The high temperatures and strong magnetic fields of the solar corona form streams of solar wind that expand through the Solar System into interstellar space. At 09:33 UT on 28 April 2021 Parker Solar ...Probe entered the magnetized atmosphere of the Sun 13 million km above the photosphere, crossing below the Alfvén critical surface for five hours into plasma in casual contact with the Sun with an Alfvén Mach number of 0.79 and magnetic pressure dominating both ion and electron pressure. The spectrum of turbulence below the Alfvén critical surface is reported. Magnetic mapping suggests the region was a steady flow emerging on rapidly expanding coronal magnetic field lines lying above a pseudostreamer. The sub-Alfvénic nature of the flow may be due to suppressed magnetic reconnection at the base of the pseudostreamer, as evidenced by unusually low densities in this region and the magnetic mapping.
We present a combined observational and theoretical analysis to investigate the nature of plasma turbulence at kinetic scales in the Earth's magnetosheath. In the first decade of the kinetic range, ...just below the ion gyroscale, the turbulence was found to be similar to that in the upstream solar wind: predominantly anisotropic, low-frequency and kinetic Alfvén in nature. A key difference, however, is that the magnetosheath ions are typically much hotter than the electrons, , which, together with , leads to a change in behavior in the second decade, close to electron scales. The turbulence here is characterized by an increased magnetic compressibility, following a mode we term the inertial kinetic Alfvén wave, and a steeper spectrum of magnetic fluctuations, consistent with the prediction that we obtain from a set of nonlinear equations. This regime of plasma turbulence may also be relevant for other astrophysical environments with , such as the solar corona, hot accretion flows, and regions downstream of collisionless shocks.
Endochondral ossification is the process by which the embryonic cartilaginous model of most bones contributes to longitudinal growth and is gradually replaced by bone. During endochondral ...ossification, chondrocytes proliferate, undergo hypertrophy and die; the cartilage extracellular matrix they construct is then invaded by blood vessels, osteoclasts, bone marrow cells and osteoblasts, the last of which deposit bone on remnants of cartilage matrix. The sequential changes in chondrocyte behaviour are tightly regulated by both systemic factors and locally secreted factors, which act on receptors to effect intracellular signalling and activation of chondrocyte-selective transcription factors. Systemic factors that regulate the behaviour of chondrocytes in growth cartilage include growth hormone and thyroid hormone, and the local secreted factors include Indian hedgehog, parathyroid hormone-related peptide, fibroblast growth factors and components of the cartilage extracellular matrix. Transcription factors that play critical roles in regulation of chondrocyte gene expression under the control of these extracellular factors include Runx2, Sox9 and MEF2C. The invasion of cartilage matrix by the ossification front is dependent on its resorption by members of the matrix metalloproteinase family, as well as the presence of blood vessels and bone-resorbing osteoclasts. This review, which places an emphasis on recent advances and current areas of debate, discusses the complex interactions between cell types and signalling pathways that govern endochondral ossification.
Objectives
To explore the association between orthostatic hypotension (OH) and frailty for hospitalized older patients and their vulnerable subgroups.
Design
A prospective, observational ...cross-sectional study.
Participants
693 older patients admitted to a geriatric evaluation and management unit.
Measurements
Barthel Index, Lawton’s instrumental activities of daily living, clinical frailty scale, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, and polypharmacy.
Results
Overall, the prevalence of OH and frailty was 26% and 36%, respectively. Subjects with OH were older, thinner, more commonly to have weakness, slowness, poorer physical function and higher levels of frailty. The prevalence of OH was substantially increased as higher levels of CFS (p for trend <0.001). Multivariate logistic regression showed significant association between OH and frailty (OR: 1.8, 95% CI: 1.2-2.7), but the association attenuated after adjustment for physical function. (OR: 1.4, 95% CI: 0.7-2.6). Nevertheless, associations between OH and frailty remained significant among vulnerable subgroups like women, subjects having weakness, slowness, poor cognitive function, polypharmacy or any IADL limitation.
Conclusions
OH in hospitalized older patients was associated with frailty and multiple complex care needs, especially in the vulnerable subgroups. Further study is needed to clarify the roles of OH in clinical practice.
The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how ...cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a "genome organizer" that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.
Background and purpose
Physical activity is associated with a reduced incidence of first‐time stroke. However, few studies have examined the effect of pre‐stroke physical activity on post‐stroke ...complications and clinical outcomes.
Methods
A total of 39 835 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2009 were analyzed according to five levels of severity as determined by National Institutes of Health Stroke Scale score upon hospital admission. Pre‐stroke physical activity was defined in the Taiwan Stroke Registry as dedicated leisure‐time physical activity for at least 30 min/day for 3 days/week for more than 6 months. A Cox model was used to compare complications and outcomes between active and inactive groups.
Results
The active and inactive groups were similar in age distribution and stroke type distribution, but the active group had better National Institutes of Health Stroke Scale scores upon admission. The active group also had significantly fewer post‐stroke complications. Active patients had lower hospital mortality and better functional outcomes upon discharge as per the modified Rankin Scale. Improved functional status in the active group was significant at 1, 3 and 6 months post‐stroke.
Conclusion
Dedicated leisure‐time physical activity for at least 30 min/day, at least three times per week for more than 6 months was associated with decreased stroke severity, fewer post‐stroke complications, lower mortality and better outcomes.
