FGFR-ERK signaling is an essential component of tissue separation

AbstractFormation of a constriction and tissue separation between parent and young polyp is a hallmark of the Hydra budding process and controlled by fibroblast growth factor receptor (FGFR) signaling. Appearance of a cluster of cells positive for double phosphorylated ERK (dpERK) at the late separation site indicated that the RAS/MEK/ERK pathway might be a downstream target of the Hydra Kringelchen FGFR. In fact, inhibition of ERK phosphorylation by the MEK inhibitor U0126 reversibly delayed bud detachment and prevented formation of the dpERK-positive cell cluster indicating de novo-phosphorylation of ERK at the late bud base. In functional studies, a dominant-negative Kringelchen FGFR prevented bud detachment as well as appearance of the dpERK-positive cell cluster. Ectopic expression of full length Kringelchen, on the other hand, induced a localized rearrangement of the actin cytoskeleton at sites of constriction, localized ERK-phosphorylation and autotomy of the body column. Our data suggest a model in which (i) the Hydra FGFR targets, via an unknown pathway, the actin cytoskeleton to induce a constriction and (ii) FGFR activates MEK/ERK signaling at the late separation site to allow tissue separation

Tuning SMSI Kinetics on Pt-loaded TiO2_2(110) by Choosing the Pressure: A Combined UHV / Near-Ambient Pressure XPS Study

Pt catalyst particles on reducible oxide supports often change their activity significantly at elevated temperatures due to the strong metal-support interaction (SMSI), which induces the formation of an encapsulation layer around the noble metal particles. However, the impact of oxidizing and reducing treatments at elevated pressures on this encapsulation layer remains controversial, partly due to the 'pressure gap' between surface science studies and applied catalysis. In the present work, we employ synchrotron-based near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) to study the effect of O$_2$ and H$_2$ on the SMSI-state of well-defined Pt/TiO$_2$(110) catalysts at pressures of up to 0.1 Torr. By tuning the O$_2$ pressure, we can either selectively oxidize the TiO$_2$ support or both the support and the Pt particles. Catalyzed by metallic Pt, the encapsulating oxide overlayer grows rapidly in 1x10$^{-5}$ Torr O$_2$, but orders of magnitudes less effective at higher O$_2$ pressures, where Pt is in an oxidic state. While the oxidation/reduction of Pt particles is reversible, they remain embedded in the support once encapsulation has occurred

Comparison of anti-oxidant activities of seventy herbs that have been used in Korean traditional medicine

Many herbs have been used as therapeutics in Korean traditional medicine. In view of their clinical indications, anti-oxidant activity may contribute to their pharmacological effects. However, anti-oxidant information on these plants has not been available. In this study, seventy herbs which have been used in Korean traditional medicine were selected and screened for anti-oxidant activity using their water extracts. The anti-oxidant activity was assessed by their ability to inhibit three oxidation reactions; luminol/Fenton reagent, 2, 7-dichlorodihydrofluorescein (DCHF)/Fenton reagent and DCHF/peroxynitrite. In each assay, 70 herbs were divided into two groups; anti-oxidant group which inhibited the respective oxidation reaction and was majority (about 60 herbs), and pro-oxidant group which enhanced the oxidation reaction but was minority (more or less 10 herbs). When the herbs were listed in the order of their anti-oxidant strength, the orders obtained from each assay were found to be quite similar. The upper top rankers (more or less 10 herbs) in each assay showed strong activity compared to the others. The uppermost rankers in each assay were Rubus coreanus Miquel/ Rubus schizostylus, Schisandra chinensis Baillon/ Schizandra chinensis and Terminalia chebula Retzius/ Terminalia chebula. Of the pro-oxidant herbs, about 4-5 herbs were strongly pro-oxidant, which enhanced the control oxidation reactions to 150-300%. But the meaning of this observation is not known since few of them in one assay were also anti-oxidant in other assays. The results obtained in the present study may serve as information for understanding pharmacological effects of these herbs and developing new drugs from them

Adiponutrin Functions as a Nutritionally Regulated Lysophosphatidic Acid Acyltransferase

SummaryNumerous studies in humans link a nonsynonymous genetic polymorphism (I148M) in adiponutrin (ADPN) to various forms of fatty liver disease and liver cirrhosis. Despite its high clinical relevance, the molecular function of ADPN and the mechanism by which I148M variant affects hepatic metabolism are unclear. Here we show that ADPN promotes cellular lipid synthesis by converting lysophosphatidic acid (LPA) into phosphatidic acid. The ADPN-catalyzed LPA acyltransferase (LPAAT) reaction is specific for LPA and long-chain acyl-CoAs. Wild-type mice receiving a high-sucrose diet exhibit substantial upregulation of Adpn in the liver and a concomitant increase in LPAAT activity. In Adpn-deficient mice, this diet-induced increase in hepatic LPAAT activity is reduced. Notably, the I148M variant of human ADPN exhibits increased LPAAT activity leading to increased cellular lipid accumulation. This gain of function provides a plausible biochemical mechanism for the development of liver steatosis in subjects carrying the I148M variant

Effect of Internet-Based Cognitive Behavioral Humanistic and Interpersonal Training vs Internet-Based General Health Education on Adolescent Depression in Primary Care

Importance: Although 13% to 20% of American adolescents experience a depressive episode annually, no scalable primary care model for adolescent depression prevention is currently available. Objective: To study whether competent adulthood transition with cognitive behavioral humanistic and interpersonal training (CATCH-IT) lowers the hazard for depression in at-risk adolescents identified in primary care, as compared with a general health education (HE) attention control. Design, Setting, and Participants: This multicenter, randomized clinical trial, a phase 3 single-blind study, compares CATCH-IT with HE. Participants were enrolled from 2012 to 2016 and assessed at 2, 6, 12, 18, and 24 months postrandomization in a primary care setting. Eligible adolescents were aged 13 to 18 years with subsyndromal depression and/or history of depression and no current depression diagnosis or treatment. Of 2250 adolescents screened for eligibility, 446 participants completed the baseline interview, and 369 were randomized into CATCH-IT (n = 193) and HE (n = 176). Interventions: The internet-based intervention, CATCH-IT, is a 20-module (15 adolescent modules and 5 parent modules) online psychoeducation course that includes a parent program, supported by 3 motivational interviews. Main Outcomes and Measures: Time to event for depressive episode; depressive symptoms at 6 months. Results: Of 369 participants (mean [SD] age, 15.4 [1.5] years; 251 women [68%]) included in this trial, 193 were randomized into CATCH-IT and 176 into HE. Among these participants, 28% had both a past episode and subsyndromal depression; 12% had a past episode only, 59% had subsyndromal depression only, and 1% had borderline subsyndromal depression. The outcome of time to event favored CATCH-IT but was not significant with intention-to-treat analyses (unadjusted hazard ratio [HR], 0.59; 95% CI, 0.27-1.29; P = .18; adjusted HR, 0.53; 95% CI, 0.23-1.23; P = .14). Adolescents with higher baseline Center for Epidemiologic Studies Depression scale (CES-D ) scores showed a significantly stronger effect of CATCH-IT on time to event relative to those with lower baseline scores (HR 0.82; 95% CI, 0.67-0.99; P = .04). For example, the hazard ratio for a CES-D score of 15 was 0.20 (95% CI, 0.05-0.77), compared with a hazard ratio of 1.44 (95% CI, 0.41-5.03) for a CES-D score of 5. In both CATCH-IT and HE groups, depression symptoms declined and functional scores increased. Conclusions and Relevance: For preventing depressive episodes CATCH-IT may be better than HE for at-risk adolescents with subsyndromal depression. Also CATCH-IT may be a scalable approach to prevent depressive episodes in adolescents in primary care

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Two warm Neptunes transiting HIP 9618 revealed by TESS and Cheops

peer reviewedHIP 9618 (HD 12572, TOI-1471, TIC 306263608) is a bright (G = 9.0 mag) solar analogue. TESS photometry revealed the star to have two candidate planets with radii of 3.9 ± 0.044 R (HIP 9618 b) and 3.343 ± 0.039 R (HIP 9618 c). While the 20.77291 d period of HIP 9618 b was measured unambiguously, HIP 9618 c showed only two transits separated by a 680-d gap in the time series, leaving many possibilities for the period. To solve this issue, CHEOPS performed targeted photometry of period aliases to attempt to recover the true period of planet c, and successfully determined the true period to be 52.56349 d. High-resolution spectroscopy with HARPS-N, SOPHIE, and CAFE revealed a mass of 10.0 ± 3.1M for HIP 9618 b, which, according to our interior structure models, corresponds to a 6.8 ± 1.4 per cent gas fraction. HIP 9618 c appears to have a lower mass than HIP 9618 b, with a 3-sigma upper limit of 50 d, opening the door for the atmospheric characterization of warm (Teq < 750 K) sub-Neptunes

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UuStB Koeln(38)-8206902 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman