Iodine

Intrusion Experiments to Measure Territory Size: Development of the Method, Tests through Simulations, and Application in the Frog Allobates femoralis

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Max Ringler, Eva Ringler, Daniela Magaña Mendoza, Walter Hödl Territoriality is a widespread behaviour in animals and its analysis is crucial in several areas of behavioural, ecological and evolutionary research. Commonly, territory size is assessed through territory mapping and the application of simple area estimators such as minimum convex polygons. In the present study we demonstrate that territory size can be determined adequately with an active approach through intrusion experiments, a technique that is commonly used in behavioural research in other contexts. Tests with simulated data indicate that a minimum of twelve trials needs to be performed to establish reliable orders of relative territory size. To estimate absolute territory size, detailed hull techniques are most appropriate when analyzing point patterns of intrusion experiments, while the local convex hull estimator enables the construction of internal utilization distributions based on such point patterns. Additionally we suggest a ‘stretch the centre’ approach to emphasize the actual process of intrusion experiments in the construction of internal utilization distributions. To demonstrate the utility of the method, we apply all findings from the simulations to data from fieldwork with the model species Allobates femoralis, a territorial aromobatid frog from the lowland rainforest of French Guiana.]]>

MicroRNA-Mediated Positive Feedback Loop and Optimized Bistable Switch in a Cancer Network Involving miR-17-92

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Yichen Li, Yumin Li, Hui Zhang, Yong Chen MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in many key biological processes, including development, cell differentiation, the cell cycle and apoptosis, as central post-transcriptional regulators of gene expression. Recent studies have shown that miRNAs can act as oncogenes and tumor suppressors depending on the context. The present work focuses on the physiological significance of miRNAs and their role in regulating the switching behavior. We illustrate an abstract model of the Myc/E2F/miR-17-92 network presented by Aguda et al. (2008), which is composed of coupling between the E2F/Myc positive feedback loops and the E2F/Myc/miR-17-92 negative feedback loop. By systematically analyzing the network in close association with plausible experimental parameters, we show that, in the presence of miRNAs, the system bistability emerges from the system, with a bistable switch and a one-way switch presented by Aguda et al. instead of a single one-way switch. Moreover, the miRNAs can optimize the switching process. The model produces a diverse array of response-signal behaviors in response to various potential regulating scenarios. The model predicts that this transition exists, one from cell death or the cancerous phenotype directly to cell quiescence, due to the existence of miRNAs. It was also found that the network involving miR-17-92 exhibits high noise sensitivity due to a positive feedback loop and also maintains resistance to noise from a negative feedback loop.]]>

Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Erin K. Purcell, Liqian Liu, Paul V. Thomas, R. Keith Duncan The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitabilityare unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD) on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs) are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type) potassiumcurrent by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (∼30%), ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.]]>

Attack Resilience of the Evolving Scientific Collaboration Network

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Xiao Fan Liu, Xiao-Ke Xu, Michael Small, Chi K. Tse Stationary complex networks have been extensively studied in the last ten years. However, many natural systems are known to be continuously evolving at the local (“microscopic”) level. Understanding the response to targeted attacks of an evolving network may shed light on both how to design robust systems and finding effective attack strategies. In this paper we study empirically the response to targeted attacks of the scientific collaboration networks. First we show that scientific collaboration network is a complex system which evolves intensively at the local level – fewer than 20% of scientific collaborations last more than one year. Then, we investigate the impact of the sudden death of eminent scientists on the evolution of the collaboration networks of their former collaborators. We observe in particular that the sudden death, which is equivalent to the removal of the center of the egocentric network of the eminent scientist, does not affect the topological evolution of the residual network. Nonetheless, removal of the eminent hub node is exactly the strategy one would adopt for an effective targeted attack on a stationary network. Hence, we use this evolving collaboration network as an experimental model for attack on an evolving complex network. We find that such attacks are ineffectual, and infer that the scientific collaboration network is the trace of knowledge propagation on a larger underlying social network. The redundancy of the underlying structure in fact acts as a protection mechanism against such network attacks.]]>

Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Silvia Y. Bando, Maryana C. Alegro, Edson Amaro, Alexandre V. Silva, Luiz H. M. Castro, Hung-Tzu Wen, Leandro de A. Lima, Helena Brentani, Carlos Alberto Moreira-Filho Background

Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). In order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations.

Methodology/Principal Findings

DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi.

Conclusions/Significance

CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions.

]]>

Regional Selection Acting on the OFD1 Gene Family

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Ti-Cheng Chang, Jessica L. Klabnik, Wan-Sheng Liu The OFD1 (oral-facial-digital, type 1) gene is implicated in several developmental disorders in humans. The X-linked OFD1 (OFD1X) is conserved in Eutheria. Knowledge about the Y-linked paralog (OFD1Y) is limited. In this study, we identified an OFD1Y on the bovine Y chromosome, which is expressed differentially from the bovine OFD1X. Phylogenetic analysis indicated that: a) the eutherian OFD1X and OFD1Y were derived from the pair of ancestral autosomes during sex chromosome evolution; b) the autosomal OFD1 pseudogenes, present in Catarrhini and Murinae, were derived from retropositions of OFD1X after the divergence of primates and rodents; and c) the presence of OFD1Y in the ampliconic region of the primate Y chromosome is an indication that the expansion of the ampliconic region may initiate from the X-degenerated sequence. In addition, we found that different regions of OFD1/OFD1X/OFD1Y are under differential selection pressures. The C-terminal half of OFD1 is under relaxed selection with an elevated Ka/Ks ratio and clustered positively selected sites, whereas the N-terminal half is under stronger constraints. This study provides some insights into why the OFD1X gene causes OFD1 (male-lethal X-linked dominant) and SGBS2 & JSRDs (X-linked recessive) syndromes in humans, and reveals the origin and evolution of the OFD1 family, which will facilitate further clinical investigation of the OFD1-related syndromes.]]>

Graph Constrained Discriminant Analysis: A New Method for the Integration of a Graph into a Classification Process

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Vincent Guillemot, Arthur Tenenhaus, Laurent Le Brusquet, Vincent Frouin Integrating gene regulatory networks (GRNs) into the classification process of DNA microarrays is an important issue in bioinformatics, both because this information has a true biological interest and because it helps in the interpretation of the final classifier. We present a method called graph-constrained discriminant analysis (gCDA), which aims to integrate the information contained in one or several GRNs into a classification procedure. We show that when the integrated graph includes erroneous information, gCDA's performance is only slightly worse, thus showing robustness to misspecifications in the given GRNs. The gCDA framework also allows the classification process to take into account as many a priori graphs as there are classes in the dataset. The gCDA procedure was applied to simulated data and to three publicly available microarray datasets. gCDA shows very interesting performance when compared to state-of-the-art classification methods. The software package gcda, along with the real datasets that were used in this study, are available online: http://biodev.cea.fr/gcda/.]]>

Muscle-Bound Primordial Stem Cells Give Rise to Myofiber-Associated Myogenic and Non-Myogenic Progenitors

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Elad Segev, Gabi Shefer, Rivka Adar, Noa Chapal-Ilani, Shalev Itzkovitz, Inna Horovitz, Yitzhak Reizel, Dafna Benayahu, Ehud Shapiro Myofiber cultures give rise to myogenic as well as to non-myogenic cells. Whether these myofiber-associated non-myogenic cells develop from resident stem cells that possess mesenchymal plasticity or from other stem cells such as mesenchymal stem cells (MSCs) remain unsolved. To address this question, we applied a method for reconstructing cell lineage trees from somatic mutations to MSCs and myogenic and non-myogenic cells from individual myofibers that were cultured at clonal density. Our analyses show that (i) in addition to myogenic progenitors, myofibers also harbor non-myogenic progenitors of a distinct, yet close, lineage; (ii) myofiber-associated non-myogenic and myogenic cells share the same muscle-bound primordial stem cells of a lineage distinct from bone marrow MSCs; (iii) these muscle-bound primordial stem-cells first part to individual muscles and then differentiate into myogenic and non-myogenic stem cells.]]>

attract: A Method for Identifying Core Pathways That Define Cellular Phenotypes

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Jessica C. Mar, Nicholas A. Matigian, John Quackenbush, Christine A. Wells attract is a knowledge-driven analytical approach for identifying and annotating the gene-sets that best discriminate between cell phenotypes. attract finds distinguishing patterns within pathways, decomposes pathways into meta-genes representative of these patterns, and then generates synexpression groups of highly correlated genes from the entire transcriptome dataset. attract can be applied to a wide range of biological systems and is freely available as a Bioconductor package and has been incorporated into the MeV software system.]]>

Identification of Novel NPRAP/δ-Catenin-Interacting Proteins and the Direct Association of NPRAP with Dynamin 2

Scott Christley et al. — Fri, 14 Oct 2011 21:00:00 +0000

by Carolina Koutras, Georges Lévesque Neural plakophilin-related armadillo protein (NPRAP or δ-catenin) is a neuronal-specific protein that is best known for its interaction with presenilin 1 (PS1). Interestingly, the hemizygous loss of NPRAP is associated with severe mental retardation in cri du chat syndrome (CDCS), and mutations in PS1 cause an aggressive, early-onset form of Alzheimer's disease. Until recently, studies on the function of NPRAP have focused on its ability to modulate dendritic protrusion elaboration through its binding to cell adhesion and scaffolding molecules. However, mounting evidence indicates that NPRAP participates in intracellular signaling and exists in the nucleus, where it modulates gene expression. This apparent bifunctional nature suggests an elaborate neuronal role, but how NPRAP came to participate in such distinct subcellular events remains a mystery. To gain insight into this pathway, we immunoprecipitated NPRAP from human SH SY5Y cells and identified several novel interacting proteins by mass spectrometry. These included neurofilament alpha-internexin, interferon regulatory protein 2 binding factors, and dynamins 1 and 2. We further validated dynamin 2/NPRAP colocalization and direct interaction in vivo, confirming their bona fide partnership. Interestingly, dynamin 2 has established roles in endocytosis and actin assembly, and both of these processes have the potential to interface with the cell adhesion and intracellular signaling processes that involve NPRAP. Our data provide new avenues for approaching NPRAP biology and suggest a broader role for this protein than previously thought.]]>