Botanical Literature Goes Global:The Biodiversity Heritage Library

Scholars in the natural sciences rely on historic literature more than any other branch of science.Yet much of this material has limited global distribution and much of it is available in only a few select libraries.This wealth of knowledge is available only to those few who can gain direct access to significant library collections,a situation that is considered one of the chief impediments to the efficiency of research in the field.Community support and new technologies led to the formation of the Biodiversity Heritage Library.The BHL is an international collaboration of natural history libraries working together to make biodiversity literature available for use by the widest possible audience through open access and sustainable management.     

Synthesis of natural-product-based compound libraries

Natural products cover a diversity space not yet available from synthetic libraries, with an unrivalled success rate as drug leads. The combinatorial synthesis of non-oligomeric natural-product-based libraries, however, is still limited to few examples because access to easily modified units strongly depends on the availability of a core structure either from a natural source, or through a suitable synthetic route. Only a few resourceful groups have managed the latter approach for more demanding multifunctional natural drug leads, such as epothilones.     

Open resource metagenomics: a model for sharing metagenomic libraries

Both sequence-based and activity-based exploitation of environmental DNA have provided unprecedented access to the genomic content of cultivated and uncultivated microorganisms. Although researchers deposit microbial strains in culture collections and DNA sequences in databases, activity-based metagenomic studies typically only publish sequences from the hits retrieved from specific screens. Physical metagenomic libraries, conceptually similar to entire sequence datasets, are usually not straightforward to obtain by interested parties subsequent to publication. In order to facilitate unrestricted distribution of metagenomic libraries, we propose the adoption of open resource metagenomics, in line with the trend towards open access publishing, and similar to culture- and mutant-strain collections that have been the backbone of traditional microbiology and microbial genetics. The concept of open resource metagenomics includes preparation of physical DNA libraries, preferably in versatile vectors that facilitate screening in a diversity of host organisms, and pooling of clones so that single aliquots containing complete libraries can be easily distributed upon request. Database deposition of associated metadata and sequence data for each library provides researchers with information to select the most appropriate libraries for further research projects. As a starting point, we have established the Canadian MetaMicroBiome Library (CM²BL [1]). The CM²BL is a publicly accessible collection of cosmid libraries containing environmental DNA from soils collected from across Canada, spanning multiple biomes. The libraries were constructed such that the cloned DNA can be easily transferred to Gateway® compliant vectors, facilitating functional screening in virtually any surrogate microbial host for which there are available plasmid vectors. The libraries, which we are placing in the public domain, will be distributed upon request without restriction to members of both the academic research community and industry. This article invites the scientific community to adopt this philosophy of open resource metagenomics to extend the utility of functional metagenomics beyond initial publication, circumventing the need to start from scratch with each new research project.     

Understanding differences between synthetic and natural antibodies can help improve antibody engineering

Synthetic libraries are a major source of human-like antibody (Ab) drug leads. To assess the similarity between natural Abs and the products of these libraries, we compared large sets of natural and synthetic Abs using “CDRs Analyzer,” a tool we introduce for structural analysis of Ab-antigen (Ag) interactions. Natural Abs, we found, recognize their Ags by combining multiple complementarity-determining regions (CDRs) to create an integrated interface. Synthetic Abs, however, rely dominantly, sometimes even exclusively on CDRH3. The increased contribution of CDRH3 to Ag binding in synthetic Abs comes with a substantial decrease in the involvement of CDRH2 and CDRH1. Furthermore, in natural Abs CDRs specialize in specific types of non-covalent interactions with the Ag. CDRH1 accounts for a significant portion of the cation-pi interactions; CDRH2 is the major source of salt-bridges and CDRH3 accounts for most hydrogen bonds. In synthetic Abs this specialization is lost, and CDRH3 becomes the main sources of all types of contacts. The reliance of synthetic Abs on CDRH3 reduces the complexity of their interaction with the Ag: More Ag residues contact only one CDR and fewer contact 3 CDRs or more. We suggest that the focus of engineering attempts on CDRH3 results in libraries enriched with variants that are not natural-like. This may affect not only Ag binding, but also Ab expression, stability and selectivity. Our findings can help guide library design, creating libraries that can bind more epitopes and Abs that better mimic the natural antigenic interactions.     

