Visualizing the Effect of an Electrostatic Gate with Angle-Resolved Photoemission Spectroscopy

Electrostatic gating is pervasive in materials science, yet its effects on the electronic band structure of materials has never been revealed directly by angle-resolved photoemission spectroscopy (ARPES), the technique of choice to non-invasively probe the electronic band structure of a material. By means of a state-of-the-art ARPES setup with sub-micron spatial resolution, we have investigated a heterostructure composed of Bernal-stacked bilayer graphene (BLG) on hexagonal boron nitride and deposited on a graphite flake. By voltage biasing the latter, the electric field effect is directly visualized on the valence band as well as on the carbon 1s core level of BLG. The band gap opening of BLG submitted to a transverse electric field is discussed and the importance of intralayer screening is put forward. Our results pave the way for new studies that will use momentum-resolved electronic structure information to gain insight on the physics of materials submitted to the electric field effect

A large chromosomal inversion affects antimicrobial sensitivity of Escherichia coli to sodium deoxycholate

Resistance to antimicrobials is normally caused by mutations in the drug targets or genes involved in antimicrobial activation or expulsion. Here we show that an Escherichia coli strain, named DOC14, selected for increased resistance to the bile salt sodium deoxycholate, has no mutations in any ORF, but instead has a 2.1 Mb chromosomal inversion. The breakpoints of the inversion are two inverted copies of an IS5 element. Besides lowering deoxycholate susceptibility, the IS5-mediated chromosomal inversion in the DOC14 mutant was found to increase bacterial survival upon exposure to ampicillin and vancomycin, and sensitize the cell to ciprofloxacin and meropenem, but does not affect bacterial growth or cell morphology in a rich medium in the absence of antibacterial molecules. Overall, our findings support the notion that a large chromosomal inversion can benefit bacterial cells under certain conditions, contributing to genetic variability available for selection during evolution. The DOC14 mutant paired with its isogenic parental strain form a useful model as bacterial ancestors in evolution experiments to study how a large chromosomal inversion influences the evolutionary trajectory in response to various environmental stressors.fals

Intervención temprana de dientes supernumerarios en dentición primaria: Reporte y seguimiento de caso clínico

Resumen: El mesiodens es un diente supernumerario que se encuentra en la zona de los incisivos centrales superiores, cuyo diagnóstico temprano es fundamental ya que permite la extracción oportuna del mismo previniendo posibles alteraciones a futuro como son:  el desarrollo de quistes, malposición de los dientes adyacentes, retraso de erupción, diastema interincisal, reabsorción apical de dientes vecinos. Reporte de caso: Paciente masculino, de 6 años con 11 meses de edad, que presentó mesiodens doble, cuyo hallazgo fue radiológico, mediante una panorámica, requisito de la odontóloga para control odontológico general, en el cual se pudo observar la presencia de dos dientes supernumerarios, los cuales estaban provocando la rotación de los incisivos permanentes superiores. El tratamiento se basó en la extracción quirúrgica temprana de los dientes supernumerarios, para determinar el abordaje fue necesario la realización de un estudio tomográfico, una vez determinada el proceso de extracción, y posteriormente la recuperación del paciente, y seguimiento radiográfico y clínico, se logró  la erupción adecuada de los incisivos centrales superiores permanentes, hasta la actualidad se realizan controles periódicos y la colocación de placas de expansión superior e inferior. Conclusión: En este caso el tratamiento es la extracción temprana, y debido al diagnóstico oportuno y las condiciones óptimas del paciente como son: la reabsorción radicular fisiológica de los dientes primarios, la ubicación de los dientes supernumerarios, así como el estadio de Nolla de los incisivos centrales superiores, permite que el  tratamiento elegido sea el óptimo  y con las condiciones menos traumáticas posibles

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Transplant Acceptance Following Anti-CD4 Versus Anti-CD40L Therapy: Evidence for Differential Maintenance of Graft-Reactive T Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73145/1/j.1600-6143.2008.02372.x.pd

El efecto del papel mediador de la comunicaci?n de la responsabilidad social empresarial en la relaci?n entre la responsabilidad social empresarial y el desempe?o financiero: Un an?lisis en la industria pesquera del Per?

A lo largo de los ?ltimos a?os, han surgido un mayor n?mero de empresas interesadas en la Responsabilidad Social Empresarial (RSE) como un eje fundamental para poder cumplir con sus objetivos econ?micos, sociales y medioambientales en las comunidades donde realizan sus actividades. En ese sentido, se esperar?a que la RSE generar? beneficios financieros para las empresas; sin embargo, los resultados en la literatura no han sido concluyentes respecto a esta relaci?n. Por ello, investigaciones recientes proponen la adici?n de variables mediadoras tales como la comunicaci?n de la RSE para capturar mejor esta relaci?n. En ese sentido, se propone un modelo cuantitativo aplicado a la industria pesquera peruana que incorpora la comunicaci?n de la RSE como variable mediadora en la relaci?n entre la RSE y desempe?o financiero. Asimismo, se plantean estrategias de recolecci?n de datos a trav?s de encuestas en 105 empresas y la formulaci?n del modelo. Se espera que este trabajo contribuya a la literatura sobre la RSE y los beneficios de su aplicaci?n en cada una de sus dimensiones, base sobre la cual las empresas podr?n tomar decisiones m?s informadas sobre la aplicaci?n de RSE

