Activity

DCS also reduced intracellular and extracellular asyn levels, increased following lysosomal inhibition, independently from autophagic degradation, suggesting that other mechanisms are also involved. Collectively, these findings suggest that DCS exerts on-line and off-line effects on the expression, aggregation and autophagic degradation of asyn, indicating a till unknown neuroprotective role of tDCS.Laser-driven proton acceleration is a growing field of interest in the high-power laser community. One of the big challenges related to the most routinely used laser-driven ion acceleration mechanism, Target-Normal Sheath Acceleration (TNSA), is to enhance the laser-to-proton energy transfer such as to maximize the proton kinetic energy and number. A way to achieve this is using nanostructured target surfaces in the laser-matter interaction. In this paper, we show that nanowire structures can increase the maximum proton energy by a factor of two, triple the proton temperature and boost the proton numbers, in a campaign performed on the ultra-high contrast 10 TW laser at the Lund Laser Center (LLC). The optimal nanowire length, generating maximum proton energies around 6 MeV, is around 1-2 [Formula see text]m. This nanowire length is sufficient to form well-defined highly-absorptive NW forests and short enough to minimize the energy loss of hot electrons going through the target bulk. Results are further supported by Particle-In-Cell simulations. Systematically analyzing nanowire length, diameter and gap size, we examine the underlying physical mechanisms that are provoking the enhancement of the longitudinal accelerating electric field. The parameter scan analysis shows that optimizing the spatial gap between the nanowires leads to larger enhancement than by the nanowire diameter and length, through increased electron heating.Axillary lymph node status is an important prognostic factor for breast cancer patients and sentinel lymph node biopsy (SLNB) is a less invasive surgical proxy. We examined if consecutively derived molecular subtypes from primary breast cancers provide additional predictive value for SLNB status. 1556 patients with a breast cancer > 10 mm underwent primary surgical procedure including SLNB and tumor specimens were assigned with a transcriptomics-based molecular subtype. 1020 patients had a negative sentinel node (SN) and 536 a positive. A significant association between tumor size and SN status (p  less then  0.0001) was found across all samples, but no association between size and SN status (p = 0.14) was found for BasL tumors. A BasL subtype was a predictor of an SN-negative status (p = 0.001, OR 0.58, 95% CI 0.38;0.90) and among the BasL, postmenopausal status was a predictor for SN-negative status (p = 0.01). Overall survival was significantly lower (p = 0.02) in patients with BasL tumors and a positive SN. Interestingly, we identified a significant correlation between hormone receptor activity and SN status within the BasL subtype. Taken together, molecular subtypes and hormone receptor activity of breast cancers add predictive value for SLNB status.Rectal cancer (RC) appears to behave differently compared with colon cancer. We aimed to analyze existence of different subtypes of RC depending on distinct features (age of onset and the presence of synchronous primary malignant neoplasms). selleckchem We compared the clinicopathological, familial and molecular features of three different populations diagnosed with RC (early-onset RC [EORC], late-onset RC, and synchronous RC [SRC]). Eighty-five RCs were identified and were evaluated according to their microsatellite instability, CpG Island Methylator Phenotype (CIMP) and chromosomal instability, as assessed by Next Generation Sequencing and microarray-based comparative genomic hybridization approaches. The results were subjected to cluster analysis. SRCs displayed the most specific characteristics including a trend for the development of multiple malignant neoplasms, a greater proportion of CIMP-High tumors (75%) and more frequent genomic alterations. These findings were confirmed by a clustering analysis that stratified RCs according to their genomic alterations. We also found that EORCs exhibited their own features including an important familial cancer component and a remarkable rate of mutations in TP53 (53%). Together, heterogeneity in RC characteristics by age of disease-onset and SRC warrants further study to optimize tailored prevention, detection and intervention strategies-particularly among young adults.In a high-speed single-molecule experiment with a force probe, a protein is tethered between two substrates that are manipulated to exert force on the system. To avoid nonspecific interactions between the protein and nearby substrates, the protein is usually attached to the substrates through long, flexible linkers. This approach precludes measurements of mechanical properties with high spatial and temporal resolution, for rapidly exerted forces are dissipated into the linkers. Because mammalian hearing operates at frequencies reaching tens to hundreds of kilohertz, the mechanical processes that occur during transduction are of very short duration. Single-molecule experiments on the relevant proteins therefore cannot involve long tethers. We previously characterized the mechanical properties of protocadherin 15 (PCDH15), a protein essential for human hearing, by tethering an individual monomer through very short linkers between a probe bead held in an optical trap and a pedestal bead immobilized on a glass coverslip. Because the two confining surfaces were separated by only the length of the tethered protein, hydrodynamic coupling between those surfaces complicated the interpretation of the data. To facilitate our experiments, we characterize here the anisotropic and position-dependent diffusion coefficient of a probe in the presence of an effectively infinite wall, the coverslip, and of the immobile pedestal.Rhizosphere and root endophytic bacteria are crucial for plant development, but the question remains if their composition is similar and how environmental conditions, such as water content, affect their resemblance. Ricinus communis L., a highly drought resistant plant, was used to study how varying soil water content affected the bacterial community in uncultivated, non-rhizosphere and rhizosphere soil, and in its roots. Additionally, the bacterial community structure was determined in the seeds of R. communis at the onset of the experiment. Plants were cultivated in soil at three different watering regimes, i.e. 50% water holding capacity (WHC) or adjusted to 50% WHC every two weeks or every month. Reducing the soil water content strongly reduced plant and root dry biomass and plant development, but had little effect on the bacterial community structure. The bacterial community structure was affected significantly by cultivation of R. communis and showed large variations over time. After 6 months, the root endophytic bacterial community resembled that in the seeds more than in the rhizosphere.