Combined electrical transport and capacitance spectroscopy of a MoS2−LiNbO3{\mathrm{MoS_2-LiNbO_3}} field effect transistor

We have measured both the current-voltage ($I_\mathrm{SD}$-$V_\mathrm{GS}$) and capacitance-voltage ($C$-$V_\mathrm{GS}$) characteristics of a $\mathrm{MoS_2-LiNbO_3}$ field effect transistor. From the measured capacitance we calculate the electron surface density and show that its gate voltage dependence follows the theoretical prediction resulting from the two-dimensional free electron model. This model allows us to fit the measured $I_\mathrm{SD}$-$V_\mathrm{GS}$ characteristics over the \emph{entire range} of $V_\mathrm{GS}$. Combining this experimental result with the measured current-voltage characteristics, we determine the field effect mobility as a function of gate voltage. We show that for our device this improved combined approach yields significantly smaller values (more than a factor of 4) of the electron mobility than the conventional analysis of the current-voltage characteristics only.Comment: to appear in Applied Physics Letter

Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes

Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae

Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail

Enhanced sequential carrier capture into individual quantum dots and quantum posts controlled by surface acoustic waves

Individual self-assembled Quantum Dots and Quantum Posts are studied under the influence of a surface acoustic wave. In optical experiments we observe an acoustically induced switching of the occupancy of the nanostructures along with an overall increase of the emission intensity. For Quantum Posts, switching occurs continuously from predominantely charged excitons (dissimilar number of electrons and holes) to neutral excitons (same number of electrons and holes) and is independent on whether the surface acoustic wave amplitude is increased or decreased. For quantum dots, switching is non-monotonic and shows a pronounced hysteresis on the amplitude sweep direction. Moreover, emission of positively charged and neutral excitons is observed at high surface acoustic wave amplitudes. These findings are explained by carrier trapping and localization in the thin and disordered two-dimensional wetting layer on top of which Quantum Dots nucleate. This limitation can be overcome for Quantum Posts where acoustically induced charge transport is highly efficient in a wide lateral Matrix-Quantum Well.Comment: 11 pages, 5 figure

Combined inhibition of Aurora-A and ATR kinase results in regression of MYCN-amplified neuroblastoma

Amplification of MYCN is the driving oncogene in a subset of high-risk neuroblastoma. The MYCN protein and the Aurora-A kinase form a complex during S phase that stabilizes MYCN. Here we show that MYCN activates Aurora-A on chromatin, which phosphorylates histone H3 at serine 10 in S phase, promotes the deposition of histone H3.3 and suppresses R-loop formation. Inhibition of Aurora-A induces transcription-replication conflicts and activates the Ataxia telangiectasia and Rad3 related (ATR) kinase, which limits double-strand break accumulation upon Aurora-A inhibition. Combined inhibition of Aurora-A and ATR induces rampant tumor-specific apoptosis and tumor regression in mouse models of neuroblastoma, leading to permanent eradication in a subset of mice. The therapeutic efficacy is due to both tumor cell-intrinsic and immune cell-mediated mechanisms. We propose that targeting the ability of Aurora-A to resolve transcription-replication conflicts is an effective therapy for MYCN-driven neuroblastoma (141 words)

Dynamic Acoustic Control of Individual Optically Active Quantum Dot-like Emission Centers in Heterostructure Nanowires

We probe and control the optical properties of emission centers forming in radial het- erostructure GaAs-Al0.3Ga0.7As nanowires and show that these emitters, located in Al0.3Ga0.7As layers, can exhibit quantum-dot like characteristics. We employ a radio frequency surface acoustic wave to dynamically control their emission energy and occupancy state on a nanosec- ond timescale. In the spectral oscillations we identify unambiguous signatures arising from both the mechanical and electrical component of the surface acoustic wave. In addition, differ- ent emission lines of a single quantum dot exhibit pronounced anti-correlated intensity oscilla- tions during the acoustic cycle. These arise from a dynamically triggered carrier extraction out of the quantum dot to a continuum in the radial heterostructure. Using finite element modeling and Wentzel-Kramers-Brillouin theory we identify quantum tunneling as the underlying mech- anism. These simulation results quantitatively reproduce the observed switching and show that in our systems these quantum dots are spatially separated from the continuum by > 10.5 nm.Comment: This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Nano Letters, copyright \c{copyright} American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/nl404043

Combined inhibition of Aurora-A and ATR kinases results in regression of MYCN-amplified neuroblastoma

Amplification of MYCN is the driving oncogenic change in a subset of high-risk neuroblastomas. The MYCN protein and the Aurora-A kinase form a complex during the S phase that stabilizes MYCN. Here we show that MYCN activates Aurora-A on chromatin, which phosphorylates histone H3 at serine 10 in the S phase, promotes the deposition of histone H3.3 and suppresses R-loop formation. Inhibition of Aurora-A induces transcription–replication conflicts and activates ataxia telangiectasia and Rad3-related (ATR) kinase, which limits double-strand break accumulation upon Aurora-A inhibition. Combined inhibition of Aurora-A and ATR kinases induces rampant tumor-specific apoptosis and tumor regression in mouse models of neuroblastoma, leading to permanent eradication in a subset of mice. The therapeutic efficacy is due to both tumor cell-intrinsic and immune cell-mediated mechanisms. We propose that targeting the ability of Aurora-A to resolve transcription–replication conflicts is an effective therapy for MYCN-driven neuroblastoma

Cellulose-Enriched Microbial Communities from Leaf-Cutter Ant (Atta colombica) Refuse Dumps Vary in Taxonomic Composition and Degradation Ability

Deconstruction of the cellulose in plant cell walls is critical for carbon flow through ecosystems and for the production of sustainable cellulosic biofuels. Our understanding of cellulose deconstruction is largely limited to the study of microbes in isolation, but in nature, this process is driven by microbes within complex communities. In Neotropical forests, microbes in leaf-cutter ant refuse dumps are important for carbon turnover. These dumps consist of decaying plant material and a diverse bacterial community, as shown here by electron microscopy. To study the portion of the community capable of cellulose degradation, we performed enrichments on cellulose using material from five Atta colombica refuse dumps. The ability of enriched communities to degrade cellulose varied significantly across refuse dumps. 16S rRNA gene amplicon sequencing of enriched samples identified that the community structure correlated with refuse dump and with degradation ability. Overall, samples were dominated by Bacteroidetes, Gammaproteobacteria, and Betaproteobacteria. Half of abundant operational taxonomic units (OTUs) across samples were classified within genera containing known cellulose degraders, including Acidovorax, the most abundant OTU detected across samples, which was positively correlated with cellulolytic ability. A representative Acidovorax strain was isolated, but did not grow on cellulose alone. Phenotypic and compositional analyses of enrichment cultures, such as those presented here, help link community composition with cellulolytic ability and provide insight into the complexity of community-based cellulose degradation.Biological and Environmental Research/[DE-FC02-07ER64494]/BER/Estados UnidosNational Science Foundation/[DGE-1256259]/NSF/Estados UnidosNational Science Foundation/[DEB-0747002]/NSF/Estados UnidosNational Science Foundation/[MCB-0702025]/NSF/Estados UnidosNational Institutes of Health/[T32 GM07215]/NIH/Estados UnidosUniversidad de Costa Rica/[]/UCR/Costa RicaMinisterio de Ciencia, Tecnología y Telecomunicaciones/[]/MICITT/Costa RicaUniversity of Wisconsin-Madison's Hilldale Undergraduate Faculty Research Fellowship/[]//Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM