The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma

The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel–/– mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg-driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the Eμ-Myc lymphoma cells but, counterintuitively, c-rel–/– Eμ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B cells from 4-week-old, wild-type and c-rel–/– Eμ-Myc mice. Extensive changes in gene expression were not seen at this age, but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Quantitative PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant Eμ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover, Bach2 expression was also downregulated in c-rel–/– TCL1-Tg mice and RelA Thr505Ala mutant Eμ-Myc mice. Analysis of wild-type Eμ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel–/– mice. Confirming the relevance of these findings to human disease, analysis of chromatin immunoprecipitation sequencing data revealed that Bach2 is a c-Rel and NF-κB target gene in transformed human B cells, whereas treatment of Burkitt's lymphoma cells with inhibitors of the NF-κB/IκB kinase pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. These data reveal a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context-dependent complexity of NF-κB signalling in cancer

Sediment Composition Influences Spatial Variation in the Abundance of Human Pathogen Indicator Bacteria within an Estuarine Environment

Faecal contamination of estuarine and coastal waters can pose a risk to human health, particularly in areas used for shellfish production or recreation. Routine microbiological water quality testing highlights areas of faecal indicator bacteria (FIB) contamination within the water column, but fails to consider the abundance of FIB in sediments, which under certain hydrodynamic conditions can become resuspended. Sediments can enhance the survival of FIB in estuarine environments, but the influence of sediment composition on the ecology and abundance of FIB is poorly understood. To determine the relationship between sediment composition (grain size and organic matter) and the abundance of pathogen indicator bacteria (PIB), sediments were collected from four transverse transects of the Conwy estuary, UK. The abundance of culturable Escherichia coli, total coliforms, enterococci, Campylobacter, Salmonella and Vibrio spp. in sediments was determined in relation to sediment grain size, organic matter content, salinity, depth and temperature. Sediments that contained higher proportions of silt and/or clay and associated organic matter content showed significant positive correlations with the abundance of PIB. Furthermore, the abundance of each bacterial group was positively correlated with the presence of all other groups enumerated. Campylobacter spp. were not isolated from estuarine sediments. Comparisons of the number of culturable E. coli, total coliforms and Vibrio spp. in sediments and the water column revealed that their abundance was 281, 433 and 58-fold greater in sediments (colony forming units (CFU)/100 g) when compared with the water column (CFU/100 ml), respectively. These data provide important insights into sediment compositions that promote the abundance of PIB in estuarine environments, with important implications for the modelling and prediction of public health risk based on sediment resuspension and transport

Decay rates of faecal indicator bacteria from sewage and ovine faeces in brackish and freshwater microcosms with contrasting suspended particulate matter concentrations

AbstractTo safeguard human health, legislative measures require the monitoring of faecal indicator bacteria (FIB) concentrations in recreational and shellfish waters. Consequently, numerous studies have focussed on FIB survival in the water column and more recently in estuarine sediments. However, there is a paucity of information regarding the influence of contrasting suspended particulate matter (SPM) concentrations on the survival of FIB in the water column of estuaries. Here, microcosms containing freshwater or brackish water with low, high and extreme SPM concentrations were inoculated with sewage and ovine faeces and the decay rate of Escherichia coli, coliforms and enterococci were determined by enumeration over five consecutive days. E. coli derived from ovine faeces proliferated and persisted at high levels in both freshwater and brackish microcosms (no decay), whereas ovine enterococci demonstrated a net decay over the duration of the experiment. Furthermore, SPM concentration had a significant effect on the decay rates of both E. coli and enterococci from ovine faeces in brackish microcosms, but decay rate was greater at low SPM concentrations for E. coli, whereas the opposite was observed for enterococci, whose decay rates increased as SPM concentration increased. E. coli, enterococci and coliforms derived from wastewater demonstrated a net decay in both freshwater and brackish microcosms, with contrasting effects of SPM concentration on decay rate. In addition, some FIB groups demonstrated contrasting responses (decay or proliferation) in the first 24h following inoculation into freshwater versus brackish microcosms. Overall, SPM concentrations influenced the proliferation and decay rates of FIB in brackish waters, but had minimal influence in freshwater. These results demonstrate that the survival rates of FIB in aquatic environments are system specific, species and source dependent, and influenced by SPM concentration. This study has important implications for catchment-based risk assessments and source apportionment of FIB pollution in aquatic environments

Using chemical, microbial and fluorescence techniques to understand contaminant sources and pathways to wetlands in a conservation site

Nutrients and faecal contaminants can enter wetland systems in a number of ways, with both biological and potentially human-health implications. In this study we used a combination of inorganic chemistry, dissolved organic matter (DOM) fluorescence and Escherichia coli and total coliform (TC) count techniques to study the sources and multiple pathways of contamination affecting a designated sand dune site of international conservation importance, surrounded by agricultural land. Analysis of stream samples, groundwater and dune slack wetlands revealed multiple input pathways. These included riverbank seepage, runoff events and percolation of nutrients from adjacent pasture into the groundwater, as well as some on-site sources. The combined techniques showed that off-site nutrient inputs into the sand dune system were primarily from fertilisers, revealed by high nitrate concentrations, and relatively low tryptophan-like fulvic-like ratios < 0.4 Raman units (R.U.). The E. coli and TC counts recorded across the site confirm a relatively minor source of bacterial and nutrient inputs from on-site grazers. Attenuation of the nutrient concentrations in streams, in groundwater and in run-off inputs occurs within the site, restoring healthier groundwater nutrient concentrations showing that contaminant filtration by the sand dunes provides a valuable ecosystem service. However, previous studies show that this input of nutrients has a clear adverse ecological impact

