Genomics in 2011: challenges and opportunities

As we come to the end of 2011, Genome Biology has asked some members of our Editorial Board for their views on the state of play in genomics. What was their favorite paper of 2011? What are the challenges in their particular research area? Who has had the biggest influence on their careers? What advice would they give to young researchers embarking on a career in research?     

Research versus practice: The dilemmas of research ethics in the era of learning health‐care systems

In this article we attempt to answer the question of how the ethical and conceptual framework (ECF) for a learning health‐care system (LHS) affects some of the main controversies in research ethics by addressing five key problems of research ethics: (a) What is the difference between practice and research? (b) What is the relationship between research ethics and clinical ethics? (c) What is the ethical relevance of the principle of clinical equipoise? (d) Does participation in research require a higher standard of informed consent than the practice of medicine? and (e) What ethical principle should take precedence in medicine? These questions allow us to construct two opposite idealized positions on the distinction between research and practice: the integration model and the segregation model of research and practice. We then compare the ECF for an LHS with these two idealized positions. We argue that the ECF for a LHS does not, in fact, solve these problems, but that it is a third, separate position in the relationship between research ethics and clinical ethics. Moreover, we suggest that the ECF for a LHS raises new ethical problems that require additional ethical analysis and justification. Our article contributes to the discussion on the relationship between research ethics and clinical ethics, revealing that although a learning health‐care system may significantly change the landscape of health care, some ethical dilemmas still require resolving on both theoretical and policy‐making levels.     

Primatology: the beginning

The journal Primates was founded by Kinji Imanishi (1902–1992) in 1957: It is the oldest and longest-running international primatology journal in the world. In this series of dialogues between Tetsuro Matsuzawa, Editor-in-Chief of Primates and the General Director of the Japan Monkey Centre (JMC) and Juichi Yamagiwa, former Editor-in-Chief of Primates and the Museum Director of the JMC, we look back at the achievements of our spiritual ancestors in primate research and talk about the back story of Imanishi and his fellow primatologists: founding the JMC as a research institute focused on primates and launching this journal. What was their motivation? What challenges did they face? What is their continued influence on the field right up to the present? What will be the legacy of our influence on the discipline?     

Position matters: variability in the spatial pattern of BMP modulators generates functional diversity

Bone morphogenetic proteins (BMPs) perform a variety of functions during development. Considering a single BMP, what enables its multiple roles in tissues of varied sizes and shapes? What regulates the spatial distribution and activity patterns of the BMP in these different developmental contexts? Some BMP functions require controlling spread of the BMP morphogen, while others require formation of localized, high concentration peaks of BMP activity. Here we review work in Drosophila that describes spatial regulation of the BMP encoded by decapentaplegic (dpp) indifferent developmental contexts. We concentrate on extracellular modulation of BMP function and discuss the mechanisms that generate concentrated peaks of Dpp activity, subdivide territories of different activity levels or regulate spread of the Dpp morphogen from a point source. We compare these findings with data from vertebrates and non‐model organisms to discuss how changes in the regulation of Dpp distribution by extracellular modulators may lead to variability in dpp function in different species. genesis 49:698–718, 2011. © 2011 Wiley‐Liss, Inc.     

The role of insect pollinators in avocado production: A global review

Insect pollination increases the yield and quality of many crops and therefore, understanding the role of insect pollinators in crop production is necessary to sustainably increase yields. Avocado Persea americana benefits from insect pollination, however, a better understanding of the role of pollinators and their contribution to the production of this globally important crop is needed. In this study, we carried out a systematic literature review and meta-analysis of studies investigating the pollination ecology of avocado to answer the following questions: (a) Are there any research gaps in terms of geographic location or scientific focus? (b) What is the effect of insect pollinators on avocado pollination and production? (c) Which pollinators are the most abundant and effective and how does this vary across location? (d) How can insect pollination be improved for higher yields? (e) What are the current evidence gaps and what should be the focus of future research? Research from many regions of the globe has been published, however, results showed that there is limited information from key avocado producing countries such as Mexico and the Dominican Republic. In most studies, insects were shown to contribute greatly to pollination, fruit set and yield. Honeybees Apis mellifera were important pollinators in many regions due to their efficiency and high abundance, however, many wild pollinators also visited avocado flowers and were the most frequent visitors in over 50% of studies. This study also highlighted the effectiveness of stingless bees (Meliponini) and blow flies (Calliphoridae) as avocado pollinators although, for the majority of flower visitors, there is a lack of data on pollinator efficiency. For optimal yields, growers should ensure a sufficient abundance of pollinators in their orchards either through increasing honeybee hive density or, for a more sustainable approach, by managing wild pollinators through practices that protect or promote natural habitat.     

