Magnetic inflation and stellar mass. III. revised parameters for the component stars of NSVS 07394765

We perform a new analysis of the M-dwarf–M-dwarf eclipsing binary system NSVS 07394765 in order to investigate the reported hyper-inflated radius of one of the component stars. Our analysis is based on archival photometry from the Wide Angle Search for Planets, new photometry from the 32 cm Command Module Observatory telescope in Arizona and the 70 cm telescope at Thacher Observatory in California, and new high-resolution infrared spectra obtained with the Immersion Grating Infrared Spectrograph on the Discovery Channel Telescope. The masses and radii we measure for each component star disagree with previously reported measurements. We show that both stars are early M-type main-sequence stars without evidence for youth or hyper-inflation ( = - ☉ M M + 1 0.661 0.036 0.008 , = - ☉ M M + 2 0.608 0.028 0.003 , = - ☉ + R1 0.599 0.019 R 0.032 , = - ☉ + R2 0.625 0.027 R 0.012 ), and we update the orbital period and eclipse ephemerides for the system. We suggest that the likely cause of the initial hyper-inflated result is the use of moderate-resolution spectroscopy for precise radial velocity measurements.Published versio

The Robustness of Pathway Analysis in Identifying Potential Drug Targets in Non-Small Cell Lung Carcinoma

The identification of genes responsible for causing cancers from gene expression data has had varied success. Often the genes identified depend on the methods used for detecting expression patterns, or on the ways that the data had been normalized and filtered. The use of gene set enrichment analysis is one way to introduce biological information in order to improve the detection of differentially expressed genes and pathways. In this paper we show that the use of network models while still subject to the problems of normalization is a more robust method for detecting pathways that are differentially overrepresented in lung cancer data. Such differences may provide opportunities for novel therapeutics. In addition, we present evidence that non-small cell lung carcinoma is not a series of homogeneous diseases; rather that there is a heterogeny within the genotype which defies phenotype classification. This diversity helps to explain the lack of progress in developing therapies against non-small cell carcinoma and suggests that drug development may consider multiple pathways as treatment targets

Deletion of a Single beta-Catenin Allele in Osteocytes Abolishes the Bone Anabolic Response to Loading

The Wnt/β-catenin signaling pathway is essential for bone cell viability and function and for skeletal integrity. To determine if β-catenin in osteocytes plays a role in the bone anabolic response to mechanical loading, 18- to 24-week-old osteocyte β-catenin haploinsufficient mice (Dmp1-Cre × β-catenin fl/ + ; HET cKO) were compared with their β-catenin fl/fl (control) littermates. Trabecular bone volume (BV/TV) was significantly less (58.3%) in HET cKO females versus controls, whereas male HET cKO and control mice were not significantly different. Trabecular number was significantly less in HET cKO mice compared with controls for both genders, and trabecular separation was greater in female HET cKO mice. Osteoclast surface was significantly greater in female HET cKO mice. Cortical bone parameters in males and females showed subtle or no differences between HET cKO and controls. The right ulnas were loaded in vivo at 100 cycles, 2 Hz, 2500 µϵ, 3 days per week for 3 weeks, and the left ulnas served as nonloaded controls. Calcein and alizarin complexone dihydrate were injected 10 days and 3 days before euthanization, respectively. Micro-computed tomography (µCT) analysis detected an 8.7% and 7.1% increase in cortical thickness in the loaded right ulnas of male and female control mice, respectively, compared with their nonloaded left ulnas. No significant increase in new cortical bone formation was observed in the HET cKO mice. Histomorphometric analysis of control mice showed a significant increase in endocortical and periosteal mineral apposition rate (MAR), bone-formation rate/bone surface (BFR/BS), BFR/BV, and BFR/TV in response to loading, but no significant increases were detected in the loaded HET cKO mice. These data show that deleting a single copy of β-catenin in osteocytes abolishes the anabolic response to loading, that trabecular bone in females is more severely affected and suggest that a critical threshold of β-catenin is required for bone formation in response to mechanical loading

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Formation of the blood–brain barrier: Wnt signaling seals the deal

Capillaries in the brain are especially selective in determining which blood-borne components gain access to neurons. The structural elements of this blood–brain barrier (BBB) reside at the tight junction, an intercellular protein complex that welds together adjacent endothelial cell membranes in the microvasculature. In this issue, Liebner et al. (Liebner, S., M. Corada, T. Bangsow, J. Babbage, A. Taddei, C.J. Czupalla, M. Reis, A. Felici, H. Wolburg, M. Fruttiger, et al. 2008. J. Cell Biol. 183: 409–417) report that Wnt signaling plays an active role in the development of the BBB by regulating expression of key protein constituents of the tight junction. Such mechanistic insight has implications for a variety of neuropathological states in which the BBB is breached

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer