bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilogue: Toward a Comprehensive Theory of Alzheimer's Disease‐Challenges, Caveats, and Parameters
Authors: KHACHATURIAN ZAVEN S.
Published: July 2010

Abstract:The task of developing a unifying theory of Alzheimer's disease faces several impediments. The most difficult include: the impact of scientific orthodoxy on the acceptance of new ideas; the uncertain relationship between aging and disease(s); the long time course of the degenerative process; the heterogeneity in the genotype and phenotype of the disease; the complex interactions among genetic and other risk factors (many of which are not yet known); the poorly understood nonlinear relationships between the neurobiological and the clinical phenotypes of the disease‐namely, viewing clinical symptoms asemergent behavior(s)of a complex system; and the paucity of appropriate models or modeling systems forhumandisease(s) such as Alzheimer's.
Towards a Public Health Approach to Bioethics
Authors: LANE SANDRA D. , RUBINSTEIN ROBERT A. , CIBULA DON , WEBSTER NOAH
Published: July 2010

Abstract: In this paper we examine the central commitments of bioethical enquiry and reasoning from a public health perspective. We argue that a core element of American national culture is individualism, which resonates in scholarly and popular debates. Our contention is that the habitus of bioethical debate is in large measure animated by an overriding concern with the individual, and the resulting social practice of the community has been to downplay the importance and legitimacy of group‐level health care dilemmas. This paper calls for re‐focusing of bioethics by employing a public health perspective, which would include a population focus, evidence‐based research topics, and engagement of the ethical dilemmas that arise from decisions concerning prevention. Racial and ethnic health disparities throughout the life span of a population in central New York State are used to illustrate the need for a public health focus in bioethics.
The Practice and Politics of Archaeology in Egypt
Authors: MESKELL LYNN
Published: July 2010

Abstract: Archaeologists working in Egypt have rarely considered the local/global ramifications and responsibilities of their field practices: many continue to operate under what might be termed the residual effects of colonialism. Taking an explicitly postcolonial stance I argue that there is much more at stake than the intellectual enterprise. This paper outlines the ways in which scholars could undertake a more engaged archaeology and how we might more closely be involved with the people and pasts of modern Egypt. The connected tensions of tourism and terrorism are foregrounded, demonstrating that heritage issues are salient to both spheres. Finally, I explore the nation's relationship to its pharaonic past over the past few centuries and include some contemporary articulations and representations.
Ethics in Anthropology: Dilemmas and Conundrums
Authors: COMITAS LAMBROS
Published: July 2010

Abstract: This paper is a call for awareness and continual examination of the multifaceted nature of ethics and closely related ideas as they relate to anthropology. At the very least, the lack of common understanding of these ideas has been and continues to be a pressing prblem for all who practice anthropology. In this vein, abbreviated etymologies of these critical concepts are put forth as prologue to forays into ethics in the academy and of science as context for ethical maneuver. Shifting conditions in anthropology are then described in relation to altered ethical orders with examples of early hints of the contemporary scene being drawn from Oscar Lewis's commentary on the raucous reception in Mexico of his book The Children of Sanchez.
Modulation of Cell Death in the Rat Thymus: Light and Electron Microscopic Investigations
Authors: QUAGLINO DANIELA , CAPRI MIRIAM , RONCHETTI IVONNNE PASQUALI
Published: July 2010

Abstract: In mammals, the thymus is the primary central organ of the lymphoid system; after birth, it progressively diminishes in size, undergoing gradual atrophy. Physiological maturation and/or involution of the thymus may be accelerated by endogenous or exogenous factors. Exposure to extremely low frequency EMF seems to interfere with thymic cell death. Data suggest that, in the rat model, a prolonged exposure to 50 Hz electric and magnetic fields, independently from field strength, seems to affect thymic cell death and possibly thymic physiology, since alterations in the balance of cell death and other parameters such as mitoses might interfere with the positive and negative selection of thymocytes and with the immunosurveillance properties of the thymus.
Mitochondrial Control of Cell Death Induced by HIV‐1‐Encoded Proteins
Authors: FERRI KARINE F. , JACOTOT ETIENNE , BLANCO JULIÀ , ESTÉ JOSÉ A. , KROEMER GUIDO
Published: July 2010

Abstract: In most examples of physiological or pathological cell death, mitochondrial membrane permeabilization (MMP) constitutes an early critical event of the lethal process. Signs of MMP that precede nuclear apoptosis include the translocation of cytochrome c and apoptosis‐inducing factor (AIF) from mitochondria to an extra‐mitochondrial localization, as well as the dissipation of the mitochondrial transmembrane potential. MMP also occurs in HIV‐1‐induced apoptosis. Different HIV‐1 encoded proteins (Env, Vpr, Tat, PR) can directly or indirectly trigger MMP, thereby causing cell death. The gp120/gp41 Env complex constitutes an example for an indirect MMP inducer. Env expressed on the plasma membrane of HIV‐1 infected (or Env‐transfected) cells mediates cell fusion with CD4/CXCR4‐expressing uninfected cells. After a cell type‐dependent latency period, syncytia then undergo MMP and apoptosis. Vpr exemplifies a direct MMP inducer. Vpr binds to the adenine nucleotide translocator (ANT), a mitochondrial inner membrane protein which also interacts with apoptosis‐regulatory proteins from the Bcl‐2/Bax family. Binding of Vpr to ANT favors formation of a non‐specific pore leading to MMP. The structural motifs of the Vpr protein involved in MMP are conserved among most pathogenic HIV‐1 isolates and determine the cytotoxic effect of Vpr. These data suggest the possibility that viruses employ multiple strategies to regulate host cell apoptosis by targeting mitochondria.
Morphologic, Biochemical and Molecular Mitochondrial Changes during Reperfusion Phase following Brief Renal Ischemia
Authors: BENÍTEZ‐BRIBIESCA LUIS , GÓMEZ‐CAMARILLO MADAÍ , CASTELLANOS‐JUÁREZ EMILIO , MRAVKO ELIZABETH , SÁNCHEZ‐SUÁREZ PATRICIA
Published: July 2010

Abstract: Ischemia/reperfusion of organs and cells induces apoptosis through a complicated series of changes in mitochondria, mainly the generation of oxygen free radicals, permeability transitions, calcium translocations, and release of apoptogenic factors such as cytochrome c and Bcl‐2 family members. The liberation of these factors occurs very early after reoxygenation and it has been assumed that it takes place without any structural alteration of the mitochondrial membranes. The aim of this study was to detect ultrastructural changes of mitochondria in the initial stages of reperfusion at the time when Bcl‐2 and succinic dehydrogenase, located in the outer and inner membranes, respectively, were released. Ischemia/reperfusion was produced in adult rats by clamping one renal artery for 60 min and reoxygenating for 60, 120, 180, and 240 min. A model of chemical hypoxia with intra‐arterial 50 mM sodium azide served as comparison, allowing free blood flow for 30, 60, 120 and 180 min. Light and electron microscopy, immunostaining for Bcl‐2, and enzyme histochemistry for succinic dehydrogenase were performed. Our results showed mitochondrial swelling, rupture of inner and outer membranes, and leakage of mitochondrial matrix into the cytoplasm in ischemia after 120 min of reperfusion. Bcl‐2 immunoreactivity and focal lowering of SDH reactivity were also noted and became more pronounced at the same time that the mitochondrial ultrastructure demonstrated more evident changes including rupture of the inner and outer membranes. Our studies seem to indicate that in early ischemia‐reperfusion and in chemical hypoxia‐induced apoptosis, the earliest ultrastructural changes take place in mitochondria and that swelling and rupture of mitochondrial membranes occur in parallel with the loss of Bcl‐2 and SDH activity.
Role of ECM Remodeling in Thyroid Hormone‐Dependent Apoptosis during Anuran Metamorphosis
Authors: DAMJANOVSKI SASHKO , AMANO TOSIKAZU , LI QING , UEDA SHUICHI , SHI YUN‐BO , ISHIZUYA‐OKA ATSUKO
Published: July 2010

Abstract: Programmed cell death or apoptosis is an important aspect in organogenesis and tissue remodeling. It is precisely controlled both temporally and spatially during development. Amphibian metamorphosis is an excellent model to study developmental control of apoptosis in vertebrates. This process involves the transformation of essentially every organ/tissue as tadpoles change to frogs, yet is controlled by a single hormone, thyroid hormone (TH). Although different organs and tissues undergo vastly different developmental changes, including de novo development and total resorption, most require apoptotic elimination of at least some cell types. Such properties and the dependence on TH make frog metamorphosis a unique model to isolate and functionally characterize genes participating in the regulation of tissue specific cell death during organ development in vertebrates. Indeed, molecular studies of the TH‐dependent gene regulation cascade have led to the discovery of a group of genes encoding matrix metalloproteinases (MMPs) participating in metamorphosis. In vivo and in vitro studies have provided strong evidence to support a role of MMP‐mediated remodeling of the extracellular matrix in regulating apoptotic tissue remodeling during metamorphosis.
The Central Role of Phosphatidylserine in the Phagocytosis of Apoptotic Thymocytes
Authors: SCHLEGEL ROBERT A. , CALLAHAN MELISSA K. , WILLIAMSON PATRICK
Published: July 2010

Abstract: Apoptotic thymocytes inactivate the aminophospholipid translocase, which transports phosphatidylserine (PS) to the inner leaflet of the plasma membrane, and activate the scramblase, which randomizes phospholipids across the membrane and brings PS to the cell surface. Although different macrophages use at least two different systems to recognize and engulf apoptotic thymocytes, both systems recognize PS on the apoptotic target. Thymocytes treated with Ca2+ and ionophore to inactivate the translocase and activate the scramblase immediately expose PS on their surface and are immediately recognized and phagocytosed. These targets, on which PS has been artificially exposed, are recognized by the PS exposed on their surface. However, they apparently also engage the vitronectic receptor, a lectin‐like receptor and CD14. All of these receptors are implicated in the phagocytosis of apoptotic thymocytes, suggesting that loss of asymmetry and/or exposure of PS is sufficient to generate the ligands recognized by those receptors. The role of PS is not confined to the target cell surface, however. PS is constitutively exposed on the surface of macrophages and is as necessary for apoptotic cell engulfment as is recognition of PS on the target cell surface.
Mixing and Burning in Stars
Authors: ARNETT DAVID
Published: July 2010

Abstract: The role of hydrodynamic mixing in astrophysics is reviewed, emphasizing connections with simulations by computer and with laser physics experiments. Computer technology now allows two‐dimensional (2D) simulations, with complex microphysics, of stellar hydrodynamics and evolutionary sequences, and holds the promise for 3D. Careful validation of astrophysical methods, by laboratory experiment, by critical comparison of numerical and analytical methods, and by observation are necessary for the development of simulation methods with reliable predictive capability. Recent and surprising results from isotopic patterns in presolar grains, 2D hydrodynamic simulations of stellar evolution, and laser tests and computer simulations of Richtmeyer‐Meshkov and Rayleigh‐Taylor instabilities are discussed and related to stellar evolution and supernovae.
Influence of the Tachocline on Solar Evolution
Authors: BRUN A. S. , ZAHN J.‐P.
Published: July 2010

Abstract: Recently, helioseismic observations have revealed the presence of a shear layer at the base of the convective zone related to the transition from differential rotation in the convection zone to almost uniform rotation in the radiative interior, the tachocline. At present, this layer extends only over a few percent of the solar radius and no definitive explanations have been given for the thinness. Following Spiegel and Zahn (1992, The solar tachocline, Astron. Astrophys. 265: 106–114), who invoke anisotropic turbulence to stop the spread of the tachocline deeper in the radiative zone as the Sun evolves, we give some justifications for their hypothesis by taking into account recent results on rotating shear instability (Richard & Zahn, 1999, Astron. Astrophys.). We study the impact of the macroscopic motions present in this layer on the Sun's structure and evolution by introducing a macroscopic diffusivity DT in updated solar models. We find that a time dependent treatment of the tachocline significantly improves the agreement between computed and observed surface chemical species, such as the 7Li and modify the internal structure of the Sun (Brun, Turck‐Chièze & Zahn, 1999, in Astrophys. J.).
Radiation, Radicals, and Images
Authors: MITCHELL JAMES B. , RUSSO ANGELO , KUPPUSAMY PERIANNAN , KRISHNA MURALI C.
Published: July 2010

Abstract: Nitroxide stable free radicals exhibit varied chemical and biological properties. Their biological applications have been greatly expanded over the past few years. Not only have they been shown to exhibit potent antioxidant and radioprotective properties, but also they can serve as in vivo functional imaging probes that non‐invasively report on the oxygen status and redox properties of tissue, which may have utility in clinical biomedical research.
Oxidative Stress, Mitochondrial Respiration, and Parkinson's Disease
Authors: COHEN GERALD
Published: July 2010

Abstract: When either oxidizing species, such as H2O2 or oxy‐radicals, are present in excess or cellular anti‐oxidant defenses are lowered, a state of oxidative stress exists. Parkinson's disease is characterized by the loss of dopamine (DA) neurons, which leads to overactivity of the surviving DA neurons and an increase in neurotramsmitter release and turnover. The increased metabolism of DA neurotransmitter by monoamine oxidase (MAO) can be looked upon as an endogenous oxidative stress, leading to damage to Complex I‐linked mitochondrial respiration. It remains an open question to what extent the mitochondrial damage seen in Parkinson's disease is of genetic origin and how much is caused by H2O2 generated during enhanced turnover of DA, especially during treatment with L‐dopa.
Free Radicals and Antioxidants in the Year 2000: A Historical Look to the Future
Authors: GUTTERIDGE JOHN M.C. , HALLIWELL BARRY
Published: July 2010

Abstract:In the late 1950's free radicals and antioxidants were almost unheard of in the clinical and biological sciences but chemists had known about them for years in the context of radiation, polymer and combustion technology. Daniel Gilbert, Rebeca Gerschman and their colleagues related the toxic effects of elevated oxygen levels on aerobes to those of ionizing radiation, and proposed that oxygen toxicity is due to free radical formation, in a pioneering paper in 1956. Biochemistry owes much of its early expansion to the development and application of chromatographic and electrophoretic techniques, especially as applied to the study of proteins. Thus, superoxide dismutase (SOD) enzymes (MnSOD, CuZnSOD, FeSOD) were quickly identified. By the 1980's Molecular Biology had evolved from within biochemistry and microbiology to become a dominant new discipline, with DNA sequencing, recombinant DNA technology, cloning, and the development of PCR representing milestones in its advance. As a biological tool to explore reaction mechanisms, SOD was a unique and valuable asset. Its ability to inhibit radical reactions leading to oxidative damagein vitrooften turned out to be due to its ability to prevent reduction of iron ions by superoxide. Nitric oxide (NO·) provided the next clue as to how SOD might be playing a critical biological role. Although NO· is sluggish in its reactions with most biomolecules it is astoundingly reactive with free radicals, including superoxide. Overall, this high reactivity of NO· with radicals may be beneficialin vivo, e.g. by scavenging peroxyl radicals and inhibiting lipid peroxidation. If reactive oxygen species are intimately involved with the redox regulation of cell functions, as seems likely from current evidence, it may be easier to understand why attempts to change antioxidant balance in aging experiments have failed. The cell will adapt to maintain its redox balance. Indeed, transgenic animals over‐expressing antioxidants show some abnormalities of function. There must therefore be a highly complex interrelationship between dietary, constitutive, and inducible antioxidants within the body, under genetic control. The challenge for the new century is to be able to understand these relationships, and how to manipulate them to our advantage to prevent and treat disease.
Neuroprotective Strategies in Parkinson's Disease Using the Models of 6‐Hydroxydopamine and MPTPa
Authors: GRÜNBLATT EDNA , MANDEL SILVIA , YOUDIM MOUSSA B.H.
Published: July 2010

Abstract:The etiology of Parkinson's disease is not known. Nevertheless a significant body of biochemical data from human brain autopsy studies and those from animal models point to an on going process of oxidative stress in the substantia nigra which could initiate dopaminergic neurodegeneration. It is not known whether oxidative stress is a primary or secondary event. Nevertheless, oxidative stress as induced by neurotoxins 6‐hydroxydopamine and MPTP (N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) has been used in animal models to investigate the process of neurodegeneration with intend to develop antioxidant neuroprotective drugs. It is apparent that in these animal models radical scavengers, iron chelators, dopamine agonists, nitric oxide synthase inhibitors and certain calcium channel antagonists do induce neuroprotection against such toxins if given prior to the insult. Furthermore, recent work from human and animal studies has provided also evidence for an inflammatory process. This expresses itself by proliferation of activated microglia in the substantia nigra, activation and translocation of transcription factors, NF κ‐β and elevation of cytotoxic cytokines TNFα, IL1‐β, and IL6. Both radical scavengers and iron chelators prevent LPS (lipopolysaccharide) and iron induced activation of NF κ‐B. If an inflammatory response is involved in Parkinson's disease it would be logical to consider antioxidants and the newly developed non‐steroid anti‐inflammatory drugs such as COX2 (cyclo‐oxygenase) inhibitors as a form of treatment. However to date there has been little or no success in the clinical treatment of neurodegenerative diseases per se (Parkinson's disease, ischemia etc.), where neurons die, while in animal models the same drugs produce neuroprotection. This may indicate that either the animal models employed are not reflective of the events in neurodegenerative diseases or that because neuronal death involves a cascade of events, a single neuroprotective drug would not be effective. Thus, consideration should be given to multi‐neuroprotective drug therapy in Parkinson's disease, similar to the approach taken in AIDS and cancer therapy.
Microglial Contribution to Oxidative Stress in Alzheimer's Disease
Authors: COLTON CAROL A. , CHERNYSHEV OLGA N. , GILBERT DANIEL L. , VITEK MICHAEL P.
Published: July 2010

Abstract: Microglia are the CNS macrophage and are a primary cellular component of plaques in Alzheimer's disease (AD) that may contribute to the oxidative stress associated with chronic neurodegeneration. We now report that superoxide anion production in microglia or macrophages from 3 different species is increased by long term exposure (24 hours) to Aβ peptides. Since Aβ competes for the uptake of opsonized latex beads and for the production of superoxide anion by opsonized zymosan, a likely site of action are membrane receptors associated with the uptake of opsonized particles or fibers. The neurotoxic fibrillar peptides Aβ (1–42) and human amylin increase radical production whereas a non‐toxic, non‐fibrillar peptide, rat amylin, does not. We also report that the effect of Aβ peptides on superoxide anion production is not associated with a concomitant increase in nitric oxide (NO) production in either human monocyte derived macrophages (MDM) or hamster microglia from primary cultures. Since NO is known to protect membrane lipids and scavenge superoxide anion, the lack of Aβ‐mediated induction of NO production in human microglia and macrophages may be as deleterious as the over‐production of superoxide anion induced by chronic exposure to Aβ peptides.
Reactive Species in Sickle Cell Disease
Authors: ASLAN MUTAY , THORNLEY‐BROWN DENYSE , FREEMAN BRUCE A.
Published: July 2010

Abstract: The red cell is a relatively abundant locus of both free radical generation and reaction. Erythrocytes have a high content of unsaturated membrane lipids, a rich oxygen supply and are densely packed with redox‐active hemoglobin residues. In response, red cells have a highly evolved and well‐integrated network of oxidant defense mechanisms that lend an ability to withstand oxidative stress. In the case of congenital hemoglobin mutations that underlie sickle cell disease, they become very susceptible to free radical‐mediated injury by virtue of enhanced endogenous rates of production of reactive species and impairment of tissue free radical defense mechanisms. In sickle cell disease, a combination of these susceptibility factors are hypothesized to lead to an overall impairment of vascular function, in large part due to loss of “bioactive” nitric oxide via the free radical‐mediated consumption of this vasoactive molecule.
Daniel L. Gilbert: Explorer of Life
Authors: GILBERT CLAIRE , GILBERT RAYMOND L.
Published: July 2010

Abstract: From the time Dan was 12 years old to the present, he always was the explorer of life. He was very fortunate in having an opportunity to see how life exists in several human societies around the world. His many professional foreign travels are presented. Dan went to a 1959 meeting in Argentina, to England in 1963, and to Chile in 1963. After he married Claire, she accompanied him on his 44 day around the world trip in 1965 and on all his later foreign trips. In 1966, there was a Latin American trip on the way to doing research at a laboratory in Chile. Next on his travels was being a consultant in Venezuela in 1969 and attending a meeting in Russia in 1972. His son Raymond joined in trips to France in 1977, to Australia in 1983, to a 1990 trip to a Peruvian meeting, and finally joined the 1991 meeting to a meeting in Japan, with a side trip to China where Dan gave lectures. The last 2 foreign trips for Dan with Claire, but not with Raymond, were the meetings in 1994 in Buenos Aires, Argentina, and the 1998 meeting, which was held in both Israel and Jordan.
Neuropeptides, Neurotransmitters, Neurosteroids, and the Onset of Puberty
Authors: GENAZZANI A. R. , BERNARDI F. , MONTELEONE P. , LUISI S. , LUISI M.
Published: July 2010

Abstract: Puberty results from withdrawal of the “gonadostat” mechanisms and from increased gonadotropin sensitivity to GnRH. It has been hypothesized that GnRH release may be modulated by a non‐steroid‐mediated mechanism. Modifications of neuropeptides, neurotransmitters, and neurosteroids may underlie the onset of pubertal processes. Neuropeptides mainly involved in the control of GnRH release are opioids, neuropeptide Y (NPY), galanin, and corticotropin‐releasing factor (CRF), whereas neurotransmitters are noradrenaline, dopamine, serotonin, melatonin and γ‐aminobutyric acid (GABA). Norepinephrine, epinephrine, and dopamine stimulate GnRH, whereas the effect of serotonin on hypothalamic‐pituitary‐ovarian axis seems to be norepinephrine‐mediated. Neurosteroids are steroid hormones that bind to the GABA‐A receptor, synthesized in the brain de novo or from blood‐borne precursors. DHEA, a GABA‐A antagonistic neurosteroid, and allopregnanolone, a GABA‐A agonistic neurosteroid, may be important in the onset of gonadarche. In conclusion, the onset of puberty derives from the complex interplay among neuropeptides, neurotransmitters, and neurosteroids that occurs in the awakening of hypothalamic‐pituitary‐ovarian axis.
Follicular Atresia and Luteolysis Evidence of a Role for N‐Cadherin
Authors: MAKRIGIANNAKIS ANTONIS , COUKOS GEORGE , BLASCHUK OREST , COUTIFARIS CHRISTOS
Published: July 2010

Abstract: Studies suggest that cell‐cell interactions may regulate apoptosis; and, in particular, the calcium‐dependent cell adhesion molecule N‐cadherin has been shown to be capable of modulating this process. Here, we review the evidence that N‐cadherin is expressed by human granulosa cells (GCs) and mediates cell‐cell adhesion between GCs. There is strong correlation between N‐cadherin expression by granulosa or luteal cells and follicular survival in isolated follicles and archival tissue sections. There exists a strong expression of the molecule by GCs in follicles of the resting pool, of growing antral follicles, and of healthy corpora lutea. In contrast, the molecule is lost in degenerating GCs of atretic follicles and in luteal cells of the late luteal phase. Further, the experimental evidence demonstrates that cell‐cell adhesion is critical to the survival of GCs and that N‐cadherin‐mediated cell‐cell adhesion is a critical mediator of survival signals and inhibits apoptosis in these cells. Possible mechanisms by which apoptosis may be triggerred in GCs include the downregulation of N‐cadherin, which is mediated, at least in part, through the enzymatic cleavage of the extracellular domain of the molecule. Collectively, these observations suggest that downregulation of N‐cadherin or the absence of a functional extracellular domain of the molecule prevent GC aggregation and is associated with GC apoptosis. We propose that N‐cadherin‐mediated GC signaling plays a central role in follicular and luteal cell survival.
Placental Corticotropin‐Releasing Factor An Update
Authors: FADALTI M. , PEZZANI I. , COBELLIS L. , SPRINGOLO F. , PETROVEC M. M. , AMBROSINI G. , REIS F. M. , PETRAGLIA F.
Published: July 2010

Abstract: Corticotropin‐releasing factor (CRF) produced in placenta has paracrine effects within placenta, decidua, and myometrium and endocrine effects on mother and fetus. CRF is a potent local regulator of myometrial contractility and of prostaglandin release, Recently, urocortin, a new member of the CRF family, has been localized in human placenta and membranes. Urocortin mimics some of the local effects of CRF in intrauterine tissues, that is, increase of adrenocorticotrophic hormone (ACTH) and prostagiandin release and myometrial contractility. A local CRF‐BP modulates the paracrine effects of CRF and urocortin. The various CRF receptor subtypes are well distributed in placenta and membranes. CRH also acts on placental blood vasculature and has an action on fetal adrenal gland to stimulate the productlon of the steroid DHEA‐S. In nonpregnant women, plasma CRF levels are low; they become higher during the first and second trimesters of pregnancy. A clear increase is evident at term and when CRF‐BP levels decrease. Women with preterm labor show high CRF and low CRF‐BP levels, supporting an involvement of this pathway in mechanism of parturition.
Clinical Implications of the Ovarian/Endometrial Renin‐Angiotensin‐Aldosterone System
Authors: HASSAN E. , CREATSAS G. , MASTORAKOS G. , MICHALAS S.
Published: July 2010

Abstract:New organ‐specific functions of angiotensin II have recently been described: the importance of its role in the regulation of secretory epithelial function in many tissues including components of the reproductive tract has been documented. The source of angiotensin II in these tissues is the reproductive tract itself, and there is considerable evidence to suggest a distinct renin‐angiotensin‐aldosterone system in the ovary and uterus. Two main subtypes of angiotensin II receptors are recognized as angiotensin‐receptor I and II, according to their sensitivity to the angiotensin II antagonists. However, the presence of angiotensin II receptors in the male and female reproductive tract suggests a multiplicity of roles that are unrelated to their primary functions or to each other. The renin‐angiotensin‐aldosterone system is a major determinant of sodium balance in pregnancy. More recently RT‐PCR methods have revealed angiotensinogen transcription in the smooth muscle of spiral anteries of the decidua; a specific allele of this gene may be associated with hypertension in pregnancy as well as in pre‐eclampsia. We investigated the evolution of plasma renin activity and aldosterone levels during normal and hypertensive pregnancy. Both were found to increase progressively during all three trimesters of normotensive pregnancy. Plasma renin activity in hypertensive women remained unchanged during all three trimesters of pregnancy. Plasma aldosterone levels in hypertensive women increased progressively during all three trimesters of pregnancy. However, plasma aldosterone levels remained significantly lower than the ones of normotensive pregnant women. These increased aldosterone levels were noticed despite unchanged renin levels. Further clinical studies investigating the renin‐angiotensin‐aldosterone system in the pathogenesis of pregnancy hypertension are needed. A renin‐independent role of aldosterone in this pathological entity is suggested.
Anemia in Pregnancy
Authors: SIFAKIS S. , PHARMAKIDES G.
Published: July 2010

Abstract: Anemia is one of the most frequent complications related to pregnancy. Normal physiologic changes in pregnancy affect the hemoglobin (Hb), and there is a relative or absolute reduction in Hb concentration. The most common true anemias during pregnancy are iron deficiency anemia (approximately 75%) and folate deficiency megaloblastic anemia, which are more common in women who have inadequate diets and who are not receiving prenatal iron and folate supplements. Severe anemia may have adverse effects on the mother and the fetus. Anemia with hemoglobin levels less than 6 gr/dl is associated with poor pregnancy outcome. Prematurity, spontaneous abortions, low birth weight, and fetal deaths are complications of severe maternal anemia. Nevertheless, a mild to moderate iron deficiency does not appear to cause a significant effect on fetal hemoglobin concentration. An Hb level of 11 gr/dl in the late first trimester and also of 10 gr/dl in the second and third trimesters are suggested as lower limits for Hb concentration. In an iron‐deficient state, iron supplementation must be given and follow‐up is indicated to diagnose iron‐unresponsive anemias.
Role of Leptin in Reproduction
Authors: MANTZOROS CHRISTOS S.
Published: July 2010

Abstract: Leptin is a 16‐kDa adipocyte‐secreted protein the serum levels of which reflect mainly the amount of energy stores but are also influenced by short‐term energy imbalance as well as several cytokines and hormones. Leptin, by binding to specific receptors, alters the expression of several hypothalamic neuropeptides that regulate neuroendocrine function as well as energy intake and expenditure. More specifically, accumulating evidence suggests that this hormone may serve to signal to the brain information on the critical amount of fat stores that are necessary for LHRH secretion and activation of the hypothalamic‐pituitary‐gonadal axis. Rising leptin levels have been associated with initiation of puberty in animals and humans and normal leptin levels are needed for maintenance of menstrual cycles and normal reproductive function. Moreover, circadian and ultradian variations of leptin levels are associated with minute to minute variations of LH and estradiol in normal women. Falling leptin levels in response to starvation result in decreased estradiol levels and amenorrhea in subjects with anorexia nervosa or strenuously exercising athletes. In addition, leptin has a potentially important role during pregnancy and in the physiology of the neonate. Finally, recent evidence suggests that leptin may influence ovarian steroidogenesis directly, but the exact role of intra‐ovarian leptin action in the physiology and pathophysiology of the human reproductive system needs to be further elucidated.
Update on Chlamydia trachomatis
Authors: GUASCHINO S. , DE SETA F.
Published: July 2010

Abstract: Chlamydia trachomatis is one the most important sexually transmitted diseases; it can cause serious sequelae despite the absence of symptoms in some people. It's estimated that about 25% of women who have acute salpingitis become infertile, and chlamydial infection is the commonest cause. The introduction of screening programs for its detection are still a topic of discussion. The literature shows that the total cost of examination and treatment of complications known to be associated with genital chlamydial infection (PID, chronic pelvic pain, tubal factor infertility) is generally higher than the total cost of a large‐scale Chlamydia screening program. The selection of a diagnostic test for detection of chlamydial genital infection depends on availability, local expertise, and prevalence of Chlamydia trachomatis in the test population. Cell culture is too expensive in nonendemic regions, so the use of non‐culture techniques is very attractive. PCR (polymerase chain reaction) and LCR (ligase chain reaction) are actually the two most commonly used alternatives to conventional methods for detecting STD agents. In fact, PCR and LCR have proved useful for detection of Chlamydia trachomatis in cervical and urethral samples both in symptomatic and asymptomatic women. Recently, testing of first‐void urine (FVU) specimens with these techniques has shown that the amplification tests are as sensitive as tests with endocervical swab cultures.
Osteopenic Syndromes in the Adolescent Female
Authors: LYRITIS G. P. , SCHOENAU E. , SKARANTAVOS G.
Published: July 2010

