Glucose induced MAPK signalling influences NeuroD1-mediated activation and nuclear localization

AbstractThe helix–loop–helix transcription factor NeuroD1 (also known as Beta2) is involved in β-cell survival during development and insulin gene transcription in adults. Here we show NeuroD1 is primarily cytoplasmic at non-stimulating glucose concentrations (i.e. 3 mM) in MIN6 β-cells and nuclear under stimulating conditions (i.e. 20 mM). Quantification revealed that NeuroD1 was in 40–45% of the nuclei at 3 mM and 80–90% at 20 mM. Treatment with the MEK inhibitor PD98059 or substitution of a serine for an alanine at a potential mitogen-activated protein kinase phosphorylation site (S274) in NeuroD1 significantly increased the cytoplasmic level at 20 mM glucose. The rise in NeuroD1-mediated transcription in response to glucose also correlated with the change in sub-cellular localization, a response attenuated by PD98059. The data strongly suggest that glucose-stimulation of the MEK–ERK signalling pathway influences NeuroD1 activity at least partially through effects on sub-cellular localization

Intrinsic Geometric Structure of c=−2c=-2 Quantum Gravity

We couple c=-2 matter to 2-dimensional gravity within the framework of dynamical triangulations. We use a very fast algorithm, special to the c=-2 case, in order to test scaling of correlation functions defined in terms of geodesic distance and we determine the fractal dimension d_H with high accuracy. We find d_H=3.58(4), consistent with a prediction coming from the study of diffusion in the context of Liouville theory, and that the quantum space-time possesses the same fractal properties at all distance scales similarly to the case of pure gravity

Permanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3

Artículo de publicación ISIOBJECTIVE—NEUROG3 plays a central role in the development of both pancreatic islets and enteroendocrine cells. Homozygous hypomorphic missense mutations in NEUROG3 have been recently associated with a rare form of congenital malabsorptive diarrhea secondary to enteroendocrine cell dysgenesis. Interestingly, the patients did not develop neonatal diabetes but childhood-onset diabetes. We hypothesized that null mutations in NEUROG3 might be responsible for the disease in a patient with permanent neonatal diabetes and severe congenital malabsorptive diarrhea. RESEARCH DESIGN AND METHODS—The single coding exon of NEUROG3 was amplified and sequenced from genomic DNA. The mutant protein isoforms were functionally characterized by measuring their ability to bind to an E-box element in the NEUROD1 promoter in vitro and to induce ectopic endocrine cell formation and cell delamination after in ovo chicken endoderm electroporation. RESULTS—Two different heterozygous point mutations in NEUROG3 were identified in the proband [c.82G.T (p.E28X) and c.404T.C (p.L135P)], each being inherited from an unaffected parent. Both in vitro and in vivo functional studies indicated that the mutant isoforms are biologically inactive. In keeping with this, no enteroendocrine cells were detected in intestinal biopsy samples from the patient. CONCLUSIONS—Severe deficiency of neurogenin 3 causes a rare novel subtype of permanent neonatal diabetes. This finding confirms the essential role of NEUROG3 in islet development and function in humans

Percolation in Models of Thin Film Depositions

We have studied the percolation behaviour of deposits for different (2+1)-dimensional models of surface layer formation. The mixed model of deposition was used, where particles were deposited selectively according to the random (RD) and ballistic (BD) deposition rules. In the mixed one-component models with deposition of only conducting particles, the mean height of the percolation layer (measured in monolayers) grows continuously from 0.89832 for the pure RD model to 2.605 for the pure RD model, but the percolation transition belong to the same universality class, as in the 2- dimensional random percolation problem. In two- component models with deposition of conducting and isolating particles, the percolation layer height approaches infinity as concentration of the isolating particles becomes higher than some critical value. The crossover from 2d to 3d percolation was observed with increase of the percolation layer height.Comment: 4 pages, 5 figure

Mean square performance evaluation in frequency domain for an improved adaptive feedback cancellation in hearing aids

We consider an adaptive linear prediction based feedback canceller for hearing aids that exploits two (an external and a shaped) noise signals for a bias-less adaptive estimation. In particular, the bias in the estimate of the feedback path is reduced by synthesizing the high-frequency spectrum of the reinforced signal using a shaped noise signal. Moreover, a second shaped (probe) noise signal is used to reduce the closed-loop signal correlation between the acoustic input and the loudspeaker signal at low frequencies. A power-transfer-function analysis of the system is provided, from which the effect of the system parameters and adaptive algorithms [normalized least mean square (NLMS) and recursive least square (RLS)] on the rate of convergence, the steady-state behaviour and the stability of the feedback canceller is explicitly found. The derived expressions are verified through computer simulations. It is found that, as compared to feedback canceller without probe noise, the cost of achieving an unbiased estimate of the feedback path using the feedback canceller with probe noise is a higher steady-state misadjustment for the RLS algorithm, whereas a slower convergence and a higher tracking error for the NLMS algorithm

