This comprehensive account of the history of Chinese lexicography is the first book on the subject to be published in English. It traces the development of Chinese lexicography over three millennia, from the Zhou Dynasty to the Qing Dynasty. Revealing how the emergence of lexicographical culture in ancient China was linked to the teaching of ancient characters, it describes the subsequent development of primers, thesauruses, and dictionaries of all major types, including those of dialects and technical terms. These works originated (...) and appeared in ancient China, predating their western counterparts by hundreds of years: and in one form or another most of them remain in use today. (shrink)

One approach to understanding how the human cognitive system stores and operates with quantifiers such as “some,” “many,” and “all” is to investigate their interaction with the cognitive mechanisms for estimating and comparing quantities from perceptual input (i.e., nonsymbolic quantities). While a potential link between quantifier processing and nonsymbolic quantity processing has been considered in the past, it has never been discussed extensively. Simultaneously, there is a long line of research within the field of numerical cognition on the relationship between (...) processing exact number symbols (such as “3” or “three”) and nonsymbolic quantity. This accumulated knowledge can potentially be harvested for research on quantifiers since quantifiers and number symbols are two different ways of referring to quantity information symbolically. The goal of the present review is to survey the research on the relationship between quantifiers and nonsymbolic quantity processing mechanisms and provide a set of research directions and specific questions for the investigation of quantifier processing. (shrink)

A natural heme deficiency that exists in cells outside of the circulation broadly compromises the heme contents and functions of heme proteins in cells and tissues. Recently, we found that the signaling molecule, nitric oxide (NO), can trigger or repress the deployment of intracellular heme in a concentration‐dependent hormetic manner. This uncovers a new role for NO and sets the stage for it to shape numerous biological processes by controlling heme deployment and consequent heme protein functions in biology.

The heme‐containing cytochromes P‐450 are a ubiquitous family of monooxygenase isozymes responsible for the oxidative metabolism of a wide variety of endogenous as well as exogenous compounds. Many of the compounds metabolized by this enzyme system are effectively detoxified and converted to derivatives more easily eliminated from the organism. However, some compounds can be activated to reactive species capable of eliciting a cascade of toxic lesions, including cancer. Since its discovery nearly 30 years ago, the cytochrome P‐450 enzyme system has (...) received a great deal of attention, particularly in the areas of their mechanisms of metabolism, range of substrate specificity, the purification and characterization of the multiple isozymes and, more recently, the regulation of expression of specific forms. This review will discuss current notions concerning the expression of at least one cytochrome P‐450 isozyme and future directions that should lead to a more complete understanding of cytochrome P‐450 gene expression in general, particularly as it impacts upon biochemical pharmacology. (shrink)

Humans accumulate porphyrins in the body mostly during the course of porphyrias, diseases caused by defects in the enzymes of the heme biosynthesis pathway and that produce acute attacks, skin lesions and liver cancer. In contrast, some wild mammals and birds are adapted to accumulate porphyrins without injurious consequences. Here we propose viewing such physiological adaptations as potential solutions to human porphyrias, and suggest certain wild animals as models. Given the enzymatic activity and/or the patterns of porphyrin excretion and accumulation, (...) the fox squirrel, the great bustard and the Eurasian eagle owl may constitute overlooked models for different porphyrias. The Harderian gland of rodents, where large amounts of porphyrins are synthesized, presents an underexplored potential for understanding the carcinogenic/toxic effect of porphyrin accumulation. Investigating how these animals avoid porphyrin pathogenicity may complement the use of laboratory models for porphyrias and provide new insights into the treatment of these disorders. (shrink)

The transcription factor Nrf2 is the master regulator of cellular stress response, facilitating the expression of cytoprotective genes, including those responsible for drug detoxification, immunomodulation, and iron metabolism. FDA‐approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are non‐specific alkylating agents exerting side effects. Nrf2 is under feedback regulation through its target gene, transcriptional repressor Bach1. Specifically, in Parkinson's disease and other neurodegenerative diseases with Bach1 dysregulation, excessive Bach1 accumulation interferes with Nrf2 activation. Bach1 (...) is a heme sensor protein, which, upon heme binding, is targeted for proteasomal degradation, relieving the repression of Nrf2 target genes. Ideally, a combination of Nrf2 stabilization and Bach1 inhibition is necessary to achieve the full therapeutic benefits of Nrf2 activation. Here, we discuss recent advances and future perspectives in developing small molecule inhibitors of Bach1, highlighting the significance of the Bach1/Nrf2 signaling pathway as a promising neurotherapeutic strategy. (shrink)

El propósito de Levinas coincide con el intento moderno de recuperación de la verdad y del sentido aunque en una dirección y contenidos distintos. Si en Hegel la Aufhebung tendía a la Totalidad y lo Mismo , para Husserl será esencial la apertura de Mundo que tiene lugar ya en la experiencia de conciencia del ego trascendental, mientras que Heidegger, por su parte, primará la pregunta por el Ser. El intento de Levinas, en cambio, no será recomponer la relación entre (...) el yo, por un lado, y el mundo, lo absoluto, las cosas o el ser, por el otro, sino la recuperación de la relación entre yo-y-otro. No es un simple cambio en la dirección o en el contenido del sentido de la reflexión filosófica, sino un intento serio de encontrar una nueva significación, «otra manera que ser» que no termine siendo otro proyecto más de integración y síntesis. Lo que propone Levinas es una auténtica salida para la que traza el itinerario que va del ser al otro, recurriendo sencillamente a la experiencia que cotidianamente se nos impone a cada uno de nosotros con un peso incontestable, a saber: la presencia de las diferencias, de lo asimétrico, en definitiva, la manifestación del otro en tanto que otro. Es esta experiencia heterónoma ordinaria, esta vivencia diaria de la alteridad como dato primordial del fenómeno de la intersubjetividad el ámbito que ha intentado explorar nuestro autor. ¿Acaso es esta responsabilidad así sentida conjugable con una experiencia filosófica universal? ¿La responsabilidad puede llevarse hasta el límite de la substitución por el otro, hasta la de-posición del Yo sin identidad? ¿Qué tipo de relación puede darse con algo absolutamente asimétrico, exterior, previo e irreductible? ¿De dónde viene esa asignación apremiante de responsabilidad que llega hasta arrojarme en la obsesión y el asedio? ¿Cómo puede ser éticamente plausible un mandato tan traumatizante y violento que termina por convertir al sujeto en rehén, sustituido ya por los otros? ¿Es posible conciliar la libertad y la autónoma decisión del sujeto con una consideración de la subjetividad como «heme aquí», absoluta pasividad expuesta a los otros y vulnerabilidad de una piel que se ofrece al ultraje y la herida?. En definitiva: ¿es la subjetividad algo de lo que partimos o a lo que llegamos? (shrink)

P.F. Strawson is one of the most famous Kantian philosophers and interpretators of Kant’s “Critique of Pure Reason”. This study is dedicated to reconstruction of this interpretation. It is also dedicated to the analysis of the story and place of Strawson’s interpretation in the history of his own philosophical career. I show how Strawson reads Kant’s text, what strategies of interpretation he adopts and what problems he faces. In “Individuals” and “The Bounds of Sense” Strawson explicitly associates himself with Kant (...) and considers himself as Kantian philosopher. Kantian philosophy for Strawson is the descriptive, anti-sceptical metaphysics that seeks to explicate our basic conceptual sсheme. However, due to various criticism, Strawson had to abandon descriptive metaphysics and to change his intellectual figures. On of the main heroes of “Skepticism and Naturalism” - his late book - becomes Hume. The second part of the paper is dedicated to the explanation of the transition from Kant to Hume. In this work, Strawson argues for some kind of soft Hume-like naturalism instead of previously held descriptive metaphysics. This kind of naturalism is more modest than metaphysics. It does not pretend to be the main and the most fundamental of all the philosophical studies. It is simply an analysis of one of the possible philosophical perspective. The stand point of ordinary believes. (shrink)

Background Chemotherapy and/or radiotherapy treatments may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of therapies on future reproductive autonomy are a major concern. While a few options are open to post-pubertal patients, the only immediate option currently open to pre-pubertal girls is cryopreservation of ovarian tissue and subsequent transplantation. The aim of the study was to address a current gap in knowledge regarding the offer (...) of fertility preservation by Ovarian Tissue Cryopreservation for prepubescent girls with cancer, and to explore current practices and attitudes of Canadian, French and Moroccan pediatric heme oncologists. The comparative perspective is relevant since legal frameworks surrounding fertility preservation and funding offered by the healthcare system vary greatly. Methods An online survey was sent to the 45 pediatric oncology centers in Canada, France and Morocco. Results A total of 39 centers responded. OTC is offered by almost all pediatric heme oncologists in France, very few in Canada, and none in Morocco. For pediatric hematologists/oncologists who do not propose fertility preservation in Canada, the reasons are: the technique is still experimental, it is not available locally and cost of the technique for the family. 97% of Canadian and 100% of Moroccan pediatric hematologists/oncologists think OTC should be funded by the healthcare system as it is in France and in the province of Quebec in Canada. Conclusions The results of this study show tremendous diversity in the provision of OTC across countries, whereby its offer is correlated with legislation and funding. We argue that the current reality, in which this technology is often not offered to families, raises ethical issues related to justice and equity of access, as well as informed consent and future reproductive autonomy. (shrink)

In eukaryotes, small amounts of nitrite confer cytoprotection against ischemia/reperfusion‐related tissue damage in vivo, possibly via reduction to nitric oxide (NO) and inhibition of mitochondrial function. Several hemeproteins are involved in this protective mechanism, starting with deoxyhemoglobin, which is capable of reducing nitrite. In facultative aerobic bacteria, such as Pseudomonas aeruginosa, nitrite is reduced to NO by specialized heme‐containing enzymes called cd1 nitrite reductases. The details of their catalytic mechanism are summarized below, together with a hypothesis on the biological role (...) of the unusual d1‐heme, which, in the reduced state, shows unique properties (very high affinity for nitrite and exceptionally fast dissociation of NO). Our results support the idea that the nitrite‐based reactions of contemporary eukaryotes are a vestige of earlier bacterial biochemical pathways. The evidence that nitrite reductase activities of enzymes with different cellular roles and biochemical features still exist today highlights the importance of nitrite in cellular homeostasis. (shrink)

'His mind and hand went together' said Hemings and Condell of the speed of Shakespeare. But the conceptual language of literary criticism, be it moralistic or political, has long been too slow to the properly responsive to Shakespeare's meaning. With the help of both Renaissance philosophers and present-day actors, Sudden Shakepeare seeks to locate the underlying secrets of Shakespeare's dynamic power. It offers a technical language wihch, close to Shakespeare's own, is capable of responding suddenly to the speed, transforming shape, (...) and power of Shakespeare's way of thinking as it comes into meaning. (shrink)

Studies of the regulation of heme oxygenase by synthetic metalloporphyrins reveal that within this group of compounds there exist both inducers and inhibitors of the synthesis of this enzyme or of its catalytic function. The ability of metalloporphyrins to alter heme catabolism is of considerable experimental and clinical interest since such alterations may have consequences for other aspects of heme homeostasis, including its synthesis and its function in the form of cytochrome(s) P‐450. Examples of the metabolic effects – and their (...) potential clinical and pharmacological consequences – produced by two synthetic metalloporphyrins, Sn‐protoporphyrin and Co‐protoporphyrin, are discussed. (shrink)

The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is (...) rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules. (shrink)

Resumen El presente artículo investiga los fundamentos creacionales del mesianismo en el pensamiento del pensador judío Emmanuel Levinas. Revisando diversos escritos judíos y filosóficos del autor se muestra que el ser humano, creado a partir de la nada, separado, soberano en su dependencia, está convo cado a ser responsable y a promover la vida de los demás, sustituyendo, incluso, a los otros, poniéndose en su lugar, asumiendo sus pesares y dolores, haciéndo se cargo de ese modo del sufrimiento universal. Con (...) todo, para Levinas el “yo” es quien está llamado a asumir su singular vocación mesiánica, a afirmar “heme aquí”. Y este mismo Yo es aquel, que antes de toda decisión, ha sido elegido para soportar toda la responsabilidad del Mundo y en consecuencia es el llamado a ser “Mesías”.This article investigates the creationalfoundations of messianism in the thought of the Jewish thinker Emmanuel Levinas. Reviewing various Jewish andphilosophical writ- ings of the author it is shown that the human being, created from nothingg, separated, sovereign in his dependence, is summoned to be responsible and promote the lives of others, even replac- ing others, putting himself in hisplace, assuming his sorrows andpains, thereby taking charge of universal suffering. However, for Levinas the “I” is the one who is called to assume his singular messianic vocation, to affirm “here I am”. And this same “I” is the one who, before any decision, has been chosen to bear all the responsibility of the World and conse- quently is the call to be “Messiah”. (shrink)

Throughout its matrix of atoms, myoglobin has a network of cavities that are inhabited for short lengths of time by ligands released by photolysis from the myoglobin heme. The purpose or effect of this cavity network is not clear. A recently published kinetic scheme that fits data from many native and mutant myoglobin oxygen photolysis experiments can be modified easily into a kinetic scheme that includes kinetic proofreading. Proofreading would provide protection against contaminants and, specifically, might help protect the cell (...) from carbon monoxide poisoning. Here we present a two‐part model: (1) myoglobin represented by a kinetic description, which includes proofreading reactions associated with the cavities, and (2) a reaction–diffusion description of a myocyte model in which the part 1 myoglobin acts as a mobile buffer in simultaneous carbon monoxide and oxygen gradients. The non‐equilibrium nature of part 2 should promote the proofreading function of part 1. A simulation using the model demonstrates that the cavity system can in principle proofread, reducing mitochondrial enzyme contamination. BioEssays 26:422–433, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Carbon monoxide (CO), a product of organic oxidation processes, arises in vivo during cellular metabolism, most notably heme degradation. CO binds to the heme iron of most hemoproteins. Tissue hypoxia following hemoglobin saturation represents a principle cause of CO‐induced mortality in higher organisms, though cellular targets cannot be excluded. Despite extreme toxicity at high concentrations, low concentrations of CO can confer cytoprotection during ischemia/reperfusion or inflammation‐induced tissue injury. Likewise, heme oxygenase, an enzyme that produces CO, biliverdin and iron, as well (...) as a secondary increase in ferritin synthesis, from the oxidation of heme, can confer protection in vivo and in vitro. CO has been shown to affect several intracellular signaling pathways, including guanylate cyclase, which generates guanosine 3′:5′ cyclic monophosphate and the mitogen‐activated protein kinases (MAPK). Such pathways mediate, in part, the known vasoregulatory, anti‐inflammatory, anti‐apoptotic and anti‐proliferative effects of this gas. Exogenous CO delivered at low concentrations is showing therapeutic potential as an anti‐inflammatory agent and as such can modulate numerous pathophysiological states. This review will delve into the biological significance and medical applications of this gas molecule. BioEssays 26:270–280, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Shakespeare's Four Folios were published between 1623 and 1685. Although 'folio' refers to the large size of the books, it is also a reflection of the standing in which the plays and their author were held. Up until the publication of the First Folio , works of literature had never before been produced in such large and luxurious a format. In each of the folios, the 26 plays are arranged in genres of Comedies, Histories and Tragedies and include introductory notes (...) by the editors, Heming and Condell. Routledge/Thoemmes Press have re-published the Four Folios in their original size and format, as they would have appeared in the 17th Century. (shrink)

In this article, David Shemin, who is now in retirement, describes how in 1944 he ingested 66 g of 15N‐labeled glycine in order to determine the half‐life of hemoglobin and other blood proteins. The ramifications of the experiment led to the unravelling of the biosynthesis of porphyrins and the role of glycine and α‐aminolevulinic acid in heme, vitamin B12 and chlorophyll synthesis.

Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformational change to CytOx, causing inhibition. (...) In times of stress, ATP‐dependent inhibition is switched off and the activity of CytOx is exclusively determined by the membrane potential, leading to an increase in ROS production. The second mechanism for respiratory control depends on the quantity of electron transfer to the Heme aa3 of CytOx. When ATP is bound to CytOx the enzyme is inhibited, and ROS formation is decreased, although the mitochondrial membrane potential is increased. (shrink)