Targeted bacterial conjugation mediated by synthetic cell-to-cell adhesions.

Genetic interventions on microbiomes, for clinical or biotechnological purposes, remain challenging. Conjugation-based delivery of genetic cargo is still unspecific and limited by low conjugation rates. Here we report an approach to overcome these problems, based on a synthetic bacterial adhesion system. Mating assemblers consist on a synthetic adhesion formed by the expression on the surface of donor and target cells of specific nanobodies (Nb) and their cognate antigen (Ag). The Nb-Ag bridge increased 1-3 logs transfer of a variety of plasmids, especially in liquid media, confirming that cell-cell docking is a main determinant limiting mating efficiency. Synthetic cell-to-cell adhesion allows efficient conjugation to targeted recipients, enhancing delivery of desired genes to a predefined subset of prey species, or even specific pathogenic strains such as enterohemorrhagic Escherichia coli (EHEC), within a bacterial community. The synthetic conjugation enhancer presented here optimizes plasmid delivery by selecting the target hosts with high selectivity.

The impact of lockdown on the learning gap: family and school divisions in times of crisis.

The lockdown of schools in Spain to confront the effects of COVID-19 caused an enormous impact at both societal and educational levels. Schools and families had to react rapidly to a new teaching and learning scenario without the benefit of previous planning or government guidelines. In this context, some schools were better able to adapt to the new circumstances than others. Likewise, the structure and size of families' economic, social and cultural capital produced significant differences in the learning opportunities for children from different backgrounds. This article assesses the impact of the school lockdown on the learning gap between children from different social backgrounds in Catalonia. Based on 35,419 responses to an online survey administered between 26 and 30 March 2020 to families with children aged between 3 and 18, the authors' analysis shows that learning opportunities varied significantly. Middle-class families were able to maintain higher standards of education quality in a critical context, while children from socially disadvantaged families had few learning opportunities both in terms of time and learning experiences (schoolwork and maintenance of after-school activities). Results differed by type of school (public/private) where students were enrolled, family economic, social and cultural capital, and family living conditions. In the final part of the article, the authors highlight the importance of the role of the school in ensuring learning opportunities for children from low socioeconomic backgrounds, and they discuss some policy implications of their findings.

L'impact du confinement sur les écarts en matière d'apprentissage : disparités familiales et scolaires en période de crise ­ La fermeture des écoles en Espagne durant le confinement pour faire face aux effets de la COVID-19 a eu d'immenses répercussions sur les plans sociétal et éducatif. Les écoles et les familles ont rapidement réagi au nouveau scénario de l'enseignement et de l'apprentissage sans pouvoir s'appuyer sur une planification préalable ou des directives gouvernementales. Dans ce contexte, certaines écoles ont réussi mieux que d'autres à s'adapter à ces nouvelles circonstances. De même, la structure et la taille du capital économique, social et culturel des familles a montré qu'en fonction de leur milieu, les enfants avaient des possibilités d'apprendre très inégales. Cet article évalue l'impact de la fermeture des écoles en Espagne durant le confinement sur les écarts en matière d'apprentissage chez des enfants de différents milieux sociaux en Catalogne. S'appuyant sur 35 419 réponses à une enquête en ligne menée entre le 26 et le 30 mars 2020 auprès de familles avec des enfants âgés de trois à dix-huit ans, l'analyse des auteurs révèle de considérables disparités concernant les possibilités d'apprendre. Les familles de la classe moyenne ont réussi à maintenir un niveau d'éducation élevé dans cette situation critique, tandis que dans les familles défavorisées sur le plan social, les possibilités des enfants étaient restreintes, tant en termes de temps que d'expériences éducatives (devoirs et maintien d'activités extrascolaires). Les résultats étaient différents en fonction du type d'établissement (public/privé) où les élèves étaient inscrits, de la situation économique de la famille, du capital social et culturel de cette dernière et de ses conditions de vie. Dans la dernière partie de l'article, les auteurs soulignent l'importance du rôle de l'école pour garantir la possibilité d'apprendre aux enfants de milieux socio-économiquement faibles. Ils abordent en outre un certain nombre de conséquences qu'entraînent leurs constatations pour les politiques en matière d'éducation.

El impacto del cierre escolar en la brecha de aprendizaje: divisiones familiares y escolares en tiempos de crisis ­ El cierre de escuelas en España para hacer frente a los efectos de la COVID-19 causó un enorme impacto tanto a nivel social como educativo. Escuelas y familias tuvieron que reaccionar rápidamente a un nuevo escenario de enseñanza y aprendizaje sin contar con planificación previa o con directrices gubernamentales. En este contexto, algunas escuelas fueron capaces de adaptarse mejor a las nuevas circunstancias que otras. Asimismo, la estructura y el tamaño del capital económico, social y cultural de las familias produjeron diferencias significativas en las oportunidades de aprendizaje de los niños y niñas de diferentes orígenes. Este artículo evalúa el impacto del cierre de las escuelas en la brecha de aprendizaje entre el alumnado de diferentes orígenes sociales en Cataluña. Sobre la base de 35.419 respuestas a una encuesta en línea realizada entre el 26 y el 30 de marzo de 2020 a familias con hijos e hijas de entre 3 y 18 años, el análisis muestra que las oportunidades de aprendizaje varían significativamente. Las familias de clase media pudieron mantener niveles más altos de calidad educativa en un contexto crítico, mientras que los niños de familias socialmente desfavorecidas tuvieron pocas oportunidades de aprendizaje, tanto en términos de tiempo como de experiencias de aprendizaje (tareas escolares y mantenimiento de las actividades extraescolares). Los resultados difieren según el tipo de escuela (pública o privada) en que estaban matriculados los estudiantes, el capital económico, social y cultural de la familia y sus condiciones de vida. En la parte final del artículo, se destaca la importancia del papel de la escuela para garantizar las oportunidades de aprendizaje de los niños procedentes de entornos socioeconómicos bajos, y se examinan algunas de las repercusiones en clave de política educativa.

Psychological and Sociocultural Determinants in Childhood Asthma Disease: Impact on Quality of Life.

Asthma is the most common chronic disease in childhood. The presence of this pathology in children leads to the appearance of different alterations (physical, psychological, social, etc.). Due to their high influence, the aim of this study is to understand these psychological and sociocultural determinants and their impact on the quality of life of asthmatic children. In order to determine the influence of these determinants on quality of life, a narrative review of 48 articles collected in different databases was carried out. Emotions are the most powerful precursor to producing an asthmatic attack. Anxiety and depression are the pathologies that appear frequently associated with childhood asthma, together with Attention-Deficit/Hyperactivity Disorder. In addition, the personality of these children seems to be characterized by shyness and impulsivity, although exceptionally it has been associated with psychopathic behaviors, aggressiveness, and cases of psychosis. School performance is impaired and bullying occurs more frequently. Likewise, dysfunctional family relationships and lower socioeconomic status have a negative impact on the severity and management of asthma. In short, the quality of life of asthmatic children is lower due to the presence of the aforementioned psychological and sociocultural determinants.

COVID-19 school closures and cumulative disadvantage: Assessing the learning gap in formal, informal and non-formal education.

Reducing physical contact has been the most common strategy adopted by governments to reduce the spread of the COVID-19 disease. It has led most countries to close their schools. Previous evidence on the effects of teacher strikes, summer holidays, armed conflicts or any other cause of school closure on learning suggest that the effects of COVID-19 will be highly significant for some and will vary depending on students' previous performance, family characteristics, age or education track, among other factors. Recent evidence shows that learning losses during school closures have been widespread and especially intense among the more disadvantaged students. In this article we evaluate the magnitude of the gap regarding opportunities to learn in formal, informal and non-formal education between families depending on their cultural and economic capital. An online survey (n = 35,937) was carried out during the second week of the confinement (March 2020) in Catalonia. The survey targeted families with children between three and eighteen years. The responses show remarkable social inequalities in opportunities to learn. In this article, we describe the magnitude of the learning gap between social groups and explore which are the most significant factors that explain educational inequalities. Our findings reveal a process of cumulative disadvantage that results from unequal opportunities in formal, informal and non-formal education and underline the need to address both school and family factors to mitigate the impact of the pandemic on learning opportunities.

Telomere-based risk models for the early diagnosis of clinically significant prostate cancer.

BACKGROUND: The objective of this study was to explore telomere-associated variables (TAV) as complementary biomarkers in the early diagnosis of prostate cancer (PCa), analyzing their application in risk models for significant PCa (Gleason score > 6). METHODS: As part of a larger prospective longitudinal study of patients with suspicion of PCa undergoing prostate biopsy according to clinical practice, a subgroup of patients (n = 401) with PSA 3-10 ng/ml and no prior biopsies was used to evaluate the contribution of TAV to discern non-significant PCa from significant PCa. The cohort was randomly split for training (2/3) and validation (1/3) of the models. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate TAV in peripheral blood mononucleated cells. Models were generated following principal component analysis and random forest and their utility as risk predictors was evaluated by analyzing their predictive capacity and accuracy, summarized by ROC curves, and their clinical benefit with decision curves analysis. RESULTS: The median age of the patients was 63 years, with a median PSA of 5 ng/ml and a percentage of PCa diagnosis of 40.6% and significant PCa of 19.2%. Two TAV-based risk models were selected (TAV models 1 and 2) with an AUC ≥ 0.83 in the full study cohort, and AUC > 0.76 in the internal validation cohort. Both models showed an improvement in decision capacity when compared to the application of the PCPT-RC in the low-risk probabilities range. In the validation cohort, with TAV models 1 and 2, 33% /48% of biopsies would have been avoided losing 0/10.3% of significant PCa, respectively. The models were also tested and validated on an independent, retrospective, non contemporary cohort. CONCLUSIONS: Telomere analysis through TAV should be considered as a new risk-score biomarker with potential to increase the prediction capacity of significant PCa in patients with PSA between 3-10 ng/ml.

Respiratory pathogens in bronchoalveolar lavage in a Puerto Rican population infected with the human immunodeficiency virus.

OBJECTIVE: To describe the respiratory pathogens found in the bronchoalveolar lavage of a Puerto Rican population infected with the human immunodeficiency virus (HIV). BACKGROUND: Empirical treatment is an accepted strategy for management of HIV-related pneumonia, but it is usually recommended for countries that have knowledge of the prevalent organisms in their population. In Puerto Rico, we have relied on data from the United States, but ethnic and geographical differences have been reported. DESIGN: Case series of a HIV-infected population admitted to an academic hospital in Puerto Rico because of respiratory symptoms and who underwent diagnostic standard bronchoalveolar lavage. RESULTS: From August 1998 to March 2000, 32 bronchoalveolar lavages (BAL) were performed in 31 Puerto Rican HIV patients. Nine (31%) were female. Mean age was 37 years old. Predominant mode of infection of the virus was intravenous drug use in men and heterosexual contact in women. BAL was diagnostic in 17/32 (53%) of the cases. Identified respiratory pathogens were Pneumocystis carinii (5), Mycobacterium tuberculosis (4), Staphylococcus aureus (2), Pseudomonas aeuruginosa (1), Bordetella bronchiseptica (1), viridans streptococcus (1), Histoplasma capsulatum (1), Cytomegalovirus (1), and, Mycobacterium kansassi (1). Retrospective review of medical records of non bronchoscoped patients for the period added six culture confirmed tuberculosis cases increasing tuberculosis rate to 18% (10/56). CONCLUSIONS: Tuberculosis appears to be a more frequent pathogen in Puerto Rico than is reported in the United States. A larger study is needed to confirm this finding and thus to clarify whether an initial presumption of tuberculosis should be assumed in the Puerto Rican HIV population.

Atomic force microscopy reveals two phases in single stranded DNA self-assembled monolayers.

We have investigated the structure of single-stranded (ss) DNA self-assembled monolayers (SAMs) on gold by combining peak force tapping, Kelvin probe and phase contrast atomic force microscopy (AFM) techniques. The adhesion, surface potential and phase shift signals show heterogeneities in the DNA film structure at two levels: microscale and nanoscale; which cannot be clearly discerned in the topography. Firstly, there is multilayer aggregation covering less than 5% of the surface. The DNA multilayers seem to be ordered phases and their existence suggests that DNA end-to-end interaction can play a role in the self-assembly process. Secondly, we find the formation of two phases in the DNA monolayer, which differ both in surface energy and surface potential. We relate the two domains to differences in the packing density and in the ssDNA conformation. The discovered heterogeneities in ssDNA SAMs provide a new scenario in our vision of these relevant films that have direct consequences on their biological, chemical and physical properties.

Characterization of pncA gene mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from Mexico.

Numerous studies have linked mutations in the pncA gene with resistance to pyrazinamide (Z) in Mycobacterium tuberculosis. However, variations in these mutations are specific to the country of origin of the isolate. The aim of this study was to characterize changes in pncA gene sequence in isolates of M. tuberculosis with resistance to Z, from patients in Mexico. M. tuberculosis isolates were recovered from individuals suspected of carrying drug resistant tuberculosis and respective susceptibility tests were developed. In isolates with resistance to pyrazinamide the pncA gene and its promoter were analyzed by capillary sequencing. From 127 drug-resistant isolates collected, 42 (33%) were resistant to pyrazinamide. The pncA sequences showed 26 changes in 34 (81%) isolates: 18 SNPs (n=26, 62%), four insertions (n=4, 9.5%) and four deletions (n=4, 9.5%). Absence of modifications was observed in eight (19%) sequences/isolates. The most frequent changes were the mutations L120P (n=7) and K96R (n=4). Twelve changes found are reported for the first time. This is the first description of pncA gene modifications in pyrazinamide resistant isolates originating in Mexico. We conclude that the diversity of changes in pncA indicates the presence of a noteworthy variety of pyrazinamide resistant strains occurring in the area.

Thermodynamics and kinetics of the nickel(II)-salicylhydroxamic acid system. Phenol rotation induced by metal ion binding.

The kinetics and the equilibria of Ni(II) binding to p-hydroxybenzohydroxamic acid (PHBHA) and salicylhydroxamic acid (SHA) have been investigated in an aqueous solution at 25 degrees C and I=0.2 M by the stopped-flow method. Two reaction paths involving metal binding to the neutral acid and to its anion have been observed. Concerning PHBHA, the rate constants of the forward and reverse steps are k1=(1.9+/-0.1)x10(3) M-1 s-1 and k-1=(1.1+/-0.1)x10(2) s-1 for the step involving the undissociated PHBHA and k2=(3.2+/-0.2)x10(4) M-1 s-1 and k-2=1.2+/-0.2 s-1 for the step involving the anion. Concerning SHA, the analogous rate constants are k1=(2.6+/-0.1)x10(3) M-1 s-1, k-1=(1.3+/-0.1)x10(3) s-1, k2=(5.4+/-0.2)x10(3) M-1 s-1, and k-2=6.3+/-0.5 s-1. These values indicate that metal binding to the anions of the two acids concurs with the Eigen-Wilkins mechanism and that the phenol oxygen is not involved in the chelation. Moreover, a slow effect was observed in the SHA-Ni(II) system, which has been put down to rotation of the benzene ring around the C-C bond. Quantum mechanical calculations at the B3LYP/lanL2DZ level reveal that the phenol group in the most stable form of the Ni(II) chelate is in trans position relative to the carbonyl oxygen, contrary to the free SHA structure, where the phenol and carbonyl oxygen atoms both have cis configuration. These results bear out the idea that the complex formation is coupled with phenol rotation around the C-C bond.