Gene Systems Network Inferred from Expression Profiles in Hepatocellular Carcinogenesis by Graphical Gaussian Model

Hepatocellular carcinoma (HCC) in a liver with advanced-stage chronic hepatitis C (CHC) is induced by hepatitis C virus, which chronically infects about 170 million people worldwide. To elucidate the associations between gene groups in hepatocellular carcinogenesis, we analyzed the profiles of the genes characteristically expressed in the CHC and HCC cell stages by a statistical method for inferring the network between gene systems based on the graphical Gaussian model. A systematic evaluation of the inferred network in terms of the biological knowledge revealed that the inferred network was strongly involved in the known gene-gene interactions with high significance (P<10−4), and that the clusters characterized by different cancer-related responses were associated with those of the gene groups related to metabolic pathways and morphological events. Although some relationships in the network remain to be interpreted, the analyses revealed a snapshot of the orchestrated expression of cancer-related groups and some pathways related with metabolisms and morphological events in hepatocellular carcinogenesis, and thus provide possible clues on the disease mechanism and insights that address the gap between molecular and clinical assessments

Global Collapses and Expansions in Star-Forming Clouds

Spectral molecular line profile observations of star-forming molecular clouds sometimes show distinct red asymmetric double-peaked molecular line profiles with weaker blue peaks and stronger red peaks. For some star-forming molecular clouds, such molecular transitions with red asymmetric line profiles and blue asymmetric line profiles (i.e. blue asymmetric double-peaked molecular line profiles with weaker red peaks and stronger blue peaks) may coexist in spatially resolved spectral observations, while for others, such molecular transitions with red asymmetric line profiles may completely dominate in spatially resolved spectral observations. Blue asymmetric line profiles are usually interpreted as signals of central core collapses, while red asymmetric line profiles remain unexplained. In this paper, we advance a spherically symmetric self-similar hydrodynamic model framework for envelope expansions with core collapses (EECC) of a general polytropic molecular gas cloud under self-gravity. Based on such EECC hydrodynamic cloud models, we perform tracer molecular line profile calculations using the publicly available RATRAN code for star-forming clouds with spectroscopic signatures of red asymmetric line profiles. The presence of red asymmetric line profiles from molecular cloud cores indicates that EECC processes are most likely an essential hydrodynamic process of star formation. With spatial distributions, we explore various profiles of molecular lines for several tracer molecules in different settings of EECC dynamic models with and without shocks.Comment: 12 pages, 7 figures, accepted for publication in MNRA

Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice

Acknowledgments and Disclosures This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no biomedical financial interests or potential conflicts of interest.Peer reviewedPublisher PD

In vitro and in vivo effects of insulin-producing cells generated by xeno-antigen free 3D culture with RCP piece

To establish widespread cell therapy for type 1 diabetes mellitus, we aimed to develop an effective protocol for generating insulin-producing cells (IPCs) from adipose-derived stem cells (ADSCs). We established a 3D culture using a human recombinant peptide (RCP) petaloid μ-piece with xeno-antigen free reagents. Briefly, we employed our two-step protocol to differentiate ADSCs in 96-well dishes and cultured cells in xeno-antigen free reagents with 0.1 mg/mL RCP μ-piece for 7 days (step 1), followed by addition of histone deacetylase inhibitor for 14 days (step 2). Generated IPCs were strongly stained with dithizone, anti-insulin antibody at day 21, and microstructures resembling insulin secretory granules were detected by electron microscopy. Glucose stimulation index (maximum value, 4.9) and MAFA mRNA expression were significantly higher in 3D cultured cells compared with conventionally cultured cells (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of streptozotocin-induced diabetic nude mice converted to normoglycaemic state around 14 days after transplantation of 96 IPCs under kidney capsule or intra-mesentery. Histological evaluation revealed that insulin and C-peptide positive structures existed at day 120. Our established xeno-antigen free and RCP petaloid μ-piece 3D culture method for generating IPCs may be suitable for clinical application, due to the proven effectiveness in vitro and in vivo

Characterizing the velocity field in hydrodynamical simulations of low-mass star formation using spectral line profiles

When low-mass stars form, the collapsing cloud of gas and dust goes through several stages which are usually characterized by the shape of their spectral energy distributions. Such classification is based on the cloud morphology only and does not address the dynamical state of the object. In this paper we investigate the initial cloud collapse and subsequent disk formation through the dynamical behavior as reflected in the sub-millimeter spectral emission line profiles. If a young stellar object is to be characterized by its dynamical structure it is important to know how accurately information about the velocity field can be extracted and which observables provide the best description of the kinematics. Of particular interest is the transition from infalling envelope to rotating disk, because this provides the initial conditions for the protoplanetary disk, such as mass and size. We use a hydrodynamical model, describing the collapse of a core and formation of a disk, to produce synthetic observables which we compare to calculated line profiles of a simple parameterized model. Because we know the velocity field from the hydrodynamical simulation we can determine in a quantitative way how well our best-fit parameterized velocity field reproduces the original. We use a molecular line excitation and radiation transfer code to produce spectra of both our hydro dynamical simulation as well as our parameterized model. We find that information about the velocity field can reasonably well be derived by fitting a simple model to either single-dish lines or interferometric data, but preferentially by using a combination of the two. Our result shows that it is possible to establish relative ages of a sample of young stellar objects using this method, independently of the details of the hydrodynamical model.Comment: 12 pages, 11 figures, accepted for publication in A&A on June 1

Molecular Line Profiles of Collapsing Gas Clouds

Emission line profiles of tracer molecule H$_2$CO 140 GHz transition from gravitational core collapsing clouds in the dynamic process of forming protostars are calculated, using a simple ray-tracing radiative transfer model. Three self-similar dynamic inside-out core collapse models -- the conventional polytropic model, the empirical hybrid model and the isothermal model -- for star-forming molecular clouds are examined and compared. The isothermal model cannot produce observed asymmetric double-peak molecular line profiles. The conventional polytropic model, which gives flow velocity, mass density and temperature profiles self-consistently, can produce asymmetric double-peak line profiles for a core collapsing cloud. In particular, the blue peak is stronger than the red peak, consistent with a broad class of molecular line profile observations. The relative strengths of the blue and red peaks within a molecular line profile are determined by the cloud temperature gradient. The conventional polytropic model can be utilized to produce molecular line-profile templates, for extracting dynamical information from line spectra of molecular globules undergoing a gravitational core collapse. We show a sample fit using the 140 GHz H$_2$CO emission line from the central region of the molecular globule B335 by our model with $\gamma=1.2$. The calculation of line profiles and fitting processes also offer a scenario to estimate the protostellar mass, the kernel mass accretion rate, and the evolution time scale of a core collapsing cloud. Our model can be readily adapted to other tracer molecules with more or less constant abundances in star-forming clouds.Comment: 12 pages, 10 figures, accepted for publication in MNRA

Massive star formation around I05345+3157 -- I. The dense gas

We present observations of the intermediate to massive star-forming region I05345+3157 using the molecular line tracer CS(2-1) with CARMA to reveal the properties of the dense gas cores. Seven gas cores are identified in the integrated intensity map of CS(2-1). Among these, core 1 and core 3 have counterparts in the 2.7 millimeter continuum data. We suggest that core 1 and core 3 are star-forming cores that may already or will very soon harbor young massive protostars. The total masses of core 1 estimated from the LTE method and dust emission by assuming a gas-to-dust ratio are 5 +- 1 solar masses and 18 +- 6 solar masses, and that of core 3 are 15 +- 7 solar masses and 11 +- 3 solar masses. The spectrum of core 3 shows blue-skewed self-absorption, which suggests gas infall -- a collapsing core. The observed broad linewidths of the seven gas cores indicate non-thermal motions. These non-thermal motions can be interactions with nearby outflows or due to the initial turbulence; the former is observed, while the role of initial turbulence is less certain. Finally, the virial masses of the gas cores are larger than the LTE masses, which for a bound core implies a requirement on the external pressure of ~ 10^8 K/cm^3. The cores have the potential to further form massive stars.Comment: Accepted for publication in MNRA

A deeply embedded young protoplanetary disk around L1489 IRS observed by the submillimeter array

Circumstellar disks are expected to form early in the process that leads to the formation of a young star, during the collapse of the dense molecular cloud core. It is currently not well understood at what stage of the collapse the disk is formed or how it subsequently evolves. We aim to identify whether an embedded Keplerian protoplanetary disk resides in the L1489 IRS system. Given the amount of envelope material still present, such a disk would respresent a very young example of a protoplanetary disk. Using the Submillimeter Array (SMA) we have observed the HCO$^+$ $J=$ 3--2 line with a resolution of about 1$''$. At this resolution a protoplanetary disk with a radius of a few hundred AUs should be detectable, if present. Radiative transfer tools are used to model the emission from both continuum and line data. We find that these data are consistent with theoretical models of a collapsing envelope and Keplerian circumstellar disk. Models reproducing both the SED and the interferometric continuum observations reveal that the disk is inclined by 40$^\circ$ which is significantly different to the surrounding envelope (74$^\circ$). This misalignment of the angular momentum axes may be caused by a gradient within the angular momentum in the parental cloud or if L1489 IRS is a binary system rather than just a single star. In the latter case, future observations looking for variability at sub-arcsecond scales may be able to constrain these dynamical variations directly. However, if stars form from turbulent cores, the accreting material will not have a constant angular momentum axis (although the average is well defined and conserved) in which case it is more likely to have a misalignment of the angular momentum axes of the disk and the envelope.Comment: 11 pages, 13 figures, accepted by A&