Catálogo de publicaciones - revistas

<jats:p>DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify more than 2000 fountain-like structures of chromatin contacts in human and mouse genomes, indicative of coupling of DNA replication forks. Replication fork interaction not only occurs between sister forks but also involves forks from two distinct origins to predetermine replication termination. Termination-associated chromatin fountains are sensitive to replication stress and lead to coupled forks–associated genomic deletions in cancers. These findings reveal the spatial organization of DNA replication forks within the chromatin context.</jats:p>

<jats:p>Many examples of exposed giant dike swarms can be found where lateral magma flow has exceeded hundreds of kilometers. We show that massive magma flow into dikes can be established with only modest overpressure in a magma body if a large enough pathway opens at its boundary and gradual buildup of high tensile stress has occurred along the dike pathway prior to the onset of diking. This explains rapid initial magma flow rates, modeled up to about 7400 cubic meters per second into a dike ~15-kilometers long, which propagated under the town of Grindavík, Southwest Iceland, in November 2023. Such high flow rates provide insight into the formation of major dikes and imply a serious hazard potential for high–flow rate intrusions that propagate to the surface and transition into eruptions.</jats:p>

<jats:p>Power conversion efficiencies (PCEs) of inverted perovskite solar cells (PSCs) have been improved by the use of a self-assembled monolayer (SAM) hole transport layer. Long-term stability of PSCs requires keeping the SAM compact under the perovskite layer during operation. We found that strong polar solvents in the perovskite precursor desorb the SAM if it is anchored on substrates by hydrogen-bonded, rather than covalently bonded, hydroxyl groups. We used atomic-layer deposition to create an indium tin oxide substrate with a fully covalent hydroxyl-covered surface for SAM anchoring, as well as a SAM with a trimethoxysilane group that exhibited strong tridentate anchoring to the substrate. The resulting PSCs achieved PCEs of 24.8 (certified 24.6) and 23.2% with aperture areas of 0.08 and 1.01 square centimeters, respectively. The devices retained 98.9 and 98.2% of the initial PCE after 1000 hours damp-heat test and operation in maximum power point tracking at 85°C for 1200 hours under standard illumination, respectively.</jats:p>

<jats:p> When ecological and evolutionary dynamics occur on comparable timescales, persistence of the ensuing eco-evolutionary dynamics requires both ecological and evolutionary stability. This unites key questions in ecology and evolution: How do species coexist, and what maintains genetic variation in a population? In this work, we investigated a host-parasitoid system in which pea aphid hosts rapidly evolve resistance to <jats:italic>Aphidius ervi</jats:italic> parasitoids. Field data and mathematical simulations showed that heterogeneity in parasitoid dispersal can generate variation in parasitism-mediated selection on hosts through time and space. Experiments showed how evolutionary trade-offs plus moderate host dispersal across this selection mosaic cause host-parasitoid coexistence and maintenance of genetic variation in host resistance. Our results show how dispersal can stabilize both the ecological and evolutionary components of eco-evolutionary dynamics. </jats:p>

<jats:p>The minor spliceosome, which is responsible for the splicing of U12-type introns, comprises five small nuclear RNAs (snRNAs), of which only one is shared with the major spliceosome. In this work, we report the 3.3-angstrom cryo–electron microscopy structure of the fully assembled human minor spliceosome pre-B complex. The atomic model includes U11 small nuclear ribonucleoprotein (snRNP), U12 snRNP, and U4atac/U6atac.U5 tri-snRNP. U11 snRNA is recognized by five U11-specific proteins (20K, 25K, 35K, 48K, and 59K) and the heptameric Sm ring. The 3′ half of the 5′-splice site forms a duplex with U11 snRNA; the 5′ half is recognized by U11-35K, U11-48K, and U11 snRNA. Two proteins, CENATAC and DIM2/TXNL4B, specifically associate with the minor tri-snRNP. A structural analysis uncovered how two conformationally similar tri-snRNPs are differentiated by the minor and major prespliceosomes for assembly.</jats:p>

<jats:p>Overgeneralization of fear to harmless situations is a core feature of anxiety disorders resulting from acute stress, yet the mechanisms by which fear becomes generalized are poorly understood. In this study, we show that generalized fear in mice results from a transmitter switch from glutamate to γ-aminobutyric acid (GABA) in serotonergic neurons of the lateral wings of the dorsal raphe. Similar change in transmitter identity was found in the postmortem brains of individuals with posttraumatic stress disorder (PTSD). Overriding the transmitter switch in mice prevented the acquisition of generalized fear. Corticosterone release and activation of glucocorticoid receptors mediated the switch, and prompt antidepressant treatment blocked the cotransmitter switch and generalized fear. Our results provide important insight into the mechanisms involved in fear generalization.</jats:p>

<jats:p>Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced through nonribosomal peptide synthetases (NRPSs), megasynthetases that activate and join individual amino acids in an assembly line fashion. In this work, we describe a detailed phylogenetic analysis of several bacterial NRPSs that led to the identification of yet undescribed recombination sites within the thiolation (T) domain that can be used for NRPS engineering. We then developed an evolution-inspired “eXchange Unit between T domains” (XUT) approach, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments.</jats:p>

<jats:p> Brassinosteroids are steroidal phytohormones that regulate plant development and physiology, including adaptation to environmental stresses. Brassinosteroids are synthesized in the cell interior but bind receptors at the cell surface, necessitating a yet to be identified export mechanism. Here, we show that a member of the ATP-binding cassette (ABC) transporter superfamily, ABCB19, functions as a brassinosteroid exporter. We present its structure in both the substrate-unbound and the brassinosteroid-bound states. Bioactive brassinosteroids are potent activators of ABCB19 ATP hydrolysis activity, and transport assays showed that ABCB19 transports brassinosteroids. In <jats:italic>Arabidopsis thaliana</jats:italic> , ABCB19 and its close homolog, ABCB1, positively regulate brassinosteroid responses. Our results uncover an elusive export mechanism for bioactive brassinosteroids that is tightly coordinated with brassinosteroid signaling. </jats:p>

<jats:p>When I was chancellor of the University of North Carolina at Chapel Hill, I tried never to miss the annual concert of the Triangle Youth Symphony. When people asked me why I was such a regular, I complimented the music but also suggested that there were potential future college science majors on the stage. The strong correlation between scientific and musical ability is an association familiar to many scientists, but in recent years, the connections between music and the mind have begun receiving broader attention, partly because of an unexpected partnership between the former long-time director of the US National Institutes of Health Francis Collins, and soprano opera superstar Renée Fleming. I caught up with Collins and Fleming for an extended chat about their shared curiosity regarding the science of music and health.</jats:p>

<jats:p>Despite apparently minimal seabird deaths, grave concern for the next breeding season</jats:p>