Stimulation of Adenosine A 3 Receptors in Cerebral Ischemia: Neuronal Death, Recovery, or Both?

The role of the adenosine A 3 receptor continues to baffle, and, despite an increasing number of studies, the currently available data add to, rather than alleviate, the existing confusion. The reported effects of adenosine A 3 receptor stimulation appear to depend on the pattern of drug administration (acute vs. chronic), dose, and type of the target tissue. Thus, while acute exposure to A 3 receptor agonists protects against myocardial ischemia, it is severely damaging when these agents are given shortly prior to cerebral ischemia. Mast cells degranulate when their A 3 receptors are stimulated. Degranulation of neutrophils is, on the other hand, impaired. While reduced production of reactive nitrogen species has been reported following activation of A 3 receptors in collagen-induced arthritis, the process appears to be enhanced in cerebral ischemia. Indeed, immunocytochemical studies indicate that both pre- and postischemic treatment with A 3 receptor antagonist dramatically reduces nitric oxide synthase in the affected hippocampus. Even more surprisingly, low doses of A 3 receptor agonists seem to enhance astrocyte proliferation, while high doses induce their apoptosis. This review concentrates on the studies of cerebral A 3 receptors and, based on the available evidence, discusses the possibility of adenosine A 3 receptor serving as an integral element of the endogenous cerebral neuroprotective complex consisting of adenosine and its receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75391/1/j.1749-6632.1999.tb07984.x.pd

Neuron-oligodendrocyte myelination co-culture derived from embryonic rat spinal cord and cerebral cortex

An in vitro myelination model derived from rat central nervous system (CNS) remains to be established. Here, we describe a simple and reproducible myelination culture method using dissociated neuron-oligodendrocyte (OL) co-cultures from either the embryonic day 16 (E16) rat spinal cord or cerebral cortex. The dissociated cells are plated directly on poly-L-lysine-coated cover slips and maintained in a modified myelination medium that supports both OL and neuron differentiation. The spinal cord derived OL progenitor cells develop quickly into myelin basic protein (MBP)+ mature OLs and start to myelinate axons around 17 days in vitro (DIV17). Myelination reaches its peak around six weeks (DIV40) and the typical nodes of Ranvier are revealed by paranodal proteins Caspr and juxaparanodal protein Kv1.2 immunoreactivity. Electron microscopy (EM) shows typical myelination cytoarchitecture and synaptic organization. In contrast, the cortical-derived co-culture requires triiodothyronine (T3) in the culture medium for myelination. Finally, either hypomyelination and/or demyelination can be induced by exposing proinflammatory cytokines or demyelinating agents to the co-culture, suggesting the feasibility of this modified in vitro myelination model for myelin-deficit investigation

Monoamine oxidase A and A/B knockout mice display autistic-like features

This is the published version, also available electronically from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8876069&fileId=S1461145712000715Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOA deficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problem

Averages of b-hadron properties at the end of 2006

This article reports the world averages for measurements on b-hadron properties obtained by the Heavy Flavor Averaging Group (HFAG) using the available results at the end of 2006. In the averaging, the input parameters used in the various analyses are adjusted (rescaled) to common values, and all known correlations are taken into account. The averages include lifetimes, neutral meson mixing parameters, parameters of semileptonic decays, branching fractions of B decays to final states with open charm, charmonium and no charm, and measurements related to CP asymmetries.This article reports the world averages for measurements on b-hadron properties obtained by the Heavy Flavor Averaging Group (HFAG) using the available results at the end of 2006. In the averaging, the input parameters used in the various analyses are adjusted (rescaled) to common values, and all known correlations are taken into account. The averages include lifetimes, neutral meson mixing parameters, parameters of semileptonic decays, branching fractions of B decays to final states with open charm, charmonium and no charm, and measurements related to CP asymmetries

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Genomic variation in tomato, from wild ancestors to contemporary breeding accessions

[EN] Background: Domestication modifies the genomic variation of species. Quantifying this variation provides insights into the domestication process, facilitates the management of resources used by breeders and germplasm centers, and enables the design of experiments to associate traits with genes. We described and analyzed the genetic diversity of 1,008 tomato accessions including Solanum lycopersicum var. lycopersicum (SLL), S. lycopersicum var. cerasiforme (SLC), and S. pimpinellifolium (SP) that were genotyped using 7,720 SNPs. Additionally, we explored the allelic frequency of six loci affecting fruit weight and shape to infer patterns of selection. Results: Our results revealed a pattern of variation that strongly supported a two-step domestication process, occasional hybridization in the wild, and differentiation through human selection. These interpretations were consistent with the observed allele frequencies for the six loci affecting fruit weight and shape. Fruit weight was strongly selected in SLC in the Andean region of Ecuador and Northern Peru prior to the domestication of tomato in Mesoamerica. Alleles affecting fruit shape were differentially selected among SLL genetic subgroups. Our results also clarified the biological status of SLC. True SLC was phylogenetically positioned between SP and SLL and its fruit morphology was diverse. SLC and “cherry tomato” are not synonymous terms. The morphologically-based term “cherry tomato” included some SLC, contemporary varieties, as well as many admixtures between SP and SLL. Contemporary SLL showed a moderate increase in nucleotide diversity, when compared with vintage groups. Conclusions: This study presents a broad and detailed representation of the genomic variation in tomato. Tomato domestication seems to have followed a two step-process; a first domestication in South America and a second step in Mesoamerica. The distribution of fruit weight and shape alleles supports that domestication of SLC occurred in the Andean region. Our results also clarify the biological status of SLC as true phylogenetic group within tomato. We detect Ecuadorian and Peruvian accessions that may represent a pool of unexplored variation that could be of interest for crop improvement.We are grateful to the gene banks for their collections that made this study possible. We thank Syngenta Seeds for providing genotyping data for 42 accessions. We would like to thank the Supercomputing and Bioinnovation Center (Universidad de Malaga, Spain) for providing computational resources to process the SNAPP phylogenetic tree. This research was supported in part by the USDA/NIFA funded SolCAP project under contract number to DF and USDA AFRI 2013-67013-21229 to EvdK and DF.Blanca Postigo, JM.; Montero Pau, J.; Sauvage, C.; Bauchet, G.; Illa, E.; Díez Niclós, MJTDJ.; Francis, D.... (2015). Genomic variation in tomato, from wild ancestors to contemporary breeding accessions. BMC Genomics. 16(257):1-19. https://doi.org/10.1186/s12864-015-1444-1S11916257Tanksley SD, McCouch SR. Seed banks and molecular maps: unlocking genetic potential from the wild. Science (80-). 1997;277:1063–6.Doebley JF, Gaut BS, Smith BD. The molecular genetics of crop domestication. Cell. 2006;127:1309–21.Gepts P. A comparison between crop domestication, classical plant breeding, and genetic engineering. Crop Sci. 2002;42:1780.Weigel D, Nordborg M. Natural variation in Arabidopsis. How do we find the causal genes? Plant Physiol. 2005;138:567–8.Peralta IE, Spooner DM, Knapp S, Anderson C. Taxonomy of wild tomatoes and their relatives (Solanum sect. Lycopersicoides, sect. Juglandifolia, sect. Lycopersicon; Solanaceae). Syst Bot Monogr. 2008;84:1–186.Rick CM, Fobes JF. Allozyme variation in the cultivated tomato and closely related species. Bull Torrey Bot Club. 1975;102:376–84.Zuriaga E, Blanca J, Nuez F. Classification and phylogenetic relationships in Solanum section Lycopersicon based on AFLP and two nuclear gene sequences. Genet Resour Crop Evol. 2008;56:663–78.Zuriaga E, Blanca J, Cordero L, Sifres A, Blas-Cerdán WG, Morales R, et al. Genetic and bioclimatic variation in Solanum pimpinellifolium. Genet Resour Crop Evol. 2008;56:39–51.Blanca J, Cañizares J, Cordero L, Pascual L, Diez MJ, Nuez F. Variation revealed by SNP genotyping and morphology provides insight into the origin of the tomato. PLoS One. 2012;7:e48198.Rick CM. Natural variability in wild species of Lycopersicon and its bearing on tomato breeding. Genet Agrar. 1976;30:249–59.Rick CM, Holle M. Andean Lycopersicon esculentum var. cerasiforme: genetic variation and its evolutionary significance. Econ Bot. 1990;44:69–78.Nakazato T, Franklin RA, Kirk BC, Housworth EA. Population structure, demographic history, and evolutionary patterns of a green-fruited tomato, Solanum peruvianum (Solanaceae), revealed by spatial genetics analyses. Am J Bot. 2012;99:1207–16.Rick CM, Butler L. Cytogenetics of the Tomato. Adv Genet. 1956;8:267–382. Advances in Genetics.Jenkins JA. The origin of the cultivated tomato. Econ Bot. 1948;2:379–92.Nesbitt TC, Tanksley SD. Comparative sequencing in the genus lycopersicon: implications for the evolution of fruit size in the domestication of cultivated tomatoes. Genetics. 2002;162:365–79.Ranc N, Muños S, Santoni S, Causse M. A clarified position for Solanum lycopersicum var cerasiforme in the evolutionary history of tomatoes (solanaceae). BMC Plant Biol. 2008;8:130.De Candolle A. Origin of cultivated plants. 2nd ed. London: Trench, Paul; 1886.Miller JC, Tanksley SD. RFLP analysis of phylogenetic relationships and genetic variation in the genus Lycopersicon. Theor Appl Genet. 1990;80:437–48.Williams CE, Clair DAS. Phenetic relationships and levels of variability detected by restriction fragment length polymorphism and random amplified polymorphic DNA analysis of cultivated and wild accessions of Lycopersicon esculentum. Genome. 1993;36:619–30.Park YH, West MAL, St Clair DA. Evaluation of AFLPs for germplasm fingerprinting and assessment of genetic diversity in cultivars of tomato (Lycopersicon esculentum L). Genome. 2004;47:510–8.Sim S-C, Robbins MD, Van Deynze A, Michel AP, Francis DM. Population structure and genetic differentiation associated with breeding history and selection in tomato (Solanum lycopersicum L.). Heredity (Edinb). 2011;106:927–35.Sim S-C, Robbins MD, Chilcott C, Zhu T, Francis DM. Oligonucleotide array discovery of polymorphisms in cultivated tomato (Solanum lycopersicum L) reveals patterns of SNP variation associated with breeding. BMC Genomics. 2009;10:466.Sim S-C, Durstewitz G, Plieske J, Wieseke R, Ganal MW, Van Deynze A, et al. Development of a large SNP genotyping array and generation of high-density genetic maps in tomato. PLoS One. 2012;7:e40563.Frary A, Nesbitt TC, Grandillo S, Knaap E, Cong B, Liu J, et al. fw2.2: a quantitative trait locus key to the evolution of tomato fruit size. Science. 2000;289:85–8.Liu J, Van Eck J, Cong B, Tanksley SD. A new class of regulatory genes underlying the cause of pear-shaped tomato fruit. Proc Natl Acad Sci U S A. 2002;99:13302–6.Xiao H, Jiang N, Schaffner E, Stockinger EJ, van der Knaap E. A retrotransposon-mediated gene duplication underlies morphological variation of tomato fruit. Science. 2008;319:1527–30.Cong B, Barrero LS, Tanksley SD. Regulatory change in YABBY-like transcription factor led to evolution of extreme fruit size during tomato domestication. Nat Genet. 2008;40:800–4.Muños S, Ranc N, Botton E, Bérard A, Rolland S, Duffé P, et al. Increase in tomato locule number is controlled by two single-nucleotide polymorphisms located near WUSCHEL. Plant Physiol. 2011;156:2244–54.Chakrabarti M, Zhang N, Sauvage C, Muños S, Blanca J, Cañizares J, et al. A cytochrome P450 regulates a domestication trait in cultivated tomato. Proc Natl Acad Sci U S A. 2013;110:17125–30.Rodríguez GR, Muños S, Anderson C, Sim S-C, Michel A, Causse M, et al. Distribution of SUN, OVATE, LC, and FAS in the tomato germplasm and the relationship to fruit shape diversity. Plant Physiol. 2011;156:275–85.Sim S-C, Van Deynze A, Stoffel K, Douches DS, Zarka D, Ganal MW, et al. High-density SNP genotyping of tomato (Solanum lycopersicum L) reveals patterns of genetic variation due to breeding. PLoS One. 2012;7:e45520.Sauvage C, Segura V, Bauchet G, Stevens R, Thi Do P, Nikoloski Z, et al. Genome Wide Association in tomato reveals 44 candidate loci for fruit metabolic traits. Plant Physiol. 2014;165:1120–32.Hamilton JP, Sim S-C, Stoffel K, Van Deynze A, Buell CR, Francis DM. Single nucleotide polymorphism discovery in cultivated tomato via sequencing by synthesis. Plant Genome J. 2012;5:17.Patterson NJ, Price AL, Reich D. Population structure and eigenanalysis. PLoS Genet. 2006;2:e190.Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38:904–9.Kosman E, Leonard KJ. Similarity coefficients for molecular markers in studies of genetic relationships between individuals for haploid, diploid, and polyploid species. Mol Ecol. 2005;14:415–24.Adler D. vioplot: Violin plot. 2005.Jost L. Gst and its relatives do not measure differentiation. Mol Ecol. 2008;17:4015–26.Excoffier L, Lischer H. Arlequin suite ver 3.5: A new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour. 2010;10:564–7.Huson DH, Bryant D. Application of phylogenetic networks in evolutionary studies. Mol Ecol Evol. 2006;23:254–67.Knight R, Maxwell P, Birmingham A, Carnes J, Caporaso JG, Easton BC, et al. PyCogent: a toolkit for making sense from sequence. Genome Biol. 2007;8:R171.Szpiech ZA, Jakobsson M, Rosenberg NA. ADZE: a rarefaction approach for counting alleles private to combinations of populations. Bioinformatics. 2008;24:2498–504.Bradbury PJ, Zhang Z, Kroon DE, Casstevens TM, Ramdoss Y, Buckler ES. TASSEL: software for association mapping of complex traits in diverse samples. Bioinformatics. 2007;23:2633–5.Cleveland WS. Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc. 1979;74:829.R Core Team. R: A Language and Environment for Statistical Computing. 2013.Sinnot RS. Virtues of the haversine. Sky Telesc. 1984;68:159.Hijmans RJ, Etten JV. raster: Geographic data analysis and Modeling. 2013.Bryant D, Bouckaert R, Felsenstein J, Rosenberg NA, RoyChoudhury A. Inferring species trees directly from biallelic genetic markers: bypassing gene trees in a full coalescent analysis. Mol Biol Evol. 2012;29:1917–32.Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol. 2007;7:214.Rambaut A. Tracer v.1.5. 2009.Huang Z, van der Knaap E. Tomato fruit weight 11.3 maps close to fasciated on the bottom of chromosome 11. Theor Appl Genet. 2011;123:465–74.Guo M, Rupe MA, Dieter JA, Zou J, Spielbauer D, Duncan KE, et al. Cell Number Regulator1 affects plant and organ size in maize: implications for crop yield enhancement and heterosis. Plant Cell. 2010;22:1057–73.Sambrook J, Fritsch EF, Maniatis T. Molecular cloning. New York: Cold Spring Harbor Laboratory Press; 1989.Lin T, Zhu G, Zhang J, Xu X, Yu Q, Zheng Z, et al. Genomic analyses provide insights into the history of tomato breeding. Nat Genet. 2014;46:1220–6.Platt A, Horton M, Huang YS, Li Y, Anastasio AE, Mulyati NW, et al. The scale of population structure in Arabidopsis thaliana. PLoS Genet. 2010;6:e1000843.Pressoir G, Berthaud J. Patterns of population structure in maize landraces from the Central Valleys of Oaxaca in Mexico. Heredity (Edinb). 2004;92:88–94.Koenig D, Jiménez-Gómez JM, Kimura S, Fulop D, Chitwood DH, Headland LR, et al. Comparative transcriptomics reveals patterns of selection in domesticated and wild tomato. Proc Natl Acad Sci U S A. 2013;110:e2655–62.Nakazato T, Housworth EA. Spatial genetics of wild tomato species reveals roles of the Andean geography on demographic history. Am J Bot. 2011;98:88–98.United States. Office of Experimental Stations. Experimental Station Recod, Volumen 39. Volume 39. Washington, DC, USA: United States. Office of Experimental Stations; 1918.Merk HL, Yames SC, Van Deynze A, Tong N, Menda N, Mueller LA, et al. Trait diversity and potential for selection indeces based on variation among regionally adapted processing tomato germplasm. J Am Soc Hortic Sci. 2012;137:427–37