Showing papers by "Tel Aviv University published in 2008"

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

The role of executive function and attention in gait

Abstract: Until recently, gait was generally viewed as a largely automated motor task, requiring minimal higher-level cognitive input. Increasing evidence, however, links alterations in executive function and attention to gait disturbances. This review discusses the role of executive function and of attention in healthy walking and gait disorders while summarizing the relevant, recent literature. We describe the variety of gait disorders that may be associated with different aspects of executive function, and discuss the changes occurring in executive function as a result of aging and disease as well the potential impact of these changes on gait. The attentional demands of gait are often tested using dual tasking methodologies. Relevant studies in healthy adults and patients are presented, as are the possible mechanisms responsible for the deterioration of gait during dual tasking. Lastly, we suggest how assessments of executive function and attention could be applied in the clinical setting as part of the process of identifying and understanding gait disorders and fall risk.

Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis

Abstract: The microbiota of the mammalian intestine depend largely on dietary polysaccharides as energy sources. Most of these polymers are not degradable by the host, but herbivores can derive 70% of their energy intake from microbial breakdown — a classic example of mutualism. Moreover, dietary polysaccharides that reach the human large intestine have a major impact on gut microbial ecology and health. Insight into the molecular mechanisms by which different gut bacteria use polysaccharides is, therefore, of fundamental importance. Genomic analyses of the gut microbiota could revolutionize our understanding of these mechanisms and provide new biotechnological tools for the conversion of polysaccharides, including lignocellulosic biomass, into monosaccharides.

Diffusion Tensor Imaging (DTI)-based White Matter Mapping in Brain Research: A Review

Abstract: Diffusion tensor imaging (DTI) has become one of the most popular MRI techniques in brain research, as well as in clinical practice. The number of brain studies with DTI is growing steadily and, over the last decade, has produced more than 700 publications. Diffusion tensor imaging enables visualization and characterization of white matter fascicli in two and three dimensions. Since the introduction of this methodology in 1994, it has been used to study the white matter architecture and integrity of the normal and diseased brains (multiple sclerosis, stroke, aging, dementia, schizophrenia, etc.). Although it provided image contrast that was not available with routine MR techniques, unique information on white matter and 3D visualization of neuronal pathways, many questions were raised regarding the origin of the DTI signal. Diffusion tensor imaging is constantly validated, challenged, and developed in terms of acquisition scheme, image processing, analysis, and interpretation. While DTI offers a powerful tool to study and visualize white matter, it suffers from inherent artifacts and limitations. The partial volume effect and the inability of the model to cope with non-Gaussian diffusion are its two main drawbacks. Nevertheless, when combined with functional brain mapping, DTI provides an efficient tool for comprehensive, noninvasive, functional anatomy mapping of the human brain. This review summarizes the development of DTI in the last decade with respect to the specificity and utility of the technique in radiology and anatomy studies.

Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution.

Abstract: We present here the hologenome theory of evolution, which considers the holobiont (the animal or plant with all of its associated microorganisms) as a unit of selection in evolution. The hologenome is defined as the sum of the genetic information of the host and its microbiota. The theory is based on four generalizations: (1) All animals and plants establish symbiotic relationships with microorganisms. (2) Symbiotic microorganisms are transmitted between generations. (3) The association between host and symbionts affects the fitness of the holobiont within its environment. (4) Variation in the hologenome can be brought about by changes in either the host or the microbiota genomes; under environmental stress, the symbiotic microbial community can change rapidly. These points taken together suggest that the genetic wealth of diverse microbial symbionts can play an important role both in adaptation and in evolution of higher organisms. During periods of rapid changes in the environment, the diverse microbial symbiont community can aid the holobiont in surviving, multiplying and buying the time necessary for the host genome to evolve. The distinguishing feature of the hologenome theory is that it considers all of the diverse microbiota associated with the animal or the plant as part of the evolving holobiont. Thus, the hologenome theory fits within the framework of the 'superorganism' proposed by Wilson and Sober.

Modelling and analysis of gene regulatory networks

Abstract: Gene regulatory networks have an important role in every process of life, including cell differentiation, metabolism, the cell cycle and signal transduction. By understanding the dynamics of these networks we can shed light on the mechanisms of diseases that occur when these cellular processes are dysregulated. Accurate prediction of the behaviour of regulatory networks will also speed up biotechnological projects, as such predictions are quicker and cheaper than lab experiments. Computational methods, both for supporting the development of network models and for the analysis of their functionality, have already proved to be a valuable research tool.

The importance of certain assemblages of birds as “information‐centres” for food‐finding

Abstract: Summary Evidence is presented to support the hypothesis that communal roosts, breeding colonies and certain other bird assemblages have been evolved primarily for the efficient exploitation of unevenly-distributed food sources by serving as “information-centres”. Predation-pressure is regarded as being the most important factor “shaping” the assemblages. The shaping involves the choice of inaccessible or otherwise safe sites, optimum dispersal, mutual awareness of attack and joint defensive tactics, and serves to minimise the vulnerability to predation which would otherwise result when birds mass together in conspicuous, and often predictable centres.

MicroRNAs accurately identify cancer tissue origin

Abstract: MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that is involved in oncogenesis and shows remarkable tissue specificity. Their potential for tumor classification suggests they may be used in identifying the tissue in which cancers of unknown primary origin arose, a major clinical problem. We measured miRNA expression levels in 400 paraffin-embedded and fresh-frozen samples from 22 different tumor tissues and metastases. We used miRNA microarray data of 253 samples to construct a transparent classifier based on 48 miRNAs. Two-thirds of samples were classified with high confidence, with accuracy >90%. In an independent blinded test-set of 83 samples, overall high-confidence accuracy reached 89%. Classification accuracy reached 100% for most tissue classes, including 131 metastatic samples. We further validated the utility of the miRNA biomarkers by quantitative RT-PCR using 65 additional blinded test samples. Our findings demonstrate the effectiveness of miRNAs as biomarkers for tracing the tissue of origin of cancers of unknown primary origin.

The Psychology of Transcending the Here and Now

Abstract: People directly experience only themselves here and now but often consider, evaluate, and plan situations that are removed in time or space, that pertain to others' experiences, and that are hypothetical rather than real. People thus transcend the present and mentally traverse temporal distance, spatial distance, social distance, and hypotheticality. We argue that this is made possible by the human capacity for abstract processing of information. We review research showing that there is considerable similarity in the way people mentally traverse different distances, that the process of abstraction underlies traversing different distances, and that this process guides the way people predict, evaluate, and plan near and distant situations.

Mechanics of membrane fusion.

Abstract: Diverse membrane fusion reactions in biology involve close contact between two lipid bilayers, followed by the local distortion of the individual bilayers and reformation into a single, merged membrane. We consider the structures and energies of the fusion intermediates identified in experimental and theoretical work on protein-free lipid bilayers. On the basis of this analysis, we then discuss the conserved fusion-through-hemifusion pathway of merger between biological membranes and propose that the entire progression, from the close juxtaposition of membrane bilayers to the expansion of a fusion pore, is controlled by protein-generated membrane stresses.

A meta-analysis of work demand stressors and job performance: examining main and moderating effects

Abstract: We quantitatively integrated 169 samples (N= 35,265 employees) that have been used to investigate the relationships of the following 7 work-related stressors with job performance: role ambiguity, role conflict, role overload, job insecurity, work–family conflict, environmental uncertainty, and situational constraints. Overall, we obtained a negative mean correlation between each job performance measure and each stressor included in our analyses. As hypothesized, role ambiguity and situational constraints were most strongly negatively related to performance, relative to the other work-related stressors. Analysis of moderators revealed that (a) the negative correlation of role overload and performance was higher among managers relative to nonmanagers; (b) publication year moderated the relation of role ambiguity and role overload with performance, although in opposite directions; (c) the correlations obtained for published versus unpublished studies were not significantly different; and (d) using the Rizzo et al. scale of role ambiguity and role conflict decreased the magnitude of the correlations of these stressors with performance, relative to other scales. Theoretical contributions, future research directions, and practical implications are discussed.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Associations with Neonatal Anthropometrics

Abstract: Objective: To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. Research Design and Methods: Eligible pregnant women underwent a standard 75 gm OGTT between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skinfolds > 90th percentile or percent body fat > 90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's gender. Results: Among 23,316 HAPO study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-hour, and 2-hour plasma glucose higher by one standard deviation. Conclusions: These findings confirm the link between maternal glucose and neonatal adiposity, and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biologic relationship influencing fetal growth.

Axcaliber: A method for measuring axon diameter distribution from diffusion MRI

Abstract: The diameter of a myelinated nerve axon is directly proportional to its conduction velocity, so the axon diameter distribution helps determine the channel capacity of nervous transmission along fascicles in the central (CNS) and peripheral nervous systems (PNS). Previously, this histological information could only be obtained using invasive tissue biopsies. Here we propose a new NMR-based approach that employs a model of water diffusion within “restricted” cylindrical axons to estimate their diameter distribution within a nerve bundle. This approach can be combined with MRI to furnish an estimate of the axon diameter distribution within each voxel. This method is validated by comparing the diameter distributions measured using the NMR and histological techniques on sciatic and optic nerve tissue specimens. The axon diameter distribution measured in each voxel of porcine spinal cord using MRI and using histological methods were similar. Applications are expected in longitudinal studies designed to follow nerve growth in normal and abnormal development, as well as in diagnosing disorders and diseases affecting specific populations of axons in the CNS and PNS.

Deep photo: model-based photograph enhancement and viewing

Abstract: In this paper, we introduce a novel system for browsing, enhancing, and manipulating casual outdoor photographs by combining them with already existing georeferenced digital terrain and urban models. A simple interactive registration process is used to align a photograph with such a model. Once the photograph and the model have been registered, an abundance of information, such as depth, texture, and GIS data, becomes immediately available to our system. This information, in turn, enables a variety of operations, ranging from dehazing and relighting the photograph, to novel view synthesis, and overlaying with geographic information. We describe the implementation of a number of these applications and discuss possible extensions. Our results show that augmenting photographs with already available 3D models of the world supports a wide variety of new ways for us to experience and interact with our everyday snapshots.

Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy

Abstract: Background Despite guidelines recommending avoidance of peanuts during infancy in the United Kingdom (UK), Australia, and, until recently, North America, peanut allergy (PA) continues to increase in these countries. Objective We sought to determine the prevalence of PA among Israeli and UK Jewish children and evaluate the relationship of PA to infant and maternal peanut consumption. Methods A clinically validated questionnaire determined the prevalence of PA among Jewish schoolchildren (5171 in the UK and 5615 in Israel). A second validated questionnaire assessed peanut consumption and weaning in Jewish infants (77 in the UK and 99 in Israel). Results The prevalence of PA in the UK was 1.85%, and the prevalence in Israel was 0.17% (P Conclusions We demonstrate that Jewish children in the UK have a prevalence of PA that is 10-fold higher than that of Jewish children in Israel. This difference is not accounted for by differences in atopy, social class, genetic background, or peanut allergenicity. Israeli infants consume peanut in high quantities in the first year of life, whereas UK infants avoid peanuts. These findings raise the question of whether early introduction of peanut during infancy, rather than avoidance, will prevent the development of PA.

