Photodetachment spectroscopy of the FH2– and FD2– anions allows for the direct observation of reactive resonances in the benchmark reaction F + H2 → HF + H. Using cooled anion precursors and a ...high-resolution electron spectrometer, we observe several narrow peaks not seen in previous experiments. Theoretical calculations, based on a highly accurate F + H2 potential energy surface, convincingly assign these peaks to resonances associated with quasibound states in the HF + H and DF + D product arrangements and with a quasibound state in the transition state region of the F + H2 reaction. The calculations also reveal quasibound states in the reactant arrangement, which have yet to be resolved experimentally.
NUP98
is a recurrent partner gene in translocations causing acute myeloid leukemias and myelodisplastic syndrome. The expression of NUP98 fusion oncoproteins has been shown to induce mitotic spindle ...defects and chromosome missegregation, which correlate with the capability of NUP98 fusions to cause mitotic checkpoint attenuation. We show that NUP98 oncoproteins physically interact with the APC/C
Cdc20
in the absence of the NUP98 partner protein RAE1, and prevent the binding of the mitotic checkpoint complex to the APC/C
Cdc20
. NUP98 oncoproteins require the GLEBS-like domain present in their NUP98 moiety to bind the APC/C
Cdc20
. We found that NUP98 wild-type is a substrate of APC/C
Cdc20
prior to mitotic entry, and that its binding to APC/C
Cdc20
is controlled via phosphorylation of a PEST sequence located within its C-terminal portion. We identify S606, within the PEST sequence, as a key target site, whose phosphorylation modulates the capability of NUP98 to interact with APC/C
Cdc20
. We finally provide evidence for an involvement of the peptidyl-prolyl isomerase PIN1 in modulating the possible conformational changes within NUP98 that lead to its dissociation from the APC/C
Cdc20
during mitosis. Our results provide novel insight into the mechanisms underlying the aberrant capability of NUP98 oncoproteins to interact with APC/C
Cdc20
and to interfere with its function.
Blood gas and tissue pH regulation depend on the ability of the brain to sense CO2 and/or H+ and alter breathing appropriately, a homeostatic process called central respiratory chemosensitivity. We ...show that selective expression of the proton-activated receptor GPR4 in chemosensory neurons of the mouse retrotrapezoid nucleus (RTN) is required for CO2-stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO2. Reintroduction of GPR4 into RTN neurons restored CO2-dependent RTN neuronal activation and rescued the ventilatory phenotype. Additional elimination of TASK-2 (K2P5), a pH-sensitive K+ channel expressed in RTN neurons, essentially abolished the ventilatory response to CO2. The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.
The spindle checkpoint of the cell division cycle senses kinetochores that are not attached to microtubules and prevents precocious onset of anaphase, which can lead to aneuploidy. The nuclear ...division cycle 80 complex (Ndc80C) is a major microtubule receptor at the kinetochore. Ndc80C also mediates the kinetochore recruitment of checkpoint proteins. We found that the checkpoint protein kinase monopolar spindle 1 (Mps1) directly bound to Ndc80C through two independent interactions. Both interactions involved the microtubule-binding surfaces of Ndc80C and were directly inhibited in the presence of microtubules. Elimination of one such interaction in human cells caused checkpoint defects expected from a failure to detect unattached kinetochores. Competition between Mps1 and microtubules for Ndc80C binding thus constitutes a direct mechanism for the detection of unattached kinetochores.
The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G4C2 repeat expansion in C9ORF72. Efforts to combat neurodegeneration associated with "c9FTD/ALS" are ...hindered by a lack of animal models recapitulating disease features. We developed a mouse model to mimic both neuropathological and clinical c9FTD/ALS phenotypes. We expressed (G4C2)66 throughout the murine central nervous system by means of somatic brain transgenesis mediated by adeno-associated virus. Brains of 6-month-old mice contained nuclear RNA foci, inclusions of poly(Gly-Pro), poly(Gly-Ala), and poly(Gly-Arg) dipeptide repeat proteins, as well as TDP-43 pathology. These mouse brains also exhibited cortical neuron and cerebellar Purkinje cell loss, astrogliosis, and decreased weight. (G4C2)66 mice also developed behavioral abnormalities similar to clinical symptoms of c9FTD/ALS patients, including hyperactivity, anxiety, antisocial behavior, and motor deficits.
