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71.
Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis) 下载免费PDF全文
W. Chris Funk Robert E. Lovich Paul A. Hohenlohe Courtney A. Hofman Scott A. Morrison T. Scott Sillett Cameron K. Ghalambor Jesus E. Maldonado Torben C. Rick Mitch D. Day Nicholas R. Polato Sarah W. Fitzpatrick Timothy J. Coonan Kevin R. Crooks Adam Dillon David K. Garcelon Julie L. King Christina L. Boser Nicholas Gould William F. Andelt 《Molecular ecology》2016,25(10):2176-2194
The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction‐site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome‐wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential. 相似文献
72.
Nikisha Carty Nadège Berson Karsten Tillack Christina Thiede Diana Scholz Karsten Kottig Yalda Sedaghat Christina Gabrysiak George Yohrling Heinz von der Kammer Andreas Ebneth Volker Mack Ignacio Munoz-Sanjuan Seung Kwak 《PloS one》2015,10(4)
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Major pathological hallmarks of HD include inclusions of mutant huntingtin (mHTT) protein, loss of neurons predominantly in the caudate nucleus, and atrophy of multiple brain regions. However, the early sequence of histological events that manifest in region- and cell-specific manner has not been well characterized. Here we use a high-content histological approach to precisely monitor changes in HTT expression and characterize deposition dynamics of mHTT protein inclusion bodies in the recently characterized zQ175 knock-in mouse line. We carried out an automated multi-parameter quantitative analysis of individual cortical and striatal cells in tissue slices from mice aged 2–12 months and confirmed biochemical reports of an age-associated increase in mHTT inclusions in this model. We also found distinct regional and subregional dynamics for inclusion number, size and distribution with subcellular resolution. We used viral-mediated suppression of total HTT in the striatum of zQ175 mice as an example of a therapeutically-relevant but heterogeneously transducing strategy to demonstrate successful application of this platform to quantitatively assess target engagement and outcome on a cellular basis. 相似文献
73.
Takayuki Yasunaga Sylvia Hoff Christoph Schell Martin Helmst?dter Oliver Kretz Sebastian Kuechlin Toma A. Yakulov Christina Engel Barbara Müller Robert Bensch Olaf Ronneberger Tobias B. Huber Soeren S. Lienkamp Gerd Walz 《The Journal of cell biology》2015,211(5):963-973
Motile cilia polarization requires intracellular anchorage to the cytoskeleton; however, the molecular machinery that supports this process remains elusive. We report that Inturned plays a central role in coordinating the interaction between cilia-associated proteins and actin-nucleation factors. We observed that knockdown of nphp4 in multiciliated cells of the Xenopus laevis epidermis compromised ciliogenesis and directional fluid flow. Depletion of nphp4 disrupted the subapical actin layer. Comparison to the structural defects caused by inturned depletion revealed striking similarities. Furthermore, coimmunoprecipitation assays demonstrated that the two proteins interact with each other and that Inturned mediates the formation of ternary protein complexes between NPHP4 and DAAM1. Knockdown of daam1, but not formin-2, resulted in similar disruption of the subapical actin web, whereas nphp4 depletion prevented the association of Inturned with the basal bodies. Thus, Inturned appears to function as an adaptor protein that couples cilia-associated molecules to actin-modifying proteins to rearrange the local actin cytoskeleton. 相似文献
74.
Blake Ushijima Patrick Videau Andrew H. Burger Amanda Shore-Maggio Christina M. Runyon Mareike Sudek Greta S. Aeby Sean M. Callahan 《Applied and environmental microbiology》2014,80(7):2102-2109
Identification of a pathogen is a critical first step in the epidemiology and subsequent management of a disease. A limited number of pathogens have been identified for diseases contributing to the global decline of coral populations. Here we describe Vibrio coralliilyticus strain OCN008, which induces acute Montipora white syndrome (aMWS), a tissue loss disease responsible for substantial mortality of the coral Montipora capitata in Kāne‘ohe Bay, Hawai‘i. OCN008 was grown in pure culture, recreated signs of disease in experimentally infected corals, and could be recovered after infection. In addition, strains similar to OCN008 were isolated from diseased coral from the field but not from healthy M. capitata. OCN008 repeatedly induced the loss of healthy M. capitata tissue from fragments under laboratory conditions with a minimum infectious dose of between 107 and 108 CFU/ml of water. In contrast, Porites compressa was not infected by OCN008, indicating the host specificity of the pathogen. A decrease in water temperature from 27 to 23°C affected the time to disease onset, but the risk of infection was not significantly reduced. Temperature-dependent bleaching, which has been observed with the V. coralliilyticus type strain BAA-450, was not observed during infection with OCN008. A comparison of the OCN008 genome to the genomes of pathogenic V. coralliilyticus strains BAA-450 and P1 revealed similar virulence-associated genes and quorum-sensing systems. Despite this genetic similarity, infections of M. capitata by OCN008 do not follow the paradigm for V. coralliilyticus infections established by the type strain. 相似文献
75.
de Melo Reis RA Ventura AL Schitine CS de Mello MC de Mello FG 《Neurochemical research》2008,33(8):1466-1474
Müller cells represent the main type of glia present in the retina interacting with most, if not all neurons in this tissue.
