Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of ...animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.
ABSTRACT
We present the discovery with Keck of the extremely infrared (IR) luminous transient AT 2017gbl, coincident with the Northern nucleus of the luminous infrared galaxy (LIRG) IRAS 23436+5257. ...Our extensive multiwavelength follow-up spans ∼900 d, including photometry and spectroscopy in the optical and IR, and (very long baseline interferometry) radio and X-ray observations. Radiative transfer modelling of the host galaxy spectral energy distribution and long-term pre-outburst variability in the mid-IR indicate the presence of a hitherto undetected dust obscured active galactic nucleus (AGN). The optical and near-IR spectra show broad ∼2000 km s−1 hydrogen, He i, and O i emission features that decrease in flux over time. Radio imaging shows a fast evolving compact source of synchrotron emission spatially coincident with AT 2017gbl. We infer a lower limit for the radiated energy of 7.3 × 1050 erg from the IR photometry. An extremely energetic supernova would satisfy this budget, but is ruled out by the radio counterpart evolution. Instead, we propose AT 2017gbl is related to an accretion event by the central supermassive black hole, where the spectral signatures originate in the AGN broad line region and the IR photometry is consistent with re-radiation by polar dust. Given the fast evolution of AT 2017gbl, we deem a tidal disruption event (TDE) of a star a more plausible scenario than a dramatic change in the AGN accretion rate. This makes AT 2017gbl the third TDE candidate to be hosted by a LIRG, in contrast to the so far considered TDE population discovered at optical wavelengths and hosted preferably by post-starburst galaxies.
...we evaluate evidence suggesting that a specialised infection cell—the transpressorium—is necessary for invasive growth. First of all, a hard hydrophobic surface 6 must be recognised by M. oryzae, ...which requires the Pmk1 mitogen-activated protein kinase (MAPK) signalling pathway. ...the 3-celled conidium undergoes autophagy and an iron-dependent programmed cell death process, called ferroptosis, before its contents are trafficked to the appressorium 9,10. The initiation of autophagy requires both Pmk1 and cell cycle progression, but is also linked to starvation stress and a target of rapamycin (TOR) kinase–dependent metabolic checkpoint 11, because appressoria only develop in the absence of exogenous nutrients.
Many young, massive stars are found in close binaries. Using population synthesis simulations we predict the likelihood of a companion star being present when these massive stars end their lives as ...core-collapse supernovae (SNe). We focus on stripped-envelope SNe, whose progenitors have lost their outer hydrogen and possibly helium layers before explosion. We use these results to interpret new Hubble Space Telescope observations of the site of the broad-lined Type Ic SN 2002ap, 14 years post-explosion. For a subsolar metallicity consistent with SN 2002ap, we expect a main-sequence (MS) companion present in about two thirds of all stripped-envelope SNe and a compact companion (likely a stripped helium star or a white dwarf/neutron star/black hole) in about 5% of cases. About a quarter of progenitors are single at explosion (originating from initially single stars, mergers, or disrupted systems). All of the latter scenarios require a massive progenitor, inconsistent with earlier studies of SN 2002ap. Our new, deeper upper limits exclude the presence of an MS companion star >8-10 M , ruling out about 40% of all stripped-envelope SN channels. The most likely scenario for SN 2002ap includes nonconservative binary interaction of a primary star initially 23 M . Although unlikely (<1% of the scenarios), we also discuss the possibility of an exotic reverse merger channel for broad-lined Type Ic events. Finally, we explore how our results depend on the metallicity and the model assumptions and discuss how additional searches for companions can constrain the physics that govern the evolution of SN progenitors.
Background: The natural history of hepatitis C virus (HCV) infection remains uncertain. Previous data concerning rates of progression are from studies using estimated dates of infection and single ...liver biopsy scores. We prospectively studied the rate of progression of fibrosis in HCV infected patients by repeat liver biopsies without intervening treatment. Patients: We studied 214 HCV infected patients (126 male; median age 36 years (range 5–8)) with predominantly mild liver disease who were prospectively followed without treatment and assessed for risk factors for progression of liver disease. Interbiopsy interval was a median of 2.5 years. Paired biopsies from the same patient were scored by the same pathologist. Results: Seventy of 219 (33%) patients showed progression of at least 1 fibrosis point in the Ishak score; 23 progressed at least 2 points. Independent predictors of progression were age at first biopsy and any fibrosis on first biopsy. Factors not associated with progression were: necroinflammation, duration of infection, alcohol consumption, alanine aminotransferase levels, current or past hepatitis B virus infection, ferritin, HCV genotype, and steatosis or iron deposition in the initial biopsy. Conclusions: One third of patients with predominantly mild hepatitis C showed significant fibrosis progression over a median period of 30 months. Histologically, mild hepatitis C is a progressive disease. The overall rate of fibrosis progression in patients with hepatitis C was low but increased in patients who were older or had fibrosis on their index biopsy. These data suggest that HCV infection will place an increasing burden on health care services in the next 20 years.
The rice blast fungus Magnaporthe oryzae infects plants with a specialized cell called an appressorium, which uses turgor to drive a rigid penetration peg through the rice leaf cuticle. Here, we show ...that NADPH oxidases (Nox) are necessary for septin-mediated reorientation of the F-actin cytoskeleton to facilitate cuticle rupture and plant cell invasion. We report that the Nox2–NoxR complex spatially organizes a heteroligomeric septin ring at the appressorium pore, required for assembly of a toroidal F-actin network at the point of penetration peg emergence. Maintenance of the cortical F-actin network during plant infection independently requires Nox1, a second NADPH oxidase, which is necessary for penetration hypha elongation. Organization of F-actin in appressoria is disrupted by application of antioxidants, whereas latrunculin-mediated depolymerization of appressorial F-actin is competitively inhibited by reactive oxygen species, providing evidence that regulated synthesis of reactive oxygen species by fungal NADPH oxidases directly controls septin and F-actin dynamics.
A non-aqueous zinc-polyaniline secondary battery was fabricated with polyaniline Emeraldine base as cathode and zinc metal as anode in an electrolyte consisting of 0.3 M ...zinc-bis(trifluoromethyl-sulfonyl) imide Zn(TFSI) sub(2) dissolved in propylene carbonate. We observed that the formation of the battery required a prerequisite condition to stabilize the interfaces in order to maintain a stable capacity. The battery suffered from Zn dissolution which induces a competition between concurrent Zn dissolution and plating when the battery is in charge mode, and thus inefficient cycles are obtained. The capacity and couiombic efficiency of the battery depends on the charge-discharge rates. We propose cycling protocols at different rates to determine the steady-state rates of competing reactions. When the cell is cycled at > or =1 C rate, the couiombic efficiency improves. The maximum capacity and energy densities of the battery are 148 mAhg super(-1) and 127 mWhg super(-1), respectively for discharge at C/2. The battery was successively charged/ discharged at constant current densities (1C rate), and high cycling stability was obtained for more than 1700 cycles at 99.8% efficiency. Zinc dissolution and self discharge of the battery were investigated after 24 h of standby. The investigation showed that the battery experiences a severe self-discharge of 48% per day.
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