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MYC oncogene elicits tumorigenesis associated with embryonic, ribosomal biogenesis, and tissue-lineage dedifferentiation gene expression changes
No full textMYC is a transcription factor frequently overexpressed in cancer. To determine how MYC drives the neoplastic phenotype, we performed transcriptomic analysis using a panel of MYC-driven autochthonous transgenic mouse models. We found that MYC elicited gene expression changes mostly in a tissue- and lineage-specific manner across B-cell lymphoma, T-cell acute lymphoblastic lymphoma, hepatocellular carcinoma, renal cell carcinoma, and lung adenocarcinoma. However, despite these gene expression changes being mostly tissue-specific, we uncovered a convergence on a common pattern of upregulation of embryonic stem cell gene programs and downregulation of tissue-of-origin gene programs across MYC-driven cancers. These changes are representative of lineage dedifferentiation, that may be facilitated by epigenetic alterations that occur during tumorigenesis. Moreover, while several cellular processes are represented among embryonic stem cell genes, ribosome biogenesis is most specifically associated with MYC expression in human primary cancers. Altogether, MYC’s capability to drive tumorigenesis in diverse tissue types appears to be related to its ability to both drive a core signature of embryonic genes that includes ribosomal biogenesis genes as well as promote tissue and lineage specific dedifferentiation
A grand master of seismology and mentoring [Don Helmberger]
No full textI joined Don Helmberger’s group in the summer of 2008, after getting a Master’s degree in China from Sidao Ni, another graduate student of Don’s. I was very excited, because Don has a giant academic family tree and I thought I would become Don’s last student, which is quite an honor in the Chinese culture, so-called the “final apprentice”. I was wrong! Don had another seven students after me and the final apprentice honor went to Voon-Hui Lai. Over Don’s long career, he had scores of students, many of whom are now big names in academia, especially in the United States and in China, because Don mentored a number of Chinese students
Diamond electrode facilitated electrosynthesis of water and wastewater treatment oxidants
No full textWhile diamond electrodes have been commonly used to generate •OH to treat a variety of persistent water and wastewater micropollutants, mass transfer limitations and the non-selective, short-lived nature of the •OH restrict the degradation to the solution at, or near, the electrode surface. However, diamond electrodes can generate oxidizing species that facilitate micropollutant degradation in the bulk water solution. These include persulfate, sulfate radicals, peroxodiphosphate, ferrate, permanganate, reactive chlorine species, hydrogen peroxide, and ozone, which have been reported during electrochemical treatment of water with diamond electrodes. Although still restricted to specialized applications, recent studies, summarized in this review, have proven the electrogeneration of these additional oxidant species to be effective. They have shown the adaptability and potential of diamond electrode-based water treatment to mitigate the presence of micropollutants in water
Hydrodynamics of Collisions and Close Encounters between Stellar Black Holes and Main-sequence Stars
No full textRecent analyses have shown that close encounters between stars and stellar black holes occur frequently in dense star clusters. Depending upon the distance at closest approach, these interactions can lead to dissipating encounters such as tidal captures and disruptions, or direct physical collisions, all of which may be accompanied by bright electromagnetic transients. In this study, we perform a wide range of hydrodynamic simulations of close encounters between black holes and main-sequence stars that collectively cover the parameter space of interest, and we identify and classify the various possible outcomes. In the case of nearly head-on collisions, the star is completely disrupted with roughly half of the stellar material becoming bound to the black hole. For more distant encounters near the classical tidal-disruption radius, the star is only partially disrupted on the first pericenter passage. Depending upon the interaction details, the partially disrupted stellar remnant may be tidally captured by the black hole or become unbound (in some cases, receiving a sufficiently large impulsive kick from asymmetric mass loss to be ejected from its host cluster). In the former case, the star will undergo additional pericenter passages before ultimately being disrupted fully. Based on the properties of the material bound to the black hole at the end of our simulations (in particular, the total bound mass and angular momentum), we comment upon the expected accretion process and associated electromagnetic signatures that are likely to result
Alkyne-Tagged Raman Probes for Local Environmental Sensing by Hydrogen–Deuterium Exchange
No full textAlkyne-tagged Raman probes have shown high promise for noninvasive and sensitive visualization of small biomolecules to understand their functional roles in live cells. However, the potential for alkynes to sense cellular environments that goes beyond imaging remains to be further explored. Here, we report a general strategy for Raman imaging-based local environment sensing by hydrogen–deuterium exchange (HDX) of terminal alkynes (termed alkyne-HDX). We first demonstrate, in multiple Raman probes, that deuterations of the alkynyl hydrogens lead to remarkable shifts of alkyne Raman peaks for about 130 cm–1, providing resolvable signals suited for imaging-based analysis with high specificity. Both our analytical derivation and experimental characterizations subsequently establish that HDX kinetics are linearly proportional to both alkyne pKas and environmental pDs. After validating the quantitative nature of this strategy, we apply alkyne-HDX to sensing local chemical and cellular environments. We establish that alkyne-HDX exhibits high sensitivity to various DNA structures and demonstrates the capacity to detect DNA structural changes in situ from UV-induced damage. We further show that this strategy is also applicable to resolve subtle pD variations in live cells. Altogether, our work lays the foundation for utilizing alkyne-HDX strategy to quantitatively sense the local environments for a broad spectrum of applications in complex biological systems
Supernatant Phase in Polyelectrolyte Complex Coacervation: Cluster Formation, Binodal, and Nucleation
No full textThis work studies the structure and thermodynamics of the supernatant phase in polyelectrolyte complex coacervation, a relatively unexplored area. By combining the cluster theory in dilute solution with our recently developed mean-field theory for inhomogeneous polyelectrolyte solutions (Zhang, P.; Wang, Z.-G. Macromolecules 2021, 54, 10994), we systematically investigate the structure of finite-sized clusters formed by oppositely charged polyions in symmetric dilute solutions and how these clusters affect the binodal, spinodal, and nucleation for polyelectrolyte complex coacervation. We find that both the polyion concentration deep inside the cluster and the interfacial tension decrease with increasing the cluster size, reaching their respective bulk coexistence values with corrections inversely proportional to the cluster radius. The polyion concentration in the supernatant phase at coexistence is several orders of magnitude higher than that obtained under the uniform mixing approximation. For most relevant conditions away from the critical point, the supernatant phase consists predominantly of polyion pairs. By examining the nucleation barrier in supersaturated solutions, we can determine a pseudo-spinodal when the barrier is a few multiples of the thermal energy. The location of this pseudo-spinodal is similarly shifted to much higher concentrations than predicted under the uniform mixing approximation. Making the volume approximation for the clusters, we obtain simple analytical expressions for the cluster formation free energy, the modified binodal, and the pseudo-spinodal. In particular, we propose a simple approximate formula for estimating the concentration of the coexisting supernatant phase in terms of the chain length, interfacial tension, and the polyion concentration in the coacervate phase
Molybdenum-Mediated Coupling of Carbon Monoxide to a C₃ Product on a Single Metal Site
No full textThe synthesis and characterization of a series of naphthalenediyl-diphosphine molybdenum complexes are reported. A novel dicarbonyl–Mo complex (3) converts to a bis(siloxy)acetylene complex (5) upon reduction and treatment with a silyl electrophile, Me₃SiCl. This process shows exclusive C–C coupling distinct from the previously reported phenylene-linked analogue that undergoes C–O cleavage. Further CO catenation can be engendered from 5 under mild conditions providing metallacyclobutenone complex 6, with a C₃O₃ organic motif derived from CO. Differences in reactivity are assigned to the nature of the arene linker, where the naphthalenediyl fragment shows a propensity for η⁴ binding previously not observed for phenylene. Consistent with this hypothesis, a Mo precursor with a 1,3-cyclohexadienediyl-based linker was prepared which also showed exclusive formation of a bis(siloxy)acetylene complex and subsequent coupling of a third CO molecule
Clapeyron.jl: An Extensible, Open-Source Fluid Thermodynamics Toolkit
No full textThermodynamic models are often vital when characterizing complex systems, particularly natural gas, electrolyte, polymer, pharmaceutical, and biological systems. However, their implementations have historically been abstruse and cumbersome, and as such, the only options available were black box commercial tools. In this article, we present Clapeyron.jl: a pioneering attempt at an open-source fluid thermodynamics toolkit to build and make use of thermodynamic models. This toolkit is built using Julia, a modern language for scientific computing known for its ease of use, extensibility, and first-class support for differentiable programming. We currently support more models than any package available, including standard cubic (SRK, PR, PSRK, etc.), activity coefficient (NRTL, UNIFAC, etc.), COSMO-based, and the venerable SAFT equations. The property estimation methods supported are extensive, including bulk, VLE, LLE, VLLE, and critical properties. With Clapeyron.jl, researchers and enthusiasts alike will be able to focus on the application and worry less about the implementation
Automated solid phase assisted synthesis of a heparan sulfate disaccharide library
No full textHeparan sulfate (HS) regulates a wide range of biological events, including blood coagulation, cancer development, cell differentiation, and viral infections. It is generally recognized that structures of HS can critically impact its biological functions. However, with complex structures of naturally existing HS, systematic investigations into the structure–activity relationship (SAR) of HS and efforts to unlock its “sulfation code” have been largely limited due to the challenges in preparing diverse HS oligosaccharide sequences. Herein, we report an automated machine-aided solid-phase strategy that significantly expedited the assembly of HS disaccharides. The key strategically protected advanced disaccharide intermediates were immobilized onto Synphase lanterns. Divergent deprotections and sulfations of the disaccharides were achieved on the lanterns in high yields. In addition, the full synthetic process was automated, enabling the reproducible production of HS disaccharides. A library of 16 HS disaccharides with diverse sulfation patterns was prepared via this method. Compared to the traditional HS synthesis, this new strategy led to a reduction of 50% of the number of synthetic steps and over 80% of the number of column purification steps needed from the disaccharide intermediates, significantly improving the overall synthetic efficiency. The potential utility of the method was highlighted in a microarray study using the synthetic HS disaccharide library with fibroblast growth factor-2 (FGF-2), which yielded insights into the SAR of HS/FGF-2 interactions
Speckle-resolved optical coherence tomography for mesoscopic imaging within scattering media
No full textLight scattering poses a challenge for imaging deep in scattering media as the ballistic light exponentially attenuates with depth. In contrast to the ballistic light, the multiply scattered light penetrates deeper and also contains information about the sample. One technique to image deeper is to selectively detect only a subset of the multiply scattered light, namely the ’snake’ photons, which are predominantly forward scattered and retain more direct information than the more strongly scattered light. In this work, we develop a technique, termed speckle-resolved optical coherence tomography (srOCT), for efficiently detecting these ’snake’ photons to enable imaging deeper in scattering media. The system couples spatio-angular filtering with speckle-resolved interferometric detection to preferentially and efficiently detect the weakly scattered ’snake’ photons. With our proof-of-concept system, we demonstrate depth-resolved imaging beyond the ballistic limit, up to a depth of 90 round-trip MFPs in a scattering phantom and a depth of 4.5 mm of chicken tissue at 0.4 mm axial and lateral resolution