A stable chemokine gradient controls directional persistence of migrating dendritic cells

Navigation of dendritic cells (DCs) from the site of infection to lymphoid organs is guided by concentration gradients of CCR7 ligands. How cells interpret chemokine gradients and how they couple directional sensing to polarization and persistent chemotaxis has remained largely elusive. Previous experimental systems were limited in the ability to control fast de novo formation of the final gradient slope, long-lasting stability of the gradient and to expose cells to dynamic stimulation. Here, we used a combination of microfluidics and quantitative in vitro live cell imaging to elucidate the chemotactic sensing strategy of DCs. The microfluidic approach allows us to generate soluble gradients with high spatio-temporal precision and to analyze actin dynamics, cell polarization, and persistent directional migration in both static and dynamic environments. We demonstrate that directional persistence of DC migration requires steady-state characteristics of the soluble gradient instead of temporally rising CCL19 concentration, implying that spatial sensing mechanisms control chemotaxis of DCs. Kymograph analysis of actin dynamics revealed that the presence of the CCL19 gradient is essential to stabilize leading edge protrusions in DCs and to determine directionality, since both cytoskeletal polarization and persistent chemotaxis are abrogated in the range of seconds when steady-state gradients are perturbed. In contrast to Dictyostelium amoeba, DCs are unable to decode oscillatory stimulation of soluble chemokine traveling waves into a directional response toward the wave source. These findings are consistent with the notion that DCs do not employ adaptive temporal sensing strategies that discriminate temporally increasing and decreasing chemoattractant concentrations in our setting. Taken together, in our experimental system DCs do not depend on increasing absolute chemokine concentration over time to induce persistent migration and do not integrate oscillatory stimulation. The observed capability of DCs to migrate with high directional persistence in stable gradients but not when subjected to periodic temporal cues, identifies spatial sensing as a key requirement for persistent chemotaxis of DCs

Influence of Sleeve Gastrectomy on NASH and Type 2 Diabetes Mellitus

Background. Nonalcoholic fatty liver disease is present in up to 85% of adipose patients and may proceed to nonalcoholic steatohepatitis (NASH). With insulin resistance and obesity being the main risk factors for NASH, the effect of isolated sleeve gastrectomy (ISG) on these parameters was examined. Methods. 236 patients underwent ISG with intraoperative liver biopsy from December 2002 to September 2009. Besides demographic data, pre-operative weight/BMI, HbA1c, AST, ALT, triglycerides, HDL and LDL levels were determined. Results. A significant correlation of NASH with higher HbA1c, AST and ALT and lower levels for HDL was observed (P < .05, <.0001, <.0001, <.01, resp.). Overall BMI decreased from 45.0 ± 6.8 to 29.7 ± 6.5 and 31.6 ± 4.4 kg/m2 at 1 and 3 years. An impaired weight loss was demonstrated for patients with NASH and patients with elevated HbA1c (plateau 28.08 kg/m2 versus 29.79 kg/m2 and 32.30 kg/m2 versus 28.79 kg/m2, resp.). Regarding NASH, a significant improvement of AST, ALT, triglyceride and HDL levels was shown (P < .0001 for all). A resolution of elevated HbA1c was observed in 21 of 23 patients. Summary. NASH patients showed a significant loss of body weight and amelioration of NASH status. ISG can be successfully performed in these patients and should be recommended for this subgroup

Oxygen and helium in stripped-envelope supernovae

We present an analysis of 507 spectra of 173 stripped-envelope (SE) supernovae (SNe) discovered by the untargeted Palomar Transient Factory (PTF) and intermediate PTF (iPTF) surveys. Our sample contains 55 Type IIb SNe (SNe IIb), 45 Type Ib SNe (SNe Ib), 56 Type Ic SNe (SNe Ic), and 17 Type Ib/c SNe (SNe Ib/c). We have compared the SE SN subtypes via measurements of the pseudo-equivalent widths (pEWs) and velocities of the He I λλ5876, 7065 and O I λ7774 absorption lines. Consistent with previous work, we find that SNe Ic show higher pEWs and velocities in O I λ7774 compared to SNe IIb and Ib. The pEWs of the He I λλ5876, 7065 lines are similar in SNe Ib and IIb after maximum light. The He I λλ5876, 7065 velocities at maximum light are higher in SNe Ib compared to SNe IIb. We identify an anticorrelation between the He I λ7065 pEW and O I λ7774 velocity among SNe IIb and Ib. This can be interpreted as a continuum in the amount of He present at the time of explosion. It has been suggested that SNe Ib and Ic have similar amounts of He, and that lower mixing could be responsible for hiding He in SNe Ic. However, our data contradict this mixing hypothesis. The observed difference in the expansion rate of the ejecta around maximum light of SNe Ic (Vm = √2Ek/Mej ≈ 15 000 km s−1) and SNe Ib (Vm ≈ 9000 km s−1) would imply an average He mass difference of ∼1.4 M⊙, if the other explosion parameters are assumed to be unchanged between the SE SN subtypes. We conclude that SNe Ic do not hide He but lose He due to envelope stripping

Searches for lepton-flavour-violating decays of the Higgs boson into eτ and μτ in \sqrt{s} = 13 TeV pp collisions with the ATLAS detector

Abstract This paper presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ, performed using data collected with the ATLAS detector at the LHC. The searches are based on a data sample of proton-proton collisions at a centre-of-mass energy s $$\sqrt{s}$$ = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. Leptonic (τ → ℓνℓντ) and hadronic (τ → hadrons ντ) decays of the τ-lepton are considered. Two background estimation techniques are employed: the MC-template method, based on data-corrected simulation samples, and the Symmetry method, based on exploiting the symmetry between electrons and muons in the Standard Model backgrounds. No significant excess of events is observed and the results are interpreted as upper limits on lepton-flavour-violating branching ratios of the Higgs boson. The observed (expected) upper limits set on the branching ratios at 95% confidence level, B $$\mathcal{B}$$ (H → eτ) < 0.20% (0.12%) and B $$\mathcal{B}$$ (H → μτ ) < 0.18% (0.09%), are obtained with the MC-template method from a simultaneous measurement of potential H → eτ and H → μτ signals. The best-fit branching ratio difference, B $$\mathcal{B}$$ (H → μτ) → B $$\mathcal{B}$$ (H → eτ), measured with the Symmetry method in the channel where the τ-lepton decays to leptons, is (0.25 ± 0.10)%, compatible with a value of zero within 2.5σ