Metabolic turnover and dynamics of modified ribonucleosides by ¹³C labeling

Tandem mass spectrometry (MS/MS) is an accurate tool to assess modified ribonucleosides and their dynamics in mammalian cells. However, MS/MS quantification of lowly abundant modifications in non-ribosomal RNAs is unreliable, and the dynamic features of various modifications poorly understood. Here, we developed a 13C labeling approach, called 13C-dynamods, to quantify the turnover of base modifications in newly transcribed RNA. This turnover-based approach helped to resolve mRNA from ncRNA modifications in purified RNA or free ribonucleoside samples, and showed the distinct kinetics of the N6-methyladenosine (m6A) versus 7-methylguanosine (m7G) modification in polyA+-purified RNA. We uncovered that N6,N6-dimethyladenosine (m62A) exhibits distinct turnover in small RNAs and free ribonucleosides when compared to known m62A-modified large rRNAs. Finally, combined measurements of turnover and abundance of these modifications informed on the transcriptional versus posttranscriptional sensitivity of modified ncRNAs and mRNAs, respectively, to stress conditions. Thus, 13C-dynamods enables studies of the origin of modified RNAs at steady-state and subsequent dynamics under non-stationary conditions. These results open new directions to probe the presence and biological regulation of modifications in particular RNAs

Treadmill walking differently affects body composition and metabolic parameters of female rats from normal or small litters

This work assessed whether walking affects bodily development and metabolic parameters of female rats raised in small litters (three pups, group S) or control litters (nine pups, group C). After weaning, some of the rats had five sessions per week of a 30-min treadmill walking (CE and SE), while the others remained sedentary (CS and SS) until the age of 120 days. Exercise caused a reduction of body weight (CS/CE = 1.18), Lee index (CS/CE = 1.04), fasting blood glucose (CS/CE = 1.35), mesenteric (CS/CE = 1.23), and ovarian fat (CS/CE = 1.33) in CE, but only glucose was decreased in SE (SS/SE = 1.16). The diameter of adipocytes decreased to a half in the small-litter groups. Exercise increased subcutaneous (CS/CE = 0.88 and SS/SE = 0.71), but decreased retroperitoneal adipocytes (CS/CE = 1.2 and SS/SE = 1.3). Litter size reduction had little impact on females at the age of 120 days, but the light physical activity seemed insufficient to counteract all the effects of lactational overfeeding. On the other hand, pups from exercised mothers had a decrease in their biometric and glycemic indexes, demonstrating the transgenerational action of regular, although light, exercise

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia.

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4-866.3). NOTCH1 mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRAS mut and FBXW7 mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL

Resting metabolic rate and body composition in postmenopausal women

Objective: The present study evaluated the relationship between resting metabolic rate (RMR) and body composition of postmenopausal women. Methods: Thirty physically inactive women participated in the study, and their age average was 54,33 5,20 years old. Oxygen consumption was measured by indirect calorimetry after 12 hours of fasting and the values were calculated according to the equation of Weir. Body composition was obtained by the method of skinfolds and the measurement of waist circumference (WC) was used to assess abdominal fat. The linear correlation of Pearson was used to establish correlations between the variables. Results: We found significant correlations of TMR with the CC (0.42) and the lean mass (LM) (r = 0.48). Conclusions:The variables of body composition that can be involved in the determination of the RMR are LM and WC. Arq Bras Endocrinol Metab, 2009;53(6):755-953675575

Manual del SoftwareIfs Construction kit para generar imágenes que representan fractales mediante sistemas de funciones iteradas

Los últimos avances en matemáticas en el campo de geometría fractal han permitido el surgimiento de una gran variedad de aplicaciones informáticas útiles para la representación de conjuntos fractales. Este trabajo pretende presentar a IFSConstruction Kit como una opción para construir fractales con base en los sistemas de funciones iteradas

A database for curating the associations between killer cell immunoglobulin-like receptors and diseases in worldwide populations

The killer cell immunoglobulin-like receptors (KIR) play a fundamental role in the innate immune system, through their interactions with human leucocyte antigen (HLA) molecules, leading to the modulation of activity in natural killer (NK) cells, mainly related to killing pathogen-infected cells. KIR genes are hugely polymorphic both in the number of genes an individual carries and in the number of alleles identified. We have previously developed the Allele Frequency Net Database (AFND, http://www.allelefrequencies.net), which captures worldwide frequencies of alleles, genes and haplotypes for several immune genes, including KIR genes, in healthy populations, covering >4 million individuals. Here, we report the creation of a new database within AFND, named KIR and Diseases Database (KDDB), capturing a large quantity of data derived from publications in which KIR genes, alleles, genotypes and/or haplotypes have been associated with infectious diseases (e.g. hepatitis C, HIV, malaria), autoimmune disorders (e.g. type I diabetes, rheumatoid arthritis), cancer and pregnancy-related complications. KDDB has been created through an extensive manual curation effort, extracting data on more than a thousand KIR-disease records, comprising >50 000 individuals. KDDB thus provides a new community resource for understanding not only how KIR genes are associated with disease, but also, by working in tandem with the large data sets already present in AFND, where particular genes, genotypes or haplotypes are present in worldwide populations or different ethnic groups. We anticipate that KDDB will be an important resource for researchers working in immunogenetics. Database URL: http://www.allelefrequencies.net/diseases

PENGARUH HARGA DAN DESAIN PRODUK TERHADAP KEPUTUSAN PEMBELIAN MEBEL PADA UD. JEPARA INDAH KOTA PASURUAN

The purpose of this research is to examine the influence of price, and product design on furniture purchasing decision at UD. Jepara Indah Pasuruan City. This study uses multiple linier regression analysis on 100 respondents that have been determined using purposive sampling technique as a method of sampling by using questionnaires for data collection. The results of this study revealed that prices have a positive and significant effect on purchasing decision of furniture in UD. Jepara Indah and product design have a positive and significant impact on purchasing decision of furniture in UD. Jepara Indah