Micro-level economic factors and incentives in Children's energy balance related behaviours findings from the ENERGY European cross-section questionnaire survey

<p>Abstract</p> <p>Background</p> <p>To date, most research on obesogenic environments facing school children has focused on physical and socio-cultural environments. The role of economic factors has been investigated to a much lesser extent. Our objective was to explore the association of micro-level economic factors and incentives with sports activities and intake of soft drinks and fruit juice in 10-12 year-old school children across Europe, and to explore price sensitivity in children’s soft drink consumption and correlates of this price sensitivity.</p> <p>Methods</p> <p>Data for the study originate from a cross-sectional survey undertaken in seven European countries (Belgium, Greece, Hungary, Netherlands, Norway, Slovenia and Spain) in 2010 among 10-12 year-old school children and their parents. In total, 7234 child questionnaires and 6002 parent questionnaires were completed. The child questionnaire included questions addressing self-reported weekly intake of soft drinks and fruit juices and time spent on sports activities, perception of parental support for sports activities, use of pocket money for soft drinks and perceived price responsiveness. Parent questionnaires included questions addressing the role of budget and price considerations in decisions regarding children’s sports activities, soft drink consumption, home practices and rules and socio-demographic background variables. Data were analysed using multiple linear regression and discrete-choice (ordered probit) modelling.</p> <p>Results</p> <p>Economic factors were found to be associated with children’s sports participation and sugary drink consumption, explaining 27% of the variation in time for sports activities, and 27% and 12% of the variation in the children’s soft drink and juice consumption, respectively. Parents’ financial support was found to be an important correlate (Beta =0.419) of children’s sports activities. Children’s pocket money was a strong correlate (Beta =21.034) of soft drink consumption. The majority of the responding children reported to expect that significantly higher prices of soft drinks would lead them to buy less soft drinks with their own pocket money, but a majority of parents did not expect higher soft drink prices to reduce their children’s soft drink consumption.</p> <p>Conclusions</p> <p>We conclude that economic factors, especially parents’ financial support and amount of pocket money, appear to be of importance for children’s sports participation and soft drink consumption, respectively.</p

Are Damage Spreading Transitions Generically in the Universality Class of Directed Percolation?

We present numerical evidence for the fact that the damage spreading transition in the Domany-Kinzel automaton found by Martins {\it et al.} is in the same universality class as directed percolation. We conjecture that also other damage spreading transitions should be in this universality class, unless they coincide with other transitions (as in the Ising model with Glauber dynamics) and provided the probability for a locally damaged state to become healed is not zero.Comment: 10 pages, LATE

Diagnosing the Clumpy Protoplanetary Disk of the UXor Type Young Star GM Cephei

UX Orionis stars (UXors) are Herbig Ae/Be or T Tauri stars exhibiting sporadic occultation of stellar light by circumstellar dust. GM\,Cephei is such a UXor in the young ($\sim4$~Myr) open cluster Trumpler\,37, showing prominent infrared excess, emission-line spectra, and flare activity. Our photometric monitoring (2008--2018) detects (1)~an $\sim$3.43~day period, likely arising from rotational modulation by surface starspots, (2)~sporadic brightening on time scales of days due to accretion, (3)~irregular minor flux drops due to circumstellar dust extinction, and (4)~major flux drops, each lasting for a couple of months with a recurrence time, though not exactly periodic, of about two years. The star experiences normal reddening by large grains, i.e., redder when dimmer, but exhibits an unusual "blueing" phenomenon in that the star turns blue near brightness minima. The maximum extinction during relatively short (lasting $\leq 50$~days) events, is proportional to the duration, a consequence of varying clump sizes. For longer events, the extinction is independent of duration, suggestive of a transverse string distribution of clumps. Polarization monitoring indicates an optical polarization varying $\sim3\%$--8$\%$, with the level anticorrelated with the slow brightness change. Temporal variation of the unpolarized and polarized light sets constraints on the size and orbital distance of the circumstellar clumps in the interplay with the young star and scattering envelope. These transiting clumps are edge-on manifestations of the ring- or spiral-like structures found recently in young stars with imaging in infrared of scattered light, or in submillimeter of thermalized dust emission.Comment: 20 pages, 9 figure