Clock genes, pancreatic function and diabetes

Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes.This work was supported by grants from the Ministerio de Economía (BFU2013-42789)This work was supported by grants from Generalitat Valenciana (PROMETEO/2011/080

Sensitive and specific detection of explosives in solution and vapour by surface-enhanced Raman spectroscopy on silver nanocubes

Surface-enhanced Raman spectroscopy (SERS) has been widely utilised as a sensitive analytical technique for the detection of trace levels of organic molecules. The detection of organic compounds in the gas phase is particularly challenging due to the low concentration of adsorbed molecules on the surface of the SERS substrate. This is particularly the case for explosive materials, which typically have very low vapour pressures, limiting the use of SERS for their identification. In this work, silver nanocubes (AgNCs) were developed as a highly sensitive SERS substrate with very low limit-of-detection (LOD) for explosive materials down to the femtomolar (10−15 M) range. Unlike typical gold-based nanostructures, the AgNCs were found suitable for the detection of both aromatic and aliphatic explosives, enabling detection with high specificity at low concentration. SERS studies were first carried out using a model analyte, Rhodamine-6G (Rh-6G), as a probe molecule. The SERS enhancement factor was estimated as 8.71 × 1010 in this case. Further studies involved femtomolar concentrations of 2,4-dinitrotoluene (DNT) and nanomolar concentrations of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), as well as vapour phase detection of DNT

A modernização do baixo elétrico no samba: análise de transcrições do baixista Luizão Maia na década de 1970

O que se buscou neste trabalho foi encontrar as raízes que fundamentam as bases musicais do samba, bem como as estragégias presentes na construção de uma linha de baixo neste gênero, tanto no que herdou das origens da música europeia, quanto naquilo que incorporou da cultural musical africana. Depois disso, através da transcrição e análise das linhas de baixo de duas versões do samba Águas de Março, música de autoria de Tom Jobim e gravadas nos discos Elis (1972) e Elis & Tom (1974), buscouqse identificar os padrões rítmicos, melódicos, técnicos e interpretativos mais presentes e marcantes do estilo de Luizão Maia. Percebemos haver grande escassez de trabalhos sobre baixo elétrico no samba, e aparentemente nenhuma dissertação ou tese sobre Luizão, apesar de ser considerado pela maior parte dos baixistas como o criador da linguagem musical do samba no baixo elétrico; “The modernization of electric bass in samba: analysis of transcriptions of bassist Luizão Maia in the 1970’s”. ABSTRACT: This work intended to find the roots that guides the musical bases of samba, as well as the strategies present in the construction of a samba’s bass line, both in what it inherited from the origins of european music, and in what was incorporated from african’s musical culture. After that, through the transcription and analysis of the bass lines of two versions of the samba Águas de Março, written by Tom Jobim and recorded on the albuns Elis (1972) and Elis & Tom (1974), we sought to identify the rhythmic and melodic patterns, as well the technical and interpretive elements more present and salient in the style of Luizão Maia. We perceive a big gap on works of electric bass in samba, and apparently no dissertations or thesis of Luizão Maia, although he’s considered by most bassists as the creator of the musical language of samba on electric bass

The pancreatic β-cell in ageing: Implications in age-related diabetes

The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt fi-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity. However, a precise understanding of the pancreatic fi-cell response in ageing is still lacking. In this review, we summarize the age-related alterations, adaptations and/or failures of fi-cells at the molecular, morphological and functional levels in mouse and human. Age-associated alterations include processes such as fi-cell proliferation, apoptosis and cell identity that can influence fi-cell mass. Age-related changes also affect fi-cell function at distinct steps including electrical activity, Ca2+ signaling and insulin secretion, among others. We will consider the potential impact of these alterations and those mediated by senescence pathways on fi-cells and their implications in age-related T2D. Finally, given the great diversity of results in the field of fi-cell ageing, we will discuss the sources of this heterogeneity. A better understanding of fi-cell biology during ageing, particularly at older ages, will improve our insight into the contribution of fi-cells to ageassociated T2D and may boost new therapeutic strategies

Andreu Morell i Marco: un poeta oblidat dels anys setanta

Aquest poeta forma part del corrent de poesia no-realista i experimental de la literatura catalana durant els nays setanta. en aquest article ens hem centraten l'anàlisi dels seus tres llibres publicats: Òliba de la foscúria (1980), L'ésser fosc (1980) i Espai de la Tenebra(1986

Exposure to bisphenol-a during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice

sem informaçãoBisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β96113sem informaçãosem informaçãosem informaçã

Phase Quantification of Heterogeneous Surfaces Using DFT-Simulated Valence Band Photoemission Spectra

Quantifying the crystallographic phases present at a surface is an important challenge in fields such as functional materials and surface science. X-ray photoelectron spectroscopy (XPS) is routinely employed in surface characterization to identify and quantify chemical species through core line analysis. Valence band (VB) spectra contain characteristic but complex features that provide information on the electronic density of states (DoS) and thus can be understood theoretically using density functional theory (DFT). Here, we present a method of fitting experimental photoemission spectra with DFT models for quantitative analysis of heterogeneous systems, specifically mapping the anatase to rutile ratio across the surface of mixed-phase TiO2 thin films. The results were correlated with mapped photocatalytic activity measured using a resazurin-based smart ink. This method allows large-scale functional and surface composition mapping in heterogeneous systems and demonstrates the unique insights gained from DFT-simulated spectra on the electronic structure origins of complex VB spectral features

Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells

Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60-70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway