Cornell University

About: Cornell University is a education organization based out in Ithaca, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 102246 authors who have published 235546 publications receiving 12283673 citations. The organization is also known as: Cornell & CUI.

Cyclosporine induces cancer progression by a cell-autonomous mechanism

Abstract: Malignancy is a common and dreaded complication following organ transplantation. The high incidence of neoplasm and its aggressive progression, which are associated with immunosuppressive therapy, are thought to be due to the resulting impairment of the organ recipient's immune-surveillance system. Here we report a mechanism for the heightened malignancy that is independent of host immunity. We show that cyclosporine (cyclosporin A), an immunosuppressant that has had a major impact on improving patient outcome following organ transplantation, induces phenotypic changes, including invasiveness of non-transformed cells, by a cell-autonomous mechanism. Our studies show that cyclosporine treatment of adenocarcinoma cells results in striking morphological alterations, including membrane ruffling and numerous pseudopodial protrusions, increased cell motility, and anchorage-independent (invasive) growth. These changes are prevented by treatment with monoclonal antibodies directed at transforming growth factor-beta (TGF-beta). In vivo, cyclosporine enhances tumour growth in immunodeficient SCID-beige mice; anti-TGF-beta monoclonal antibodies but not control antibodies prevent the cyclosporine-induced increase in the number of metastases. Our findings suggest that immunosuppressants like cyclosporine can promote cancer progression by a direct cellular effect that is independent of its effect on the host's immune cells, and that cyclosporine-induced TGF-beta production is involved in this.

m 6 A RNA methylation promotes XIST -mediated transcriptional repression

Abstract: The long non-coding RNA X-inactive specific transcript (XIST) mediates the transcriptional silencing of genes on the X chromosome. Here we show that, in human cells, XIST is highly methylated with at least 78 N^6-methyladenosine (m^6A) residues—a reversible base modification of unknown function in long non-coding RNAs. We show that m^6A formation in XIST, as well as in cellular mRNAs, is mediated by RNA-binding motif protein 15 (RBM15) and its paralogue RBM15B, which bind the m^6A-methylation complex and recruit it to specific sites in RNA. This results in the methylation of adenosine nucleotides in adjacent m^6A consensus motifs. Furthermore, we show that knockdown of RBM15 and RBM15B, or knockdown of methyltransferase like 3 (METTL3), an m^6A methyltransferase, impairs XIST-mediated gene silencing. A systematic comparison of m^6A-binding proteins shows that YTH domain containing 1 (YTHDC1) preferentially recognizes m^6A residues on XIST and is required for XIST function. Additionally, artificial tethering of YTHDC1 to XIST rescues XIST-mediated silencing upon loss of m^6A. These data reveal a pathway of m^6A formation and recognition required for XIST-mediated transcriptional repression.

The Environment of Poverty: Multiple Stressor Exposure, Psychophysiological Stress, and Socioemotional Adjustment

Abstract: The one in five children growing up in poverty in America have elevated risk for socioemotional difficulties. One contributing factor to their elevated risk may be exposure to multiple physical and psychosocial stressors. This study demonstrated that 8- to 10-year-old, low-income, rural children (N = 287) confront a wider array of multiple physical (substandard housing, noise, crowding) and psychosocial (family turmoil, early childhood separation, community violence) stressors than do their middle-income counterparts. Prior research on self-reported distress among inner-city minority children is replicated and extended among low-income, rural White children with evidence of higher levels of self- and parent-reported psychological distress, greater difficulties in self-regulatory behavior (delayed gratification), and elevated psychophysiological stress (resting blood pressure, overnight neuroendocrine hormones). Preliminary mediational analyses with cross-sectional data suggest that cumulative stressor exposure may partially account for the well-documented, elevated risk of socioemotional difficulties accompanying poverty.

Improving the Density of Jammed Disordered Packings Using Ellipsoids

Abstract: Packing problems, such as how densely objects can fill a volume, are among the most ancient and persistent problems in mathematics and science. For equal spheres, it has only recently been proved that the face-centered cubic lattice has the highest possible packing fraction \({\varphi}={\pi}{/}\sqrt{18}{\approx}0.74\) . It is also well known that certain random (amorphous) jammed packings have φ ≈ 0.64. Here, we show experimentally and with a new simulation algorithm that ellipsoids can randomly pack more densely—up to φ= 0.68 to 0.71for spheroids with an aspect ratio close to that of M&M9s Candies—and even approach φ ≈ 0.74 for ellipsoids with other aspect ratios. We suggest that the higher density is directly related to the higher number of degrees of freedom per particle and thus the larger number of particle contacts required to mechanically stabilize the packing. We measured the number of contacts per particle Z ≈ 10 for our spheroids, as compared to Z ≈ 6 for spheres. Our results have implications for a broad range of scientific disciplines, including the properties of granular media and ceramics, glass formation, and discrete geometry.

Ten questions concerning the large-eddy simulation of turbulent flows

Abstract: In the past 30 years, there has been considerable progress in the development of large-eddy simulation (LES) for turbulent flows, which has been greatly facilitated by the substantial increase in computer power. In this paper, we raise some fundamental questions concerning the conceptual foundations of LES and about the methodologies and protocols used in its application. The 10 questions addressed are stated at the end of the introduction. Several of these questions highlight the importance of recognizing the dependence of LES calculations on the artificial parameter Δ (i.e. the filter width or, more generally, the turbulence resolution length scale). The principle that LES predictions of turbulence statistics should depend minimally on Δ provides an alternative justification for the dynamic procedure.