HIFs and tumors--causes and consequences

For most organisms oxygen is essential fo life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counter act possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an alpha- and a beta-subunit. HIF-1 alpha protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.     

Cross-reactivity between storage and dust mites and between mites and shrimp

Many patients have sensitivities to multiple species of storage and house dust mites. It is not clear if this is because patients have multiple sensitivities to species-specific mite allergens or if these mites share many cross-reacting allergens. Our objective was to further define the cross-allergenicity between several species of storage and house dust mites using crossed-immunoelectrophoresis (CIE), crossed-radioimmunoelectrophoresis (CRIE), immunoblotting, and ELISA. CIE and CRIE reactions revealed that storage mites shared two cross-antigenic molecules and one of these bound IgE in a serum pool from mite allergic patients. Antibody in anti-sera built to each species of mite recognized many SDS–PAGE resolved proteins of other mite species and this suggested the potential for other cross-reactive allergens. Among patient sera, IgE bound to many different proteins but few had IgE that bound to a protein with common molecular weights across the mite species and this suggested mostly species-specific allergens. Antiserum built to each mite species precipitated one protein in shrimp extracts that bound anti-Der p 10 (tropomyosin) and IgE in the serum pool. Anti-Der p 10 showed strong binding to shrimp tropomyosin but very little to any of the mite proteins. ELISA showed the mite extracts contained very little tropomyosin. The storage and dust mites investigated contain mostly species-specific allergens and very small amounts of the pan-allergen tropomyosin compared to shrimp and snail.     

Astrocytes and Synaptosomes Transport and Metabolize Lactate and Acetate Differently

Astrocytes transport the monocarboxylate acetate, but synaptosomes do not. The reason for this is unknown, because both preparations express monocarboxylate transporters (MCT). The transport and metabolism of lactate, another monocarboxylate, was examined in these two preparations, and the results were compared to those for acetate. Lactate transport is more rapid in astrocytes than in synaptosomes, but of lower affinity (Kms of 17 and 4 mM, respectively). Lactate (0.2 mM) is metabolized to CO2 more rapidly in synaptosomes than in astrocytes (rates of 0.37 and 0.07 nmol x mg protein(-1) x min(-1), respectively). The reason for this is unclear, but cellular differences in lactate dehydrogenase isotype expression may be involved. Acetate is metabolized to CO2 more rapidly in astrocytes than in synaptosomes (rates of 0.43 and 0.02 nmol x mg protein(-1) x min(-1), respectively). This is likely due to cellular differences in the expression of monocarboxylate transporter subtypes.     

Ontogeny and phylogeny of endothermy and torpor in mammals and birds

Endothermic thermoregulation in small, altricial mammals and birds develops at about one third to half of adult size. The small size and consequently high heat loss in these young should result in more pronounced energetic challenges than in adults. Thus, employing torpor (a controlled reduction of metabolic rate and body temperature) during development would allow them to save energy. Although torpor during development in endotherms is likely to occur in many species, it has been documented in only a few. In small, altricial birds (4 orders) and marsupials (1 order), which are poikilothermic at hatching/birth, the development of competent endothermic thermoregulation during cold exposure appears to be concurrent with the capability to display torpor (i.e. poikilothermy is followed by heterothermy), supporting the view that torpor is phylogenetically old and likely plesiomorphic. In contrast, in small, altricial placental mammals (2 orders), poikilothermy at birth is followed first by a homeothermic phase after endothermic thermoregulation is established; the ability to employ torpor develops later (i.e. poikilothermy-homeothermy-heterothermy). This suggests that in placentals torpor is a derived trait that evolved secondarily after a homeothermic phase in certain taxa perhaps as a response to energetic challenges. As mammals and birds arose from different reptilian lineages, endothermy likely evolved separately in the two classes, and given that the developmental sequence of torpor differs between marsupials and placentals, torpor seems to have evolved at least thrice.     

Cytoskeleton and mitochondrial morphology and function

It has been well established that the cytoskeleton is an essential modulator of cell morphology and motility, intracytoplasmic transport and mitosis, however cytoskeletal linkage to the organelles has not been unequivocally demonstrated. Indeed, cytoskeleton appears to be essential in determining and modulating gene phenotype as a function of cellular environment. According to recent studies, the organization of the cytoskeleton network together with associated protein(s) could be essential in regulating mitochondrial function and particularly the permeability of the mitochondrial outer membrane to ADP. The aim of this chapter is to summarize the main properties of the cytoskeletal environment of mitochondria and the possible role(s) of this network in mitochondrial function in myocytes.     

Genomics and microarray for detection and diagnostics

Genomics provided biomedical scientists an inventory of all genes and sequences present in a living being. This provides an unique opportunity to the scientists to predict and study biological functions of these genes. The changes in the gene expression regulated by genomic sequences therefore reflect changes in the molecular processes working in a cell or tissue in response to external factors including exposure to toxic compounds and pathogens. Microarray offers a biotechnological revolution with the help of DNA chemistry, silicon chip technology and optics to be used to monitor gene expression for thousands of genes in one single experiment. Briefly, 20,000 to 100,000 unique DNA molecules get applied by a robot to the surface of silicon wafers (approximately the size of a microscope slide). Using a single microarray experiment, the expression level of 20,000 to 100,000 genes will be examined in one single experiment. Genomics and microarray have a significant role and impact on the design and development of modern detection and diagnostic tools in several different ways. Microarray tools are now used on regular basis for monitoring gene expression of large number of genes and also frequently applied to DNA sequence analysis, immunology, genotyping, and molecular diagnosing. For diagnostics, these tools can be used to distinguish and differentiate between different DNA fragments that differ by as little as a single nucleotide polymorphism (SNP). These microarrays can be divided based on the gene density spots that will be high density (>10,000 spots) per slide, medium (< 1000 > 100) and low density (< 100). High-density arrays have proven to be very useful in disease diagnosis especially in diagnosis and classification of different types of cancers. These microarray tools hold tremendous potential for pathogen detection, which will be comprised, of unique sets of genes (also referred to as "signatures") able to unambiguously identify the species and strain of pathogens of interest.     

ERPs to nouns and verbs--congruences and differences

The results of the multivariate analysis of variance confirmed statistically significant differences in latency and amplitude of some ERPs waves to nouns and ERPs to verbs. ERPs to nouns differ from ERPs to verbs by a significantly longer latency and greater amplitude of some waves. A comparison of the characteristics of ERPs to nouns and ERPs to verbs separately in males and females produced basically identical results; in females, however, there are much fewer significant differences than in males. Interaction between the site of the recording electrode and features of ERPs to words of different word classes however could not be demonstrated.     

Cadmium and transport of ions and substances across cell membranes and epithelia

Toxic metals such as cadmium (Cd²⁺) pose serious risks to human health. However, even though the importance of Cd²⁺ as environmental health hazards is now widely appreciated, the specific mechanisms by which it produces its adverse effects have yet to be fully elucidated. Cd²⁺ is known to enter cells, it binds and interacts with a multitude of molecules, it may indirectly induce oxidative stress and interfere with gene expression and repair of DNA. It also interacts with transport across cell membranes and epithelia and may therefore disturb the cell’s homeostasis and function. Interaction with epithelial transport, especially in the kidney and the liver, may have serious consequences in general health. A lot of research still needs to be done to understand the exact way in which Cd²⁺ interferes with these transport phenomena. It is not always clear whether Cd²⁺ has primary or secondary effects on cell membrane transport. In the present review we try to summarize the work that has been done up to now and to critically discuss the relevance of the experimental work in vitro with respect to the in vivo situation.     

Reciprocity and Ethical Tuberculosis Treatment and Control

This paper explores the notion of reciprocity in the context of active pulmonary and laryngeal tuberculosis (TB) treatment and related control policies and practices. We seek to do three things: First, we sketch the background to contemporary global TB care and suggest that poverty is a key feature when considering the treatment of TB patients. We use two examples from TB care to explore the role of reciprocity: isolation and the use of novel TB drugs. Second, we explore alternative means of justifying the use of reciprocity through appeal to different moral and political theoretical traditions (i.e., virtue ethics, deontology, and consequentialism). We suggest that each theory can be used to provide reasons to take reciprocity seriously as an independent moral concept, despite any other differences. Third, we explore general meanings and uses of the concept of reciprocity, with the primary intention of demonstrating that it cannot be simply reduced to other more frequently invoked moral concepts such as beneficence or justice. We argue that reciprocity can function as a mid-level principle in public health, and generally, captures a core social obligation arising once an individual or group is burdened as a result of acting for the benefit of others (even if they derive a benefit themselves). We conclude that while more needs to be explored in relation to the theoretical justification and application of reciprocity, sufficient arguments can be made for it to be taken more seriously as a key principle within public health ethics and bioethics more generally.     

Biotechnology and bioremediation: successes and limitations

With advances in biotechnology, bioremediation has become one of the most rapidly developing fields of environmental restoration, utilizing microorganisms to reduce the concentration and toxicity of various chemical pollutants, such as petroleum hydrocarbons, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, phthalate esters, nitroaromatic compounds, industrial solvents, pesticides and metals. A number of bioremediation strategies have been developed to treat contaminated wastes and sites. Selecting the most appropriate strategy to treat a specific site can be guided by considering three basic principles: the amenability of the pollutant to biological transformation to less toxic products (biochemistry), the accessibility of the contaminant to microorganisms (bioavailability) and the opportunity for optimization of biological activity (bioactivity). Recent advances in the molecular genetics of biodegradation and studies on enzyme-tailoring and DNA-shuffling are discussed in this paper.     

Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies

Excessive scars form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient's quality of life, both physically and psychologically. Multiple studies on hypertrophic scar and keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction. In this review we summarize the current understanding of the pathophysiology underlying keloid and hypertrophic scar formation and discuss established treatments and novel therapeutic strategies.     

Pleasure and disgust: memories and associations of pleasant and unpleasant odours in Germany and Japan

The question of whether odour experiences have a function inthe cultures of the technically industrialized world was investigatedby interviews with German (166) and Japanese (88) subjects.They were asked to name pleasant and unpleasant odours frommemory and to give associations regarding them. The participantsenumerated 2040 odours and 3520 associations. Although Japanesesubjects in general gave less information than the Germans,the results for both cultures were very similar in quality aswell as quantity. The odour memories included the whole physicaland social environment and the associations showed the far-reachingeffect of odour experiences. Both pleasant and unpleasant odourswere remembered to an equal extent. Most of the odours recalledwere assessed similarly by the subjects, as either pleasantor unpleasant. Obviously, individual likings or aversions aredominated by underlying evaluations common to all subjects ofboth cultures. Uniformly judged odours were, for example, odoursof plants (pleasant) and odours of rotten and decomposed things(unpleasant). It is discussed whether this finding reflectspreprogrammed survival strategies. The few cultural differenceswhich were found seemed to reflect different life habits, normsand values in the two countries.     

Neurosecretion and Salt and Water Balance in the Annelida and Crustacea

The possible role of the neurosecretory system in regulationof salt and water has been studied in the annelids and crustaceans.In the earthworm, Lumbricus terrestris, a brain factor influences'the salt and osmotic concentration of the blood and coelomicfluid. Removal of the brain results in the increase of waterinflux with a decrease in the salt and osmotic concentrationsof the body fluids. The decreases in salt and osmotic concentrationscan be prevented by the implantation of the brain or the injectionof brain homogenates. In the freshwater crayfish, Procambarus clarkii, a factor, presumablysecreted in the brain and released in the eyestalk, seems tomaintain the normal permeability of the body surfaces to water.Eyestalk removal, which eliminates the release site, resultsin the increased influx of water with a decrease in the saltconcentration of the blood. A brain factor also seems to beinvolved in maintaining the sodium and osmotic concentrationsof the blood. In the semi-terrestrial grapsid crab, Metopograpsus messor,the thoracic ganglion, under the control of an eyestalk element,secretes a factor involved in increasing the permeability ofthe body surfaces to water. The removal of the eyestalks, theimplantation of the thoracic ganglion, or the injection of extractsof thoracic ganglia, results in changes in the osmotic concentrationof the blood tending toward that of the medium. In all threespecies studied, the neuroendocrine factors seem to be involvedprimarily in the regulation of the permeability of the bodysurfaces to water.     

Cobalt and antimony: genotoxicity and carcinogenicity

The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with DNA repair systems, still need further investigation.     

Synergies and trade-offs between insect and pathogen resistance in maize leaves and roots

Determining links between plant defence strategies is important to understand plant evolution and to optimize crop breeding strategies. Although several examples of synergies and trade-offs between defence traits are known for plants that are under attack by multiple organisms, few studies have attempted to measure correlations of defensive strategies using specific single attackers. Such links are hard to detect in natural populations because they are inherently confounded by the evolutionary history of different ecotypes. We therefore used a range of 20 maize inbred lines with considerable differences in resistance traits to determine if correlations exist between leaf and root resistance against pathogens and insects. Aboveground resistance against insects was positively correlated with the plant's capacity to produce volatiles in response to insect attack. Resistance to herbivores and resistance to a pathogen, on the other hand, were negatively correlated. Our results also give first insights into the intraspecific variability of root volatiles release in maize and its positive correlation with leaf volatile production. We show that the breeding history of the different genotypes (dent versus flint) has influenced several defensive parameters. Taken together, our study demonstrates the importance of genetically determined synergies and trade-offs for plant resistance against insects and pathogens.     

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.     

Dogs and Practices of Community and Neighboring

ABSTRACT

Dogs are important facilitators of social interaction. However, little attention has been given to the specific mechanisms through which these relations proceed, or to the ways that dogs help to broker, maintain, and even disrupt social relations. This paper addresses this absence through an indepth qualitative analysis of the everyday experiences of 24 dog owning households who live in apartments in Sydney, Australia. It shows that dogs encourage people to spend more time outside, make people recognizable within their neighborhood, provide a topic of conversation, and actively solicit the attention of strangers. Dogs help make people recognizable and identifiable to others, while also creating social distance. The paper connects to broader literature on neighboring and community practice to show that community relations shaped by dogs involve practices of inclusion as well as exclusion. Exclusion provides an important motivation for new community formation.     

Myosins and pathology: genetics and biology

This article summarizes current knowledge on the genetics and possible molecular mechanisms of Human pathologies resulted from mutations within the genes encoding several myosin isoforms. Mutations within the genes encoding some myosin isoforms have been found to be responsible for blindness (myosins III and VIIA), deafness (myosins I, IIA, IIIA, VI, VIIA and XV) and familial hypertrophic cardiomyopathy (beta cardiac myosin heavy chain and both the regulatory and essential light chains). Myosin III localizes predominantly to photoreceptor cells and is proved to be engaged in the vision process in Drosophila. In the inner ear, myosin I is postulated to play a role as an adaptive motor in the tip links of stereocilia of hair cells, myosin IIA seems to be responsible for stabilizing the contacts between adjacent inner ear hair cells, myosin VI plays a role as an intracellular motor transporting membrane structures within the hair cells while myosin VIIA most probably participates in forming links between neighbouring stereocilia and myosin XV probably stabilizes the stereocilia structure. About 30% of patients with familial hypertrophic cardiomyopathy have mutations within the genes encoding the beta cardiac myosin heavy chain and both light chains that are grouped within the regions of myosin head crucial for its functions. The alterations lead to the destabilization of sarcomeres and to a decrease of the myosin ATPase activity and its ability to move actin filaments.