Coleycolon3097

Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using Kras(LA1) mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic Kras(G12D). However, blocking p53 during TBI significantly suppresses the expansion of Kras(G12D)-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma.Cytokinesis is the final stage of cell division and produces two independent daughter cells. TGF-beta inhibitor clinical trial Vesicles derived from internal membrane stores, such as the Golgi, lysosomes, and early and recycling endosomes accumulate at the intracellular bridge (ICB) during cytokinesis. Here, we use electron tomography to show that many ICB vesicles are not independent but connected, forming a newly described ICB vesicular structure - narrow tubules that are often branched. These 'midbody tubules' labelled with horseradish peroxidase (HRP) within 10 min after addition to the surrounding medium demonstrating that they are derived from endocytosis. HRP-labelled vesicles and tubules were observed at the rim of the ICB after only 1 min, suggesting that midbody tubules are likely to be generated by local endocytosis occurring at the ICB rim. Indeed, at least one tubule was open to the extracellular space, indicative of a local origin within the ICB. Inhibition of cholesterol-dependent endocytosis by exposure to methyl-β-cyclodextrin and filipin reduced formation of HRP-labelled midbody tubules, and induced multinucleation following ICB formation. In contrast, dynamin inhibitors, which block clathrin-mediated endocytosis, induced multinucleation but had no effect on the formation of HRP-labelled midbody tubules. Therefore, our data reveal the existence of a cholesterol-dependent endocytic pathway occurring locally at the ICB, which contributes to the accumulation of vesicles and tubules that contribute to the completion of cytokinesis.In-cell NMR allows obtaining atomic-level information on biological macromolecules in their physiological environment. Soluble proteins may interact with the cellular environment in different ways either specifically, with their functional partners, or non-specifically, with other cellular components. Such behaviour often causes the disappearance of the NMR signals. Here we show that by introducing mutations on the human protein profilin 1, used here as a test case, the in-cell NMR signals can be recovered. In human cells both specific and non-specific interactions are present, while in bacterial cells only the effect of non-specific interactions is observed. By comparing the NMR signal recovery pattern in human and bacterial cells, the relative contribution of each type of interaction can be assessed. This strategy allows detecting solution in-cell NMR spectra of soluble proteins without altering their fold, thus extending the applicability of in-cell NMR to a wider range of proteins.This is the first record of Leishmania detection in foxes in Greece. Spleen, lymph nodes, bone marrow and blood samples were collected from 47 red foxes (Vulpes vulpes) found dead or captured, narcotized and freed after bleeding, from November 2009 to 2011, in Fthiotida prefecture, central Greece. This is an endemic for canine leishmaniasis area with several human visceral leishmaniasis cases. The samples were tested for Leishmania infantum and Leishmania tropica by molecular methods (polymerase chain reaction (PCR) and restriction fragment length polymorphism) and serology (indirect immunofluorescent antibody test; when blood samples were available). Leishmania infantum DNA was detected in 28 animals (59·5%). PCR positivity was related to animal age, sex, weight, characteristics of the area trapped, presence of leishmaniasis symptoms and presence of endo- and ecto-parasites. The results were related to dog seropositivity obtained earlier in the area. The findings support the hypothesis that this wild canid may serve as a reservoir for Leishmania in areas where the sandfly vectors are found. In the prefectures of Larisa and Magnisia, adjacent to Fthiotida, Phlebotomus perfiliewi and Phlebotomus tobbi (known vectors of L. infantum) have been reported.The emergence of monodispersity during particle growth on a liquid substrate was investigated both by experimental methods and by computer simulation. Monodispersity arises through a novel mechanism (termed "shared coarsening"), associated with the spatial distribution of the particles; smaller particles are simultaneously consumed by several larger particles. Particle monodispersity was predicted by kinetic Monte Carlo simulation for suitable substrate adsorption probability and adatom diffusion length conditions. High particle monodispersity is predicted for low adsorption probability and low/intermediate diffusion length values. Experimentally, the formation of uniformly sized copper nanoparticles by physical vapor deposition on a liquid substrate was demonstrated. These results demonstrate, by experiment and simulation, the facile production of monodisperse particles on liquid substrates.In this study we analyse the implications for cognitive function of recovery from stunting in early childhood. More specifically, we test whether children who met the definition for stunted at age 2, but not at age 5, perform better in cognitive tests than children who remain stunted over this period. The sample is drawn from the Birth to Twenty Cohort Study, a prospective data set of children born in 1990 in urban South Africa. The measure of cognitive function that we use is based on the Revised Denver Prescreening Developmental Questionnaire implemented when the children were age 5. We employ multivariate regression in the analysis to control for child-specific characteristics, socio-economic status, the home environment and caregiver inputs. We find that recovery from stunting is not uncommon among young children in our sample. However, children who recover from stunting by age 5 still perform significantly worse on cognitive tests than children who do not experience early malnutrition, and almost as poorly as children who remain stunted. These findings suggest that the timing of nutritional inputs in the early years is key in a child's cognitive development, with implications for school readiness and achievement.A novel combination of two rare pathogenic cystic fibrosis-causing mutations, p.S1159P and p.Y569H, was detected in a patient of 17 years age who suffered from pancreatic insufficiency of unknown etiology. Both mutations were previously described in compound heterozygous patients with moderate lung disease, who carried p.F508del on the other allele. However, this newly described combination of alleles is unusually associated with general gastrointestinal manifestations. Both mutations managed to be identified by virtue of using the Ion PGM next-generation sequencing (NGS) platform, thereby making our work a “proof of concept” for clinical application of a new NGS technology in conjunction with the developed software for variant annotation.Reaction of acenaphthoquinone with N-phenyl-o-phenylenediamine in methanol in presence of HCl yielded 7-phenylacenaphtho[1,2-b]quinoxalin-7-ium chloride, [1][Cl]. [1][Cl] is brightly fluorescencent in dichloromethane (λex = 403 nm and λem = 442, 464, 488 nm) and water (λex = 408 nm and λem = 545 nm). Density functional theory (DFT) and time dependent (TD) DFT calculations on [1](+) at the B3LYP level of the theory elucidated that the origin of the lower energy excitation at around 400 nm is due to π → π(*) transition. [1](+) is redox active and exhibits a reversible cathodic wave at -0.66 V referenced to Fc(+)/Fc couple due to [1](+)/[1](•) redox couple. Electrogenerated neutral radical analogue [1](•) was characterized by electron paramagnetic resonance (EPR), UV-vis spectra and DFT calculations. DNA binding studies using the techniques of UV-vis absorption, fluorescence, circular dichroism (CD) spectra, viscosity, gel electrophoresis, hydrodynamic, isothermal titration calorimetry (ITC) and UV optical melting studies of [1][Cl] revealed that [1](+) is a strong DNA intercalator obeying neighbor exclusion principle. ITC experiment authenticated that the binding of [1](+) to DNA is entropy driven.A fast-responsive fluorescent phenylamine-oligothiophene sensor 2TBDA was reported. This sensor exhibited highly selective and sensitive detection of Hg(2+) ion in THF/H2O (7/3, v/v) solution through fluorescence quenching. The detection was not affected by the coexistence of other competitive metal ions. In addition, the detection limit was found to be as low as 3.841 × 10(-7) M.The 30 wt% of ZnO (weight percentage of ZnO has been optimised) incorporated tris- (8-hydroxyquinoline)aluminum (Alq3) has been synthesised and coated on to glass substrates using dip coating method. The structural and optical properties of the Alq3/ZnO composite film after thermal annealing from 50 to 300 °C insteps 50° has been studied and reported. XRD pattern reveals the presence of crystalline ZnO in all the annealed films. The films annealed above 150 °C reveal the presence of crystalline Alq3 along with crystalline ZnO. The FTIR spectra confirm the presence of hydroxyquinoline and ZnO vibration in all the annealed composite films. The composite films annealed above 150 °C show a partial sublimation and degradation of hydroxyquinoline compounds. The ZnO incorporated composite films (Alq3/ZnO) exhibit two emission peaks, one corresponding to ZnO at 487 nm and another at 513 nm due to Alq3. The films annealed at 200 °C exhibit maximum photoluminescence (PL) intensity than pristine film at 513 nm when excited at 390 nm.We built a polarization fluorescence correlation spectroscopy system to analyze the variation of the correlation function in rotational diffusion based on the length of rod-like fluorescent particles. Because the rotational diffusion of particles in liquid depends on the relative polarization states of the laser source and particle fluorescence, we compared the amplitudes of the rotational diffusion using the autocorrelation function in different polarization states. For experiments that depend on the length of the fluorescent particles, we prepared three kinds of quantum rod samples with a width of 6.5 ± 0.5 nm and lengths of 17 ± 3, 40 ± 3, and 46 ± 3 nm. Through the experiment, we obtained the hydrodynamic radii of each particle using the rotational diffusion coefficient 10.7 ± 0.8, 13.4 ± 0.7, and 14.1 ± 0.4 nm with the length of the particles. All the obtained values for radii are 3 nm larger than the calculated equivalent radii of spheres with the same volume as the rod samples. Through a fraction analysis by polarization state, we confirmed that the ratio of rotational fraction for polarization increases with the aspect ratio of the actual particle.