Hard Thermal Loops and Chiral Lagrangians

Chiral symmetry is used as the guiding principle to derive hard thermal loop effects in chiral perturbation theory. This is done by using a chiral invariant background field method for the non-linear sigma model and the Wess-Zumino-Witten lagrangian, with and without external vector and axial vector sources. It is then shown that the n-point hard thermal loop is the leading thermal correction for the Green function of n point vector soft quark currents.Comment: 15 pages, Revtex, references added, typos corrected, final version to appear in Phys. Rev.

A Component of the Xanthomonadaceae Type IV Secretion System Combines a VirB7 Motif with a N0 Domain Found in Outer Membrane Transport Proteins

Type IV secretion systems (T4SS) are used by Gram-negative bacteria to translocate protein and DNA substrates across the cell envelope and into target cells. Translocation across the outer membrane is achieved via a ringed tetradecameric outer membrane complex made up of a small VirB7 lipoprotein (normally 30 to 45 residues in the mature form) and the C-terminal domains of the VirB9 and VirB10 subunits. Several species from the genera of Xanthomonas phytopathogens possess an uncharacterized type IV secretion system with some distinguishing features, one of which is an unusually large VirB7 subunit (118 residues in the mature form). Here, we report the NMR and 1.0 Å X-ray structures of the VirB7 subunit from Xanthomonas citri subsp. citri (VirB7XAC2622) and its interaction with VirB9. NMR solution studies show that residues 27–41 of the disordered flexible N-terminal region of VirB7XAC2622 interact specifically with the VirB9 C-terminal domain, resulting in a significant reduction in the conformational freedom of both regions. VirB7XAC2622 has a unique C-terminal domain whose topology is strikingly similar to that of N0 domains found in proteins from different systems involved in transport across the bacterial outer membrane. We show that VirB7XAC2622 oligomerizes through interactions involving conserved residues in the N0 domain and residues 42–49 within the flexible N-terminal region and that these homotropic interactions can persist in the presence of heterotropic interactions with VirB9. Finally, we propose that VirB7XAC2622 oligomerization is compatible with the core complex structure in a manner such that the N0 domains form an extra layer on the perimeter of the tetradecameric ring

Capacidades dinámicas como determinantes de la capacidad de innovación en Colombia

La industria manufacturera colombiana presenta bajos niveles de innovación, esto puede deberse a factores como la baja capacidad para innovar, aprender y adaptarse al entorno, entre las que puede existir una relación que es poco estudiada. Por tanto, el objetivo principal de este artículo es realizar un acercamiento sobre la influencia conjunta de la capacidad de aprendizaje y de adaptación sobre la capacidad para innovar en las empresas industriales colombianas. Para ello se analizaron 1.571 empresas registradas en la Encuesta de Desarrollo e Innovación Tecnológica Industrial 2017-2018, mediante un diseño no experimental, transversal, descriptivo y correlacional-causal, utilizando para ello modelos de correlación y de regresión logit. Los principales resultados permiten entender que individualmente la capacidad de aprendizaje y de adaptación influyen positivamente en la probabilidad de desarrollar la capacidad de innovación. El estudio logra concluir que la existencia conjunta de estas dos capacidades dinámicas potencia parcialmente el desarrollo de la capacidad de innovación

Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance

Resumen del póster presentado a la Conferencia: FASEB SRC: Liver Biology: Fundamental Mechanisms and Translational Applications, celebrada en Keystone-Colorado (US) del 6 al 11 de julio de 2014.[Background and Aims: Accumulation evidence links obesity-induced inflammation as an important contributor to the induction of insulin resistance. Moreover, insulin resistance plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and non alcoholic fatty liver disease. Cyclooxygenase-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory factors used, we have evaluated whether this lack of expression under mild pro-inflammatory conditions might constitute a permissive condition for the onset of insulin resistance. [Methods]: We evaluated the role of COX-2 expression in hepatocytes in a model of insulin resistance and altered energy homeostasis induced by high fat diet by metabolic parameters in transgenic mice constitutively expressing human COX-2 in hepatocytes. [Results]: COX-2 expression in hepatocytes protects from high fat diet-induced hepatic steatosis, obesity and hence insulin resistance, as demonstrated by a decreased hepatic steatosis, adiposity and adipocyte area, an enhanced insulin sensitivity and glucose tolerance, decreased plasmatic and hepatic triglycerides and free fatty acids levels, increased adiponectin/leptin ratio and decreased levels of pro-inflammatory cytokines. COX-2 transgenic mice exhibited increased whole body energy expenditure and fatty acid oxidation. Moreover, when hepatic insulin signaling was analyzed, an increase in insulin receptor-mediated Akt phosphorylation was found in hCOX-2 transgenic mice. Similar results were obtained in human and murine hepatic cells expressing a COX-2 transgene. [Conclusion]: Constitutively expression of COX-2 in hepatocytes protects against adiposity, inflammation and hepatic insulin resistance in mice under high fat diet.Peer Reviewe

Bacterial Killing Via A Type Iv Secretion System.

Type IV secretion systems (T4SSs) are multiprotein complexes that transport effector proteins and protein-DNA complexes through bacterial membranes to the extracellular milieu or directly into the cytoplasm of other cells. Many bacteria of the family Xanthomonadaceae, which occupy diverse environmental niches, carry a T4SS with unknown function but with several characteristics that distinguishes it from other T4SSs. Here we show that the Xanthomonas citri T4SS provides these cells the capacity to kill other Gram-negative bacterial species in a contact-dependent manner. The secretion of one type IV bacterial effector protein is shown to require a conserved C-terminal domain and its bacteriolytic activity is neutralized by a cognate immunity protein whose 3D structure is similar to peptidoglycan hydrolase inhibitors. This is the first demonstration of the involvement of a T4SS in bacterial killing and points to this special class of T4SS as a mediator of both antagonistic and cooperative interbacterial interactions.6645

Transmissibility, hospitalization, and intensive care admissions due to omicron compared to delta variants of SARS-CoV-2 in Catalonia: A cohort study and ecological analysis

The transmissibility of omicron using variant screening data from primary care practices (PCP) and hospital admissions. In addition, we used this data from PCP to establish the two periods when delta and omicron were, respectively, dominant (above 95% of cases). After that, we performed a population-based cohort analysis to calculate the rates of hospital and intensive care unit (ICU) admissions for both periods and to estimate reduction in severity. Rate ratios (RR) and 95% confidence intervals (95% CI) were calculated and stratified by age and vaccination status. In a second analysis, the differential substitution model in primary care vs. hospitals allowed us to obtain a population-level average change in severity.We have included 48,874 cases during the delta period and 560,658 during the omicron period. During the delta period, on average, 3.8% of the detected cases required hospitalization for COVID-19. This percentage dropped to 0.9% with omicron [RR of 0.46 (95% CI: 0.43 to 0.49)]. For ICU admissions, it dropped from 0.8 to 0.1% [RR 0.25 (95% CI: 0.21 to 0.28)]. The proportion of cases hospitalized or admitted to ICU was lower in the vaccinated groups, independently of the variant. Omicron was associated with a reduction in risk of admission to hospital and ICU in all age and vaccination status strata. The differential substitution models showed an average RR between 0.19 and 0.50.Both independent methods consistently show an important decrease in severity for omicron relative to delta. The systematic reduction happens regardless of age. The severity is also reduced for non-vaccinated and vaccinated groups, but it remains always higher in the non-vaccinated population. This suggests an overall reduction in severity, which could be intrinsic to the omicron variant. The fact is that the RR in ICU admission is systematically smaller than in hospitalization points in the same direction.MC received funding from la Caixa Foundation ID 100010434, under agreement LCF/PR/GN17/50300003. MC, CP, and SA received funding from Ministerio de Ciencia, Innovación y Universidades and FEDER, with the project PGC2018-095456- B-I00.Objectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Design-Based Research in CALL

The purpose of this volume is to expand and refine our understanding of the use of design-based research (DBR) in CALL by contributing to the growing body of literature in this area. We have tried our best to strike a balance between theoretical considerations and concrete examples of DBR. The first section of this volume focuses on theoretical perspectives and ideas that can inform the use of DBR in CALL. The second section contains studies that illustrate DBR through concrete instances of its operationalization. We hope this volume will be a useful source of information and inspiration for those considering to further explore DBR in CALL. For updates on DBR in CALL, please visit the companion site to this volume: https://sites.google.com/site/designbasedresearch/https://lib.dr.iastate.edu/language_books/1006/thumbnail.jp

Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). DARS2 variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes. Methods: We reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants' impact on mtAspRS structure and mitochondrial function. Results: We found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. DARS2 variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNAAsp binding, aspartyl-adenosine-5'-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast DARS2 ortholog showed severely affected mitochondrial function. Conclusions: DARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis

Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study

Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003-0.138]) in the overall group; 0.0 (95% CI [0-0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004-0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p < .0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated