Parental competences in fathers and mothers of very-low-birth-weight preterm infants

Objective: The goal was to analyze parental competences in Spanish families with very-low-birth-weight infants (≤32 weeks and/or less 1500 g) over 18 months of corrected age. Background: Parenting in families of very preterm infants is an interesting focus of research as we advance in the knowledge of how parental competences can have an important impact on child development. Method: Sixty-eight mothers and 56 fathers completed measures of parental competences, sociofamily risk, parental stress, social support, and emotional symptoms. Clinical characteristics and neonatal medical risk data were collected after birth. Statistical analyses were performed to compare parental competences with those of mothers and fathers of non-preterm infants. Generalized estimating equations were used for analysis, adjusted by family unit. Results: Mothers and fathers of preterm infants score higher in most dimensions of parental competences compared to a control group. Focusing on the preterm population, mothers score higher than fathers in daily involvement and mentalization and lower in parental self-care. When studied separately, we found different scores for fathers and mothers in parental competences (sociofamily risk, parental stress, social support, and emotional symptoms). Conclusion: Parents of preterm infants present better parental competences than parents of non-preterm infants when their children reach 18 months of age. It is important to consider the differences in parental competences between the mothers and fathers of these children. Implications: Our findings suggest the need to address parental competences to develop preventive and adaptive strategies in parents of preterm infants to promote positive parenting.This paper is part of the project PID2019‐110484RB‐I00 funded by MCIN/AEI/ 0.13039/501100011033. It was also funded by the 2017 (PI0052/2017) and 2019 (ITI‐0019‐2019) Cadiz‐integrated territorial initiative for biomedical research and the European Regional Development Fund (ERDF) 2014–2020, Andalusian Ministry of Health and Families, Spain. Funding informatio

Substrate-induced dimerization of engineered monomeric variants of triosephosphate isomerase from Trichomonas vaginalis

"The dimeric nature of triosephosphate isomerases (TIMs) is maintained by an extensive surface area interface of more than 1600 angstrom 2. TIMs from Trichomonas vaginalis (TvTIM) are held in their dimeric state by two mechanisms: a ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A) is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.

Structural basis for redox regulation of cytoplasmic and chloroplastic triosephosphate isomerases from Arabidopsis thaliana

"In plants triosephosphate isomerase (TPI) interconyerts glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP) during glycolysis, gluconeogenesis, and the Calvin-Benson cycle. The nuclear genome of land plants encodes two tpi genes, one gene product is located in the cytoplasm and the other is imported into the chloroplast. Herein we report the crystal structures of the TPIs from the vascular plant Arabidopsis thaliana (AtTPIs) and address their enzymatic modulation by redox agents. Cytoplasmic TPI (cTPI) and chloroplast TPI (pdTPI) share more than 60% amino acid identity and assemble as (beta-alpha)(8) dimers with high structural homology. cTPI and pdTPI harbor two and one accessible thiol groups per monomer respectively. cTPI and pdTPI present a cysteine at an equivalent structural position (C13 and C15 respectively) and cTPI also contains a specific solvent accessible cysteine at residue 218 (cTPI-C218). Site directed mutagenesis of residues pdTPI-C15, cTPI-C13, and cTPI-C218 to serine substantially decreases enzymatic activity, indicating that the structural integrity of these cysteines is necessary for catalysis. AtTPIs exhibit differential responses to oxidative agents, cTPI is susceptible to oxidative agents such as diamide and H2O2, whereas pdTPI is resistant to inhibition. Incubation of AtTPIs with the sulfhydryl conjugating reagents methylmethane thiosulfonate (MMTS) and glutathione inhibits enzymatic activity. However, the concentration necessary to inhibit pdTPI is at least two orders of magnitude higher than the concentration needed to inhibit cTPI. Western-blot analysis indicates that residues cTPI-C13, cTPI-C218, and pdTPI-C15 conjugate with glutathione. In summary, our data indicate that AtTPIs could be redox regulated by the derivatization of specific AtTPI cysteines (cTPI-C13 and pdTPI-C15 and cTPI-C218). Since AtTPIs have evolved by gene duplication, the higher resistance of pdTPI to redox agents may be an adaptive consequence to the redox environment in the chloroplast.

Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition

Vascular endothelial growth factor (VEGF) is up-regulated during mesothelial to mesenchymal transition (MMT) and has been associated with peritoneal membrane dysfunction in peritoneal dialysis (PD) patients. It has been shown that normal and malignant mesothelial cells (MCs) express VEGF receptors (VEGFRs) and co-receptors and that VEGF is an autocrine growth factor for mesothelioma. Hence, we evaluated the expression patterns and the functional relevance of the VEGF/VEGFRs/co-receptors axis during the mesenchymal conversion of MCs induced by peritoneal dialysis. Omentum-derived MCs treated with TGF-β1 plus IL-1β (in vitro MMT) and PD effluent-derived MCs with non-epithelioid phenotype (ex vivo MMT) showed down-regulated expression of the two main receptors Flt-1/VEGFR-1 and KDR/VEGFR-2, whereas the co-receptor neuropilin-1 (Nrp-1) was up-regulated. The expression of the Nrp-1 ligand semaphorin-3A (Sema-3A), a functional VEGF competitor, was repressed throughout the MMT process. These expression pattern changes were accompanied by a reduction of the proliferation capacity and by a parallel induction of the invasive capacity of MCs that had undergone an in vitro or ex vivo MMT. Treatment with neutralizing anti-VEGF or anti-Nrp-1 antibodies showed that these molecules played a relevant role in cellular proliferation only in naïve omentum-derived MCs. Conversely, treatment with these blocking antibodies, as well as with recombinant Sema-3A, indicated that the switched VEGF/VEGFRs/co-receptors axis drove the enhanced invasion capacity of MCs undergoing MMT. In conclusion, the expression patterns of VEGFRs and co-receptors change in MCs during MMT, which in turn would determine their behaviour in terms of proliferation and invasion in response to VEGFThis work was supported by grant SAF2010-21249 from the ‘‘Ministerio de Economía y Competitividad’’ to M.L.C. and by grant S2010/BMD-2321 from ‘‘Comunidad Autónoma de Madrid’’ to M.L.C. and R.S. This work was also partially supported by grants PI 09/0776 from ‘‘Fondo de Investigaciones Sanitarias’’ to A.A., and RETICS 06/0016 (REDinREN, Fondos FEDER, EU) to R.S

Uso de nisina y quitosano para la inhibición de Staphylococcus aureus resistente a antibióticos y asociado a mastitis bovina

This study describes the antibiotic resistance patterns of Staphylococcus aureus isolates from cows with mastitis, as well as their in vitro susceptibility to nisin, chitosan and the nisin/chitosan composite. From milk samples obtained from sick cows, 53 S. aureus isolated were identified, the profile of antibiotic resistance was analyzed. The results showed a high frequency of resistance to beta-lactams group, mainly penicillin, dicloxacillin and ampicillin. In addition, multiresistance was detected in some isolates, since they showed tolerance to 3 or 4 different groups of antibiotics, highlighting the isolates AMC-9 (resistant to three groups) and AMC-23 (resistant to four groups). It is also noted that all isolates were susceptible to levofloxacin. On the other hand, the in vitro susceptibility of the isolates to nisin, chitosan and the nisin/chitosan composite was analyzed determining the Minimum Inhibitory Concentration (MIC). The results indicated 100 % of the isolates were susceptible to chitosan and to the nisin/chitosan composite and 47.1 % to nisin. The effect of chitosan and nisin/chitosan composite on the multi-resistant isolates AMC-9 and AMC-23 was bactericidal. These results show the potential of the antimicrobial compounds chitosan, nisin/chitosan to be used as therapeutic agents against bovine mastitis.En este trabajo se describen los patrones de resistencia a antibióticos de aislados de Staphylococcus aureus obtenidos de vacas con mastitis, así como su susceptibilidad in vitro a nisina, quitosano y al compósito nisina/quitosano. A partir de muestras de leche obtenidas de vacas enfermas se aislaron e identificaron 53 S. aureus, a los cuales se les analizó el perfil de resistencia a antibióticos. Los resultados evidenciaron una alta frecuencia de resistencia hacia el grupo de los beta-lactámicos, principalmente a penicilina, dicloxacilina y ampicilina. Asimismo, se detectó multirresistencia en algunos aislados, ya que mostraron tolerancia a 3 o 4 grupos de antibióticos, destacando los aislados AMC-9 (resistente a tres grupos) y AMC-23 (resistente a cuatro grupos). También se resalta que todos los aislados fueron susceptibles a levofloxacina. Por otra parte, se analizó la susceptibilidad in vitro de los aislados a nisina, quitosano y al compósito nisina/quitosano, mediante la determinación de la concentración mínima inhibitoria. Los resultados indican que el 100 % de los aislados fue susceptible a quitosano y al compósito nisina/quitosano y el 47.1 % a la nisina. El efecto del quitosano y del compósito nisina/quitosano sobre los aislados multirresistentes AMC-9 y AMC-23 fue bactericida. Estos resultados revelan el potencial de los compuestos antimicrobianos quitosano y nisina/quitosano para ser utilizados como agentes terapéuticos contra la mastitis bovina

Arabidopsis immune responses triggered by cellulose‐ and mixed‐linked glucan‐derived oligosaccharides require a group ofleucine‐rich repeat malectinreceptor kinases

[EN] The plant immune system perceives a diversity of carbohydrate ligands from plant and microbial cell walls through the extracellular ectodomains (ECDs) of pattern recognition receptors (PRRs), which activate pattern-triggered immunity (PTI). Among these ligands are oligosaccharides derived from mixed-linked b- 1,3/b-1,4-glucans (MLGs; e.g. b-1,4-D-(Glc)2-b-1,3-D-Glc, MLG43) and cellulose (e.g. b-1,4-D-(Glc)3, CEL3). The mechanisms behind carbohydrate perception in plants are poorly characterized except for fungal chitin oligosaccharides (e.g. b-1,4-D-(GlcNAc)6, CHI6), which involve several receptor kinase proteins (RKs) with LysM-ECDs. Here, we describe the isolation and characterization of Arabidopsis thaliana mutants impaired in glycan perception (igp) that are defective in PTI activation mediated by MLG43 and CEL3, but not by CHI6. igp1–igp4 are altered in three RKs – AT1G56145 (IGP1), AT1G56130 (IGP2/IGP3) and AT1G56140 (IGP4) – with leucine-rich-repeat (LRR) and malectin (MAL) domains in their ECDs. igp1 harbors point mutation E906K and igp2 and igp3 harbor point mutation G773E in their kinase domains, whereas igp4 is a T-DNA insertional loss-of-function mutant. Notably, isothermal titration calorimetry (ITC) assays with purified ECDRKs of IGP1 and IGP3 showed that IGP1 binds with high affinity to CEL3 (with dissociation constant KD = 1.19 0.03 lM) and cellopentaose (KD = 1.40 0.01 lM), but not to MLG43, supporting its function as a plant PRR for cellulose-derived oligosaccharides. Our data suggest that these LRR-MAL RKs are components of a recognition mechanism for both cellulose- and MLG-derived oligosaccharide perception and downstream PTI activation in Arabidopsis.SIGrant PID-2021-126006OB-100 from the Spanish Ministry of Science and Innovation to AMThis work has also been financially supported by the ‘Severo Ochoa (SO) Programme for Centres of Excellence in R&D’ from the Agencia Estatal de Investigaci on (AEI) of Spain (grants SEV-2016-0672 (2017-2021) and CEX2020-000999-S (2022-2025) to the CBGP). In the frame of the SO program, HM and PF-C were supported with postdoctoral fellowships. MM-D, DJB and DR were recipients of PhD Fellows PRE2019-088120 and PRE2019-091276 (SEV-2016- 0672) from AEI, and IND2017/BIO-7800 from Madrid Regional Government, respectively. Research in the lab of JS was financially supported by the University of Lausanne, the European Research Council (ERC) (grant agreement no. 716358) and the Swiss National Science Foundation (grant no. 310030_204526)

Arabidopsis immune responses triggered by cellulose- and mixed-linked glucan-derived oligosaccharides require a group of leucine-rich repeat malectin receptor kinases

18 Päg.The plant immune system perceives a diversity of carbohydrate ligands from plant and microbial cell walls through the extracellular ectodomains (ECDs) of pattern recognition receptors (PRRs), which activate pattern-triggered immunity (PTI). Among these ligands are oligosaccharides derived from mixed-linked β-1,3/β-1,4-glucans (MLGs; e.g. β-1,4-D-(Glc)2 -β-1,3-D-Glc, MLG43) and cellulose (e.g. β-1,4-D-(Glc)3 , CEL3). The mechanisms behind carbohydrate perception in plants are poorly characterized except for fungal chitin oligosaccharides (e.g. β-1,4-d-(GlcNAc)6 , CHI6), which involve several receptor kinase proteins (RKs) with LysM-ECDs. Here, we describe the isolation and characterization of Arabidopsis thaliana mutants impaired in glycan perception (igp) that are defective in PTI activation mediated by MLG43 and CEL3, but not by CHI6. igp1-igp4 are altered in three RKs - AT1G56145 (IGP1), AT1G56130 (IGP2/IGP3) and AT1G56140 (IGP4) - with leucine-rich-repeat (LRR) and malectin (MAL) domains in their ECDs. igp1 harbors point mutation E906K and igp2 and igp3 harbor point mutation G773E in their kinase domains, whereas igp4 is a T-DNA insertional loss-of-function mutant. Notably, isothermal titration calorimetry (ITC) assays with purified ECD-RKs of IGP1 and IGP3 showed that IGP1 binds with high affinity to CEL3 (with dissociation constant KD  = 1.19 ± 0.03 μm) and cellopentaose (KD  = 1.40 ± 0.01 μM), but not to MLG43, supporting its function as a plant PRR for cellulose-derived oligosaccharides. Our data suggest that these LRR-MAL RKs are components of a recognition mechanism for both cellulose- and MLG-derived oligosaccharide perception and downstream PTI activation in Arabidopsis.This work was supported by grant RTI2018-096975-B-I00 from the Spanish Ministry of Science, Innovation and Universities to AM and grant PID-2021-126006OB-100 from the Spanish Ministry of Science and Innovation to AM. This work has also been financially supported by the ‘Severo Ochoa (SO) Programme for Centres of Excellence in R&D’ from the Agencia Estatal de Investigación (AEI) of Spain (grants SEV-2016-0672 (2017-2021) and CEX2020-000999-S (2022-2025) to the CBGP). In the frame of the SO program, HM and PF-C were supported with postdoctoral fellowships. MM-D, DJB and DR were recipients of PhD Fellows PRE2019-088120 and PRE2019-091276 (SEV-2016-0672) from AEI, and IND2017/BIO-7800 from Madrid Regional Government, respectively. Research in the lab of JS was financially supported by the University of Lausanne, the European Research Council (ERC) (grant agreement no. 716358) and the Swiss National Science Foundation (grant no. 310030_204526).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020‐000999‐S)Peer reviewe

Residual pulmonary infiltrates, symptoms and diffusion impairment at one‐year after severe COVID‐19 infection have different associated factors

Menendez R, Mendez R, Latorre A, Gonzalez-Jimenez P, Peces-Barba G, Molina M, et al. Residual pulmonary infiltrates, symptoms and diffusion impairment at 1-year after severe COVID-19 infection have different associated factors. J Intern Med. 2023;00:1-13. Introduction. After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, patients may show lung sequelae on radiology and functional impairment at the 1-year followup. We aimed to describe the persistence of symptoms, radiological alterations, or reduced diffusing capacity of the lung for carbon monoxide (DLCO) at 1-year follow-up in patients from the Spanish Registry RECOVID. Methods. RECOVID collected symptom and radiological and functional lung tests data on hospitalized patients with coronavirus disease 2019 during the acute phase and at the 6- and 12-month follow-up visits. Results. Of the 2500 enrolled survivors (90% admitted to the ward), 1874 had follow-up visits for up to a year. Of these, 42% continued to present with symptoms, 27% had radiological sequelae and 31% had reduced DLCO. Independently associated factors included female sex, asthma and the requirement for invasive or non-invasive mechanical ventilation. Complete radiological resolution was 72.2% at 12 months; associated factors with incomplete recovery were age, male sex, oxygen or respiratory support, corticosteroids and an initial SpO(2)/FiO(2) = 2. Reduced D-LCO was observed in 31% of patients at 12 months; associated factors were older age, female sex, smoking habit, SpO(2)/FiO(2) = 2 and the requirement of respiratory support.At 12 months, a proportion of the asymptomatic patients showed reduced D-LCO (9.5%), radiological findings (25%) or both (11%). Conclusions. The factors associated with symptom persistence, incomplete radiological resolution and D-LCO <80% differed according to age, sex, comorbidities and respiratory support. The burden of symptoms, reduced D-LCO and incomplete radiological resolution were considerable in patients with SARS-CoV-2 pneumonia at the 1-year follow-up after hospitalisation

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured