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The tree of life is the fundamental biological roadmap for navigating the evolution and properties of life on Earth, and yet remains largely unknown. Even angiosperms (flowering plants) are fraught with data gaps, despite their critical role in sustaining terrestrial life. Today, high-throughput sequencing promises to significantly deepen our understanding of evolutionary relationships. Here, we describe a comprehensive phylogenomic platform for exploring the angiosperm tree of life, comprising a set of open tools and data based on the 353 nuclear genes targeted by the universal Angiosperms353 sequence capture probes. The primary goals of this article are to (i) document our methods, (ii) describe our first data release, and (iii) present a novel open data portal, the Kew Tree of Life Explorer (https://treeoflife.kew.org). We aim to generate novel target sequence capture data for all genera of flowering plants, exploiting natural history collections such as herbarium specimens, and augment it with mined public data. Our first data release, described here, is the most extensive nuclear phylogenomic data set for angiosperms to date, comprising 3099 samples validated by DNA barcode and phylogenetic tests, representing all 64 orders, 404 families (96%⁠) and 2333 genera (17%⁠). A “first pass” angiosperm tree of life was inferred from the data, which totaled 824,878 sequences, 489,086,049 base pairs, and 532,260 alignment columns, for interactive presentation in the Kew Tree of Life Explorer. This species tree was generated using methods that were rigorous, yet tractable at our scale of operation. Despite limitations pertaining to taxon and gene sampling, gene recovery, models of sequence evolution and paralogy, the tree strongly supports existing taxonomy, while challenging numerous hypothesized relationships among orders and placing many genera for the first time. The validated data set, species tree and all intermediates are openly accessible via the Kew Tree of Life Explorer and will be updated as further data become available. This major milestone toward a complete tree of life for all flowering plant species opens doors to a highly integrated future for angiosperm phylogenomics through the systematic sequencing of standardized nuclear markers. Our approach has the potential to serve as a much-needed bridge between the growing movement to sequence the genomes of all life on Earth and the vast phylogenomic potential of the world’s natural history collections. [Angiosperms; Angiosperms353; genomics; herbariomics; museomics; nuclear phylogenomics; open access; target sequence capture; tree of life.], This work was supported by grants from the Calleva Foundation and the Sackler Trust to the Plant and Fungal Trees of Life project at the Royal Botanic Gardens, Kew. Additional support was received from the Garfield Weston Foundation, as part of the Global Tree Seed Bank Programme.

We examined the impact of successive alignment quality-control steps on downstream phylogenomic analyses. We applied a recently published phylogenomics pipeline that was developed for the Angiosperms353 target-sequence-capture probe set to the flowering plant order Celastrales. Our final dataset consists of 158 species, including at least one exemplar from all 109 currently recognized Celastrales genera. We performed nine quality-control steps and compared the inferred resolution, branch support, and topological congruence of the inferred gene and species trees with those generated after each of the first six steps. We describe and justify each of our quality-control steps, including manual masking, in detail so that they may be readily applied to other lineages. We found that highly supported clades could generally be relied upon even if stringent orthology and alignment quality-control measures had not been applied. But separate instances were identified, for both concatenation and coalescence, wherein a clade was highly supported before manual masking but then subsequently contradicted. These results are generally reassuring for broad-scale analyses that use phylogenomics pipelines, but also indicate that we cannot rely exclusively on these analyses to conclude how challenging phylogenetic problems are best resolved.

Objective: The lesions of Parkinson disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded a-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous a-synuclein to misfold. Here, we characterized and quantified the axonal transport of a-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. Methods: We grew primary cortical mouse neurons in microfluidic devices to separate somata from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent a-synuclein fibrils and their transfer to second-order neurons. Results: Fibrillar a-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar a-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. Interpretation: These results support the hypothesis that the progression of Parkinson disease can be caused by neuron-to-neuron spread of a-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be trans-synaptic gives hope that a-synuclein fibrils could be intercepted by drugs during the extracellular phase of their journey. ANN NEUROL 2012;72:517–524

Melanins, pigments of diverse origin and chemical function, have been subjects of interest for a long time (Aristotle, in “Historia Animalia”, 315 B.C.). These natural cosmetics of skin, hair, and feathers usually occur in the form of insoluble fine granules in certain dendritic cells of the epidermis. The term melanin (μɛλαζ = black) is, however, misleading and confusing since not all biogenetically related pigments are black. The melanogenic enzyme, tyrosinase, is known to catalyze the biosynthesis of not only black but also red to brown, or even yellow pigments, e.g. pheomelanins (208, 266). On the other hand, the fascinating colors in the feathers of birds, skins of reptiles and fishes and the blue eyes in animals are optical phenomena due to diffraction, light absorption and scattering, interference, that are produced by melanin granules either in combination or not, with other pigmentary colors (94, 156) and by complex formation of the granules with heavy metals (21, 156).

Publisher Summary This chapter discusses the chemical and biological aspects of melanin in condensed form. Melanin, the natural cosmetics of skin, hair, and feathers, represent broadly a group of natural and synthetic pigments of diverse origin and chemical functions. In nature, they usually occur in the form of insoluble fine granules accumulated in certain parts of animal and plant tissues. Some related synthetic melanins are also known. These are named after the compounds from which they were prepared via chemical and enzymatic oxidation, such as tyrosine-melanin, dopa-melanin, and catechol-melanin. The pigmentation of human skin has substantial protective, social, and cosmetic significance. Although melanins lack well-defined physical and spectral characteristics, they possess some effective chemical properties by acting as redox polymers, ion exchangers, and radical scavengers. The extensive studies of these chemical reactivities of melanin and putative melanin precursors have led researchers to infiltrate into many areas of scientific research, including the molecular biology of pigment-related genes.

Publisher Summary This chapter discusses the chemical and biological aspects of melanin in condensed form. Melanin, the natural cosmetics of skin, hair, and feathers, represent broadly a group of natural and synthetic pigments of diverse origin and chemical functions. In nature, they usually occur in the form of insoluble fine granules accumulated in certain parts of animal and plant tissues. Some related synthetic melanins are also known. These are named after the compounds from which they were prepared via chemical and enzymatic oxidation, such as tyrosine-melanin, dopa-melanin, and catechol-melanin. The pigmentation of human skin has substantial protective, social, and cosmetic significance. Although melanins lack well-defined physical and spectral characteristics, they possess some effective chemical properties by acting as redox polymers, ion exchangers, and radical scavengers. The extensive studies of these chemical reactivities of melanin and putative melanin precursors have led researchers to infiltrate into many areas of scientific research, including the molecular biology of pigment-related genes.

FAK (focal adhesion kinase) is a nonreceptor protein-tyrosine kinase activated by tyrosine phosphorylation following integrin-mediated cell adhesion. Oncogenic Src promotes enhanced and deregulated FAK tyrosine phosphorylation which has been proposed to contribute to altered cell growth and/or morphological properties associated with transformation. In this study, an inducible FAK expression system was used to study the potential role of FAK in v-Src transformation. Our results portray FAK as a major v-Src substrate that also plays a role in recruiting v-Src to phosphorylate substrates CAS (Crk-associated substrate) and paxillin. The FAK Tyr-397 autophosphorylation site was necessary for this scaffolding function, but was not required for v-Src to stably interact with and phosphorylate FAK. FAK was also shown to negatively regulate v-Src mediated phosphorylation of the FAK-related kinase PYK2. Despite these effects, FAK does not play an essential role in targeting v-Src to major cellular substrates including CAS and paxillin. Nor is FAK strictly required to achieve the altered morphological and growth characteristics of v-Src transformed cells.

The European dye stuff industry originally provided the main stimulus for development of the chemistry of carbazoles since the discovery of the first member of the group, carbazole (1) from coal tar in 1872 by Graebe and Glazer (35). The isolation of carbazole as a degradation product of strychnine (2) by Clemo and Perkin (18) in 1924 provided further impetus for progress in the chemistry of carbazoles. N-Vinylcarbazole (3) was subsequently synthesised (12) and polymers based on vinyl carbazoles were developed subsequently (95) with the dye stuff industries and polymer industry contributing largely to further development of the chemistry of carbazoles up to 1960. The discovery of the first naturally occurring carbazole, the alkaloid murrayanine (4)* from Murraya koinigii Spreng; may be considered a further landmark in development of the chemistry and biology of carbazoles; the report on its structure was, however, published only in 1965 (12). Carbazole, methylcarbazole and dimethylcarbazole were isolated from soil humus in 1967 by Haworth et al. (14). More recently there has been added interest in the chemistry of carbazoles due to their use in electrophotography and related areas.

Bose Institute, 93/1, A, P, CRoad, Calcutta- 700 009 Manuscriptreceived 27 June 1988, revised 7 November 1988,accepted 18 November 1988 Murrayazolinol- A Minor Carbazole Alkaloid from Murraya koenigii Spreng. &nbsp

Bose Institute, Calcutta-700 009 Mukoline and mukolidine, two new carbazole alkaloids from \(Murrya\) \(koenigii\) Spreng., have been assigned the structueres 6-hydroxy-metbyl·l-methoxy carbazole and 6-formyl-1-methoxy carbazole, respectively.

Bose Institute, Calcutta-700 009 Manuscript received 17 May 1984, revised 29 July 1985, accepted 11 September 1985 Details of the structure of heptazolidine, a carbazole alkaloid isolated from Clausena heptaphylla Wt. and Am. is reported.

Bose Institute, 98/1 1 A. P. C. Road, Calcutta-700 009 Tryptophan Participation in Melanogenesis : Modification of Raper-Mason-Pawelek Scheme of Melanin Formation1 &nbsp

Bose Institute, Calcutta-700 009 Manuscript received 17 May 1984, revised 29 July 1985, accepted 11 September 1988 Synthesis of heptazolidine, a carbazole alkaloid from Clausena heptaphylla Wt. and Arn. has been reported to confirm the structure of the alkaloid.

Chemistry Department, Bose Institute, Calcutta-700 009 Manuscript received 17 September 1986, accepted 9 March 1987 First synthesis or linear pyranocarbazole ring system (11) and the thermal synthesis or norgirinimbine (13) have been reported. Antimony trichloride has been reported as a decarboxylatiog agent.

Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Calcutta-700 009 Manuscript received 17 February 1981, accepted 22 July 1981 Indole under biomimetic hydroxylation using Udenfriend reaction gives rise to melanin and other products. The results pose a question whether indole could be an alternative substrate for biomelanin.

Bose Institute Calcutta-700 009 Manuscript received 29 August 1980, accepted 18 December 1980 Thin Layer Chromatographic Studies with Some Carbazoles : Hydrochloric Acid-A Convenient Spray Reagent for Carbazole Alkaloids.

Department of Chemistry, Bose Institute, Calcutta-700 009 Manuscript received 21 August1980, revised 2 July 1981, accepted 1 October 1981 Girinimbine and Koenimbine from \({Murraya}\)\({exotica}\) Linn.

In continuation of our studies on Murraya exotica Linn. (Syn. M. paniculata) from which we reported mexoticin1 (1), hibiscetin heptamethyl ether,2 carbazole alkaloids, murrayazoline, mahanimbine and girinimbine,3 we now report the structure of a new antibiotic dimeric coumarin named mexolide (2) having an unusual cyclohexene system similar to that in cyclobissuberodiene4 [thamnosin5 (3)].