Abstract: Low bone density in growing girls and mature young women is usually a finding that needs an explanation and further clinical investigation. Population‐based epidemiologic studies on osteoporosis in young persons do not exist. As a disease, osteoporosis among children and adolescents is rare, and since 1965 only 100 cases of idiopathic juvenile osteoprososis have been reported. When osteoporosis occurs in children, it is usually secondary to an underlying medical disorder (e.g., anorexia nervosa, leukemia) or to medications, but occasionally no identifiable primary cause can be detected. It may also be the result of a genetic disorder such as osteogenesis imperfecta. On the other hand, osteopenia in growing and young persons seems much commoner and needs further investigation. Adolescence is a period of increased calcium requirement, and girls with an underlying bone disease are at higher risk for bone demineralization. An additional point of interest is the changes in the geometry of bones through their continuous adaptation to simultaneous skeletal and muscular growth. Bones, through the mechanostat mechanism, adapt to mechanical loading by differentiating their geometry. A recent finding in this direction is that before and during the teenage years there is an environmental effect of physical activity and nutrition on hip geometry. Another important finding is an age‐dependent increase in bone cross‐sectional area and bone strength index in the absence of an increase in volumetric spongiosa bone density and cortical bone density. Girls, in comparison to boys, deposit more calcium in their bones during puberty, thus probably preparing their skeleton for the forthcoming events of pregnancy and lactation.
Identification and Psychic Closure: A Dynamic Structuralist Approach of the Psyche
Authors: VAN DE VIJVER GERTRUDIS
Published: July 2010

Abstract:In this paper, the emergence of psychic structures is conceived within a dynamic structuralist framework, developed in dialogue with the semiotic and dynamic viewpoint on levels from evolutionary systems theory. If psychic structures emerge, it is because they are particular kinds of organizationally closed systems that interpret the variety from below (the biological level) for the level above (the social level). the mechanism of psychic closure is presented as the key mechanism for the constitution of psychic structures, and is interpreted in terms of identification: an identificatory judgment is a self‐referential, closing judgment that involves a reinterpretation of the level below (the organic body) and is addressed to the level above (the fellow human being). The way in which identification has worked determines the kinds of psychic structures that are formed and also leads to different kinds of signifying practices. Different types of identification are discussed and a brief presentation of clinical arguments serves to illustrate the determinative role of identification in the formation of psychic structures.
Conceptual Closure: How Memories are Woven into an Interconnected Worldview
Authors: GABORA LIANE M.
Published: July 2010

Abstract:This paper describes a tentative model for how discrete memories transform into an interconnected conceptual network, or worldview, wherein relationships between memories are forged by way of abstractions. The model draws on Kauffman's theory of how an information‐evolving system can emerge through the formation and closure of an autocatalytic network. Here, the information units are not catalytic molecules, but memories and abstractions, and the process that connects them is not catalysis but reminding events (i.e., one memory evokes another). The result is a worldview that both structures, and is structured by, self‐triggered streams of thought.
Levels of Control and Closure in Complex Semiotic Systems
Authors: JOSLYN CLIFF
Published: July 2010

Abstract:It is natural to advance closures asatomicprocesses of universal evolution, and to analyze this concept specifically. Real complex systems like organisms and complex mechanisms cannot exist at either extreme of complete closure or lack of closure, nevertheless we should consider the properties of closures in general, the introduction of boundaries, a corresponding stability, the establishment of system autonomy and identity, and thereby the introduction of emergent new systems of potentially new types. Our focus should move from simple physical closure of common objects and classical self‐organizing systems tosemioticallyclosed systems that maintain cyclic relations of perception, interpretation, decision, and action with their environments. Thus, issues arise concerning the use and interpretation of symbols, representations, and/or internal models (whether explicit or implicit) by the system; and the syntactic, semantic, and pragmatic relations among the sign tokens, their interpretations, and their use or function for the systems in question. Primitive semiotic closures are hypothesized as equivalent to simple control systems, and in turn equivalent to simple organisms. This leads us directly to the grand hierarchical control theories of Turchin, Powers, and Albus, which provide an explicit mechanism for the formation of new levels within complex semiotically closed systems.
Varieties ofChemicalClosure: Three Kinds of Coherence Observed in Chemical Systems, and Their Relation to Societal Integration
Authors: EARLEY JOSEPH E.
Published: July 2010

Abstract:Covalent bonding within chemical molecules and the internal electronic structure of atoms involve closure of phase relations in electronic wave functions, as suggested de Broglie by many years ago. The structures of crystals involving positive and negative ions can be understood in terms of replication of unit cells that may be classified in terms of symmetry. The main principle involved in crystal symmetry can be understood by examining possible patterns in decorative borders. A more widely applicable type of chemical closure occurs in oscillating reactions (dissipative structures), in which an autocatalytic process is balanced by some exit reaction. As is the case for the other types of chemical coherence, the number of distinct types of oscillating reactions is rather small. Otherwise puzzling aspects of human social and organizational behavior may be clarified by analogy with chemical oscillating reactions.
Syntactic Autonomy: Why There is No Autonomy Without Symbols and How Self‐Organizing Systems Might Evolve Them
Authors: ROCHA LUIS MATEUS
Published: July 2010

