Investigating the beneficial traits of Trichoderma hamatum GD12 for sustainable agriculture-insights from genomics.

This is the final version of the article. Available from the publisher via the DOI in this record.Trichoderma hamatum strain GD12 is unique in that it can promote plant growth, activate biocontrol against pre- and post-emergence soil pathogens and can induce systemic resistance to foliar pathogens. This study extends previous work in lettuce to demonstrate that GD12 can confer beneficial agronomic traits to other plants, providing examples of plant growth promotion in the model dicot, Arabidopsis thaliana and induced foliar resistance to Magnaporthe oryzae in the model monocot rice. We further characterize the lettuce-T. hamatum interaction to show that bran extracts from GD12 and an N-acetyl-β-D-glucosamindase-deficient mutant differentially promote growth in a concentration dependent manner, and these differences correlate with differences in the small molecule secretome. We show that GD12 mycoparasitises a range of isolates of the pre-emergence soil pathogen Sclerotinia sclerotiorum and that this interaction induces a further increase in plant growth promotion above that conferred by GD12. To understand the genetic potential encoded by T. hamatum GD12 and to facilitate its use as a model beneficial organism to study plant growth promotion, induced systemic resistance and mycoparasitism we present de novo genome sequence data. We compare GD12 with other published Trichoderma genomes and show that T. hamatum GD12 contains unique genomic regions with the potential to encode novel bioactive metabolites that may contribute to GD12's agrochemically important traits.This work was supported by a Biotechnology and Biological Sciences Research Council grant BB/I014691/1 to Murray Grant and Chris R. Thornto

Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma

Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow‐up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison. Loss of nuclear BAP1 (nBAP1) protein expression was observed in 54% (88/165) UMs. nBAP1 expression proved to be a significant independent prognostic parameter: it identified two subgroups within monosomy 3 (M3) UM, which are known to have a high risk of metastasis. Strikingly, nBAP1‐positiveM3 UMs were associated with prolonged survival compared to nBAP1‐negative M3 UMs (Log rank, p = 0.014). nBAP1 protein loss did not correlate with a BAP1 mutation in 23% (6/26) of the UMs analysed. Cytoplasmic BAP1 protein (cBAP1) expression was also observed in UM: although appearing ‘predominantly diffuse’ in most nBAP1‐negative UM, a distinct ‘focal perinuclear’ expression pattern – localized immediately adjacent to the cis Golgi – was seen in 31% (18/59). These tumours tended to carry loss‐of‐function BAP1 mutations. Our study demonstrates loss of nBAP1 expression to be the strongest prognostic marker in UM, confirming its importance in UM progression. Our data suggest that non‐genetic mechanisms account for nBAP1 loss in a small number of UMs. In addition, we describe a subset of nBAP1‐negative UM, in which BAP1 is sequestered in perinuclear bodies, most likely within Golgi, warranting further mechanistic investigation

Muc5b Is the Major Polymeric Mucin in Mucus from Thoroughbred Horses With and Without Airway Mucus Accumulation

Mucus accumulation is a feature of inflammatory airway disease in the horse and has been associated with reduced performance in racehorses. In this study, we have analysed the two major airways gel-forming mucins Muc5b and Muc5ac in respect of their site of synthesis, their biochemical properties, and their amounts in mucus from healthy horses and from horses with signs of airway mucus accumulation. Polyclonal antisera directed against equine Muc5b and Muc5ac were raised and characterised. Immunohistochemical staining of normal equine trachea showed that Muc5ac and Muc5b are produced by cells in the submucosal glands, as well as surface epithelial goblet cells. Western blotting after agarose gel electrophoresis of airway mucus from healthy horses, and horses with mucus accumulation, was used to determine the amounts of these two mucins in tracheal wash samples. The results showed that in healthy horses Muc5b was the predominant mucin with small amounts of Muc5ac. The amounts of Muc5b and Muc5ac were both dramatically increased in samples collected from horses with high mucus scores as determined visually at the time of endoscopy and that this increase also correlated with increase number of bacteria present in the sample. The change in amount of Muc5b and Muc5ac indicates that Muc5b remains the most abundant mucin in mucus. In summary, we have developed mucin specific polyclonal antibodies, which have allowed us to show that there is a significant increase in Muc5b and Muc5ac in mucus accumulated in equine airways and these increases correlated with the numbers of bacteria

