High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.

Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as "collateral" damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR) treatment, HZE (1 GeV Fe(26+) high mass, high charge, and high energy relativistic particles) and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs), but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5-24 h after irradiation) in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the "DSB response" were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing "extended night." This response was not apparent in gamma-irradiated plants

Probiotics and gastrointestinal disease: successes, problems and future prospects

Gastrointestinal disease is a major cause of morbidity and mortality worldwide each year. Treatment of chronic inflammatory gastrointestinal conditions such as ulcerative colitis and Crohn's disease is difficult due to the ambiguity surrounding their precise aetiology. Infectious gastrointestinal diseases, such as various types of diarrheal disease are also becoming increasingly difficult to treat due to the increasing dissemination of antibiotic resistance among microorganisms and the emergence of the so-called 'superbugs'. Taking into consideration these problems, the need for novel therapeutics is essential. Although described for over a century probiotics have only been extensively researched in recent years. Their use in the treatment and prevention of disease, particularly gastrointestinal disease, has yielded many successful results, some of which we outline in this review. Although promising, many probiotics are hindered by inherent physiological and technological weaknesses and often the most clinically promising strains are unusable. Consequently we discuss various strategies whereby probiotics may be engineered to create designer probiotics. Such innovative approaches include; a receptor mimicry strategy to create probiotics that target specific pathogens and toxins, a patho-biotechnology approach using pathogen-derived genes to create more robust probiotic stains with increased host and processing-associated stress tolerance profiles and meta-biotechnology, whereby, functional metagenomics may be used to identify novel genes from diverse and vastly unexplored environments, such as the human gut, for use in biotechnology and medicine

Combined metagenomic and phenomic approaches identify a novel salt tolerance gene from the human gut microbiome

In the current study, a number of salt-tolerant clones previously isolated from a human gut metagenomic library were screened using Phenotype MicroArray (PM) technology to assess their functional capacity. One clone, SMG 9, was found to be positive for utilisation/transport of L-carnitine (a well-characterised osmoprotectant) in the presence of 6% w/v sodium chloride (NaCl). Subsequent experiments revealed a significant growth advantage in minimal media containing NaCl and L-carnitine. Fosmid sequencing revealed putative candidate genes responsible for the phenotype. Subsequent cloning of two genes did not replicate the L-carnitine-associated phenotype, although one of the genes, a σ54-dependent transcriptional regulator, did confer salt tolerance to Escherichia coli when expressed in isolation. The original clone, SMG 9, was subsequently found to have lost the original observed phenotype upon further investigation. Nevertheless, this study demonstrates the usefulness of a phenomic approach to assign a functional role to metagenome-derived clones

Metagenomic Identification of a Novel Salt Tolerance Gene from the Human Gut Microbiome Which Encodes a Membrane Protein with Homology to a brp/blh-Family beta-Carotene 15,15\u27-Monooxygenase

The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane

Malnutrition in the elderly

Changes that occur naturally throughout the ageing process place the elderly population at greater risk of malnourishment. This review discusses the significance, causes, consequences and assessment of malnutrition in the elderly

Scaling Immiscible Flow in Porous Media

Centrifuge modelling is a technique that has proved useful in the study of miscible transport processes through porous media. This report presents a discussion on the feasibility of modelling immiscible flow processes using a geotechnical centrifuge, with particular reference to the phenomena of fingering and residual entrapment. The analysis of scaling for the mechanism of fingering indicates that unstable wetting displacements can be modelled using centrifuge testing techniques. However, scaling analyses for the mechanism of capillary entrapment show that above certain critical Capillary and Bond numbers, the degree of non-aqueous phase liquid entrapment will be lower in a centrifuge model than the corresponding prototype. Nonetheless, it is argued this does not prohibit centrifuge modelling from making a useful contribution towards the study of immiscible flow processes in porous media

Draft Genome Sequence of Campylobacter fetus subsp. fetus CITCf01, Isolated from a Patient with Subacute Bacterial Endocarditis

Campylobacter fetus is a Gram-negative, zoonotic pathogen and a member of the class Epsilonproteobacteria. We report the draft genome sequence of C. fetus subsp. fetus CITCf01, isolated from a patient with subacute bacterial endocarditis. CITCf01 grew under aerobic, microaerobic, and anaerobic conditions, and at 42°C, an unusual combination of growth conditions

Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study.

PURPOSE: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS: High PET score was associated with inferior EFS, before (P .4). CONCLUSION: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL

Centrifuge modelling of contaminant transport processes

Over the past decade, research workers have started to investigate problems of subsurface contaminant transport through physical modelling on a geotechnical centrifuge. A major advantage of this apparatus is its ability to model complex natural systems in a controlled laboratory environment In this paper, we discusses the principles and scaling laws related to the centrifugal modelling of contaminant transport, and presents four examples of recent work that has been carried out in this area. The first two of these examples illustrate the use of centrifugal techniques to investigate contaminant transport mechanisms in geologic formations, while the latter two illustrate the use of the centrifuge as a tool for investigating site remediation strategies. The scope of this work serves to demonstrate the contribution that centrifuge modelling techniques can make in the areas of environmental engineering and contaminant hydrology

Algorithm 743: WAPR: A FORTRAN routine for calculating real values of the W-function

We implement W-function approximation scheme described by Barry et al. A range of tests of the approximations is included so that the code can be assessed on any given machine. Users can calculate W(x) by specifying x itself or by specifying an offset from −exp(−1), the latter option necessitated by rounding errors that can arise for x close to −exp(−1). Results of running the code on a SUN workstation are included