Comparison of CcrM-dependent methylation in and by nanopore sequencing.

Bacteria rely on DNA methylation for restriction-modification systems and epigenetic control of gene expression. Here, we use direct detection of methylated bases by nanopore sequencing to monitor global DNA methylation in Alphaproteobacteria, where use of this technique has not yet been reported. One representative of this order, , relies on DNA methylation to control cell cycle progression, but it is unclear whether other members of this order, such as , depend on the same systems.

MucR protein: Three decades of studies have led to the identification of a new H-NS-like protein.

MucR belongs to a large protein family whose members regulate the expression of virulence and symbiosis genes in α-proteobacteria species. This protein and its homologs were initially studied as classical transcriptional regulators mostly involved in repression of target genes by binding their promoters. Very recent studies have led to the classification of MucR as a new type of Histone-like Nucleoid Structuring (H-NS) protein.

Comparison of CcrM-dependent methylation in and by nanopore sequencing.

Bacteria rely on DNA methylation for restriction-modification systems and epigenetic control of gene expression. Here, we use direct detection of methylated bases by nanopore sequencing to monitor global DNA methylation in Alphaproteobacteria, where use of this technique has not yet been reported. One representative of this order, , relies on DNA methylation to control cell cycle progression, but it is unclear whether other members of this order, such as , depend on the same systems.

MucR acts as an H-NS-like protein to silence virulence genes and structure the nucleoid.

Histone-like nucleoid structuring (H-NS) and H-NS-like proteins coordinate host-associated behaviors in many pathogenic bacteria, often through forming silencer/counter-silencer pairs with signal-responsive transcriptional activators to tightly control gene expression. and related bacteria do not encode H-NS or homologs of known H-NS-like proteins, and it is unclear if they have other proteins that perform analogous functions during pathogenesis. In this work, we provide compelling evidence for the role of MucR as a novel H-NS-like protein in .

Evaluation of a new device to treat negative dysphotopsia.

Purpose: To evaluate the efficacy and safety of Negative Dysphotopsia (ND) Ring implantation for treating and preventing ND.

Setting: Multicentric tertiary eye hospitals.

Design: Prospective interventional cohort study.

A novel formamidase is required for riboflavin biosynthesis in invasive bacteria.

Biosynthesis of riboflavin (RF), the precursor of the redox cofactors FMN and FAD, was thought to be well understood in bacteria, with all the pathway enzymes presumed to be known and essential. Our previous research has challenged this view by showing that, in the bacterium Sinorhizobium meliloti, deletion of the ribBA gene encoding the enzyme that catalyzes the initial steps on the RF biosynthesis pathway only causes a reduction in flavin secretion rather than RF auxotrophy. This finding led us to hypothesize that RibBA participates in the biosynthesis of flavins destined for secretion, whereas S.

Uncovering the Hidden Credentials of Virulence.

Bacteria in the genus are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world's most common zoonoses. strains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals.

Characterizing the transport and utilization of the neurotransmitter GABA in the bacterial pathogen Brucella abortus.

The neurotransmitter gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the human brain; however, it is becoming more evident that this non-proteinogenic amino acid plays multiple physiological roles in biology. In the present study, the transport and function of GABA is studied in the highly infectious intracellular bacterium Brucella abortus. The data show that 3H-GABA is imported by B.

Effect Of Leaf Extract On Platelet Count In Chronic Immune Thrombocytopenic Purpura: A Case Series.

The leaves of have been used to treat thrombocytopenia in Dengue fever in areas where the virus is endemic. This case series describes the use of leaf liquid extract (CPLE) as an adjunctive therapy for four patients receiving standard-of-care treatment for chronic immune thrombocytopenic purpura (ITP). The cases presented here indicate that CPLE may prove beneficial in the management of chronic ITP for patients interested in alternative therapy before progressing to second-line treatments.

The Cation Diffusion Facilitator Family Protein EmfA Confers Resistance to Manganese Toxicity in Brucella abortus 2308 and Is an Essential Virulence Determinant in Mice.

The gene designated in the 2308 genome encodes an ortholog of the cation diffusion facilitator family protein EmfA which has been linked to resistance to Mn toxicity in A null mutant derived from strain 2308 displays increased sensitivity to elevated levels of Mn in the growth medium compared to that of the parent strain but wild-type resistance to Fe, Mg, Zn, Cu, Co, and Ni. Inductively coupled plasma mass spectroscopy also indicates that the mutant retains significantly higher levels of cellular Mn after exposure to this metal than the parent strain, which is consistent with the proposed role of EmfA as a Mn exporter. Phenotypic analysis of mutants indicates that EmfA plays a much more important role in maintaining Mn homeostasis and preventing the toxicity of this metal in than does the Mn-responsive transcriptional regulator Mur.

That's the Way You Do It.

About one-third of the proteins encoded by the bacterial genomes that have been sequenced to date are proteins of "unknown function." Studies aimed at defining the biological functions of these proteins represent an important frontier in prokaryotic biology. The study presented by J.

Identifying the region responsible for Brucella abortus MucR higher-order oligomer formation and examining its role in gene regulation.

MucR is a member of the Ros/MucR family of prokaryotic zinc-finger proteins found in the α-proteobacteria which regulate the expression of genes required for the successful pathogenic and symbiotic interactions of these bacteria with the eukaryotic hosts. The structure and function of their distinctive zinc-finger domain has been well-studied, but only recently the quaternary structure of the full length proteins was investigated demonstrating their ability to form higher-order oligomers. The aim of this study was to identify the region of MucR involved in higher-order oligomer formation by analysing deletion and point mutants of this protein by Light Scattering, and to determine the role that MucR oligomerization plays in the regulatory function of this protein.

The Manganese-Dependent Pyruvate Kinase PykM Is Required for Wild-Type Glucose Utilization by Brucella abortus 2308 and Its Virulence in C57BL/6 Mice.

Pyruvate kinase plays a central role in glucose catabolism in bacteria, and efficient utilization of this hexose has been linked to the virulence of strains in mice. The brucellae produce a single pyruvate kinase which is an ortholog of the manganese (Mn)-dependent pyruvate kinase PykM. A biochemical analysis of the pyruvate kinase and phenotypic analysis of a mutant defective in high-affinity Mn import indicate that this enzyme is an authentic PykM ortholog which functions as a Mn-dependent enzyme The loss of PykM has a negative impact on the capacity of the parental 2308 strain to utilize glucose, fructose, and galactose but not on its ability to utilize ribose, xylose, arabinose, or erythritol, and a mutant displays significant attenuation in C57BL/6 mice.

Endoribonuclease YbeY Is Linked to Proper Cellular Morphology and Virulence in Brucella abortus.

The YbeY endoribonuclease is one of the best-conserved proteins across the kingdoms of life. In the present study, we demonstrated that YbeY in is linked to a variety of important activities, including proper cellular morphology, mRNA transcript levels, and virulence. Deletion of in led to a small-colony phenotype when the bacteria were grown on agar medium, as well as to significant aberrations in the morphology of the bacterial cell as evidenced by electron microscopy.

Just When We Thought We Knew Everything We Needed To Know about Zn Acquisition and Bacterial Pathogenesis.

It is well established that high-affinity zinc importers play essential roles in bacterial virulence, but the studies described by Moreau et al. in this issue (G. B.

Transcriptome-Wide Identification of Hfq-Associated RNAs in Brucella suis by Deep Sequencing.

Unlabelled: Recent breakthroughs in next-generation sequencing technologies have led to the identification of small noncoding RNAs (sRNAs) as a new important class of regulatory molecules. In prokaryotes, sRNAs are often bound to the chaperone protein Hfq, which allows them to interact with their partner mRNA(s). We screened the genome of the zoonotic and human pathogen Brucella suis 1330 for the presence of this class of RNAs.

Short- and Long-term weight changes among United States veterans with diffuse large B-cell lymphoma treated with CHOP chemotherapy.

Identifying weight changes associated with treatment of diffuse large B-cell lymphoma (DLBCL) has the potential to improve the long-term health of survivors. A retrospective cohort of United States veterans with a new diagnosis of DLBCL between October 1, 1998 and September 30, 2008, with follow-up until April 23, 2013, was assembled. Weight changes were evaluated before, during, and after treatment in 1935 DLBCL patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without rituximab (CHOP+/- R).

The quest for a true One Health perspective of brucellosis.

One Health is an interdisciplinary collaboration that aims at mitigating risks to human health arising from microorganisms present in non-human animal species, which have the potential to be transmitted and cause disease in humans. Different degrees of scientific collaboration and sectoral integration are needed for different types of zoonotic diseases, depending on the health and associated economic gains that can be expected from a One Health approach. Indeed, mitigating zoonotic risks related to emerging diseases with pandemic potential is different from mitigating risks related to endemic zoonotic diseases like brucellosis.

Coordinated zinc homeostasis is essential for the wild-type virulence of Brucella abortus.

Unlabelled: Metal homeostasis in bacterial cells is a highly regulated process requiring intricately coordinated import and export, as well as precise sensing of intracellular metal concentrations. The uptake of zinc (Zn) has been linked to the virulence of Brucella abortus; however, the capacity of Brucella strains to sense Zn levels and subsequently coordinate Zn homeostasis has not been described. Here, we show that expression of the genes encoding the zinc uptake system ZnuABC is negatively regulated by the Zn-sensing Fur family transcriptional regulator, Zur, by direct interactions between Zur and the promoter region of znuABC.

Comparative effectiveness of anthracycline-containing chemotherapy in United States veterans age 80 and older with diffuse large B-cell lymphoma.

Objectives: While anthracycline-based treatment can cure diffuse large B-cell lymphoma, most patients over age 80 do not receive doxorubicin due to toxicity concerns. This study evaluated this practice, as patients age 80 and older are largely excluded from clinical trials. The primary outcome of interest was overall survival.

A randomized phase II trial investigating the effect of platelet function inhibition on circulating tumor cells in patients with metastatic breast cancer.

Background: Blockade of platelet activation and aggregation can inhibit metastasis in preclinical models and is associated with cancer prevention. To test whether disruption of platelet function with clopidogrel and aspirin would decrease the number of circulating tumor cells (CTCs) in patients with metastatic breast cancer, a randomized phase II study was performed.

Methods: Patients with metastatic breast cancer who were not currently receiving cytotoxic chemotherapy were eligible.

Bacterial persistence: finding the "sweet spot".

Studies described by Eisele et al. (2013) and Xavier et al. (2013) in this issue of Cell Host & Microbe show that the bacterial pathogens Salmonella and Brucella exploit the increased levels of glucose present in alternatively activated macrophages to sustain chronic infections in experimentally infected mice.