Search for: All records

The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and showed that STAG2 is uniquely tumor-suppressive among all core and auxiliary cohesin components. The heterodimeric complex components PAXIP1 and PAGR1 have highly correlated effects with STAG2 in human lung cancer cell lines, are tumor suppressors in vivo, and are epistatic to STAG2 in oncogenic KRAS-driven lung tumorigenesis in vivo. STAG2 inactivation elicits changes in gene expression, chromatin accessibility, and 3D genome conformation that impact the cancer cell state. Gene expression and chromatin accessibility similarities between STAG2- and PAXIP1-deficient neoplastic cells further relate STAG2-cohesin to PAXIP1/PAGR1. These findings reveal a STAG2-PAXIP1/PAGR1 tumor-suppressive axis and uncover novel PAXIP1-dependent and PAXIP1-independent STAG2-cohesin–mediated mechanisms of lung tumor suppression.

Morphing matter that change shapes and properties in response to external stimuli have gained significant interests in material science, robotics, biomedical engineering, wearables, architecture, and design. Along with functional advances, there is growing pressure and interest in considering the environmental impact of morphing matter during its life cycle. The unique manufacturing and usage of morphing matter means that existing sustainable design frameworks and principles for general physical products may not apply directly. For example, manufacturing morphing matter often requires designing and predicting materials' behaviors over time, and using devices fabricated with morphing matter often involves harnessing renewable energy and self‐reconfiguration, which pose unique sustainability opportunities and challenges. This study reflects and summarizes the field's practice in sustainable manufacturing, transport, use, and end‐of‐life handling of morphing matter. The term “sustainable morphing matter” (SMM) is coined, suggesting that sustainability‐conscious factors can become an integral component of morphing matter. In addition, ways to apply sustainability‐conscious factors to augment the existing design pipeline of morphing matter are presented, and more quantitative and algorithmic‐level developments are needed to apply these factors rigorously to the design process.

Floodplain inundation has been viewed as a type of binary process set by the relative elevation between river stage and levee crest. However, recent reports in the literature show that this perception may have limited applicability. In particular, through‐bank channels, conduits that cross the main river levees or banks, facilitate conditions for an “inundation continuum,” or inundation for a range of sub‐bankfull flows. Moreover, through‐bank channels and their networks provide a direct hydraulic connection between the main river and the floodplain interior. We analyzed through‐bank channel structure and floodplain topography and compared them to river surface elevation to provide greater insight on floodplain inundation processes. Results show that well‐developed levees with through‐bank channels facilitate frequent through‐bank inundation. Where levees are poorly developed, floodplain inundation occurs by overbank flow. Therefore, for a given discharge through‐bank and overbank inundation may occur simultaneously. For the Congaree River floodplain, we infer that this dichotomy of inundation processes leads to temporally and spatially complex inundation flow paths for a given river stage. Further, our analyses reveal that the inundation continuum concept should be considered in the context of having vertical, longitudinal, lateral, and temporal components.