Clone size distributions in networks of genetic similarity

We build networks of genetic similarity in which the nodes are organisms sampled from biological populations. The procedure is illustrated by constructing networks from genetic data of a marine clonal plant. An important feature in the networks is the presence of clone subgraphs, i.e. sets of organisms with identical genotype forming clones. As a first step to understand the dynamics that has shaped these networks, we point up a relationship between a particular degree distribution and the clone size distribution in the populations. We construct a dynamical model for the population dynamics, focussing on the dynamics of the clones, and solve it for the required distributions. Scale free and exponentially decaying forms are obtained depending on parameter values, the first type being obtained when clonal growth is the dominant process. Average distributions are dominated by the power law behavior presented by the fastest replicating populations.Comment: 17 pages, 4 figures. One figure improved and other minor changes. To appear in Physica

Treatment of fabry disease: Current and emerging strategies

Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency of the enzyme α-galactosidase A (GLA). Absent or reduced enzyme activity leads to impaired catabolism of neutral glycosphingolipids, particularly globotriaosylceramide (Gb3), resulting in intracellular deposition of such lipids. Clinical manifestations in hemizygote males include angiokeratoma, hypohydrosis, acroparesthesia, abdominal pain, proteinuria, renal insufficiency, left ventricular hypertrophy and cerebrovascular accidents. Heterozygote women may present with mild to severe signs and symptoms. Since year 2001, enzyme replacement therapy (ERT) is the only specific treatment for Fabry disease. The beneficial effect of ERT on different organs/systems has been extensively evaluated, and an improvement in renal function, cardiac mass and quality of life has been reported. Different treatment approaches are currently on development. One of them implies the use of the active-site-specific chaperone 1-deoxygalactonojirimycin that acts facilitating folding of mutant GLA in the endoplasmic reticulum and increasing its lysosomal residual activity. Reduction of Gb3 deposits has been shown in lymphoblasts from Fabry patients with missense mutations and transgenic mouse model expressing a missense mutation GLA. Gene therapy has been also developed as a potential option for treatment of Fabry disease. This review will discuss these novel therapeutic options along with their advantages and limitations.Fil: Rozenfeld, Paula Adriana. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Neumann, Pablo M.. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentin

Network analysis identifies weak and strong links in a metapopulation system

The identification of key populations shaping the structure and connectivity of metapopulation systems is a major challenge in population ecology. The use of molecular markers in the theoretical framework of population genetics has allowed great advances in this field, but the prime question of quantifying the role of each population in the system remains unresolved. Furthermore, the use and interpretation of classical methods are still bounded by the need for a priori information and underlying assumptions that are seldom respected in natural systems. Network theory was applied to map the genetic structure in a metapopulation system by using microsatellite data from populations of a threatened seagrass, Posidonia oceanica, across its whole geographical range. The network approach, free from a priori assumptions and from the usual underlying hypotheses required for the interpretation of classical analyses, allows both the straightforward characterization of hierarchical population structure and the detection of populations acting as hubs critical for relaying gene flow or sustaining the metapopulation system. This development opens perspectives in ecology and evolution in general, particularly in areas such as conservation biology and epidemiology, where targeting specific populations is crucial

Fractal and Transfractal Recursive Scale-Free Nets

We explore the concepts of self-similarity, dimensionality, and (multi)scaling in a new family of recursive scale-free nets that yield themselves to exact analysis through renormalization techniques. All nets in this family are self-similar and some are fractals - possessing a finite fractal dimension - while others are small world (their diameter grows logarithmically with their size) and are infinite-dimensional. We show how a useful measure of "transfinite" dimension may be defined and applied to the small world nets. Concerning multiscaling, we show how first-passage time for diffusion and resistance between hub (the most connected nodes) scale differently than for other nodes. Despite the different scalings, the Einstein relation between diffusion and conductivity holds separately for hubs and nodes. The transfinite exponents of small world nets obey Einstein relations analogous to those in fractal nets.Comment: Includes small revisions and references added as result of readers' feedbac

Evolutionary and Ecological Trees and Networks

Evolutionary relationships between species are usually represented in phylogenies, i.e. evolutionary trees, which are a type of networks. The terminal nodes of these trees represent species, which are made of individuals and populations among which gene flow occurs. This flow can also be represented as a network. In this paper we briefly show some properties of these complex networks of evolutionary and ecological relationships. First, we characterize large scale evolutionary relationships in the Tree of Life by a degree distribution. Second, we represent genetic relationships between individuals of a Mediterranean marine plant, Posidonia oceanica, in terms of a Minimum Spanning Tree. Finally, relationships among plant shoots inside populations are represented as networks of genetic similarity.Comment: 6 pages, 5 figures. To appear in Proceedings of the Medyfinol06 Conferenc

Vertex routing models

A class of models describing the flow of information within networks via routing processes is proposed and investigated, concentrating on the effects of memory traces on the global properties. The long-term flow of information is governed by cyclic attractors, allowing to define a measure for the information centrality of a vertex given by the number of attractors passing through this vertex. We find the number of vertices having a non-zero information centrality to be extensive/sub-extensive for models with/without a memory trace in the thermodynamic limit. We evaluate the distribution of the number of cycles, of the cycle length and of the maximal basins of attraction, finding a complete scaling collapse in the thermodynamic limit for the latter. Possible implications of our results on the information flow in social networks are discussed.Comment: 12 pages, 6 figure

Transition from fractal to non-fractal scalings in growing scale-free networks

Real networks can be classified into two categories: fractal networks and non-fractal networks. Here we introduce a unifying model for the two types of networks. Our model network is governed by a parameter $q$. We obtain the topological properties of the network including the degree distribution, average path length, diameter, fractal dimensions, and betweenness centrality distribution, which are controlled by parameter $q$. Interestingly, we show that by adjusting $q$, the networks undergo a transition from fractal to non-fractal scalings, and exhibit a crossover from `large' to small worlds at the same time. Our research may shed some light on understanding the evolution and relationships of fractal and non-fractal networks.Comment: 7 pages, 3 figures, definitive version accepted for publication in EPJ

Crispr/cas9 editing for gaucher disease modelling

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the acid \u3b2-glucosidase gene (GBA1). Besides causing GD, GBA1 mutations constitute the main genetic risk factor for developing Parkinson\u2019s disease. The molecular basis of neurological manifestations in GD remain elusive. However, neuroinflammation has been proposed as a key player in this process. We exploited CRISPR/Cas9 technology to edit GBA1 in the human monocytic THP-1 cell line to develop an isogenic GD model of monocytes and in glioblastoma U87 cell lines to generate an isogenic GD model of glial cells. Both edited (GBA1 mutant) cell lines presented low levels of mutant acid \u3b2-glucosidase expression, less than 1% of residual activity and massive accumulation of substrate. Moreover, U87 GBA1 mutant cells showed that the mutant enzyme was retained in the ER and subjected to proteasomal degradation, triggering unfolded protein response (UPR). U87 GBA1 mutant cells displayed an increased production of interleukin-1\u3b2, both with and without inflammosome activation, \u3b1-syn accumulation and a higher rate of cell death in comparison with wild-type cells. In conclusion, we developed reliable, isogenic, and easy-to-handle cellular models of GD obtained from commercially accessible cells to be employed in GD pathophysiology studies and high-throughput drug screenings