Melatonin,clock genes and mitochondria in sepsis

After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.     

The Chemistry of the Universe: Historical Roots of Modern Cosmochemistry

During the second half of the twentieth century, the domain of geochemistry has greatly expanded and the field is today often seen as a branch of an extended chemistry of the Earth, called cosmochemistry. This paper is a historical introduction to cosmochemistry in which the wider cosmic aspects are surveyed up to about 1915, when nuclear physics changed the scene. These wider aspects or themes include, firstly, the attempts to determine the relative abundances of the elements, secondly, the extension of geochemistry to include physical geochemistry, thirdly, the study of meteorites and, fourthly, the spectroscopic study of the stars within the astrochemical tradition. Because of the lack of reliable data, a great deal of the protocosmochemistry described in the present paper was speculative. Nonetheless, by 1915 the contours of the cosmochemistry of the future were just visible and the developments here singled out can thus be seen as belonging to the prehistory of modern cosmochemistry.     

Aristotle, Copernicus, Bruno: centrality, the principle of movement and the extension of the Universe

This paper¹ studies the different conceptions of both centrality and the principle or starting point of motion in the Universe held by Aristotle and later on by Copernicanism until Kepler and Bruno. According to Aristotle, the true centre of the Universe is the sphere of the fixed stars. This is also the starting point of motion. From this point of view, the diurnal motion is the fundamental one. Our analysis gives pride of place to De caelo II, 10, a chapter of Aristotle’s text which curiously allows an ‘Alpetragian’ reading of the transmission of motion.In Copernicus and the Copernicans, natural centrality is identified with the geometrical centre and, therefore, the Sun is acknowledged as the body through which the Deity acts on the world and it also plays the role of the principle and starting point of cosmic motion. This motion, however, is no longer diurnal motion, but the annual periodical motion of the planets. Within this context, we pose the question of to what extent it is possible to think that, before Kepler, there is a tacit attribution of a dynamic or motive role to the Sun by Copernicus, Rheticus, and Digges.For Bruno, since the Universe is infinite and homogeneous and the relationship of the Deity with it is one of indifferent presence everywhere, the Universe has no absolute centre, for any point is a centre. By the same token, there is no place that enjoys the prerogative of being—as being the seat of God—the motionless principle and starting point of motion.     

Galanin – 25 years with a multitalented neuropeptide

The skin, the largest organ of the body, functions as a barrier between the body proper and the external environment, as it is constantly exposed to noxious stressors. During the last few years, the concept of an interactive network involving cutaneous nerves, the neuroendocrine axis, and the immune system has emerged. The neuroendocrine system of the skin is composed of locally produced neuroendocrine mediators that interact with specific receptors. Among these mediators are neuropeptides, including members of the galanin peptide family--galanin, galanin-message-associated peptide, galanin-like peptide, and alarin--which are produced in neuronal as well as nonneuronal cells in the skin. Here we review the expression of the galanin peptides and their receptors in the skin, and the known functions of galanin peptides in different compartments of the skin. We discuss these data in light of the role of the galanin peptide family in inflammation and cell proliferation.     

Crustal layering, simplicity, and the oil industry: The alteration of an epistemic paradigm by a commercial environment

This paper proposes that the gradual alteration of the predominant epistemic paradigm in crustal seismology in the interwar period—namely, simplicity—came about because of the strong influence of a particular commercial environment, i.e. the oil industry. I begin by demonstrating the interwar predominance of Jeffreys’ ‘simplicity postulate’ and his probabilistic epistemology, highlighting the espousal by several seismologists (Bullen, Stoneley, Byerly), whose crustal models drew on mathematical idealisations. Next, I demonstrate that the renunciation of simplicity in the 1930s came about too quickly, and, above all, too heterodoxically to have been the result of new geological evidence. Rather, I argue, the paradigm shift among seismologists was a result of the significant rise in seismic exploration generated by the oil industry. Driven by market demands, American petroleum companies pioneered new technologies, organised research initiatives, and trained young geophysicists who, through the fusion of experimentalism and field experience, brought about fundamental progress in earthquake seismology. Remarkably, historians of science have almost entirely failed to recognise the interwar primacy of the simplicity paradigm as well as its subsequent renunciation. More importantly, they have failed to acknowledge the role the oil industry played in contributing to this renunciation and to the development of new paradigms in seismology.     

Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain

The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid amide hydrolase, which catalyzes the metabolism of anandamide, was significantly lower during the dark phase, thus providing a possible explaination for the increase in anandamide levels. However, the activities of monoacylglycerol lipase and diacylglycerol lipase, two of the possible enzymes catalyzing the degradation and biosynthesis of 2-AG, respectively, changed significantly only in the striatum. These data suggest that the levels of the two major endocannabinoids might be under the control of endogenous factors known to undergo diurnal variations, and underscore the different roles, suggested by previous studies, of anandamide and 2-AG in neurophysiological processes.Received 9 December 2003; received after revision 15 January 2004; accepted 20 January 2004     

Chemistry and Chemists at the London Institution 1807-1912

The London Institution, established in the City of London in 1807, was devoted, as its full title proclaimed, to the 'advancement of Literature and the Diffusion of Useful Knowledge'. With its extensive lecture programme, splendid reference library, reading rooms, laboratory and other amenities, it provided for its members a scientific and cultural centre, modelled on the highly successful and fashionable Royal Institution in London's West End. Among its scientific activities, chemistry long maintained a leading role, in terms of both the sheer volume and variety of its presentations, and the high standing of its lecturers; they included Faraday, Playfair, Hofmann, Roscoe, Odling, Norman Lockyer, Meldola, and Sir William Ramsay, as well as other visiting lecturers, specially selected for their ability to present their subject in an interesting and attractive fashion to a wider lay public. The laboratory of the Institution, although limited in size and facilities, was the scene of instruction in practical chemistry, and between 1863 and 1884 attained the reputation of a significant centre of chemical research during the successive tenure of the professorship in chemistry by J. A. Wanklyn and H. E. Armstrong. Their publications, appearing under the device 'From the Laboratory of the London Institution', were a frequent feature of the leading chemical periodicals. Thus, within its many-sided activities, the Institution promoted significantly the public appreciation of the function of chemistry, as a contributor both to pure knowledge, and to technical and economic progress. It achieved this in an environment of influential City merchants, manufacturers and financiers and doubtless led to beneficient, if unrecorded, consequences. It was only towards the close of the nineteenth century, when the universities had become increasingly concerned with the systematic study of the discipline, that chemistry lost its direct impact in the London Institution, but continued to maintain a presence within its cultural framework.     

Fred Neufeld and pneumococcal serotypes: foundations for the discovery of the transforming principle

During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today’s knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld’s contributions in this development, which have remained largely unknown.     

Leibniz on the requisites of an exact arithmetical quadrature

In this paper we will try to explain how Leibniz justified the idea of an exact arithmetical quadrature. We will do this by comparing Leibniz's exposition with that of John Wallis. In short, we will show that the idea of exactitude in matters of quadratures relies on two fundamental requisites that, according to Leibniz, the infinite series have, namely, that of regularity and that of completeness. In the first part of this paper, we will go deeper into three main features of Leibniz's method, that is: it is an infinitesimal method, it looks for an arithmetical quadrature and it proposes a result that is not approximate, but exact. After that, we will deal with the requisite of the regularity of the series, pointing out that, unlike the inductive method proposed by Wallis, Leibniz propounded some sort of intellectual recognition of what is invariant in the series. Finally, we will consider the requisite of completeness of the series. We will see that, although both Wallis and Leibniz introduced the supposition of completeness, the German thinker went beyond the English mathematician, since he recognized that it is not necessary to look for a number for the quadrature of the circle, given that we have a series that is equal to the area of that curvilinear figure.     

The ‘Darwin-Marx correspondence’: a correction and revision

The logical links between the Judaeo-Christian doctrine of creation and the practice of natural philosophy on the one hand, and the rejection of belief in demonic agency on the other, were made explicit in the seventeenth century by, among others, Balthasar Bekker (1634–98), whose ideas I argue to have been not without influence. In section 1, I present the accounts of three historians of the opposition to belief in witchcraft and of the decline of the witch-persecution, Hugh Trevor-Roper, Keith Thomas, and Brian Easlea. In section 2, I maintain that Bekker has been underestimated both by Trevor-Roper and by Easlea. In section 3, I investigate more generally some of the connections between the new natural philosophy and belief in supernatural interventions, cast doubt on the view that rejection of belief in witchcraft and the devil requires rejection of belief in creation, and thus supplement or qualify the accounts of Trevor-Roper, Thomas, and Easlea of why belief in witchcraft faded away.     

系统论视野下小流域生态补偿机制构建思路——以秋浦河为例

针对小流域生态补偿实践中存在的补偿标准偏低、静态、管理体制不健全、补偿方式单一等弊端,采用系统研究、文献分析、实证检验等方法,揭示了秋浦河流域生态补偿机制,包括流域协调与管理机制;生态补偿法律机制;多元补偿方式机制;政府主导,市场参与的多元融资机制;公众参与、监督机制;动态补偿机制;科学确定补偿标准机制。基于秋浦河上游生态服务主导效应因子价值、生态保护成本、发展机会成本,下游社会经济发展实际,2009年下游补偿上游金额为41448．0277。秋浦河流域生态补偿机制构建,有利于促进秋浦河流域上、下游协调发展与社会公平,可为我国小流域生态补偿构建与实践提供借鉴与参考。     

Pre- and post-natal ontogeny of neutral endopeptidase 24-11 ('enkephalinase') studied by in vitro autoradiography in the rat.

Neutral endopeptidase (NEP, enkephalinase, CALLA) which is present in various neural and non-neural tissues, is able to cleave a variety of regulatory peptides. The distribution of NEP has been studied during rat pre- and post-natal development by autoradiography after in vitro binding of the tritiated inhibitor [3H]HACBO-Gly to whole-body and organ sections. In the central nervous system (CNS), where the presence of NEP has been related to the termination of the action of enkephalins, the external layer of the olfactory bulbs is the only structure prominently labeled before birth. Other CNS structures rich in NEP in the adult, such as the nigrostriatal tract, are progressively labeled after birth. Outside the CNS, the progressive appearance of NEP in the kidney, the lungs and the salivary glands suggests its concomitant involvement in adult physiological functions, including fluid balance control, possibly by cleaving the atrial natriuretic peptide (ANP) and other peptides. On the other hand, transient or enhanced expression of NEP is observed during the development of several organs such as the sensory organs, the heart and the major blood vessels, the intestine, the bones and the genital tubercle. In addition to the still incompletely known physiological functions of the enzyme, the developmental pattern of its expression in several tissues strongly suggests a modulatory role for NEP in the ontogeny of a large number of organs.     

Internal interactions within the human circadian system: the masking effect

In the realm of human circadian rhythms, the masking effect is defined as the change in the course of deep body temperature induced by changes in the degree of physical activity, or by the alteration between sleep and wake. This effect is particularly obvious during internal desynchronization where the rhythms of deep body temperature, and the sleep-wake sleep cycle - i.e. one of the masking factors - run with different periods. Every sleep onset is accompanied by a rapid drop, and wake onset by a rapid rise in deep body temperature, each one with an overshoot of about 50% of the steady state variations. When rhythms are calculated, with the dominant temperature period as the screening period, exclusively from data obtained during sleep episodes, on the one hand, and from those obtained exclusively during wake, on the other, two average cycles emerge: the 'sleep temperature curve' and the 'wake temperature curve'. Both run in parallel but are separated by the 'masking effect'. As derived from many experiments, the mean masking effect amounts to 0.28 +/- 0.06 degree C. The masking effect also depends to some extent on the phase of the temperature rhythm; it is larger than average around the temperature maximum and during the descending phase of the temperature cycle, where the alertness commonly is highest and the probability to sleep, in general, and the REM sleep propensity, in particular, are smaller than average. This also can be interpreted to indicate that the sleep temperature curve is phase advanced relative to the wake temperature curve; this, on the average, by 0.9 +/- 0.3 h. If the individually determined amount of masking is added to the temperature data obtained during sleep, or subtracted from the temperature data obtained during wake, a temperature curve emerges that can be thought of as being 'purified' of the masking effect. Analyses of this artificial curve allow estimation of that part of the internal interactions uninfluenced by the masking effect. On the average, about half of the amount of interaction between the rhythm of sleep-wake and that of deep body temperature is explained by the masking effect, whereas the other half is 'oscillatory interaction'. Both types of interaction are inherent and inseparable parts of the circadian clock mechanism, as can be deduced from model considerations.     

高原列车车窗压差自平衡装置的研究与设计

高原列车由于经常往返于高原与平原之间,车窗中空玻璃内外的压差频繁变化,导致玻璃表面发生频繁往复的微变形,不但影响车厢的气密性,更降低了车窗及车窗贴膜的使用寿命,徒增了铁路运行成本。现行的高原列车,尚没有理想的装置可对其影响进行有效控制。车窗压差自平衡装置的研制,是针对现行高原列车车窗结构的改进。通过设计气压测控系统,实时监测外界大气压的变化,调整中空玻璃内的气压,从鬲使内外压差达到平衡,补偿车窗玻璃表面的微变形。     

Early microbiota,antibiotics and health

The colonization of the neonatal digestive tract provides a microbial stimulus required for an adequate maturation towards the physiological homeostasis of the host. This colonization, which is affected by several factors, begins with facultative anaerobes and continues with anaerobic genera. Accumulating evidence underlines the key role of the early neonatal period for this microbiota-induced maturation, being a key determinant factor for later health. Therefore, understanding the factors that determine the establishment of the microbiota in the infant is of critical importance. Exposure to antibiotics, either prenatally or postnatally, is common in early life mainly due to the use of intrapartum prophylaxis or to the administration of antibiotics in C-section deliveries. However, we are still far from understanding the impact of early antibiotics and their long-term effects. Increased risk of non-communicable diseases, such as allergies or obesity, has been observed in individuals exposed to antibiotics during early infancy. Moreover, the impact of antibiotics on the establishment of the infant gut resistome, and on the role of the microbiota as a reservoir of resistance genes, should be evaluated in the context of the problems associated with the increasing number of antibiotic resistant pathogenic strains. In this article, we review and discuss the above-mentioned issues with the aim of encouraging debate on the actions needed for understanding the impact of early life antibiotics upon human microbiota and health and for developing strategies aimed at minimizing this impact.     

The plague fighter: Wu Lien-teh and the beginning of the Chinese public health system

At the end of 1910, when the Qing dynasty was on the verge of collapse and the whole Chinese empire in a process of transformation, North Manchuria was devastated by a large pneumonic plague epidemic. The Russian and Japanese governments wanted to use the outbreak of the disease as a pretext to invade north-east China, making plague an issue of international politics. At this dramatic moment the empire relied on the skills of the young Chinese doctor Wu Lien-teh, the first Chinese medical graduate from Cambridge. Wu investigated the disease on the spot, chaired an international plague conference in Shenyang (Manchuria) in April 1911, and, later on, became the figurehead of fundamental public health reforms in Republican China. Highly ambitious, striving for personal fame and international renown for China, supported by an excellent network of personal connections, and equipped with a medical training considered the best in the world at the time, he launched on a startling career as one of China's key medical reformers and international representatives. His history is an example of the inseparable links between personal fate and historical events, and between the interests of scientists, medical men, politicians, and businessmen on the national and international stages.     

Photon emission of phagocytes in relation to stress and disease

Phagocytes, the first-line cells of the body's defence mechanisms against invading pathogens, kill microorganisms by means of lysosomal degradative enzymes and highly toxic reactive oxygen intermediates. The reactive oxygen compounds are produced, in a process called the ‘respiratory burst’, by the NADPH oxidase complex in plasma membranes, and by myeloperoxidase in phagolysosomes after degranulation. These processes generate electronically excited states which, on relaxation, emit photons, giving rise to phagocyte chemiluminescence (CL). This paper describes the conditions for the measurement of CL, and reviews the activity of phagocytes from individuals undergoing stress or disease. The capability of phagocytes to emit photons reflects remarkably well the pathophysiological state of the host. In many cases even the magnitude of the stress, the presence of a pathogen in the body, or the activity of the disease can be estimated. Physiological changes, e.g. in the reproductive cycle, can also be predicted.