Determining the Competitive Edge: Diversified Dairy Production Systems in the United States and the European Union

Agricultural and Food Policy, Farm Management, Livestock Production/Industries, Production Economics, Productivity Analysis,

A Novel Signaling Network Essential for Regulating Pseudomonas aeruginosa Biofilm Development

The important human pathogen Pseudomonas aeruginosa has been linked to numerous biofilm-related chronic infections. Here, we demonstrate that biofilm formation following the transition to the surface attached lifestyle is regulated by three previously undescribed two-component systems: BfiSR (PA4196-4197) harboring an RpoD-like domain, an OmpR-like BfmSR (PA4101-4102), and MifSR (PA5511-5512) belonging to the family of NtrC-like transcriptional regulators. These two-component systems become sequentially phosphorylated during biofilm formation. Inactivation of bfiS, bfmR, and mifR arrested biofilm formation at the transition to the irreversible attachment, maturation-1 and -2 stages, respectively, as indicated by analyses of biofilm architecture, and protein and phosphoprotein patterns. Moreover, discontinuation of bfiS, bfmR, and mifR expression in established biofilms resulted in the collapse of biofilms to an earlier developmental stage, indicating a requirement for these regulatory systems for the development and maintenance of normal biofilm architecture. Interestingly, inactivation did not affect planktonic growth, motility, polysaccharide production, or initial attachment. Further, we demonstrate the interdependency of this two-component systems network with GacS (PA0928), which was found to play a dual role in biofilm formation. This work describes a novel signal transduction network regulating committed biofilm developmental steps following attachment, in which phosphorelays and two sigma factor-dependent response regulators appear to be key components of the regulatory machinery that coordinates gene expression during P. aeruginosa biofilm development in response to environmental cues

World squid fisheries

Peer reviewedPublisher PD

Bistability in a Metabolic Network Underpins the De Novo Evolution of Colony Switching in Pseudomonas fluorescens

Phenotype switching is commonly observed in nature. This prevalence has allowed the elucidation of a number of underlying molecular mechanisms. However, little is known about how phenotypic switches arise and function in their early evolutionary stages. The first opportunity to provide empirical insight was delivered by an experiment in which populations of the bacterium Pseudomonas fluorescens SBW25 evolved, de novo, the ability to switch between two colony phenotypes. Here we unravel the molecular mechanism behind colony switching, revealing how a single nucleotide change in a gene enmeshed in central metabolism (carB) generates such a striking phenotype. We show that colony switching is underpinned by ON/OFF expression of capsules consisting of a colanic acid-like polymer. We use molecular genetics, biochemical analyses, and experimental evolution to establish that capsule switching results from perturbation of the pyrimidine biosynthetic pathway. Of central importance is a bifurcation point at which uracil triphosphate is partitioned towards either nucleotide metabolism or polymer production. This bifurcation marks a cell-fate decision point whereby cells with relatively high pyrimidine levels favour nucleotide metabolism (capsule OFF), while cells with lower pyrimidine levels divert resources towards polymer biosynthesis (capsule ON). This decision point is present and functional in the wild-type strain. Finally, we present a simple mathematical model demonstrating that the molecular components of the decision point are capable of producing switching. Despite its simple mutational cause, the connection between genotype and phenotype is complex and multidimensional, offering a rare glimpse of how noise in regulatory networks can provide opportunity for evolution

Cardiac Sarcoidosis: When and How to Treat Inflammation

Sarcoidosis is a complex, multisystem inflammatory disease with a heterogeneous clinical spectrum. Approximately 25% of patients with systemic sarcoidosis will have cardiac involvement that portends a poorer outcome. The diagnosis, particularly of isolated cardiac sarcoidosis, can be challenging. A paucity of randomised data exist on who, when and how to treat myocardial inflammation in cardiac sarcoidosis. Despite this, corticosteroids continue to be the mainstay of therapy for the inflammatory phase, with an evolving role for steroid-sparing and biological agents. This review explores the immunopathogenesis of inflammation in sarcoidosis, current evidence-based treatment indications and commonly used immunosuppression agents. It explores a multidisciplinary treatment and monitoring approach to myocardial inflammation and outlines current gaps in our understanding of this condition, emerging research and future directions in this field

SETDB1 Is Involved in Postembryonic DNA Methylation and Gene Silencing in Drosophila

DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells. However, the factors and mechanisms involved in dynamic, postembryonic DNA methylation remain unclear. Methylation of lysine 9 in histone H3 (H3-K9) by members of the Su(var)3–9 family of histone methyltransferases (HMTs) triggers embryonic DNA methylation in Arthropods and Chordates. Here, we demonstrate that Drosophila SETDB1 (dSETDB1) can mediate DNA methylation and silencing of genes and retrotransposons. We found that dSETDB1 tri-methylates H3-K9 and binds methylated CpA motifs. Tri-methylation of H3-K9 by dSETDB1 mediates recruitment of DNA methyltransferase 2 (Dnmt2) and Su(var)205, the Drosophila ortholog of mammalian “Heterochromatin Protein 1”, to target genes for dSETDB1. By enlisting Dnmt2 and Su(var)205, dSETDB1 triggers DNA methylation and silencing of genes and retrotransposons in Drosophila cells. DSETDB1 is involved in postembryonic DNA methylation and silencing of Rt1b{} retrotransposons and the tumor suppressor gene retinoblastoma family protein 1 (Rb) in imaginal discs. Collectively, our findings implicate dSETDB1 in postembryonic DNA methylation, provide a model for silencing of the tumor suppressor Rb, and uncover a role for cell type-specific DNA methylation in Drosophila development

Caenorhabditis elegans: a model to monitor bacterial air quality

<p>Abstract</p> <p>Background</p> <p>Low environmental air quality is a significant cause of mortality and morbidity and this question is now emerging as a main concern of governmental authorities. Airborne pollution results from the combination of chemicals, fine particles, and micro-organisms quantitatively or qualitatively dangerous for health or for the environment. Increasing regulations and limitations for outdoor air quality have been decreed in regards to chemicals and particles contrary to micro-organisms. Indeed, pertinent and reliable tests to evaluate this biohazard are scarce. In this work, our purpose was to evaluate the <it>Caenorhaditis elegans </it>killing test, a model considered as an equivalent to the mouse acute toxicity test in pharmaceutical industry, in order to monitor air bacterial quality.</p> <p>Findings</p> <p>The present study investigates the bacterial population in dust clouds generated during crop ship loading in harbor installations (Rouen harbor, Normandy, France). With a biocollector, airborne bacteria were impacted onto the surface of agar medium. After incubation, a replicate of the colonies on a fresh agar medium was done using a velvet. All the replicated colonies were pooled creating the "Total Air Sample". Meanwhile, all the colonies on the original plate were isolated. Among which, five representative bacterial strains were chosen. The virulence of these representatives was compared to that of the "Total Air Sample" using the <it>Caenorhaditis elegans </it>killing test. The survival kinetic of nematodes fed with the "Total Air Sample" is consistent with the kinetics obtained using the five different representatives strains.</p> <p>Conclusions</p> <p>Bacterial air quality can now be monitored in a one shot test using the <it>Caenorhaditis elegans </it>killing test.</p

Does the Degree of Hepatocellular Carcinoma Tumor Necrosis following Transarterial Chemoembolization Impact Patient Survival?

Purpose. The association between transarterial chemoembolization- (TACE-) induced HCC tumor necrosis measured by the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and patient survival is poorly defined. We hypothesize that survival will be superior in HCC patients with increased TACE-induced tumor necrosis. Materials and Methods. TACE interventions were retrospectively reviewed. Tumor response was quantified via dichotomized (responders and nonresponders) and the four defined mRECIST categories. Results. Median survival following TACE was significantly greater in responders compared to nonresponders (20.8 months versus 14.9 months, p=0.011). Survival outcomes also significantly varied among the four mRECIST categories (p=0.0003): complete, 21.4 months; partial, 20.8; stable, 16.8; and progressive, 7.73. Only progressive disease demonstrated significantly worse survival when compared to complete response. Multivariable analysis showed that progressive disease, increasing total tumor diameter, and non-Child-Pugh class A were independent predictors of post-TACE mortality. Conclusions. Both dichotomized (responders and nonresponders) and the four defined mRECIST responses to TACE in patients with HCC were predictive of survival. The main driver of the survival analysis was poor survival in the progressive disease group. Surprisingly, there was small nonsignificant survival benefit between complete, partial, and stable disease groups. These findings may inform HCC treatment decisions following first TACE