Identification of non-canonical Wnt receptors required for Wnt-3a-induced early differentiation of human neural stem cells

Wnt proteins preferentially activate either β-catenin-dependent or β-cateninindependent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1 and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3ainduced neuronal differentiation. However, pair-wise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX and NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 co-immunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4 and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling

Helichrysum stoechas (L.) Moench reduces body weight gain and modulates mood disorders via inhibition of silent information regulator 1 (SIRT1) by arzanol

The prevalence of obesity is steadily rising, making safe and more efficient anti-obesity treatments an urgent medical need. Growing evidence correlates obesity and comorbidities, including anxiety and depression, with the development of a low-grade inflammation in peripheral and central tissues. We hypothesized that attenuating neuroinflammation might reduce weight gain and improve mood. We investigated the efficacy of a methanolic extract from Helichrysum stoechas (L.) Moench (HSE), well-known for its anti-inflammatory properties, and its main constituent arzanol (AZL). HPLC-ESI-MS2 and HPLC-UV were used to characterize the extract. HSE effects on mood and feeding behavior was assessed in mice. The mechanism of action of HSE and AZL was investigated in hippocampus samples and SH-SY5Y cells by western blotting and immunofluorescence. Oral administration of HSE for 3 weeks limited weight gain with no significant decrease in food intake. HSE produced an anxiolytic-like and antidepressant-like phenotype comparable to diazepam and amitriptyline, respectively, in the absence of locomotor and cognitive impairments and induced neuroprotective effects in glutamate-exposed SH-SY5Y cells. A dose-dependent reduction of SIRT1 expression was detected in SH-SY5Y cells and in hippocampal samples from HSE-treated mice. The inhibition of the SIRT1-FoxO1 pathway was induced in the hypothalamus. Molecular docking studies proposed a mechanism of SIRT1 inhibition by AZL, confirmed by the evaluation of inhibitory effects on SIRT1 enzymatic activity. HSE limited weight gain and comorbidities through an AZL-mediated SIRT1 inhibition. These activities indicate HSE an innovative therapeutic perspective for obesity and associated mood disorders

Safety of 41 flavouring compounds providing a herbal flavour and belonging to different chemical groups for use as feed additives in all animal species (FEFANA asbl)

: Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of 41 compounds to provide a Herbal flavour and belonging to different chemical groups, when used as sensory additives in feed for all animal species. Fourteen out of the 41 compounds were tested in tolerance studies in chickens for fattening, piglets, cattle for fattening and Atlantic salmon. No adverse effects were observed in the tolerance studies at 10-fold the intended level. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the 14 tested compounds were safe for these species at the proposed use level and conclusions were extrapolated to all animal species. For the remaining 27 compounds, read-across from structurally similar compounds tested in tolerance trials and belonging to the same chemical group was applied. The FEEDAP Panel concluded that these 27 compounds were safe for all animal species at the proposed use level. No safety concern would arise for the consumer and the environment from the use of the 41 compounds up to the maximum proposed use level in feed

Unlocking hidden mineral resources: Characterization and potential of bitterns as alternative sources of critical raw materials

Mineral extraction from seawater brines has emerged as a viable solution to reduce Europe's reliance on imported Critical Raw Materials (CRM). However, the economic viability of this approach hinges on the local demand for sodium chloride, the primary product of such extraction processes. This study investigates the potential of residual brines, commonly known as "bitterns," generated during solar sea-salt extraction in traditional saltworks, as an alternative source of minerals. The Mediterranean region, encompassing South-European, NorthAfrican, Near East coasts, and parts of the Atlantic regions, is particularly conducive to exploring this prospect due to its extensive solar sea salt industry. Saltworks in the region, adopting various operational strategies based on feed quality or local climate conditions, produce different types of bitterns, each holding a latent resource potential that has remained largely unexplored. Within the framework of the EU-funded SEArcularMINE project, it was conducted an extensive analytical campaign to characterize bitterns collected from a diverse saltworks network. The analysis revealed the presence of sodium, potassium, magnesium, chloride, sulfate, and bromide in concentrations ranging from g/ kg, while boron, calcium, lithium, rubidium, and strontium were found in the mg/kg range. Additionally, trace elements (TEs) such as cobalt, cesium, gallium, and germanium were detected at concentrations in the order of mu g/kg. Detailed results on the composition of bitterns are presented, emphasizing the distinct characteristics observed at different sites. The estimated potential for mineral recovery from these bitterns is approximately 190 euro/m3, considering the production capacity of about 9 Mm3 per year in the Mediterranean area. This finding underscores the significant contribution that mineral recovery from bitterns could make in securing access to CRMs for the European Union

How Photogenerated I2 Induces I-Rich Phase Formation in Lead Mixed Halide Perovskites

Bandgap tunability of lead mixed halide perovskites (LMHPs) is a crucial characteristic for versatile optoelectronic applications. Nevertheless, LMHPs show the formation of iodide-rich (I-rich) phase under illumination, which destabilizes the semiconductor bandgap and impedes their exploitation. Here, it is shown that how I2 , photogenerated upon charge carrier trapping at iodine interstitials in LMHPs, can promote the formation of I-rich phase. I2 can react with bromide (Br- ) in the perovskite to form a trihalide ion I2 Br- (Iδ- -Iδ+ -Brδ- ), whose negatively charged iodide (Iδ- ) can further exchange with another lattice Br- to form the I-rich phase. Importantly, it is observed that the effectiveness of the process is dependent on the overall stability of the crystalline perovskite structure. Therefore, the bandgap instability in LMHPs is governed by two factors, i.e., the density of native defects leading to I2 production and the Br- binding strength within the crystalline unit. Eventually, this study provides rules for the design of chemical composition in LMHPs to reach their full potential for optoelectronic devices

Planck intermediate results. VIII. Filaments between interacting clusters

About half of the baryons of the Universe are expected to be in the form of filaments of hot and low density intergalactic medium. Most of these baryons remain undetected even by the most advanced X-ray observatories which are limited in sensitivity to the diffuse low density medium. The Planck satellite has provided hundreds of detections of the hot gas in clusters of galaxies via the thermal Sunyaev-Zel'dovich (tSZ) effect and is an ideal instrument for studying extended low density media through the tSZ effect. In this paper we use the Planck data to search for signatures of a fraction of these missing baryons between pairs of galaxy clusters. Cluster pairs are good candidates for searching for the hotter and denser phase of the intergalactic medium (which is more easily observed through the SZ effect). Using an X-ray catalogue of clusters and the Planck data, we select physical pairs of clusters as candidates. Using the Planck data we construct a local map of the tSZ effect centered on each pair of galaxy clusters. ROSAT data is used to construct X-ray maps of these pairs. After having modelled and subtracted the tSZ effect and X-ray emission for each cluster in the pair we study the residuals on both the SZ and X-ray maps. For the merging cluster pair A399-A401 we observe a significant tSZ effect signal in the intercluster region beyond the virial radii of the clusters. A joint X-ray SZ analysis allows us to constrain the temperature and density of this intercluster medium. We obtain a temperature of kT = 7.1 +- 0.9, keV (consistent with previous estimates) and a baryon density of (3.7 +- 0.2)x10^-4, cm^-3. The Planck satellite mission has provided the first SZ detection of the hot and diffuse intercluster gas.Comment: Accepted by A&

A hot mini-Neptune and a temperate, highly eccentric sub-Saturn around the bright K-dwarf TOI-2134

Funding: ACC and TGW acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant number ST/R003203/1. RDH is funded by the UK Science and Technology Facilities Council (STFC)’s Ernest Rutherford Fellowship (grant no. ST/V004735/1). SD is funded by the UK Science and Technology Facilities Council (grant no. ST/V004735/1). BSL is funded by a UK Science and Technology Facilities Council (STFC) studentship (ST/V506679/1). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement SCORE no. 851555).We present the characterisation of an inner mini-Neptune in a 9.2292005±0.0000063 day orbit and an outer mono-transiting sub-Saturn planet in a 95.50+0.36-0.25 day orbit around the moderately active, bright (mv = 8.9 mag) K5V star TOI-2134. Based on our analysis of five sectors of TESS data, we determine the radii of TOI-2134b and c to be 2.69±0.16 R⊕ for the inner planet and 7.27±0.42 R⊕ for the outer one. We acquired 111 radial-velocity spectra with HARPS-N and 108 radial-velocity spectra with SOPHIE. After careful periodogram analysis, we derive masses for both planets via Gaussian Process regression: 9.13+0.78-0.76 M⊕ for TOI-2134b and 41.89+7.69-7.83 M⊕ for TOI-2134c. We analysed the photometric and radial-velocity data first separately, then jointly. The inner planet is a mini-Neptune with density consistent with either a water-world or a rocky core planet with a low-mass H/He envelope. The outer planet has a bulk density similar to Saturn’s. The outer planet is derived to have a significant eccentricity of 0.67+0.05-0.06 from a combination of photometry and RVs. We compute the irradiation of TOI-2134c as 1.45±0.10 times the bolometric flux received by Earth, positioning it for part of its orbit in the habitable zone of its system. We recommend further RV observations to fully constrain the orbit of TOI-2134c. With an expected Rossiter-McLaughlin (RM) effect amplitude of 7.2±1.3 m-1, we recommend TOI-2134c for follow-up RM analysis to study the spin-orbit architecture of the system. We calculate the Transmission Spectroscopy Metric, and both planets are suitable for bright-mode NIRCam atmospheric characterisation.Publisher PDFPeer reviewe

Performance and first measurements of the MAGIC stellar intensity interferometer

In recent years, a new generation of optical intensity interferometers has emerged, leveraging the existing infrastructure of Imaging Atmospheric Cherenkov Telescopes (IACTs). The MAGIC telescopes host the MAGIC-SII system (Stellar Intensity Interferometer), implemented to investigate the feasibility and potential of this technique on IACTs. After the first successful measurements in 2019, the system was upgraded and now features a real-time, dead-time-free, 4-channel, GPU-based correlator. These hardware modifications allow seamless transitions between MAGIC’s standard very-high-energy gamma-ray observations and optical interferometry measurements within seconds. We establish the feasibility and potential of employing IACTs as competitive optical Intensity Interferometers with minimal hardware adjustments. The measurement of a total of 22 stellar diameters are reported, 9 corresponding to reference stars with previous comparable measurements, and 13 with no prior measurements. A prospective implementation involving telescopes from the forthcoming Cherenkov Telescope Array Observatory’s Northern hemisphere array, such as the first prototype of its Large-Sized Telescopes, LST-1, is technically viable. This integration would significantly enhance the sensitivity of the current system and broaden the UV-plane coverage. This advancement would enable the system to achieve competitive sensitivity with the current generation of long-baseline optical interferometers over blue wavelengths

Planck early results III : First assessment of the Low Frequency Instrument in-flight performance

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