Epidemic infectious gastrointestinal illness aboard U.S. Navy ships deployed to the Middle East during peacetime operations – 2000–2001

BACKGROUND: Infectious gastrointestinal illness (IGI) outbreaks have been reported in U.S. Navy ships and could potentially have an adverse mission impact. Studies to date have been anecdotal. METHODS: We conducted a retrospective analysis of weekly reported disease and non-battle injury health data collected in 2000 – 2001 from 44 U.S. Navy ships while sailing in the 5(th )Fleet (Persian Gulf and nearby seas). RESULTS: During this period, 11 possible IGI outbreaks were identified. Overall, we found 3.3 outbreaks per 100 ship-weeks, a mean outbreak duration of 4.4 weeks, and a mean cumulative ship population attack rate of 3.6%. Morbidity, represented by days lost due to personnel being placed on sick-in-quarters status, was higher during outbreak weeks compared to non-outbreak weeks (p = 0.002). No clear seasonal distribution was identified. CONCLUSION: Explosive outbreaks due to viruses and bacteria with the potential of incapacitating large proportions of the crew raise serious concerns of mission impact and military readiness

Metal-macrofauna interactions determine microbial community structure and function in copper contaminated sediments

Peer reviewedPublisher PD

The effects of tea extracts on proinflammatory signaling

BACKGROUND: Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea. METHODS: Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1β, IL-6, IL-8, TNFα and PGE(2 )release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-κB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays. RESULTS: Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation CONCLUSION: Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

<p>Abstract</p> <p>Background</p> <p>Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of <it>Curcuma longa</it>. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.</p> <p>Methods</p> <p>Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an <it>in vitro </it>APC activity assay.</p> <p>Results</p> <p>We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells.</p> <p>Conclusions</p> <p>We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin.</p

A new investigation of electron neutrino appearance oscillations with improved sensitivity in the MiniBooNE+ experiment

Submitted as whitepaper for Snowmass'13 proceedings - 8 pages, 3 figures; version 2: Minor change to title and author listSubmitted as whitepaper for Snowmass'13 proceedings - 8 pages, 3 figures; version 2: Minor change to title and author listWe propose the addition of scintillator to the existing MiniBooNE detector to allow a test of the neutral-current/charged-current (NC/CC) nature of the MiniBooNE low-energy excess. Scintillator will enable the reconstruction of 2.2 MeV $\gamma$s from neutron-capture on protons following neutrino interactions. Low-energy CC interactions where the oscillation excess is observed should have associated neutrons with less than a 10% probability. This is in contrast to the NC backgrounds that should have associated neutrons in approximately 50% of events. We will measure these neutron fractions with $\nu_\mu$ CC and NC events to eliminate that systematic uncertainty. This neutron-fraction measurement requires $6.5\times10^{20}$ protons on target delivered to MiniBooNE with scintillator added in order to increase the significance of an oscillation excess to over $5\sigma$. This new phase of MiniBooNE will also enable additional important studies such as the spin structure of nucleon ($\Delta s$) via NC elastic scattering, a low-energy measurement of the neutrino flux via \numu ^{12}C \rightarrow \mu^{-} ^{12}N_\textrm{g.s.} scattering, and a test of the quasielastic assumption in neutrino energy reconstruction. These topics will yield important, highly-cited results over the next 5 years for a modest cost, and will help to train Ph.D. students and postdocs. This enterprise offers complementary information to that from the upcoming liquid Argon based MicroBooNE experiment. In addition, MicroBooNE is scheduled to receive neutrinos in early 2014, and there is minimal additional cost to also deliver beam to MiniBooNE

Dark Matter Search in a Proton Beam Dump with MiniBooNE

6 pages, 7 figures6 pages, 7 figure