Improved network performance via antagonism: From synthetic rescues to multi‐drug combinations

Recent research shows that a faulty or sub‐optimally operating metabolic network can often be rescued by the targeted removal of enzyme‐coding genes – the exact opposite of what traditional gene therapy would suggest. Predictions go as far as to assert that certain gene knockouts can restore the growth of otherwise nonviable gene‐deficient cells. Many questions follow from this discovery: What are the underlying mechanisms? How generalizable is this effect? What are the potential applications? Here, I approach these questions from the perspective of compensatory perturbations on networks. Relations are drawn between such synthetic rescues and naturally occurring cascades of reaction inactivation, as well as their analogs in physical and other biological networks. I specially discuss how rescue interactions can lead to the rational design of antagonistic drug combinations that select against resistance and how they can illuminate medical research on cancer, antibiotics, and metabolic diseases. Editor's suggested further reading in BioEssays The evolutionary context of robust and redundant cell biological mechanisms Abstract Reprogramming cell fates: reconciling rarity with robustness Abstract     

Neural stem cells: From fly to vertebrates

Our goal in this review is to explore the relationship between Drosophila and vertebrate neural stem cell development by comparing progress in each system with the aim of answering several central questions in stem cell biology: (a) How are stem cells formed? (b) Do stem cells divide symmetrically or asymmetrically? (c) How is stem cell fate maintained? (d) How is stem cell differentiation initiated? (e) How are different stem cell fates determined? (f) How “plastic” are different neural stem cell fates? (g) How do neural stem cells produce different progeny? and (h) What regulates stem cell proliferation versus quiescence? Not surprisingly, research in Drosophila and vertebrate systems each have their own biases, strengths, and weaknesses; we hope that by directly comparing progress in each field, new experiments and interpretations in both vertebrate and Drosophila research will become apparent. It has become increasingly clear that vertebrates and Drosophila share many fundamental mechanisms of neurogenesis, validating a comparative approach. © 1998 John Wiley & Sons, Inc. J Neurobiol 36: 111–127, 1998     

The genetics and molecular biology of the titin/connectin-like proteins of invertebrates

Conclusions A substantial amount of information has been gathered about the structure and function of twitchin/titin-related proteins in the invertebrates. This has been obtained through sequence analysis and the analysis of loss-offunction phenotypes inC. elegans andDrosophila. Nevertheless, a number of fascinating questions remain, including: (i) Why are these invertebrate proteins all of approx. 700–800 kDa? In terms of sarcomeric organization, what is the significance of this size? (ii) Why do three of these proteins consist of a mixture of Ig and Fn domains, whereas UNC-89 contains only Ig domains? This is even more interesting because the structures of Ig and Fn domains are very similar (118). What is the significance of the repeating pattern of groups of Ig and Fn domains (e.g. Fn-Fn-Ig)? (iii) How are twitchin and the synchronous muscle isoform of projectin situated on the surface of thick filaments? That is, do they form polymers or are they located at discrete locations with intervening gaps? (iv) What is the mechanism by which the fundamentally similar projectin isoforms get localized to different sarcomeric locations? (v) If the data onAplysia twitchin can be extended to the muscles of other invertebrates, what is the mechanism by which twitchin inhibits the rate of relaxation? How does phosphorylation of twitchin relieve this inhibition? (vi) What are the substrates for the protein kinase domains of nematode twitchin and insect projectin? If rMLCs are indeed the substrates, how would and why does this phosphorylation take place for the IFM isoform of projectin, which resides primarily in the I band? If rMLCs are the substrates, given the stoichiometry of approx. 1∶50 for twitchin:myosin, and the likely fixed position of twitchin along the thick filament, how does phosphorylation of just a few rMLCs result in a physiological effect (e.g. inhibition of relaxation)? What is the true activator for the twitchin and projectin kinases? (vii) How does UNC-89 participate in M-line assembly? (viii) What are the biochemical and physiological functions of intestinal brush border twitchin? A number of investigators will enjoy pursuing these and other questions for some time in the future.     

Fire,Heroes and the Cosmic: Aesthetic Resonances of Fire‐walking in Northern Greece

In the Greek village of Mavrolefki in Thrace, a small number of women and men. about ten in number, once a year, on the feast day of St. Constantine, undertake a series of rites, ranging from dancing to the icons, blood sacrifice, to the most spectacular fire‐walking (pyrovasia). It is the last which brings spectators from all over Greece and further afield. The principal participants, however, are known as the anastenarides (shakers, tremblers). Several concerns are addressed in the paper. Given the peculiar mix of proceedings, the first is to lay out the components of the affair, asking what's going on? Furthermore, there are the conceptual issues. What aesthetic is being implicated? What emotions are being brought into play? What does the event amount to? In addressing such questions the paper draws on certain aesthetic formulations of the Hindu rasa theory.     

Utilizing Saccharomyces in the classroom: a versatile organism for teaching and learning

In the world of higher education, one of the struggles instructors face in the classroom is engaging students in the material. A second discussion in higher education pedagogy is how to weigh content versus activity in the science classroom. How should college teaching be set up when students now have every fact ever found at their fingertips on a device no larger than a half sandwich? What is the correct balance in the classroom between content/ knowledge and activity? As instructors grapple with these questions, a new type of learning experience called the Course Based Undergraduate Research Experience (CURE) has been developed, whereby students engage in an authentic research question in a classroom and laboratory setting. CUREs have been shown to be effective learning experiences for students but can be difficult to implement. Saccharomyces cerevisiae is a versatile and easy to use organism in the classroom that can be used for a wide variety of classroom activities. Described herein are a number of ways an instructor can use yeast in the classroom for authentic research experiences, especially focused towards a CURE.     

Optimal trait scoring for age estimation

What are the effects that genetics has had on Anthropological research and how can we think anthropologically about Genetics? Just as genetic data have encouraged new hypotheses about human phenotypic variation, evolutionary history, population interaction, and environmental effects, so too has Anthropology offered to genetic studies a new interpretive locus in its history and perspective. This introduction examines how the fields of Anthropology and Genetics have arrived at a crucial moment at which their interaction requires careful examination and critical reflection. The papers discussed here exemplify how we may engage in such a trans-disciplinary conversation. They speak to the future of thoughtful interaction between genetic and anthropological literature and seek a new integration that embodies the holism of the human biological sciences.     

PINCH: More than just an adaptor protein in cellular response

Particularly interesting new cysteine‐histidine‐rich protein (PINCH) is a LIM‐domain‐only adaptor protein involved in protein recruitment, subsequent assembly of multi‐protein complexes, and subcellular localization of these complexes. PINCH is developmentally regulated and its expression is critical for proper cytoskeletal organization and extracellular matrix adhesion. Although PINCH has no catalytic abilities, the PIP (PINCH–ILK–parvin) complex serves as a link between integrins and components of growth factor receptor kinase and GTPase signaling pathways. Accordingly, PINCH‐mediated signaling induces cell migration, spreading, and survival. Further research on the signaling cascades affected by PINCH is key to appreciating its biological significance in cell fate and systems maintenance, as the developmental functions of PINCH may extend to disease states and the cellular response to damage. PINCH is implicated in a diverse array of diseases including renal failure, cardiomyopathy, nervous system degeneration and demyelination, and tumorigenesis. This review presents evidence for PINCH's structural and functional importance in normal cellular processes and in pathogenesis. The current data for PINCH expression in nervous system disease is substantial, but due to the complex and ubiquitous nature of this protein, our understanding of its function in pathology remains unclear. In this review, an overview of studies identifying PINCH binding partners, their molecular interactions, and the potentially overlapping role(s) of PINCH in cancer and in nervous system diseases will be discussed. Many questions remain regarding PINCH's role in cells. What induces cell‐specific PINCH expression? How does PINCH expression contribute to cell fate in the central nervous system? More broadly, is PINCH expression in disease a good thing? Clarifying the ambiguous functions of PINCH expression in the central nervous system and other systems is important to understand more clearly signaling events both in health and disease. J. Cell. Physiol. 226: 940–947, 2011. © 2010 Wiley‐Liss, Inc.     

The Structure of the Individual Mental Lexicon from the Standpoint of L. S. Vygotsky's Ideas

Research on the structure of an individual's mental lexicon has shown that, among the set of concepts belonging to a single semantic field, there is typically one particular concept that stands out. The processes of storage, identification, and retrieval of this concept are faster and more successful than they are for the others. For example, in the vertical hierarchy of the concept fruit—apple—antonovka [McIntosh to give a familiar U. S. example—Trans.], apple plays this type of lead role and also occupies the most prominent position in the horizontal series apple—pear—plum—cherries—orange. Concepts with such characteristics are referred to as basic, source, or primary concepts. What is the reason for their special status?     

Bottom-up and top-down effects in a tritrophic system: the population fluctuations of Plutella xylostella and its parasitoid,Oomyzus sokolowskii on the cauliflower cultivars in field conditions

The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae), has worldwide distribution and found wherever cruciferous plants is grown. In this study, fluctuations of parasitism rate of P. xylostella by Oomyzus sokolowskii on different cauliflower cultivars were evaluated in the field during 2011 at research station of the Shahed University (South of Tehran). This investigation was conducted on the eight cauliflower cultivars including Smilla, Snow mystique, White cloud, Buris, Galiblanka, Snow crown, SG and Tokita in a randomised complete block design with five replications. The results showed that density of total larva and pupa of the diamondback moth on Buris and Snow crown cultivars is lower than other cultivars. The highest and the lowest percentage of parasitism by O. sokolowskii was observed on Buris cultivar (7.93?±?0.91%) and SG cultivar (1.28?±?0.36%) during the season, respectively.     

‘Live has an atmosphere of its own’: azadari,ethical orientation,and tuned presence in Shi‘i media praxis

Among producers of Shi‘i Islamic media in Pakistan, the quality of being live as an atmosphere capable of mediation has gained efficacy along with changes in media for religious dispensation. Central to the importance of live recordings are the ways they are perceived to most effectively mediate the ethical, ritual, and transhistorical contours of azadari, a word that describes the ways in which the personages held in esteem by the Shi‘a are mourned and commemorated. What are these qualities of being live that see recordings attributed the qualities of a good, moral atmosphere? By building on ethnographic research into the relationship between Shi‘i practices of azadari and their technological mediation, this article aims to provide greater insights into what atmosphere can do for anthropology, with the suggestion that it acts as a way of recognizing different thresholds of intensity and change.     

In Lieu of an Introduction

Nikolai Veresov: Tatiana, in this volume of our journal we publish a selection of your articles. Two of your other articles were published in Soviet Psychology in the 1970s. Introducing you to the readers of that journal, James Wertsch (1978) wrote: "The author … is one of the leading young investigators from the Luria school of neurolinguistics. She has studied and conducted extensive research both with Luria and with A. A. Leontiev, a major figure in Soviet psycholinguistics. Her analysis of inner speech as a mechanism in speech production reveals the strong influence that L. S. Vygotsky has had on Soviet psychology."¹ But first of all, I suppose our readers would be interested in learning more about your life, about events that preceded your scientific achievements. Could you please tell us briefly about your childhood and your family? How did your parents influence your course of life and your occupational choice? What did they do?     

Two pacing spikes on the T wave in a single-chamber pacemaker: What is the mechanism?

We report a case of a 54-year-old female, known symptomatic sick sinus syndrome, who had undergone a single-chamber pacemaker (VVI, St. Jude Medical, VERITY ADxXL SC SN 2413520) implantation in 2011. Electrocardiography (ECG) performed on a recent visit to the pacemaker clinic showed intermittent double pacing spikes on top of the T wave (Fig. 1A). What is the mechanism?     

Disclosure of genetic information obtained through research

The rapid expansion of information and knowledge of genetics has implications for the question of whether, and under what circumstances, information discovered in the course of genetic research should be conveyed to research participants and/or their relatives. The aim of this paper is to propose an ethically defensible solution to a specific case example illustrating this problem. To do this we reviewed the literature to find answers to the following three questions: (1) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research to research participants? (2) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research to the relatives of research subjects? and (3) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research about former research participants who are now deceased? Our conclusion is that current U.S. federal guidelines governing the use of human subjects in research, as well as much of the current literature, do not adequately address the familial dimension inherent in genetic research, are virtually silent on the issue of sharing information of relevance to family members, and do not protect the deceased. It is our belief that this omission needs to be corrected and that explicit guidance on this issue needs to be provided to institutional review boards and researchers alike.     

Understanding the Human Genome Project: a biographical approach

This article analyzes a number of recently published autobiographies by leading participants in the Human Genome Project (HGP), in order to determine to what extent they may further our understanding of the history, scientific significance and societal impact of this major research endeavor. Notably, I will focus on three publications that fall under this heading, namely The common thread by John Sulston (2002/2003), The language of God (2006) by Francis Collins and A life decoded by Craig Venter (2007).1 Sulston's autobiography was co-authored by science writer Georgina Ferry. What may we learn from these autobiographical sources about the dynamics of scientific change? What is their added value in understanding science in general and the HGP in particular? These questions will be elaborated in three directions: on the level of knowledge (epistemology), power (politics) and the Self (ethics). On the epistemological level, genomics is often presented as a paradigm shift in the life sciences, a tremendous up-scaling of research, an “informatization” of life. Autobiographies may reveal how this shift – usually discussed in more general terms from a philosophy of science or science studies perspective – manifests itself on an individual scale, on a micro-epistemological level. On the political level, autobiographies may inform us about the micro-politics of scientific change. Finally, on the level of Self, autobiographies may allow us to analyze how researchers, through practices of Self, are actively engaged in constituting themselves as responsible subjects in the face of unpredictable dynamics and unforeseen dilemmas.