Toxicity of Amyloid β Peptide: Tales of Calcium,Mitochondria, and Oxidative Stress

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Abeta) peptides. Although the disease undoubtedly reflects the interaction of complex multifactorial processes, Abeta itself is toxic to neurons in vitro and the load of Abeta in vivo correlates well with the degree of cognitive impairment. There has therefore been considerable interest in the mechanism(s) of Abeta neurotoxicity. We here review the basic biology of Abeta processing and consider some of the major areas of focus of this research. It is clear that both AD and Abeta toxicity are characterized by oxidative stress, alterations in the activity of enzymes of intermediary metabolism, and mitochondrial dysfunction, especially impaired activity of cytochrome c oxidase. Studies in vitro also show alterations in cellular calcium signaling. We consider the mechanisms proposed to mediate cell injury and explore evidence to indicate which of these many changes in function are primary and which secondary.     

The Evolution of the idea of homeostasis: Determinism,stochastics, and chaos–self-organization

Homeostasis is a basic concept in investigating all living systems. Homeostasis and life are synonyms to a certain extent. The concept of homeostasis has been studied and developed for more than 150 years; however, only the 21st century brought us close to understanding homeostasis as a state of a biosystem and a continuous process. The chaos and self-organization theory (CSOT) proves that the conventional views based on determinism (functional analysis) or stochastics (when stochastic uncertainty or certainty occurs) cannot describe homeostasis as defined by W.B. Cannon and his followers. The new CSOT shows a clear boundary between determinism, stochastics (and deterministic chaos), and third-type systems, which have five special properties (principles of self-organization) and can be described in terms of quasiattractors. Kinematics is understood as the motion of quasi-attractors in the phase spaces of states. Complexity is introduced as the rate of evolution of complex biological systems, differing from the definition by Prigogine–Glansdorff. At the same time, concepts of uncertainty of the first and second types and an analog of the Heisenberg calculus are introduced for complexity. According to these concepts, complex biosystems are transferred from the area of traditional science to a new area of the theory of chaos and self-organization.     

Serum γ-glutamyltransferase: independent predictor of risk of diabetes, hypertension, metabolic syndrome, and coronary disease

Serum γ-glutamyltransferase (GGT) is associated with oxidative stress and hepatic steatosis. The extent to which its value in determining incident cardiometabolic risk (coronary heart disease (CHD), metabolic syndrome (MetS), hypertension and type 2 diabetes) is independent of obesity needs to be further explored in ethnicities. After appropriate exclusions, a cohort of 1,667 adults of a general population (age 52 ±11 years) was evaluated prospectively at 4 year's follow-up using partly Cox proportional hazard regressions. GGT activity was measured kinetically, and values were log-transformed for analyses. MetS was identified by Adult Treatment Panel-III criteria modified for male abdominal obesity. Median (interquartile range) GGT activity was 24.9 (17.0; 35.05) U/l in men, 17.0 (12.3; 24.0) U/l in women. In linear regression analysis, while smoking status was not associated, (male) sex, sex-dependent age, alcohol usage, BMI, fasting triglycerides and C-reactive protein (CRP) were significant independent determinants of circulating GGT. Each 1-s.d. increment in (= 0.53 ln GGT) GGT activity significantly predicted in each sex incident hypertension (hazard ratio (HR) 1.20 (95% confidence interval (CI) 1.10; 1.31)), and similarly MetS, after adjustment for age, alcohol usage, smoking status, BMI and menopause. Strongest independent association existed with diabetes (HR 1.3 (95% CI 1.1; 1.5)) whereas GGT activity tended to marginally predict CHD independent of total bilirubin but not of BMI. Higher serum total bilirubin levels were protective against CHD risk in women. We conclude that elevated serum GGT confers, additively to BMI, risk of hypertension, MetS, and type 2 diabetes but only mediates adiposity against CHD risk.     

Conflicting perceptions of the fetus: person, patient, 'nobody', commodity?

