1,359 research outputs found
Isolation and Characterization of Multi-Protein Complexes Enriched in the K-Cl Co-transporter 2 From Brain Plasma Membranes
Kcc2 plays a critical role in determining the efficacy of synaptic inhibition, however, the cellular mechanisms neurons use to regulate its membrane trafficking, stability and activity are ill-defined. To address these issues, we used affinity purification to isolate stable multi-protein complexes of K-Cl Co-transporter 2 (Kcc2) from the plasma membrane of murine forebrain. We resolved these using blue-native polyacrylamide gel electrophoresis (BN-PAGE) coupled to LC-MS/MS and label-free quantification. Data are available via ProteomeXchange with identifier PXD021368. Purified Kcc2 migrated as distinct molecular species of 300, 600, and 800 kDa following BN-PAGE. In excess of 90% coverage of the soluble N- and C-termini of Kcc2 was obtained. In total we identified 246 proteins significantly associated with Kcc2. The 300 kDa species largely contained Kcc2, which is consistent with a dimeric quaternary structure for this transporter. The 600 and 800 kDa species represented stable multi-protein complexes of Kcc2. We identified a set of novel structural, ion transporting, immune related and signaling protein interactors, that are present at both excitatory and inhibitory synapses, consistent with the proposed localization of Kcc2. These included spectrins, C1qa/b/c and the IP3 receptor. We also identified interactors more directly associated with phosphorylation; Akap5, Akap13, and Lmtk3. Finally, we used LC-MS/MS on the same purified endogenous plasma membrane Kcc2 to detect phosphorylation sites. We detected 11 sites with high confidence, including known and novel sites. Collectively our experiments demonstrate that Kcc2 is associated with components of the neuronal cytoskeleton and signaling molecules that may act to regulate transporter membrane trafficking, stability, and activity
Is Our Universe Natural?
It goes without saying that we are stuck with the universe we have.
Nevertheless, we would like to go beyond simply describing our observed
universe, and try to understand why it is that way rather than some other way.
Physicists and cosmologists have been exploring increasingly ambitious ideas
that attempt to explain why certain features of our universe aren't as
surprising as they might first appear.Comment: Invited review for Nature, 11 page
Fluids in cosmology
We review the role of fluids in cosmology by first introducing them in
General Relativity and then by applying them to a FRW Universe's model. We
describe how relativistic and non-relativistic components evolve in the
background dynamics. We also introduce scalar fields to show that they are able
to yield an inflationary dynamics at very early times (inflation) and late
times (quintessence). Then, we proceed to study the thermodynamical properties
of the fluids and, lastly, its perturbed kinematics. We make emphasis in the
constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book
"Computational and Experimental Fluid Mechanics with Applications to Physics,
Engineering and the Environment". Version 2: typos corrected and references
expande
The Impact of Flavour Changing Neutral Gauge Bosons on B->X_s gamma
The branching ratio of the rare decay B->X_s gamma provides potentially
strong constraints on models beyond the Standard Model. Considering a general
scenario with new heavy neutral gauge bosons, present in particular in Z' and
gauge flavour models, we point out two new contributions to the B->X_s gamma
decay. The first one originates from one-loop diagrams mediated by gauge bosons
and heavy exotic quarks with electric charge -1/3. The second contribution
stems from the QCD mixing of neutral current-current operators generated by
heavy neutral gauge bosons and the dipole operators responsible for the B->X_s
gamma decay. The latter mixing is calculated here for the first time. We
discuss general sum rules which have to be satisfied in any model of this type.
We emphasise that the neutral gauge bosons in question could also significantly
affect other fermion radiative decays as well as non-leptonic two-body B
decays, epsilon'/epsilon, anomalous (g-2)_mu and electric dipole moments.Comment: 31 pages, 5 figures; version published on JHEP; added magic QCD
numbers for flavour-violating Z gauge boson contribution to B -> X_s gamm
Flavor Violating Higgs Decays
We study a class of nonstandard interactions of the newly discovered 125 GeV
Higgs-like resonance that are especially interesting probes of new physics:
flavor violating Higgs couplings to leptons and quarks. These interaction can
arise in many frameworks of new physics at the electroweak scale such as two
Higgs doublet models, extra dimensions, or models of compositeness. We rederive
constraints on flavor violating Higgs couplings using data on rare decays,
electric and magnetic dipole moments, and meson oscillations. We confirm that
flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h ->
tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low
energy constraints. We estimate the current LHC limits on h -> tau mu and h ->
tau e decays by recasting existing searches for the SM Higgs in the tau-tau
channel and find that these bounds are already stronger than those from rare
tau decays. We also show that these limits can be improved significantly with
dedicated searches and we outline a possible search strategy. Flavor violating
Higgs decays therefore present an opportunity for discovery of new physics
which in some cases may be easier to access experimentally than flavor
conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu
-> 3e bounds to include large loop contributions, corrected single top
constraints; conclusions unchanged; matches version to be published in JHEP;
v3: included 2-loop contributions in mu -> e conversion, improved discussion
of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions
unchange
Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis
The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD
Artificial graphene as a tunable Dirac material
Artificial honeycomb lattices offer a tunable platform to study massless
Dirac quasiparticles and their topological and correlated phases. Here we
review recent progress in the design and fabrication of such synthetic
structures focusing on nanopatterning of two-dimensional electron gases in
semiconductors, molecule-by-molecule assembly by scanning probe methods, and
optical trapping of ultracold atoms in crystals of light. We also discuss
photonic crystals with Dirac cone dispersion and topologically protected edge
states. We emphasize how the interplay between single-particle band structure
engineering and cooperative effects leads to spectacular manifestations in
tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference
Is standard breast-conserving therapy (BCT) in elderly breast cancer patients justified? A prospective measurement of acute toxicity according CTC-classification
<p>Abstract</p> <p>Background</p> <p>Breast conserving therapy (BCT) is an accepted treatment for early-stage breast cancer. This study aimed to measure prospectively acute radiation-related toxicity and to create a comprehensive data base for long-term temporal analyses of 3D conformal adjuvant radiotherapy. The specific aspect of age has been neglected by traditional research. Therefore, the impact of age on acute BCT toxicity should be also specifically adressed.</p> <p>Methods</p> <p>Toxicity was measured in 109 patients at initiation (t1), during radiotherapy (t2-t7), and 6 weeks after treatment completion (t8) using a new topographic module. Organ systems were recorded in 15 scales and scored according to symptom intensity (grade 0-5) based on CTC (Common Toxicity Criteria) -classification. Radiotherapy was virtually CT-based planned and applied with 6-MeV-photons. Mean total dose was 60.1 Gy. Patients were stratified by age in 3 Groups: <50, 50-60, and >60 years.</p> <p>Results</p> <p>Registered toxicity was generally low. Mean overall-grade climbed from 0.29-0.40 (t1-t7), and dropped to 0.23 (t8). Univariate analyses revealed slightly higher toxicity in older (> 60 years) versus young patients (< 50 years) in 2 scales only: breast-symmetry (p = 0.033), and arm function (p = 0.007). However, in the scale "appetite" toxicity was higher in younger (< 50 years) versus older (> 60 years) patients (p = 0.039). Toxicity differences in all other scales were not significant. Between older (> 60 years) and midaged patients (50-60 years) no significant differences in toxicity were found. This was also true for the comparison between young (< 50 years) versus midaged patient groups (50-60 years).</p> <p>Conclusion</p> <p>The treatment concept of BCT for breast cancer is generally well tolerated. The toxicity-measurement with the new topographic module is feasible. Not modified standard treatment for BC should be performed in elderly women.</p
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