Age-related subproteomic analysis of mouse liver and kidney peroxisomes

<p>Abstract</p> <p>Background</p> <p>Despite major recent advances in the understanding of peroxisomal functions and how peroxisomes arise, only scant information is available regarding this organelle in cellular aging. The aim of this study was to characterize the changes in the protein expression profile of aged versus young liver and kidney peroxisome-enriched fractions from mouse and to suggest possible mechanisms underlying peroxisomal aging. Peroxisome-enriched fractions from 10 weeks, 18 months and 24 months C57bl/6J mice were analyzed by quantitative proteomics.</p> <p>Results</p> <p>Peroxisomal proteins were enriched by differential and density gradient centrifugation and proteins were separated by two-dimensional electrophoresis (2-DE), quantified and identified by mass spectrometry (MS). In total, sixty-five proteins were identified in both tissues. Among them, 14 proteins were differentially expressed in liver and 21 proteins in kidney. The eight proteins differentially expressed in both tissues were involved in β-oxidation, α-oxidation, isoprenoid biosynthesis, amino acid metabolism, and stress response. Quantitative proteomics, clustering methods, and prediction of transcription factors, all indicated that there is a decline in protein expression at 18 months and a recovery at 24 months.</p> <p>Conclusion</p> <p>These results indicate that some peroxisomal proteins show a tissue-specific functional response to aging. This response is probably dependent on their differential regeneration capacity. The differentially expressed proteins could lead several cellular effects: such as alteration of fatty acid metabolism that could alert membrane protein functions, increase of the oxidative stress and contribute to decline in bile salt synthesis. The ability to detect age-related variations in the peroxisomal proteome can help in the search for reliable and valid aging biomarkers.</p

MacroH2A subtypes contribute antagonistically to the transcriptional regulation of the ribosomal cistron during seasonal acclimatization of the carp fish

<p>Abstract</p> <p>Background</p> <p>Incorporation of histone variants into chromatin is one of the epigenetic mechanisms used for regulation of gene expression. Macro (m)H2A is a histone variant that has two different subtypes in vertebrates: mH2A1 and mH2A2. It is known that mH2A is associated with gene silencing, but recent studies indicate that these mH2A subtypes could contribute more widely to transcriptional regulation. We have previously demonstrated that the gene-reprogramming response mediates adaptation of the carp fish to its environment, and that ribosomal gene transcription is seasonally regulated in carp. However, there have been few studies investigating how epigenetic mechanisms contribute to environmental adaptation and, in particular, to ribosomal cistron regulation.</p> <p>Results</p> <p>In this paper, we report the occurrence of differential incorporation of mH2A subtypes into chromatin during seasonal adaptation in the carp, an event that concurs with opposing transcriptional states. Moreover, we observed that enrichment of mH2A1 in the ribosomal cistron during winter, and conversely, enrichment of mH2A2 during summer. mH2A1 consistently colocalizes with a heterochromatin marker (H3K27me2; histone H3 trimethylated at lysine 27) and mH2A2 with a euchromatin marker (H3K4me3; histone H3 trimethylated at lysine 4). Similar results were found for the L41gene, with enrichment of mH2A in the promoter region.</p> <p>Conclusions</p> <p>We have characterized both mH2A subtypes from carp fish, and evaluated their participation in the regulation of the ribosomal cistron. Our findings indicate that differential incorporation of mH2A subtypes into the ribosome could regulate gene expression during the acclimatization process in carp. Our results reveal differential chromatin incorporation of the mH2A subtypes during the environmental adaptation process, correlating wtih antagonistic transcriptional states in the carp ribosomal cistron.</p

Drug properties and host factors contribute to biochemical presentation of drug-induced liver injury: a prediction model from a machine learning approach

Drug-induced liver injury (DILI) presentation varies biochemically and histologically. Certain drugs present quite consistent injury patterns, i.e., DILI signatures. In contrast, others are manifested as broader types of liver injury. The variety of DILI presentations by a single drug suggests that both drugs and host factors may contribute to the phenotype. However, factors determining the DILI types have not been yet elucidated. Identifying such factors may help to accurately predict the injury types based on drugs and host information and assist the clinical diagnosis of DILI. Using prospective DILI registry datasets, we sought to explore and validate the associations of biochemical injury types at the time of DILI recognition with comprehensive information on drug properties and host factors. Random forest models identified a set of drug properties and host factors that differentiate hepatocellular from cholestatic damage with reasonable accuracy (69-84%). A simplified logistic regression model developed for practical use, consisting of patient’s age, drug’s lipoaffinity, and hybridization ratio, achieved a fair prediction (68%-74%), but suggested potential clinical usability, computing the likelihood of liver injury type based on two properties of drugs taken by a patient and patient’s age. In summary, considering both drug and host factors in evaluating DILI risk and phenotypes open an avenue for future DILI research and aid in the refinement of causality assessment.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI 18/01804; PT20/00127) and Agencia Española del Medicamento. Plataforma ISCiii de Investigación Clínica and CIBERehd are funded by Instituto de Salud Carlos III. IAA holds a Sara Borrell research contract from the National Health System, Instituto de Salud Carlos III (CD20/00083)

Anterior segment changes following intravitreal bevacizumab injection for treatment of neovascular glaucoma

The purpose of this study was to describe anterior segment changes in a prospective, interventional, noncomparative case series of patients with neovascular glaucoma secondary to proliferative diabetic retinopathy treated with intravitreal bevacizumab. Five consecutive patients with neovascular glaucoma and a refractory, symptomatic elevation of intraocular pressure and pronounced anterior segment congestion received intravitreal bevacizumab 1.25 mg/0.05 mL. Follow-up examinations were performed at 4-16 weeks by the same specialists, with testing performed at hour 48, week 1, and months 1, 3, and 6 after intravitreal bevacizumab. We observed a significant difference (P = 0.021) between initial and mean neovascularization at three months in all the quadrants. At three months, median intraocular pressure was 19 ± 5.38 (range 12-26) mmHg. In three of the five cases, diode laser cyclophotocoagulation was required, and in one case a trabeculectomy was performed. One patient showed complete synechial angle closure 48 hours after treatment which required cyclodestructive procedures to normalize intraocular pressure. Intravitreal bevacizumab achieves complete regression of neovascularization in neovascular glaucoma secondary to proliferative diabetic retinopathy, and this regression is stable when associated with treatment of the underlying disease and should be investigated more thoroughly as an adjunct in the management of neovascular glaucoma

Las inundaciones recientes en Galicia

Las inundaciones en Galicia tienen un carácter particular. Los factores que intervienen en su desarrollo son variados pero, en general, están más asociadas a eventos derivados de un largo período de abundante precipitación, propios de las condiciones climáticas en que se inscribe\ud la región, que a aquellos otros, menos frecuentes, de corta duradón y elevada intensidad. Por otra parte, al tratarse de un territorio en donde la casi totalidad de sus principales cursos fluviales se encuentran regularizados por embalses para el aprovechamiento hidroeléctrico, los efectos de estas crecidas sólo se dejan sentir en los pequeños cursos que carecen de dicho aprovechamiento, por lo que las consecuencias hidrológicas son limitadas en el espacio y en el tiempo. Finalmente, la ausencia de infomnación hidrométríca de base en estos pequeños cursos fluviales, nos ha llevado a presentar simulaciones de eventos en una de las cuencas más afectadas por las tradicionales inundaciones como es la del río Sar, en la comarca de A Mahía, que se extiende entre la ciudad de Santiago de Compostela y el núcleo urbano de Padrón, en el fondo de la ría de Arousa.The inundations in Galicia have a particular character. The factors that intervene in the development\ud are varied but, generally, are most associated to derived events of a long period of\ud abundant precipitation, proper of the climatic conditions in that inscribes the region, that those\ud other, less frequented, of short duration and elevated intensity.\ud On the other hand, upon be tried of a territory in where the almost totality of the course fluvial principals find regularized by dammed for profit hydroelectric, the grown effects of these alone let to feel in the little courses\ud that lack of tell profit, why the consequences hydro are limited in the space and in the time. Finally,\ud the absence of information hydrologic of little base in these fluvial courses, has at us carried\ud to present simulations of events in one of the most affected basins by traditional inundations\ud as is of the "río Sar", in the "comarca de A Mahía", that extend between the city of "Santiago de\ud Compostela" and the urban nucleus of "Padrón", in the background of to "ría de Arousa"

Overtone spectra and intensities of tetrahedral molecules in boson-realization models

The stretching and bending vibrational spectrum and the intensities of infrared transitions in a tetrahedral molecule are studied in two boson-realization models, where the interactions between stretching and bending vibrations are described by a quadratic cross term and by Fermi resonance terms, called harmonically coupled and Fermi resonance boson-realization model, respectively. The later is a development of our recent model. As an example, the two models are applied to the overtone spectrum and the intensities of silicon tetrafluorde. Those models provide fits to the published experimental vibrational eigenvalues with standard deviations 1.956 cm$^{-1}$ and 0.908 cm$^{-1}$, respectively. The intensities of infrared transitions of its complete vibrations are calculated in the two models, and results show a good agreement with the observed data.Comment: 14 pages Revtex, no figure, to appear in Annals of Physic

Psychometric properties of 4-item questionnaire for sleep habits and time in a South American paediatric population

Objectives: To assess the psychometric properties of 4-item questionnaire about sleep habits and time in South American children (3-10 years) and adolescents (11-18 years). Material and Methods: We evaluated 459 participants from seven South American cities. Two items from week and weekend days wake up time and bedtime were asked twice, with a 2-week interval. We calculated time spent in bed (subtracting wake up time from bedtime). Participants also answered the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) sleep time questionnaire. Results: The questionnaire showed acceptable temporal stability in children and adolescents on total days (rho >= 0.30; p<0.05). For total days, the questionnaire presented acceptable convergent validity only in children (rho from 0.48 to 0.62; p <= 0.01) compared with the HELENA questionnaire. Conclusion: The 4-item questionnaire is a reliable and valid tool for children; however, its validity is not consistent in adolescents for sleep habits and time

Top quark forward-backward asymmetry in R-parity violating supersymmetry

The interaction of bottom squark-mediated top quark pair production, occurring in the R-parity violating minimal supersymmetric standard model (MSSM), is proposed as an explanation of the anomalously large $t\bar{t}$ forward-backward asymmetry (FBA) observed at the Tevatron. We find that this model can give a good fit to top quark data, both the inclusive and invariant mass-dependent asymmetries, while remaining consistent (at the 2-$\sigma$ level) with the total and differential production cross-sections. The scenario is challenged by strong constraints from atomic parity violation (APV), but we point out an extra diagram for the effective down quark-Z vertex, involving the same coupling constant as required for the FBA, which tends to weaken the APV constraint, and which can nullify it for reasonable values of the top squark masses and mixing angle. Large contributions to flavor-changing neutral currents can be avoided if only the third generation of sparticles is light.Comment: 24 pages, 7 figures. v3: included LHC top production cross section data; model still consistent at 2 sigma leve

Improved Antibiotic Susceptibility Test of Orientia tsutsugamushi by Flow Cytometry Using Monoclonal Antibody

Orientia tsutsugamushi causes scrub typhus, which is endemic in many countries in the Asia-Pacific region including Korea. Recent emergence of doxycycline-resistant strains from Thailand has underlined the importance of the susceptibility tests of O. tsutsugamushi to antibiotics. To improve the flow cytometric technique for the susceptibility test, we applied a monoclonal antibody (MAb) in the quantification of O. tsutsugamushi. With using MAb FS15, we determined the doxycycline susceptibility of two strains, Boryong and AFSC-4 strain which is reported to be doxycycline-sensitive and resistant, respectively. The growth of both strains was inhibited to below 10% of the control in the presence of 0.1 µg/mL or higher concentrations of doxycycline. We suggest that our approach is more quantitative and reproducible than the conventional microscopic methods