Causes and consequences of stress

Stress involves real or perceived changes within an organismin the environment that activate an organism's attempts to copeby means of evolutionarily ancient neural and endocrine mechanisms.Responses to acute stressors involve catecholamines releasedin varying proportion at different sites in the sympatheticand central nervous systems. These responses may interact withand be complemented by intrinsic rythms and responses to chronicor intermittent stressors involving the hypothalamic-pituitary-adrenalaxis. Varying patterns of responses to stressors are also affectedby an animal's assessment of their prospects for successfulcoping. Subsequent central and systemic consequences of thestress response include apparent changes in affect, motivation,and cognition that can result in an altered relationship toenvironmental and social stimuli. This review will summarizerecent developments in our understanding of the causes and consequencesof stress. Special problems that need to be explored involvethe manner in which ensembles of adaptive responses are assembled,how autonomic and neurohormonal reflexes of the stress responsecome under the influence of environmental stimuli, and how somespecific aspects of the stress response may be integrated intothe life history of a species.     

Causes and consequences of lymphatic disease

The visceral manifestations of lymphatic disorders (lymphangiomatosis and lymphangiectasia) are particularly severe. Any pathology of the lymphatic vasculature, whether superficial or internal, regional, or systemic, is predominated by the appearance of lymphedema, the characteristic form of tissue edema that occurs when lymphatic dysfunction supervenes. Disease manifestations may include dysregulation of body fluid homeostasis, immune traffic impairment, and disturbances of lipid and protein reabsorption from the gut lumen. The appearance of lymphatic edema invokes complex biological alterations. Many of these changes seem to relate uniquely to chronic lymphatic edema, including a profound stimulus to collagen and adipose deposition. Despite the recent advances in our understanding of these disorders, substantial knowledge gaps remain; these gaps inhibit our ability to accurately identify, categorize, treat, and prevent these diseases. Future diagnostic, therapeutic, and reproductive decisions for affected individuals require an accurate knowledge of the clinical and laboratory presentation, mode of inheritance, treatment response, outcomes, and prognosis.     

Causes and consequences of plant-associated biofilms

The rhizosphere is the critical interface between plant roots and soil where beneficial and harmful interactions between plants and microorganisms occur. Although microorganisms have historically been studied as planktonic (or free-swimming) cells, most are found attached to surfaces, in multicellular assemblies known as biofilms. When found in association with plants, certain bacteria such as plant growth promoting rhizobacteria not only induce plant growth but also protect plants from soil-borne pathogens in a process known as biocontrol. Contrastingly, other rhizobacteria in a biofilm matrix may cause pathogenesis in plants. Although research suggests that biofilm formation on plants is associated with biological control and pathogenic response, little is known about how plants regulate this association. Here, we assess the biological importance of biofilm association on plants.     

Causes and consequences of Robertsonian exchange

At least two types of Robertsonian exchange are now known in the acrocentric chromosomes of man. Both types involve breakage in the arms adjacent to the centromere. Evidence is presented for a third type of exchange, one involving breakage within the centromere itself, in the grasshopper Percassa rugifrons. In this species, which is regularly homozygous for a single fusion metacentric, the eighteen rod autosomes have small but pronounced granules at the centric end of the chromosome. When C-banded these granules show differential Giemsa staining and appear to represent centromeric chromomeres; these chromomeres are lacking in the metacentric fusion product. Equivalent fusions may have occurred in some mammal species too and possible examples of this are discussed in sheep and mice. The Percassa fusion has led to a modification in both the frequency and the distribution of chiasmata as judged by a comparison of these properties in the metacentric relative to the two next smallest rod equivalents. Comparable modifications are known to occur in other naturally occurring fusions but these changes are certainly not automatic consequences of fusion since they are not shown in at least some newly produced fusion mutants.     

Bias in normalization: Causes,consequences, detection and remedies

Introduction Normalization is an optional step in LCIA that is used to better understand the relative importance and magnitude of the impact category indicator results. It is used for error checking, as a first step in weighting, and for standalone presentation of results. A normalized score for a certain impact category is obtained by determining the ratio of the category indicator result of the product and that of a reference system, such as the world in a certain year or the population of a specific area in a certain year. Biased Normalization In determining these two quantities, the numerator, the denominator, or both can suffer from incompleteness due to a lack of emission data and/or characterisation factors. This leads to what we call a biased normalization. As a consequence. the normalized category indicator result can be too low or too high. Some examples from hypothetical and real case studies demonstrate this. Consequences of Biased Normalization Especially when for some impact categories the normalized category indicator result is right, for others too low, and for others too high, severe problems in using normalized scores can show up. It is shown how this may affect the three types of usage of normalized results: error checking, weighting and standalone presentation. Detection and Remedies of Biased Normalization Some easy checks are proposed that at least alert the LCA practitioner of the possibility of a biased result. These checks are illustrated for an example system on hydrogen production. A number of remedies of this problem is possible. These are discussed. In particular, casedependent normalization is shown to solve some problems, but on the expense of creating other problems. Discussion It appears that there is only one good solution: databases and tables of characterisation factors must be made more completely, so that the risk of detrimental bias is reduced. On the other hand, the use of the previously introduced checks should become a standard element in LCA practice, and should be facilitated with LCA software. ESS-Submission Editor: Duane A. Tolle (tolled@battelle.org)     

Dyslipidemia in renal disease: Causes,consequences and treatment

The prevalence of chronic renal insufficiency and its complications, including dyslipidemia, is increasing. Although the characteristics of dyslipidemia in chronic renal insufficiency and its pathophysiology are well known, its cardiovascular and renal impact and the most effective therapeutic approach are poorly defined.     