Müller cells have been claimed to function as optic fibers in the retina delivering light to photoreceptors with minimal distortion
and low loss [Franze et al (2007) Proc Natl Acad Sci 104:8287–8292]. Most of the mediators found in the brain are also detected
in the retinal tissue, and glia cells are active players in the synthesis, release, signaling and uptake of major mediators
of synaptic function. Müller glia trophic factors may regulate many different aspects of neuronal circuitry during synaptogenesis,
differentiation, neuroprotection and survival of photoreceptors, Retinal Ganglion Cells (RGCs) and other targets in the retina.
Here we review the role of several transmitters and trophic factors that participate in the neuron-glia loop in the retina.
Special issue article in honor of Dr. Ricardo Tapia. 相似文献
76.
Impact of Plant Functional Group, Plant Species, and Sampling Time on the Composition of nirK-Type Denitrifier Communities in Soil 下载免费PDF全文
Christina Bremer Gesche Braker Diethart Matthies Andreas Reuter Christof Engels Ralf Conrad 《Applied microbiology》2007,73(21):6876-6884
We studied the influence of eight nonleguminous grassland plant species belonging to two functional groups (grasses and forbs) on the composition of soil denitrifier communities in experimental microcosms over two consecutive years. Denitrifier community composition was analyzed by terminal restriction fragment length polymorphism (T-RFLP) of PCR-amplified nirK gene fragments coding for the copper-containing nitrite reductase. The impact of experimental factors (plant functional group, plant species, sampling time, and interactions between them) on the structure of soil denitrifier communities (i.e., T-RFLP patterns) was analyzed by canonical correspondence analysis. While the functional group of a plant did not affect nirK-type denitrifier communities, plant species identity did influence their composition. This effect changed with sampling time, indicating community changes due to seasonal conditions and a development of the plants in the microcosms. Differences in total soil nitrogen and carbon, soil pH, and root biomass were observed at the end of the experiment. However, statistical analysis revealed that the plants affected the nirK-type denitrifier community composition directly, e.g., through root exudates. Assignment of abundant T-RFs to cloned nirK sequences from the soil and subsequent phylogenetic analysis indicated a dominance of yet-unknown nirK genotypes and of genes related to nirK from denitrifiers of the order Rhizobiales. In conclusion, individual species of nonleguminous plants directly influenced the composition of denitrifier communities in soil, but environmental conditions had additional significant effects. 相似文献
77.
Koufaki M Detsi A Theodorou E Kiziridi C Calogeropoulou T Vassilopoulos A Kourounakis AP Rekka E Kourounakis PN Gaitanaki C Papazafiri P 《Bioorganic & medicinal chemistry》2004,12(18):4835-4841
Novel hybrids of lipoic acid and trolox connected through triamine spacers as well as analogues in which the lipoic acid was attached at different positions of the chroman moiety of vitamin E through an amide bond, were synthesized and exhibited strong inhibition of the microsomal lipid peroxidation. Moreover, the new molecules, at 1 microM concentration, reduced reperfusion arrhythmias and MDA content on isolated rat heart preparations, with the 2- and 5-subtituted chromans possessing the better cardioprotective activity. 相似文献
78.
Böttcher S Maresch C Granzow H Klupp BG Teifke JP Mettenleiter TC 《Journal of virology》2008,82(12):6009-6016
Herpesviruses specify a ubiquitin-specific protease activity located within their largest tegument protein. Although its biological role is still largely unclear, mutation within the active site abolished deubiquitinating (DUB) activity and decreased virus replication in vitro and in vivo. To further elucidate the role of DUB activity for herpesvirus replication, the conserved active-site cysteine at amino acid position 26 within pUL36 of Pseudorabies virus (PrV) (Suid herpesvirus 1), a neurotropic alphaherpesvirus, was mutated to serine. Whereas one-step growth kinetics of the resulting mutant virus PrV-UL36(C(26)S) were moderately reduced, plaque size was decreased to 62% of that of the wild-type virus. Ultrastructural analysis revealed large accumulations of unenveloped nucleocapsids in the cytoplasm, but incorporation of the tegument protein pUL37 was not abolished. After intranasal infection with PrV-UL36(C(26)S) mice showed survival times two times longer than those of mice infected with wild-type or rescued virus. Thus, the DUB activity is important for PrV replication in vitro and for neuroinvasion in mice. 相似文献
79.
Nonalcoholic fatty liver disease and measures of early brain health in middle‐aged adults: The CARDIA study 下载免费PDF全文
80.
Feng DM Wai JM Kuduk SD Ng C Murphy KL Ransom RW Reiss D Chang RS Harrell CM MacNeil T Tang C Prueksaritanont T Freidinger RM Pettibone DJ Bock MG 《Bioorganic & medicinal chemistry letters》2005,15(9):2385-2388
A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. 相似文献