Differences in Apoptosis and Cell Cycle Distribution between Human Melanoma Cell Lines UACC903 and UACC903(+6), before and after UV Irradiation

Introduction of human chromosome 6 into malignant melanoma cell line UACC903 resulted in generation of the chromosome 6-mediated suppressed cell subline UACC903(+6) that displays attenuated growth rate, anchorage-dependency, and reduced tumorigenicity. We have showed that overexpression of a chromosome 6-encoded tumor suppressor gene led to partial suppression to UACC903 cell growth. We now describe the differences in apoptosis and cell cycle between UACC903 and UACC903(+6) before and after UV irradiation. MTT assay revealed 86.92±8.24% of UACC903 cells viable, significantly (p<0.01) higher than 48.76±5.31% of UACC903(+6), at 24 hr after 254-nm UV irradiation (40 J/M2). Before UV treatment, flow cytometry analysis revealed 6.06±0.20% apoptosis in UACC903, significantly (p=0.01) lower than 6.67±0.15% in UACC903(+6). The G0/G1, S and G2/M phase cells of UACC903 were, respectively, 54.10±0.59%, 22.31±0.50% and 16.85±0.25%, all significantly (p<0.01) different from the corresponding percentages (58.82±0.35%, 20.48±0.05%, and 13.17±0.45%) of UACC903(+6). After the UV treatment, UACC903 cells in apoptosis, G0/G1, S, and G2/M became 12.59±0.17%, 38.90±0.67%, 19.74±0.70%, and 27.01±0.66%, respectively, while UACC903(+6) cells were 24.16±0.48%, 37.97±0.62%, 19.20±0.52%, and 15.69±0.14%. TUNEL assay revealed 2.31±0.62% apoptosis in UACC903, significantly (p<0.01) lower than 9.60±1.14% of UACC903(+6), and a linear and exponential increase of apoptosis, respectively, in response to the UV treatment. These results indicate that UACC903(+6) cells have a greater tendency to undergo apoptosis and are thus much more sensitive to UV irradiation. Our findings further suggest a novel mechanism for chromosome 6-mediated suppression of tumorigenesis and metastasis, i.e., through increased cell death

Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder

This work is licensed under a Creative Commons Attribution 4.0 International License.Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical–cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical–cerebellar networks and visuomotor impairments in ASD have not yet been clarified. Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined. Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex. Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar–cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.NIMH K23 (MH092696)NIMH R01 (MH112734)Kansas Center for Autism Research and Training (K-CART) Research Investment Council Strategic Initiative GrantNICHD U54 Kansas Intellectual and Developmental Disabilities Research Center Award (U54HD090216)National Natural Science Foundation of China Award (grant no. 81371527

Magnetic and structural transitions in La0.4_{0.4}Na0.6_{0.6}Fe2_2As2_2 single crystals

La$_{0.4}$Na$_{0.6}$Fe$_2$As$_2$ single crystals have been grown out of an NaAs flux in an alumina crucible and characterized by measuring magnetic susceptibility, electrical resistivity, specific heat, as well as single crystal x-ray and neutron diffraction. La$_{0.4}$Na$_{0.6}$Fe$_2$As$_2$ single crystals show a structural phase transition from a high temperature tetragonal phase to a low-temperature orthorhombic phase at T$_s$\,=\,125\,K. This structural transition is accompanied by an anomaly in the temperature dependence of electrical resistivity, anisotropic magnetic susceptibility, and specific heat. Concomitant with the structural phase transition, the Fe moments order along the \emph{a} direction with an ordered moment of 0.7(1)\,$\mu_{\textup{B}}$ at \emph{T}\,=\,5 K. The low temperature stripe antiferromagnetic structure is the same as that in other \emph{A}Fe$_{2}$As$_{2}$ (\emph{A}\,=\,Ca, Sr, Ba) compounds. La$_{0.5-x}$Na$_{0.5+x}$Fe$_2$As$_2$ provides a new material platform for the study of iron-based superconductors where the electron-hole asymmetry could be studied by simply varying La/Na ratio.Comment: 9 pages, 7 figures, to appear in Physical Review

Specificity of mouse GM2 activator protein and beta-N-acetylhexosaminidases A and B. Similarities and differences with their human counterparts in the catabolism of GM2.