Cold-induced thermogenesis in humans Brychta, R J; Chen, K Y
European journal of clinical nutrition,
03/2017, Letnik:
71, Številka:
3
Journal Article
Recenzirano
Odprti dostop
A basic property of endothermic thermoregulation is the ability to generate heat by increasing metabolism in response to cold ambient temperatures to maintain a stable core body temperature. This ...process, known as cold-induced thermogenesis (CIT), has been measured in humans as early as 1780 by Antoine Lavoisier, but has found renewed interest because of the recent 'rediscovery' of thermogenic, cold-activated brown adipose tissue (BAT) in adult humans. In this review, we summarize some of the key findings of the work involving CIT over the past two centuries and highlight some of the seminal studies focused on this topic. There has been a substantial range of variability in the reported CIT in these studies, from 0 to 280% above basal metabolism. We identify and discuss several potential sources of this variability, including both methodological (measurement device, cold exposure temperature and duration) and biological (age and body composition of subject population) discrepancies. These factors should be considered when measuring CIT going forward to better assess whether BAT or other thermogenic organs are viable targets to combat chronic positive energy balance based on their relative capacities to elevate human metabolism.
With their fascinating biological profiles and stunningly complex molecular architectures, the polycyclic polyprenylated acylphloroglucinols (PPAPs) have long provided a fertile playing field for ...synthetic organic chemists. In particular, the recent advent of innovative synthetic methods and strategies together with CC bond‐forming reactions and asymmetric catalysis have revitalized this field tremendously. Consequently, PPAP targets which once seemed beyond reach have now been synthesized. This Review aims to highlight the recent achievements in the total synthesis of PPAPs, as well as notable methods developed for the construction of the bicyclo3.3.1 core of these chemically and biologically intriguing molecules.
Recently completed total syntheses and the ingenious synthetic approaches developed for the construction of the biologically significant polycyclic polyprenylated acylphloroglucinols (PPAPs) are presented in this Review. The state‐of‐the‐art synthetic methods and strategies, current limitations, as well as the outlook for this field are highlighted.
Pancreatic ductal adenocarcinoma (PDA) is the most lethal of common human malignancies, with no truly effective therapies for advanced disease. Preclinical studies have suggested a therapeutic ...benefit of targeting the Hedgehog (Hh) signaling pathway, which is activated throughout the course of PDA progression by expression of Hh ligands in the neoplastic epithelium and paracrine response in the stromal fibroblasts. Clinical trials to test this possibility, however, have yielded disappointing results. To further investigate the role of Hh signaling in the formation of PDA and its precursor lesion, pancreatic intraepithelial neoplasia (PanIN), we examined the effects of genetic or pharmacologic inhibition of Hh pathway activity in three distinct genetically engineered mouse models and found that Hh pathway inhibition accelerates rather than delays progression of oncogenic Kras-driven disease. Notably, pharmacologic inhibition of Hh pathway activity affected the balance between epithelial and stromal elements, suppressing stromal desmoplasia but also causing accelerated growth of the PanIN epithelium. In striking contrast, pathway activation using a small molecule agonist caused stromal hyperplasia and reduced epithelial proliferation. These results indicate that stromal response to Hh signaling is protective against PDA and that pharmacologic activation of pathway response can slow tumorigenesis. Our results provide evidence for a restraining role of stroma in PDA progression, suggesting an explanation for the failure of Hh inhibitors in clinical trials and pointing to the possibility of a novel type of therapeutic intervention.
Time-resolved 3D-DSA (4D-DSA) enables viewing vasculature from any desired angle and time frame. We investigated whether these advantages may facilitate treatment planning and the feasibility of ...using 4D-DSA as a single imaging technique in AVM/dural arteriovenous fistula radiosurgery.
Twenty consecutive patients (8 dural arteriovenous fistulas and 12 AVMs; 13 men and 7 women; mean age, 45 years; range, 18-64 years) who were scheduled for gamma knife radiosurgery were recruited (November 2014 to October 2015). An optimal volume of reconstructed time-resolved 3D volumes that defines the AVM nidus/dural arteriovenous fistula was sliced into 2D-CT-like images. The original radiosurgery treatment plan was overlaid retrospectively. The registration errors of stereotactic 4D-DSA were compared with those of integrated stereotactic imaging. AVM/dural arteriovenous fistula volumes were contoured, and disjoint and conjoint components were identified. The Wilcoxon signed rank test and the Wilcoxon rank sum test were adopted to evaluate registration errors and contoured volumes of stereotactic 4D-DSA and integration of stereotactic MR imaging and stereotactic 2D-DSA.
Sixteen of 20 patients were successfully registered in Advanced Leksell GammaPlan Program. The registration error of stereotactic 4D-DSA was smaller than that of integrated stereotactic imaging (
= .0009). The contoured AVM volume of 4D-DSA was smaller than that contoured on the integration of MR imaging and 2D-DSA, while major inconsistencies existed in cases of dural arteriovenous fistula (
= .042 and 0.039, respectively, for measurements conducted by 2 authors).
Implementation of stereotactic 4D-DSA data for gamma knife radiosurgery for brain AVM/dural arteriovenous fistula is feasible. The ability of 4D-DSA to demonstrate vascular morphology and hemodynamics in 4 dimensions potentially reduces the target volumes of irradiation in vascular radiosurgery.
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