Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy‐rich chains. PolyP is involved in diverse functions in mammalian systems—from cell signaling to blood clotting. One exciting avenue of research is a new nonenzymatic post‐translational modification, termed lysine polyphosphorylation, wherein polyP chains are covalently attached to lysine residues of target proteins. While the modification was first characterized in budding yeast, (...) recent work has now identified the first human targets. There is significant promise in this area of biomedical research, but a number of technical issues and knowledge gaps present challenges to rapid progress. In this review, the current state of the field is summarized and existing roadblocks related to the study of lysine polyphosphorylation in higher eukaryotes are introduced. It is discussed how limited methods to identify targets of polyphosphorylation are further impacted by low concentration, unknown regulatory enzymes, and sequestration of polyP into compartments in mammalian systems. Furthermore, suggestions on how these obstacles could be addressed or what their physiological relevance may be within mammalian cells are presented. (shrink)

: All known life requires phosphorus (P) in the form of inorganic phosphate (PO43x or Pi) and phosphate-containing organic molecules. Pi serves as the backbone of the nucleic acids that constitute genetic material and as the major repository of chemical energy for metabolism in polyphosphate bonds. Arsenic (As) lies directly below P on the periodic table and so the two elements share many chemical properties, although their chemistries are sufficiently dissimilar that As cannot directly replace P in (...) modern biochemistry. Arsenic is toxic because As and P are similar enough that organisms attempt this substitution. We hypothesize that ancient biochemical systems, analogous to but distinct from those known today, could have utilized arsenate in the equivalent biological role as phosphate. Organisms utilizing such ‘ weird life ’ biochemical pathways may have supported a ‘ shadow biosphere ’ at the time of the origin and early evolution of life on Earth or on other planets. Such organisms may even persist on Earth today, undetected, in unusual niches. (shrink)

Hypoxia hampers ATP production and threatens cell survival. Since cellular energetics tightly controls cell responses and fate, ATP levels and dynamics are of utmost importance. An integrated mathematical model of ATP synthesis by the mitochondrial oxidative phosphorylation/electron transfer chain system has been recently published :e36, 2005). This model was validated under static conditions. To evaluate its performance under dynamical situations, we implemented and simulated it . Inner membrane potential and [NADH] were used as indicators of mitochondrial function. Root mean squared (...) error was used to compare simulations and experiments :39155–39165, 2003). Steady-state experimental data were reproduced within 2–6%. Model dynamics were evaluated under: baseline, activation of NADH production, addition of ADP, addition of inorganic phosphate, oxygen exhaustion. In all phases, except the last one, ΔΨ and [NADH] as well as oxygen consumption, were reproduced . Under anoxia, simulated ΔΨ markedly depolarized . In conclusion, the model reproduces dynamic data as long as oxygen is present. Anticipated improvement by the inclusion of ATP consumption and explicit Krebs cycle are under evaluation. (shrink)

Bacteria have evolved advanced strategies for surviving during nutritional stress, including expression of specialized enzyme systems that allow them to grow on unusual nutrient sources. Inorganic phosphate (Pi) is limiting in most ecosystems, hence organisms have developed a sophisticated, enzymatic machinery known as carbon‐phosphorus (C‐P) lyase, allowing them to extract phosphate from a wide range of phosphonate compounds. These are characterized by a stable covalent bond between carbon and phosphorus making them very hard to break down. Despite (...) the challenges involved in both synthesizing and catabolizing phosphonates, they are widespread in nature. The enzymes required for the bacterial C‐P lyase pathway have been identified and for the most part structurally characterized. Nevertheless, the mechanistic principles governing breakdown of phosphonate compounds remain enigmatic. In this review, an overview of the C‐P lyase pathway is provided and structural aspects of the involved enzyme complexes are discussed with a special emphasis on the role of ATP‐binding cassette (ABC) proteins. (shrink)

Bacteria have evolved advanced strategies for surviving during nutritional stress, including expression of specialized enzyme systems that allow them to grow on unusual nutrient sources. Inorganic phosphate (Pi) is limiting in most ecosystems, hence organisms have developed a sophisticated, enzymatic machinery known as carbon‐phosphorus (C‐P) lyase, allowing them to extract phosphate from a wide range of phosphonate compounds. These are characterized by a stable covalent bond between carbon and phosphorus making them very hard to break down. Despite (...) the challenges involved in both synthesizing and catabolizing phosphonates, they are widespread in nature. The enzymes required for the bacterial C‐P lyase pathway have been identified and for the most part structurally characterized. Nevertheless, the mechanistic principles governing breakdown of phosphonate compounds remain enigmatic. In this review, an overview of the C‐P lyase pathway is provided and structural aspects of the involved enzyme complexes are discussed with a special emphasis on the role of ATP‐binding cassette (ABC) proteins. (shrink)

Release of the ATP hydrolysis product ortophosphate (Pi) from the active site of myosin is central in chemo‐mechanical energy transduction and closely associated with the main force‐generating structural change, the power‐stroke. Despite intense investigations, the relative timing between Pi‐release and the power‐stroke remains poorly understood. This hampers in depth understanding of force production by myosin in health and disease and our understanding of myosin‐active drugs. Since the 1990s and up to today, models that incorporate the Pi‐release either distinctly before or (...) after the power‐stroke, in unbranched kinetic schemes, have dominated the literature. However, in recent years, alternative models have emerged to explain apparently contradictory findings. Here, we first compare and critically analyze three influential alternative models proposed previously. These are either characterized by a branched kinetic scheme or by partial uncoupling of Pi‐release and the power‐stroke. Finally, we suggest critical tests of the models aiming for a unified picture. (shrink)

In explicating his version of the Organism View, Eric Olson argues that you begin to exist only after twinning is no longer possible and that you cannot survive a process of inorganic replacement. Assuming the correctness of the Organism View, but pace Olson, I argue in this paper that the Organism View does not require that you believe either proposition. The claim I shall make about twinning helps to advance a debate that currently divides defenders of the Organism View, (...) while the claim I shall make about inorganic replacement will help to put the Organism View on a par with its rival views by allowing it to accommodate a plausible intuition that its rivals can accommodate, namely, the intuition that you can survive a process of inorganic replacement. Both claims, I shall also argue, are important for those who are interested in the identity condition of a human organism, even if they do not hold the view that you are essentially an organism. (shrink)

Nowadays, batteries play an important role in a lot of different applications like energy storage, electro-mobility, consumer electronic and so on. All the battery types have a common factor that is their complexity, independently of its nature. Usually, the batteries have an electrochemical nature. Several different test are accomplished to check the batteries performance, and commonly, it is predictable how they work depending of their technology. The present research describes the hybrid intelligent system created to accomplish fault detection over a (...) Lithium Iron Phosphate—LiFePO4 power cell type, commonly used in electro-mobility applications. The approach is based on the cell temperatures behaviour for voltage and current specific values. Taken into account the operating range of a real system based on a LiFePO4 cell, a large set of points of operation have been used to achieve the dataset. The different behaviour zones have been obtained by clustering as a first step. Then, different regression techniques have been used over each cluster. Polynomial regression, artificial neural networks and support vector regression were the combined techniques to develop the hybrid intelligent model proposed. The intelligent system gives very good results over the operating range, detecting all the faults tested during the validation. (shrink)

Initially identified as a key phosphoinositide that controls membrane trafficking at the Golgi complex, phosphatidylinositol‐4‐phosphate (PI4P) has emerged as a key molecule in the regulation of a diverse array of cellular functions. In this review we will discuss selected examples of the findings that in the last few years have significantly increased our awareness of the regulation and roles of PI4P in the Golgi complex and beyond. We will also highlight the role of PI4P in infection and cancer. We (...) believe that, with the increasing number of regulators and effectors of PI4P identified, the time is ripe for a more integrated approach of study. A first step in this direction is the delineation of PI4P‐centered molecular networks that we provide using data from low and high throughput studies in yeast and mammals. (shrink)

Phosphatidylinositol 5‐phosphate (PtdIns5P), the least characterized among the three phosphatidylinositol monophosphates, is emerging as a bioactive lipid involved in the control of several cellular functions. Similar to PtdIns3P, it is present in low amounts in mammalian cells, and can be detected at the plasma membrane and endomembranes as well as in the nucleus. Changes in PtdIns5P levels are observed in mammalian cells following specific stimuli or stresses, and in human diseases. Recently, the contribution of several enzymes such as PIKfyve, (...) myotubularins, and type II PtdInsP‐kinases to PtdIns5P metabolism has gained a strong experimental support. Here, we provide a picture emerging from recent studies showing how this lipid can be generated and act as a regulator of membrane and cytoskeleton dynamics, and as a modulator of gene expression. We briefly summarize the current methods and tools for studying PtdIns5P, and discuss how PtdIns5P can integrate and coordinate different functions in a spatiotemporal manner. (shrink)

If literary avant-garde journals and their communities have been, in the twentieth century, a space for creating, if not sustaining, major political utopias, it should help explain why this “literary communism,” as Jean-Luc Nancy called it, is not a weakened or substitutional form of politics. No myth without narration, no implementation without an instrumentation, no organic unity without a political organ voicing its claim, in short: no organicity without an organon. But can there be a (literary) community that does not (...) aim at the achievement of its own assumed truth, a form of writing in common that does not serve to convey a meaning, but bears witness, in its very form, to the fragmentation of meaning? This essay examines three attempts of an affi rmative answer to this question by reappraising three interrelated experimental cases: Jena around 1800 and the Athenaeum journal of the Early Romantics; Walter Benjamin’s journal projects, from the Angelus Novus to the prison camp journal at the end of his life; Maurice Blanchot and the failed trans-European project of what was arguably the most ambitious intellectual journal enterprise of the century, the Revue internationale in the early 1960s. (shrink)

Phosphatidylinositol 3‐phosphate (PtdIns3P) is generated on the cytosolic leaflet of cellular membranes, primarily by phosphorylation of phosphatidylinositol by class II and class III phosphatidylinositol 3‐kinases. The bulk of this lipid is found on the limiting and intraluminal membranes of endosomes, but it can also be detected in domains of phagosomes, autophagosome precursors, cytokinetic bridges, the plasma membrane and the nucleus. PtdIns3P controls cellular functions through recruitment of specific protein effectors, many of which contain FYVE or PX domains. Cellular processes (...) known to be controlled by PtdIns3P and its effectors include endosomal fusion, sorting and motility, autophagy, cytokinesis, regulated exocytosis and signal transduction. Here we discuss how Ptdins3P is generated on specific cellular membranes, how its localizations and functions can be studied, and how its effectors serve to control cellular functions.Editor's suggested further reading in BioEssays:Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signalingAbstractHow does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity?AbstractPhosphatidylinositol‐3,4,5‐trisphosphate: Tool of choice for class I PI 3‐kinasesAbstractPhosphatidylinositol‐4‐phosphate: The Golgi and beyondAbstract. (shrink)

What separates Mario Perniola from other philosophers of his generation, is his programmatic inquiry into the dark side of humanities, what I here call ‘dank humanities’ – with a focus on topics hard to catch, and sides of experience and interpretation which evade simple pleasure and order. Often his thinking finds a niche where one can feel barely human or sense something that in the end evades interpretation. Suggestive in tone, it inquired into these topics also in a way that (...) made his thinking hard to classify as philosophy, cultural studies and/or psychoanalysis. In my article on his work, I aspire to think of it more commonly as a form of overall humanities, and to see it as a programmatic attempt to nail the potentials of the humanities to reach beyond our pleasures, understanding and safety-driven metaphysics. (shrink)

Attempts to find an authentically ecological outlook in Marx’s philosophy of nature are ultimately unsuccessful. Although Marx does at times point the way toward a truly ecological dialectic, he does not himself follow that way. Instead, he proposes a problematic of technological liberation and mastery of nature that preserves many of the dualisms of that tradition of domination with which he ostensibly wishes to break.

This paper explores the concept of "inorganic sexuality" in the work of Italian writer and philosopher Mario Perniola. The main objective is to develop the controversial and original aspects of Perniola's thought within his aesthetic theory of feeling. Perniola elaborates the so-called "thing that feels", namely a feeling in which the neutral and impersonal dimensions of the things flow into organic life and vice versa. This perspective, as will be clarified, by dissolving the vitalist and spiritualist drives of the (...) subject, enlarges the horizon of aesthetic feeling by welcoming what is commonly left outside of it: the inorganic and material world, in its surprising aspects, but also in its uncanny and disturbing ones. Therefore, the main goal of this paper is to show the significance and the value of neutral sexuality, which opens up a space of experiences beyond the traditional metaphysical oppositions such as masculine/feminine, organic/inorganic, alive/dead, real/virtual, gender/sex. (shrink)

Attempts to find an authentically ecological outlook in Marx’s philosophy of nature are ultimately unsuccessful. Although Marx does at times point the way toward a truly ecological dialectic, he does not himself follow that way. Instead, he proposes a problematic of technological liberation and mastery of nature that preserves many of the dualisms of that tradition of domination with which he ostensibly wishes to break.

Animation victims: an abridged history of animated response -- Animated history -- The movement of accessories -- Fabric extensions and textual supplements from modern and antique fragments -- The movement of snakes -- Pneumatic impulses and bygone appendages from Philo to Warburg -- The afterlife of crystals -- Art historical biology and the animation of the inorganic -- Inorganic culture -- Nudes in the forest -- Models, sciences, and legends in a landscape by Léger -- Malicious houses -- (...) Animism and animosity in German architecture and film from Mies to Murnau -- Daphne's legacy -- Architecture, psychoanalysis, and petrification. (shrink)

Most of the essential cellular components, like nucleic acids, lipids and sugars, are phosphorylated. The phosphate equilibrium in Escherichia coli is regulated by the phosphate (Pi) input from the surrounding medium. Some 90 proteins are synthesized at an increased rate during Pi starvation and the global control of the cellular metabolism requires cross‐talk with other regulatory mechanisms. Since the Pi concentration is normally low in E. coli's natural habitat, these cells have devised a mechanism for synthesis of about (...) 15 proteins to accomplish two specific functions: transport of Pi and its intracellular regulation. The synthesis of these proteins is controlled by two genes (the phoB‐phoR operon), involving both negative and positive functions. PhoR protein is a histidine protein kinase, induced in Pi starvation and is a transmembrane protein. It phosphorylates the regulator protein PhoB which is also Pi starvation‐induced. The PhoB phosphorylated form binds specifically to a DNA sequence of 18 nucleotides (the pho Box), which is part of the promoters of the Pho genes. The genes controlled by phoB constitute the Pho regulon.The repression of phoA (the gene encoding alkaline phosphatase) by high Pi concentrations in the medium requires the presence of an intact Pst operon (pstS, pstC, pstA, pstB and phoU) and phoR. The products of pstA and pstC are membrane bound, whereas the product of pstS is periplasmic and PstB and PhoU proteins are cytoplasmic. The function of the PhoU protein may be regulated by cofactor nucleotides and may be involved in signaling the activation of the regulon via PhoR. (shrink)

Pyridoxal 5′‐phosphate, the vitamin B6 derivative, acts as the coenzyme of many enzymes involved in amino acid metabolism. Exceptionally, this compound was found covalently bound to glycogen phosphorylase, the key enzyme in the regulation of glycogen metabolism. Although it is essential for the function of phosphorylase, its direct role has remained an enigma. We have recently found that the glucose moiety of pyridoxal (5′)diphospho (1)‐α‐D‐glucose, a conjugate of pyridoxal 5′‐phosphate and glucose 1‐phosphate through a pyrophosphate linkage, is (...) transferred to the nonreducing end of glycogen, forming a new α‐1,4‐glucosidic linkage. This finding emphasizes the importance of the direct phosphate‐phosphate interaction between the coenzyme and the substrate in the phosphorylase catalytic reaction. We have proposed a catalytic mechanism for phosphorylase in which the phosphate group of pyridoxal 5′‐phosphate acts as an electrophile to the phosphate group of glucose 1‐phosphate. This appears to represent the first instance of the direct involvement of a phosphate group in catalysis by enzymes. (shrink)

Doubled lives -- Autobiography -- Automatic life, so life: Descartes -- Order catastrophically unknown: Freud -- The blushing machine: Derrida -- Translation -- The point if at all: Cixous and Celan -- Naming the mechanical angel: Benjamin -- Raw war: Schmitt, Jønger, and Joyce -- Resonance -- Bloodless coup: Bataille, Nancy, and Barthes -- The audible life of the image: Godard -- Meditations for the birds: Descartes.