Eclipsing binary millisecond pulsars (MSPs; the so-called black widows and redbacks) can provide important information about accretion history, pulsar irradiation of their companion stars, and the ...evolutionary link between accreting X-ray pulsars and isolated MSPs. However, the formation of such systems is not well understood, nor the difference in progenitor evolution between the two populations of black widows and redbacks. Whereas both populations have orbital periods between 0.1 and 1.0 days, their companion masses differ by an order of magnitude. In this paper, we investigate the formation of these systems via the evolution of converging low-mass X-ray binaries by employing the MESA stellar evolution code. Our results confirm that one can explain the formation of most of these eclipsing binary MSPs using this scenario. More notably, we find that the determining factor for producing either black widows or redbacks is the efficiency of the irradiation process, such that the redbacks absorb a larger fraction of the emitted spin-down energy of the radio pulsar (resulting in more efficient mass loss via evaporation) compared to that of the black widow systems. We argue that geometric effects (beaming) are responsible for the strong bimodality of these two populations. Finally, we conclude that redback systems do not evolve into black widow systems with time.
CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin ...mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated KrasG12D mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.
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•Generation of mouse lines with Cre-dependent and constitutive Cas9 expression•Viral/nonviral delivery of sgRNA to the brain, vasculature, immune cells, and lung•Modeling of competition between gain- and loss-of-function mutations in lung cancer•A convenient platform for achieving efficient genome editing in vivo
Viral and nonviral delivery of sgRNAs in CRISPR-Cas9 knockin mice enables diverse genome engineering applications in biology and disease modeling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
B cell receptor (BCR) signaling pathway components represent promising treatment targets in diffuse large B cell lymphoma (DLBCL) and additional B cell tumors. BCR signaling activates spleen tyrosine ...kinase (SYK) and downstream pathways including PI3K/AKT and NF-κB. In previous studies, chemical SYK blockade selectively decreased BCR signaling and induced apoptosis of BCR-dependent DLBCLs. Herein, we characterize distinct SYK/PI3K-dependent survival pathways in DLBCLs with high or low baseline NF-κB activity including selective repression of the pro-apoptotic HRK protein in NF-κB-low tumors. We also define SYK/PI3K-dependent cholesterol biosynthesis as a feed-forward mechanism of maintaining the integrity of BCRs in lipid rafts in DLBCLs with low or high NF-κB. In addition, SYK amplification and PTEN deletion are identified as selective genetic alterations in primary “BCR”-type DLBCLs.
•SYK/PI3K inhibition decreases NF-κB activity in DLBCLs with high basal NF-κB•SYK/PI3K blockade induces HRK-dependent apoptosis in DLBCLs with low basal NF-κB•In all BCR-dependent DLBCLs, SYK/PI3K signaling regulates cholesterol biosynthesis•Primary “BCR” DLBCLs selectively exhibit SYK amplification or PTEN deletion
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The formation path to ultracompact X-ray binaries (UCXBs) with black hole (BH) accretors is still unclear. In the classical formation scenario, it is difficult to eject the massive envelope ...of the progenitor star of the BH via the common envelope process. Given that some neutron stars (NSs) in binary systems evidently have birth masses close to ∼2.0
M
⊙
, we explore here the possibility that BH-UCXBs may form via the accretion-induced collapse (AIC) of accreting NSs, assuming that these previously evolved in low-mass X-ray binaries to masses all the way up to the maximum limit of an NS. We demonstrate this formation path by modeling a few cases of NS-UCXBs with initial NS masses close to the maximum mass of an NS that evolve into BH-UCXBs after the NS accretes material from its He white dwarf (WD) companion. We follow the evolution of the post-AIC BH-UCXB and, based on simple arguments, we anticipate that there is about one BH-UCXB with an AIC origin and a He WD donor within the current sample of known UCXBs and that two to five such BH-UCXBs may be detected in gravitational waves by LISA. In addition, we find that the X-ray luminosity of NS-UCXBs near their orbital period minimum exceeds ∼10
39
erg s
−1
, and thus, such systems may appear as ultraluminous X-ray sources.
