Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts.

Background: Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies.

Methods: We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia.

Cellulose mediates attachment of Salmonella enterica Serovar Typhimurium to tomatoes.

Fresh fruit and vegetables are important components of a healthy and balanced diet. However, they are increasingly being recognized as important vehicles for transmission of human pathogens that were traditionally classified as zoonotic. There is a significant gap in our knowledge and understanding of the mechanisms by which human pathogens colonize and survive on or in fruits and vegetables.

Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA.

GcvB is one of the most highly conserved Hfq-associated small RNAs in Gram-negative bacteria and was previously reported to repress several ABC transporters for amino acids. To determine the full extent of GcvB-mediated regulation in Salmonella, we combined a genome-wide experimental approach with biocomputational target prediction. Comparative pulse expression of wild-type versus mutant sRNA variants revealed that GcvB governs a large post-transcriptional regulon, impacting ~1% of all Salmonella genes via its conserved G/U-rich domain R1.

Search for a dark matter annihilation signal from the galactic center halo with H.E.S.S.

A search for a very-high-energy (VHE; ≥100  GeV) γ-ray signal from self-annihilating particle dark matter (DM) is performed towards a region of projected distance r∼45-150  pc from the Galactic center. The background-subtracted γ-ray spectrum measured with the High Energy Stereoscopic System (H.E.

Gramicidin A backbone and side chain dynamics evaluated by molecular dynamics simulations and nuclear magnetic resonance experiments. I: molecular dynamics simulations.

Gramicidin A (gA) channels provide an ideal system to test molecular dynamics (MD) simulations of membrane proteins. The peptide backbone lines a cation-selective pore, and due to the small channel size, the average structure and extent of fluctuations of all atoms in the peptide will influence ion permeation. This raises the question of how well molecular mechanical force fields used in MD simulations and potential of mean force (PMF) calculations can predict structure and dynamics as well as ion permeation.

Gramicidin A backbone and side chain dynamics evaluated by molecular dynamics simulations and nuclear magnetic resonance experiments. II: nuclear magnetic resonance experiments.

Motional properties are important for understanding protein function and are accessible to NMR relaxation measurements. The goal of this study is to investigate the internal dynamics occurring in gramicidin A (gA) channels in order to provide benchmark experimental data for comparison with the results of molecular dynamics simulations. We therefore synthesized several (15)N isotope-enriched gA samples, covering all backbone residues as well as the Trp indole side chains for NMR relaxation experiments.

From a single-band metal to a high-temperature superconductor via two thermal phase transitions.

The nature of the pseudogap phase of cuprate high-temperature superconductors is a major unsolved problem in condensed matter physics. We studied the commencement of the pseudogap state at temperature T* using three different techniques (angle-resolved photoemission spectroscopy, polar Kerr effect, and time-resolved reflectivity) on the same optimally doped Bi2201 crystals. We observed the coincident, abrupt onset at T* of a particle-hole asymmetric antinodal gap in the electronic spectrum, a Kerr rotation in the reflected light polarization, and a change in the ultrafast relaxational dynamics, consistent with a phase transition.

The challenge of relating gene expression to the virulence of Salmonella enterica serovar Typhimurium.

The first decade of transcriptomic studies of Salmonella enterica serovar Typhimurium focused upon gene expression in vitro, and during the infection of mammalian cells. The published regulons and stimulons show that the three Type Three Secretion Systems of S. Typhimurium respond to a diverse range of environmental conditions, and are controlled by a hierarchy of regulatory proteins.

Nucleoid-associated protein HU controls three regulons that coordinate virulence, response to stress and general physiology in Salmonella enterica serovar Typhimurium.

The role of the HU nucleoid-associated proteins in gene regulation was examined in Salmonella enterica serovar Typhimurium. The dimeric HU protein consists of different combinations of its α and β subunits. Transcriptomic analysis was performed with cultures growing at 37 °C at 1, 4 and 6 h after inoculation with mutants that lack combinations of HU α and HU β.

An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

Background: In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice.

Methodology/principal Findings: We constructed deletion mutations of 5 TCA cycle genes in S.

Transcriptomic analysis of Escherichia coli O157:H7 and K-12 cultures exposed to inorganic and organic acids in stationary phase reveals acidulant- and strain-specific acid tolerance responses.

The food-borne pathogen Escherichia coli O157:H7 is commonly exposed to organic acid in processed and preserved foods, allowing adaptation and the development of tolerance to pH levels otherwise lethal. Since little is known about the molecular basis of adaptation of E. coli to organic acids, we studied K-12 MG1655 and O157:H7 Sakai during exposure to acetic, lactic, and hydrochloric acid at pH 5.

Microarray analysis of response of Salmonella during infection of HLA-B27- transfected human macrophage-like U937 cells.

Background: Human leukocyte antigen (HLA)-B27 is strongly associated with the development of reactive arthritis (ReA) in humans after salmonellosis. Human monocytic U937 cells transfected with HLA-B27 are less able to eliminate intracellular Salmonella enterica serovar Enteritidis than those transfected with control HLA antigens (e.g.

Unphosphorylated CsgD controls biofilm formation in Salmonella enterica serovar Typhimurium.

The transcriptional regulator CsgD of Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major regulator of biofilm formation required for the expression of csgBA, which encodes curli fimbriae, and adrA, coding for a diguanylate cyclase. CsgD is a response regulator with an N-terminal receiver domain with a conserved aspartate (D59) as a putative target site for phosphorylation and a C-terminal LuxR-like helix-turn-helix DNA binding motif, but the mechanisms of target gene activation remained unclear.

The effect of a forensic fellowship program on general psychiatry residents' in-training examination outcomes.

This article describes how the establishment and existence of a forensic psychiatry fellowship program was associated with improvements in general psychiatry residents' scores on the Psychiatry Resident In-training Examination (PRITE). Four consecutive years of general psychiatry residents' PRITE scores spanning 2 years before and 2 years after implementation of the forensic fellowship program at our institution were compared. Mixed-model statistical analyses accounting for repeated measurements of individual residents across the periods indicated statistically significant improvement in forensic content scores and several other subspecialty areas in which our institution offers educational fellowship programs.

Genome-wide analysis of the H-NS and Sfh regulatory networks in Salmonella Typhimurium identifies a plasmid-encoded transcription silencing mechanism.

The conjugative IncHI1 plasmid pSfR27 from Shigella flexneri 2a strain 2457T encodes the Sfh protein, a paralogue of the global transcriptional repressor H-NS. Sfh allows pSfR27 to be transmitted to new bacterial hosts with minimal impact on host fitness, providing a 'stealth' function whose molecular mechanism has yet to be determined. The impact of the Sfh protein on the Salmonella enterica serovar Typhimurium transcriptome was assessed and binding sites for Sfh in the Salmonella Typhimurium genome were identified by chromatin immunoprecipitation.

Signatures of mutation and selection in the cancer genome.

The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained.

BABAR: an R package to simplify the normalisation of common reference design microarray-based transcriptomic datasets.

Background: The development of DNA microarrays has facilitated the generation of hundreds of thousands of transcriptomic datasets. The use of a common reference microarray design allows existing transcriptomic data to be readily compared and re-analysed in the light of new data, and the combination of this design with large datasets is ideal for 'systems'-level analyses. One issue is that these datasets are typically collected over many years and may be heterogeneous in nature, containing different microarray file formats and gene array layouts, dye-swaps, and showing varying scales of log2- ratios of expression between microarrays.

The transcriptional programme of Salmonella enterica serovar Typhimurium reveals a key role for tryptophan metabolism in biofilms.

Background: Biofilm formation enhances the capacity of pathogenic Salmonella bacteria to survive stresses that are commonly encountered within food processing and during host infection. The persistence of Salmonella within the food chain has become a major health concern, as biofilms can serve as a reservoir for the contamination of food products. While the molecular mechanisms required for the survival of bacteria on surfaces are not fully understood, transcriptional studies of other bacteria have demonstrated that biofilm growth triggers the expression of specific sets of genes, compared with planktonic cells.

Salicylidene acylhydrazide-mediated inhibition of type III secretion system-1 in Salmonella enterica serovar Typhimurium is associated with iron restriction and can be reversed by free iron.

Salmonella enterica serovar Typhimurium is an animal and zoonotic pathogen of worldwide importance. Intestinal colonization, induction of enteritis and systemic translocation by this bacterium requires type III protein secretion. Strategies that target this process have the potential to control infection, pathology and transmission.

Up the Tower of Psychobabel: does lexical anarchy impede research into 'psychological stress'?

The terminology relating to 'psychological stress' is so confused and ambiguous that research in this field - and application of its results - must surely be hampered. Relevant words with conflicting usages and scientific definitions include 'stress' itself, 'stressor', 'strain', 'challenge', 'demand', 'threat', 'resource', 'coping' and 'mental load'. 'Stress' and 'anxiety' are often confounded.

Network analysis of the transcriptional pattern of young and old cells of Escherichia coli during lag phase.

Background: The aging process of bacteria in stationary phase is halted if cells are subcultured and enter lag phase and it is then followed by cellular division. Network science has been applied to analyse the transcriptional response, during lag phase, of bacterial cells starved previously in stationary phase for 1 day (young cells) and 16 days (old cells).

Results: A genome scale network was constructed for E.

The H-NS-like protein StpA represses the RpoS (sigma 38) regulon during exponential growth of Salmonella Typhimurium.

StpA is a paralogue of the nucleoid-associated protein H-NS that is conserved in a range of enteric bacteria and had no known function in Salmonella Typhimurium. We show that 5% of the Salmonella genome is regulated by StpA, which contrasts with the situation in Escherichia coli where deletion of stpA only had minor effects on gene expression. The StpA-dependent genes of S.

PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data.

High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques.

Identifying nearby accelerators of ultrahigh energy cosmic rays using ultrahigh energy (and very high energy) photons.

Ultrahigh energy photons (UHE, E>10(19) eV) are inevitably produced during the propagation of approximately 10(20) eV protons in extragalactic space. Their short interaction lengths (<20 Mpc) at these energies, combined with the impressive sensitivity of the Pierre Auger Observatory detector to these particles, makes them an ideal probe of nearby ultrahigh energy cosmic ray (UHECR) sources. We here discuss the particular case of photons from a single nearby (within 30 Mpc) source in light of the possibility that such an object might be responsible for several of the UHECR events published by the Auger collaboration.