalizations of algebras with cummutative subspace lattices. This paper is concerned with density properties of finite rank operators and of various Classes of compact operators in such modules. It is shown that every finite rank operator of a norm closed masa bimodule H is in the trace norm closure of the rank one subspace of H. An important consequence is that the rank one subspace of a strongly reflexive masa bimodule (that is, one which is the reflexive hull of its rank one operators ) is dense in the module in the weak operator topology. However, in contrast to the situation for algebras, it is shown that such density need not hold in the ultraweak topology. A new method of representing masa bimodules is introduced. This uses a novel concept of all omega-topology. With the appropriate notion of omega-support, a correspondence is established between reflexive masa bimodules and their omega-supports. It is shown that, if a l(2)-closed masa bimodule contains a tract class operator then it must contain rank one operators. indeed, every such operator is in the l(2)-norm closure of the rank one subspace of the module. Consequently the weak closure of any masa bimodule of trace class operators is strongly reflexive. However. the trace norm closure of the rank one subspace need not contain all trace class operators of the module. Also, it is shown that there exists a CSL algebra which contains no trace class operators yet contains an operator belonging to l(p) for all p > 1. From this it follows that a transitive bimodule spanned by the rank one operators it contains need not be dense in l(p) for 1 less than or equal to p < infinity. As an application, it is shown that there exists a commutative subspace lattice L such that L is non-synthetic but every weakly closed algebra which contains a mesa and has invariant lattice L coincides with Alg L. (C) 1998 Academic Press

Prostasomes: a role in prostatic disease?

Prostasomes are membrane-bound secretory vesicles, in the nanometre diameter range, secreted by the prostatic ductal epithelium [1] into the lumen, where they form part of the ejaculate. Although known to have specific biological properties, their physiological role and overall significance remain far more debatable. There has been comparatively little written about these structures since their detection two decades ago, and this may help explain the relative lack of awareness of prostasomes within the urological community