The antidepressant effect of hypericum perforatum extract Ze 117 is associated with reduced possibilities of drug interactions than hypericum perforatum extract LI 160.

Hypericum perforatum (HP) is the most extensively investigated medicinal herbs with antidepressant effect. Differences showed by HP extracts in their antidepressant effect and their clinical consequence of HP-drug interactions have been related with HP extract different composition, particularly regarding to their primary ingredients hyperforin and hypericin content. Experimental data and clinical trials have shown that low-hyperforin-content HP has a comparable antidepressant efficacy in the treatment of mild/moderate depression (1) (2). However, hyperforin is responsible for CYP3A4 induction via activation of a nuclear steroid/pregnane and xenobiotic receptor (SXR/PXR) and hypericin is a P-glycoprotein inducing compound (3), which are the main origin of HP-drug interactions. Changes in cytochrome P-450 (CYP-450) activity could modulate the effect of different drugs. Some of the reported interactions are based on findings from in vitro studies but the clinical importance of which remain to be demonstrated. Two different hypericum extracts, Ze 117 and LI 160, which are differently composed, Ze 117 (0.15-0.25% hypericin, 0.5% hyperforin) and LI 160 (0.3% hypericin, 4-6% hyperforin) were checked regarding their antidepressant-like activity vs. classical antidepressants with and without liver CYP 450 enzyme activity modulation by cimetidine. Experimental procedures followed the ECC Directives and were approved by local authorities. Male Wistar rats (n=6 per group, 6 months old, weight 314±25 g, Charles River-Spain) were injected (i.p. once a day) with Ze 117 (20 mg/kg, Zeller AG), LI 160 (20 mg/kg, Lichtwer Pharma AG), imipramine (IMI) (10.9 mg/kg, Novartis SL), fluoxetine (FLU) (5 mg/kg, Lilly and Dista) or saline (SAL), in presence and absence of cimetidine (CIM) (50 mg/kg, Rimsa) during 20 days. The forced swim test (4) was used for the evaluation of the antidepressant-like effect. The opend-field test was used for the evaluation of the motor activity. The total CYP 450 content of the liver was measure using spectrophotometry methods in liver microsomes. Results are expressed as mean±sem and were compared by Student t test and ANOVA test followed by Bonferroni post-test. The drugs antidepressant effect (reduction of the immobility time) ranking order was: i) without cimetidine’s CYP-450 inhibition: IMI 109±33s >Ze 117 163±21s =FLU165±29s >LI 160 201±234s >SAL 224±17s, pLI 160 144±13s >FLU 171±21s >Ze 117 188±10 >SAL 219±20s, pLI 160 >Ze 117 >SAL, p<0.05). LI 160 significantly reduced the liver CYP-450 total content with respect to SAL (-43.3%, p<0.05) while Ze 117 had lower effect (-25.9%, p<0.05). In conclusion, hypericum perforatum extract Ze 117 shows higher antidepressant effect and lower inhibitory effect of the total CYP 450 liver content than hypericum perforatum extract LI 160. Liver CYP 450 inhibition by cimetidine increased the antidepressant of LI 160 but did not modify the antidepressant effect of Ze 117. (1)Fiebich BL, Knörle R, Appel K et al. (2011) Fitoterapia 82(3):474-480. (2)Singer A, Schmidt M, Hauke W et al. (2011) Phytomedicine 18(8-9):739-742. (3)Mannel M. (2004) Drug Saf 27(11):773-797. (4)Castagné V, Moser P, Roux S et al. (2011) Curr Protoc Neurosci 55:8.10A.1-8.10A.14.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

COP1 destabilizes DELLA proteins in Arabidopsis

Fil: Blanco Touriñán, Noel. Universidad Politécnica de Valencia. Instituto de Biologίa Molecular y Celular de Plantas. Valencia, Spain. - Consejo Superior de Investigaciones Cientίficas - Universidad Politécnica de Valencia. Instituto de Biologίa Molecular y Celular de Plantas. Valencia, Spain.Fil: Legris, Martina. CONICET. Fundaciόn Instituto Leloir. Instituto de Investigaciones Bioquίmicas de Buenos Aires, Buenos Aires, Argentina.Fil: Minguet, Eugenio G. Universidad Politécnica de Valencia. Instituto de Biologίa Molecular y Celular de Plantas. Valencia, Spain. - Consejo Superior de Investigaciones Cientίficas - Universidad Politécnica de Valencia. Instituto de Biologίa Molecular y Celular de Plantas. Valencia, Spain.Fil: Costigliolo Rojas, Cecilia. CONICET. Fundaciόn Instituto Leloir. Instituto de Investigaciones Bioquίmicas de Buenos Aires, Buenos Aires, Argentina.Fil: Nohales, Marίa A. University of Southern California. Department of Neurology, Keck School of Medicine, Los Angeles, CA, USA.Fil: Iniesto, Elisa. Consejo Superior de Investigaciones Cientίficas. Centro Nacional de Biotecnología. Departamento de Genética Molecular de Plantas. Madrid, Spain.Fil: Pacín, Manuel. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina. - CONICET – Universidad de Buenos Aires. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina.Fil: Casal, Jorge José. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina. - CONICET – Universidad de Buenos Aires. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina.DELLA transcriptional regulators are central components in the control of plant growth responses to the environment. This control is considered to be mediated by changes in the metabolism of the hormones gibberellins (GAs), which promote the degradation of DELLAs. However, here we show that warm temperature or shade reduced the stability of a GA-insensitive DELLA allele in Arabidopsis thaliana. Furthermore, the degradation of DELLA induced by the warmth preceded changes in GA levels and depended on the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1). COP1 enhanced the degradation of normal and GA-insensitive DELLA alleles when coexpressed in Nicotiana benthamiana. DELLA proteins physically interacted with COP1 in yeast, mammalian, and plant cells. This interaction was enhanced by the COP1 complex partner SUPRESSOR OF phyA-105 1 (SPA1). The level of ubiquitination of DELLA was enhanced by COP1 and COP1 ubiquitinated DELLA proteins in vitro. We propose that DELLAs are destabilized not only by the canonical GA-dependent pathway but also by COP1 and that this control is relevant for growth responses to shade and warm temperature.grafs., fot

Magnetic and morphological characterization of Nd2Fe14B magnets with different quality grades at low temperature 5-300 K

An increasing number of cryogenic devices may benefit from the use of Nd2Fe14B permanent magnets. However, it is necessary to precisely know their behavior because magnetization varies significantly due to Spin Reorientation Transition. In this work, magnetic and morphological characterization of Nd2Fe14B commercial polycrystalline magnets with different quality grades from 5 to 300 K is provided. A set of magnets ranging from N35 to N52 quality have been analyzed. Mean grain dimension as well as material composition elements are provided. Higher quality magnets show smaller mean grain dimensions. Regarding cryogenic temperatures, the well know spin transition effect appears in all the magnets as expected, however, the transition temperature occurs at different temperatures in a range from 112 to 120 K which is lower than those obtained for single crystal samples. Moreover, the relative variation of the remanence from 300 to 5 K is lower than 4% while the maximum expected variation is in average 11%. As extra information, the same analyzes are provided for additional quality grades N40M, N40S, N40SH and N40UH.The research leading to these results has received funding from the European Community's Seventh Framework Programme ([FP7/2007-2013]) under grant agreement n° 263014

COP1 destabilizes DELLA proteins in Arabidopsis

DELLA transcriptional regulators are central components in the control of plant growth responses to the environment. This control is considered to be mediated by changes in the metabolism of the hormones gibberellins (GAs), which promote the degradation of DELLAs. However, here we show that warm temperature or shade reduced the stability of a GA-insensitive DELLA allele in Arabidopsis thaliana. Furthermore, the degradation of DELLA induced by the warmth preceded changes in GA levels and depended on the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1). COP1 enhanced the degradation of normal and GAinsensitive DELLA alleles when coexpressed in Nicotiana benthamiana. DELLA proteins physically interacted with COP1 in yeast, mammalian, and plant cells. This interaction was enhanced by the COP1 complex partner SUPRESSOR OF phyA-105 1 (SPA1). The level of ubiquitination of DELLA was enhanced by COP1 and COP1 ubiquitinated DELLA proteins in vitro. We propose that DELLAs are destabilized not only by the canonical GA-dependent pathway but also by COP1 and that this control is relevant for growth responses to shade and warm temperature.Fil: Blanco Touriñán, Noel. Universidad Politécnica de Valencia; EspañaFil: Legris, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Minguet, Eugenio G.. Universidad Politécnica de Valencia; EspañaFil: Costigliolo Rojas, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Nohales, María A.. University of Southern California; Estados UnidosFil: Iniesto, Elisa. Consejo Superior de Investigaciones Científicas; EspañaFil: García León, Marta. Consejo Superior de Investigaciones Científicas; EspañaFil: Pacín, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Heucken, Nicole. Universitat Dusseldorf; AlemaniaFil: Blomeier, Tim. Universitat Dusseldorf; AlemaniaFil: Locascio, Antonella. Universidad Politécnica de Valencia; EspañaFil: Cerný, Martin. Mendel University in Brno; República ChecaFil: Esteve Bruna, David. Universidad Politécnica de Valencia; EspañaFil: Díez Díaz, Mónica. Univerdiad Catolica de Valencia; EspañaFil: Brzobohatý, Bretislav. Mendel University in Brno; República ChecaFil: Frerigmann, Henning. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Zurbriggen, Matías D.. Universitat Dusseldorf; AlemaniaFil: Kay, Steve A.. University of Southern California; Estados UnidosFil: Rubio, Vicente. Consejo Superior de Investigaciones Científicas; EspañaFil: Blázquez, Miguel A.. Universidad Politécnica de Valencia; EspañaFil: Casal, Jorge José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Alabadí, David. Universidad Politécnica de Valencia; Españ

LEED-IV study of the rutile TiO2(110)-1x2 surface with a Ti-interstitial added-row reconstruction

4 pages, 2 figures, 1 table.-- PACS nrs.: 61.14.Hg; 68.35.Bs; 68.47.Gh.Upon sputtering and annealing in UHV at 1000 K the rutile TiO2(110) surface undergoes a 1x1 --> 1x2 phase transition. The resulting 1x2 surface is Ti rich, formed by strands of double Ti rows as seen on scanning tunneling microscopic images, but its detailed structure and composition have been subject to debate in the literature for years. Recently, Park et al. [Phys. Rev. Lett. 96 226105 (2006)] have proposed a model where Ti atoms are located on interstitial sites with Ti2O stoichiometry. This model, when it is analyzed using LEED-IV data [Phys. Rev. Lett. 96 0055502 (2006)] does not yield an agreement between theory and experiment as good as the previous best fit for Onishi and Iwasawa's model for the long-range 1x2 reconstruction. Therefore, the Ti2O3 added row is the preferred one from the point of view of low-energy electron diffraction.This work has been financed by the CYCIT (Grant No. MAT-2005-3866). M.B.R. acknowledges Spanish CSIC for financial support through I3P program. The Barcelona Supercomputer Center (http://www.bsc.es/) is acknowledged for computing time.Peer reviewe

COP1 destabilizes DELLA proteins in Arabidopsis

DELLA transcriptional regulators are central components in the control of plant growth responses to the environment. This control is considered to be mediated by changes in the metabolism of the hormones gibberellins (GAs), which promote the degradation of DELLAs. However, here we show that warm temperature or shade reduced the stability of a GA-insensitive DELLA allele in Arabidopsis thaliana. Furthermore, the degradation of DELLA induced by the warmth preceded changes in GA levels and depended on the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1). COP1 enhanced the degradation of normal and GA-insensitive DELLA alleles when coexpressed in Nicotiana benthamiana. DELLA proteins physically interacted with COP1 in yeast, mammalian, and plant cells. This interaction was enhanced by the COP1 complex partner SUPRESSOR OF phyA-105 1 (SPA1). The level of ubiquitination of DELLA was enhanced by COP1 and COP1 ubiquitinated DELLA proteins in vitro. We propose that DELLAs are destabilized not only by the canonical GA-dependent pathway but also by COP1 and that this control is relevant for growth responses to shade and warm temperature.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness and Agencia Española de Investigación/Fondo Europeo para el Desarrollo Regional/Unión Europea (grants BIO2016-79133-P to D.A. and BIO2013-46539-R and BIO2016-80551-R to V.R.); the European Union SIGNAT-Research and Innovation Staff Exchange (Grant H2020-MSCA-RISE-2014-644435 to M.A.B., D.A., and J.J.C.); the Argentinian Agencia Nacional de Promoción Científica y Tecnológica (Grant Proyectos de Investigación Científica y Tecnológica-2016-1459 to J.J.C.); Universidad de Buenos Aires (grant 20020170100505BA to J.J.C.); the National Institute of General Medical Sciences of the National Institutes of Health (awards R01GM067837 and R01GM056006 to S.A.K.); the German Research Foundation (DFG) under Germany’s Excellence Strategy/Initiative (Cluster of Excellence on Plant Sciences – Excellence Cluster EXC-2048/1, Project ID 390686111 to M.D.Z.); the International Max Planck Research School of the Max Planck Society; the Universities of Düsseldorf and of Cologne to T.B.; Nordrhein Westfalen Bioeconomy Science Center-FocusLabs CombiCom to N.H. and M.D.Z.; and Ministry of Education, Youth and Sports of the Czech Republic (Project LQ1601 Central European Institute of Technology 2020 to B.B. and M.C.). N.B.-T., E.I., and M.G.-L. were supported by Ministerio de Economía y Competitividad-Formación de Personal Investigador Program fellowships

A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies

High open-circuit voltage in transition metal dichalcogenide solar cells

The conversion efficiency of ultra-thin solar cells based on layered materials has been limited by their open-circuit voltage, which is typically pinned to a value under 0.6 V. Here we report an open-circuit voltage of 1.02 V in a 120 nm-thick vertically stacked homojunction fabricated with substitutionally doped MoS2. This high open-circuit voltage is consistent with the band alignment in the MoS2 homojunction, which is more favourable than in widely-used TMDC heterostructures. It is also attributed to the high performance of the substitutionally doped MoS2, in particular the p-type material doped with Nb, which is demonstrated by the observation of electroluminescence from tunnelling graphene/BN/MoS2 structures in spite of the indirect nature of bulk MoS2. We find that illuminating the TMDC/metal contacts decreases the measured open-circuit voltage in MoS2 van der Waals homojunctions because they are photoactive, which points to the need of developing low-resistance, ohmic contacts to doped MoS2 in order to achieve high efficiency in practical devices. The high open-circuit voltage demonstrated here confirms the potential of layered transition-metal dichalcogenides for the development of highly efficient, ultra-thin solar cells

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). Results: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(-16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(-7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. Conclusion: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women

p38γ is essential for cell cycle progression and liver tumorigenesis

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)–cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease