Prevalence and patterns of higher-order drug interactions in Escherichia coli.

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems

Transmediación y transformatización en la ficción televisiva de Ecuador: análisis de recepción de narrativas de humor

Ecuadorian television is 56 years old, time in which fiction has been part of the program and has established itself as one of the most offered genres in audiovisual channels with open signal. Currently, comedy is the mark of national fiction that have been placed among the most seen and at the same time, have been case of study about interactions with the audience for media besides television and the conversion from one format to another, without discarding characters and locations. This paper compiles the results of a longitudinal research carried out between 2010 and 2015 by OBITEL Ecuador on transmedia reception and “transformat” of five national comedy fictions from an actual perspective to understand the changes of this communication process. Virtual ethnography has been used as methodological strategy. It is concluded that national fictions are “transformazing” and transmediazing to broadcasters for internal reasons but other national fictions are changed only media, being Facebook the space where audiences continue showing greater support of the comedy fictions that have had high ratings in other years. In a global scenario where technology is changing the ways in which media content is consumed, the results of this work contribute to reception researches about Ecuadorian television, a process that requires more studies by the dynamics that is reaching.La televisión ecuatoriana tiene 57 años, tiempo en el que la ficción ha sido parte de la programación y se ha consolidado como uno de los géneros audiovisuales más ofertados de los canales de señal abierta. Actualmente, el humor es la marca de las ficciones nacionales que se han ubicado entre las más vistas y, al mismo tiempo, se han constituido en estudios de caso sobre interacciones con las audiencias por medios de comunicación distintos a la televisión y conversión de un formato a otro formato, sin desechar personajes y locaciones. Este artículo registra los resultados de una investigación longitudinal realizada entre 2010 y 2015 por OBITEL Ecuador sobre recepción transmediática y “transformatizada” de cinco ficciones nacionales de humor desde una perspectiva presente para comprender los cambios de ese proceso comunicativo. Como estrategia metodológica, se ha usado la etnografía virtual. Se concluye que las ficciones nacionales se han “transformatizado” y transmediatizado por razones internas a las emisoras mientras que otras se han transmediado por la aplicación de la ley, es Facebook en el las audiencias siguen mostrando un acompañamiento mayor de las ficciones de humor que tuvieron altos índices de audiencia en otros años. En un escenario mundial donde la tecnología está modificando las formas en las que se consumen los contenidos mediáticos, los resultados de este trabajo aportan a las investigaciones sobre recepción de la televisión ecuatoriana, proceso que precisa de más estudios por las dinámicas que está alcanzando

Non-pharmacological, non-surgical interventions for urinary incontinence in older persons : A systematic review of systematic reviews. The SENATOR project ONTOP series

This work was supported by the European Union Seventh Framework program (FP7/2007–2013) under grant agreement n° 305930Peer reviewedPostprin

High‐Throughput Screen of Natural Product Extracts in A Yeast Model of Polyglutamine Proteotoxicity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106714/1/cbdd12259.pd

Navigating Identity Uncertainty: Identity Distress During the COVID-19 Pandemic

The long-term effects of the COVID-19 pandemic have only recently begun to be explored. Among college students, who were faced with sudden and unprecedented changes and challenges, it is likely that COVID-19 detrimentally impacted the establishment of a sense of self, a key developmental task of the college years. However, no research has examined the relationships among COVID-19 related worries, identity distress, and psychological and academic adjustment. To address these gaps in the current study, we examined the prevalence of identity distress, the relationship between COVID-19 related worries and identity distress, and the direct and indirect associations between COVID-19 related worries and psychological and academic adjustment among a sample of 1627 college students (M-age = 20.51, SD = 2.21). Findings indicated that over a third of the sample reported high levels of identity distress and that COVID-19 related worries were negatively associated, both directly and indirectly through identity distress, with psychological and academic adjustment

Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts

As part of the International Cooperative Biodiversity Groups (ICBG) Program, we were interested in identifying biologically active unfolded protein response (UPR) inducing compounds from marine microorganisms isolated from Costa Rican biota. With this aim in mind we have now generated more than 33,000 unique prefractionated natural product extracts from marine and terrestrial organisms that have been submitted to the Center of Chemical Genomics (CCG) at the University of Michigan for high throughput screening (HTS). An effective complementary cell-based assay to identify novel modulators of UPR signaling was used for screening extracts. Active fractions were iteratively subjected to reverse-phase HPLC chromatographic analysis, and together with lobophorin A, B, E, and F (1–4), three new lobophorin congeners, designated as CR1 (5), CR2 (6), and CR3 (7) were isolated. Herein, we report that secondary assays revealed that the new lobophorins induced UPR-associated gene expression, inhibited oral squamous cell carcinoma cell growth, and led to UPR-dependent cell death in murine embryonic fibroblast (MEF) cells.International Cooperative Biodiversity Groups/[U01 TW007404]/ICBG/Estados UnidosNational Institutes of Health/[DK042394]/NIH/Estados UnidosNational Institutes of Health/[DK088227]/NIH/Estados UnidosNational Institutes of Health/[HL052173]/NIH/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Químic

Efecto del 2,4 Diclorofenoxiacético en la inducción de callos a partir de limbos foliares de Ipomoea batatas (L.) Lam. “camote”

Ipomoea batatas (L.) Lam. “camote”, es un cultivo rústico, de importancia nacional por su valor energético y la presencia de antocianinas ycarotenos. Su manejo agronómico implica su propagación asexual mediante esquejes, siendo la biotecnología vegetal una buena alternativapara la multiplicación masiva, conservación in vitro y/o mejoramiento del cultivo, para ello se hacen uso de reguladores de crecimientovegetal. Uno de ellos es el 2,4 Diclorofenoxiacético (2,4-D), el cual a bajas concentraciones se comporta como una auxina inductora en lageneración de callos. Ante la necesidad de conocimiento en esta área, se propuso como objetivo de investigación determinar el efecto del2,4 Diclorofenoxiacético en la inducción de callos a partir de limbos foliares de I. batatas “camote”. En laboratorio se cultivaron explantes apartir de limbos foliares previamente desinfectados de hojas jóvenes de I. batatas de la variedad amarilla, en medio de cultivo MS,suplementado con ácido 2,4-Diclorofenoxiacético (2,4-D), a las concentraciones de 0 μM; 9,48 μM; 11, 3 μM y 13, 56 μM, empleándose undiseño completamente aleatorizado. A los 50 días de evaluación no se encontró diferencias estadísticamente significativas, sin embargo, enla concentración de 9,48 μM μM de 2,4-D se observó la presencia de un 100 % de callos. Se concluye que el ácido 2,4-Diclorofenoxiacéticoa la concentración de 9,48 μM es favorable en la inducción de callos a partir de limbos foliares de I. batatas (L.) Lam. “camote”. Palabras clave: Embriones somáticos, limbo, camote, 2,4 Diclorofenoxiacético. Abstract Ipomoea batatas (L.) Lam. “camote”, is a rustic crop, of national importance for its energy value and the presence of anthocyanins andcarotenes. Its agronomic management implies its asexual propagation through cuttings, being plant biotechnology a good alternative formassive multiplication, in vitro conservation and/or crop improvement, for this, plant growth regulators are used. One of them is 2.4-Dichlorophenoxyacetic (2.4-D), which at low concentrations behaves as an inducer auxin in the generation of calluses. Given the need forknowledge in this area, it was proposed as a research objective to determine the effect of 2.4-Dichlorophenoxyacetic acid on the inductionof calluses from leaf blades of I. batatas. In the laboratory, explants were grown from previously disinfected leaf blades of young leaves of I.batatas of the yellow variety, in the MS culture medium, supplemented with 2.4-Dichlorophenoxyacetic acid (2.4-D), at the concentrationsof 0 μM; 9.48 μM; 11.3 μM y 13.56 μM, using a completely randomized design. At 50 days of evaluation, no statistically significant differenceswere found, however, at the 9.48 μM concentration of 2.4-D the presence of 100% calluses was observed. It is concluded that 2.4-Dichlorophenoxyacetic acid at a concentration of 9.48 μM is favorable in the induction of calluses from leaf blades of I. batatas (L.) Lam."sweet potato". Keywords: Somatic embryos, limbus, sweet potato, 2,4 Dichlorophenoxyacetic. *Autor para correspondencia: [email protected] DOI: http://dx.doi.org/10.17268/rebiol.2021.41.01.1

Spanish guidelines for the use of targeted deep sequencing in myelodysplastic syndromes and chronic myelomonocytic leukaemia

The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of patients. These mutations contribute to a better classification and risk stratification of the patients. Currently, clinical laboratories include NGS genomic analyses in their routine clinical practice, in an effort to personalize the diagnosis, prognosis and treatment of MDS and CMML. NGS technologies have reduced the cost of large-scale sequencing, but there are additional challenges involving the clinical validation of these technologies, as continuous advances are constantly being made. In this context, it is of major importance to standardize the generation, analysis, clinical interpretation and reporting of NGS data. To that end, the Spanish MDS Group (GESMD) has expanded the present set of guidelines, aiming to establish common quality standards for the adequate implementation of NGS and clinical interpretation of the results, hoping that this effort will ultimately contribute to the benefit of patients with myeloid malignancies

Contribution for new genetic markers of rheumatoid arthritis activity and severity : sequencing of the tumor necrosis factor-alpha gene promoter

© 2007 Fonseca et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedThe objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.This work was supported by grant POCTI/SAU-ESP/59111/2004 from Fundação Ciência e Tecnologia.info:eu-repo/semantics/publishedVersio

Effects of Trophic Skewing of Species Richness on Ecosystem Functioning in a Diverse Marine Community

Widespread overharvesting of top consumers of the world’s ecosystems has “skewed” food webs, in terms of biomass and species richness, towards a generally greater domination at lower trophic levels. This skewing is exacerbated in locations where exotic species are predominantly low-trophic level consumers such as benthic macrophytes, detritivores, and filter feeders. However, in some systems where numerous exotic predators have been added, sometimes purposefully as in many freshwater systems, food webs are skewed in the opposite direction toward consumer dominance. Little is known about how such modifications to food web topology, e.g., changes in the ratio of predator to prey species richness, affect ecosystem functioning. We experimentally measured the effects of trophic skew on production in an estuarine food web by manipulating ratios of species richness across three trophic levels in experimental mesocosms. After 24 days, increasing macroalgal richness promoted both plant biomass and grazer abundance, although the positive effect on plant biomass disappeared in the presence of grazers. The strongest trophic cascade on the experimentally stocked macroalgae emerged in communities with a greater ratio of prey to predator richness (bottom-rich food webs), while stronger cascades on the accumulation of naturally colonizing algae (primarily microalgae with some early successional macroalgae that recruited and grew in the mesocosms) generally emerged in communities with greater predator to prey richness (the more top-rich food webs). These results suggest that trophic skewing of species richness and overall changes in food web topology can influence marine community structure and food web dynamics in complex ways, emphasizing the need for multitrophic approaches to understand the consequences of marine extinctions and invasions