Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination

The glycolytic PFKFB3 enzyme is widely overexpressed in cancer cells and an emerging anti-cancer target. Here, we identify PFKFB3 as a critical factor in homologous recombination (HR) repair of DNA double-strand breaks. PFKFB3 rapidly relocates into ionizing radiation (IR)-induced nuclear foci in an MRN-ATM-γH2AX-MDC1-dependent manner and co-localizes with DNA damage and HR repair proteins. PFKFB3 relocalization is critical for recruitment of HR proteins, HR activity, and cell survival upon IR. We develop KAN0438757, a small molecule inhibitor that potently targets PFKFB3. Pharmacological PFKFB3 inhibition impairs recruitment of ribonucleotide reductase M2 and deoxynucleotide incorporation upon DNA repair, and reduces dNTP levels. Importantly, KAN0438757 induces radiosensitization in transformed cells while leaving non-transformed cells unaffected. In summary, we identify a key role for PFKFB3 enzymatic activity in HR repair and present KAN0438757, a selective PFKFB3 inhibitor that could potentially be used as a strategy for the treatment of cancer

Variation of NO2 and NOx concentrations between and within 36 European study areas: Results from the ESCAPE study

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Prospects for e+e- physics at Frascati between the phi and the psi

We present a detailed study, done in the framework of the INFN 2006 Roadmap, of the prospects for e+e- physics at the Frascati National Laboratories. The physics case for an e+e- collider running at high luminosity at the phi resonance energy and also reaching a maximum center of mass energy of 2.5 GeV is discussed, together with the specific aspects of a very high luminosity tau-charm factory. Subjects connected to Kaon decay physics are not discussed here, being part of another INFN Roadmap working group. The significance of the project and the impact on INFN are also discussed. All the documentation related to the activities of the working group can be found in http://www.roma1.infn.it/people/bini/roadmap.html.Comment: INFN Roadmap Report: 86 pages, 25 figures, 9 table

Specific food preferences of older adults with a poor appetite. A forced-choice test conducted in various care settings

A poor appetite in older adults is an important determinant of reduced food intake and undernutrition. Food preferences may influence food intake. The aim of this study was to investigate food preferences of older adults with a poor appetite and compare these with preferences of older adults with a good appetite. Older adults (n = 349, aged 65–101 years) in nursing/residential care homes, hospitals or at home receiving home care participated in a computer-based forced-choice food preference assessment. Self-reported appetite in the past week was classified as ‘good’ or ‘poor’ using a validated instrument. Food preferences were determined by counting the relative frequency of choices for food images according to 11 dichotomous categories: high/low 1) protein; 2) fat; 3) carbohydrates; 4) fiber; 5) variation; and 6) animal/vegetarian proteins; 7) sweet/savory taste; 8) solid/liquid texture; 9) dairy/non-dairy; with/without 10) sauce or 11) color variation. Specific food preferences in participants with a poor appetite were identified by one-sample t-tests comparing frequencies to the expected value of 48. Preference differences between those with a good and a poor appetite were analyzed using GLM adjusting for confounders. The results showed that older adults with a poor appetite (n = 113; 32.4%) preferred variation (51.6 vs. 48, P < 0.001), color variation (55.9 vs. 48, P < 0.01), non-dairy (53.0 vs. 48, P < 0.001), high-fiber (51.8 vs. 48, P < 0.05), and solid texture (53.5 vs. 48, P < 0.05). Participants with a poor appetite had a higher frequency score for variation than participants with a good appetite (51.6 vs. 48.5, P < 0.001). In conclusion, older adults with a poor appetite may have specific food preferences. Their preference for variation differs from those with a good appetite. These results may be used to develop meals that are preferred by older adults with poor appetite in order to increase food intake and prevent undernutrition