ABSTRACT
Close-orbit low-mass X-ray binaries (LMXBs), radio binary millisecond pulsars (BMSPs) with extremely low-mass helium white dwarfs (ELM He WDs) and ultra-compact X-ray binaries (UCXBs) are ...all part of the same evolutionary sequence. It is therefore of uttermost importance to understand how these populations evolve from one specie to another. Moreover, UCXBs are important gravitational wave (GW) sources and can be detected by future space-borne GW observatories. However, the formation and evolutionary link between these three different populations of neutron star (NS) binaries are not fully understood. In particular, a peculiar fine-tuning problem has previously been demonstrated for the formation of these systems. In this investigation, we test a newly suggested magnetic braking prescription and model the formation and evolution of LMXBs. We compute a grid of binary evolution models and present the initial parameter space of the progenitor binaries which successfully evolve all the way to produce UCXBs. We find that the initial orbital period range of LMXBs, which evolve into detached NS + ELM He WD binaries and later UCXBs, becomes significantly wider compared to evolution with a standard magnetic braking prescription, and thus helps to relieve the fine-tuning problem. However, we also find that formation of wide-orbit BMSPs is prohibited for strong versions of this new magnetic braking prescription, which therefore calls for a revision of the prescription. Finally, we present examples of the properties of UCXBs as Galactic GW sources and discuss their detection by the LISA, TianQin, and Taiji observatories.
The splitting of water photoelectrochemically into hydrogen and oxygen represents a promising technology for converting solar energy to fuel. The main challenge is to ensure that photogenerated holes ...efficiently oxidize water, which generally requires modification of the photoanode with an oxygen evolution catalyst (OEC) to increase the photocurrent and reduce the onset potential. However, because excess OEC material can hinder light absorption and decrease photoanode performance, its deposition needs to be carefully controlled--yet it is unclear which semiconductor surface sites give optimal improvement if targeted for OEC deposition, and whether sites catalysing water oxidation also contribute to competing charge-carrier recombination with photogenerated electrons. Surface heterogeneity exacerbates these uncertainties, especially for nanostructured photoanodes benefiting from small charge-carrier transport distances. Here we use super-resolution imaging, operated in a charge-carrier-selective manner and with a spatiotemporal resolution of approximately 30 nanometres and 15 milliseconds, to map both the electron- and hole-driven photoelectrocatalytic activities on single titanium oxide nanorods. We then map, with sub-particle resolution (about 390 nanometres), the photocurrent associated with water oxidation, and find that the most active sites for water oxidation are also the most important sites for charge-carrier recombination. Site-selective deposition of an OEC, guided by the activity maps, improves the overall performance of a given nanorod--even though more improvement in photocurrent efficiency correlates with less reduction in onset potential (and vice versa) at the sub-particle level. Moreover, the optimal catalyst deposition sites for photocurrent enhancement are the lower-activity sites, and for onset potential reduction the optimal sites are the sites with more positive onset potential, contrary to what is obtainable under typical deposition conditions. These findings allow us to suggest an activity-based strategy for rationally engineering catalyst-improved photoelectrodes, which should be widely applicable because our measurements can be performed for many different semiconductor and catalyst materials.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Despite their importance as signaling hubs, the function of mitochondria-ER contact sites in mitochondrial quality control pathways remains unexplored. Here we describe a mechanism by which Mfn2, a ...mitochondria-ER tether, gates the autophagic turnover of mitochondria by PINK1 and parkin. Mitochondria-ER appositions are destroyed during mitophagy, and reducing mitochondria-ER contacts increases the rate of mitochondrial degradation. Mechanistically, parkin/PINK1 catalyze a rapid burst of Mfn2 phosphoubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane, dissociating mitochondria from the ER. We additionally demonstrate that a major portion of the facilitatory effect of p97 on mitophagy is epistatic to Mfn2 and promotes the availability of other parkin substrates such as VDAC1. Finally, we reconstitute the action of these factors on Mfn2 and VDAC1 ubiquitination in a cell-free assay. We show that mitochondria-ER tethering suppresses mitophagy and describe a parkin-/PINK1-dependent mechanism that regulates the destruction of mitochondria-ER contact sites.
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