The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical ...microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor-somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations.
Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 μM ouabain 100 nM blebbistatin) or ...chronic myocardial Na
load (PLM
mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLM
), transgenic (PLM
), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by
Na,
P,
C NMR followed by
H-NMR metabolomic profiling. Elevated Na
leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorates the metabolic changes. In silico modelling indicates altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Na
overload or inhibition of Na/Ca
may be a new approach to ameliorate metabolic dysregulation in heart failure.
Abstract
Low dimensional quantum magnets are interesting because of the emerging collective behavior arising from strong quantum fluctuations. The one-dimensional (1D)
S
= 1/2 Heisenberg ...antiferromagnet is a paradigmatic example, whose low-energy excitations, known as spinons, carry fractional spin
S
= 1/2. These fractional modes can be reconfined by the application of a staggered magnetic field. Even though considerable progress has been made in the theoretical understanding of such magnets, experimental realizations of this low-dimensional physics are relatively rare. This is particularly true for rare-earth-based magnets because of the large effective spin anisotropy induced by the combination of strong spin–orbit coupling and crystal field splitting. Here, we demonstrate that the rare-earth perovskite YbAlO
3
provides a realization of a quantum spin
S
= 1/2 chain material exhibiting both quantum critical Tomonaga–Luttinger liquid behavior and spinon confinement–deconfinement transitions in different regions of magnetic field–temperature phase diagram.
A means of encoding and decoding data using wireless orbital angular momentum (OAM) modes is proposed and analysed. Source data symbols are used to select an OAM mode, which is generated using an ...8-element circular array. A 2-element array is used to detect the mode by estimating the phase gradient of the received signal, and hence identifying the transmitted data symbol. The results are presented in terms of mode estimation error.
In principle, a complex assembly of strongly interacting electrons can self-organize into a wide variety of collective states, but relatively few such states have been identified in practice. We ...report that, in the close vicinity of a metamagnetic quantum critical point, high-purity strontium ruthenate Sr3Ru2O7 possesses a large magnetoresistive anisotropy, consistent with the existence of an electronic nematic fluid. We discuss a striking phenomenological similarity between our observations and those made in high-purity two-dimensional electron fluids in gallium arsenide devices.
Intratumoral hypoxia and immunity have been correlated with patient outcome in various tumor settings. However, these factors are not currently considered for treatment selection in head and neck ...cancer (HNC) due to lack of validated biomarkers. Here we sought to develop a hypoxia-immune classifier with potential application in patient prognostication and prediction of response to targeted therapy.
A 54-gene hypoxia-immune signature was constructed on the basis of literature review. Gene expression was analyzed
using the The Cancer Genome Atlas (TCGA) HNC dataset (
= 275) and validated using two independent cohorts (
= 130 and 123). IHC was used to investigate the utility of a simplified protein signature. The spatial distribution of hypoxia and immune markers was examined using multiplex immunofluorescence staining.
Unsupervised hierarchical clustering of TCGA dataset (development cohort) identified three patient subgroups with distinct hypoxia-immune phenotypes and survival profiles: hypoxia
/immune
, hypoxia
/immune
, and mixed, with 5-year overall survival (OS) rates of 71%, 51%, and 49%, respectively (
= 0.0015). The prognostic relevance of the hypoxia-immune gene signature was replicated in two independent validation cohorts. Only PD-L1 and intratumoral CD3 protein expression were associated with improved OS on multivariate analysis. Hypoxia
/immune
and hypoxia
/immune
tumors were overrepresented in "inflamed" and "immune-desert" microenvironmental profiles, respectively. Multiplex staining demonstrated an inverse correlation between CA-IX expression and prevalence of intratumoral CD3
T cells (
= -0.5464;
= 0.0377), further corroborating the transcription-based classification.
We developed and validated a hypoxia-immune prognostic transcriptional classifier, which may have clinical application to guide the use of hypoxia modification and targeted immunotherapies for the treatment of HNC.
Purpose
Symptoms of Multiple Sclerosis (MS) differentially impact upon quality of life (QoL) and a comprehensive measure is required for use in observational and interventional studies. This study ...examines the abbreviated World Health Organisation Quality of Life tool (WHOQOL-BREF) which was designed to be used as a broad measure of QoL across different cultures and diseases.
Methods
Data were collected from 3186 subjects as part of the TONiC study in MS and was examined with a systematic, iterative approach using Rasch analysis to investigate the internal construct validity of the WHOQOL-BREF.
Results
Mean age was 49.8 years (SD 11.8), disease duration was 11.2 years (SD 9.6) and 73.2% were female. Subjects represented all stages of MS with EDSS scores of 0–4, 4.5–6.5, 7–7.5 and ≥ 8 seen in 49.8%, 38.5%, 6.8% and 4.9% of patients, respectively. Using a super-item approach, it was possible to demonstrate fit to the assumptions of the Rasch model for 3 of the 4 domains of the WHOQOL-BREF (physical, psychological and environment) as well as a broad 24-item total score. In addition, item subsets derived from the stem of each question were shown to function as novel scales measuring impact and life satisfaction. We have provided transformation tables from ordinal raw scores to interval scales where data are complete.
Conclusions
The validation of multiple conceptual frameworks validates the WHOQOL-BREF as a powerful and flexible end-point for use in clinical trials and in testing conceptual models of factors influencing QoL in MS.
A two-element time-modulated array system which can be configured to provide active electronic null scanning is presented. The received signal from each element of the array is time switched and ...combined to provide a phase-modulated output in which the depth of modulation is dependent on the angle of arrival of the received signal. The angular response of the array at the first harmonic of the switching frequency exhibits a deep null which can be scanned in angle to plusmn90deg by controlling the mark-space ratio of the element switching waveform
Neonatal encephalopathy due to hypoxia-ischemia is associated with adverse neurodevelopmental effects. The involvement of branched chain amino acids (BCAAs) in this is largely unexplored. Transport ...of BCAAs at the plasma membrane is facilitated by SLC7A5/SLC3A2, which increase with hypoxia. We hypothesized that hypoxia would alter BCAA transport and metabolism in the neonatal brain. We investigated this using an organotypic forebrain slice culture model with, the SLC7A5/SLC3A2 inhibitor, 2-Amino-2-norbornanecarboxylic acid (BCH) under normoxic or hypoxic conditions. We subsequently analysed the metabolome and candidate gene expression. Hypoxia was associated with increased expression of SLC7A5 and SLC3A2 and an increased tissue abundance of BCAAs. Incubation of slices with
C-leucine confirmed that this was due to increased cellular uptake. BCH had little effect on metabolite abundance under normoxic or hypoxic conditions. This suggests hypoxia drives increased cellular uptake of BCAAs in the neonatal mouse forebrain, and membrane mediated transport through SLC7A5 and SLC3A2 is not essential for this process. This indicates mechanisms exist to generate the compounds required to maintain essential metabolism in the absence of external nutrient supply. Moreover, excess BCAAs have been associated with developmental delay, providing an unexplored mechanism of hypoxia mediated pathogenesis in the developing forebrain.
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