NetB, a New Toxin That Is Associated with Avian Necrotic Enteritis Caused by Clostridium perfringens

For over 30 years a phospholipase C enzyme called alpha-toxin was thought to be the key virulence factor in necrotic enteritis caused by Clostridium perfringens. However, using a gene knockout mutant we have recently shown that alpha-toxin is not essential for pathogenesis. We have now discovered a key virulence determinant. A novel toxin (NetB) was identified in a C. perfringens strain isolated from a chicken suffering from necrotic enteritis (NE). The toxin displayed limited amino acid sequence similarity to several pore forming toxins including beta-toxin from C. perfringens (38% identity) and alpha-toxin from Staphylococcus aureus (31% identity). NetB was only identified in C. perfringens type A strains isolated from chickens suffering NE. Both purified native NetB and recombinant NetB displayed cytotoxic activity against the chicken leghorn male hepatoma cell line LMH; inducing cell rounding and lysis. To determine the role of NetB in NE a netB mutant of a virulent C. perfringens chicken isolate was constructed by homologous recombination, and its virulence assessed in a chicken disease model. The netB mutant was unable to cause disease whereas the wild-type parent strain and the netB mutant complemented with a wild-type netB gene caused significant levels of NE. These data show unequivocally that in this isolate a functional NetB toxin is critical for the ability of C. perfringens to cause NE in chickens. This novel toxin is the first definitive virulence factor to be identified in avian C. perfringens strains capable of causing NE. Furthermore, the netB mutant is the first rationally attenuated strain obtained in an NE-causing isolate of C. perfringens; as such it has considerable vaccine potential

The ultraviolet colour of globular clusters in M31: a core density effect?

We investigate the effect of stellar density on the ultraviolet (UV) emission from M31's globular clusters (GCs). Published far-UV (FUV) and near-UV (NUV) colours from Galaxy Evolution and Explorer (GALEX) observations are used as a probe into the temperature of the horizontal branch (HB) stars in these clusters. From these data, we demonstrate a significant relationship between the core density of a cluster and its FUV-NUV colour, with dense clusters having bluer ultraviolet colours. These results are consistent with a population of (FUV bright) extreme-HB (EHB) stars, the production of which is related to the stellar density in the clusters. Such a relationship may be expected if the formation of EHB stars is enhanced in dense clusters due to dynamical interactions. We also consider the contribution of low mass X-ray binaries (LMXBs) to the integrated FUV luminosity of a cluster. We note that two of the three metal rich clusters, identified by Rey et al. 2007 as having a FUV excess, are known to host LMXBs in outburst. Considering the FUV luminosity of Galactic LMXBs, we suggest that a single LMXB is unlikely to produce more than 10% of the observed FUV luminosity of clusters that contain a significant population of blue-HB stars.Comment: Accepted for publication in MNRAS, 9 pages, 6 figures and 1 tabl

Selective Involvement of the Amygdala in Systemic Lupus Erythematosus

BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE. METHODS AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 × 10(−6) mm(2)/s; p = 0.006 and 949 × 10(−6) mm(2)/s; p = 0.019, respectively) was lower than in healthy control participants (1152 × 10(−6) mm(2)/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 × 10(−6) mm(2)/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 × 10(−6) mm(2)/s) and also lower (p = 0.001) than in healthy control participants. CONCLUSIONS: This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies

Gravel-bed river floodplains are the ecological nexus of glaciated mountain landscapes

Sherpa Romeo green journal: open accessGravel-bed river floodplains in mountain landscapes disproportionately concentrate diverse habitats, nutrient cycling, productivity of biota, and species interactions. Although stream ecologists know that river channel and floodplain habitats used by aquatic organisms are maintained by hydrologic regimes that mobilize gravel-bed sediments, terrestrial ecologists have largely been unaware of the importance of floodplain structures and processes to the life requirements of a wide variety of species. We provide insight into gravel-bed rivers as the ecological nexus of glaciated mountain landscapes. We show why gravel-bed river floodplains are the primary arena where interactions take place among aquatic, avian, and terrestrial species from microbes to grizzly bears and provide essential connectivity as corridors for movement for both aquatic and terrestrial species. Paradoxically, gravel-bed river floodplains are also disproportionately unprotected where human developments are concentrated. Structural modifications to floodplains such as roads, railways, and housing and hydrologicaltering hydroelectric or water storage dams have severe impacts to floodplain habitat diversity and productivity, restrict local and regional connectivity, and reduce the resilience of both aquatic and terrestrial species, including adaptation to climate change. To be effective, conservation efforts in glaciated mountain landscapes intended to benefit the widest variety of organisms need a paradigm shift that has gravel-bed rivers and their floodplains as the central focus and that prioritizes the maintenance or restoration of the intact structure and processes of these critically important systems throughout their length and breadth.Ye

A field investigation of phreatophyte-induced fluctuations in the water table

This is the published version. Copyright American Geophysical Union[1] Hydrographs from shallow wells in vegetated riparian zones frequently display a distinctive pattern of diurnal water table fluctuations produced by variations in plant water use. A multisite investigation assessed the major controls on these fluctuations and the ecohydrologic insights that can be gleaned from them. Spatial and temporal variations in the amplitude of the fluctuations are primarily a function of variations in (1) the meteorological drivers of plant water use, (2) vegetation density, type, and vitality, and (3) the specific yield of sediments in the vicinity of the water table. Past hydrologic conditions experienced by the riparian zone vegetation, either in previous years or earlier within the same growing season, are also an important control. Diurnal water table fluctuations can be considered a diagnostic indicator of groundwater consumption by phreatophytes at most sites, so the information embedded within these fluctuations should be more widely exploited in ecohydrologic studies

Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D

Medulloblastoma is the most common malignant brain tumor of childhood. Despite numerous advances, clinical challenges range from recurrent and progressive disease to long-term toxicities in survivors. The lack of more effective, less toxic therapies results from our limited understanding of medulloblastoma growth. Although TP53 is the most commonly altered gene in cancers, it is rarely mutated in medulloblastoma. Accumulating evidence, however, indicates that TP53 pathways are disrupted in medulloblastoma. Wild-typep53-induced phosphatase 1 (WIP1 or PPM1D) encodes a negative regulator of p53. WIP1 amplification (17q22-q23) and its overexpression have been reported in diverse cancer types. We examined primary medulloblastoma specimens and cell lines, and detected WIP1 copy gain and amplification prevalent among but not exclusively in the tumors with 17q gain and isochromosome 17q (i17q), which are among the most common cytogenetic lesions in medulloblastoma. WIP1 RNA levels were significantly higher in the tumors with 17q gain or i17q. Immunoblots confirmed significant WIP1 protein in primary tumors, generally higher in those with 17q gain or i17q. Under basal growth conditions and in response to the chemotherapeutic agent, etoposide, WIP1 antagonized p53-mediated apoptosis in medulloblastoma cell lines. These results indicate that medulloblastoma express significant levels of WIP1 that modulate genotoxic responsiveness by negatively regulating p53