A symposium was held at the University of California, San Diego, to honor the contributions of Nobel Laureate, George Palade, to cell biology. The speakers included Günter Blobel, on the structure and function of nuclear pore complexes; Peter Walter, on the unfolded protein response in health and disease; Randy Schekman, on human disease-linked mutations in the COPII machinery; Scott Emr, on the regulation of plasma membrane composition by selective endocytosis; Roger Kornberg, on the structure and function of the transcription machinery; Peter Novick, on the regulation of rab GTPases along the secretory pathway; Jim Spudich, on the mechanism of the enigmatic myosin VI motor; and Joe Goldstein, on the function of the Niemann-Pick C (NPC)-linked gene products, NPC1 and NPC2, in cholesterol transport. Their work showcased the multidisciplinary nature, diversity, and vitality of cell biology. In the words of George Palade, their talks also illustrated “how cell biology could be used to understand disease and how disease could be used to discover normal cell biology.” An integrated understanding of the cellular machinery will be essential in tackling the plethora of questions and challenges posed by completion of the human genome and for understanding the molecular mechanisms underlying human disease.
This Theme Issue is dedicated to the topic ‘Mechanics: from nano to macro’ and marks the 75th birthday of Dr J. Michael T. Thompson, Fellow of the Royal Society, whose current affiliations are as follows: (i) Honorary Fellow, Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge; (ii) Emeritus Professor of Nonlinear Dynamics, Department of Civil, Environmental and Geomatic Engineering, University College London; and (iii) Professor of Theoretical and Applied Dynamics (Distinguished Sixth Century Chair, part-time), University of Aberdeen. He also serves as Chairman of the Board of Directors at ES-Consult (consulting engineers) in Copenhagen, Denmark. The pertinent question that arises from the very start is: should we first salute Michael and then describe the Theme Issue, or vice versa? Indeed, according to Blaise Pascal (1623–1662), the last thing one discovers in composing a work is what to put first. I would like to take the liberty of deviating from the tradition of the Philosophical Transactions and start with the tribute to Michael; after all he is the prime cause of this Theme Issue.
theoretical and applied mechanics; nanomechanics; macromechanics
Lactose permease of Escherichia coli (LacY) is highly dynamic, and sugar binding causes closing of a large inward-facing cavity with opening of a wide outward-facing hydrophilic cavity. Therefore, lactose/H+ symport via LacY very likely involves a global conformational change that allows alternating access of single sugar- and H+-binding sites to either side of the membrane. Here, in honor of Stephan H. White’s seventieth birthday, we review in camera the various biochemical/biophysical approaches that provide experimental evidence for the alternating access mechanism.
Lactose; Permease; Symport; Transport; Membrane; Membrane protein
Understanding the link between neurobiology and cognition requires that neuroscience moves beyond mere structure-function correlations. An explicit systems perspective is needed in which putative mechanisms of how brain function is constrained by brain structure are mathematically formalized and made accessible for experimental investigation. Such a systems approach critically rests on a better understanding of brain connectivity in its various forms. Since 2002, frontier topics of connectivity and neural system analysis have been discussed in a multidisciplinary annual meeting, the Brain Connectivity Workshop (BCW), bringing together experimentalists and theorists from various fields. This article summarizes some of the main discussions at the two most recent workshops, 2006 at Sendai, Japan, and 2007 at Barcelona, Spain: (i) investigation of cortical micro- & macrocircuits, (ii) models of neural dynamics at multiple scales, (iii) analysis of “resting state” networks, and (iv) linking anatomical to functional connectivity. Finally, we outline some central challenges and research trajectories in computational systems neuroscience for the next years.
neural systems analysis; effective connectivity; nonlinear dynamics; fMRI; EEG; MEG; DCM; model comparison; resting state; microcircuits
To Darwin, parasites were fascinating examples of adaptation but their significance as selective factors for a wide range of phenomena has only been studied in depth over the last few decades. This work has had its roots in behavioural/evolutionary ecology on the one hand, and in population biology/ecology on the other, thus shaping a new comprehensive field of ‘evolutionary parasitology’. Taking parasites into account has been a success story and has shed new light on several old questions such as sexual selection, the evolution of sex and recombination, changes in behaviour, adaptive life histories, and so forth. In the process, the topic of ecological immunology has emerged, which analyses immune defences in a framework of costs and benefits. Throughout, a recurrent theme is how to appropriately integrate the underlying mechanisms as evolved boundary conditions into a framework of studying the adaptive value of traits. On the conceptual side, major questions remain and await further study.
parasitism; evolution; virulence; ecological immunology
On 18 February 1998, a ‘Stress symposium’ was held at the Rand Afrikaans University (RAU) in Johannesburg, South Africa. The meeting brought together people from both the plant and the human oxidative stress field, which was exemplified by a talk entitled ‘Heat shock proteins in host-pathogen interactions: plants versus humans’. There were moments when it appeared as if the main difference between plants and humans was, as sung by Julos Beaucarne, that ‘the human plant is the only one to be able to water itself…’
The Second Annual Symposium of the Global Cancer Genomics Consortium (GCGC) was held at the Tata Memorial Center in Mumbai, India, from November 19 to 20, 2012. Founded in late 2010, the GCGC aims to provide a platform for highly productive, collaborative efforts on next-generation cancer research through bridging the latest scientific and technology developments with clinical oncology challenges. This year’s presenters brought together highly innovative interdisciplinary views and strategies to meet major challenges in cancer research. The symposium featured 3 major themes: OMICS approaches toward the identification of cancer molecular drivers, single-cell analysis in cancer, and clinical and translational genomics. Each theme was represented in presentations of new findings, with an obvious implication in cross-disciplinary components of OMICs and an overwhelming participation by students. In summary, the GCGC symposium provided a discussion and congregation of the latest advances in basic and translational cancer research and offered the participants with a highly cooperative network environment for future collaboration.
genomics medicine; anticancer target; cancer therapy
A recent meeting entitled Frontiers in Live Cell Imaging was attended by more than 400 cell biologists, physicists, chemists, mathematicians, and engineers. Unlike typical special topics meetings, which bring together investigators in a defined field primarily to review recent progress, the purpose of this meeting was to promote cross-disciplinary interactions by introducing emerging methods on the one hand and important biological applications on the other. The goal was to turn live cell imaging from a “technique” used in cell biology into a new exploratory science that combines a number of research fields.
The Kitasato Symposium 2009: New Prospects for Cytokine Inhibition was held in Berlin, Germany from 7 to 9 May 2009. The key aims of this meeting were to bring together a group of front-line researchers and rheumatologists to evaluate the use of cytokine blockade and to examine the role of certain cytokines in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. A keynote lecture delivered by Professor Jean-Michel Dayer provided an up-to-date overview of the interactions occurring between the immune system and acute phase proteins. Other speakers discussed the role of cytokines in rheumatoid arthritis, including their role in joint destruction, as well as their regulatory role upon T cells and B cells. The involvement of cytokines in other autoimmune diseases was also addressed.
Negative alcohol-related consequences often occur during specific events and in specific contexts (eg., 21st birthday celebrations and tailgating parties). A lack of available event- and context-specific interventions suggests the need to better understand factors associated with heavy drinking in these contexts, with an eye toward developing specific interventions. The purpose of this research was to lay the foundation for developing personalized normative feedback interventions for 21st birthday celebratory drinking and tailgating drinking by evaluating whether students overestimate norms in these specific contexts, as they do more generally.
Perceived descriptive norms and alcohol consumption were assessed at event- and context-specific levels in two studies. Study 1 included 119 students turning 21 years old who reported their 21st birthday drinking behavior and estimated the typical number of drinks consumed by students celebrating (their 21st birthday. Study 2 included 140 undergraduates drawn from a stratified random sample who reported their behavior regarding drinking and tailgating and their perceived norms for typical drinking and tailgating behavior.
Results from Study 1 revealed that students overestimated peer drinking during 21st birthday celebrations, and this overestimation was associated with heavier drinking on one’s own 21st birthday. In Study 2, students underestimated the percentage of tailgaters who drank but overestimated typical consumption. Overestimation was consistently associated with heavier drinking during tailgating.
Successful correction of general normative misperceptions has been shown to reduce drinking in other research. Documentation of normative misperceptions for specific events and context provided by these results represents an important step in developing event- and context-specific interventions utilizing specific normative feedback.
While research has documented heavy drinking practices and associated negative consequences of college students turning 21, few studies have examined prevention efforts aimed to reduce high-risk drinking during 21st birthday celebrations. The present study evaluated the comparative efficacy of a general prevention effort (i.e., BASICS) and event specific prevention in reducing 21st birthday drinking and related negative consequences. Furthermore, this study evaluated inclusion of peers in interventions and mode of intervention delivery (i.e., in-person vs. web).
Participants included 599 college students (46% male) who intended to consume at least five/four drinks (men/women respectively) on their 21st birthday. After completing a screening/baseline assessment approximately one week before turning 21, participants were randomly assigned to one of six conditions: 21st birthday in-person BASICS, 21st birthday web BASICS, 21st birthday in-person BASICS plus friend intervention, 21st birthday web BASICS plus friend intervention, BASICS, or an attention control. A follow-up assessment was completed approximately one week after students’ birthdays.
Results indicated a significant intervention effect for BASICS in reducing blood alcohol content reached and number of negative consequences experienced. All three in-person interventions reduced negative consequences experienced. Results for the web-based interventions varied by drinking outcome and whether or not a friend was included.
Overall, results provide support for both general intervention and ESP approaches across modalities for reducing extreme drinking and negative consequences associated with turning 21. These results suggest there are several promising options for campuses seeking to reduce both use and consequences associated with 21st birthday celebrations.
Alcohol; alcohol-related problems; college students; event-specific drinking; event-specific prevention; 21st birthday
This is a special issue of Genetica that has its origins in a symposium held in honor of Richard G. Harrison at Ithaca, New York on July 22–23. Former students of Rick Harrison organized the symposium and most of the speakers were former students, as well. The quality and breadth of the talks were a testament to Rick’s influence as a thinker, synthesizer, and mentor and it is only appropriate to reflect on Rick’s contributions to the fields of evolutionary ecology, systematics, and genetics in this preface to the symposium articles.
This historical treatise documents the unbroken legacy of the West family of chiropractors which has flourished in Canada for over 100 years. Part I, unearths the origins, development and careers of Archibald West, the founder of this dynasty, his son Samuel and grandson Stephen. Part II, not yet ready for publication, will delve into the lives of Archibald’s brother Samson and his chiropractic progeny, as well as a nephew of Stephen and another relative of Frederick West.
West; chiropractic; Canada; genealogy; West; chiropratique; Canada; généalogie
This historical paper documents the unbroken legacy of the West family of chiropractors which has flourished in Canada for over 100 years. Part I, unearthed the origins, development and careers of Archibald West, the founder of this dynasty, his son Samuel and grandson Stephen. Part II, delves into the life of Archie’s brother Samson, and Samson’s chiropractic progeny: grandsons David and Neil, and great granddaughter Megan. Then it goes back to look at Stephen West’s nephew, R. Ian Buchanan and ends with a descendant of another branch of the family tree, James L. West.
history; chiropractic; West; histoire; chiropratique; West
To many biophysical characterisation techniques, biological membranes appear as two-dimensional structures with details of their third dimension hidden within a 5 nm profile. Probing this structure requires methods able to discriminate multiple layers a few Ångströms thick. Given sufficient resolution, neutron methods can provide the required discrimination between different biochemical components, especially when selective deuteration is employed. We have used state-of-the-art neutron reflection methods, with resolution enhancement via magnetic contrast variation to study an oriented model membrane system. The model is based on the Escherichia coli outer membrane protein OmpF fixed to a gold surface via an engineered cysteine residue. Below the gold is buried a magnetic metal layer which, in a magnetic field, displays different scattering strengths to spin-up and spin-down neutrons. This provides two independent datasets from a single biological sample. Simultaneous fitting of the two datasets significantly refines the resulting model. A β-mercaptoethanol (βME) passivating surface, applied to the gold to prevent protein denaturation, is resolved for the first time as an 8.2 ± 0.6 Å thick layer, demonstrating the improved resolution and confirming that this layer remains after OmpF assembly. The thiolipid monolayer (35.3 ± 0.5 Å), assembled around the OmpF is determined and finally a fluid DMPC layer is added (total lipid thickness 58.7 ± 0.9 Å). The dimensions of trimeric OmpF in isolation (53.6 ± 2.5 Å), after assembly of lipid monolayer (57.5 ± 0.9 Å) and lipid bilayer (58.7 ± 0.9 Å), are precisely determined and show little variation.
Celebrating 300 years since the birth of Carl Linnaeus (1707–1778), a meeting was held in June 2007 to review recent progress made in understanding the origins and evolutionary radiation of the animals. The year 2008 celebrates the 250th anniversary of the publication of the 10th edition of Linnaeus' Systema Naturae, generally considered to be the starting point of zoological nomenclature. With subsequent advances in comparative taxonomic and systematic studies, Darwin's discovery of evolution by natural selection, the birth of phylogenetic systematics, and the wider interest in biodiversity, it is salutary to consider that many of the major advances in our understanding of animal evolution have been made in recent years. Phylogenetic systematics, drawing from evidence provided by genotype, phenotype and an understanding of the link between them through comparative embryological and evolutionary developmental studies, has provided a wide consensus of the major branching patterns of the tree of life. More importantly, the integrated approaches discussed in the 16 contributions to this volume highlight the identity and nature of problematic taxa, the missing data, errors in existing analytical procedures and the promise of a wealth of additional characters from genomes that need to be accumulated and assessed in providing a definitive Systema Naturae.
Linnaeus; animal evolution; evo–devo; phylogenetics
In 2009 the International Society for Computational Biology (ISCB) started to roll out regional bioinformatics conferences in Africa, Latin America and Asia. The open and competitive bid for the first meeting in Asia (ISCB-Asia) was awarded to Asia-Pacific Bioinformatics Network (APBioNet) which has been running the International Conference on Bioinformatics (InCoB) in the Asia-Pacific region since 2002. InCoB/ISCB-Asia 2011 is held from November 30 to December 2, 2011 in Kuala Lumpur, Malaysia. Of 104 manuscripts submitted to BMC Genomics and BMC Bioinformatics conference supplements, 49 (47.1%) were accepted. The strong showing of Asia among submissions (82.7%) and acceptances (81.6%) signals the success of this tenth InCoB anniversary meeting, and bodes well for the future of ISCB-Asia.
Long-chain polyprenols and polyprenyl-phosphates are ubiquitous and essential components of cellular membranes throughout all domains of life. Polyprenyl-phosphates, which include undecaprenyl-phosphate in bacteria and the dolichyl-phosphates in archaea and eukaryotes, serve as specific membrane-bound carriers in glycan biosynthetic pathways responsible for the production of cellular structures such as N-linked protein glycans and bacterial peptidoglycan. Polyprenyl-phosphates are the only form of polyprenols with a biochemically-defined role; however, unmodified or esterified polyprenols often comprise significant percentages of the cellular polyprenol pool. The strong evolutionary conservation of unmodified polyprenols as membrane constituents and polyprenyl-phosphates as preferred glycan carriers in biosynthetic pathways is poorly understood. This review surveys the available research to explore why unmodified polyprenols have been conserved in evolution and why polyprenyl-phosphates are universally and specifically utilized for membrane-bound glycan assembly.
polyprenol; polyprenyl-phosphate; dolichol; dolichyl-phosphate; N-linked glycosylation
David Geffen School of Medicine faculty, representing a wide range of disciplines, engaged speakers nationally known for their expertise on complementary, alternative and integrative medicine (CAIM) and its investigation at a January, 2008 symposium on the campus of the University of California, Los Angeles. The forum was created to educate the UCLA Institutional Review Board (IRB), and lively participation by School of Medicine faculty helped bring IRB members up to speed on controversies surrounding CAIM research. The symposium demonstrated that academics who are neither proponents nor detractors of CAIM can facilitate cross talk between opposing camps, elucidating questions important to its evaluation by those charged with protecting research subjects. It also brought attention to the universality of quandaries facing CAIM investigators and to the ingenuity with which they have addressed many of them.
attitudes towards CAM; cost-benefit analysis; double blind randomized controlled clinical trial; experimental study; quality of life trials
A consensus meeting on autoimmune pancreatitis (AIP) was held in Seoul on August 31, 2007. Many Korean and Japanese gastroenterologist interested in AIP participated in the joint symposium, and issues related to histology, radiology, clinical manifestation, serology, and diagnostic criteria were discussed. This joint meeting indicated the need for unified diagnostic criterion for AIP in Korea and Japan. Here, we provide a summary of the symposium presentations and discussions.
Autoimmune pancreatitis; Consensus; Korea; Japan
Optogenetics is a research field that uses gene therapy to deliver a gene encoding a light-activated protein to cells providing light-regulated control of targeted cell pathways. The technology is a popular tool in many fields of neuroscience, used to transiently switch cells on and off, for example, to map neural circuits. In inherited retinal degenerative diseases, where loss of vision results from the loss of photoreceptors, optogenetics can be applied to either augment the function of surviving photoreceptors or confer light sensitivity to naturally nonlight sensitive retinal cells, such as a bipolar cells. This can be achieved either by the light sensitive protein integrating with native internal signaling pathways, or by using a dual function membrane protein that integrates light signaling with an ion channel or pump activity. Exposing treated cells to light of the correct wavelength activates the protein, resulting in cellular depolarization or hyperpolarization that triggers neurological signaling to the visual cortex.
While there is a lot of interest in optogenetics as a pan-disease clinical treatment for end-stage application in the inherited degenerative diseases of the retina, research to date has been limited to nonhuman clinical studies. To address the clinical translational needs of this technology, the Foundation Fighting Blindness and Massachusetts Eye and Ear Infirmary cohosted an International Optogenetic Therapies for Vision Workshop, which was held at Massachusetts Eye and Ear Infirmary, Boston, Massachusetts on June 1, 2012.
optogenetics; vision; retina; gene therapy