The structure and dynamic properties of the complete histidine phosphotransfer domain of the chemotaxis specific histidine autokinase CheA from Thermotoga maritima

The bacterial histidine autokinase CheA contains a histidine phosphotransfer (Hpt) domain that accepts a phosphate from the catalytic domain and donates the phosphate to either target response regulator protein, CheY or CheB. The Hpt domain forms a helix-bundle structure with a conserved four-helix bundle motif and a variable fifth helix. Observation of two nearly equally populated conformations in the crystal structure of a Hpt domain fragment of CheA from Thermotoga maritima containing only the first four helices suggests more mobility in a tightly packed helix bundle structure than previously thought. In order to examine how the structures of Hpt domain homologs may differ from each other particularly in the conformation of the last helix, and whether an alternative conformation exists in the intact Hpt domain in solution, we have solved a high-resolution, solution structure of the CheA Hpt from T. maritima and characterized the backbone dynamics of this protein. The structure contains a four-helix bundle characteristic of histidine phosphotransfer domains. The position and orientation of the fifth helix resembles those in known Hpt domain crystal and solution structures in other histidine kinases. The alternative conformation that was reported in the crystal structure of the CheA Hpt from T. maritima missing the fifth helix is not detected in the solution structure, suggesting a role for the fifth helix in providing stabilizing forces to the overall structure

Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>One of the challenges facing the tuberculosis (TB) control programmes in resource-limited settings is lack of rapid techniques for detection of drug resistant TB, particularly multi drug resistant tuberculosis (MDR TB). Results obtained with the conventional indirect susceptibility testing methods come too late to influence a timely decision on patient management. More rapid tests directly applied on sputum samples are needed. This study compared the sensitivity, specificity and time to results of four direct drug susceptibility testing tests with the conventional indirect testing for detection of resistance to rifampicin and isoniazid in <it>M. tuberculosis</it>. The four direct tests included two in-house phenotypic assays – Nitrate Reductase Assay (NRA) and Microscopic Observation Drug Susceptibility (MODS), and two commercially available tests – Genotype^®MTBDR and Genotype^®MTBDR<it>plus </it>(Hain Life Sciences, Nehren, Germany).</p> <p>Methods</p> <p>A literature review and meta-analysis of study reports was performed. The Meta-Disc software was used to analyse the reports and tests for sensitivity, specificity, and area under the summary receiver operating characteristic (sROC) curves. Heterogeneity in accuracy estimates was tested with the Spearman correlation coefficient and Chi-square.</p> <p>Results</p> <p>Eighteen direct DST reports were analysed: NRA – 4, MODS- 6, Genotype MTBDR^®– 3 and Genotype^®MTBDR<it>plus </it>– 5. The pooled sensitivity and specificity for detection of resistance to rifampicin were 99% and 100% with NRA, 96% and 96% with MODS, 99% and 98% with Genotype^®MTBDR, and 99% and 99% with the new Genotype^®MTBDR<it>plus</it>, respectively. For isoniazid it was 94% and 100% for NRA, 92% and 96% for MODS, 71% and 100% for Genotype^®MTBDR, and 96% and 100% with the Genotype^®MTBDR<it>plus</it>, respectively. The area under the summary receiver operating characteristic (sROC) curves was in ranges of 0.98 to 1.00 for all the four tests. Molecular tests were completed in 1 – 2 days and also the phenotypic assays were much more rapid than conventional testing.</p> <p>Conclusion</p> <p>Direct testing of rifampicin and isoniazid resistance in <it>M. tuberculosis </it>was found to be highly sensitive and specific, and allows prompt detection of MDR TB.</p

Reference gene validation for quantitative RT-PCR during biotic and abiotic stresses in Vitis vinifera

Grapevine is one of the most cultivated fruit crop worldwide with Vitis vinifera being the species with the highest economical importance. Being highly susceptible to fungal pathogens and increasingly affected by environmental factors, it has become an important agricultural research area, where gene expression analysis plays a fundamental role. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is currently amongst the most powerful techniques to perform gene expression studies. Nevertheless, accurate gene expression quantification strongly relies on appropriate reference gene selection for sample normalization. Concerning V. vinifera, limited information still exists as for which genes are the most suitable to be used as reference under particular experimental conditions. In this work, seven candidate genes were investigated for their stability in grapevine samples referring to four distinct stresses (Erysiphe necator, wounding and UV-C irradiation in leaves and Phaeomoniella chlamydospora colonization in wood). The expression stability was evaluated using geNorm, NormFinder and BestKeeper. In all cases, full agreement was not observed for the three methods. To provide comprehensive rankings integrating the three different programs, for each treatment, a consensus ranking was created using a non-weighted unsupervised rank aggregation method. According to the last, the three most suitable reference genes to be used in grapevine leaves, regardless of the stress, are UBC, VAG and PEP. For the P. chlamydospora treatment, EF1, CYP and UBC were the best scoring genes. Acquaintance of the most suitable reference genes to be used in grapevine samples can contribute for accurate gene expression quantification in forthcoming studiesinfo:eu-repo/semantics/publishedVersio