TY - CHAP AB - Small photochromic molecules are widespread in nature and serve as switches for a plethora of light-controlled processes. In a typical photoreceptor, the different geometries and polarities of the photochrome isomers are tightly coupled to functionally relevant conformational changes in the proteins. The past decade has seen extensive efforts to mimic nature and create proteins controlled by synthetic photochromes in the laboratory. Here, we discuss the role of molecular modeling to gain a structural understanding of photochromes and to design light-controlled peptides and proteins. We address several fundamental questions: What are the molecular structures of photochromes, particularly for metastable isomers that cannot be addressed experimentally? How are the structures of bistable photoisomers coupled to the conformational states of peptides and proteins? Can we design light-controlled proteins rapidly and reliably? After an introduction to the principles of molecular modeling, we answer these questions by examining systems that range from the size of isolated photochromes, to that of peptides and large cell surface receptors, each from its unique computational perspective. AU - Harald Janovjak AU - Isacoff, Ehud Y ID - 3724 T2 - Photosensitive Molecules for the Control of Biological Function TI - Structure-based design of light-controlled proteins VL - 55 ER - TY - JOUR AB - The pink dolphin (Inia geoffrensis) is widely distributed along the Amazon and Orinoco basins, covering an area of approximately 7 million km2. Previous morphological and genetic studies have proposed the existence of at least two evolutionary significant units: one distributed across the Orinoco and Amazon basins and another confined to the Bolivian Amazon. The presence of barriers in the riverine environment has been suggested to play a significant role in shaping present-day patterns of ecological and genetic structure for this species. In the present study, we examined the phylogeographic structure, lineage divergence time and historical demography using mitochondrial (mt)DNA sequences in different pink dolphin populations distributed in large and small spatial scales, including two neighbouring Brazilian Amazon populations. mtDNA control region (CR) analysis revealed that the Brazilian haplotypes occupy an intermediate position compared to three previously studied geographic locations: the Colombian Amazon, the Colombian Orinoco, and the Bolivian Amazon. On a local scale, we have identified a pattern of maternal isolation between two neighbouring populations from Brazil. Six mtDNA CR haplotypes were identified in Brazil with no sharing between the two populations, as well as specific cytochrome b (cyt b) haplotypes identified in each locality. In addition, we analyzed autosomal microsatellites to investigate male-mediated gene flow and demographic changes within the study area in Brazil. Data analysis of 14 microsatellite loci failed to detect significant population subdivision, suggesting that male-mediated gene flow may maintain homogeneity between these two locations. Moreover, both mtDNA and microsatellite data indicate a major demographic collapse within Brazil in the late Pleistocene. Bayesian skyline plots (BSP) of mtDNA data revealed a stable population for Colombian and Brazilian Amazon lineages through time, whereas a population decline was demonstrated in the Colombian Orinoco lineage. Moreover, BSP and Tajima's D and Fu's Fs tests revealed a recent population expansion exclusively in the Bolivian sample. Finally, we estimated that the diversification of the Inia sp. lineage began in the Late Pliocene (approximately 3.1 Mya) and continued throughout the Pleistocene. AU - Hollatz, Claudia AU - Vilaça, Sibelle AU - Fernandes Redondo, Rodrigo A AU - Marmontel, Míriam AU - Baker, Cyndi AU - Santos, Fabrício ID - 3770 IS - 4 JF - Biological Journal of the Linnean Society TI - The Amazon River system as an ecological barrier driving genetic differentiation of the pink dolphin (Inia geoffrensis) VL - 102 ER - TY - JOUR AB - The small-sized frugivorous bat Carollia perspicillata is an understory specialist and occurs in a wide range of lowland habitats, tending to be more common in tropical dry or moist forests of South and Central America. Its sister species, Carollia brevicauda, occurs almost exclusively in the Amazon rainforest. A recent phylogeographic study proposed a hypothesis of origin and subsequent diversification for C. perspicillata along the Atlantic coastal forest of Brazil. Additionally, it also found two allopatric clades for C. brevicauda separated by the Amazon Basin. We used cytochrome b gene sequences and a more extensive sampling to test hypotheses related to the origin and diversification of C. perspicillata plus C. brevicauda clade in South America. The results obtained indicate that there are two sympatric evolutionary lineages within each species. In C. perspicillata, one lineage is limited to the Southern Atlantic Forest, whereas the other is widely distributed. Coalescent analysis points to a simultaneous origin for C. perspicillata and C. brevicauda, although no place for the diversification of each species can be firmly suggested. The phylogeographic pattern shown by C. perspicillata is also congruent with the Pleistocene refugia hypothesis as a likely vicariant phenomenon shaping the present distribution of its intraspecific lineages. AU - Pavan, Ana AU - Martins, Felipe AU - Santos, Fabrício AU - Ditchfield, Albert AU - Fernandes Redondo, Rodrigo A ID - 3771 IS - 3 JF - Biological Journal of the Linnean Society TI - Patterns of diversification in two species of short-tailed bats (Carollia Gray, 1838): the effects of historical fragmentation of Brazilian rainforests. VL - 102 ER - TY - JOUR AU - Barton, Nicholas H ID - 3778 IS - 2 JF - Heredity TI - Estimating linkage disequilibria VL - 106 ER - TY - CHAP AB - During the development of multicellular organisms, cell fate specification is followed by the sorting of different cell types into distinct domains from where the different tissues and organs are formed. Cell sorting involves both the segregation of a mixed population of cells with different fates and properties into distinct domains, and the active maintenance of their segregated state. Because of its biological importance and apparent resemblance to fluid segregation in physics, cell sorting was extensively studied by both biologists and physicists over the last decades. Different theories were developed that try to explain cell sorting on the basis of the physical properties of the constituent cells. However, only recently the molecular and cellular mechanisms that control the physical properties driving cell sorting, have begun to be unraveled. In this review, we will provide an overview of different cell-sorting processes in development and discuss how these processes can be explained by the different sorting theories, and how these theories in turn can be connected to the molecular and cellular mechanisms driving these processes. AU - Krens, Gabriel AU - Heisenberg, Carl-Philipp J ED - Labouesse, Michel ID - 3791 T2 - Forces and Tension in Development TI - Cell sorting in development VL - 95 ER - TY - JOUR AB - Molecular noise, which arises from the randomness of the discrete events in the cell, significantly influences fundamental biological processes. Discrete-state continuous-time stochastic models (CTMC) can be used to describe such effects, but the calculation of the probabilities of certain events is computationally expensive. We present a comparison of two analysis approaches for CTMC. On one hand, we estimate the probabilities of interest using repeated Gillespie simulation and determine the statistical accuracy that we obtain. On the other hand, we apply a numerical reachability analysis that approximates the probability distributions of the system at several time instances. We use examples of cellular processes to demonstrate the superiority of the reachability analysis if accurate results are required. AU - Didier, Frédéric AU - Henzinger, Thomas A AU - Mateescu, Maria AU - Wolf, Verena ID - 3364 IS - 21 JF - Theoretical Computer Science TI - Approximation of event probabilities in noisy cellular processes VL - 412 ER - TY - JOUR AB - Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release. AU - Vyleta, Nicholas AU - Smith, Stephen ID - 469 IS - 12 JF - European Journal of Neuroscience TI - Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor VL - 31 ER - TY - JOUR AB - BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals. AU - Schlögl, Alois AU - Vidaurre, Carmen AU - Sander, Tilmann ID - 490 JF - Computational Intelligence and Neuroscience TI - BioSig: The free and open source software library for biomedical signal processing VL - 2011 ER - TY - JOUR AB - In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static. AU - Eichner, Alexander AU - Sixt, Michael K ID - 491 IS - 198 JF - Science Signaling TI - Setting the clock for recirculating lymphocytes VL - 4 ER - TY - JOUR AB - Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy. AU - Schraivogel, Daniel AU - Weinmann, Lasse AU - Beier, Dagmar AU - Tabatabai, Ghazaleh AU - Eichner, Alexander AU - Zhu, Jia AU - Anton, Martina AU - Sixt, Michael K AU - Weller, Michael AU - Beier, Christoph AU - Meister, Gunter ID - 518 IS - 20 JF - EMBO Journal TI - CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells VL - 30 ER -