From Rings to Bulges: Evidence for Rapid Secular Galaxy Evolution at z ~ 2 from Integral Field Spectroscopy in the SINS Survey

Abstract: We present Hα integral field spectroscopy of well-resolved, UV/optically selected z ~ 2 star-forming galaxies as part of the SINS survey with SINFONI on the ESO VLT. Our laser guide star adaptive optics and good seeing data show the presence of turbulent rotating star-forming outer rings/disks, plus central bulge/inner disk components, whose mass fractions relative to the total dynamical mass appear to scale with the [N II]/Hα flux ratio and the star formation age. We propose that the buildup of the central disks and bulges of massive galaxies at z ~ 2 can be driven by the early secular evolution of gas-rich proto-disks. High-redshift disks exhibit large random motions. This turbulence may in part be stirred up by the release of gravitational energy in the rapid "cold" accretion flows along the filaments of the cosmic web. As a result, dynamical friction and viscous processes proceed on a timescale of <1 Gyr, at least an order of magnitude faster than in z ~ 0 disk galaxies. Early secular evolution thus drives gas and stars into the central regions and can build up exponential disks and massive bulges, even without major mergers. Secular evolution along with increased efficiency of star formation at high surface densities may also help to account for the short timescales of the stellar buildup observed in massive galaxies at z ~ 2.

FireDock: a web server for fast interaction refinement in molecular docking

Abstract: Structural details of protein-protein interactions are invaluable for understanding and deciphering biological mechanisms. Computational docking methods aim to predict the structure of a protein-protein complex given the structures of its single components. Protein flexibility and the absence of robust scoring functions pose a great challenge in the docking field. Due to these difficulties most of the docking methods involve a two-tier approach: coarse global search for feasible orientations that treats proteins as rigid bodies, followed by an accurate refinement stage that aims to introduce flexibility into the process. The FireDock web server, presented here, is the first web server for flexible refinement and scoring of protein-protein docking solutions. It includes optimization of side-chain conformations and rigid-body orientation and allows a high-throughput refinement. The server provides a user-friendly interface and a 3D visualization of the results. A docking protocol consisting of a global search by PatchDock and a refinement by FireDock was extensively tested. The protocol was successful in refining and scoring docking solution candidates for cases taken from docking benchmarks. We provide an option for using this protocol by automatic redirection of PatchDock candidate solutions to the FireDock web server for refinement. The FireDock web server is available at http://bioinfo3d.cs.tau.ac.il/FireDock/.

Network-based prediction of human tissue-specific metabolism

Abstract: Direct in vivo investigation of mammalian metabolism is complicated by the distinct metabolic functions of different tissues. We present a computational method that successfully describes the tissue specificity of human metabolism on a large scale. By integrating tissue-specific gene- and protein-expression data with an existing comprehensive reconstruction of the global human metabolic network, we predict tissue-specific metabolic activity in ten human tissues. This reveals a central role for post-transcriptional regulation in shaping tissue-specific metabolic activity profiles. The predicted tissue specificity of genes responsible for metabolic diseases and tissue-specific differences in metabolite exchange with biofluids extend markedly beyond tissue-specific differences manifest in enzyme-expression data, and are validated by large-scale mining of tissue-specificity data. Our results establish a computational basis for the genome-wide study of normal and abnormal human metabolism in a tissue-specific manner.

4-points congruent sets for robust pairwise surface registration

Abstract: We introduce 4PCS, a fast and robust alignment scheme for 3D point sets that uses wide bases, which are known to be resilient to noise and outliers. The algorithm allows registering raw noisy data, possibly contaminated with outliers, without pre-filtering or denoising the data. Further, the method significantly reduces the number of trials required to establish a reliable registration between the underlying surfaces in the presence of noise, without any assumptions about starting alignment. Our method is based on a novel technique to extract all coplanar 4-points sets from a 3D point set that are approximately congruent, under rigid transformation, to a given set of coplanar 4-points. This extraction procedure runs in roughly O(n2 + k) time, where n is the number of candidate points and k is the number of reported 4-points sets. In practice, when noise level is low and there is sufficient overlap, using local descriptors the time complexity reduces to O(n + k). We also propose an extension to handle similarity and affine transforms. Our technique achieves an order of magnitude asymptotic acceleration compared to common randomized alignment techniques. We demonstrate the robustness of our algorithm on several sets of multiple range scans with varying degree of noise, outliers, and extent of overlap.

Folding and binding cascades: dynamic landscapes and population shifts.

Abstract: Whereas previously we have successfully utilized the folding funnels concept to rationalize binding mechanisms (Ma B, Kumar S, Tsai CJ, Nussinov R, 1999, Protein Eng 12:713-720) and to describe binding (Tsai CJ, Kumar S, Ma B, Nussinov R, 1999, Protein Sci 8:1181-1190), here we further extend the concept of folding funnels, illustrating its utility in explaining enzyme pathways, multimolecular associations, and allostery. This extension is based on the recognition that funnels are not stationary; rather, they are dynamic, depending on the physical or binding conditions (Tsai CJ, Ma B, Nussinov R, 1999, Proc Natl Acad Sci USA 96:9970-9972). Different binding states change the surrounding environment of proteins. The changed environment is in turn expressed in shifted energy landscapes, with different shapes and distributions of populations of conformers. Hence, the function of a protein and its properties are not only decided by the static folded three-dimensional structure; they are determined by the distribution of its conformational substates, and in particular, by the redistributions of the populations under different environments. That is, protein function derives from its dynamic energy landscape, caused by changes in its surroundings.

Computational geometry algorithms library

Abstract: The CGAL C++ library offers geometric data structures and algorithms that are reliable, efficient, easy to use, and easy to integrate in existing software. Use of de facto standard libraries like CGAL increases productivity, because they allow software developers to focus on the application layer. This course is an overview of CGAL geometric algorithms and data structures. The lectures cover:•CGAL for 2D vector graphics, including Boolean operations on Bezier curves, offsets, simplification, and geometry on the sphere.•CGAL for 3D point sets, including principal component analysis, bounding volumes, simplification, outlier removal, normal estimation, normal orientation, denoising, triangulation, and surface reconstruction.•CGAL for mesh-based modeling and processing, including Boolean operations, convex decomposition, simplification, and parameterization.•CGAL for mesh generation, including surface and volume mesh generation, from 3D images, implicit functions, or polyhedral surfaces.The introductory lecture covers non-geometric topics: the exact geometric computing paradigm that makes CGAL reliable without sacrificing efficiency and the generic programming paradigm that facilitates integration into existing software.

Skeleton extraction by mesh contraction

Abstract: Extraction of curve-skeletons is a fundamental problem with many applications in computer graphics and visualization. In this paper, we present a simple and robust skeleton extraction method based on mesh contraction. The method works directly on the mesh domain, without pre-sampling the mesh model into a volumetric representation. The method first contracts the mesh geometry into zero-volume skeletal shape by applying implicit Laplacian smoothing with global positional constraints. The contraction does not alter the mesh connectivity and retains the key features of the original mesh. The contracted mesh is then converted into a 1D curve-skeleton through a connectivity surgery process to remove all the collapsed faces while preserving the shape of the contracted mesh and the original topology. The centeredness of the skeleton is refined by exploiting the induced skeleton-mesh mapping. In addition to producing a curve skeleton, the method generates other valuable information about the object's geometry, in particular, the skeleton-vertex correspondence and the local thickness, which are useful for various applications. We demonstrate its effectiveness in mesh segmentation and skinning animation.

Amyloids: Not Only Pathological Agents but Also Ordered Nanomaterials†

Abstract: Amyloid fibers constitute one of the most abundant and important naturally occurring self-associated assemblies. A variety of protein and peptide molecules with various amino acid sequences form these highly stable and well-organized assemblies under diverse conditions. These assemblies display phase states ranging from liquid crystals to rigid nanotubes. The potential applications of these supramolecular assemblies exceed those of synthetic polymers since the building blocks may introduce biological function in addition to mechanical properties. Here we review the structural characteristics of amyloidal supramolecular assemblies, their potential use as either natural or de novo designed sequences, and the range of applications that have been demonstrated so far.