PTEN mutations are common in sporadic microsatellite stable colorectal cancer

The tumour suppressor gene PTEN, located at chromosome sub-band 10q23.3, encodes a dual-specificity phosphatase that negatively regulates the phosphatidylinositol 3′-kinase (PI3 K)/Akt-dependent cellular survival pathway. PTEN is frequently inactivated in many tumour types including glioblastoma, prostate and endometrial cancers. While initial studies reported that PTEN gene mutations were rare in colorectal cancer, more recent reports have shown an approximate 18% incidence of somatic PTEN mutations in colorectal tumours exhibiting microsatellite instability (MSI+). To verify the role of this gene in colorectal tumorigenesis, we analysed paired normal and tumour DNA from 41 unselected primary sporadic colorectal cancers for PTEN inactivation by mutation and/or allelic loss. We now report PTEN gene mutations in 19.5% (8/41) of tumours and allele loss, including all or part of the PTEN gene, in a further 17% (7/41) of the cases. Both PTEN alleles were affected in over half (9/15) of these cases showing PTEN genetic abnormalities. Using immunohistochemistry, we have further shown that all tumours harbouring PTEN alterations have either reduced or absent PTEN expression and this correlated strongly with later clinical stage of tumour at presentation (P = 0.02). In contrast to previous reports, all but one of the tumours with PTEN gene mutations were microsatellite stable (MSI-), suggesting that PTEN is involved in a distinct pathway of colorectal tumorigenesis that is separate from the pathway of mismatch repair deficiency. This work therefore establishes the importance of PTEN in primary sporadic colorectal cancer

Neisseria meningitidis Differentially Controls Host Cell Motility through PilC1 and PilC2 Components of Type IV Pili

Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P) that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC2) brings a new model to light for the analysis of the interplay between pathogenic bacteria and human host cells

Additive noise properties of active matrix flatâ panel imagers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134764/1/mp6721.pd

Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases

© The Author(s) 2018. Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD

Matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry for fast and accurate identification of clinically relevant Aspergillus species

AbstractNew Aspergillus species have recently been described with the use of multilocus sequencing in refractory cases of invasive aspergillosis. The classical phenotypic identification methods routinely used in clinical laboratories failed to identify them adequately. Some of these Aspergillus species have specific patterns of susceptibility to antifungal agents, and misidentification may lead to inappropriate therapy. We developed a matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry (MS)‐based strategy to adequately identify Aspergillus species to the species level. A database including the reference spectra of 28 clinically relevant species from seven Aspergillus sections (five common and 23 unusual species) was engineered. The profiles of young and mature colonies were analysed for each reference strain, and species‐specific spectral fingerprints were identified. The performance of the database was then tested on 124 clinical and 16 environmental isolates previously characterized by partial sequencing of the β‐tubulin and calmodulin genes. One hundred and thirty‐eight isolates of 140 (98.6%) were correctly identified. Two atypical isolates could not be identified, but no isolate was misidentified (specificity: 100%). The database, including species‐specific spectral fingerprints of young and mature colonies of the reference strains, allowed identification regardless of the maturity of the clinical isolate. These results indicate that MALDI‐TOF MS is a powerful tool for rapid and accurate identification of both common and unusual species of Aspergillus. It can give better results than morphological identification in clinical laboratories

A Very Fast Three-Dimensional Impurity Profile Simulation Incorporating An Accumulated Diffusion Length and Its Application to the Design of Power MOSFETs

In this paper, we introduce a method for the fast simulation of 3D impurity profile simulation We analytically integrated the approximated non-linear transport equation and derived an analytical equation of 3D non-linear diffusion by introducing a new physical parameter, called the Accumulated Diffusion Length (ADL). This method allows us to simulate a 3D-profile by using a coupled 1D simulator and analytical equations, where the ADL is obtained during 1D simulation. Our new methodology is implemented in the 3D process simulator, SPIRIT-IWADL. Our 3D-TCAD system composed of SPIRIT-IIIIADL and our in-house device simulator was applied to the design of 3D-shaped power MOSFETs. 1

Performance evaluation of damper control settings for operation of multiple-zone variable air volume reheat system in different building applications and climate types

Choosing the right control strategies is an important task for effective operation of variable air volume reheat (VAVR) system in commercial buildings. In this design, dampers’ position inside air terminal units (ATUs) are modulated to adjust the amount of air supply volume based on thermal zones’ cooling or heating demand. A minimum air flow fraction (MAFF) is set for damper settings of ATUs to avoid under-ventilation problem in thermal zones. This study investigated the impact of MAFF value on various performance aspects of multiple-zone VAVR design in different building applications and climate types. A five-storey commercial building for three applications of school, office and retail in four climate types of tropical monsoon, hot desert, Mediterranean and humid continental have been simulated in EnergyPlus building simulation software. The results of simulations have shown that lowering MAFF value in ATUs would reduce the required reheat coil energy to maintain precise air supply temperature at part load cooling scenarios. Nonetheless, this reduction could have some implications on thermal comfort and indoor air quality level of thermal zones in a multiple-zone arrangement. It was concluded that in general it is an energy efficient control strategy to keep MAFF value to as low as 0.1 for high ventilation rate spaces like classrooms in school buildings (except for hot desert climate). On the other hand, it is advisable to not reduce MAFF value below 0.3 for low ventilation rate spaces like office areas to avoid any air quality issues in thermal zones

Crystallographic structure reveals phosphorylated pilin from Neisseria : phosphoserine sites modify type IV pilus surface chemistry and fibre morphology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72468/1/j.1365-2958.1999.01184.x.pd

Triggered optical coherence tomography for capturing rapid periodic motion

Quantitative cross-sectional imaging of vocal folds during phonation is potentially useful for diagnosis and treatments of laryngeal disorders. Optical coherence tomography (OCT) is a powerful technique, but its relatively low frame rates makes it challenging to visualize rapidly vibrating tissues. Here, we demonstrate a novel method based on triggered laser scanning to capture 4-dimensional (4D) images of samples in motu at audio frequencies over 100 Hz. As proof-of-concept experiments, we applied this technique to imaging the oscillations of biopolymer gels on acoustic vibrators and aerodynamically driven vibrations of the vocal fold in an ex vivo calf larynx model. Our results suggest that triggered 4D OCT may be useful in understanding and assessing the function of vocal folds and developing novel treatments in research and clinical settings

Utilisation du MALDI-TOF-MS pour l’identification rapide et precise des especes cliniques de Scedosporium et de Pseudallescheria

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