Different constructions of the fetus lie at the centre of reproductive, abortion and disability politics. Recent developments mean that, within the same hospital, a fetus may be perceived in contrasting and potentially conflicting ways. It is also argued that the status given to the fetus is directly relevant to the status given to pregnant women. During group discussions facilitated by an ethicist, health-care staff highlighted various perceptions of the fetus which included: person; patient; 'nobody'; commodity. Perhaps not surprisingly in view of the current legal situation, staff tended to claim that it is usually the pregnant women who decides how her fetus will be constructed, and the practitioner who responds to this. However, various ways in which practitioners might influence women's perceptions of their fetus are highlighted, as are some ways in which the perceptions of staff might be influenced. This paper illustrates how sensitive health-care staff will need to be if they are indeed to respond to, rather than shape, women's constructions of their fetus.     

The mechanism of photoinhibition in vivo: Re-evaluation of the roles of catalase, α-tocopherol, non-photochemical quenching, and electron transport

Photoinhibition of photosystem II (PSII) occurs when the rate of light-induced inactivation (photodamage) of PSII exceeds the rate of repair of the photodamaged PSII. For the quantitative analysis of the mechanism of photoinhibition of PSII, it is essential to monitor the rate of photodamage and the rate of repair separately and, also, to examine the respective effects of various perturbations on the two processes. This strategy has allowed the re-evaluation of the results of previous studies of photoinhibition and has provided insight into the roles of factors and mechanisms that protect PSII from photoinhibition, such as catalases and peroxidases, which are efficient scavengers of H(2)O(2); α-tocopherol, which is an efficient scavenger of singlet oxygen; non-photochemical quenching, which dissipates excess light energy that has been absorbed by PSII; and the cyclic and non-cyclic transport of electrons. Early studies of photoinhibition suggested that all of these factors and mechanisms protect PSII against photodamage. However, re-evaluation by the strategy mentioned above has indicated that, rather than protecting PSII from photodamage, they stimulate protein synthesis, with resultant repair of PSII and mitigation of photoinhibition. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial.     

Plasticity of gene‐regulatory networks controlling sex determination: of masters,slaves, usual suspects,newcomers, and usurpators

Sexual dimorphism is one of the most pervasive and diverse features of animal morphology, physiology, and behavior. Despite the generality of the phenomenon itself, the mechanisms controlling how sex is determined differ considerably among various organismic groups, have evolved repeatedly and independently, and the underlying molecular pathways can change quickly during evolution. Even within closely related groups of organisms for which the development of gonads on the morphological, histological, and cell biological level is undistinguishable, the molecular control and the regulation of the factors involved in sex determination and gonad differentiation can be substantially different. The biological meaning of the high molecular plasticity of an otherwise common developmental program is unknown. While comparative studies suggest that the downstream effectors of sex‐determining pathways tend to be more stable than the triggering mechanisms at the top, it is still unclear how conserved the downstream networks are and how all components work together. After many years of stasis, when the molecular basis of sex determination was amenable only in the few classical model organisms (fly, worm, mouse), recently, sex‐determining genes from several animal species have been identified and new studies have elucidated some novel regulatory interactions and biological functions of the downstream network, particularly in vertebrates. These data have considerably changed our classical perception of a simple linear developmental cascade that makes the decision for the embryo to develop as male or female, and how it evolves.     

Cytogenetic biomonitoring of inhabitants of a large uranium mineralization area: the municipalities of Monte Alegre, Prainha, and Alenquer, in the State of Pará, Brazil

