Convenient synthesis of carbamates, S-alkyl thiocarbamates, and N,N′-disubstituted urea derivatives of methoxycarbonylsulfenyl isocyanate

Convenient simple and suitable methods for the synthesis of carbamates, N,N′-unsymmetrically disubstituted ureas, and S-alkyl thiocarbamates derived from CH3OC(O)SNCO in one-step are provided. Reactions are operationally simple and have high selectivity toward nitrogen, oxygen, and sulfur nucleophiles. The absence of solvents coupled with high yields and short reaction times make these procedures very attractive for synthesis.Fil: Torrico Vallejos, Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Hey Hawkins, Evamarie. Universitat Leipzig; AlemaniaFil: Della Vedova, Carlos Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentin

Mechanistic insight into the reaction catalysed by bacterial type II dehydroquinases

DHQ2 (type II dehydroquinase), which is an essential enzyme in Helicobacter pylori and Mycobacterium tuberculosis and does not have any counterpart in humans, is recognized to be an attractive target for the development of new antibacterial agents. Computational and biochemical studies that help understand in atomic detail the catalytic mechanism of these bacterial enzymes are reported in the present paper. A previously unknown key role of certain conserved residues of these enzymes, as well as the structural changes responsible for triggering the release of the product from the active site, were identified. Asp89*/Asp88* from a neighbouring enzyme subunit proved to be the residue responsible for the deprotonation of the essential tyrosine to afford the catalytic tyrosinate, which triggers the enzymatic process. The essentiality of this residue is supported by results from site-directed mutagenesis. For H. pylori DHQ2, this reaction takes place through the assistance of a water molecule, whereas for M. tuberculosis DHQ2, the tyrosine is directly deprotonated by the aspartate residue. The participation of a water molecule in this deprotonation reaction is supported by solvent isotope effects and proton inventory studies. MD simulation studies provide details of the required motions for the catalytic turnover, which provides a complete overview of the catalytic cycle. The product is expelled from the active site by the essential arginine residue and after a large conformational change of a loop containing two conserved arginine residues (Arg109/Arg108 and Arg113/Arg112), which reveals a previously unknown key role for these residues. The present study highlights the key role of the aspartate residue whose blockage could be useful in the rational design of inhibitors and the mechanistic differences between both enzymesFinancial support from the Comunidad de Madrid (S2010-BMD-2457 to F.G.), Xunta de Galicia (10PXIB2200122PR and GRC2010/12 to C.G.-B.) and the Spanish Ministry of Science and Innovation (SAF2009-13914-C02-02 to F.G. and SAF2010-15076 to C.G.-B.) is 5076 to CGB and BFU2008-01588/BMC to MJvR) is gratefully acknowledged. C.C. and A.P. thank the Spanish Ministry of Science and Innovation for their respective FPU fellowshipsS

Ethnicity strongly influences body fat distribution determining serum adipokine profile and metabolic derangement in childhood obesity

Background: Body fat content and distribution in childhood is influenced by sex and puberty, but interethnic differences in the percentage and distribution of body fat also exist. The abdominal visceral/subcutaneous fat ratio has been the main feature of body fat distribution found to associate with the serum adipokine profile and metabolic derangement in adulthood obesity. This has also been assumed for childhood obesity despite the known singularities of this disease in the pediatric age in comparison to adults. Objective: We aimed to investigate the effect of ethnicity, together with sex and pubertal status, on body fat content and distribution, serum adipokine profile, metabolic impairment and liver steatosis in children and adolescents with obesity. Patients and Methods: One hundred and fifty children with obesity (50% Caucasians/50% Latinos; 50% males/50% females) were studied. Body fat content and distribution were studied by whole body DXA-scan and abdominal magnetic resonance, and their relationships with liver steatosis (as determined by ultrasonography), glycemia, insulinemia, lipid metabolism, uric acid, total and HMW-adiponectin, leptin, leptin-receptor, and sex steroid levels were explored. Results: Latino patients had more severe truncal obesity (higher trunk/lower limb fat ratio, odds ratio 10.00; p < 0.05) and higher prevalence of liver steatosis than Caucasians regardless of sex or pubertal status, but there were no difference in the visceral/subcutaneous abdominal fat ratio, except for pubertal females. A higher trunk/lower limb fat ratio, but not the visceral/subcutaneous abdominal fat ratio, was associated with adipokine profile impairment (higher free leptin index and lower adiponectin levels), insulin resistance and dyslipidemia, and was further enhanced when liver steatosis was present (p < 0.05). A higher abdominal visceral/subcutaneous fat ratio was observed in prepubertal children (p < 0.01), except for Latino females, whereas predominant subcutaneous fat deposition was observed in adolescents. Conclusion: Ethnicity is one of the main determinants of increased trunk body fat accumulation in Latino children with obesity, which is best estimated by the trunk/lower limb fat ratio and related to the development of metabolic derangement and liver steatosis.This work was supported by CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and the Instituto de Salud Carlos III, FIS (FIS grant numbers PI09/91060; FIS 10/00747; FIS 13/01295; and FIS 16/00485

RhIGF-1 treatment increases bone mineral density and trabecular bone structure in children with PAPP-A2 deficiency

KARGER: "This is the peer-reviewed but unedited manuscript version of the following article: Hormone Research in Paediatrics 89.3 (2018): 200-204 DOI: 10.1159/000486336. The final, published version is available at http://www.karger.com/. http://doi.org/10.1159/000486336]."Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25∗) resulting in a premature stop codon. Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2in patient 1 and from 0.763 to 0.829 g/cm2in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.The authors are funded by Fondos de Investigación Sanitaria and FEDER (Grants PI1302195 and PI1600485 to J.A.), Ministerio de Ciencia e Innovación (BFU2014-51836-C2-2-R to J.A.C.), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (J.A.), and Fundación Endocrinología y Nutrició

Response to growth hormone in patients with RNPC3 mutations

Peer reviewe

Conformational transferability of the sulfenyl carbonyl group -SC(O)- in cyclic thioesters

The molecular and crystal structure of two dithiolactones (formally dimers of ε-caprothiolactone and ω-hexadecathiolactone) have been determined by X-ray diffraction at low temperature, revealing that the thioester group is planar with a synperiplanar orientation of the C═O double bond with respect to the S—C single bond. This conformational behavior is in contrast to that found for the smaller cyclic members of this family, where the antiperiplanar conformation is enforced. It is hypothesized that strain effects play a major role for the energy balance in the conformational preference. In this context, the molecular, vibrational (infrared and Raman), and electronic properties of ε-caprothiolactone have also been analyzed by using a combined experimental, including gas-phase helium I photoelectron spectroscopy, and computational approach.Fil: Dugarte Jiménez, Nahir Yerely. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; ArgentinaFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; ArgentinaFil: Hey Hawkins, Evamarie. Universitat Leipzig; AlemaniaFil: Lönnecke, Peter. Universitat Leipzig; AlemaniaFil: Stadlbauer, Sven. Universitat Leipzig; AlemaniaFil: Ge, Mao Fa. Chinese Academy of Sciences; República de ChinaFil: Li, Yao. Chinese Academy of Sciences; República de ChinaFil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; ArgentinaFil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; ArgentinaFil: Della Védova, Carlos Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentin

Clustering and redshift-space distortions in interacting dark energy cosmologies

We investigate the spatial properties of the large scale structure (LSS) of the Universe in the framework of coupled dark energy (cDE) cosmologies. Using the public halo catalogues from the CoDECS simulations -- the largest set of N-body experiments to date for such cosmological scenarios -- we estimate the clustering and bias functions of cold dark matter (CDM) haloes, both in real- and redshift-space. Moreover, we investigate the effects of the dark energy (DE) coupling on the geometric and dynamic redshift-space distortions, quantifying the difference with respect to the concordance LambdaCDM model. At z~0, the spatial properties of CDM haloes in cDE models appear very similar to the LambdaCDM case, even if the cDE models are normalized at last scattering in order to be consistent with the latest Cosmic Microwave Background (CMB) data. At higher redshifts, we find that the DE coupling produces a significant scale-dependent suppression of the halo clustering and bias function. This effect, that strongly depends on the coupling strength, is not degenerate with sigma8 at scales r<5-10 Mpc/h. Moreover, we find that the coupled DE strongly affects both the linear distortion parameter, beta, and the pairwise peculiar velocity dispersion, sigma12. Although the models considered in this work are found to be all in agreement with presently available observational data, the next generation of galaxy surveys will be able to put strong constraints on the level of coupling between DE and CDM exploiting the shape of redshift-space clustering anisotropies.Comment: 11 pages, 7 figures. Minor changes, references added. MNRAS publishe

Labelling of electronic cigarettes : regulations and current practice.

More stringent enforcement of regulations is needed to ensure not only the user's safety and awareness, but also the safeguarding of the environment