Catálogo de publicaciones - revistas

<jats:p>Ephrin type-A receptor 2 (EphA2) is a receptor tyrosine kinase that initiates both ligand-dependent tumor-suppressive and ligand-independent oncogenic signaling. We used time-resolved, live-cell fluorescence spectroscopy to show that the ligand-free EphA2 assembles into multimers driven by two types of intermolecular interactions in the ectodomain. The first type entails extended symmetric interactions required for ligand-induced receptor clustering and tumor-suppressive signaling that inhibits activity of the oncogenic extracellular signal–regulated kinase (ERK) and protein kinase B (AKT) protein kinases and suppresses cell migration. The second type is an asymmetric interaction between the amino terminus and the membrane proximal domain of the neighboring receptors, which supports oncogenic signaling and promotes migration in vitro and tumor invasiveness in vivo. Our results identify the molecular interactions that drive the formation of the EphA2 multimeric signaling clusters and reveal the pivotal role of EphA2 assembly in dictating its opposing functions in oncogenesis.</jats:p>

<jats:p> When evaluating the effect of carbon dioxide (CO <jats:sub>2</jats:sub> ) changes on Earth’s climate, it is widely assumed that instantaneous radiative forcing from a doubling of a given CO <jats:sub>2</jats:sub> concentration (IRF <jats:sub>2×CO2</jats:sub> ) is constant and that variances in climate sensitivity arise from differences in radiative feedbacks or dependence of these feedbacks on the climatological base state. Here, we show that the IRF <jats:sub>2×CO2</jats:sub> is not constant, but rather depends on the climatological base state, increasing by about 25% for every doubling of CO <jats:sub>2</jats:sub> , and has increased by about 10% since the preindustrial era primarily due to the cooling within the upper stratosphere, implying a proportionate increase in climate sensitivity. This base-state dependence also explains about half of the intermodel spread in IRF <jats:sub>2×CO2</jats:sub> , a problem that has persisted among climate models for nearly three decades. </jats:p>

<jats:p> The development of functionally distinct catalysts for enantioselective synthesis is a prominent yet challenging goal of synthetic chemistry. In this work, we report a family of chiral <jats:italic>N</jats:italic> -heterocyclic carbene (NHC)–ligated boryl radicals as catalysts that enable catalytic asymmetric radical cycloisomerization reactions. The radical catalysts can be generated from easily prepared NHC-borane complexes, and the broad availability of the chiral NHC component provides substantial benefits for stereochemical control. Mechanistic studies support a catalytic cycle comprising a sequence of boryl radical addition, hydrogen atom transfer, cyclization, and elimination of the boryl radical catalyst, wherein the chiral NHC subunit determines the enantioselectivity of the radical cyclization. This catalysis allows asymmetric construction of valuable chiral heterocyclic products from simple starting materials. </jats:p>

<jats:p> Many metallic quantum materials display anomalous transport phenomena that defy a Fermi liquid description. Here, we use numerical methods to calculate thermal and charge transport in the doped Hubbard model and observe a crossover separating high- and low-temperature behaviors. Distinct from the behavior at high temperatures, the Lorenz number <jats:inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi>L</mml:mi> </mml:math> </jats:inline-formula> becomes weakly doping dependent and less sensitive to parameters at low temperatures. At the lowest numerically accessible temperatures, <jats:inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi>L</mml:mi> </mml:math> </jats:inline-formula> roughly approaches the Wiedemann-Franz constant <jats:inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:msub> <mml:mi>L</mml:mi> <mml:mn>0</mml:mn> </mml:msub> </mml:mrow> </mml:math> </jats:inline-formula> , even in a doped Mott insulator that lacks well-defined quasiparticles. Decomposing the energy current operator indicates a compensation between kinetic and potential contributions, which may help to clarify the interpretation of transport experiments beyond Boltzmann theory in strongly correlated metals. </jats:p>

<jats:p> A <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.jdpower.com/business/press-releases/2023-us-mobility-confidence-index-mci-study">survey published in October 2023</jats:ext-link> revealed what seemed to be a paradox. Over the past decade, self-driving vehicles have improved immeasurably, but public trust in the technology is low and falling. Only 37% of Americans said they would be comfortable riding in a self- driving vehicle, down from 39% in 2022 and 41% in 2021. Those that have used the technology express more enthusiasm, but the rest have seemingly had their confidence shaken by the failure of the technology to live up to its hype. </jats:p>

<jats:p>Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then widely redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for rapid future activation. Hence, multifaceted pioneer TF–enhancer interaction underpins pluripotency progression in embryos, including a distinctive state in E3.5 ICM that bridges totipotency and pluripotency.</jats:p>

<jats:p>The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial pathogens, both in vitro and in gnotobiotic mice. Whereas single species alone had negligible effects, colonization resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explained these ecological patterns through the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Furthermore, we applied our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.</jats:p>