Uranium is a natural radioactive metallic element; its effect on the organism is cumulative, and chronic exposure to this element can induce carcinogenesis. Three cities of the Amazon region—Monte Alegre, Prainha, and Alenquer—in North Brazil, are located in one of the largest uranium mineralization areas of the world. Radon is a radioactive gas, part of uranium decay series and readily diffuses through rock. In Monte Alegre, most of the houses are built of rocks removed from the Earth’s crust in the forest, where the uranium reserves lie. The objective of the present work is to determine the presence or absence of genotoxicity and risk of carcinogenesis induced by natural exposure to uranium and radon in the populations of these three cities. The frequency of micronuclei (MN) and chromosomal aberrations (CA) showed no statistically significant differences between the control population and the three study populations (P > 0.05). MN was also analyzed using the fluorescence in situ hybridization (FISH) technique, with a centromere-specific probe. No clastogenic and/or aneugenic effects were found in the populations. Using FISH analysis, other carcinogenesis biomarkers were analyzed, but neither the presence of the IGH/BCL2 translocation nor an amplification of the MYC gene and 22q21 region was detected. Clastogenicity and DNA damage were also not found in the populations analyzed using the alkaline comet assay. The mitotic index showed no cytotoxicity in the analyzed individuals’ lymphocytes. Once we do not have data concerning radiation doses from other sources, such as cosmic rays, potassium, thorium, or anthropogenic sources, it is hard to determine if uranium emissions in this geographic region where our study population lives are too low to cause significant DNA damage. Regardless, genetic analyses suggest that the radiation in our study area is not high enough to induce DNA alterations or to interfere with mitotic apparatus formation. It is also possible that damages caused by radiation doses undergo cellular repair.     

Amino acid sequences of hemoglobin β chains of five species of pinnipeds:Neophoca cinerea,Otaria byronia,Eumetopias jubatus,Pusa hispida,andPagophilus groenlandica

Pinnipeds (Otariidae, Odobenidae, and Phocidae) in the order Carnivora have one or two types (Hb I and Hb II) of hemoglobin components. These hemoglobins consist of identicalβ chains and differentα chains. We determined the complete amino acid sequences of the hemoglobinβ chain of three species of Otariidae (Australian sea lion, South American sea lion, and northern sea lion) and two species of Phocidae (ringed seal and harp seal) from intactβ chain and chemical cleavage fragments. The sequences are similar toβ chains of the already known sequences of pinnipeds. These sequences were compared with those of other carnivores (Mustelidae, Ursidae, Canidae, and Felidae) and adult human hemoglobinβ chain. Using Artiodactyla (pig) as an outgroup, we find that the tree constructed by means of phylogenetic analysis shows that Odobenidae is closest to Otariidae, and that Otariidae and Odobenidae are closer to Mustelidae than to Phocidae.     

Bioremediation of a petroleum‐contaminated cryic soil: Effects of phosphorus,nitrogen, and temperature

Bioremediation has been shown to be an effective means of treating petroleum‐contaminated soils in cold areas, although the conditions required to maximize bioremediation in cold region (cryic) soils are not well documented. A laboratory study was conducted to investigate the effects of nitrogen and phosphorus levels and temperature on petroleum bioremediation. A cryic entisol contaminated with diesel fuel was treated with nitrogen (0, 400, 800, or 1200 mg/kg of soil) and phosphorus (0, 60, 120, or 180 mg/kg of soil) and incubated at two temperatures (10 and 20°C). At 10°C, bioremediation rates were not affected by fertility treatments. At 20°C, reaction rates were increased by the addition of P, but unaffected by N. Regardless of fertility regime, the rate of diesel loss was much greater in soil incubated at 20°C than in soil incubated at 10°C.     

Fitness of wild‐caught Drosophila melanogaster females: allozyme variants of GPDH, ADH, PGM, and EST

We have collected several hundred Drosophila melanogaster flies (near Davis, California), isolated them individually, without anesthesia, at the collecting site, and estimated the fitness components of the wild‐caught females under different environmental conditions. The fitness parameters measured are fecundity, oviposition rate, and productivity (egg‐to‐adult viability, development rate, and number of progeny). The environmental variables are two temperatures (22°C and 28°C) and two densities (‘scant’ and ‘crowded’). After the fitness measurements are completed for each individual female, its genotype is determined at four loci encoding enzymes: GPDH and ADH, located on chromosome II and PGM and EST‐C, located on chromosome III. Density has a large significant effect on productivity; temperature has significant effects on fecundity, oviposition rate, and development rate. The experiments show that allozyme polymorphisms are associated with selection effects. Fitness differences between allozyme genotypes occur for all fitness components, except oviposition rate. But which genotype is superior depends on the environmental conditions; heterozygotes exhibit higher fitness than homozygotes in a number of cases, but inferior in others. A unique feature of the present experiments is that the experimental flies are wild‐caught females rather than laboratory‐bred individuals. This revised version was published online in July 2006 with corrections to the Cover Date.     

Hallmarks of cancer: of all cancer cells,all the time?

In two landmark articles, Hanahan and Weinberg synthesized into one conceptual framework 'the hallmarks of cancer', a massive amount of information describing the characteristics of a cancer cell. Although this is neither the intention nor the belief of the authors, hallmarks are often interpreted as applying to a canonic cancer cell, or equally to all cells within a cancer. In this article, we clarify the separate concepts of causes, oncogenic events, signal transduction programs, and hallmarks to show that there is no unimodal relation between these concepts but a complex network of interrelations that vary in different cells, between cells, and at different times in any given cell. We consider cancer as an evolving, dynamic, and heterogeneous system, explaining, at least in part, the difficulty of treating cancer and supporting the use of simultaneous, multitarget therapies.     

Termination of translation: interplay of mRNA,rRNAs and release factors?

Termination of translation in eukaryotes has focused recently on functional anatomy of polypeptide chain release factor, eRF1, by using a variety of different approaches. The tight correlation between the domain structure and different functions of eRF1 has been revealed. Independently, the role of prokaryotic RF1/2 in GTPase activity of RF3 has been deciphered, as well as RF3 function itself.     

War of Ontology Worlds: Mathematics,Computer Code,or Esperanto?

The use of structured knowledge representations-ontologies and terminologies-has become standard in biomedicine. Definitions of ontologies vary widely, as do the values and philosophies that underlie them. In seeking to make these views explicit, we conducted and summarized interviews with a dozen leading ontologists. Their views clustered into three broad perspectives that we summarize as mathematics, computer code, and Esperanto. Ontology as mathematics puts the ultimate premium on rigor and logic, symmetry and consistency of representation across scientific subfields, and the inclusion of only established, non-contradictory knowledge. Ontology as computer code focuses on utility and cultivates diversity, fitting ontologies to their purpose. Like computer languages C++, Prolog, and HTML, the code perspective holds that diverse applications warrant custom designed ontologies. Ontology as Esperanto focuses on facilitating cross-disciplinary communication, knowledge cross-referencing, and computation across datasets from diverse communities. We show how these views align with classical divides in science and suggest how a synthesis of their concerns could strengthen the next generation of biomedical ontologies.     

Control hunting of wild animals: health,money, or pleasure?

In many parts of the world, millions of wildlife species are hunted for sport, food, skins, and other products. In recent years, a backlash has emerged from certain groups of society against this long-standing human pursuit. However, attitudes towards the control of wild animals to reduce the health risk to other animals, to lessen agricultural damage, or to protect game species, may generate a different reaction, where even killing is tolerated. In this paper, we analyze the public’s acceptance of control hunting in Andalusia (southern Spain). Our results suggest that lethal control to improve domestic animal health is highly accepted (75%) is more controversial when animals are killed for damaging crops (59% acceptance) and is highly unaccepted when the goal is to enhance game species numbers (22% acceptance). Older people and males, in particular, accept more readily some of these control-hunting measures. These results are needed to understand better the public attitudes on which conservation managers can base their decisions when control hunting is required.     

Spectacles of migrant ‘illegality’: the scene of exclusion,the obscene of inclusion

Abstract

Border policing and immigration law enforcement produce a spectacle that enacts a scene of ‘exclusion’. Such spectacles render migrant ‘illegality’ visible. Thus, these material practices help to generate a constellation of images and discursive formations, which repetitively supply migrant ‘illegality’ with the semblance of an objective fact. Yet, the more these spectacles fuel anti-immigrant controversy, the more the veritable inclusion of the migrants targeted for exclusion proceeds apace. Their ‘inclusion’ is finally devoted to the subordination of their labour, which is best accomplished only insofar as their incorporation is persistently beleaguered with exclusionary campaigns that ensure that this inclusion is itself a form of subjugation. At stake, then, is a larger sociopolitical (and legal) process of inclusion through exclusion. This we may comprehend as the obscene of inclusion. The castigation of ‘illegals’ thereby supplies the rationale for essentializing citizenship inequalities as categorical differences that then may be racialized.