Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies

Sequential decoupling of negative-energy states in Douglas-Kroll-Hess theory

Here, we review the historical development, current status, and prospects of Douglas--Kroll--Hess theory as a quantum chemical relativistic electrons-only theory.Comment: 15 page

Randomised single centre double-blind placebo controlled phase II trial of Tocovid SupraBio in combination with pentoxifylline in patients suffering long-term gastrointestinal adverse effects of radiotherapy for pelvic cancer: The PPALM study.

BACKGROUND: Preclinical data suggest that combined gamma-tocotrienol with pentoxifylline ameliorates radiotherapy-induced gastrointestinal damage. AIM: To test whether gastrointestinal symptoms arising after radiotherapy, and persisting after maximal medical therapy, can be improved using Tocovid SupraBio 200 mg and pentoxifylline 400 mg orally twice daily for one year. Patients stratified by severity of symptoms, and randomised to active treatment or matched placebo were assessed after 12 months. The primary end point was improvement in gastrointestinal symptoms measured using the Inflammatory Bowel Disease Questionnaire, bowel subset score. Changes in bio-markers of fibrosis were assessed. RESULTS: 62 patients, median age 66, 34(55%) treated for prostate, 21(34%) gynaecological, 6(10%) anal and one(1%) rectal cancer were recruited; 40(65%) randomised to treatment, 22(35%) to placebo, 39 months (median) after radiotherapy completion. Gamma tocotrienol was not detected in serum in 41% of treated patients, despite good compliance with study medication. Treatment was completed in 28(70%) and 17(77%) patients in the treatment and placebo groups respectively. No improvement in symptom scores nor in quality of life was identified. Thirteen serious adverse events occurred. A transient ischaemic attack, was possibly related to pentoxifylline, others were assessed as unlikely to be related to treatment. Levels of EGF, PDGF and FGF were significantly reduced and consistent trends in reduced inflammation were seen during treatment but were not sustained once treatment ended. SUMMARY: This single centre study closed prematurely and therefore data interpretation is of necessity limited. No clinical benefit was demonstrated. However, biochemical data suggest that this intervention does have anti-inflammatory and anti-fibrotic effects

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio

Neutron Scattering and Its Application to Strongly Correlated Systems

Neutron scattering is a powerful probe of strongly correlated systems. It can directly detect common phenomena such as magnetic order, and can be used to determine the coupling between magnetic moments through measurements of the spin-wave dispersions. In the absence of magnetic order, one can detect diffuse scattering and dynamic correlations. Neutrons are also sensitive to the arrangement of atoms in a solid (crystal structure) and lattice dynamics (phonons). In this chapter, we provide an introduction to neutrons and neutron sources. The neutron scattering cross section is described and formulas are given for nuclear diffraction, phonon scattering, magnetic diffraction, and magnon scattering. As an experimental example, we describe measurements of antiferromagnetic order, spin dynamics, and their evolution in the La(2-x)Ba(x)CuO(4) family of high-temperature superconductors.Comment: 31 pages, chapter for "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancin

Coherent states for exactly solvable potentials

A general algebraic procedure for constructing coherent states of a wide class of exactly solvable potentials e.g., Morse and P{\"o}schl-Teller, is given. The method, {\it a priori}, is potential independent and connects with earlier developed ones, including the oscillator based approaches for coherent states and their generalizations. This approach can be straightforwardly extended to construct more general coherent states for the quantum mechanical potential problems, like the nonlinear coherent states for the oscillators. The time evolution properties of some of these coherent states, show revival and fractional revival, as manifested in the autocorrelation functions, as well as, in the quantum carpet structures.Comment: 11 pages, 4 eps figures, uses graphicx packag

Haematogenous Staphylococcus aureus meningitis. A 10-year nationwide study of 96 consecutive cases

BACKGROUND: Haematogenous Staphylococcus aureus meningitis is rare but associated with high mortality. Knowledge about the disease is still limited. The objective of this study was to evaluate demographic and clinical prognostic features of bacteraemic S. aureus meningitis. METHODS: Nationwide surveillance in Denmark from 1991 to 2000 with clinical and bacteriological data. Risks of death were estimated by Cox proportional hazards regression analysis. RESULTS: Among 12480 cases of S. aureus bacteraemia/sepsis, we identified 96 cases of non-surgical bacteraemic S. aureus meningitis (0.8%). Incidence rates were 0.24 (95% confidence interval [CI], 0.18 to 0.30)/100 000 population between 1991–1995 and 0.13 (CI, 0.08 to 0.17)/100 000 population between 1996–2000. Mortality was 56%. After adjustment, only co morbidity (hazard ratio [HR], 3.45; CI, 1.15 to 10.30) and critical illness (Pitt score ≥ 4) (HR, 2.14; CI, 1.09 to 4.19) remained independent predictors of mortality. CONCLUSION: The incidence, but not mortality of bacteraemic S. aureus meningitis decreased during the study period. Co morbidity and critical illness were independent predictors of a poor outcome

Holographic zero sound at finite temperature in the Sakai-Sugimoto model

In this paper, we study the fate of the holographic zero sound mode at finite temperature and non-zero baryon density in the deconfined phase of the Sakai-Sugimoto model of holographic QCD. We establish the existence of such a mode for a wide range of temperatures and investigate the dispersion relation, quasi-normal modes, and spectral functions of the collective excitations in four different regimes, namely, the collisionless quantum, collisionless thermal, and two distinct hydrodynamic regimes. For sufficiently high temperatures, the zero sound completely disappears, and the low energy physics is dominated by an emergent diffusive mode. We compare our findings to Landau-Fermi liquid theory and to other holographic models.Comment: 1+24 pages, 19 figures, PDFTeX, v2: some comments and references added, v3: some clarifications relating to the different regimes added, matches version accepted for publication in JHEP, v4: corrected typo in eq. (3.18