Abstract:Two different types of agency are discussed that are based on dynamically coherent and incoherent couplings with an environment, respectively. I propose that until a private syntax (syntactic autonomy) is discovered by dynamically coherent agents, there are no significant or interesting types of closure or autonomy. When syntactic autonomy is established, then, because of a process of description‐based selected self‐organization, open‐ended evolution is enabled. At this stage, in addition to dynamics, agents depend on localized, symbolic memory, thus adding a level of dynamic incoherence to their interaction with the environment. Furthermore, it is the appearance of syntactic autonomy that enables much more interesting types of closures among agents sharing the same syntax. To investigate how we can study the emergence of syntax from dynamic systems, experiments with cellular automata leading to emergent computation that solves nontrivial tasks are discussed. RNA editing is also mentioned as a process that may have been used to obtain a primordial biological code necessary for open‐ended evolution.
Closure and Anticlosure in the Realm of Quantum Gravity: Why Evolution Needs No Origin
Authors: CONRAD MICHAEL
Published: July 2010

Abstract:Dynamic systems with suitable nonlinearities yield self‐organizing behavior. The evolution continues until the relationship among the components becomes self‐consistent; that is, until it reaches closure. Disruptions of closure that allow for continued change are also characteristic of biological evolution. Are the requisite nonlinearities add‐ons that give an essentially linear world the appearance of circularity, or do they have their origin in the underlying physics of the universe? The picture developed here fits to the latter view.
Spontaneous Order, Autocatakinetic Closure, and the Development of Space‐Time
Authors: SWENSON ROD
Published: July 2010

Abstract:Over its 4.6 billion year history, the time‐dependent behavior of planet Earth, from the origin and emergence of life to the explosive globalization of human culture today, shows the progressive and accelerating production of increasingly more highly ordered dynamic states. Understanding our place as both productions and producers in this rapidly accelerating global becoming is a requisite step to the meaningful grounding of virtually every other discipline, most particularly those disciplines relating to the endeavors and activities of humans themselves. Recent advances in the study of spontaneous ordering provide both a minimal ontological framework required for causally addressing such systems, and the nomological basis for understanding the ubiquitous or universal generic nature of such ordering itself. This paper briefly outlines the main points.
Genetic Diversity in the Matrix Metalloproteinase Family: Effects on Function and Disease Progressiona
Authors: HENNEY ADRIANO M. , YE SHU , ZHANG BAIPING , JORMSJÖ SOPHIA , WHATLING CARL , ERIKSSON PER , HAMSTEN ANDERS
Published: July 2010

Abstract: Atherosclerosis is an example of a complex trait, where the course of the disease is influenced by a combination of common variation in a constellation of genes and the effect of a wide range of environmental variables. Thus, the underlying disease mechanisms will be modulated by genetic diversity and the effect this diversity has on an individual's response to environmental challenges such as smoking, diet, and exercise. Unlike the consequences of mutations in severe single‐gene disorders on protein function, the impact of individual common, functionally important sequence changes in genes contributing to multifactorial diseases is likely to be very small. The challenge is to dissect the contribution that each of these genes makes to the disease process. We have tackled this by identifying common genetic variants, studying their effects on function, and applying them to the analysis of association in appropriately structured and suitably powered studies. Even with our incomplete understanding of the disease, the list of potential candidate genes we could study is vast; but, we do know from pathological studies that a wide spectrum of structural architecture exists in atherosclerotic plaques, suggesting that remodeling of vascular connective tissue is fundamentally important. Matrix remodeling is controlled by a complex network of cell and matrix interactions, the net outcome of which is the product of a balance between synthetic and degradative processes. Our work has focused on the family of enzymes and inhibitors most directly associated with matrix turnover‐the matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs, tissue inhibitors of MPs). We specifically searched for functionally relevant genetic variants that might modulate the delicate control of matrix turnover. Using these molecular genetic strategies to investigate the impact of natural genetic variation on vascular matrix remodeling has begun to shed new light on the importance of these genes in atherogenesis.
The Extracellular Matrix Dynamically Regulates Smooth Muscle Cell Responsiveness to PDGFa
Authors: RAINES ELAINE W. , KOYAMA HIDENORI , CARRAGHER NEIL O.
Published: July 2010

Abstract:Focal accumulation of smooth muscle (SMC) within the arterial intima contributes to the formation of lesions of atherosclerosis. Platelet‐derived growth factor (PDGF) is a potent stimulant of SMC migration and proliferation in culture that may play a role in the accumulation of SMC in atherogenesis. SMCs normally reside in the media of the artery wall surrounded by extracellular matrix (ECM), including type I collagen. In atherogenesis, the ECM is degraded, new ECM components, such as fibronectin, are synthesized and assembled, and these alterations in ECM components are associated with changes in SMC phenotype. To model the changes in ECM in normal and diseased arteries, we have analyzed SMCs cultured on different forms of type I collagen. Our studies demonstrate that integrin‐mediated signals from various forms of type I collagen lead to specific and rapid modulation of the integrin signaling complex, including cytoskeletal connections, and of the responsiveness of SMC to PDGF stimulation.