NF-κB p50 facilitates neutrophil accumulation during LPS-induced pulmonary inflammation

BACKGROUND: Transcription factors have distinct functions in regulating immune responses. During Escherichia coli pneumonia, deficiency of NF-κB p50 increases gene expression and neutrophil recruitment, suggesting that p50 normally limits these innate immune responses. p50-deficient mice were used to determine how p50 regulates responses to a simpler, non-viable bacterial stimulus in the lungs, E. coli lipopolysaccharide (LPS). RESULTS: In contrast to previous results with living E. coli, neutrophil accumulation elicited by E. coli LPS in the lungs was decreased by p50 deficiency, to approximately 30% of wild type levels. Heat-killed E. coli induced neutrophil accumulation which was not decreased by p50 deficiency, demonstrating that bacterial growth and metabolism were not responsible for the different responses to bacteria and LPS. p50 deficiency increased the LPS-induced expression of κB-regulated genes essential to neutrophil recruitment, including KC, MIP-2, ICAM-1, and TNF-α suggesting that p50 normally limited this gene expression and that decreased neutrophil recruitment did not result from insufficient expression of these genes. Neutrophils were responsive to the chemokine KC in the peripheral blood of p50-deficient mice with or without LPS-induced pulmonary inflammation. Interleukin-6 (IL-6), previously demonstrated to decrease LPS-induced neutrophil recruitment in the lungs, was increased by p50 deficiency, but LPS-induced neutrophil recruitment was decreased by p50 deficiency even in IL-6 deficient mice. CONCLUSION: p50 makes essential contributions to neutrophil accumulation elicited by LPS in the lungs. This p50-dependent pathway for neutrophil accumulation can be overcome by bacterial products other than LPS and does not require IL-6

Exponential dichotomies of evolution operators in Banach spaces

This paper considers three dichotomy concepts (exponential dichotomy, uniform exponential dichotomy and strong exponential dichotomy) in the general context of non-invertible evolution operators in Banach spaces. Connections between these concepts are illustrated. Using the notion of Green function, we give necessary conditions and sufficient ones for strong exponential dichotomy. Some illustrative examples are presented to prove that the converse of some implication type theorems are not valid

Family dairy farms in the Podlasie province, Poland: farm typology according to farming system

The aim of this paper is to establish a farm typology according to the dairy farming systems in the western part of the Podlasie province. Data of 39 variables was collected by a survey to owners of 123 family farms. A two-stage multivariate analysis was conducted in order to determine farm typology. Three principal components were detected, explaining 80.4% of the total variance. The cluster analysis identified five groups of farms. In two groups the cow productivity is the biggest in the area. A third group contains the smallest and lowest cow productivity farms, with high proportion of non-agricultural activities. One of the two remaining groups has better soil quality and medium cow productivity. The other group has low or medium soil quality but cow productivity is higher than in the fourth group. The SWOT analysis shows different weaknesses and strengths for different groups, as well as those common to a larger number of groups. Weaknesses are related to small farm size, large number of workers, low or medium soil quality and low or medium level of technology. Strengths are related to a large share of fodder crops, low livestock density, diversification of agrarian activities and acceptable cow productivity. On the other hand, general opportunities are linked to the EU-CAP evolution and to the presence of cooperatives in the region, whereas general threats derive from a hypothetic increase of feed prices and quantity of milk produced in the EU, which could lead to a fall in milk prices.El objetivo de este trabajo es establecer tipologías de sistemas lecheros en el oeste de Podlasia (Polonia). Se analizaron 39 variables a partir de encuestas realizadas a propietarios de 123 explotaciones. Tras el análisis multivariante en dos etapas (factorial y cluster) se encontraron tres componentes principales que explican el 80,4% de la varianza total y se obtuvieron cinco grupos de explotaciones. En dos de los grupos la productividad de las vacas es la mayor de la zona. Un tercer grupo tiene las granjas más pequeñas y menos productivas, con una mayor proporción de actividades no agrarias. El cuarto tiene los suelos de mejor calidad y una productividad de las vacas media y el quinto tiene suelos de calidad media o baja pero una productividad de las vacas superior. En general, las debilidades están relacionadas con una escasa dimensión de las granjas, un elevado número de trabajadores, una baja o media calidad de los suelos y un bajo o mediano nivel de tecnología. Las fortalezas están relacionadas con la abundancia de cultivos forrajeros, una carga ganadera baja, una aceptable diversificación agraria y una aceptable productividad de las vacas. Las principales oportunidades están ligadas a la evolución de la PAC de la UE y a la presencia de cooperativas para la comercialización de la leche. Las principales amenazas derivan de los posibles incrementos de precios de los alimentos para el ganado y de leche producida en la UE, que puede conducir a una caída de los precios de venta de la leche

The Effect of an Enhanced Recovery Protocol on Pediatric Colorectal Surgical Patient Outcomes at a Single Institution

