PredUs: a web server for predicting protein interfaces using structural neighbors

We describe PredUs, an interactive web server for the prediction of protein–protein interfaces. Potential interfacial residues for a query protein are identified by ‘mapping’ contacts from known interfaces of the query protein’s structural neighbors to surface residues of the query. We calculate a score for each residue to be interfacial with a support vector machine. Results can be visualized in a molecular viewer and a number of interactive features allow users to tailor a prediction to a particular hypothesis. The PredUs server is available at: http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:PredUs

Calcium Looping for Thermochemical Storage: Assessment of Intrinsic Reaction Rate and Estimate of Kinetic/Transport Parameters for Synthetic CaO/Mayenite Particles from TGA Data

Mayenite-supported CaO represents an affordable and safetycompliant candidate material for thermochemical storage processes. We here analyze the thermogravimetric analysis (TGA) performance of synthetic CaO/mayenite micrometric powder under carbonatation/calcination looping and develop a model to interpret and analyze the experimental results. In the experimental campaign, calcination is run at 900 degrees C, while the carbonatation temperature is varied between 600 and 800 degrees C. For the carbonatation reaction, a generalized shrinking core model assuming a thermodynamically consistent first-order kinetic and a conversion-dependent diffusivity of CO2 inside the porous CaCO3 layer is validated through TGA carbonatation tests conducted with CO2/N-2 mixtures at different compositions. Interestingly, the kinetic constant of this reaction is found to be relatively insensitive to the temperature in the interval considered. In contrast, diffusion-limited regimes are never found for the calcination reaction so that this phase of the cycle can be predicted based on a single kinetic constant of the heterogeneous reaction. This constant is found to follow the typical Arrhenius-type dependence on temperature. Sizably different kinetic and transport parameters are obtained in the first carbonation performed on virgin CaO/mayenite particles with respect to those associated with subsequent cycles. When different parameters are afforded for the first and following cycles, the shrinking core model proposed closely predicts the TGA data over five CaO/CaCO3 cycles. The results found constitute an essential preliminary piece of information for designing equipment geometry and operating conditions of industrial-scale reactors. In this respect, knowledge of the parameters defining the intrinsic reaction rates and diffusive transport is essential in defining the optimal conversion of the material associated with minimal looping time

A diet enriched in omega-3 PUFA and inulin prevents type 1 diabetes by restoring gut barrier integrity and immune homeostasis in NOD mice

IntroductionThe integrity of the gut barrier (GB) is fundamental to regulate the crosstalk between the microbiota and the immune system and to prevent inflammation and autoimmunity at the intestinal level but also in organs distal from the gut such as the pancreatic islets. In support to this idea, we recently demonstrated that breakage of GB integrity leads to activation of islet-reactive T cells and triggers autoimmune Type 1 Diabetes (T1D). In T1D patients as in the NOD mice, the spontaneous model of autoimmune diabetes, there are alterations of the GB that specifically affect structure and composition of the mucus layer; however, it is yet to be determined whether a causal link between breakage of the GB integrity and occurrence of autoimmune T1D exists. MethodsHere we restored GB integrity in the NOD mice through administration of an anti-inflammatory diet (AID- enriched in soluble fiber inulin and omega 3-PUFA) and tested the effect on T1D pathogenesis. ResultsWe found that the AID prevented T1D in NOD mice by restoring GB integrity with increased mucus layer thickness and higher mRNA transcripts of structural (Muc2) and immunoregulatory mucins (Muc1 and Muc3) as well as of tight junction proteins (claudin1). Restoration of GB integrity was linked to reduction of intestinal inflammation (i.e., reduced expression of IL-1 beta, IL-23 and IL-17 transcripts) and expansion of regulatory T cells (FoxP3(+) Treg cells and IL-10(+) Tr1 cells) at the expenses of effector Th1/Th17 cells in the intestine, pancreatic lymph nodes (PLN) and intra-islet lymphocytes (IIL) of AID-fed NOD mice. Importantly, the restoration of GB integrity and immune homeostasis were associated with enhanced concentrations of anti-inflammatory metabolites of the omega 3/omega 6 polyunsaturated fatty acids (PUFA) and arachidonic pathways and modifications of the microbiome profile with increased relative abundance of mucus-modulating bacterial species such as Akkermansia muciniphila and Akkermansia glycaniphila. DiscussionOur data provide evidence that the restoration of GB integrity and intestinal immune homeostasis through administration of a tolerogenic AID that changed the gut microbial and metabolic profiles prevents autoimmune T1D in preclinical models

A Network of SCOP Hidden Markov Models and Its Analysis

<p>Abstract</p> <p>Background</p> <p>The Structural Classification of Proteins (SCOP) database uses a large number of hidden Markov models (HMMs) to represent families and superfamilies composed of proteins that presumably share the same evolutionary origin. However, how the HMMs are related to one another has not been examined before.</p> <p>Results</p> <p>In this work, taking into account the processes used to build the HMMs, we propose a working hypothesis to examine the relationships between HMMs and the families and superfamilies that they represent. Specifically, we perform an all-against-all HMM comparison using the HHsearch program (similar to BLAST) and construct a network where the nodes are HMMs and the edges connect similar HMMs. We hypothesize that the HMMs in a connected component belong to the same family or superfamily more often than expected under a random network connection model. Results show a pattern consistent with this working hypothesis. Moreover, the HMM network possesses features distinctly different from the previously documented biological networks, exemplified by the exceptionally high clustering coefficient and the large number of connected components.</p> <p>Conclusions</p> <p>The current finding may provide guidance in devising computational methods to reduce the degree of overlaps between the HMMs representing the same superfamilies, which may in turn enable more efficient large-scale sequence searches against the database of HMMs.</p

6. MEMS based color-VGA micro-projector system

This paper presents a complete portable laser-based projection system using twofold of one dimensional magnetic actuated MEMS linear scanning micro-mirrors. Dedicated high speed electronics was developed to drive the MEMS, detect the mirror scanning position at any time and synchronize the two mirrors and the laser pulsation. The achieved projection system head is 4.5 cm3 and is able to project colorful static images and videos (50 fps) with projection size of 50 cm diagonal at 50 cm distance with VGA (640×480 px) resolution

FragmentStore—a comprehensive database of fragments linking metabolites, toxic molecules and drugs

Consideration of biomolecules in terms of their molecular building blocks provides valuable new information regarding their synthesis, degradation and similarity. Here, we present the FragmentStore, a resource for the comparison of fragments found in metabolites, drugs or toxic compounds. Starting from 13 000 metabolites, 16 000 drugs and 2200 toxic compounds we generated 35 000 different building blocks (fragments), which are not only relevant to their biosynthesis and degradation but also provide important information regarding side-effects and toxicity. The FragmentStore provides a variety of search options such as 2D structure, molecular weight, rotatable bonds, etc. Various analysis tools have been implemented including the calculation of amino acid preferences of fragments’ binding sites, classification of fragments based on the enzyme classification class of the enzyme(s) they bind to and small molecule library generation via a fragment-assembler tool. Using the FragmentStore, it is now possible to identify the common fragments of different classes of molecules and generate hypotheses about the effects of such intersections. For instance, the co-occurrence of fragments in different drugs may indicate similar targets and possible off-target interactions whereas the co-occurrence of fragments in a drug and a toxic compound/metabolite could be indicative of side-effects. The database is publicly available at: http://bioinformatics.charite.de/fragment_store

Recognition of beta-structural motifs using hidden Markov models trained with simulated evolution

Motivation: One of the most successful methods to date for recognizing protein sequences that are evolutionarily related, has been profile hidden Markov models. However, these models do not capture pairwise statistical preferences of residues that are hydrogen bonded in β-sheets. We thus explore methods for incorporating pairwise dependencies into these models

Role of B diffusion in the interfacial Dzyaloshinskii-Moriya interaction in Ta / Co₂₀ Fe₆₀B₂₀/MgO nanowires

We report on current-induced domain wall motion in Ta/Co20Fe60B20/MgO nanowires. Domain walls are observed to move against the electron flow when no magnetic field is applied, while a field along the nanowires strongly affects the domain wall motion velocity. A symmetric effect is observed for up-down and down-up domain walls. This indicates the presence of right-handed domain walls, due to a Dzyaloshinskii-Moriya interaction (DMI) with a DMI coefficient D=+0.06mJ/m2. The positive DMI coefficient is interpreted to be a consequence of B diffusion into the Ta buffer layer during annealing, which was observed by chemical depth profiling measurements. The experimental results are compared to one-dimensional model simulations including the effects of pinning. This modeling allows us to reproduce the experimental outcomes and reliably extract a spin-Hall angle θSH=-0.11 for Ta in the nanowires, showing the importance of an analysis that goes beyond the model for perfect nanowires

The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the ClC-1 channel

Myotonia congenita (MC) is a skeletal-muscle hyperexcitability disorder caused by loss-of-function mutations in the ClC-1 chloride channel. Mutations are scattered over the entire sequence of the channel protein, with more than 30\ua0mutations located in the poorly characterized cytosolic C-terminal domain. In this study, we characterized, through patch clamp, seven ClC-1 mutations identified in patients affected by MC of various severities and located in the C-terminal region. The p.Val829Met, p.Thr832Ile, p.Val851Met, p.Gly859Val, and p.Leu861Pro mutations reside in the CBS2 domain, while p.Pro883Thr and p.Val947Glu are in the C-terminal peptide. We showed that the functional properties of mutant channels correlated with the clinical phenotypes of affected individuals. In addition, we defined clusters of ClC-1 mutations within CBS2 and C-terminal peptide subdomains that share the same functional defect: mutations between 829 and 835 residues and in residue 883 induced an alteration of voltage dependence, mutations between 851 and 859 residues, and in residue 947 induced a reduction of chloride currents, whereas mutations on 861 residue showed no obvious change in ClC-1 function. This study improves our understanding of the mechanisms underlying MC, sheds light on the role of the C-terminal region in ClC-1 function, and provides information to develop new antimyotonic drugs