A Protocol to Detect Local Affinities Involved in Proteins Distant Interactions

The tridimensional structure of a protein is constrained or stabilized by some local interactions between distant residues of the protein, such as disulfide bonds, electrostatic interactions, hydrogen links, Wan Der Waals forces, etc. The correct prediction of such contacts should be an important step towards the whole challenge of tridimensional structure prediction. The in silico prediction of the disulfide connectivity has been widely studied: most results were based on few amino-acids around bonded and non-bonded cysteines, which we call local environments of bonded residues. In order to evaluate the impact of such local information onto residue pairing, we propose a machine learning based protocol, independent from the type of contact, to detect affinities between local environments which would contribute to residues pairing. This protocol requires that learning methods are able to learn from examples corrupted by class-conditional classification noise. To this end, we propose an adapted version of the perceptron algorithm. Finally, we experiment our protocol with this algorithm on proteins that feature disulfide or salt bridges. The results show that local environments contribute to the formation of salt bridges. As a by-product, these results prove the relevance of our protocol. However, results on disulfide bridges are not significantly positive. There can be two explanations: the class of linear functions used by the perceptron algorithm is not enough expressive to detect this information, or cysteines local environments do not contribute significantly to residues pairing

Displacement damage effects due to neutron and proton irradiations on CMOS image sensors manufactured in deep submicron technology

Displacement damage effects due to proton and neutron irradiations of CMOS image sensors dedicated to imaging are presented through the analysis of the dark current behavior in pixel arrays and isolated photodiodes. The mean dark current increase and the dark current nonuniformity are investigated. Dark current histogram observations are compared to damage energy distributions based on GEANT 4 calculations. We also discuss, through annealing analysis, which defects could be responsible for the dark current in CMOS image sensors

Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice

Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning

Трехкоординатный пьезокерамический сканер на биморфных пьезо-элементах для зондового наномикроскопа

Предложена и исследована конструкция пьезокерамического сканера для наномикроскопов на основе диморфных пьезоэлементов. Построена и исследована модель сканера при помощи программы MicroCap 7.0

ClusterCAD: a computational platform for type I modular polyketide synthase design

ClusterCAD is a web-based toolkit designed to leverage the collinear structure and deterministic logic of type I modular polyketide synthases (PKSs) for synthetic biology applications. The unique organization of these megasynthases, combined with the diversity of their catalytic domain building blocks, has fueled an interest in harnessing the biosynthetic potential of PKSs for the microbial production of both novel natural product analogs and industrially relevant small molecules. However, a limited theoretical understanding of the determinants of PKS fold and function poses a substantial barrier to the design of active variants, and identifying strategies to reliably construct functional PKS chimeras remains an active area of research. In this work, we formalize a paradigm for the design of PKS chimeras and introduce ClusterCAD as a computational platform to streamline and simplify the process of designing experiments to test strategies for engineering PKS variants. ClusterCAD provides chemical structures with stereochemistry for the intermediates generated by each PKS module, as well as sequence- and structure-based search tools that allow users to identify modules based either on amino acid sequence or on the chemical structure of the cognate polyketide intermediate. ClusterCAD can be accessed at https://clustercad.jbei.org and at http://clustercad.igb.uci.edu

Orbital alignment and mass segregation in galactic nuclei via vector resonant relaxation

Supermassive black holes dominate the gravitational potential in galactic nuclei. In these dense environments, stars follow nearly Keplerian orbits and see their orbital planes relax through the potential fluctuations generated by the stellar cluster itself. For typical astrophysical galactic nuclei, the most likely outcome of this vector resonant relaxation (VRR) is that the orbital planes of the most massive stars spontaneously self-align within a narrow disc. We present a maximum entropy method to systematically determine this long-term distribution of orientations and use it for a wide range of stellar orbital parameters and initial conditions. The heaviest stellar objects are found to live within a thin equatorial disk. The thickness of this disk depends on the stars' initial mass function, and on the geometry of the initial cluster. This work highlights a possible (indirect) novel method to constrain the distribution of intermediate mass black holes in galactic nuclei.Comment: 14 pages, 17 figures, accepted for publication in MNRA

The local GLP-1 system in the olfactory bulb is required for odor-evoked cephalic phase of insulin release in mice

Objective: The olfactory bulb (OB) codes for sensory information and contributes to the control of energy metabolism by regulating foraging and cephalic phase responses. Mitral cells are the main output neurons of the OB. The glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) system in the OB (GLP-1ᴼᴮ) has been shown to be a major regulator of mitral cell activity but its function in vivo is unclear. Therefore, we investigated the role of GLP-1ᴼᴮ in foraging behavior and odor-evoked Cephalic Phase Insulin Release (CPIR)./ Methods and results: By fluorescent labeling, we confirmed the presence of GLP-1 producing neurons and the expression of GLP-1R in the mouse OB. In response to food odor presentation, we collected blood, quantified plasma insulin by ELISA and showed the existence of an odor-evoked CPIR in lean mice but its absence in obese animals. Expression of shRNA against preproglucagon mRNA in the OB resulted in blunted CPIR in lean mice. Injecting Exendin (9-39), a GLP-1R antagonist, into the OB of lean mice also resulted in decreased CPIR. Since parasympathetic cholinergic input to the pancreas is known to be partly responsible for CPIR, we systemically administered the muscarinic M3 receptor antagonist 4-DAMP which resulted in a reduced odor-evoked CPIR. Finally, local injection of Exendin (9-39) in the OB extinguished olfactory foraging in lean mice whereas the injection of the GLP-1R agonist Exendin-4 rescued the loss of foraging behavior in obese mice./ Conclusions: Our results demonstrate that GLP-1ᴼᴮ controls olfactory foraging and is required for odor-evoked CPIR. We describe a new crucial brain function for GLP-1 and GLP-1R expressed within the brain