Virus Entry, Assembly, Budding, and Membrane Rafts

As intracellular parasites, viruses rely heavily on the use of numerous cellular machineries for completion of their replication cycle. The recent discovery of the heterogeneous distribution of the various lipids within cell membranes has led to the proposal that sphingolipids and cholesterol tend to segregate in microdomains called membrane rafts. The involvement of membrane rafts in biosynthetic traffic, signal transduction, and endocytosis has suggested that viruses may also take advantage of rafts for completion of some steps of their replication cycle, such as entry into their cell host, assembly, and budding. In this review, we have attempted to delineate all the reliable data sustaining this hypothesis and to build some models of how rafts are used as platforms for assembly of some viruses. Indeed, if in many cases a formal proof of raft involvement in a virus replication cycle is still lacking, one can reasonably suggest that, owing to their ability to specifically attract some proteins, lipid microdomains provide a particular milieu suitable for increasing the efficiency of many protein-protein interactions which are crucial for virus infection and growth.     

Virus entry, assembly, budding, and membrane rafts.

As intracellular parasites, viruses rely heavily on the use of numerous cellular machineries for completion of their replication cycle. The recent discovery of the heterogeneous distribution of the various lipids within cell membranes has led to the proposal that sphingolipids and cholesterol tend to segregate in microdomains called membrane rafts. The involvement of membrane rafts in biosynthetic traffic, signal transduction, and endocytosis has suggested that viruses may also take advantage of rafts for completion of some steps of their replication cycle, such as entry into their cell host, assembly, and budding. In this review, we have attempted to delineate all the reliable data sustaining this hypothesis and to build some models of how rafts are used as platforms for assembly of some viruses. Indeed, if in many cases a formal proof of raft involvement in a virus replication cycle is still lacking, one can reasonably suggest that, owing to their ability to specifically attract some proteins, lipid microdomains provide a particular milieu suitable for increasing the efficiency of many protein-protein interactions which are crucial for virus infection and growth.     

Subjects and Objects: Metaphysics, Biology, Consciousness, and Cognition

Over the past half-century, the Freeman laboratory has accumulated a large volume of data and a correspondingly extensive interpretive framework centered around an alternative perspective on brain function, that of dynamical systems. The purpose of this paper is first briefly to summarise this work, and bring it into dialogue with other perspectives. The contents of consciousness are seen as an inevitably sparse sample of events in the perception–action cycle. The paper proceeds to an attempt to elucidate the contents of this sparse sample. A critical concept is that of selfhood, and how it presents itself phenomenologically. It is argued that our experience of selfhood is an artifact of the necessity of preservation of subject/object relations. As this part of metaphysics has been badly misunderstood, we scrutinise it at some length in quantum mechanics, biology, and cognition. It is argued that Pattee's approach, while valuable, tends to premature closure on these issues. The paper then proceeds to outline a view on how selfhood is best considered wrt the immune response. This is interrelated with phenomenology, and some data are adduced to support this central hypothesis. Finally, consequences for the social sciences in general are hinted at.     

Fear, faces, and the human amygdala

The amygdala's historical role in processing stimuli related to threat and fear is being modified to suggest a role that is broader and more abstract. Amygdala lesions impair the ability to seek out and make use of the eye region of faces, resulting in impaired fear perception. Other studies in rats and humans revive earlier proposals that the amygdala is important not only for fear perception as such, but also for detecting saliency and biological relevance. Debates about some features of this processing now suggest that while the amygdala can process fearful facial expressions in the absence of conscious perception, and while there is some degree of preattentive processing, this depends on the context and is not necessarily more rapid than cortical processing routes. A large current research effort extends the amygdala's putative role to a number of psychiatric illnesses.     

形态性状、分子性状与同源性

“同源性(homology)”是生物学中最基本的概念之一。近年来, 随着分子生物学、生物信息学、发育生物学以及进化发育遗传学等学科的快速发展, 同源性一词在形态性状的比较、核苷酸和氨基酸序列的分析以及探讨形态性状进化的分子机制等方面都有广泛应用。然而, 由于不同的研究者对同源性概念的理解有所不同, 在实际应用中难免会出现不恰当使用“同源性”一词并得出错误结论的情况。本文从不同的角度介绍了如何对同源性进行判断以及影响同源性判断的因素。并指出正确理解同源性这一概念的含义, 以及通过综合各方面的证据对同源性进行推断对于揭示基因型和表型的进化以及二者之间的关系非常重要。     

形态性状、分子性状与同源性

“同源性（homology）”是生物学中最基本的概念之一。近年来,随着分子生物学、生物信息学、发育生物学以及进化发育遗传学等学科的快速发展,同源性一词在形态性状的比较、核苷酸和氨基酸序列的分析以及探讨形态性状进化的分子机制等方面都有广泛应用。然而,由于不同的研究者对同源性概念的理解有所不同,在实际应用中难免会出现不恰当使用“同源性”一词并得出错误结论的情况。本文从不同的角度介绍了如何对同源性进行判断以及影响同源性判断的因素。并指出正确理解同源性这一概念的含义,以及通过综合各方面的证据对同源性进行推断对于揭示基因型和表型的进化以及二者之间的关系非常重要。     

Membranes,viruses, detergents,and endosomes

The fluid mosaic model for biological membranes was formulated 40 years ago. Ten years later endosomes were discovered as important prelysosomal organelles. At the outset of my research career, I was fortunate to witness both these turning points in biochemistry and cell biology from close up, and to participate in some of the studies. In this short essay, I will describe how this came about, and also try to provide some background as to the general starting situation in those not so distant pioneering years of membrane biology.     

Restricted treatments, inducements, and research participation

In this paper, I support the claim that placing certain restrictions on public access to possible new treatments is morally problematic under some exceptional circumstances. Very ill patients may find that all available standard treatments are unacceptable, either because they are ineffective or have serious adverse effects, and these patients may understandably be desperate to try something new even if this means stepping into the unknown. Faced with certain death, it is rational to want to try something new and to chance a dire outcome. Restricting possible new treatments to research trials may put these treatments scientifically, geographically or economically out of reach of these patients. For those who can get access, research restrictions could weaken, though not necessarily eliminate, the value of consent participants of such trials are able to give. Some participants may therefore be exploited for scientific purposes in the name of public interest. There are nonetheless compelling reasons for keeping some restrictive regulation in this area.     

Infection, autoimmune diseases, atherosclerosis, infarct, stroke, cancerogenesis: what is in common

The problem of the transformation of specific antibodies into nonspecific polyreactive immunoglobulins (PRIG) was considered. On the basis of the obtained data the conclusion has been made that this process can occur not only in vitro, but also in vivo. The biological consequences of such a transformation of circulated specific antibodies into PRIG or increase of PRIG reactivity because of their unblocking are discussed. It was supposed that PRIG was able to play positive role in the defence of organisms against some infections. Meanwhile, disregulation of the PRIG production in vivo can, probably, lead to their participation in induction and/or in aggravation of some danger diseases, such as autoimmune diseases, atherosclerosis, infarct, stroke, and cancer. If so, farther investigation of PRIG involvement in these pathological processes could open new ways for their curing or even prophylaxis.     

Morality, adapted

Over the last few decades, scientists have been busy debunking the myth that nonhuman animals relate to each other in a primarily competitive, aggressive way. What they have found is that many species of animal, including many of those most closely related to humans, display a remarkable range of cooperative, "prosocial" behavior. In fact, it appears that some animal societies adhere to a moral code. What is preventing us, then, from saying that the members of these societies are moral beings? Nothing important, according to a recent book. Probing further into this question, I suggest that in fact quite a lot is at risk in making this move. To integrate nonhuman animals fully into the moral domain, we may have to adapt our conception of morality in some very troublesome ways.     

Mast cells, angiogenesis, and tumour growth

Accumulation of mast cells (MCs) in tumours was described by Ehrlich in his doctoral thesis. Since this early account, ample evidence has been provided highlighting participation of MCs to the inflammatory reaction that occurs in many clinical and experimental tumour settings. MCs are bone marrow-derived tissue-homing leukocytes that are endowed with a panoply of releasable mediators and surface receptors. These cells actively take part to innate and acquired immune reactions as well as to a series of fundamental functions such as angiogenesis, tissue repair, and tissue remodelling. The involvement of MCs in tumour development is debated. Although some evidence suggests that MCs can promote tumourigenesis and tumour progression, there are some clinical sets as well as experimental tumour models in which MCs seem to have functions that favour the host. One of the major issues linking MCs to cancer is the ability of these cells to release potent pro-angiogenic factors. This review will focus on the most recent acquisitions about this intriguing field of research. This article is part of a Special Issue entitled: Mast cells in inflammation.     

A conserved Myc protein domain, MBIV, regulates DNA binding, apoptosis, transformation, and G2 arrest

The myc family of oncogenes is well conserved throughout evolution. Here we present the characterization of a domain conserved in c-, N-, and L-Myc from fish to humans, N-Myc317-337, designated Myc box IV (MBIV). A deletion of this domain leads to a defect in Myc-induced apoptosis and in some transformation assays but not in cell proliferation. Unlike other Myc mutants, MycDeltaMBIV is not a simple loss-of-function mutant because it is hyperactive for G2 arrest in primary cells. Microarray analysis of genes regulated by N-MycDeltaMBIV reveals that it is weakened for transactivation and repression but not nearly as defective as N-MycDeltaMBII. Although the mutated region is not part of the previously defined DNA binding domain, we find that N-MycDeltaMBIV has a significantly lower affinity for DNA than the wild-type protein in vitro. Furthermore, chromatin immunoprecipitation shows reduced binding of N-MycDeltaMBIV to some target genes in vivo, which correlates with the defect in transactivation. Thus, this conserved domain has an unexpected role in Myc DNA binding activity. These data also provide a novel separation of Myc functions linked to the modulation of DNA binding activity.     

Phagotherapy in terms of bacteriophage genetics: hopes, perspectives, safety, limitations

The appearance and spreading of multidrug-resistant bacterial pathogens is a consequence of the large-scale use of antibiotics in medicine. In view of this, claims for the phage therapy were renewed: in recent studies, the natural phages and their products neutralizing various proteins, as well as the bacterial products often controlled by defective prophages (bacteriocins) were applied for treatment of bacterial infections. Constructs obtained by gene engineering are increasingly used to change some bacteriophage: properties to expand the spectrum of their lytic activity and to eliminate therapeutic drawbacks of some natural phages. In this review, the problem of phage therapy is discussed in general with respect to bacteriophage properties, their genetics, structure, evolution, taking into account long-term experience of the author in the field of bacteriophage genetics. Note that the general concept of phage therapy should be developed to ensure long-term, efficient and harmless phage therapy.     

Time scales of memory, learning, and plasticity

After only about 10 days would the storage capacity of our nervous system be reached if we stored every bit of input. The nervous system relies on at least two mechanisms that counteract this capacity limit: compression and forgetting. But the latter mechanism needs to know how long an entity should be stored: some memories are relevant only for the next few minutes, some are important even after the passage of several years. Psychology and physiology have found and described many different memory mechanisms, and these mechanisms indeed use different time scales. In this prospect we review these mechanisms with respect to their time scale and propose relations between mechanisms in learning and memory and their underlying physiological basis.     

Microbes, warfare, religion, and human institutions

A significant number of practicing microbiologists are not aware of the historical impact of infectious agents on the development of human institutions. Microbes have played a profound role in warfare, religion, migration of populations, art, and in diplomacy. Boundaries of nations have changed as a result of microbial diseases. Infectious agents have terminated some kingdoms and elevated others. There is a need for microbiologists to have a historical perspective of some of the major ways in which a pathogen may influence civilized populations. Conditions may exist in contemporary society for a repeat of some of the kinds of plagues suffered by previous societies. The purpose of this paper is to review examples of situations where pathogenic microbes have forced societal modifications on centers of human population.     

Academic Freedom,Public Reactions,and Anonymity

Academic freedom can be defined as immunity against adverse reactions from the general public, designed to keep scholars unintimidated and productive even after they have published controversial ideas. Francesca Minerva claims that this notion of strict instrumental academic freedom is supported by Ronald Dworkin, and that anonymity would effectively defend the sphere of immunity implied by it. Against this, I argue that the idea defended by Minerva finds no support in the work by Dworkin referred to; that anonymity would not in most cases effectively protect the kind of immunity sought after; and that in some cases it would not even be desirable to protect scholars from public reactions to their controversial claims.     

Field biology of placozoans (Trichoplax): distribution, diversity, biotic interactions

The goal of this review is to highlight what little is known,and point to the bulk of what is yet to be learned, about thenatural history of placozoans in the field—in order tostimulate a broader search for placozoans and a fuller explorationof their distribution, diversity, and all other aspects of theirenigmatic lives. The documented geographic distribution of placozoanslies mostly in the nearshore, warm, marine waters of the tropicsand subtropics. Although placozoans have long been viewed asbenthic organisms, they can be more readily collected from thewater column, well above the sea bottom. The full life-historyof placozoans is unknown, including the nature of this abundantpelagic phase and all details of sexual reproduction and development.We note observations on the biota associated with placozoansin field collections, in particular the other regular membersof the microcommunity in which placozoans occur on our collectingplates and on some factors influencing this assemblage. Amongthe animals found are some potential predators against whichplacozoans appear to be defended, although the mechanisms arestill to be examined. Also yet to be uncovered is the full breadthof diversity in this phylum, certainly underrepresented by itssingle named species. We report here greatly expanded distributionsfor known haplotypes and fresh specimens that include a newhaplotype, and we review the evidence that many more almostcertainly await discovery. We also describe some methods forcollecting and handling these small, fragile animals.     

Mechanisms,resources, and background conditions

Distinguishing mechanistic components from mere causally relevant background conditions remains a difficulty for mechanistic accounts of explanation. By distinguishing resources from mechanical parts, I argue that we can more effectively draw this boundary. Further, the distinction makes obvious that there are distinctive resource explanations which are not captured by a traditional part-based mechanistic account. While this suggests a straightforward extension of the mechanistic model, I argue that incorporating resources and resource explanations requires moving beyond the purely local account of levels that some mechanists advocate.