The interaction of human microbial pathogens, particulate material and nutrients in estuarine environments and their impacts on recreational and shellfish waters

Anthropogenic activities have increased the load of faecal bacteria, pathogenic viruses and nutrients in rivers, estuaries and coastal areas through point and diffuse sources such as sewage discharges and agricultural runoff. These areas are used by humans for both commercial and recreational activities and are therefore protected by a range of European Directives. If water quality declines in these zones, significant economic losses can occur. Identifying the sources of pollution, however, is notoriously difficult due to the ephemeral nature of discharges, their diffuse source, and uncertainties associated with transport and transformation of the pollutants through the freshwater–marine interface. Further, significant interaction between nutrients, microorganisms and particulates can occur in the water column making prediction of the fate and potential infectivity of human pathogenic organisms difficult to ascertain. This interaction is most prevalent in estuarine environments due to the formation of flocs (suspended sediment) at the marine-freshwater interface. A range of physical, chemical and biological processes can induce the co-flocculation of microorganisms, organic matter and mineral particles resulting in pathogenic organisms becoming potentially protected from a range of biotic (e.g. predation) and abiotic stresses (e.g. UV, salinity). These flocs contain and retain macro- and micro- nutrients allowing the potential survival, growth and transfer of pathogenic organisms to commercially sensitive areas (e.g. beaches, shellfish harvesting waters). The flocs can either be transported directly to the coastal environment or can become deposited in the estuary forming cohesive sediments where pathogens can survive for long periods. Especially in response to storms, these sediments can be subsequently remobilised releasing pulses of potential pathogenic organisms back into the water column leading to contamination of marine waters long after the initial contamination event occurred. Further work, however, is still required to understand and predict the potential human infectivity of pathogenic organisms alongside the better design of early warning systems and surveillance measures for risk assessment purposes

Scaling anomaly in cosmic string background

We show that the classical scale symmetry of a particle moving in cosmic string background is broken upon inequivalent quantization of the classical system, leading to anomaly. The consequence of this anomaly is the formation of single bound state in the coupling interval \gamma\in(-1,1). The inequivalent quantization is characterized by a 1-parameter family of self-adjoint extension parameter \omega. It has been conjectured that the formation of loosely bound state in cosmic string background may lead to the so called anomalous scattering cross section for the particles, which is usually seen in molecular physics.Comment: 4 pages,1 figur

Cervical spine immobilisation following blunt trauma in pre-hospital and emergency care: a systematic review

Objectives To assess whether different cervical spine immobilisation strategies (full immobilisation, movement minimisation or no immobilisation), impact neurological and/or other outcomes for patients with suspected cervical spinal injury in the pre-hospital and emergency department setting. Design Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources MEDLINE, EMBASE, CINAHL, Cochrane Library and two research registers were searched until September 2023. Eligibility criteria All comparative studies (prospective or retrospective) that examined the potential benefits and/or harms of immobilisation practices during pre-hospital and emergency care of patients with a potential cervical spine injury (pre-imaging) following blunt trauma. Data extraction and synthesis Two authors independently selected and extracted data. Risk of bias was appraised using the Cochrane ROBINS-I tool for non-randomised studies. Data were synthesised without meta-analysis. Results Six observational studies met the inclusion criteria. The methodological quality was variable, with most studies having serious or critical risk of bias. The effect of cervical spine immobilisation practices such as full immobilisation or movement minimisation during pre-hospital and emergency care did not show clear evidence of benefit for the prevention of neurological deterioration, spinal injuries and death compared with no immobilisation. However, increased pain, discomfort and anatomical complications were associated with collar application during immobilisation. Conclusions Despite the limited evidence, weak designs and limited generalisability, the available data suggest that pre-hospital cervical spine immobilisation (full immobilisation or movement minimisation) was of uncertain value due to the lack of demonstrable benefit and may lead to potential complications and adverse outcomes. High-quality randomised comparative studies are required to address this important question

Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV

We report the STAR measurement of Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV. Using the event mixing technique, the Phi spectra and yields are obtained at mid-rapidity for five centrality bins in Au+Au collisions and for non-singly-diffractive p+p collisions. It is found that the Phi transverse momentum distributions from Au+Au collisions are better fitted with a single-exponential while the p+p spectrum is better described by a double-exponential distribution. The measured nuclear modification factors indicate that Phi production in central Au+Au collisions is suppressed relative to peripheral collisions when scaled by the number of binary collisions. The systematics of versus centrality and the constant Phi/K- ratio versus beam species, centrality, and collision energy rule out kaon coalescence as the dominant mechanism for Phi production.Comment: 6 pages, 3 figures, submitted to Phys. Rev. Let

Azimuthal anisotropy and correlations in p+p, d+Au and Au+Au collisions at 200 GeV

We present the first measurement of directed flow ($v_1$) at RHIC. $v_1$ is found to be consistent with zero at pseudorapidities $\eta$ from -1.2 to 1.2, then rises to the level of a couple of percent over the range $2.4 < |\eta| < 4$. The latter observation is similar to data from NA49 if the SPS rapidities are shifted by the difference in beam rapidity between RHIC and SPS. Back-to-back jets emitted out-of-plane are found to be suppressed more if compared to those emitted in-plane, which is consistent with {\it jet quenching}. Using the scalar product method, we systematically compared azimuthal correlations from p+p, d+Au and Au+Au collisions. Flow and non-flow from these three different collision systems are discussed.Comment: Quark Matter 2004 proceeding, 4 pages, 3 figure