Tay-Sachs disease, an inborn lysosomal disease featuring a buildup of GM2 in the brain, is caused by a deficiency of β-hexosaminidase A (Hex A) or GM2activator. Of the two human lysosomal Hex isozymes, only Hex A, not Hex B, cleaves GM2 in the presence of GM2activator. In contrast, mouse Hex B has been reported to be more active than Hex A in cleaving GM2 (Burg, J., Banerjee, A., Conzelmann, E., and Sandhoff, K. (1983) Hoppe Seyler's Z. Physiol. Chem. 364, 821–829). In two independent studies, mice with the targeted disruption of the Hexa gene did not display the severe buildup of brain GM2 or the concomitant abnormal behavioral manifestations seen in human Tay-Sachs patients. The results of these two studies were suggested to be attributed to the reported GM2 degrading activity of mouse Hex B. To clarify the specificity of mouse Hex A and Hex B and to better understand the observed results of the mouse model of Tay-Sachs disease, we have purified mouse liver Hex A and Hex B and also prepared the recombinant mouse GM2 activator. Contrary to the findings of Burget al., we found that the specificities of mouse Hex A and Hex B toward the catabolism of GM2 were not different from the corresponding human Hex isozymes. Mouse Hex A, but not Hex B, hydrolyzes GM2 in the presence of GM2activator, whereas GM2 is refractory to mouse Hex B with or without GM2 activator. Importantly, we found that, in contrast to human GM2 activator, mouse GM2activator could effectively stimulate the hydrolysis of GA2by mouse Hex A and to a much lesser extent also by Hex B. These results provide clear evidence on the existence of an alternative pathway for GM2 catabolism in mice by converting GM2 to GA2 and subsequently to lactosylceramide. They also provide the explanation for the lack of excessive GM2 accumulation in the Hexa gene-disrupted mice

An exponential decline at the bright end of the z=6 galaxy luminosity function

We present the results of a search for the most luminous star-forming galaxies at redshifts z~6 based on CFHT Legacy Survey data. We identify a sample of 40 Lyman break galaxies brighter than magnitude z'=25.3 across an area of almost 4 square degrees. Sensitive spectroscopic observations of seven galaxies provide redshifts for four, of which only two have moderate to strong Lyman alpha emission lines. All four have clear continuum breaks in their spectra. Approximately half of the Lyman break galaxies are spatially resolved in 0.7 arcsec seeing images, indicating larger sizes than lower luminosity galaxies discovered with the Hubble Space Telescope, possibly due to on-going mergers. The stacked optical and infrared photometry is consistent with a galaxy model with stellar mass ~ 10^{10} solar masses. There is strong evidence for substantial dust reddening with a best-fit A_V=0.7 and A_V>0.48 at 2 sigma confidence, in contrast to the typical dust-free galaxies of lower luminosity at this epoch. The spatial extent and spectral energy distribution suggest that the most luminous z~6 galaxies are undergoing merger-induced starbursts. The luminosity function of z=5.9 star-forming galaxies is derived. This agrees well with previous work and shows strong evidence for an exponential decline at the bright end, indicating that the feedback processes which govern the shape of the bright end are occurring effectively at this epoch.Comment: 14 pages, 11 figures, AJ in press, revised to address referee comment

Verticalization of bacterial biofilms

Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms of rod-shaped bacteria were observed at single-cell resolution and shown to develop from a disordered, two-dimensional layer of founder cells into a three-dimensional structure with a vertically-aligned core. Here, we elucidate the physical mechanism underpinning this transition using a combination of agent-based and continuum modeling. We find that verticalization proceeds through a series of localized mechanical instabilities on the cellular scale. For short cells, these instabilities are primarily triggered by cell division, whereas long cells are more likely to be peeled off the surface by nearby vertical cells, creating an "inverse domino effect". The interplay between cell growth and cell verticalization gives rise to an exotic mechanical state in which the effective surface pressure becomes constant throughout the growing core of the biofilm surface layer. This dynamical isobaricity determines the expansion speed of a biofilm cluster and thereby governs how cells access the third dimension. In particular, theory predicts that a longer average cell length yields more rapidly expanding, flatter biofilms. We experimentally show that such changes in biofilm development occur by exploiting chemicals that modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15 figure

The 95zr(n, gamma)96zr cross section from the surrogate ratio method and its effect on the s-process nucleosynthesis

The 95Zr(n,gamma)96Zr reaction cross section is crucial in the modelling of s-process nucleosynthesis in asymptotic giant branch stars because it controls the operation of the branching point at the unstable 95Zr and the subsequent production of 96Zr. We have carried out the measurement of the 94Zr(18O,16O) and 90Zr(18O,16O) reactions and obtained the gamma-decay probability ratio of 96Zr* and 92Zr* to determine the 95Zr(n,gamma)96Zr reaction cross sections with the surrogate ratio method. Our deduced maxwellian-averaged cross section of 66+-16 mb at 30 keV is close to the value recommended by Bao et al. (2000), but 30% and more than a factor of two larger than the values proposed by Toukan & Kappeler (1990) and Lugaro et al. (2014), respectively, and routinely used in s-process models. We tested the new rate in stellar models with masses between 2 and 6 Msun and metallicities 0.014 and 0.03. The largest changes - up 80% variations in 96Zr - are seen in models of mass 3-4 Msun, where the 22Ne neutron source is mildly activated. The new rate can still provide a match to data from meteoritic stardust silicon carbide grains, provided the maximum mass of the parent stars is below 4 Msun, for a metallicity of 0.03.Comment: 10 pages, 6 figures, accepted for publication in Ap