Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity

On the Propagation of a Geoeffective Coronal Mass Ejection during March 15 -- 17, 2015

The largest geomagnetic storm so far in the solar cycle 24 was produced by a fast coronal mass ejection (CME) originating on 2015 March 15. It was an initially west-oriented CME and expected to only cause a weak geomagnetic disturbance. Why did this CME finally cause such a large geomagnetic storm? We try to find some clues by investigating its propagation from the Sun to 1 AU. First, we reconstruct the CME's kinematic properties in the corona from the SOHO and SDO imaging data with the aid of the graduated cylindrical shell (GCS) model. It is suggested that the CME propagated to the west $\sim$$33^\circ$$\pm$$10^\circ$ away from the Sun-Earth line with a speed of about 817 km s$^{-1}$ before leaving the field of view of the SOHO/LASCO C3 camera. A magnetic cloud (MC) corresponding to this CME was measured in-situ by the Wind spacecraft two days later. By applying two MC reconstruction methods, we infer the configuration of the MC as well as some kinematic information, which implies that the CME possibly experienced an eastward deflection on its way to 1 AU. However, due to the lack of observations from the STEREO spacecraft, the CME's kinematic evolution in interplanetary space is not clear. In order to fill this gap, we utilize numerical MHD simulation, drag-based CME propagation model (DBM) and the model for CME deflection in interplanetary space (DIPS) to recover the propagation process, especially the trajectory, of the CME from $30 R_S$ to 1 AU. It is suggested that the trajectory of the CME was deflected toward the Earth by about $12^\circ$, consistent with the implication from the MC reconstruction at 1 AU. This eastward deflection probably contributed to the CME's unexpected geoeffectiveness by pushing the center of the initially west-oriented CME closer to the Earth.Comment: 10 pages, 5 figures, 1 table, accepted by JGR - Space Physic

Substituting or Collaborating? A Diversion-Aware Bass Model for Evaluating Impacts from Online Content Copycats

The proliferation of social media not only enables users to produce original contents, but also brings plenty of copycatting opportunities. The copying behavior over online user-generated content (UGC) can impact content originators by diverting the potential content returns (e.g., likes and retweets). To maintain the originators’ incentive of producing original contents, it is necessary for social platforms to develop targeted punishment and compensation regulations based on the diverted returns. Thus, this study proposes to explore and measure the diversion process of content consumer returns. To formulate the returns diversion caused by copycats, a Diversion-Aware Bass model (DA-Bass) is developed by introducing the substitute effect and collaborative effect. The role of content originality in the diffusion process is further estimated. Experiments have been conducted to demonstrate the proposed model’s effectiveness in supporting social platforms to trace and measure the diverted returns

Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells

Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells