Naturalizar los movimientos en el parto con epidural

Parto; anestesia epidural, posturasPart; anestèsia epidural; posturesLabor, epidural anesthesia, posturesAcompanyament per part de les llevadores a les llevadores amb analgèsia peridural per simular els moviments que realitzaria en un part natural. Les posicions verticals, la deambulació i la llibertat de moviments disminueixen el temps de part, les taxes d'instrumentació i les seves conseqüències, proporcionant a la dona control i una major satisfacció sobre el seu procés de part. Les asimetries pèlviques aconseguides amb els canvis posturals freqüents en dones amb analgèsia epidural, que no es poden moure per si mateixes, afavoreixen l'evolució del treball de part, augmentant així la taxa de parts eutòcics. La llevadora és la figura ideal per donar suport durant el part i acompanyar les gestants en aquest procés.Acompañamiento por parte de las comadronas a las parteras con analgesia peridural para simular los movimientos que realizaría en un parto natural. Las posiciones verticales, la deambulación y la libertad de movimientos disminuyen el tiempo de parto, las tasas de instrumentación y sus consecuencias, proporcionando a la mujer control y una mayor satisfacción sobre su proceso de parto. Las asimetrías pélvicas conseguidas con los cambios posturales frecuentes en mujeres con analgesia epidural, que no pueden moverse por sí mismas, favorecen la evolución del trabajo de parto, aumentando así la tasa de partos eutócicos. La matrona es la figura ideal para dar soporte durante el parto y acompañar a las gestantes en este proceso.Accompaniment by the midwives to the women in labor with epidural analgesia to simulate the movements they would perform in a natural birth. The vertical positions, the ambulation and the freedom of movements decrease the time of delivery, the rates of instrumentation and its consequences, giving the woman control and greater satisfaction about her birth process. The pelvic asymmetries achieved with frequent postural changes in women with epidural analgesia, who can not move by themselves, favor the evolution of labor, thus increasing the rate of eutocic deliveries. The midwife is the ideal figure to support during childbirth and accompany pregnant women in this process

MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer

Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-y (IFNy), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNy in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNy-stimulated genes (IySGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) depo-sition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNy stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/ MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IySGs stimulation by IFNy. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNy and may predict anti-PD1/L1 efficacy in LC

Design, Synthesis and Characterization of a Highly Effective Inhibitor for Analog-Sensitive (as) Kinases

Highly selective, cell-permeable and fast-acting inhibitors of individual kinases are sought-after as tools for studying the cellular function of kinases in real time. A combination of small molecule synthesis and protein mutagenesis, identified a highly potent inhibitor (1-Isopropyl-3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine) of a rationally engineered Hog1 serine/threonine kinase (Hog1T100G). This inhibitor has been successfully used to study various aspects of Hog1 signaling, including a transient cell cycle arrest and gene expression changes mediated by Hog1 in response to stress. This study also underscores that the general applicability of this approach depends, in part, on the selectivity of the designed the inhibitor with respect to activity versus the engineered and wild type kinases. To explore this specificity in detail, we used a validated chemogenetic assay to assess the effect of this inhibitor on all gene products in yeast in parallel. The results from this screen emphasize the need for caution and for case-by-case assessment when using the Analog-Sensitive Kinase Allele technology to assess the physiological roles of kinases

Post-transcriptional regulation of rat carnitine octanoyltransferase

672nd Meeting held at the University of Sussex, 19–21 December 2000 Speaker ManuscriptCarnitine octanoyltransferase (COT) produces three different transcripts in rat through cis- and trans-splicing reactions, which can lead to the synthesis of two proteins. The occurrence of the three COT transcripts in rat has been found in all tissues examined and does not depend on sex, fat feeding, peroxisome proliferators or hyperinsulinaemia. Rat COT exon 2 contains a putative exonic splicing enhancer (ESE) sequence. Mutation of this ESE (GAAGAAG) to AAAAAAA decreased trans-splicing in vitro, from which it is deduced that this ESE sequence is partly responsible for the formation of the three transcripts. The protein encoded by cis-spliced mRNA of rat COT is inhibited by malonyl-CoA and etomoxir. cDNA species encoding full-length wild-type COT and one double mutant COT were expressed in Saccharomyces cerevisiae. The recombinant enzymes showed full activity towards both substrates, carnitine and decanoyl-CoA. The activity of the doubly mutated H131A/H340A enzyme was similar to that of the rat peroxisomal enzyme but was completely insensitive to malonyl-CoA and etomoxir. These results indicate that the histidine residues His-131 and His-340 are the sites responsible for the interaction of these two inhibitors, which inhibit COT by interacting with the same sites.This study was supported by grant PB95-0012 from the Dirección General de Investigación Científica y Técnica, Spain, by an Ajut de Suport als Grups de Recerca de Catalunya, 1999SGR-0075 (to F. G. H.) and by a grant from the Fundació de la Marató de TV3. M. M. is a recipient of a fellowship from the Ministerio de Educación y Cultura, Dirección General de Enseñanza Superior, Spain.Peer reviewe

Naturalizar los movimientos en el parto con epidural

Parto; anestesia epidural, posturasPart; anestèsia epidural; posturesLabor, epidural anesthesia, posturesAcompanyament per part de les llevadores a les llevadores amb analgèsia peridural per simular els moviments que realitzaria en un part natural. Les posicions verticals, la deambulació i la llibertat de moviments disminueixen el temps de part, les taxes d'instrumentació i les seves conseqüències, proporcionant a la dona control i una major satisfacció sobre el seu procés de part. Les asimetries pèlviques aconseguides amb els canvis posturals freqüents en dones amb analgèsia epidural, que no es poden moure per si mateixes, afavoreixen l'evolució del treball de part, augmentant així la taxa de parts eutòcics. La llevadora és la figura ideal per donar suport durant el part i acompanyar les gestants en aquest procés.Acompañamiento por parte de las comadronas a las parteras con analgesia peridural para simular los movimientos que realizaría en un parto natural. Las posiciones verticales, la deambulación y la libertad de movimientos disminuyen el tiempo de parto, las tasas de instrumentación y sus consecuencias, proporcionando a la mujer control y una mayor satisfacción sobre su proceso de parto. Las asimetrías pélvicas conseguidas con los cambios posturales frecuentes en mujeres con analgesia epidural, que no pueden moverse por sí mismas, favorecen la evolución del trabajo de parto, aumentando así la tasa de partos eutócicos. La matrona es la figura ideal para dar soporte durante el parto y acompañar a las gestantes en este proceso.Accompaniment by the midwives to the women in labor with epidural analgesia to simulate the movements they would perform in a natural birth. The vertical positions, the ambulation and the freedom of movements decrease the time of delivery, the rates of instrumentation and its consequences, giving the woman control and greater satisfaction about her birth process. The pelvic asymmetries achieved with frequent postural changes in women with epidural analgesia, who can not move by themselves, favor the evolution of labor, thus increasing the rate of eutocic deliveries. The midwife is the ideal figure to support during childbirth and accompany pregnant women in this process

Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking

Altres ajuts: Fundació La Marató de TV3 (SGR2014-0984)GuA1-containing AMPA receptors play a key role in synaptic plasticity and cognition. Casas et al. demonstrate that the sensing of nutrients by CPT1C regulates the phosphatase activity of SAC1, and consequently PI(4)P levels, at the contact sites between the endoplasmic reticulum and the trans-Golgi network to control the trafficking of GluA1 receptors to the cell surface of neurons. Carnitine palmitoyltransferase 1C (CPT1C) is a sensor of malonyl-CoA and is located in the ER of neurons. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the brain and play a key role in synaptic plasticity. In the present study, we demonstrate across different metabolic stress conditions that modulate malonyl-CoA levels in cortical neurons that CPT1C regulates the trafficking of the major AMPAR subunit, GluA1, through the phosphatidyl-inositol-4-phosphate (PI(4)P) phosphatase SAC1. In normal conditions, CPT1C down-regulates SAC1 catalytic activity, allowing efficient GluA1 trafficking to the plasma membrane. However, under low malonyl-CoA levels, such as during glucose depletion, CPT1C-dependent inhibition of SAC1 is released, facilitating SAC1's translocation to ER-TGN contact sites to decrease TGN PI(4)P pools and trigger GluA1 retention at the TGN. Results reveal that GluA1 trafficking is regulated by CPT1C sensing of malonyl-CoA and provide the first report of a SAC1 inhibitor. Moreover, they shed light on how nutrients can affect synaptic function and cognition