127 research outputs found
The Escherichia coli transcriptome mostly consists of independently regulated modules
Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome
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AdaptaciĂłn cultural al español del instrumento de evaluaciĂłn de funcionalidad fĂsica en Unidad de Paciente CrĂtico: âThe Chelsea Critical Care Physical Assessment Tool (CPAx)â
Las Unidades de Cuidados Intensivos (UCI), presentan una
sobrevida cada vez mayor de los pacientes que ingresan a ellas,
donde se ven enfrentados a una nueva entidad fisiopatolĂłgica
llamada Debilidad Muscular Adquirida en UCI (DAUCI).
Algunos test desarrollados para la evaluaciĂłn de funciĂłn motriz,
que permiten objetivar la progresiĂłn del paciente, son la escala
de fuerza muscular del Medical Research Council (MRC), el
Functional status score for the intensive care unit (FSS-ICU) y
el âChelsea Critical Care Physical Assessment Tool (CPAx). La ventaja del CPAx radica en que este test incluye mayor informaciĂłn
asociada al funcionamiento humano como recomienda la OMS,
incorporando tanto el componente ventilatorio (que también se ve
deteriorado por DAUCI) como neuromuscular lo que permite
al profesional kinesiĂłlogo tener una herramienta objetiva mĂĄs
completa del nivel funcional del paciente.
Para que sea confiable, todo test debe ser validado en el paĂs donde
quiere aplicarse, pero antes de esto debe ser adaptado culturalmente.
El objetivo de este trabajo fue efectuar la adaptaciĂłn transcultural
(AT) al español del test de funcionalidad fĂsica de aplicaciĂłn
kinésica CPAx. Se utilizó el proceso establecido por Beaton y cols
que incluye la formación de un comité de expertos multidisciplinario
que da una visiĂłn integral a la adaptaciĂłn y una prueba piloto en
que kinesiĂłlogos de UCI sin capacitaciĂłn previa del test lo lean,
posteriormente lo apliquen y entreguen sus observaciones.
Conclusiones: Realizar la AT permite dimensionar la importancia
que tiene cada una de las etapas de este proceso. El test es el mismo,
equivalente al original, pero contiene nuestras caracterĂsticas
culturales y condiciones técnicas, que lo hace ser comprensible y
aplicable en nuestro paĂs. Esta adaptaciĂłn transcultural tambiĂ©n
es Ăștil a nivel latinoamericano; para los paĂses de habla hispana
que quieran validarlo tenerlo adaptado al español, hace el proceso
menos complejo.
Palabras clave: EvaluaciĂłn funcional, Unidad de cuidados
intensivos, CPAx, adaptaciĂłn transcultural
Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection
To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity.
Methodology/Principal Findings
Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice.
Conclusion/Significance
We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections
Comparison of hemolytic activity of the intermediate subunit of Entamoeba histolytica and Entamoeba dispar lectins
Galactose and N-acetyl-D-galactosamine-inhibitable lectin of Entamoeba histolytica has roles in pathogenicity and induction of protective immunity in rodent models of amoebiasis. Recently, the intermediate subunit of the lectin, Igl1, of E. histolytica has been shown to have hemolytic activity. However, the corresponding lectin is also expressed in a non-virulent species, Entamoeba dispar, and another subunit, Igl2, is expressed in the protozoa. Therefore, in this study, we compared the activities of Igl1 and Igl2 subunits from E. histolytica and E. dispar using various regions of recombinant Igl proteins expressed in Escherichia coli. The recombinant E. dispar Igl proteins had comparable hemolytic activities with those of E. histolytica Igl proteins. Furthermore, Igl1 gene-silenced E. histolytica trophozoites showed less hemolytic activity compared with vector-transfected trophozoites, indicating that the expression level of Igl1 protein influences the activity. These results suggest that the lower hemolytic activity in E. dispar compared with E. histolytica reflects the lower expression level of Igl1 in the E. dispar parasite
HE-LHC: The High-Energy Large Hadron Collider â Future Circular Collider Conceptual Design Report Volume 4
In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
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