Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32°C instead of 37°C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process

Female Institutional Directors on Boards and Firm Value

The aim of this research is to examine what impact female institutional directors on boards have on corporate performance. Previous research shows that institutional female directors cannot be considered as a homogeneous group since they represent investors who may or may not maintain business relations with the companies on whose corporate boards they sit. Thus, it is not only the effect of female institutional directors as a whole on firm value that has been analysed, but also the impact of pressure-resistant female directors, who represent institutional investors (investment, pension and mutual funds) that only invest in the company, and do not maintain a business relation with the firm. We hypothesize that there is a non-linear association, specifically quadratic, between institutional and pressure-resistant female directors on boards and corporate performance. Our results report that female institutional directors on boards enhance corporate performance, but when they reach a certain threshold on boards (11.72 %), firm value decreases. In line with female institutional directors, pressure-resistant female directors on boards also increase firm value, but only up to a certain figure (12.71 % on boards), above which they have a negative impact on firm performance. These findings are consistent with an inverted U-shaped relationship between female institutional directors and pressure-resistant female directors and firm performance

Insights into the design and interpretation of iCLIP experiments

Abstract Background Ultraviolet (UV) crosslinking and immunoprecipitation (CLIP) identifies the sites on RNAs that are in direct contact with RNA-binding proteins (RBPs). Several variants of CLIP exist, which require different computational approaches for analysis. This variety of approaches can create challenges for a novice user and can hamper insights from multi-study comparisons. Here, we produce data with multiple variants of CLIP and evaluate the data with various computational methods to better understand their suitability. Results We perform experiments for PTBP1 and eIF4A3 using individual-nucleotide resolution CLIP (iCLIP), employing either UV-C or photoactivatable 4-thiouridine (4SU) combined with UV-A crosslinking and compare the results with published data. As previously noted, the positions of complementary DNA (cDNA)-starts depend on cDNA length in several iCLIP experiments and we now find that this is caused by constrained cDNA-ends, which can result from the sequence and structure constraints of RNA fragmentation. These constraints are overcome when fragmentation by RNase I is efficient and when a broad cDNA size range is obtained. Our study also shows that if RNase does not efficiently cut within the binding sites, the original CLIP method is less capable of identifying the longer binding sites of RBPs. In contrast, we show that a broad size range of cDNAs in iCLIP allows the cDNA-starts to efficiently delineate the complete RNA-binding sites. Conclusions We demonstrate the advantage of iCLIP and related methods that can amplify cDNAs that truncate at crosslink sites and we show that computational analyses based on cDNAs-starts are appropriate for such methods

Properties of Neon, Magnesium, and Silicon Primary Cosmic Rays Results from the Alpha Magnetic Spectrometer

We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8 x 10(6) Ne, 2.2 x 10(6) Mg, and 1.6 x 10(6) Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays

Properties of Cosmic Helium Isotopes Measured by the Alpha Magnetic Spectrometer

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of He-3 and He-4 fluxes are presented. The measurements are based on 100 million He-4 nuclei in the rigidity range from 2.1 to 21 GV and 18 million He-3 from 1.9 to 15 GV collected from May 2011 to November 2017. We observed that the He-3 and He-4 fluxes exhibit nearly identical variations with time. The relative magnitude of the variations decreases with increasing rigidity. The rigidity dependence of the He-3/He-4 flux ratio is measured for the first time. Below 4 GV, the He-3/He-4 flux ratio was found to have a significant long-term time dependence. Above 4 GV, the He-3/He-4 flux ratio was found to be time independent, and its rigidity dependence is well described by a single power law proportional to R-Delta with Delta = 0.294 0.004. Unexpectedly, this value is in agreement with the B/O and B/C spectral indices at high energies

Towards Understanding the Origin of Cosmic-Ray Positrons

Precision measurements of cosmic ray positrons are presented up to 1 TeV based on 1.9 million positrons collected by the Alpha Magnetic Spectrometer on the International Space Station. The positron flux exhibits complex energy dependence. Its distinctive properties are (a) a significant excess starting from 25.2 +/- 1.8 GeV compared to the lower-energy, power-law trend, (b) a sharp dropoff above 284(-64)(+91) GeV, (c) in the entire energy range the positron flux is well described by the sum of a term associated with the positrons produced in the collision of cosmic rays, which dominates at low energies, and a new source term of positrons, which dominates at high energies, and (d) a finite energy cutoff of the source term of E-s = 810(-180)(+310) GeV is established with a significance of more than 4 sigma. These experimental data on cosmic ray positrons show that, at high energies, they predominantly originate either from dark matter annihilation or from other astrophysical sources

Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2 x 10(6) events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above similar to 700 GV. We observed that the nitrogen flux Phi(N) can be presented as the sum of its primary component Phi(P)(N) and secondary component Phi(S)(N), Phi(N) = Phi(P)(N) + Phi(S)(N), and we found Phi(N) is well described by the weighted sum of the oxygen flux Phi(O) (primary cosmic rays) and the boron flux Phi(B) (secondary cosmic rays), with Phi(P)(N) = (0.090 +/- 0.002) x Phi(O) and Phi(S)(N) = (0.62 +/- 0.02) x Phi(B) over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to < 30% above 1 TV

Towards Understanding the Origin of Cosmic-Ray Electrons

Precision results on cosmic-ray electrons are presented in the energy range from 0.5 GeV to 1.4 TeV based on 28.1 x 10(6) electrons collected by the Alpha Magnetic Spectrometer on the International Space Station. In the entire energy range the electron and positron spectra have distinctly different magnitudes and energy dependences. The electron flux exhibits a significant excess starting from 42.1(-5.2)(+5.4) GeV compared to the lower energy trends, but the nature of this excess is different from the positron flux excess above 25.2 +/- 1.8 GeV. Contrary to the positron flux, which has an exponential energy cutoff of 810(-180)(+310) GeV, at the 5 sigma level the electron flux does not have an energy cutoff below 1.9 TeV. In the entire energy range the electron flux is well described by the sum of two power law components. The different behavior of the cosmic-ray electrons and positrons measured by the Alpha Magnetic Spectrometer is clear evidence that most high energy electrons originate from different sources than high energy positrons

Observation of New Properties of Secondary Cosmic Rays Lithium, Beryllium, and Boron by the Alpha Magnetic Spectrometer on the International Space Station

We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4 x 10(6) nuclei collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0 +/- 0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays