Scale relativity theory and integrative systems biology: 2. Macroscopic quantum-type mechanics

In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps that have been followed in the construction of the scale relativity theory, which aims at describing the effects of a non-differentiable and fractal (i.e., explicitly scale dependent) geometry of space–time. The first paper of this series was devoted, in this new framework, to the construction from first principles of scale laws of increasing complexity, and to the discussion of some tentative applications of these laws to biological systems. In this second review and perspective paper, we describe the effects induced by the internal fractal structures of trajectories on motion in standard space. Their main consequence is the transformation of classical dynamics into a generalized, quantum-like self-organized dynamics. A Schrödinger-type equation is derived as an integral of the geodesic equation in a fractal space. We then indicate how gauge fields can be constructed from a geometric re-interpretation of gauge transformations as scale transformations in fractal space–time. Finally, we introduce a new tentative development of the theory, in which quantum laws would hold also in scale space, introducing complexergy as a measure of organizational complexity. Initial possible applications of this extended framework to the processes of morphogenesis and the emergence of prokaryotic and eukaryotic cellular structures are discussed. Having founded elements of the evolutionary, developmental, biochemical and cellular theories on the first principles of scale relativity theory, we introduce proposals for the construction of an integrative theory of life and for the design and implementation of novel macroscopic quantum-type experiments and devices, and discuss their potential applications for the analysis, engineering and management of physical and biological systems and properties, and the consequences for the organization of transdisciplinary research and the scientific curriculum in the context of the SYSTEMOSCOPE Consortium research and development agenda.     

Cancer Proteomics and the Elusive Diagnostic Biomarkers

Despite progress in genomic and proteomic technology and applications, the validation of cancer biomarkers of use as clinical early detection diagnostics has remained elusive. As described in this brief viewpoint, there are now recognized to be many types of clinical biomarkers and proteomic analyses, particularly when combined with other ‘omic analyses, have been effective in many such biomarker identifications. However, in the area of early diagnosis of cancers, the problems associated with the conversion from identification to diagnostic have largely not been overcome. Notably, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), has been particularly successful in refining the analytical steps needed to tackle this challenging issue and has provided positive insight into how to solve many of the underlying problems. The potential for developing clinical diagnostics for early detection of highly lethal cancers and possible new therapeutic strategies through proteomic analyses, as seen through these CPTAC successes, is more promising than ever.     

New York-Structural GenomiX Research Consortium (NYSGXRC): A Large Scale Center for the Protein Structure Initiative

Structural GenomiX, Inc. (SGX), four New York area institutions, and two University of California schools have formed the New York Structural GenomiX Research Consortium (NYSGXRC), an industrial/academic Research Consortium that exploits individual core competencies to support all aspects of the NIH-NIGMS funded Protein Structure Initiative (PSI), including protein family classification and target selection, generation of protein for biophysical analyses, sample preparation for structural studies, structure determination and analyses, and dissemination of results. At the end of the PSI Pilot Study Phase (PSI-1), the NYSGXRC will be capable of producing 100–200 experimentally determined protein structures annually. All Consortium activities can be scaled to increase production capacity significantly during the Production Phase of the PSI (PSI-2). The Consortium utilizes both centralized and de-centralized production teams with clearly defined deliverables and hand-off procedures that are supported by a web-based target/sample tracking system (SGX Laboratory Information Data Management System, LIMS, and NYSGXRC Internal Consortium Experimental Database, ICE-DB). Consortium management is provided by an Executive Committee, which is composed of the PI and all Co-PIs. Progress to date is tracked on a publicly available Consortium web site (http://www.nysgxrc.org) and all DNA/protein reagents and experimental protocols are distributed freely from the New York City Area institutions. In addition to meeting the requirements of the Pilot Study Phase and preparing for the Production Phase of the PSI, the NYSGXRC aims to develop modular technologies that are transferable to structural biology laboratories in both academe and industry. The NYSGXRC PI and Co-PIs intend the PSI to have a transforming effect on the disciplines of X-ray crystallography and NMR spectroscopy of biological macromolecules. Working with other PSI-funded Centers, the NYSGXRC seeks to create the structural biology laboratory of the future. Herein, we present an overview of the organization of the NYSGXRC and describe progress toward development of a high-throughput Gene→Structure platform. An analysis of current and projected consortium metrics reflects progress to date and delineates opportunities for further technology development.     

The Plant Ontology Consortium and plant ontologies

The goal of the Plant Ontology Consortium is to produce structured controlled vocabularies, arranged in ontologies, that can be applied to plant-based database information even as knowledge of the biology of the relevant plant taxa (e.g. development, anatomy, morphology, genomics, proteomics) is accumulating and changing. The collaborators of the Plant Ontology Consortium (POC) represent a number of core participant database groups. The Plant Ontology Consortium is expanding the paradigm of the Gene Ontology Consortium (http://www.geneontology.org). Various trait ontologies (agronomic traits, mutant phenotypes, phenotypes, traits, and QTL) and plant ontologies (plant development, anatomy [incl. morphology]) for several taxa (Arabidopsis, maize/corn/Zea mays and rice/Oryza) are under development. The products of the Plant Ontology Consortium will be open-source.     

Methods and Advances in Biotech

Cover illustration: Methods and Advances in Biotech. Highlights in this issue are recombinant therapeutic proteins, HIV diagnosis and 3D imaging cytometry. Image: 3D distribution of chromatin inside living intact Hela cell, imaged during metaphase (p. 53). Montage by C. Machu and O. Renaud, Institut Pasteur, Paris. www.pfid.org/automation     

Unlocking the bovine genome

The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries.     

Interview With Michael Bevan: The Arabidopsis Genome is Sequenced,What Next?

Professor Michael Bevan is at the John Innes Centre, Norwich, UK, where he is Head of the Cell and Developmental Biology Department. He was the co-ordinator of the European Union Arabidopsis Genome Sequencing Consortium, which contributed to the sequence and analysis of the complete Arabidopsis genome that was published late last year. He is the co-ordinator of the EC funded EXOTIC program and is also a member of GARNet and UK CropNet. (For more background detail on these projects, please see our Featured Organism: Arabidopsis thaliana piece, also in this issue of CFG, or visit the websites listed below).     

球药隔重楼的化学成分研究(英文)

采用硅胶柱层析、大孔吸附树脂、ODS柱层析、Sephadex LH-20和RP-C18柱层析等技术中分离得到8个化合物。通过波谱学数据和已知化合物数据比较,分别鉴定为β-谷甾醇(1),β-蜕皮激素(2),Paris SaponinsⅤ(3),Paris SaponinsⅠ(4),Paris SaponinsⅡ(5),Paris SaponinsⅦ(6),Paris Saponins H(7)和Paris SaponinsⅥ(8)。化合物1～8均为首次从球药隔重楼中分离得到。     

Breaking barriers through collaboration: the example of the Cell Migration Consortium

Understanding complex integrated biological processes, such as cell migration, requires interdisciplinary approaches. The Cell Migration Consortium, funded by a Large-Scale Collaborative Project Award from the National Institute of General Medical Science, develops and disseminates new technologies, data, reagents, and shared information to a wide audience. The development and operation of this Consortium may provide useful insights for those who plan similarly large-scale, interdisciplinary approaches.     

How to meet the 2020 GSPC target 8 in Europe: priority-setting for seed banking of native threatened plants

The contribution of the European Native Seed Conservation Network (ENSCONET, 2004-2009) and the ENSCONET Consortium (since 2010) towards meeting the 2020 Global Strategy for Plant Conservation (GSPC) target 8 was assessed in 2017. While the outcome was positive (62.7% of European threatened species already conserved ex situ in seed banks), the analysis showed that it was essential to provide guidance on which European native threatened species should be collected as a priority if the target was to be reached by 2020. In this paper we present a priority-setting method and its result, designed to guide collecting strategies across Europe to meet the 2020 GSPC target 8. The result of our study is a country-based checklist of European threatened taxa to be collected and stored ex situ across the seed banks of the ENSCONET Consortium by 2020. After discussing the results of the applied method, the ENSCONET Consortium Steering Committee has identified some key action points to support the implementation of such a collecting strategy across Europe in order to meet the 2020 GSPC target 8 for Europe.     

Investigation of fatty acid metabolism-related genes in breast cancer: Implications for Immunotherapy and clinical significance

Breast cancer (BRCA) is a major global health issue, characterized by high mortality and low early diagnosis rates. The tumor immune microenvironment (TME) of BRCA is closely linked to fatty acid metabolism (FAM). This study aimed to identify FAM-related subtypes in BRCA based on gene expression and clinical data from the Cancer Genome Atlas (TCGA) database. The study found two distinct FAM-related subtypes, each with unique immune characteristics and prognostic implications. A FAM-related risk score prognostic model was developed and validated using TCGA and International Cancer Genome Consortium (GEO) cohorts, showing potential clinical applications for chemotherapy and immunotherapy. Additionally, a nomogram was established to facilitate clinical use of the risk score. These results highlight the significant correlation between FAM genes and TME in BRCA, and demonstrate the potential clinical utility of the FAM-related risk score in informing treatment decisions for BRCA patients.     

Chemotaxonomic study of the genus Paris based on steroidal saponins

The study of saponins from the genus Paris (Trilliaceae) has led to the isolation of over 70 steroidal saponins. Their distributions in different species are summarised and possible patterns in the modifications of the aglycone moiety, based on a biosynthetic pathway for steroidal saponins, were reviewed in this study. The chemotaxonomic value of these secondary metabolites has been evaluated, and it is suggested that Paris thibetica, Paris vietnamensis, Paris delavayi and Paris pseudothibetica, which contain more active saponins, could be an ideal substitution material for Paris polyphylla Smith var. chinensis, and Paris polyphylla Smith var. yunnanensis. Distribution of the same types of saponins amongst the Trilliaceae suggests a close relationship between the Trillium and Paris.     

A future for systems and computational neuroscience in France?

This special issue of the Journal of Physiology, Paris, is an outcome of NeuroComp'06, the first French conference in Computational Neuroscience. The preparation for this conference, held at Pont-à-Mousson in October 2006, was accompanied by a survey which has resulted in an up-to-date inventory of human resources and labs in France concerned with this emerging new field of research (see team directory in http://neurocomp.risc.cnrs.fr/). This thematic JPP issue gathers some of the key scientific presentations made on the occasion of this first interdisciplinary meeting, which should soon become recognized as a yearly national conference representative of a new scientific community. The present introductory paper presents the general scientific context of the conference and reviews some of the historical and conceptual foundations of Systems and Computational Neuroscience in France.     

Modelling the effects of climate change on the potential feeding activity of Thaumetopoea pityocampa (Den. & Schiff.) (Lep., Notodontidae) in France

Aim We investigated whether climate change has affected the potential feeding activity of a winter active larva, the pine processionary moth (PPM), Thaumetopoea pityocampa L., and whether it may explain its range expansion. Location The study area is France and, at a smaller scale, the Paris Basin. Methods We used a statistical model derived from Huchon and Démolin [1970 Revue Forestière Française (special issue: La lutte biologique en forêt), 220–234] to test whether their model, updated with climate change, could explain the observed range expansion. Since Battisti and colleagues have recently shown that climate could affect survival of the PPM through its effect on feeding activity, we also developed a mechanistic model based on larval feeding requirements (night air temperature above 0 °C and temperature inside the nest above 9 °C on the preceding day). We reconstructed the geographical distribution of feeding activity and we compared the resulting change with the PPM range expansion. Results The statistical model did not successfully predict the observed expansion but the mechanistic model showed considerable change in the feeding activity of the PPM. In the Paris Basin, the PPM border coincided with a zone unfavourable for feeding activity in the period 1992–96. Feeding conditions became more favourable in the period 2001–04, and the PPM succeeded in crossing this zone. Over larger temporal and spatial scales improved feeding conditions in the north‐western part of France were forecast by the mechanistic model. Main conclusions (1) The range distribution of the PPM in the Paris Basin is no longer limited by unfavourable feeding conditions. (2) The pattern of range expansion of the PPM is now governed mainly by its dispersal capabilities and host tree distribution. (3) At the country scale, this approach gives an approximate prediction of the potential distribution of the PPM, though the model may not be reliable in mountainous regions.     

Cephalopod genomics: A plan of strategies and organization

The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, “Paths to Cephalopod Genomics- Strategies, Choices, Organization,” held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described in this white paper.     

Much ado about bacteria-to-vertebrate lateral gene transfer

When the International Human Genome Sequencing Consortium (IHGSC) published its draft of the human genome in February 2001, several genes were identified as possible bacteria-to-vertebrate transfers (BVTs). These genes were identified by their highly significant sequence similarity to bacterial genes in BLAST searches, and by their lack of matches among non-vertebrate eukaryote genes. Many were later rejected as BVTs by several methods, including recovery of probable orthologs from the genomes of incompletely sequenced eukaryotes. Whereas the BVT issue has received considerable attention, there has been no compilation of all potential BVTs considered to date, nor any proposal of a single comprehensive method for rigorously establishing the veracity of a putative BVT. In reviewing the work to date, we list all of the proteins examined and propose systematic tests to investigate whether a vertebrate gene proposed as a BVT is indeed of bacterial origin. We use the proposed strategy to test--and reject--one of the BVTs from the original IHGSC list.     

Chondrichthyan teeth from the Early Triassic Paris Biota (Bear Lake County,Idaho, USA)

A new, diverse and complex Early Triassic assemblage was recently discovered west of the town of Paris, Idaho (Bear Lake County), USA. This assemblage has been coined the Paris Biota. Dated earliest Spathian (i.e., early late Olenekian), the Paris Biota provides further evidence that the biotic recovery from the end-Permian mass extinction was well underway ca. 1.3 million years after the event. This assemblage includes mainly invertebrates, but also vertebrate remains such as ichthyoliths (isolated skeletal remains of fishes). Here we describe first fossils of Chondrichthyes (cartilaginous fishes) from the Paris Biota. The material is composed of isolated teeth (mostly grinding teeth) preserved on two slabs and representing two distinct taxa. Due to incomplete preservation and morphological differences to known taxa, the chondrichthyans from the Paris Biota are provisionally kept in open nomenclature, as Hybodontiformes gen. et sp. indet. A and Hybodontiformes gen. et sp. indet. B, respectively. The present study adds a new occurrence to the chondrichthyan fossil record of the marine Early Triassic western USA Basin, from where other isolated teeth (Omanoselache, other Hybodontiformes) as well as fin spines of Nemacanthus (Neoselachii) and Pyknotylacanthus (Ctenachanthoidea) and denticles have been described previously.