Protein-ligand docking: current status and future challenges

Understanding the ruling principles whereby protein receptors recognize, interact, and associate with molecular substrates and inhibitors is of paramount importance in drug discovery efforts. Protein-ligand docking aims to predict and rank the structure(s) arising from the association between a given ligand and a target protein of known 3D structure. Despite the breathtaking advances in the field over the last decades and the widespread application of docking methods, several downsides still exist. In particular, protein flexibility-a critical aspect for a thorough understanding of the principles that guide ligand binding in proteins-is a major hurdle in current protein-ligand docking efforts that needs to be more efficiently accounted for. In this review the key concepts of protein-ligand docking methods are outlined, with major emphasis being given to the general strengths and weaknesses that presently characterize this methodology. Despite the size of the field, the principal types of search algorithms and scoring functions are reviewed and the most popular docking tools are briefly depicted. Recent advances that aim to address some of the traditional limitations associated with molecular docking are also described. A selection of hand-picked examples is used to illustrate these features.     

Electrophysiology and glaucoma: current status and future challenges

Visual electrophysiology allows non-invasive monitoring of the function of most processing stages along the visual pathway. Here, we consider which of the available methods provides the most information concerning glaucomatous optic nerve disease. The multifocal electroretinogram (ERG), although often employed, is less affected in glaucoma than two direct measurements of retinal ganglion cell function, namely the pattern ERG (PERG) and the photopic negative response (PhNR) of the ERG. For the PERG, longitudinal studies have been reported, suggesting that this method can be used for the early detection of glaucoma; for the PhNR, no longitudinal study is available as yet. The multifocal PERG can spatially resolve ganglion cell function but its glaucomatous reduction is typically panretinal, even with only local field changes and so, its topographic resolution is of no advantage in glaucoma. The multifocal visual evoked potential promises objective perimetry and shows sensitivity and specificity comparable with standard automated perimetry but has not been established as a routine tool to date.     

Prokaryote diversity and taxonomy: current status and future challenges

The prokaryotes are by far the most abundant organisms inhabiting planet Earth. They are also by far the most diverse, both metabolically and phylogenetically; they encompass the Bacteria and the Archaea, two out of the three major divisions of living organisms. The current prokaryote species classification is based on a combination of genomic and phenotypic properties. The recommended cut-off value of 70% DNA-DNA similarity to delineate species signifies an extremely broad species definition for the prokaryotes compared with the higher eukaryotes. The number of validly named species of prokaryotes is currently slightly more than 6200. However, on the basis of small-subunit rDNA characterization of whole communities and other approaches, the more exact number of species present can be inferred to be at least two orders of magnitude larger. Classic culturing methods based on colony formation on agar are generally unsatisfactory for the recovery of bacteria from the environment. Many of the most abundant prokaryotes in nature have not yet been brought into culture. Some of these may thrive by means of as yet unknown modes of energy generation. Several novel methods have recently enabled the isolation of some interesting organisms of environmental significance. A better coverage of the prokaryote diversity on Earth depends on such innovative approaches, combined with appropriate funding.     

Taxonomy of halophilic Archaea: current status and future challenges

Several groups of Archaea, all Euryarchaeota, develop in hypersaline environments (from >10 % salt up to saturation). The cultured diversity of halophilic Archaea includes the family Halobacteriaceae of aerobic or facultative anaerobic, generally red-pigmented species (47 genera and 165 species as of February 2014) and seven representatives of four genera of methanogens, most of which obtain energy from methylated amines under anaerobic conditions. Metagenomic studies have identified an additional deep lineage of Archaea in salt lakes and ponds with brines approaching NaCl saturation. Genomic information is now available for representatives of these ‘Nanohaloarchaea’, but no members of this lineage have yet been cultured. Multilocus sequence analysis is becoming increasingly popular in taxonomic studies of the Halobacteriaceae, and such studies have demonstrated that recombination of genetic traits occurs at an extremely high frequency at least in some genera. Metagenomic studies in an Antarctic lake showed that large identical regions of up to 35 kb in length can be shared by members of different genera living together in the same environment. Such observations have important implications not only for the taxonomy of the Halobacteriaceae, but also for species concepts and questions on taxonomy and classification for prokaryotic microorganisms in general.     

Mammary gland stem cells: current status and future challenges

Distinct subsets of cells, including cells with stem cell-like properties, have been proposed to exist in normal human breast epithelium and breast carcinomas. The cellular origins of epithelial cells contributing to gland development, tissue homeostasis and cancer are, however, still poorly understood. The mouse is a widely used model of mammary gland development, both directly by studying the mouse mammary epithelial cells themselves and indirectly, by studying development, morphogenesis, differentiation and carcinogenesis of xenotransplanted human breast epithelium in vivo. While in early studies, human or mouse epithelium was implanted as fragments into the mouse gland, more recent technical progress has allowed the self-renewal capacity and differentiation potential of distinct cell populations or even individual cells to be interrogated. Here, we review and discuss similarities and differences between mouse and human gland development with particular emphasis on the identity and localization of stem cells, and the influence of the surrounding microenvironment. It is concluded that while recent advances in the field have contributed immense insight into how the normal mammary gland develops and is maintained, significant discrepancies exist between the mouse and human gland which should be taken into consideration in current and future models of mammary stem cell biology.     

Molecular structure of low density lipoprotein: current status and future challenges

This review highlights recent advances in structural studies on low density lipoprotein (LDL) with particular emphasis on the apolipoprotein moiety of LDL, apolipoprotein B100 (apoB100). Various molecular aspects of LDL are outlined and obstacles to structure determination are addressed. In this context, the prevailing conceptions of the molecular assembly of LDL and how the synergy of complementary biochemical, biophysical and molecular simulation approaches has lead to the current structural model of LDL are discussed. Evidence is presented that structural heterogeneity and the intrinsic dynamics of LDL are key determinants of the functionality of LDL in both health and disease. Some key research directions, remaining open questions and rapidly emerging new concepts for medical applications of LDL, are furthermore outlined. The article concludes by providing an outlook concerning promising future strategies for the clarification of the molecular details of LDL, in particular of apoB100, combining recent advances in molecular modeling with developments of novel experimental techniques. Although new insights into the molecular organization of LDL are forthcoming, many open questions remain unanswered. The major challenge of the next decade will certainly be the elucidation of the molecular structural and dynamic features of apoB100.     

Alien terrestrial mammals in Brazil: current status and management

The invasion of alien species is an important cause of biodiversity loss worldwide, and many mammals are considered successful invaders outside their former range, with recognized detrimental effects to native ecosystems. Our aim was to review the current literature on alien mammals that have established feral populations in Brazil and to systematize the existing knowledge. Furthermore, we evaluated the current distributions of all invasion mammals and discuss different management actions, including eradication techniques for island populations. We found 17 species of alien mammals living in the wild in Brazil. Based on the current literature and databases regarding invasive species, Lepus europaeus and Sus scrofa had the largest distributions in the Brazilian territory and seem to continue expanding their geographic distributions. Feral dogs and cats were the main alien predators threatening wildlife conservation, especially in protected areas. Further, we call attention to the invasion of Bubalus bubalis, a large species that currently thrives in isolated populations but seems to be quickly expanding its distribution. In conclusion, alien mammals are widespread in Southern and Southeastern Brazil, but at least four ungulate species (Indian sambar, horse, goat, and axis deer) still have small and isolated populations. Finally, future efforts need to evaluate the impacts of alien mammals in Brazil and techniques for their control.     

Monitoring and adaptive resistance management in Australia for Bt-cotton: current status and future challenges

In the mid-1990 s the Australian Cotton industry adopted an insect-resistant variety of cotton (Ingard) which expresses the Bt toxin Cry1Ac that is specific to a group of insects including the target Helicoverpa armigera. A conservative resistance management plan (RMP), that restricted the area planted to Ingard, was implemented to preserve the efficacy of Cry1Ac until two-gene transgenic cotton was available. In 2004/05 Bollgard II replaced Ingard as the transgenic cotton available in Australia. It improves on Ingard by incorporating an additional insecticidal protein (Cry2Ab). If an appropriate refuge is grown, there is no restriction on the area planted to Bollgard II. In 2004/05 and 2005/06 the Bollgard II acreage represented approximately 80 of the total area planted to cotton in Australia. The sensitivity of field-collected populations of H. armigera to Bt products was assayed before and subsequent to the widespread deployment of Ingard cotton. In 2002 screens against Cry2Ab were developed in preparation for replacement of Ingard with Bollgard II. There have been no reported field failures of Bollgard II due to resistance. However, while alleles that confer resistance to H. armigera in the field are rare for Cry1Ac, they are surprisingly common for Cry2Ab. We present an overview of the current approach adopted in Australia to monitor and adaptively manage resistance to Bt-cotton in field populations of H. armigera and discuss the implications of our findings to date. We also highlight future challenges for resistance management in Australia, many of which extend to other Bt-crop and pest systems.     

The Rare Disease Bank of Japan: establishment,current status and future challenges

Research on rare diseases cannot be performed without appropriate samples from patients with such diseases. Due to the limited number of such patients, securing biosamples of sufficient quality for extensive research is a challenge and represents an important barrier to the advancement of research on rare diseases. To tackle this problem, the Rare Disease Bank (RDB) was established in 2009 at the National Institute of Biomedical Innovation (NIBIO; currently, the National Institutes of Biomedical Innovation, Health and Nutrition in Japan). Since then, the RDB has focused on three objectives: (1) emphasizing the importance of collecting biosamples from patients with rare diseases, together with appropriate clinical information, from various medical facilities nationwide; (2) maintaining strict high-quality sample management standards; and (3) sharing biosamples with research scientists across Japan for the advancement of research on rare diseases. As of August 2017, the bank has collected 4147 biosamples from patients with rare diseases, including DNA, serum, plasma, and cell samples from various university hospitals and other medical institutions across the country, and provided various research institutions with 13,686 biosample aliquots from 2850 cases. In addition, the management committee has successfully established a bank system that provides high-quality biosamples together with the results of human leukocyte antigen analysis. It is anticipated that the RDB, through the collection and sharing of biosamples with the medical research community, will enhance the understanding, prevention, and treatment of rare diseases in Japan and the world at large.     

Energy crops: current status and future prospects

Energy crops currently contribute a relatively small proportion to the total energy produced from biomass each year, but the proportion is set to grow over the next few decades. This paper reviews the current status of energy crops and their conversion technologies, assesses their potential to contribute to global energy demand and climate mitigation over the next few decades, and examines the future prospects. Previous estimates have suggested a technical potential for energy crops of～400 EJ yr^?1 by 2050. In a new analysis based on energy crop areas for each of the IPCC SRES scenarios in 2025 (as projected by the IMAGE 2.2 integrated assessment model), more conservative dry matter and energy yield estimates and an assessment of the impact on non‐CO₂ greenhouse gases were used to estimate the realistically achievable potential for energy crops by 2025 to be between 2 and 22 EJ yr^?1, which will offset～100–2070 Mt CO₂‐eq. yr^?1. These results suggest that additional production of energy crops alone is not sufficient to reduce emissions to meet a 550 μmol mol^?1 atmospheric CO₂ stabilization trajectory, but is sufficient to form an important component in a portfolio of climate mitigation measures, as well as to provide a significant sustainable energy resource to displace fossil fuel resources. Realizing the potential of energy crops will necessitate optimizing the dry matter and energy yield of these crops per area of land through the latest biotechnological routes, with or without the need for genetic modification. In future, the co‐benefits of bioenergy production will need to be optimized and methods will need to be developed to extract and refine high‐value products from the feedstock before it is used for energy production.     

足迹家族研究综述

综合测度人类社会的可持续发展状态是生态经济学者追求的重要目标。足迹家族由生态足迹、碳足迹和水足迹等一系列足迹类指标整合而成,旨在为决策者系统评估与权衡人类活动的环境影响提供理论和技术支持。从理论探索、整合实践和分类比较等三方面对足迹家族的研究现状进行了综述;在此基础上围绕极具争议的足迹定义、计算方法和加权方式等问题,深入分析了阻碍当前研究进一步推进的关键性因素;指出未来应从建立足迹类型学、完善跨区域投入产出模型、细化产品和机构环境足迹标准等方面入手,推动实现足迹家族的量化整合;并首次提出了足迹家族与行星边界耦合的构想,以期为监测和预警人类活动的生态阈值、促进环境影响评价向可持续性评价转变提供科学依据。     

Role of proteomics in biomarker discovery and psychiatric disorders: current status,potentials, limitations and future challenges

Proteomic approaches have advanced clinical research towards more reliable, sensitive and specific biological diagnostic markers for diseases. Mood disorders are most difficult to diagnose and very much prevalent in society; hence, their proper diagnosis becomes essential. Despite tremendous research efforts to dissect the neurobiological basis of psychiatric disorders, the diagnosis and evaluation for such diseases is still poor. Biomarker discovery in psychiatry research has been accelerated by proteomic technologies, accepting the challenges in order to meet disease state-related investigations. Proteomics-based research for disease-specific protein signatures is expected to give a new direction in psychiatry research. Therefore, this may become a more powerful tool to predict the development, course and outcome of the disease towards personalized psychiatric ailments. The review discusses the role of proteomics in elucidating mechanisms of psychiatric disorders, current status, prospects, limitations and new possibilities towards a strong diagnostic tool in the clinical laboratory.     

Seaweed farming in Africa: current status and future potential

Journal of Applied Phycology - Global demand for seaweed and its products has increased exponentially over the last 25 years. Equally, the continent of Africa and its offshore islands have...