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<jats:p> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn <jats:sup>501</jats:sup> →Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution. </jats:p>

<jats:p>Photonic time crystals (PTCs), materials with a dielectric permittivity that is modulated periodically in time, offer new concepts in light manipulation. We study theoretically the emission of light from a radiation source placed inside a PTC and find that radiation corresponding to the momentum bandgap is exponentially amplified, whether initiated by a macroscopic source, an atom, or vacuum fluctuations, drawing the amplification energy from the modulation. The radiation linewidth becomes narrower with time, eventually becoming monochromatic in the middle of the bandgap, which enables us to propose the concept of nonresonant tunable PTC laser. Finally, we find that the spontaneous decay rate of an atom embedded in a PTC vanishes at the band edge because of the low density of photonic states.</jats:p>

<jats:p>The in vivo pathogenicity, transmissibility, and fitness of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant are not well understood. We compared these virological attributes of this new variant of concern (VOC) with those of the Delta (B.1.617.2) variant in a Syrian hamster model of COVID-19. Omicron-infected hamsters lost significantly less body weight and exhibited reduced clinical scores, respiratory tract viral burdens, cytokine and chemokine dysregulation, and lung damage than Delta-infected hamsters. Both variants were highly transmissible through contact transmission. In noncontact transmission studies Omicron demonstrated similar or higher transmissibility than Delta. Delta outcompeted Omicron without selection pressure, but this scenario changed once immune selection pressure with neutralizing antibodies—active against Delta but poorly active against Omicron—was introduced. Next-generation vaccines and antivirals effective against this new VOC are therefore urgently needed.</jats:p>

<jats:p>Semiconducting cubic boron arsenide (c-BAs) has been predicted to have carrier mobility of 1400 square centimeters per volt-second for electrons and 2100 square centimeters per volt-second for holes at room temperature. Using pump-probe transient reflectivity microscopy, we monitored the diffusion of photoexcited carriers in single-crystal c-BAs to obtain their mobility. With near-bandgap 600-nanometer pump pulses, we found a high ambipolar mobility of 1550 ± 120 square centimeters per volt-second, in good agreement with theoretical prediction. Additional experiments with 400-nanometer pumps on the same spot revealed a mobility of &gt;3000 square centimeters per volt-second, which we attribute to hot electrons. The observation of high carrier mobility, in conjunction with high thermal conductivity, enables an enormous number of device applications for c-BAs in high-performance electronics and optoelectronics.</jats:p>

<jats:p>Semiconductors with high thermal conductivity and electron-hole mobility are of great importance for electronic and photonic devices as well as for fundamental studies. Among the ultrahigh–thermal conductivity materials, cubic boron arsenide (c-BAs) is predicted to exhibit simultaneously high electron and hole mobilities of &gt;1000 centimeters squared per volt per second. Using the optical transient grating technique, we experimentally measured thermal conductivity of 1200 watts per meter per kelvin and ambipolar mobility of 1600 centimeters squared per volt per second at the same locations on c-BAs samples at room temperature despite spatial variations. Ab initio calculations show that lowering ionized and neutral impurity concentrations is key to achieving high mobility and high thermal conductivity, respectively. The high ambipolar mobilities combined with the ultrahigh thermal conductivity make c-BAs a promising candidate for next-generation electronics.</jats:p>

<jats:p>Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.</jats:p>

<jats:p>Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports but later this conclusion became controversial. We show the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and, within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic.</jats:p>

<jats:p>In the 20th century, researchers studying animal and plant signaling pathways discovered a protein domain that is shared across diverse innate immune systems: the Toll/interleukin-1/resistance gene (TIR) domain. The TIR domain is found in several protein architectures and was defined as an adaptor that mediates protein-protein interactions in animal innate immunity and developmental signaling pathways. However, studies of nerve degeneration in animals—and subsequent breakthroughs in plant, bacterial, and archaeal systems—revealed that TIR domains possess enzymatic activities. We provide a synthesis of TIR functions and the role of various related TIR enzymatic products in evolutionarily diverse immune systems. These studies may ultimately guide interventions that would span the tree of life, from treating human neurodegenerative disorders and bacterial infections to preventing plant diseases.</jats:p>

<jats:p>Plant pathogen–activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners, Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) produces signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR subclasses. In this work, we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)–ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) through ADPR polymerase–like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively. Specific binding of ADPr-ATP or di-ADPR allosterically promotes EDS1-SAG101 interaction with helper NLR N requirement gene 1A (NRG1A) in vitro and in planta. Our data reveal an enzymatic activity of TIRs that enables specific activation of the EDS1-SAG101-NRG1 immunity branch.</jats:p>