Introduction Enhanced recovery protocols (ERP) have been associated with fewer postoperative complications in adult colorectal surgery patients, but there is a paucity of data on pediatric patients. Our aim is to describe the effect of an ERP, compared to conventional care, on pediatric colorectal surgical complications. Materials and Methods We performed a single institution, retrospective cohort study (2014-2020) on pediatric (≤18 years old) colorectal surgery patients pre- and post-implementation of an ERP. Bivariate analysis and logistic regression were used to assess the effect of an ERP on return visits to the emergency room, reoperation, and readmission within 30-days. Results There were 194 patients included in this study, with 54 in the control cohort and 140 in the ERP cohort. There was no significant difference in the age, BMI, primary diagnosis, or use of laparoscopic technique between the cohorts. The ERP cohort had a significantly shorter foley duration, postoperative stay, and had nerve blocks performed. After controlling for pertinent covariates, the ERP cohort experienced higher odds of reoperation within 30 days (OR 5.83, P = .04). There was no significant difference in the other outcomes analyzed. Conclusion In this study, there was no difference in the odds of overall complications, readmission or return to the ER within 30-days of surgery. However, although infrequent, there were higher odds of returns to the OR within 30 days. Future studies are needed to analyze how adherence to individual components may influence patient outcomes to ensure patient safety during ERP implementation

Proteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts

We analyzed an ex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the differentially abundant proteins have not been described in the context of fibroblasts' aging before, but the deduced biological processes confirmed known hallmarks of aging and led to a consistent picture of eight biological categories involved in fibroblast aging, namely proteostasis, cell cycle and proliferation, development and differentiation, cell death, cell organization and cytoskeleton, response to stress, cell communication and signal transduction, as well as RNA metabolism and translation. The exhaustive analysis of protein and mRNA data revealed that 77 % of the age-associated proteins were not linked to expression changes of the corresponding transcripts. This is in line with an associated miRNA study and led us to the conclusion that most of the age-associated alterations detected at the proteome level are likely caused post-transcriptionally rather than by differential gene expression. In summary, our findings led to the characterization of novel proteins potentially associated with fibroblast aging and revealed that primary cultures of in situ aged fibroblasts are characterized by moderate age-related proteomic changes comprising the multifactorial process of aging

Genomic Characterization of Methanomicrobiales Reveals Three Classes of Methanogens

BACKGROUND:Methanomicrobiales is the least studied order of methanogens. While these organisms appear to be more closely related to the Methanosarcinales in ribosomal-based phylogenetic analyses, they are metabolically more similar to Class I methanogens. METHODOLOGY/PRINCIPAL FINDINGS:In order to improve our understanding of this lineage, we have completely sequenced the genomes of two members of this order, Methanocorpusculum labreanum Z and Methanoculleus marisnigri JR1, and compared them with the genome of a third, Methanospirillum hungatei JF-1. Similar to Class I methanogens, Methanomicrobiales use a partial reductive citric acid cycle for 2-oxoglutarate biosynthesis, and they have the Eha energy-converting hydrogenase. In common with Methanosarcinales, Methanomicrobiales possess the Ech hydrogenase and at least some of them may couple formylmethanofuran formation and heterodisulfide reduction to transmembrane ion gradients. Uniquely, M. labreanum and M. hungatei contain hydrogenases similar to the Pyrococcus furiosus Mbh hydrogenase, and all three Methanomicrobiales have anti-sigma factor and anti-anti-sigma factor regulatory proteins not found in other methanogens. Phylogenetic analysis based on seven core proteins of methanogenesis and cofactor biosynthesis places the Methanomicrobiales equidistant from Class I methanogens and Methanosarcinales. CONCLUSIONS/SIGNIFICANCE:Our results indicate that Methanomicrobiales, rather than being similar to Class I methanogens or Methanomicrobiales, share some features of both and have some unique properties. We find that there are three distinct classes of methanogens: the Class I methanogens, the Methanomicrobiales (Class II), and the Methanosarcinales (Class III)

Connecting Peptide Physicochemical and Antimicrobial Properties by a Rational Prediction Model

The increasing rate in antibiotic-resistant bacterial strains has become an imperative health issue. Thus, pharmaceutical industries have focussed their efforts to find new potent, non-toxic compounds to treat bacterial infections. Antimicrobial peptides (AMPs) are promising candidates in the fight against antibiotic-resistant pathogens due to their low toxicity, broad range of activity and unspecific mechanism of action. In this context, bioinformatics' strategies can inspire the design of new peptide leads with enhanced activity. Here, we describe an artificial neural network approach, based on the AMP's physicochemical characteristics, that is able not only to identify active peptides but also to assess its antimicrobial potency. The physicochemical properties considered are directly derived from the peptide sequence and comprise a complete set of parameters that accurately describe AMPs. Most interesting, the results obtained dovetail with a model for the AMP's mechanism of action that takes into account new concepts such as peptide aggregation. Moreover, this classification system displays high accuracy and is well correlated with the experimentally reported data. All together, these results suggest that the physicochemical properties of AMPs determine its action. In addition, we conclude that sequence derived parameters are enough to characterize antimicrobial peptides