Precolumbian archaeologists traditionally focus on periods of stability rather than change when constructing regional cultural chronologies. However, the advent of large databases of radiocarbon ...dates and the proliferation of open-source software environments such as R now allow archaeologists to understand technological transitions with greater chronological precision than has been historically possible. In this study, we employ Monte Carlo procedures, Bayes’ Theorem, the R package Bchron, and IntCal13 to address three chronological topics. We calculate the minimum number of dates required on atlatl and bow technologies to robustly date this late Holocene transition in Subarctic northwestern Canada, analyze previously published dates on organic projectile diagnostics to determine whether bows and atlatls overlapped for an observable amount of time, and estimate the years of calendric time that they overlapped. Results indicate that minimum sample sizes of 29 atlatl and 19 bow dates are required to characterize this particular transition in our study area. Actual radiocarbon dates show that bow and atlatl technologies temporally co-occurred within this region for 174 ± 135 (1σ) actual calendar years. Quantitative analyses such as these open the door to testing hypotheses that explain why and how technological transitions occur within and between (pre)historic groups.
Tradicionalmente, la arqueología Pre-Colombina se ha focalizado en los periodos de estabilidad más que en los cambios al momento de construir cronologías culturales regionales. Sin embargo, el advenimiento de amplias bases de datos de fechados radiocarbónicos y la proliferación de software ambientales de código abierto tales como el R permite a los arqueólogos reconocer las transiciones tecnológicas con un mayor grado de precisión cronológica de lo que fue históricamente posible. En este estudio empleamos el procedimiento Monte Carlo, el Teorema de Bayes, el paquete R Bchron y las curvas de calibración de IntCal13 para abordar tres temas cronológicos. Calculamos el número mínimo de dataciones que son requeridas para las tecnologías de propulsión y arco que permitan datar robustamente su transición en el noroeste subártico de Canadá, analizamos dataciones previamente publicadas para arcos y propulsores diagnósticos con el fin de determinar si las dos tecnologías de proyectil se superponían por una cantidad observable de tiempo en la prehistoria y estimamos los años calendáricos que ambas tecnologías se superponían. Los resultados indican que un tamaño mínimo de muestra de 29 dataciones sobre propulsores y 19 sobre arcos es requerido para caracterizar esta transición cultural en nuestra área de estudio. Las dataciones radiocarbónicas reales muestran que las tecnologías de arco y propulsión co-ocurrieron temporalmente dentro de la región por 174 +/- 135 (1σ) años calendáricos reales. Estos análisis cuantitativos abren la puerta al testeo de hipótesis que expliquen por qué y cómo las transiciones tecnológicas se producen dentro y entre grupos (pre) históricos.
Extensive fine-scale genetic diversity is found in many microbial species across varied environments, but for most, the evolutionary scenarios that generate the observed variation remain unclear. ...Deep sequencing of a thermophilic cyanobacterial population and analysis of the statistics of synonymous single-nucleotide polymorphisms revealed a high rate of homologous recombination and departures from neutral drift consistent with the effects of genetic hitchhiking. A sequenced isolate genome resembled an unlinked random mixture of the allelic diversity at the sampled loci. These observations suggested a quasisexual microbial population that occupies a broad ecological niche, with selection driving frequencies of alíeles rather than whole genomes.
The growth rate of atmospheric carbon dioxide (CO2) concentrations since industrialization is characterized by large interannual variability, mostly resulting from variability in CO2 uptake by ...terrestrial ecosystems (typically termed carbon sink). However, the contributions of regional ecosystems to that variability are not well known. Using an ensemble of ecosystem and land-surface models and an empirical observation-based product of global gross primary production, we show that the mean sink, trend, and interannual variability in CO2 uptake by terrestrial ecosystems are dominated by distinct biogeographic regions. Whereas the mean sink is dominated by highly productive lands (mainly tropical forests), the trend and interannual variability of the sink are dominated by semi-arid ecosystems whose carbon balance is strongly associated with circulation-driven variations in both precipitation and temperature.
Nanoscale ferroelectrics are expected to exhibit various exotic domain configurations, such as the full flux-closure pattern that is well known in ferromagnetic materials. Here we observe not only ...the atomic morphology of the flux-closure quadrant but also a periodic array of flux closures in ferroelectric PbTiO3 films, mediated by tensile strain on a GdScO3 substrate. Using aberration-corrected scanning transmission electron microscopy, we directly visualize an alternating array of clockwise and counterclockwise flux closures, whose periodicity depends on the PbTiO3 film thickness. In the vicinity of the core, the strain is sufficient to rupture the lattice, with strain gradients up to 109 per meter. Engineering strain at the nanoscale may facilitate the development of nanoscale ferroelectric devices.
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