TogoDoc server/client system: smart recommendation and efficient management of life science literature

In this paper, we describe a server/client literature management system specialized for the life science domain, the TogoDoc system (Togo, pronounced Toe-Go, is a romanization of a Japanese word for integration). The server and the client program cooperate closely over the Internet to provide life scientists with an effective literature recommendation service and efficient literature management. The content-based and personalized literature recommendation helps researchers to isolate interesting papers from the "tsunami" of literature, in which, on average, more than one biomedical paper is added to MEDLINE every minute. Because researchers these days need to cover updates of much wider topics to generate hypotheses using massive datasets obtained from public databases or omics experiments, the importance of having an effective literature recommendation service is rising. The automatic recommendation is based on the content of personal literature libraries of electronic PDF papers. The client program automatically analyzes these files, which are sometimes deeply buried in storage disks of researchers' personal computers. Just saving PDF papers to the designated folders makes the client program automatically analyze and retrieve metadata, rename file names, synchronize the data to the server, and receive the recommendation lists of newly published papers, thus accomplishing effortless literature management. In addition, the tag suggestion and associative search functions are provided for easy classification of and access to past papers (researchers who read many papers sometimes only vaguely remember or completely forget what they read in the past). The TogoDoc system is available for both Windows and Mac OS X and is free. The TogoDoc Client software is available at http://tdc.cb.k.u-tokyo.ac.jp/, and the TogoDoc server is available at https://docman.dbcls.jp/pubmed_recom.     

Screening for peptide drugs from the natural repertoire of biodiverse protein folds

Although monoclonal antibody (mAb) drugs targeting protein interactions exist, these therapeutics cannot access intracellular proteins involved in disease complexes. Moreover, mAbs are more difficult to deliver and are frequently associated with a prohibitive 'royalty stack.' Outlined here is an alternative approach based on libraries of natural, highly structured peptides that offers new opportunities for identifying effective, specific inhibitors of protein-protein interactions. Libraries of such peptides (referred to hereafter as phylomers) comprise both random and structured peptides encoded by natural genes of diverse bacterial genomes. Because the number of protein subdomain structures found in nature is limited, diverse libraries containing millions of phylomers constitute virtually all of the available classes of protein fold structures, providing a rich source of peptides that interact specifically and with high affinity to human proteins. This approach may help not only in understanding the implications of each interaction identified within the interactome but also in the development of effective drugs targeted to particular protein functions. Although phylomers are active in animal models, the challenge remains to demonstrate efficacy and safety in a clinical setting.     

New targeted approaches for the quantification of data‐independent acquisition mass spectrometry

The use of data‐independent acquisition (DIA) approaches for the reproducible and precise quantification of complex protein samples has increased in the last years. The protein information arising from DIA analysis is stored in digital protein maps (DIA maps) that can be interrogated in a targeted way by using ad hoc or publically available peptide spectral libraries generated on the same sample species as for the generation of the DIA maps. The restricted availability of certain difficult‐to‐obtain human tissues (i.e., brain) together with the caveats of using spectral libraries generated under variable experimental conditions limits the potential of DIA. Therefore, DIA workflows would benefit from high‐quality and extended spectral libraries that could be generated without the need of using valuable samples for library production. We describe here two new targeted approaches, using either classical data‐dependent acquisition repositories (not specifically built for DIA) or ad hoc mouse spectral libraries, which enable the profiling of human brain DIA data set. The comparison of our results to both the most extended publically available human spectral library and to a state‐of‐the‐art untargeted method supports the use of these new strategies to improve future DIA profiling efforts.     

Deterioration of medieval painting in the chapel of the Holy Nail, Siena (Italy) partially treated with Paraloid B72

Painted surfaces in the Chapel of the Holy Nail in the medieval ex-hospital of Siena show five areas of oxidation and blackening. Most were treated with Paraloid B72 acrylic resin 40 years ago. To study deterioration of the painted surfaces by scanning microscopy with X-ray dispersion microanalysis, fragments obtained from the five areas were analyzed directly and after hydration. Hydrated fragments treated with Paraloid showed a compact, shiny, impermeable surface. The acrylic resin forms a layer that inhibits interaction of the painting with the environment, including transpiration and gaseous exchange. Element composition of paint layers of different colours revealed gold, iron (oxides in ochre) and lead (oxide) tempered with lime and/or gypsum. A few microbial cells were found on all fragments. To study biological deterioration in the five areas, fragments were hydrated and incubated in minimal culture medium without added carbon source to select bacteria capable of using carbon sources in the medieval fresco. Analysis did not reveal any spores or hyphae, and excluded physical and mechanical damage. Bacteria of the genus Bacillus were isolated only from untreated samples. Paraloid resin forms an inert film over the mural, preventing access to microbes able to use nutrient sources in the painted layer. The screening of 16S rRNA libraries from enrichment cultures showed wide phylogenetic diversity. Forty-four percent of the clones retrieved from the clone library were affiliated with the order Firmicutes, confirming the prevalence of aerobic spore-formers among the colonizing microflora. Firmicutes therefore presumably produced extracellular material which made water available to other bacteria which may have converted thiosulphate in the medieval tempera to sulphur globules. Sulphur is a known oxidant of metallic pigments, in this case aluminium, which may explain the blackening of the untreated sample.     

Complementary DNA libraries

The generation of complete and full-length cDNA libraries for potential functional assays of specific gene sequences is essential for most molecules in biotechnology and biomedical research. The field of cDNA library generation has changed rapidly in the past 10 yr. This review presents an overview of the method available for the basic information of generating cDNA libraries, including the definition of the cDNA library, different kinds of cDNA libraries, difference between methods for cDNA library generation using conventional approaches and a novel strategy, and the quality of cDNA libraries. It is anticipated that the high-quality cDNA libraries so generated would facilitate studies involving genechips and the microarray, differential display, subtractive hybridization, gene cloning, and peptide library generation.     

An improved enrichment procedure to develop multiple repeat classes of cotton microsatellite markers

The availability of a large number of molecular markers is a prerequisite, especially in cotton, for identifying a sufficient number of informative markers for mapping and genetic analysis. Despite the global importance of the cotton crop, few informative microsatellite markers are available, primarily because of the cost associated with their development. This report describes an improved and cost-effective strategy for developing microsatellite markers. Genomic DNA was randomly sheared with nitrogen gas to obtain unbiased representation of the genome, and the fragments containing microsatellites were captured by using biotinylated oligos and streptavidin-based recovery. Six libraries enriched for 14 microsatellite motifs were constructed and screened. Nearly 4900 simple sequence repeat (SSR)-containing sequences were identified, leading to the development of more than 1200 markers in a small amount of time.     

New records of larval stages of the eel cod genus Muraenolepis Günther 1880 (Gadiformes: Muraenolepididae) from the western Antarctic Peninsula

Three newly discovered larval specimens of the genus Muraenolepis collected from the waters of the western Antarctic Peninsula are described. Knowledge of their natural history is sparse and information about their early life history is based on only a few larval stages. Here, the available literature on larval eel cods is reviewed, and the specimens placed in context.     

PCR-based diversity estimates of artificial and environmental 18S rRNA gene libraries

ABSTRACT. Environmental clone libraries constructed using small subunit ribosomal RNA (rRNA) or other gene-specific primers have become the standard molecular approach for identifying microorganisms directly from their environment. This technique includes an initial polymerase chain reaction (PCR) amplification step of a phylogenetically useful marker gene using universal primers. Although it is acknowledged that such primers introduce biases, there have been few studies if any to date systematically examining such bias in eukaryotic microbes. We investigated some implications of such bias by constructing clone libraries using several universal primer pairs targeting rRNA genes. Firstly, we constructed artificial libraries using a known mix of small cultured pelagic arctic algae with representatives from five major lineages and secondly we investigated environmental samples using several primer pairs. No primer pair retrieved all of the original algae in the artificial clone libraries and all showed a favorable bias toward the dinoflagellate Polarella glacialis and a bias against the prasinophyte Micromonas and a pennate diatom. Several other species were retrieved by only one primer pair tested. Despite this, sequences from nine environmental libraries were diverse and contained representatives from all major eukaryotic clades expected in marine samples. Further, libraries from the same sample grouped together using Bray–Curtis clustering, irrespective of primer pairs. We conclude that environmental PCR-based techniques are sufficient to compare samples, but the total diversity will probably always be underestimated and relative abundance estimates should be treated with caution.     

Multi-step parallel synthesis enabled optimization of benzofuran derivatives as pan-genotypic non-nucleoside inhibitors of HCV NS5B

In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delicate balance of inhibition across the common genotypes and mutants with <10 nM potency. In addition, the bicyclic compounds 9B exhibited improved FASSIF solubility over the tetracyclic compound MK-8876. This strategic approach demonstrated that, even within limited reaction scope, multi-step parallel libraries could provide access to more complex chemical space. This expedient access facilitates diverse, purpose-driven optimization of SAR and physicochemical properties.     

Attitudes toward Post‐Trial Access to Medical Interventions: A Review of Academic Literature,Legislation, and International Guidelines

There is currently no international consensus around post‐trial obligations toward research participants, community members, and host countries. This literature review investigates arguments and attitudes toward post‐trial access. The literature review found that academic discussions focused on the rights of research participants, but offered few practical recommendations for addressing or improving current practices. Similarly, there are few regulations or legislation pertaining to post‐trial access. If regulatory changes are necessary, we need to understand the current arguments, legislation, and attitudes towards post‐trial access and participants and community members. Given that clinical trials conducted in low‐income countries will likely continue, there is an urgent need for consideration of post‐trial benefits for participants, communities, and citizens of host countries. While this issue may not be as pressing in countries where participants have access to healthcare and medicines through public schemes, it is particularly important in regions where this may not be available.     

Wanted: new multicomponent reactions for generating libraries of polycyclic natural products

The amalgamation of two of combinatorial chemistry's most attractive concepts--natural product libraries and multicomponent reactions (MCRs)--should provide a powerful tactic for generating libraries of bioactive compounds. Yet, despite many recent advances in this area, only a few MCRs can deliver functionalized products whose structures closely resemble that of complex polycyclic natural products. A large proportion of recently developed MCRs are based on [4+2] or [3+2] cycloadditions, and isocyanide-based processes. Because of substrate limitations, however, they are not always ideally suitable for applications in diversity-oriented synthesis of natural product-like compounds. A promising area awaiting further development is the use of transition metal-catalyzed cascade reactions.     

CancerLectinDB: a database of lectins relevant to cancer

The role of lectins in mediating cancer metastasis, apoptosis as well as various other signaling events has been well established in the past few years. Data on various aspects of the role of lectins in cancer is being accumulated at a rapid pace. The data on lectins available in the literature is so diverse, that it becomes difficult and time-consuming, if not impossible to comprehend the advances in various areas and obtain the maximum benefit. Not only do the lectins vary significantly in their individual functional roles, but they are also diverse in their sequences, structures, binding site architectures, quaternary structures, carbohydrate affinities and specificities as well as their potential applications. An organization of these seemingly independent data into a common framework is essential in order to achieve effective use of all the data towards understanding the roles of different lectins in different aspects of cancer and any resulting applications. An integrated knowledge base (CancerLectinDB) together with appropriate analytical tools has therefore been developed for lectins relevant for any aspect of cancer, by collating and integrating diverse data. This database is unique in terms of providing sequence, structural, and functional annotations for lectins from all known sources in cancer and is expected to be a useful addition to the number of glycan related resources now available to the community. The database has been implemented using MySQL on a Linux platform and web-enabled using Perl-CGI and Java tools. Data for individual lectins pertain to taxonomic, biochemical, domain architecture, molecular sequence and structural details as well as carbohydrate specificities. Extensive links have also been provided for relevant bioinformatics resources and analytical tools. Availability of diverse data integrated into a common framework is expected to be of high value for various studies on lectin cancer biology. CancerLectinDB can be accessed through . Availability: CancerLectinDB is available freely for academic use from , Contact nchandra@serc.iisc.ernet.in for further information.     

Isolation of lambda and YAC clones from defined regions of the rye genome

A dispersed, rye-specific element has been used to isolate clones of rye origin from wheat plants containing only a single rye chromosome arm or segment. In this way a set of 23 YAC clones has been isolated from the short arm of rye chromosome 1 (1RS). This technique was extended to isolate clones from a small region of 1RS that contains a large number of agronomically important genes. The targeted cloning method allowed the isolation of 26 classes of lambda clones representing about 5% of the region. Ten of the lambda clones could be mapped to segments within this region. A third example of the application of this technique involved the isolation of clones from a very small but fully functional rye chromosome, the midget chromosome. These clones have allowed the confirmation of the origin of the midget from 1RL, and may provide a tool for the isolation of structural elements of cereal chromosomes. This technique allows the identification of clone libraries for any rye chromosome or chromosome arm, since substitution, addition and translocation lines are available for all rye chromosomes. Furthermore, the technique allows isolation of clones derived from segments of the rye genome recombined into wheat. The method is technically simple and both lambda and YAC libraries can be constructed. Synteny between the genomes of the cereals allows region-specific libraries from rye to be used to target regions of the wheat and barley genomes. Received: 25 June 1997 / Accepted: 11 November 1997     

Phage display in pharmaceutical biotechnology

Over the past year, methods for the construction of M13 phage-display libraries have been significantly improved and new display formats have been developed. Phage-displayed peptide libraries have been used to isolate specific ligands for numerous protein targets. New phage antibody libraries have further expanded the practical applications of the technology and phage cDNA libraries have proven useful in defining natural binding interactions. In addition, phage-display methods have been developed for the rapid determination of binding energetics at protein-protein interfaces.     

中国西南地区杨属的分类学研究（Ⅱ）

文中包括：吉隆杨的补充记载,１个新异名,１９个天然种的检索表和地理分布,该地区的杨树名录（正名和异名）。