Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression

Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products. By tuning the threshold for repression, we show that multiple binding sites can also suppress fluctuations. Our results highlight possible roles for the presence of multiple binding sites of negative autoregulators

Turing Instability in a Boundary-fed System

The formation of localized structures in the chlorine dioxide-idodine-malonic acid (CDIMA) reaction-diffusion system is investigated numerically using a realistic model of this system. We analyze the one-dimensional patterns formed along the gradients imposed by boundary feeds, and study their linear stability to symmetry-breaking perturbations (Turing instability) in the plane transverse to these gradients. We establish that an often-invoked simple local linear analysis which neglects longitudinal diffusion is inappropriate for predicting the linear stability of these patterns. Using a fully nonuniform analysis, we investigate the structure of the patterns formed along the gradients and their stability to transverse Turing pattern formation as a function of the values of two control parameters: the malonic acid feed concentration and the size of the reactor in the dimension along the gradients. The results from this investigation are compared with existing experiments.Comment: 41 pages, 18 figures, to be published in Physical Review

Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations

We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.Comment: 11 pages, 8 figure

Fundamental and harmonic emission in interplanetary type 2 radio bursts

Three interplanetary type II radio bursts which show two prominent and long duration bands in their dynamic spectra were analyzed in detail and compared to similar bands in meter wavelength type II events. These bands, which differ by a factor of about two in frequency, were interpreted in terms of fundamental and harmonic emission. The fundamental component has a greater average intensity than the harmonic, due largely to short intense brightenings. The fundamental spectral profile is more narrow than that of the harmonic, with harmonic band typically exhibiting a larger bandwidth to frequency ratio than the fundamental by a factor of two. The fundamental has a larger source size than the harmonic, 160 degrees versus 110 degrees, on average, as viewed from the Sun. Two of the events have source positions which correlate well with the associated flare positions

Association of drusen deposition with choroidal intercapillary pillars in the aging human eye

PURPOSE. To determine the pattern of drusen accumulation with age and to investigate the initial sites of deposition and their relationship to choroidal capillaries in human donor eyes from the eye bank of Moorfields Eye Hospital.METHODS. Wholemounted, hydrated preparations of the choriocapillaris and Bruch's membrane from donor eyes ranging from 42 to 95 years, with or without retinal pigment epithelium (RPE), were examined by conventional and confocal microscopy. Drusen were visualized by their autofluorescence.RESULTS. In all age groups studied autofluorescent drusen were present at the equator but were not found centrally where the vascular architecture is different, being tubular rather than a honeycomb pattern. Autofluorescing drusen were strongly associated with the lateral walls of the choriocapillaris (an area commonly known as the intercapillary pillars of the choriocapillaris (P = 0.028; Wilcoxon signed ranks test). Nonfluorescing drusen were occasionally seen centrally, but were not easily identified, and because of their large size, their localization with respect to capillary walls was not possible.CONCLUSIONS. These results strongly support the notion that autofluorescent drusen are not randomly distributed and have a specific spatial relationship to choroidal vessel walls. That equatorial drusen fluoresce, whereas central drusen do not, suggests that they may have different chemical compositions at the two sites and possibly different significance in age-related macular disease

TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore.

Two-pore domain K+ channels (K2P) are responsible for background K+ currents and regulate the resting membrane potential and cellular excitability. Their activity is controlled by a large variety of physicochemical factors and intracellular signaling pathways. The majority of these effects converge on the intracellular C-terminus of the channels, resulting in the modification of the gating at the selectivity filter. Another gating mechanism, the activation gate at the helix bundle crossing is also well documented in other K+ channel families, however, it remains uncertain whether this type of gating is functional in K2P channels. The regulation of TWIK-related spinal cord K+ channel (TRESK) is different from the other K2P channels. Regulatory factors acting via the C-terminus are not known, instead channel activity is modified by the phosphorylation/dephosphorylation of the unusually long intracellular loop between the 2nd and 3rd transmembrane segments. These unique structural elements of the regulation lead us to examine channel gating at the bundle crossing region. Ba2+ was applied to the intracellular side of excised membrane patches and the characteristics of the channel block were determined. We compared the kinetics of the development of Ba2+ block when the channels were phosphorylated (inhibited) or dephosphorylated (activated) and also in different mutants mimicking the two functional states. Neither the phosphorylation/dephosphorylation nor the point mutations influenced the development of Ba2+ block, suggesting that the conformational changes of the bundle crossing region do not contribute to the phosphorylation-dependent gating of TRESK

Pressure-induced change of the pairing symmetry in superconducting CeCu2Si2

Low-temperature (T) heat-capacity measurements under hydrostatic pressure of up to p=2.1 GPa have been performed on single-crystalline CeCu2Si2. A broad superconducting (SC) region exists in the T-p phase diagram. In the low-pressure region antiferromagnetic spin fluctuations and in the high-pressure region valence fluctuations had previously been proposed to mediate Cooper pairing. We could identify these two distinct SC regions. We found different thermodynamic properties of the SC phase in both regions, supporting the proposal that different mechanisms might be implied in the formation of superconductivity.Comment: 4 pages, 5 figure

Neural Variability and Sampling-Based Probabilistic Representations in the Visual Cortex

Neural responses in the visual cortex are variable, and there is now an abundance of data characterizing how the magnitude and structure of this variability depends on the stimulus. Current theories of cortical computation fail to account for these data; they either ignore variability altogether or only model its unstructured Poisson-like aspects. We develop a theory in which the cortex performs probabilistic inference such that population activity patterns represent statistical samples from the inferred probability distribution. Our main prediction is that perceptual uncertainty is directly encoded by the variability, rather than the average, of cortical responses. Through direct comparisons to previously published data as well as original data analyses, we show that a sampling-based probabilistic representation accounts for the structure of noise, signal, and spontaneous response variability and correlations in the primary visual cortex. These results suggest a novel role for neural variability in cortical dynamics and computations.European Union-FP7 (Marie Curie Intra-European Fellowship, Marie Curie CIG), Hungarian Academy of Sciences (Lendulet Award), Swartz Foundation, Swiss National Science Foundation, National Science Foundation, Wellcome Trus

Sugar In School Breakfasts: A School District\u27s Perspective

A recent series of emails and phone calls from parents concerned about the sugar content of Houston Independent School District’s school breakfasts revealed that a new issue had risen to the surface. This prompted us to look closely at the sugar content of our breakfast items. School districts participating in the National School Breakfast Program follow a strict set of nutritional regulations set forth by the USDA under the Healthy Hunger Free Kids Act (HHFKA) of 2010 in response to the childhood obesity epidemic. HHFKA made significant changes to the breakfast meal pattern, but did not set standards for the sugar content. Whether this is an oversight or the authors of the law intentionally did not limit sugar, the result is the same: lower fat, higher carbohydrate school breakfast meals. Herein, we would like to provide the perspective of a school food service organization concerning sugar in breakfast, and present the challenges and efforts made to provide students with healthy, well-balanced school breakfasts

New records and present status of the invasive Spotted Wing Drosophila, Drosophila suzukii (Matsumura, 1931) (Diptera) in Hungary

The spotted wing drosophila (Drosophila suzukii (Matsumura, 1931) – SWD) is one of the most recently introduced invasive pests of economical importance in Europe. It has invaded many countries in Europe and North America causing significant losses in fruit production. In 2012, the species has been detected for the first time in Hungary at a highway rest area. The following year a countrywide trapping program was conducted to monitor the spreading of the species. In 2013, thirty-three highway rest areas and furthermore cherry, strawberries, raspberries, peach, grape orchards were monitored using apple vinegar bait traps. Altogether 33 individuals of SWD have been captured in 5 localities along highways in western Hungary, including the collecting site of the first detection. On the other hand the species was not found in countryside orchards. The location of the collecting sites indicates that international transport along highways plays an important role in spreading of SWD. Highway infrastructures, like selective trash bins, or buildings may serve as refugee spots for SWD. The role of vehicle transport in the spreading of SWD is also supported by the relatively high spreading rate of SWD, which was estimated around 320–390 km year-1