Lack of Foxp3 function and expression in the thymic epithelium

Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4+ T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells

Single Nucleotide Polymorphisms in Selected Apoptotic Genes and BPDE-Induced Apoptotic Capacity in Apparently Normal Primary Lymphocytes: A Genotype-Phenotype Correlation Analysis

Apoptotic capacity (AC) in primary lymphocytes may be a marker for cancer susceptibility, and functional single nucleotide polymorphisms (SNPs) in genes involved in apoptotic pathways may modulate cellular AC in response to DNA damage. To further examine the correlation between apoptotic genotypes and phenotype, we genotyped 14 published SNPs in 11 apoptosis-related genes (i.e., p53, Bcl-2, BAX, CASP9, DR4, Fas, FasL, CASP8, CASP10, CASP3, and CASP7) and assessed the AC in response to benzo[a]pyrene-7,8-9,10-diol epoxide (BPDE) in cultured primary lymphocytes from 172 cancer-free subjects. We found that among these 14 SNPs, R72P, intron 3 16-bp del/ins, and intron 6 G>A in p53, −938C>A in Bcl-2, and I522L in CASP10 were significant predictors of the BPDE-induced lymphocytic AC in single-locus analysis. In the combined analysis of the three p53 variants, we found that the individuals with the diplotypes carrying 0-1 copy of the common p53 R-del-G haplotype had higher AC values compared to other genotypes. Although the study size may not have the statistical power to detect the role of other SNPs in AC, our findings suggest that some SNPs in genes involved in the intrinsic apoptotic pathway may modulate lymphocytic AC in response to BPDE exposure in the general population. Larger studies are needed to validate these findings for further studying individual susceptibility to cancer and other apoptosis-related diseases

Twofold efficiency increase in nanocrystalline-TiO2/polymer photovoltaic devices by interfacial modification with a lithium salt

Modification of the interface of titanium dioxide/poly[2-(2-ethylhexyloxy)-5-methoxy-1,4,-phenylenevinylene] (TiO2/MEH-PPV) nanocomposite photovoltaic devices with a lithium salt, Li[CF3SO2](2)N, is shown to result in a twofold increase in device efficiency. The devices are of the type ITO/TiO2/MEH-PPV/Au. The TiO2 layer is deposited by doctor blading a colloidal anatase paste, and the polymer is then spin-coated on top followed by thermal evaporation of gold contacts. Careful control of manufacturing conditions and use of a 35 nm polymer layer leads to a device efficiency of 0.48% for un-modified devices. The increased efficiency following Li treatment is the result of a 40% increase in both the short-circuit current and fill factor, while the open-circuit voltage remains unchanged. A maximum efficiency of 1.05% has been achieved under 80% sun illumination. This represents a record efficiency for this type of cell. Photoconductivity experiments show a substantial increase in conductivity of the TiO2 layer following Li modification. Interfacial modification is done via a simple soaking procedure, and the effect of varying the concentration of Li[CF3SO2](2)N is discussed. We report investigations into optimization and the mechanism of such improvement, for example by varying processing parameters of the modification procedure or the ionic species themselves

Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions

<p>Abstract</p> <p>Background</p> <p>It is of growing interest to develop novel approaches to initiate differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes. The purpose of this investigation was to determine if Sphingosine-1-phosphate (S1P), a native circulating bioactive lipid metabolite, plays a role in differentiation of human umbilical cord mesenchymal stem cells (HUMSCs) into cardiomyocytes. We also developed an engineered cell sheet from these HUMSCs derived cardiomyocytes by using a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm) cell sheet technology.</p> <p>Methods</p> <p>Cardiomyogenic differentiation of HUMSCs was performed by culturing these cells with either designated cardiomyocytes conditioned medium (CMCM) alone, or with 1 μM S1P; or DMEM with 10% FBS + 1 μM S1P. Cardiomyogenic differentiation was determined by immunocytochemical analysis of expression of cardiomyocyte markers and patch clamping recording of the action potential.</p> <p>Results</p> <p>A cardiomyocyte-like morphology and the expression of α-actinin and myosin heavy chain (MHC) proteins can be observed in both CMCM culturing or CMCM+S1P culturing groups after 5 days' culturing, however, only the cells in CMCM+S1P culture condition present cardiomyocyte-like action potential and voltage gated currents. A new approach was used to form PIPAAm based temperature-responsive culture surfaces and this successfully produced cell sheets from HUMSCs derived cardiomyocytes.</p> <p>Conclusions</p> <p>This study for the first time demonstrates that S1P potentiates differentiation of HUMSCs towards functional cardiomyocytes under the designated culture conditions. Our engineered cell sheets may provide a potential for clinically applicable myocardial tissues should promote cardiac tissue engineering research.</p

Isomer-Resolved Mobility-Mass Analysis of alpha-Pinene Ozonolysis Products

Highly oxygenated organic molecules (HOMs) are important sources of atmospheric aerosols. Resolving the molecular-level formation mechanisms of these HOMs from freshly emitted hydrocarbons improves the understanding of aerosol properties and their influence on the climate. In this study, we measure the electrical mobility and mass-to-charge ratio of alpha-pinene oxidation products using a secondary electrospray-differential mobility analyzer-mass spectrometer (SESI-DMA-MS). The mass-mobility spectrum of the oxidation products is measured with seven different reagent ions generated by the electrospray. We analyzed the mobility-mass spectra of the oxidation products C9-10H14-18O2-6. Our results show that acetate and chloride yield the highest charging efficiencies. Analysis of the mobility spectra suggests that the clusters have 1-5 isomeric structures (i.e., ion-molecule cluster structures with distinct mobilities), and the number is affected by the reagent ion. Most of the isomers are likely cluster isomers originating from binding of the reagent ion to different sites of the molecule. By comparing the number of observed isomers and measured mobilities and collision cross sections between standard pinanediol and pinonic acid to the values observed for C10H18O2 and C10H16O3 produced from oxidation of alpha-pinene, we confirm that pinanediol and pinonic acid are the only isomers for these elemental compositions in our experimental conditions. Our study shows that the SESI-DMA-MS produces new information from the first steps of oxidation of alpha-pinene.Peer reviewe

Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin

Lidar Observations of Stratospheric Gravity Waves From 2011 to 2015 at McMurdo (77.84°S, 166.69°E), Antarctica: 2. Potential Energy Densities, Lognormal Distributions, and Seasonal Variations

Five years of Fe Boltzmann lidar's Rayleigh temperature data from 2011 to 2015 at McMurdo are used to characterize gravity wave potential energy mass density (Epm), potential energy volume density (Epv), vertical wave number spectra, and static stability N² in the stratosphere 30–50 km. Epm (Epv) profiles increase (decrease) with altitude, and the scale heights of Epv indicate stronger wave dissipation in winter than in summer. Altitude mean (Formula presented.) and (Formula presented.) obey lognormal distributions and possess narrowly clustered small values in summer but widely spread large values in winter. (Formula presented.) and (Formula presented.) vary significantly from observation to observation but exhibit repeated seasonal patterns with summer minima and winter maxima. The winter maxima in 2012 and 2015 are higher than in other years, indicating interannual variations. Altitude mean (Formula presented.) varies by ~30–40% from the midwinter maxima to minima around October and exhibits a nearly bimodal distribution. Monthly mean vertical wave number power spectral density for vertical wavelengths of 5–20 km increases from summer to winter. Using Modern Era Retrospective Analysis for Research and Applications version 2 data, we find that large values of (Formula presented.) during wintertime occur when McMurdo is well inside the polar vortex. Monthly mean (Formula presented.) are anticorrelated with wind rotation angles but positively correlated with wind speeds at 3 and 30 km. Corresponding correlation coefficients are −0.62, +0.87, and +0.80, respectively. Results indicate that the summer-winter asymmetry of (Formula presented.) is mainly caused by critical level filtering that dissipates most gravity waves in summer. (Formula presented.) variations in winter are mainly due to variations of gravity wave generation in the troposphere and stratosphere and Doppler shifting by the mean stratospheric winds

A comprehensive K 2 and ground-based study of CRTS J035905.9+175034, an eclipsing SU UMa system with a large mass ratio

CRTS J035905.9+175034 is the first eclipsing SU UMa system for which a superoutburst has been observed by Kepler in the short-cadence mode. The light curve contains one superoutburst, eight normal outbursts (including a precursor to the superoutburst), and several minioutbursts that are present before—but not after—the superoutburst. The superoutburst began with a precursor normal outburst, and shortly after the peak of the precursor, the system developed large-amplitude superhumps that achieved their maximum amplitude after just three superhump cycles. The period excess of the initial superhump period relative to the orbital period implies a mass ratio of 0.281 ± 0.015, placing it marginally above most theoretical predictions of the highest-possible mass ratio for superhump formation. In addition, our analysis of the variations in eclipse width and depth, as well as the hot spot amplitudes, generally provides substantiation of the thermal-tidal instability model. The K 2 data, in conjunction with our ground-based time-resolved spectroscopy and photometry from 2014 to 2016, allows us to determine many of the fundamental parameters of this system