HL‐TWiM Empirical Model of High‐Latitude Upper Thermospheric Winds

We present an empirical model of thermospheric winds (High‐latitude Thermospheric Wind Model [HL‐TWiM]) that specifies F region high‐latitude horizontal neutral winds as a function of day of year, latitude, longitude, local time, and geomagnetic activity. HL‐TWiM represents the large‐scale neutral wind circulation, in geomagnetic coordinates, for the given input conditions. The model synthesizes the most extensive collection to date of historical high‐latitude wind measurements; it is based on statistical analyses of several decades of F region thermospheric wind measurements from 21 ground‐based stations (Fabry‐Perot Interferometers and Scanning Doppler Imaging Fabry‐Perot Interferometers) located at various northern and southern high latitudes and two space‐based instruments (UARS WINDII and GOCE). The geomagnetic latitude and local time dependences in HL‐TWiM are represented using vector spherical harmonics, day of year and longitude variations are represented using simple harmonic functions, and the geomagnetic activity dependence is represented using quadratic B splines. In this paper, we describe the HL‐TWiM formulation and fitting procedures, and we verify the model against the neutral wind databases used in its formulation. HL‐TWiM provides a necessary benchmark for validating new wind observations and tuning our physical understanding of complex wind behaviors. Results show stronger Universal Time variation in winds at southern than northern high latitudes. Model‐data intra‐annual comparisons in this study show semiannual oscillation‐like behavior of GOCE winds, rarely observed before in wind data

Integrative Network Biology: Graph Prototyping for Co-Expression Cancer Networks

Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure

Maintaining RNA integrity in a homogeneous population of mammary epithelial cells isolated by Laser Capture Microdissection

Background: Laser-capture microdissection (LCM) that enables the isolation of specific cell populations from complex tissues under morphological control is increasingly used for subsequent gene expression studies in cell biology by methods such as real-time quantitative PCR (qPCR), microarrays and most recently by RNA-sequencing. Challenges are i) to select precisely and efficiently cells of interest and ii) to maintain RNA integrity. The mammary gland which is a complex and heterogeneous tissue, consists of multiple cell types, changing in relative proportion during its development and thus hampering gene expression profiling comparison on whole tissue between physiological stages. During lactation, mammary epithelial cells (MEC) are predominant. However several other cell types, including myoepithelial (MMC) and immune cells are present, making it difficult to precisely determine the specificity of gene expression to the cell type of origin. In this work, an optimized reliable procedure for producing RNA from alveolar epithelial cells isolated from frozen histological sections of lactating goat, sheep and cow mammary glands using an infrared-laser based Arcturus Veritas LCM (Applied Biosystems®) system has been developed. The following steps of the microdissection workflow: cryosectioning, staining, dehydration and harvesting of microdissected cells have been carefully considered and designed to ensure cell capture efficiency without compromising RNA integrity.[br/] Results: The best results were obtained when staining 8 μm-thick sections with Cresyl violet® (Ambion, Applied Biosystems®) and capturing microdissected cells during less than 2 hours before RNA extraction. In addition, particular attention was paid to animal preparation before biopsies or slaughtering (milking) and freezing of tissue blocks which were embedded in a cryoprotective compound before being immersed in isopentane. The amount of RNA thus obtained from ca.150 to 250 acini (300,000 to 600,000 μm2) ranges between 5 to 10 ng. RNA integrity number (RIN) was ca. 8.0 and selectivity of this LCM protocol was demonstrated through qPCR analyses for several alveolar cell specific genes, including LALBA (α-lactalbumin) and CSN1S2 (αs2-casein), as well as Krt14 (cytokeratin 14), CD3e and CD68 which are specific markers of MMC, lymphocytes and macrophages, respectively.[br/] Conclusions: RNAs isolated from MEC in this manner were of very good quality for subsequent linear amplification, thus making it possible to establish a referential gene expression profile of the healthy MEC, a useful platform for tumor biomarker discovery

Diosgenin, a Steroidal Saponin, Inhibits Migration and Invasion of Human Prostate Cancer PC-3 Cells by Reducing Matrix Metalloproteinases Expression

BACKGROUND: Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum), was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. METHODS AND PRINCIPAL FINDINGS: Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN) were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF) in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt, extracellular signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that diosgenin inhibited NF-κB activity. CONCLUSION/SIGNIFICANCE: The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy