Normal Human Life Research Articles

Computational discovery of Epstein-Barr virus targeted human genes and signalling pathways.

Epstein-Barr virus (EBV) plays important roles in the origin and the progression of human carcinomas, e.g. diffuse large B cell tumors, T cell lymphomas, etc. Discovering EBV targeted human genes and signaling pathways is vital to understand EBV tumorigenesis. In this study we propose a noise-tolerant homolog knowledge transfer method to reconstruct functional protein-protein interactions (PPI) networks between Epstein-Barr virus and Homo sapiens. The training set is augmented via homolog instances and the homolog noise is counteracted by support vector machine (SVM). Additionally we propose two methods to define subcellular co-localization (i.e. stringent and relaxed), based on which to further derive physical PPI networks. Computational results show that the proposed method achieves sound performance of cross validation and independent test. In the space of 648,672 EBV-human protein pairs, we obtain 51,485 functional interactions (7.94%), 869 stringent physical PPIs and 46,050 relaxed physical PPIs. Fifty-eight evidences are found from the latest database and recent literature to validate the model. This study reveals that Epstein-Barr virus interferes with normal human cell life, such as cholesterol homeostasis, blood coagulation, EGFR binding, p53 binding, Notch signaling, Hedgehog signaling, etc. The proteome-wide predictions are provided in the supplementary file for further biomedical research.

The Chernobyl – Thirty Years After The Post – Accidental Radiological – Hygienic and Medical Consequences

As the result of the Chernobyl NPP accident more than 200 thousand square kilometers of the European territories were contaminated by Cs-137 in the amount of above 37 kBq/m2 (1 Ci/km2 ). Belorussia, Russia and Ukraine amount up to 70% of this entire affected area. More than 600 000 people were engaged in the accidental cleanup operations, 340000 were evacuated or relocated within 1986-1991. The early stage evacuation efficacy is confirmed by the absence of acute radiation syndrome among the population and by the prevented collective dose which amounts to no less than 10 000 man/Sv. The effective measure to reduce the internal radiation dose to the population at the early accidental stage was introduction of maximum tentative permissive levels of radionuclide content in the foodstuffs.Among the identified post -accident medical consequences of the Chernobyl is the radiation syndrome found in 134 emergency cleanup workers within the first 24 hours of the accident’s development. Out of that number, 28 people died within the first four months, 19 people died before 2006. The accident’s liquidators developed radiation -induced leukemia ( the attributive risk value is 45-60% ). People exposed to high radiation doses display the statistically significant 18% morbidity increase of all types of solid cancers at the doses above 150 mSv. There is the statistically significant information indicating the increased amount of thyroid cancer morbidity among those who were just children and teenagers at the time of the accident. The adverse psychological consequences are accounted for not just the fear of overexposure but also for the disturbance of the habitual lifestyle especially mindful of the forced relocation.The longterm protection measures, radionuclide decay and selfcleaning of the contaminated areas resulted in the drastic reduction of the population dose in the radioactively contaminated territories. In 2015, only in some settlements of the Briansk Region’s the mean annual effective dose to the population exceeds 1 mSv. Presently the major goal is to transfer to normal human life with the change of the legal status of radioactively contaminated settlements in which the radiation situation is back to normal.The article provides the comparative data on the Chernobyl and the Fukushima - 1 accidental consequences and emphasizes the necessity of retaining the Chernobyl experience because the rapid advancement of the atomic energy around the world makes the mitigation of the accident’s consequences a truly international mission.

In Defense of the Pig

Abstract Mill proclaimed that it is better to be a dissatisfied human than a satisfied pig because of the superior quality of human experience. Contemporary utilitarians share this commitment of our species to the superior value of normal human life, though they base this on the greater richness of such life. This article challenges that defense of this commitment on empirical, conceptual, and epistemic grounds. How do we measure the richness of a life? And who determines the value of a life? Conclusion: Utilitarianism is to be commended for its inability to justify our confidence in the superiority of human life.

Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc

The intervertebral disc (IVD) is a complex cartilaginous structure which functions to resist biomechanical loads during spinal movement. It consists of the highly viscous cartilaginous nucleus pulposus, which is surrounded laterally by a thick outer ring of fibrous cartilage-the annulus fibrosus-and sandwiched inferiorly and superiorly by the cartilage end-plates. The main extracellular matrix molecules of the disc are collagens, proteoglycans, glycoproteins and elastin. The disc also contains appreciable amounts of water, matrix-degrading protease enzymes and their inhibitors, soluble signalling molecules and various metabolic breakdown products. This review provides a comprehensive description of the biochemical composition of the extracellular matrix of the IVD and, specifically, the proteases involved in its molecular turnover. Quantitation of the turnover rates using racemization of aspartic acid as a molecular clock is also discussed. Molecular turnover rates of the major constituent matrix macromolecules of the IVD are found to be particularly slow, especially in the case of collagen. Over a normal human life span, this slow turnover may compromise the structural integrity of the IVD extracellular matrix essential for normal physiological functioning.

Okresy życia ludzkiego według Ojców Kościoła

The patristic writers variously enumerated the ages of human life. Some counted ten, some seven, six, five or four. They took number symbolism or the opinions of ancient authors as their starting point, but in their formulation the ages of human life concern not just the physical, intellectual or moral development of man but, often, also his spiritual development. They defined stages in the development of faith or love that can be described in terms analogous to those used for defining man’s age. Moreover, the patristic authors did not usually conclude their enumeration with old age. Human life passes ultimately into the age of rest (the seventh age) or into eternity (the eighth age), which has no end. Irenaeus of Lyon used the concept of the ages of life in proving that Jesus lived about fifty years. There were, in his opinion, theological arguments for such a mature age. Christ became one of us in order to accomplish the redemption and He therefore had to know all the ages of normal human life: not just birth, childhood and youth, but also maturity and old age. But the chronological and exegetical arguments Irenaeus gives are rather stretched. The most profound description of the ages of man was given by Augustine. He makes an original parallel with the seven days of creation and the seven ages of the history of the chosen people.

On nationality and global equality: a reply to Holtug

I here defend some of the positions taken in National Responsibility and Global Justice against criticisms by Nils Holtug. I reinforce my suggestion that claims about national membership being ‘morally arbitrary’ are question begging and try to show how such membership can legitimately serve as a source of special obligations. I examine the claim that the problems involved in constructing a ‘currency’ of global justice also arise in the domestic context and suggest that appealing to ‘welfare’ as the relevant currency is not a useful way of responding to cultural differences. Finally, I respond to the hypothetical case of an unequally distributed life-extending vitamin by arguing that the discovery of such a substance would change our understanding of a normal human life, and thereby raise the bar of sufficiency.

About a possible role of parasomnias as a factor of stabilization of sleep cycles

Cyclical organization of sleep is one of necessary conditions of normal human and animal life activity and one of basic manifestations of the circadian cycle. Transition from the slow-wave to the paradoxical sleep is often accompanied by brief, sometimes rhythmical motor and autonomic reactions that do not cause arousal, but seem to promote activation of the mechanisms providing the "shift" of the sleep phases. Immaturity (or damage) of the neurophysiological mechanisms responsible for the "shift" of the sleep stages leads to hindering of alternation of the sleep phases, which disturbs their normal sequence and leads to deficit of reparative and homeostatic processes; this is manifested in deterioration of the neuropsychical state during wakefulness. The data are presented which allow suggesting that as a compensatory mechanism promoting the sleep phase shift there can appear stereotypical motor or autonomic reactions - pathological parasomnia, for instance, enuresis. Episodes of the pathological parasomnia promote normalization of the sleep stage alternation and thereby affect positively recovery of its cyclical organization.

The Anatomy of Fear Extinction

Back to table of contents Previous article Next article Images in NeuroscienceFull AccessThe Anatomy of Fear ExtinctionCarol A. Tamminga M.D.Carol A. Tamminga M.D.Search for more papers by this authorPublished Online:1 Jun 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Pavlovian fear conditioning and its extinction are related laboratory procedures carried out in animals to model the mechanisms of human fear learning and its reversal. In humans, contextual (situational) fear is learned during traumatic episodes with fearful stimuli and is enhanced by genetic predisposition. The mechanisms of fear learning and extinction have been extensively studied in animals and are beginning to be examined in humans (see the study by Monk et al. in this issue). Simplistically, in the context of normal human life, fearful situations are regularly encountered; characteristically, these are managed successfully, then forgotten. However, when the fearful situation is overwhelming or the mediating neural systems function sub-optimally, fearful situations can be learned but not forgotten, creating forms of anxiety (e.g., PTSD, generalized anxiety disorder). Understanding the precise neural mechanisms of anxiety is necessary for developing selective and effective treatments; models of fear conditioning and extinction are tools to understand the neural mechanisms of anxiety. The animal literature is rich with molecular and systems research about fear conditioning and extinction. These data show that the amygdala is involved in remembering the fear-based situation, and that the extinction of that fear learning involves the medial and ventral prefrontal cortex acting on the amygdala ( Figure , right). Animal studies have implicated transmitters such as glutamate (NMDA), GABA, and cannabinoids in the mediation of fear learning and extinction in the amygdala. Excitatory projections from the ventral/medial prefrontal cortex descend to the lateral amygdala, which sends excitatory projections to the central amygdala and to the inhibitory neurons in the intercalated cell masses; these inhibitory neurons negatively modulate the central amygdala. Prefrontal cortex projections suppress amygdala-processed fear responses, thus inhibiting the fear responses and enhancing extinction. The hippocampus appears to set the limits for ventral/medial prefrontal cortex control over the fear circuitry of the lateral and central amygdala. Synaptic plasticity within the lateral amygdala mediates both fear learning and its extinction; this plasticity can likely be impacted by using selective pharmacological and cognitive tools to modulate the consequences of fear learning (e.g., anxiety) or of extinction (e.g., anxiety treatment). This research and its results are the basis for postulating that effective treatments already being used for anxiety disorders, such as cognitive behavioral therapy (CBT), can be rationally enhanced to optimize and enhance CBT action. Figure 1. The fear extinction model has its origins in the classical conditioning that Ivan Petrovich Pavlov (left) first developed in dogs. Specific molecular events within the lateral amygdala facilitate extinction of fear learning (the conditioned fear response) hypothetically by stimulating inhibitory intercalated cell mass activity on the central amygdala. Regions within the prefrontal cortex (ventral and medial aspects) have an inhibitory influence on fear learning in the lateral and central amygdala, an influence modulated by hippocampal input to the ventral/medial prefrontal cortex. Circuit drawing modified from Sotres-Bayon F, Bush DEA, LeDoux JE: Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction. Learn Mem 2004; 11:525–535.Address reprint requests to Dr. Tamminga, UT Southwestern Medical Center, Department of Psychiatry, 5323 Harry Hines Blvd., #NE5.110, Dallas, TX 75390-9070; [email protected] (e-mail). FiguresReferencesCited byDetailsCited ByHuman Psychopharmacology: Clinical and Experimental, Vol. 25, No. 1ANXIETYHippocampus, Vol. 17, No. 9 Volume 163Issue 6 June, 2006Pages 961-961THE AMERICAN JOURNAL OF PSYCHIATRY June 2006 Volume 163 Number 6 Metrics PDF download History Published online 1 June 2006 Published in print 1 June 2006

The Anatomy of Fear Extinction

Pavlovian fear conditioning and its extinction are related laboratory procedures carried out in animals to model the mechanisms of human fear learning and its reversal. In humans, contextual (situational) fear is learned during traumatic episodes with fearful stimuli and is enhanced by genetic predisposition. The mechanisms of fear learning and extinction have been extensively studied in animals and are beginning to be examined in humans (see the study by Monk et al. in this issue). Simplistically, in the context of normal human life, fearful situations are regularly encountered; characteristically, these are managed successfully, then forgotten. However, when the fearful situation is overwhelming or the mediating neural systems function sub-optimally, fearful situations can be learned but not forgotten, creating forms of anxiety (e.g., PTSD, generalized anxiety disorder). Understanding the precise neural mechanisms of anxiety is necessary for developing selective and effective treatments; models of fear conditioning and extinction are tools to understand the neural mechanisms of anxiety. The animal literature is rich with molecular and systems research about fear conditioning and extinction. These data show that the amygdala is involved in remembering the fearbased situation, and that the extinction of that fear learning involves the medial and ventral prefrontal cortex acting on the amygdala (Figure, right). Animal studies have implicated transmitters such as glutamate (NMDA), GABA, and cannabinoids in the mediation of fear learning and extinction in the amygdala. Excitatory projections from the ventral/medial prefrontal cortex descend to the lateral amygdala, which sends excitatory projections to the central amygdala and to the inhibitory neurons in the intercalated cell masses; these inhibitory neurons negatively modulate the central amygdala. Prefrontal cortex projections suppress amygdala-processed fear responses, thus inhibiting the fear responses and enhancing extinction. The hippocampus appears to set the limits for ventral/medial prefrontal cortex control over the fear circuitry of the lateral and central amygdala. Synaptic plasticity within the lateral amygdala mediates both fear learning and its extinction; this plasticity can likely be impacted by using selective pharmacological and cognitive tools to modulate the consequences of fear learning (e.g., anxiety) or of extinction (e.g., anxiety treatment). This research and its results are the basis for postulating that effective treatments already being used for anxiety disorders, such as cognitive behavioral therapy (CBT), can be rationally enhanced to optimize and enhance CBT action.

A Core Precautionary Principle*

[T]he Precautionary Principle still has neither a commonly accepted definition nor a set of criteria to guide its implementation. ‘There is,’ Freestone ... cogently observes, ‘a certain paradox in the widespread and rapid adoption of the Precautionary Principle:’ While it is applauded as a ‘good thing,’ no one is quite sure about what it really means or how it might be implemented. Advocates foresee precaution developing into ‘the fundamental principle of environmental protection policy at [all] scales.’ ... Sceptics, however, claim its popularity derives from its vagueness; that it fails to bind anyone to anything or resolve any of the deep dilemmas that characterize modern environmental policy making. 1

Windows to the World, Doors to Space: The Psychology of Space Architecture

Living in a confined environment with minimal external stimuli available, such as a space habitat, is a strain on normal human life and puts great pressure on groups and individuals. Designers working on a space habitat not only must work on its functional role, but also must integrate functionality with mental representation and symbolic meaning. Space-connection interfaces such as doors and windows act as “sensory organs” of a building. They allow inside-out communication, but also allow the user to control the flow of light and air, which in a direct or indirect way are communication mediums. In this paper the authors advocate a closer connection among architecture, anthropology and psychology in designing space habitats as part of a new concept of environmental design strategy in space architecture.

Telomerase alone extends the replicative life span of human skeletal muscle cells without compromising genomic stability.

Continuous cycles of muscle fiber necrosis and regeneration are characteristic of the muscular dystrophies, and in some cases this leads to premature replicative senescence of myoblasts in vitro. The molecular mechanism of senescence in human myoblasts is poorly understood but there is evidence to suggest that telomeric attrition may be one of the ways by which this is achieved. We report here, for the first time, the extension of normal human skeletal muscle cell replicative life span by the reconstitution of telomerase activity. The telomerase-expressing cells show no features of transformation in vitro and have stable genomes with diploid karyotypes, do not express exceptionally high levels of c-myc and have wild-type, unmethylated CDKN2A genes. In vivo, they regenerate to repair muscle injury in immunosuppressed RAG-1 mice. This work suggests that telomerase expression to repair short telomeres may aid the expansion of diploid human muscle cells and consequently attempts at gene therapy for muscle diseases.

Promise and Ritual: Profane and Sacred Symbols in Hume's Philosophy of Religion

1. A brief outline of Hume's views on religion 1 With French Enlightenment philosophers like Voltaire and d'Holbach, Hume shared a strongly negative outlook on religion. He saw it as a socially and politically dangerous force because of its dogmatism, extreme moralism or revolutionary fervour, all upsetting normal human life. But unlike these 'philosophes', Hume did more than just deride and criticize religion; he also tried to understand it. He even realized that religion was here to stay, even though in his view it was, unlike the family and other social phenomena, not a 'natural', i.e. , inevitable consequence of human nature in all circumstances. In practically all these respects, Hume seems close to someone like Spinoza. The latter's genealogical explanation of religion in terms of characteristics and processes of the imagination in combination with the emotions ( Ethics I Appendix; Tractatus Theologico-politicus ) is also found mutatis mutandis in Hume (Popkin 1979). Hume-scholars, especially philosophers, overwhelmingly concentrate on Hume's discussion of the rational justification of religious beliefs (in God's existence, moral goodness, etc. ) or of the rational acceptability of revelation and miracle. In Hume's day, these were the two lines of defence of (especially Christian) religion and so it is not surprising that he paid so much attention to these topics. In his Dialogues Concerning Natural Religion Hume critically discussed the thesis that basic religious views were in fact rationally grounded, 'natural' beliefs, part of a 'natural theology' (against Bishop Butler). In his Of Miracles he tried to demolish the possibility of a justification of religion via the acceptability of revelation and miracle (against Pascal). Yet, his critique of the rational justification of religion is at best only half the story. For intellectuals it may be what is most fascinating, but from the Humean point of view it is not the most important. If religion is not rationally grounded and yet not given up and, especially, if it is a dominant body of beliefs and practices among common people who do not or could not care about rationality, then another kind of investigation forces itself upon the 'human scientist': a Natural History of Religion 2 . This is an investigation of religion as a cultural, socio-political phenomenon which, as all human phenomena, is susceptible to change, i.e. , to taking successively different forms as human society develops. Scottish Enlightenment thinkers shared a theory of human development in four stages: hunting, gathering, farming, commerce; the development was supposed to be a 'natural progression' from the crude to the cultivated, from the simple to the complex

The old man's problem in modern industry. 1913.

THE GREAT DISCOVERIES of Metchnikoff have given the human race a new hope, a new conception of what the normal span of life ought to be. But while these discoveries have not yet reached the stage of practical application, discoveries equally remarkable in their time, in the domain of medicine and personal and public hygiene, have already accomplished a great deal in decreasing mortality and prolonging normal human life. Within the last century the popular concept of the normal milestones between youth, maturity, and old age has been very much affected. . . . now we quite earnestly speak of a young woman of forty, and of a man of sixty as being in the prime of life. Commerce, the professions, and politics—especially politics—have furnished numerous examples of the admirable vigor and useful activity of men past sixty and even seventy. We look askance at the man who dares to aspire to the highest and most trying political office of the land before having reached his fiftieth birthday. . . .

A new function of green tea: prevention of lifestyle-related diseases.

In the normal human life span, there occur lifestyle-related diseases that may be preventable with nontoxic agents. This paper deals with the preventive activity of green tea in some lifestyle-related diseases. Green tea is one of the most practical cancer preventives, as we have shown in various in vitro and in vivo experiments, along with epidemiological studies. Among various biological effects of green tea, we have focused on its inhibitory effect on TNF-alpha gene expression mediated through inhibition of NF-kappaB and AP-1 activation. Based on our recent results with TNF-alpha-deficient mice, TNF-alpha is an endogenous tumor promoter. TNF-alpha is also known to be a central mediator in chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. We therefore hypothesized that green tea might be a preventive agent for chronic inflammatory diseases. To test this hypothesis, TNF-alpha transgenic mice, which overexpress TNF-alpha only in the lungs, were examined. The TNF-alpha transgenic mouse is an animal model of human idiopathic pulmonary fibrosis which also frequently develops lung cancer. Expressions of TNF-alpha and IL-6 were inhibited in the lungs of these mice after treatment with green tea in drinking water for 4 months. In addition, judging from the results of a prospective cohort study in Saitama Prefecture, Japan, green tea helps to prevent cardiovascular disease. In this study, a decreased relative risk of death from cardiovascular disease was found for people consuming over 10 cups of green tea a day, and green tea also had life-prolonging effects on cumulative survival. These data suggest that green tea has preventive effects on both chronic inflammatory diseases and lifestyle-related diseases (including cardiovascular disease and cancer), resulting in prolongation of life span.

Dementia in Ayurveda.

The ancient Indian medical system, Ayurveda, included geriatrics as 1 of 8 medical divisions. Well-documented evidence exists for treating aging and age-related disorders including dementia. Geriatrics was termed Rasayanatantra. Cognitive function was well recognized and Sanskrit terms existed such as Buddhi for intelligence and Cittanasa (Citta means mind, nasa means loss of) for dementia. A normal human life span was considered to be 100 years. It could be prolonged to 116-120 years through the use of preventive treatments, if they were started during late youth or middle age. Treatments included herbal preparations, diet, exercise, and attention to general mode of life and social behavior. Several herbal formulations are described, including details of their composition and preparation. The mode of action of antiaging drugs was believed to occur at 3 levels. Detailed descriptions of the mode of action of several herbs are provided, and recent research confirms some of this activity.

Enough Arguments About Models of Development

A krai-level organization for the Our Home Is Russia movement has recently been established in Krasnodar Krai. This event undoubtedly had major political importance, and not just at the level of the Kuban. It also gave me serious cause to consider what lies ahead for us in the near future and whether, perhaps, the time has come when we can realistically hope to escape all the misfortunes we know so well. I joined the new movement and even agreed to head the krai organization, but not by any means out of a "call of duty." I am convinced that this is not simply another "provincial branch" of yet another capital-city party. The realities of recent years have shown that none of the pocket-sized and even smaller parties can solve the problems that face us as citizens of our country. People are waiting for things to happen. They are waiting for speculative arguments over this or that model of social development to be replaced by the creation of a normal human life.

Response: Autonomy as an Excuse for All-Too-Human Chauvinism

In debating the question of animal liberation has been my experience, if! may paraphrase Frey, that most people feel that (normal) human life is ofa much higher quality than animal life and that since the value of life is a function of its quality, animal life does not have the same value as (normal) human life. Indeed, most people feel that we are something of a special or a privileged class against which the lives of others are viewed and their value assessed. I It is not surprising that we feel this way. As Donald Griffin has pointed out, it seems plausible that would be more likely to survive and reproduce if their beliefs included confident faith in their own superiority and the assurance that exploiting other species was normal and correct behavior.2 Historically, religion, literature, and philosophy have been extensively engaged in reinforcing this instinctual faith in the preeminent worth and privilege of humanity. It has been their task to find and warmly extol those things which distinguish us from those mere animals we want to drive off the land, kill, eat, wear, and otherwise exploit and destroy to fulfill our needs and wants. It has been their job to keep our consciences clear as we bestride the world, using our overwhelming might to take control, mold the world to satisfy our idea of the good life, and kill off those who stand in our way. Selffulfillment, accomplishing our plans, achieving our

Hematopoietic Function in the Elderly

Very little information is available on the effect of aging on human bone marrow function. In reviewing both murine and human studies on bone marrow function in the elderly, it may be concluded at present that there is an increasing incidence of anemia that develops with aging in humans. Extensive animal and limited human data support decreased marrow reserve capacity with decreased hormonal responsiveness to hematologic stress as the most likely cause. In normal human life spans, marrow stem cells do not appear to wear out, and, finally, clinicians are cautioned not to attribute anemia per se simply to aging. Any elderly individual with unexplained anemia must be fully evaluated for the possibility of occult gastrointestinal blood loss, marrow failure syndrome, or hemolytic state before his/her anemia is attributed to age alone. Much additional research remains to be done on hematopoietic function in aged individuals.

Use of botulinum toxin in blepharospasm and other facial spasms.

Essential blepharospasm is an involuntary spasmodic closure of the eyelids. It frequently makes normal social human life such as reading, driving and even walking almost impossible. Botulinum toxin has been approved for investigational use for treatment of blepharospasm. We report the results and side-effects of botulinum A toxin treatment of the first 13 patients in Finland. Temporary control of spasms was achieved in all patients varying from 1 to 38 weeks with a mean of 11 weeks after the first injection. Most patients needed re-treatment after varying intervals. All complications were transient.