Search

Obesity and its associated comorbidities represent a global health challenge with a need for well-tolerated, effective, and mechanistically diverse pharmaceutical interventions. Oxyntomodulin is a gut peptide that activates the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) and reduces bodyweight by increasing energy expenditure and reducing energy intake in humans. Here we describe the pharmacological profile of the novel glucagon receptor (GCGR)/GLP-1 receptor (GLP-1R) dual agonist BI 456906.BI 456906 was characterized using cell-based in vitro assays to determine functional agonism. In vivo pharmacological studies were performed using acute and subchronic dosing regimens to demonstrate target engagement for the GCGR and GLP-1R, and weight lowering efficacy.BI 456906 is a potent, acylated peptide containing a C18 fatty acid as a half-life extending principle to support once-weekly dosing in humans. Pharmacological doses of BI 456906 provided greater bodyweight reductions in mice compared with maximally effective doses of the GLP-1R agonist semaglutide. BI 456906's superior efficacy is the consequence of increased energy expenditure and reduced food intake. Engagement of both receptors in vivo was demonstrated via glucose tolerance, food intake, and gastric emptying tests for the GLP-1R, and liver nicotinamide N-methyltransferase mRNA expression and circulating biomarkers (amino acids, fibroblast growth factor-21) for the GCGR. The dual activity of BI 456906 at the GLP-1R and GCGR was supported using GLP-1R knockout and transgenic reporter mice, and an ex vivo bioactivity assay.BI 456906 is a potent GCGR/GLP-1R dual agonist with robust anti-obesity efficacy achieved by increasing energy expenditure and decreasing food intake.

The focus of this study is on the magnetic properties of the very recently synthesized doubly ordered perovskite family NaLnCoWO6 (Ln = Y, La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, and Yb). Magnetic characterizations were performed by magnetic susceptibility vs. temperature, isothermal magnetization and heat capacity measurements. All these compounds have been determined as antiferromagnets with Neel temperatures from 4 K to 13.1 K. When the lanthanide is magnetic, additional transitions were observed below the Neel temperature which are attributed to the polarization of the magnetic Ln3+ sublattice by the ordered Co2+ one. Taking into account the magnetic ordering found in this study and the polar structure in the nine compounds NaLnCoWO6 (Ln = Y, Sm, Eu, Gd, Tb, Dy, Ho, Er, and Yb) reported before, these compounds can be classified as new Type I multiferroics.

The interest in finding experimental realization of Quantum Liquid Spin phases leads us to elaborate polycrystalline samples of the 6H-B phase of Ba3NiSb2O9 . This structure shows Ni triangular planes and the first magnetic characterizations confirm the absence of any magnetic order as expected for QLS. The samples were synthesized by treatment under HP-HT of the 6H-A phase of Ba3NiSb2O9. The optimized synthesis conditions were 2.5 GPa and 620{\deg}C. By combining several technics as XRD, NPD and TEM we show that even the obtained compound is in fact a new form of Ba3NiSb2O9, that corresponds to a new stacking along c. This preserves the presence of Ni planes but results in a loss of the hexagonal symmetry. The TEM is helpful to conclude to a trigonal symmetry at a scale of 10nm., Comment: 5 figures submitted to Journal of Solid State Chemistry on 9/12/2015_ revised version on 30/01/2016

Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans., Cell Reports, 25 (3), ISSN:2666-3864, ISSN:2211-1247

The hydroaminomethylation of arylethylenes with anilines proceeds under mild conditions in the presence of [Rh(cod) 2 BF 4 ] and dppf as catalyst system to give the corresponding branched amphetamine derivatives in good selectivity and yield.

The Tromper Wiek is a semi-enclosed bay in the western Baltic Sea where gravel extraction by means of anchor hopper dredging has been carried out for many years. After an initial refilling of the extraction craters with material

Q -domain configurations in chromium are investigated measuring X-ray diffraction due to charge-density wave satellites at (0 0 1) and (1 1 1) crystal faces. Scanning the reciprocal space around satellites at samples with and without preparation of single Q and making a reflection topography of CDW satellite (0, 0, 2±2 δ ) it was possible to show that a (0 0 1) face induces a single- Q state, even without any external anisotropy.

X-ray diffraction imaging (‘X-ray topography’) based on Thomson (charge) scattering provides information on the magnetic moments if their arrangement entails a variation in distortion. Recent results obtained on high-quality magnetic single crystals at the European synchrotron radiation facility, using the long (150 m) beamline ID19, devoted to imaging, include: (1) the observation of the domains in the low-temperature phase of magnetite, showing that the actual symmetry is triclinic (2) new results on the unusual magnetization process in hematite (3) the observation of the helimagnetic–ferromagnetic–fan phase coexistence (triple point) in manganese phosphide (4) the visualization of magneto-acoustic modes in iron borate, with striking variations in the image as a function of specimen-detector distance and (5) the imaging, through the inverse piezomagnetic effect, of the 180° antiferromagnetic domains in cobalt fluoride and of memory effects. The possible new applications of these techniques are discussed.

The NOAMP field program, carried out in the deep Northeast Atlantic from 1983 to 1986, was designed to investigate the local deep flow and the dispersion of suspended material by means of current meter, SOFAR float, turbidity and CTD data. The bottom topography of the NOAMP area (45–49°N, 17–23°W) represents a highland with hills and ridges rising up to 1000 m above the deep-sea floor (approx. 4500 m). The deep mean flow (3–5 cm s−1) runs fairly parallel to the depth contours and consists of a system of small topographically induced gyres that can trap any kind of passive admixture. During the first 50 days after release, a cluster of 14 deep-sea floats drifting at depths of around 3500 m spread steadily over an area with a diameter of about 300 km. During the following roughly 200 days a further drift of the centre of mass of the cluster—as well as a further spreading relative to the centre of mass—was hardly noticeable. Occasionally, high energetic events (benthic storms) with durations between 3 and 27 days, and maximum velocities up to 27 cm s−1 occurred directly above the deep-sea floor.

Strontium barium niobate (SBN) thin films of good quality were deposited on Si and Pt/Si substrates using a polymeric resin produced by different starting precursors. Using X-ray diffraction, the presence of SBN phase could be identified for films annealed between 500-700°C for 1 hour on both substrates. Undesired phases, such as SrNb 2 O 6 and BaNb 2 O 6 , appear crystallized in films deposited on Si over annealing temperatures between 500-700°C. However, these phases appear only at 500°C for films deposited on Pt/Si. Dielectric characterization of SBN films indicated a dielectric constant 27 and dissipation factor of 0.047 at 100 KHz. Hvsteresis loops were observed at room temperature for of SBN film annealed at 700°C for 1 hour. At 100 Hz frequency, the remanent polarization, P r , and the coercive field, E c , were 18.4 mC/cm 2 and 147.7 kV/cm, respectively.