Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this ...process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.
Agriculture is expanding into regions that are affected by salinity. This review considers the energetic costs of salinity tolerance in crop plants and provides a framework for a quantitative ...assessment of costs. Different sources of energy, and modifications of root system architecture that would maximize water vs ion up take are addressed. Energy requirements for transport of salt (NaCl) to leaf vacuoles for osmotic adjustment could be small if there are no substantial leaks back across plasma membrane and tonoplast in root and leaf. The coupling ratio of the H⁺ -ATPase also is a critical component. One proposed leak, that of Na⁺ influx across the plasma membrane through certain aquaporin channels, might be coupled to water flow, thus conserving energy. For the tonoplast, control of two types of cation channels is required for energy efficiency. Transporters controlling the Na⁺ and Cl⁻ concentrations in mitochondria and chloroplasts are largely unknown and could be a major energy cost. The complexity of the system will require a sophisticated modelling approach to identify critical transporters, apoplastic barriers and root structures. This modelling approach will inform experimentation and allow a quantitative assess ment of the energy costs of Na Cl tolerance to guide breeding and engineering of molecular components.
Ever since the first observation of all-optical switching of magnetization in the ferrimagnetic alloy GdFeCo using femtosecond laser pulses, there has been significant interest in exploiting this ...process for data-recording applications. In particular, the ultrafast speed of the magnetic reversal can enable the writing speeds associated with magnetic memory devices to be potentially pushed towards THz frequencies. This work reports the development of perpendicular magnetic tunnel junctions incorporating a stack of Tb/Co nanolayers whose magnetization can be all-optically controlled via helicity-independent single-shot switching. Toggling of the magnetization of the Tb/Co electrode was achieved using either 60 femtosecond-long or 5 picosecond-long laser pulses, with incident fluences down to 3.5 mJ/cm
, for Co-rich compositions of the stack either in isolation or coupled to a CoFeB-electrode/MgO-barrier tunnel-junction stack. Successful switching of the CoFeB-Tb/Co electrodes was obtained even after annealing at 250
C. After integration of the Tb/Co-based electrodes within perpendicular magnetic tunnel junctions yielded a maximum tunneling magnetoresistance signal of 41% and RxA value of 150 Ωμm
with current-in-plane measurements and ratios between 28% and 38% in nanopatterned pillars. These results represent a breakthrough for the development of perpendicular magnetic tunnel junctions controllable using single laser pulses, and offer a technologically-viable path towards the realization of hybrid spintronic-photonic systems featuring THz switching speeds.
Context.
The Galactic plane has been observed extensively by a large number of Galactic plane surveys from infrared to radio wavelengths at an angular resolution below 40′′. However, a 21 cm line and ...continuum survey with comparable spatial resolution is lacking.
Aims.
The first half of THOR data (
l
= 14.0°−37.9°, and
l
= 47.1°−51.2°, |
b
|≤ 1.25°) has been published in our data release 1 paper. With this data release 2 paper, we publish all the remaining spectral line data and Stokes I continuum data with high angular resolution (10′′–40′′), including a new H
I
dataset for the whole THOR survey region (
l
= 14.0−67.4° and |
b
|≤ 1.25°). As we published the results of OH lines and continuum emission elsewhere, we concentrate on the H
I
analysis in this paper.
Methods.
With the
Karl G. Jansky
Very Large Array (VLA) in C-configuration, we observed a large portion of the first Galactic quadrant, achieving an angular resolution of ≤40′′. At
L
Band, the WIDAR correlator at the VLA was set to cover the 21 cm H
I
line, four OH transitions, a series of H
nα
radio recombination lines (RRLs;
n
= 151 to 186), and eight 128 MHz-wide continuum spectral windows, simultaneously.
Results.
We publish all OH and RRL data from the C-configuration observations, and a new H
I
dataset combining VLA C+D+GBT (VLA D-configuration and GBT data are from the VLA Galactic Plane Survey) for the whole survey. The H
I
emission shows clear filamentary substructures at negative velocities with low velocity crowding. The emission at positive velocities is more smeared-out, likely due to higher spatial and velocity crowding of structures at the positive velocities. Compared to the spiral arm model of the Milky Way, the atomic gas follows the Sagittarius and Perseus Arm well, but with significant material in the inter-arm regions. With the C-configuration-only H
I
+continuum data, we produce an H
I
optical depth map of the THOR areal coverage from 228 absorption spectra with the nearest-neighbor method. With this
τ
map, we corrected the H
I
emission for optical depth, and the derived column density is 38% higher than the column density with optically thin assumption. The total H
I
mass with optical depth correction in the survey region is 4.7 × 10
8
M
⊙
, 31% more than the mass derived assuming the emission is optically thin. If we applied this 31% correction to the whole Milky Way, the total atomic gas mass would be 9.4–10.5 × 10
9
M
⊙
. Comparing the H
I
with existing CO data, we find a significant increase in the atomic-to-molecular gas ratio from the spiral arms to the inter-arm regions.
Conclusions.
The high-sensitivity and resolution THOR H
I
dataset provides an important new window on the physical and kinematic properties of gas in the inner Galaxy. Although the optical depth we derive is a lower limit, our study shows that the optical depth correction issignificant for H
I
column density and mass estimation. Together with the OH, RRL and continuum emission from the THOR survey, these new H
I
data provide the basis for high-angular-resolution studies of the interstellar medium in different phases.
Vegetation optical depth (VOD) retrieved from microwave radiometry correlates with the total amount of water in vegetation, based on theoretical and
empirical evidence. Because the total amount of ...water in vegetation varies with relative water content (as well as with biomass), this correlation
further suggests a possible relationship between VOD and plant water potential, a quantity that drives plant hydraulic behavior. Previous studies
have found evidence for that relationship on the scale of satellite pixels tens of kilometers across, but these comparisons suffer from significant
scaling error. Here we used small-scale remote sensing to test the link between remotely sensed VOD and plant water potential. We placed an L-band
radiometer on a tower above the canopy looking down at red oak forest stand during the 2019 growing season in central Massachusetts, United
States. We measured stem xylem and leaf water potentials of trees within the stand and retrieved VOD with a single-channel algorithm based on
continuous radiometer measurements and measured soil moisture. VOD exhibited a diurnal cycle similar to that of leaf and stem water potential, with
a peak at approximately 05:00 eastern daylight time (UTC−4). VOD was also positively correlated with both the measured dielectric constant and water potentials of stem xylem
over the growing season. The presence of moisture on the leaves did not affect the observed relationship between VOD and stem water potential. We
used our observed VOD–water-potential relationship to estimate stand-level values for a radiative transfer parameter and a plant hydraulic
parameter, which compared well with the published literature. Our findings support the use of VOD for plant hydraulic studies in temperate forests.
Energy costs of salinity tolerance in crop plants Tyerman, Stephen D.; Munns, Rana; Fricke, Wieland ...
The New phytologist,
January 2019, Letnik:
221, Številka:
1
Journal Article, Conference Proceeding
Molecular clouds form from the atomic phase of the interstellar medium. However, characterizing the transition between the atomic and the molecular interstellar medium (ISM) is a complex ...observational task. Here we address cloud formation processes by combining H
I
self absorption (HISA) with molecular line data. Column density probability density functions (N-PDFs) are a common tool for examining molecular clouds. One scenario proposed by numerical simulations is that the N-PDF evolves from a log-normal shape at early times to a power-law-like shape at later times. To date, investigations of N-PDFs have been mostly limited to the molecular component of the cloud. In this paper, we study the cold atomic component of the giant molecular filament GMF38.1-32.4a (GMF38a, distance = 3.4 kpc, length ~ 230 pc), calculate its N-PDFs, and study its kinematics. We identify an extended HISA feature, which is partly correlated with the
13
CO emission. The peak velocities of the HISA and
13
CO observations agree well on the eastern side of the filament, whereas a velocity offset of approximately 4 km s
−1
is found on the western side. The sonic Mach number we derive from the linewidth measurements shows that a large fraction of the HISA, which is ascribed to the cold neutral medium (CNM), is at subsonic and transonic velocities. The column density of the CNM part is on the order of 10
20
to 10
21
cm
−2
. The column density of molecular hydrogen, traced by
13
CO, is an order of magnitude higher. The N-PDFs from HISA (CNM), H
I
emission (the warm and cold neutral medium), and
13
CO (molecular component) are well described by log-normal functions, which is in agreement with turbulent motions being the main driver of cloud dynamics. The N-PDF of the molecular component also shows a power law in the high column-density region, indicating self-gravity. We suggest that we are witnessing two different evolutionary stages within the filament. The eastern subregion seems to be forming a molecular cloud out of the atomic gas, whereas the western subregion already shows high column density peaks, active star formation, and evidence of related feedback processes.
Paclitaxel-induced neuropathy is an adverse event that often leads to therapeutic disruption and patient discomfort. We attempted to replicate a previously reported association between increased ...neuropathy risk and CYP2C8*3 genotype.
Demographic, treatment, and toxicity data were collected for paclitaxel-treated breast cancer patients who were genotyped for the CYP2C8*3 K399R (rs10509681) variant. A log-rank test was used in the primary analysis of European-American patients. An additional independent replication was then attempted in a cohort of African-American patients, followed by modeling of the entire patient cohort with relevant covariates.
In the primary analysis of 209 European patients, there was an increased risk of paclitaxel-induced neuropathy related to CYP2C8*3 status HR (per allele) = 1.93 (95% CI: 1.05–3.55), overall log-rank P = 0.006. The association was replicated in direction and magnitude of effect in 107 African-American patients (P = 0.043). In the Cox model using the entire mixed-race cohort (n = 411), each CYP2C8*3 allele approximately doubled the patient's risk of grade 2+ neuropathy (P = 0.004), and non-Europeans were at higher neuropathy risk than Europeans of similar genotype (P = 0.030).
The increased risk of paclitaxel-induced neuropathy in patients who carry the CYP2C8*3 variant was replicated in two racially distinct patient cohorts.
This work reports the development of perpendicular magnetic tunnel junctions, based on a multilayered stack of Tb/Co nanolayers, in which the magnetization can be reliably toggled using a single ...optical pulse. The helicity-independent single-shot switching of the magnetization in the Tb/Co multilayered stack was achieved using either 60 fs-long or 5 ps laser pulses with incident fluences down to 4.7 mJ/cm2. The magnetic switching was achieved for a Co-rich composition window of the multilayer corresponding to layer thickness ratios tCo/tTb between 1.3-1.5. This was confirmed for the multilayer alone as well as for the multilayer coupled to aCoFeB electrode, with a structure consisting of CoFeB/Ta/Tb/CoN. The optical switching is preserved even after annealing at 250°C in magnetic tunnel junctions (MTJ) electrodes, exhibiting a tunnel magnetoresistance (TMR) of 41% and RxA value of 150 Ωμm after its integration, measured on unpatterned MTJ stacks. These results represent the first step towards the development of hybrid spintronic photonic systems with fJ switching energies.
MR imaging can be used to measure structural changes in the brains of individuals with multiple sclerosis and is essential for diagnosis, longitudinal monitoring, and therapy evaluation. The North ...American Imaging in Multiple Sclerosis Cooperative steering committee developed a uniform high-resolution 3T MR imaging protocol relevant to the quantification of cerebral lesions and atrophy and implemented it at 7 sites across the United States. To assess intersite variability in scan data, we imaged a volunteer with relapsing-remitting MS with a scan-rescan at each site.
All imaging was acquired on Siemens scanners (4 Skyra, 2 Tim Trio, and 1 Verio). Expert segmentations were manually obtained for T1-hypointense and T2 (FLAIR) hyperintense lesions. Several automated lesion-detection and whole-brain, cortical, and deep gray matter volumetric pipelines were applied. Statistical analyses were conducted to assess variability across sites, as well as systematic biases in the volumetric measurements that were site-related.
Systematic biases due to site differences in expert-traced lesion measurements were significant (
< .01 for both T1 and T2 lesion volumes), with site explaining >90% of the variation (range, 13.0-16.4 mL in T1 and 15.9-20.1 mL in T2) in lesion volumes. Site also explained >80% of the variation in most automated volumetric measurements. Output measures clustered according to scanner models, with similar results from the Skyra versus the other 2 units.
Even in multicenter studies with consistent scanner field strength and manufacturer after protocol harmonization, systematic differences can lead to severe biases in volumetric analyses.
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