Transcriptional regulation of autophagy and lysosomal function by bromodomain protein BRD4

Macroautophagy/autophagy is an intracellular recycling system that delivers cytoplasmic organelles and materials to lysosomes for degradation. This process is operated by autophagy-related (ATG) genes and tightly controlled by stress-responsive signaling pathways. Our recent study revealed that autophagy programs are transcriptionally suppressed by the BET family protein BRD4. This repression is alleviated during nutrient deprivation through the AMPK-SIRT1 pathway. Our findings therefore provide new insights into the regulation of autophagy

A new half-metallic ferromagnet K2Cr8O16 predicted by an ab-initio electronic structure calculation

The first-principles electronic structure calculation is carried out to predict that a chromium oxide K2Cr8O16 with the hollandite-type crystal structure should be a new half-metallic ferromagnet. We compare our results with recent experimental data which indicate the ferromagnetic-metal to ferromagnetic-insulator transition at T ∼ 90 K, as well as the paramagnetic-metal to ferromagnetic-metal transition at T ∼ 180 K. Based on the calculated electronic structures, we argue that the double-exchange mechanism is responsible for the observed saturated ferromagnetism and the formation of the incommensurate, long-wavelength density wave of spinless fermions caused by the Fermi-surface nesting may be the origin of the opening of the charge gap.Ministry of Education, Culture, Sports, Science and Technology of Japa

Correlation between biomarkers of exposure, effect and potential harm in the urine of electronic cigarette users.

ObjectivesTo determine if urinary biomarkers of effect and potential harm are elevated in electronic cigarette users compared with non-smokers and if elevation correlates with increased concentrations of metals in urine.Study design and settingThis was a cross-sectional study of biomarkers of exposure, effect and potential harm in urine from non-smokers (n=20), electronic cigarette users (n=20) and cigarette smokers (n=13). Participant's screening and urine collection were performed at the Roswell Park Comprehensive Cancer Center, and biomarker analysis and metal analysis were performed at the University of California, Riverside.ResultsMetallothionein was significantly elevated in the electronic cigarette group (3761±3932 pg/mg) compared with the non-smokers (1129±1294 pg/mg, p=0.05). 8-OHdG (8-hydroxy-2'-deoxyguanosine) was significantly elevated in electronic cigarette users (442.8±300.7 ng/mg) versus non-smokers (221.6±157.8 ng/mg, p=0.01). 8-Isoprostane showed a significant increase in electronic cigarette users (750.8±433 pg/mg) versus non-smokers (411.2±287.4 pg/mg, p=0.03). Linear regression analysis in the electronic cigarette group showed a significant correlation between cotinine and total metal concentration; total metal concentration and metallothionein; cotinine and oxidative DNA damage; and total metal concentration and oxidative DNA damage. Zinc was significantly elevated in the electronic cigarette users (584.5±826.6 µg/g) compared with non-smokers (413.6±233.7 µg/g, p=0.03). Linear regression analysis showed a significant correlation between urinary zinc concentration and 8-OHdG in the electronic cigarette users.ConclusionsThis study is the first to investigate biomarkers of potential harm and effect in electronic cigarette users and to show a linkage to metal exposure. The biomarker levels in electronic cigarette users were similar to (and not lower than) cigarette smokers. In electronic cigarette users, there was a link to elevated total metal exposure and oxidative DNA damage. Specifically, our results demonstrate that zinc concentration was correlated to oxidative DNA damage

Rethinking the discovery function of proof within the context of proofs and refutations

Proof and proving are important components of school mathematics and have multiple functions in mathematical practice. Among these functions of proof, this paper focuses on the discovery function that refers to invention of a new statement or conjecture by reflecting on or utilizing a constructed proof. Based on two cases in which eighth and ninth graders engaged in proofs and refutations, we demonstrate that facing a counterexample of a primitive statement can become a starting point of students’ activity for discovery, and that a proof of the primitive statement can function as a useful tool for inventing a new conjecture that holds for the counterexample. An implication for developing tasks by which students can experience this discovery function is mentioned.ArticleInternational Journal of Mathematical Education in Science and Technology. 45(7):1053-1067 (2014)journal articl

Carbazole and indolcarbazole-based systems: impact of the structural changes on the system properties

π-Conjugated diradical compounds, featuring unique unsaturated valences and radical centres in the ground state, are fundamentally important for understanding the nature of chemical bonds and have potential applications in material science [1] . During the last decade, there has been an increasing interest in the rationalization of how the structural changes stabilize (or destabilize) the diradical system. The tunability of the diradical character has been studied for different structural motifs such as the substitution pattern of lateral groups[2], the elongation of the conjugated core[3] or the molecular isomerism[4], among others. In this sense, we have recently reported an experimental/theoretical study of a family of carbazole-based diradicaloids with dicyanomethylene (DCM) groups incorporated via para (p-Cz and p-ICz) or meta positions (mCz and m-ICz) aiming to investigate how external stimuli impact on the molecular structure and supramolecular organization, and thus on the resulting optical and electronic properties. In addition, we theoretically investigate at the DFT level a set of ten indolocarbazole-based isomers substituted with DCM groups to disclose how their chemical reactivity and physical properties are affected by isomerism and different substitution pattern.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Plan Propio de Investigación de la UM

Analysis of comorbid factors that increase the COPD assessment test scores

Background: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. Methods: An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. Results: The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. Conclusions: Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognize