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The Early Cretaceous is an important time of transition in Earth history, marked by a succession of oceanic anoxic events and carbon cycle perturbations that drove changes on land and in the ocean. The need for more precise geochronologic constraints in terrestrial sediments of Early Cretaceous age that record faunal and floral transitions is especially critical. The Cedar Mountain Formation (CMF) is a continental lithostratigraphic unit that hosts a trove of paleoclimate archives and important dinosaurian fossil localities. Determining the timing of deposition of CMF strata has been an ongoing effort for many years. Here, we present new lithostratigraphic and carbon isotope chemostratigraphic data along with high‐precision radiometric ages to further constrain the Ruby Ranch Member of the CMF at a unique locality referred to as “Lake Carpenter,” where a thick section of dominantly lacustrine strata overlies fluvial‐overbank to palustrine strata more typical of other Ruby Ranch Member outcrops. A bentonite bed near the base of the section provides one of the most precise ages yet determined within the Ruby Ranch Member of 115.92 ± 0.14 Ma via CA‐ID‐TIMS U‐Pb analysis of zircons. The age and the trends in the carbon isotope record indicate that the Lake Carpenter sediments were deposited entirely within the late Aptian Stage. These unique new data provide an important step toward improving our understanding of the timing of Early Cretaceous evolutionary and paleoclimate events.

 

Enhancer of zeste homolog 2 (EZH2) catalyzes the trimethylation of histone H3 at lysine 27 via the polycomb recessive complex 2 (PRC2) and plays a time‐specific role in normal fetal liver development. EZH2 is overexpressed in hepatoblastoma (HB), an embryonal tumor. EZH2 can also promote tumorigenesis via a noncanonical, PRC2‐independent mechanism via proto‐oncogenic, direct protein interaction, including β‐catenin. We hypothesize that the pathological activation of EZH2 contributes to HB propagation in a PRC2‐independent manner.

We demonstrate that EZH2 promotes proliferation in HB tumor‐derived cell lines through interaction with β‐catenin. Although aberrant EZH2 expression occurs, we determine that both canonical and noncanonical EZH2 signaling occurs based on specific gene‐expression patterns and interaction with SUZ12, a PRC2 component, and β‐catenin. Silencing and inhibition of EZH2 reduce primary HB cell proliferation.

EZH2 overexpression promotes HB cell proliferation, with both canonical and noncanonical function detected. However, because EZH2 directly interacts with β‐catenin in human tumors and EZH2 overexpression is not equal to SUZ12, it seems that a noncanonical mechanism is contributing to HB pathogenesis. Further mechanistic studies are necessary to elucidate potential pathogenic downstream mechanisms and translational potential of EZH2 inhibitors for the treatment of HB.

 

Chemical reaction networks (CRNs) are an important tool for molecular programming, a field that is rapidly expanding our ability to deploy computer programs into biological systems for a variety of applications. However, CRNs are also difficult to work with due to their massively parallel nature, leading to the need for higher-level languages that allow for easier computation with CRNs. Recently, research has been conducted into a variety of higher-level languages for deterministic CRNs but modeling CRN parallelism, managing error accumulation, and finding natural CRN representations are ongoing challenges. We introduce Reactamole, a higher-level language for deterministic CRNs that utilizes the functional reactive programming (FRP) paradigm to represent CRNs as a reactive dataflow network. Reactamole equates a CRN with a functional reactive program, implementing the key primitives of the FRP paradigm directly as CRNs. The functional nature of Reactamole makes reasoning about molecular programs easier, and its strong static typing allows us to ensure that a CRN is well-formed by virtue of being well-typed. In this paper, we describe the design of Reactamole and how we use CRNs to represent the common datatypes and operations found in FRP. We also demonstrate the potential of this functional reactive approach to molecular programming by giving an extended example where a CRN is constructed using FRP to modulate and demodulate an amplitude modulated signal.