9,876 research outputs found
Motion of a Solitonic Vortex in the BEC-BCS Crossover
We observe a long-lived solitary wave in a superfluid Fermi gas of Li
atoms after phase-imprinting. Tomographic imaging reveals the excitation to be
a solitonic vortex, oriented transverse to the long axis of the cigar-shaped
atom cloud. The precessional motion of the vortex is directly observed, and its
period is measured as a function of the chemical potential in the BEC-BCS
crossover. The long period and the correspondingly large ratio of the inertial
to the bare mass of the vortex are in good agreement with estimates based on
superfluid hydrodynamics that we derive here using the known equation of state
in the BEC-BCS crossover
Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK
Copyright © 2014 Elsevier Inc. All rights reserved.Peer reviewedPublisher PD
LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
The serine/threonine kinase LKB1 has a conserved role in Drosophila and nematodes to co-ordinate cell metabolism. During T lymphocyte development in the thymus, progenitors need to synchronize increased metabolism with the onset of proliferation and differentiation to ensure that they can meet the energy requirements for development. The present study explores the role of LKB1 in this process and shows that loss of LKB1 prevents thymocyte differentiation and the production of peripheral T lymphocytes. We find that LKB1 is required for several key metabolic processes in T-cell progenitors. For example, LKB1 controls expression of CD98, a key subunit of the l-system aa transporter and is also required for the pre-TCR to induce and sustain the regulated phosphorylation of the ribosomal S6 subunit, a key regulator of protein synthesis. In the absence of LKB1 TCR-β-selected thymocytes failed to proliferate and did not survive. LBK1 was also required for survival and proliferation of peripheral T cells. These data thus reveal a conserved and essential role for LKB1 in the proliferative responses of both thymocytes and mature T cells
Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells
The insulin/IGF-1 (insulin-like growth factor 1)-activated protein kinase Akt (also known as protein kinase B) phosphorylates Ser(487) in the ‘ST loop’ (serine/threonine-rich loop) within the C-terminal domain of AMPK-α1 (AMP-activated protein kinase-α1), leading to inhibition of phosphorylation by upstream kinases at the activating site, Thr(172). Surprisingly, the equivalent site on AMPK-α2, Ser(491), is not an Akt target and is modified instead by autophosphorylation. Stimulation of HEK (human embryonic kidney)-293 cells with IGF-1 caused reduced subsequent Thr(172) phosphorylation and activation of AMPK-α1 in response to the activator A769662 and the Ca(2+) ionophore A23187, effects we show to be dependent on Akt activation and Ser(487) phosphorylation. Consistent with this, in three PTEN (phosphatase and tensin homologue deleted on chromosome 10)-null tumour cell lines (in which the lipid phosphatase PTEN that normally restrains the Akt pathway is absent and Akt is thus hyperactivated), AMPK was resistant to activation by A769662. However, full AMPK activation could be restored by pharmacological inhibition of Akt, or by re-expression of active PTEN. We also show that inhibition of Thr(172) phosphorylation is due to interaction of the phosphorylated ST loop with basic side chains within the αC-helix of the kinase domain. Our findings reveal that a previously unrecognized effect of hyperactivation of Akt in tumour cells is to restrain activation of the LKB1 (liver kinase B1)–AMPK pathway, which would otherwise inhibit cell growth and proliferation
National Trends in Smoking Cessation Medication Prescriptions for Smokers With Chronic Obstructive Pulmonary Disease in the United States, 2007-2012
Objectives Smoking cessation decreases morbidity and mortality due to chronic obstructive pulmonary disease (COPD). Pharmacotherapy for smoking cessation is highly effective. However, the optimal prescription rate of smoking cessation medications among smokers with COPD has not been systemically studied. The purpose of this study was to estimate the national prescription rates of smoking cessation medications among smokers with COPD and to examine any disparities therein. Methods We conducted a retrospective study using National Ambulatory Medical Care Survey data from 2007 to 2012. We estimated the national prescription rate for any smoking cessation medication (varenicline, bupropion, and nicotine replacement therapy) each year. Multiple survey logistic regression was performed to characterize the effects of demographic variables and comorbidities on prescriptions. Results The average prescription rate of any smoking cessation medication over 5 years was 3.64%. The prescription rate declined each year, except for a slight increase in 2012: 9.91% in 2007, 4.47% in 2008, 2.42% in 2009, 1.88% in 2010, 1.46% in 2011, and 3.67% in 2012. Hispanic race and depression were associated with higher prescription rates (odds ratio [OR], 5.15; 95% confidence interval [CI], 1.59 to 16.67 and OR, 2.64; 95% CI, 1.26 to 5.51, respectively). There were no significant differences according to insurance, location of the physician, or other comorbidities. The high OR among Hispanic population and those with depression was driven by the high prescription rate of bupropion. Conclusions The prescription rate of smoking cessation medications among smokers with COPD remained low throughout the study period. Further studies are necessary to identify barriers and to develop strategies to overcome them
Abundance ratios in the hot ISM of elliptical galaxies
To constrain the recipes put forth to solve the theoretical Fe discrepancy in
the hot interstellar medium of elliptical galaxies and at the same time explain
the [alpha/Fe] ratios. In order to do so we use the latest theoretical
nucleosynthetic yields, we incorporate the dust, we explore differing SNIa
progenitor scenarios by means of a self-consistent chemical evolution model
which reproduces the properties of the stellar populations in elliptical
galaxies. Models with Fe-only dust and/or a lower effective SNIa rate achieve a
better agreement with the observed Fe abundance. However, a suitable
modification to the SNIa yield with respect to the standard W7 model is needed
to fully match the abundance ratio pattern. The 2D explosion model C-DDT by
Maeda et al. (2010) is a promising candidate for reproducing the [Fe/H] and the
[alpha/Fe] ratios. (A&A format)Comment: 11 pages, 4 figures, to appear on A&
Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease
Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis
Background
Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown.
Objective
To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis.
Methods
A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis.
Results
Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1β (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases.
Conclusions
SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.This study was supported by grants from the Instituto de Salud Carlos III (ISCIII, Spain) (PI19/01166, CIBERONC: CB16/12/00400) and Fondo Europeo de Desarrollo Regional (FEDER) (EQC2019-005419-P), within the Subprograma Estatal de Infraestructuras de Investigación y Equipamiento Científico Técnico de 2019 del Ministerio de Ciencia, Innovación y Universidades, Fundación Española de Mastocitosis (FEM, Madrid, Spain ref.: FEM2019-MAGPIX and FEM2021-SAM); Asociación Española de Mastocitosis y Enfermedades Relacionadas (AEDM-CTMC-2019). We also thank the Biobank at the Hospital Virgen de la Salud (BioB-HVS) No. B.0000520, Toledo, Spain. TAR was supported by the 2019 European Academy of Allergy and Clinical Immunology Research Fellowship award. We thank our patients for their willingness to participate in this study
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