Over the past 15 years, the project of advanced European integration has followed a complex secular and cosmopolitan agenda. As that agenda has evolved, however, so have various hard-line populist ...movements with goals diametrically opposed to the ideals of a harmonious European Union. Spearheaded by figures such as Jean-Marie Le Pen, the controversial leader of France's National Front party, these radical movements have become increasingly influential and, because of their philosophical affinities with fascism and national socialism--politically worrisome.
InIntegral Europe,anthropologist Douglas Holmes posits that such movements are philosophically rooted in integralism, a sensibility that, in its most benign form, enables people to maintain their ethnic identity and solidarity within the context of an increasingly pluralistic society. Taken to irrational extremes by people like Le Pen, integralism is being used to inflame people's feelings of alienation and powerlessness, the by-products of impersonal, transnational "fast-capitalism." The consequences are an invidious politics of exclusion that spawns cultural nationalism, racism, and social disorder.
The analysis moves from northern Italy to Strasbourg and Brussels, the two venues of the European Parliament, and finally to the East End of London. This multi-sited ethnography provides critical perspective on integralism as a form of intimate cultural practice and a violent idiom of estrangement. It combines a wide-ranging review of modern and historical scholarship with two years of field research that included personal interviews with right-wing activists, among them Le Pen and neo-Nazis in inner London. Fascinating, provocative, and sobering,Integral Europeoffers a rare inside look at one of modern Europe's most unsettling political trends.
Active cell death, in its many forms, is a fundamental biological process. Studies over the past several decades have explored the functions and consequences of cellular demise and elucidated several ...of the key cell death pathways. Here, I pose five questions, or riddles, that might provide a guide to the next decade of cell death research. Focusing mainly on four types of active cell death (apoptosis, necroptosis, pyroptosis, and ferroptosis) mainly in mammals, this Perspective explores the possible research directions that might answer these riddles, or at least prompt new ones.
Active cell death, in its many forms, is a fundamental biological process, and its study over the past several decades has provided key insights into the molecular processes, functions, and consequences responsible. Here, I pose five questions, or riddles, that might provide a guide to the next decade of cell death research. Focusing mainly on four types of active cell death (apoptosis, necroptosis, pyroptosis, and ferroptosis) mainly in mammals, this Perspective explores the possible research directions that might answer these riddles, or at least prompt new ones.
In the 40years since the essentiality of polyunsaturated fatty acids (PUFA) in fish was first established by determining quantitative requirements for 18:3n−3 and 18:2n−6 in rainbow trout, essential ...fatty acid (EFA) research has gone through distinct phases. For 20years the focus was primarily on determining qualitative and quantitative EFA requirements of fish species. Nutritional and biochemical studies showed major differences between fish species based on whether C18 PUFA or long-chain (LC)-PUFA were required to satisfy requirements. In contrast, in the last 20years, research emphasis shifted to determining “optimal” levels of EFA to support growth of fish fed diets with increased lipid content and where growth expectations were much higher. This required greater knowledge of the roles and functions of EFA in metabolism and physiology, and how these impacted on fish health and disease. Requirement studies were more focused on early life stages, in particular larval marine fish, defining not only levels, but also balances between different EFAs. Finally, a major driver in the last 10–15years has been the unavoidable replacement of fish oil and fishmeal in feeds and the impacts that this can have on n−3 LC-PUFA contents of diets and farmed fish, and the human consumer. Thus, dietary n−3 in fish feeds can be defined by three levels. Firstly, the minimum level required to satisfy EFA requirements and thus prevent nutritional pathologies. This level is relatively small and easy to supply even with today's current high demand for fish oil. The second level is that required to sustain maximum growth and optimum health in fish being fed modern high-energy diets. The balance between different PUFA and LC-PUFA is important and defining them is more challenging, and so ideal levels and balances are still not well understood, particularly in relation to fish health. The third level is currently driving much research; how can we supply sufficient n−3 LC-PUFA to maintain these nutrients in farmed fish at similar or higher levels than in wild fish? This level far exceeds the biological requirements of the fish itself and to satisfy it we require entirely new sources of n−3 LC-PUFA. We cannot rely on the finite and limited marine resources that we can sustainably harvest or efficiently recycle. We need to produce n−3 LC-PUFA de novo and all possible options should be considered.
•Long-chain omega-3 fatty acids are essential nutrients for vertebrates including fish and humans, but are a finite resource.•Supra-physiological levels are required to maintain high nutritional quality of farmed products.•Aquaculture an important role in the efficient use of long-chain omega-3 and their transfer to human consumers.•Entirely new sources of long-chain omega-3 fatty acids are required and transgenic oilseed crops represent viable option.
Macroautophagy (herein referred to as autophagy) is an evolutionary ancient mechanism that culminates with the lysosomal degradation of superfluous or potentially dangerous cytosolic entities. Over ...the past 2 decades, the molecular mechanisms underlying several variants of autophagy have been characterized in detail. Accumulating evidence suggests that most, if not all, components of the molecular machinery for autophagy also mediate autophagy-independent functions. Here, we discuss emerging data on the non-autophagic functions of autophagy-relevant proteins.
Proteins that regulate macroautophagy mediate a number of non-autophagy roles in physiology and disease.
Summary
Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be ...triggered to engage molecular programs that result in cell death. Such triggers include cellular stress, oncogenic signals that engage tumor suppressor mechanisms, pathogen insults, and immune mechanisms. The best‐known forms of programmed cell death are apoptosis and a recently recognized regulated necrosis termed necroptosis. Of the two best understood pathways of apoptosis, the extrinsic and intrinsic (mitochondrial) pathways, the former is induced by the ligation of death receptors, a subset of the TNF receptor (TNFR) superfamily. Ligation of these death receptors can also induce necroptosis. The extrinsic apoptosis and necroptosis pathways regulate each other and their balance determines whether cells live. Integral in the regulation and initiation of death receptor‐mediated activation of programmed cell death is the aspartate‐specific cysteine protease (caspase)‐8. This review describes the role of caspase‐8 in the initiation of extrinsic apoptosis execution and the mechanism by which caspase‐8 inhibits necroptosis. The importance of caspase‐8 in the development and homeostasis and the way that dysfunctional caspase‐8 may contribute to the development of malignancies in mice and humans are also explored.
Metastasis is the primary cause of cancer morbidity and mortality. The process involves a complex interplay between intrinsic tumor cell properties as well as interactions between cancer cells and ...multiple microenvironments. The outcome is the development of a nearby or distant discontiguous secondary mass. To successfully disseminate, metastatic cells acquire properties in addition to those necessary to become neoplastic. Heterogeneity in mechanisms involved, routes of dissemination, redundancy of molecular pathways that can be utilized, and the ability to piggyback on the actions of surrounding stromal cells makes defining the hallmarks of metastasis extraordinarily challenging. Nonetheless, this review identifies four distinguishing features that are required: motility and invasion, ability to modulate the secondary site or local microenvironments, plasticity, and ability to colonize secondary tissues. By defining these first principles of metastasis, we provide the means for focusing efforts on the aspects of metastasis that will improve patient outcomes.
The synapse is the focus of experimental research and theory on the cellular mechanisms of nervous system plasticity and learning, but recent research is expanding the consideration of plasticity ...into new mechanisms beyond the synapse, notably including the possibility that conduction velocity could be modifiable through changes in myelin to optimize the timing of information transmission through neural circuits. This concept emerges from a confluence of brain imaging that reveals changes in white matter in the human brain during learning, together with cellular studies showing that the process of myelination can be influenced by action potential firing in axons. This Opinion article summarizes the new research on activity-dependent myelination, explores the possible implications of these studies and outlines the potential for new research.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
The BCL-2 proteins, named for the first family member to be described (B cell lympho-ma-2), are a collection of related molecules found throughout the animal kingdom. They share only limited sequence ...similarity, except in short regions called BCL-2 homology (BH) domains, and can be grouped according to which of these domains they carry and, as we will see, by their functions. There are three "flavors" of BCL-2 proteins. The pro-apoptotic BCL-2 effectors promote apoptosis by causing mitochondrial outer membrane permeabilization (MOMP). The anti-apoptotic BCL-2 proteins, which include BCL-2 itself, prevent apoptosis by preventing MOMP. The third group is a subfamily of proteins that promote apoptosis by regulating the other two types of BCL-2 molecules.
Apoptosis shapes development and differentiation, has a key role in tissue homeostasis, and is deregulated in cancer. In most cases, successful apoptosis is triggered by mitochondrial outer membrane ...permeabilization (MOMP), which defines the mitochondrial or intrinsic pathway and ultimately leads to caspase activation and protein substrate cleavage. The mitochondrial apoptotic pathway centered on MOMP is controlled by an intricate network of events that determine the balance of the cell fate choice between survival and death. Here we will review how MOMP proceeds and how the main effectors cytochrome c, a heme protein that has a crucial role in respiration, and second mitochondria-derived activator of caspase (SMAC), as well as other intermembrane space proteins, orchestrate caspase activation. Moreover, we discuss recent insights on the interplay of the upstream coordinators and initiators of MOMP, the BCL-2 family. This review highlights how our increasing knowledge on the regulation of critical checkpoints of apoptosis integrates with understanding of cancer development and has begun to translate into therapeutic clinical benefit.
The health of metazoan organisms requires an effective response to organellar and cellular damage either by repair of such damage and/or by elimination of the damaged parts of the cells or the ...damaged cell in its entirety. Here, we consider the progress that has been made in the last few decades in determining the fates of damaged organelles and damaged cells through discrete, but genetically overlapping, pathways involving the selective autophagy and cell death machinery. We further discuss the ways in which the autophagy machinery may impact the clearance and consequences of dying cells for host physiology. Failure in the proper removal of damaged organelles and/or damaged cells by selective autophagy and cell death processes is likely to contribute to developmental abnormalities, cancer, aging, inflammation, and other diseases.
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