Membrane fission by dynamin: what we know and what we need to know

The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion.     

A formalization of consensus index methods

A consensus in dex method comprises a consensus method and a consensus index that are defined on a common set of objects (e.g. classifications). For each profile of objects, the consensus method returns a consensus object representing information or structure shared among profile objects, while the consensus index returns a quantitative measure of agreement among profile objects. Since the relationship between consensus method and consensus index is poorly understood, we propose simple axioms prescribing it in the most general terms. Many taxonomic consensus index methods violate these axioms because their consensus indices measure consensus object invariants rather than profile agreement. We propose paradigms to obtain consensus index methods that measure agreement and satisfy the axioms. These paradigms salvage concepts underlying consensus index methods violating the axioms. This work was supported in part by the Faculty of Science at Memorial University of Newfoundland, and by the Natural Sciences and Engineering Research Council of Canada Under Grant A-4142.     

Human follicular dendritic cells in vitro and follicular dendritic-cell-like cells

Cell and Tissue Research - Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether...     

Insect photoperiodic calendar and circadian clock: independence, cooperation, or unity?

The photoperiodic calendar is a seasonal time measurement system which allows insects to cope with annual cycles of environmental conditions. Seasonal timing of entry into diapause is the most often studied photoperiodic response of insects. Research on insect photoperiodism has an approximately 80-year-old tradition. Despite that long history, the physiological mechanisms underlying functionality of the photoperiodic calendar remain poorly understood. Thus far, a consensus has not been reached on the role of another time measurement system, the biological circadian clock, in the photoperiodic calendar. Are the two systems physically separated and functionally independent, or do they cooperate, or is it a single system with dual output? The relationship between calendar and clock functions are the focus of this review, with particular emphasis on the potential roles of circadian clock genes, and the circadian clock system as a whole, in the transduction pathway for photoperiodic token stimulus to the overt expression of facultative diapause.     

Axioms for consensus functions on undirected phylogenetic trees

A version of Arrow's impossibility theorem is established for consensus functions on undirected phylogenetic trees.     

Implications of the ADA/EASD consensus algorithm for treatment of type 2 diabetes mellitus for primary care practitioners: Four pivotal points

Background: Type 2 diabetes mellitus (DM) is appearing in adults at an epidemic rate. Primary care clinicians will, out of necessity, provide diabetes care for most patients with type 2 DM. A systematic care plan will contribute to effective and cost-efficient management of the increasing number of diabetic patients presenting in the primary care setting.Objectives: The aims of this article were to review the consensus algorithm developed by the American Diabetes Association and the European Association for the Study of Diabetes (ADA/EASD) for the treatment of type 2 DM and to increase awareness of this document within the community that is most likely to manage patients with type 2 DM.Methods: Research was focused on the value of the consensus algorithm to primary care practitioners for the management of patients with type 2 DM.Results: Research revealed 4 aspects of the algorithm involving use of medications (including insulin) and measurement of glycosylated hemoglobin levels that would help health care providers construct a systematic and workable plan for aggressive treatment of type 2 DM.Conclusions: The 4 issues raised within the ADA/EASD consensus algorithm have a significant impact on primary care practitioners and challenge usual practices in the care of patients with type 2 DM.     

An effective docking strategy for virtual screening based on multi-objective optimization algorithm

Background  

Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design.     

Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a joint consensus conference of the Growth Hormone Research Society and the Pituitary Society

In April 2003, the Growth Hormone (GH) Research Society and The Pituitary Society developed a consensus statement to address the current status of both biochemical assessment and long-term monitoring in patients with acromegaly. They also highlighted the pitfalls of current GH and Insulin-like Growth Factor-1 (IGF-1) assay methodologies and the difficulties in defining target GH and IGF-1 levels in treated acromegaly.     

A Microbial Avenue to Cell Cycle Control in the Plant Superkingdom

Research in yeast and animals has resulted in a well-supported consensus model for eukaryotic cell cycle control. The fit of this model to early diverging eukaryotes, such as the plant kingdom, remains unclear. Using the green alga Chlamydomonas reinhardtii, we developed an efficient pipeline, incorporating robotics, semiautomated image analysis, and deep sequencing, to molecularly identify >50 genes, mostly conserved in higher plants, specifically required for cell division but not cell growth. Mutated genes include the cyclin-dependent kinases CDKA (resembling yeast and animal Cdk1) and the plant-specific CDKB. The Chlamydomonas cell cycle consists of a long G1 during which cells can grow >10-fold, followed by multiple rapid cycles of DNA replication and segregation. CDKA and CDKB execute nonoverlapping functions: CDKA promotes transition between G1 and entry into the division cycle, while CDKB is essential specifically for spindle formation and nuclear division, but not for DNA replication, once CDKA-dependent initiation has occurred. The anaphase-promoting complex is required for similar steps in the Chlamydomonas cell cycle as in Opisthokonts; however, the spindle assembly checkpoint, which targets the APC in Opisthokonts, appears severely attenuated in Chlamydomonas, based on analysis of mutants affecting microtubule function. This approach allows unbiased integration of the consensus cell cycle control model with innovations specific to the plant lineage.     

Interpreting consensus sequences based on plurality rule.

Our goal is to help researchers interpret the results of a function, based on the concept of plurality rule, that calculates a consensus of a profile of molecular bases. By expressing the plurality rule function as a composition of simpler functions, we obtain both an algorithm to calculate the consensus result and an upper bound on the number of nonequivalent results. Consequently, when used to analyze molecular sequences such as DNA or RNA, the plurality rule function yields at most 48 nonequivalent consensus results. For problems of reasonable size, we describe an algorithm to calculate the probability that each consensus result would occur if the bases were equally likely to appear at every position of the plurality rule function's input profile.     

Peptidomic analysis of the skin secretions of the pickerel frog Rana palustris identifies six novel families of structurally-related peptides

Peptidomics methodology has been used to identify and characterize structurally 26 previously undescribed peptides in the electrically stimulated skin secretions of the North American pickerel frog Rana palustris. Peptides in the secretions were analyzed by electrospray mass spectrometry and components in mass range 700-2500 Da, present in major abundance, were purified by reverse-phase HPLC. Cysteine-containing components were identified by treatment with dithiothreitol and 4-vinylpyridine and re-analysis of the derivatizated peptide by mass spectrometry. Application of these techniques led to the identification of six families of structurally-related peptides comprising (a). six peptides containing the consensus sequence Cys-Trp-Xaa-Thr-Lys-Ser-Ile-Pro-Pro-Lys/Arg-Xaa-Cys, (b). three peptides containing the consensus sequence Pro-Pro-Gly-Val-Cys-(Xaa)(3)-Lys/Arg-Arg-Cys, (c). two peptides containing the consensus sequence Ser-Phe-His-Val-Phe-Pro-Pro-Trp-Met-Cys-Lys-Xaa-Leu-Lys-Lys-Cys, (d). two peptides containing the consensus sequence Arg-Xaa-Cys-Trp-Lys-(Xaa)(2)-Asn-(Xaa)(3)-Val-Cys-Ser, (e). nine peptides containing the consensus sequence Ser-Leu-Pro-Ala-Gly-Leu-Ser-Pro, and (f). four peptides containing the consensus sequence Asp-Xaa-Gln-Asp-Arg-Trp-Xaa-Pro. The peptides did not inhibit the growth of Escherichia coli or Staphylococcus aureus and were inactive on hamster vascular or gastric smooth muscle preparations so that their biological functions, if any, remain to be established.     

Excitation relaxation dynamics of carotenoids constituting the diadinoxanthin cycle

Photosynthesis Research - Carotenoids (Cars) exhibit two functions in photosynthesis, light-harvesting and photoprotective functions, which are performed through the excited states of Cars....     

Applying undertaker cost functions to model quality assessment

Undertaker is a program designed to help predict protein structure using alignments to proteins of known structure and fragment assembly. The program generates conformations and uses cost functions to select the best structures from among the generated conformations. This paper describes the use of Undertaker's cost functions for model quality assessment. We achieve an accuracy that is similar to other methods, without using consensus‐based techniques. Adding consensus‐based features further improves our approach substantially. We report several correlation measures, including a new weighted version of Kendall's τ (τ₃) and show model quality assessment results superior to previously published results on all correlation measures when using only models with no missing atoms. Proteins 2009. © 2008 Wiley‐Liss, Inc.     

Urgently needed: a filter for the HIV-1 vaccine pipeline

Research groups worldwide are trying to make immunogens intended to elicit neutralizing antibody responses as part of a prophylactic vaccine to counter the spread of HIV-1. The relative merits of different designs can only be gauged properly through comparative studies, and particularly by evaluating human or animal antisera under identical, or comparable, conditions. Hence there is a need for assay standardization and for the creation of a centralized testing facility that could distribute consensus protocols and reagents.     

Outcomes of the second workshop of the Food Sustainable Consumption and Production Round Table Working Group 1: deriving scientifically sound rules for a sector-specific environmental assessment methodology

Purpose  

This paper illustrates the consensus achieved by the members of the European Food Sustainable Consumption and Production Round Table Working Group 1 in their second scientific workshop held in the European Commission’s Joint Research Centre site in Ispra, Italy on July 5–7, 2011. This workshop came after having run a detailed analysis, of data gaps and of methodologies, for the environmental assessment of food and drink products. In particular, the aim of this workshop was to reach consensus amongst key stakeholders on those approaches found diverging across methodologies and on which the forthcoming protocol for the ENVIronmental assessment of FOOds and Drinks (ENVIFOOD Protocol) is expected to provide guidance to the sector.     

Clinical Practice Guidelines and Consensus Statements in Oncology – An Assessment of Their Methodological Quality

BackgroundConsensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine’s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.MethodsConsensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine''s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.FindingsThirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal’s consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases.ConclusionGuidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor’s product to enhance transparency.     

An ensemble framework for clustering protein-protein interaction networks

MOTIVATION: Protein-Protein Interaction (PPI) networks are believed to be important sources of information related to biological processes and complex metabolic functions of the cell. The presence of biologically relevant functional modules in these networks has been theorized by many researchers. However, the application of traditional clustering algorithms for extracting these modules has not been successful, largely due to the presence of noisy false positive interactions as well as specific topological challenges in the network. RESULTS: In this article, we propose an ensemble clustering framework to address this problem. For base clustering, we introduce two topology-based distance metrics to counteract the effects of noise. We develop a PCA-based consensus clustering technique, designed to reduce the dimensionality of the consensus problem and yield informative clusters. We also develop a soft consensus clustering variant to assign multifaceted proteins to multiple functional groups. We conduct an empirical evaluation of different consensus techniques using topology-based, information theoretic and domain-specific validation metrics and show that our approaches can provide significant benefits over other state-of-the-art approaches. Our analysis of the consensus clusters obtained demonstrates that ensemble clustering can (a) produce improved biologically significant functional groupings; and (b) facilitate soft clustering by discovering multiple functional associations for proteins. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.