Causes and consequences of aneuploidy in cancer

Genetic instability, which includes both numerical and structural chromosomal abnormalities, is a hallmark of cancer. Whereas the structural chromosome rearrangements have received substantial attention, the role of whole-chromosome aneuploidy in cancer is much less well-understood. Here we review recent progress in understanding the roles of whole-chromosome aneuploidy in cancer, including the mechanistic causes of aneuploidy, the cellular responses to chromosome gains or losses and how cells might adapt to tolerate these usually detrimental alterations. We also explore the role of aneuploidy in cellular transformation and discuss the possibility of developing aneuploidy-specific therapies.     

Causes and consequences of centrosome abnormalities in cancer

Centrosome amplification is a hallmark of cancer. However, despite significant progress in recent years, we are still far from understanding how centrosome amplification affects tumorigenesis. Boveri''s hypothesis formulated more than 100 years ago was that aneuploidy induced by centrosome amplification promoted tumorigenesis. Although the hypothesis remains appealing 100 years later, it is also clear that the role of centrosome amplification in cancer is more complex than initially thought. Here, we review how centrosome abnormalities are generated in cancer and the mechanisms cells employ to adapt to centrosome amplification, in particular centrosome clustering. We discuss the different mechanisms by which centrosome amplification could contribute to tumour progression and the new advances in the development of therapies that target cells with extra centrosomes.     

Causes and consequences of biological diversity in soil

There is a vast diversity of organisms that live in the soil, and the activities of the total soil biota, together with the diverse forms and functions of plant roots, have critical roles in soil functioning. In this paper I discuss the likely determinants of soil diversity and also comment on recent studies that have explored whether or not there is a relationship between soil organism diversity and ecosystem function. There is little evidence to suggest that soil diversity is regulated in a predicable fashion by competition or disturbance; rather it is attributed to the nature of the soil environment, in that soil offers an extremely heterogeneous habitat, both spatially and temporally, proving unrivalled potential for niche partitioning, or resource or habitat specialisation, thereby enabling co-existence of species. Most evidence that is available suggests that there is no predictable relationship between diversity and function in soils, and that ecosystem properties are governed more by individual traits of dominant species, and by the extraordinary complexity of biotic interactions that occur between components of soil food webs. There is evidence of redundancy in soil communities with respect to soil functions, but the scale of effect of changes in soil diversity on process rates depends on which species are removed from the community and the degree to which remaining species can compensate. As in aboveground communities, therefore, it would appear that species traits and changes in species composition, and alterations in the nature of the many important species interactions that occur in soil, are likely to be the main biotic control of ecosystem function. In view of this, consideration of these important biotic interactions and their sensitivity to environmental change must be a key priority for future research.     

Isolated hepatocytes - past, present and future

The first technique for large-scale preparation of isolated hepatocytes was described in 1953 and involved perfusion of rat liver under pressure with a Ca2+-free solution containing a chelating agent. Various modifications of this technique were in use over the next ten years, until it was demonstrated that cells prepared in this manner were grossly damaged, losing most of their cytoplasmic enzymes during the preparative procedure. The successful preparation of intact isolated hepatocytes by collagenase-treatment of liver was achieved in 1967, and the widespread use of intact hepatocyte suspensions was accelerated by the development soon after of high-yield preparative techniques involving perfusion of the liver with a medium containing collagenase.The introduction of the isolated hepatocyte preparation has enabled experimental studies that otherwise would not be feasible. Important advances have been the use of cultured hepatocytes, frequently of human origin, for the investigation of the metabolism and toxicology of potential therapeutic agents. Success in this field has been achieved through the steady improvement in techniques for the maintenance in culture of differentiated hepatocytes, and in particular their cytochrome P450 complexes. Another area showing considerable promise is the employment of hepatocytes, generally from a porcine source, in temporary support systems for patients with acute liver failure. Our own studies have concentrated on the demonstration of long-range interactions between hepatocyte compartments which suggest that energy transfer between cell compartments can take place without ATP turnover.     

Causes and consequences of the evolution of reproductive proteins

Proteins involved in reproduction often evolve rapidly, raising the possibility that changes in these proteins contribute to reproductive isolation between species. We review the evidence for rapid and adaptive change in reproductive proteins in animals, focusing on studies in recently diverged vertebrates. We identify common patterns and point out promising directions for future research. In particular, we highlight the ways that integrating the different but complementary approaches of evolutionary and developmental biology will provide new insights into fertilization processes.     

Causes and consequences of oscillations in the cerebellar cortex

Cerebellar high-frequency oscillations have been observed for many decades, but their underlying mechanisms have remained enigmatic. In this issue of Neuron, two papers indicate that specific intrinsic mechanisms in the cerebellar cortex contribute to the generation of these oscillations. Middleton et al. show that GABA(A) receptor activation and nonchemical transmission are required for nicotine-dependent oscillations at 30-80 Hz and 80-160 Hz, respectively, while de Solages et al. provide evidence that recurrent inhibition by Purkinje cells is essential for oscillations around 200 Hz.     

Causes and consequences of excess resistance in cryptobiotic metazoans

Despite more than 200 yr of recognition that some microscopic metazoans survive environmental conditions far beyond those experienced in nature while in a cryptobiotic state, this phenomenon has received little attention from evolutionary biologists. The excess environmental resistance exhibited by cryptobiotic organisms cannot be viewed as an adaptation within current evolutionary biology. Rather, excess resistance may have evolved as a by-product of natural selection for tolerance to desiccation or other naturally occurring environmental agents. The combined effects of desiccation, metabolic arrest, effective stabilization of dry or frozen cells by protectant molecules, and efficient DNA repair mechanisms may have led to a protection of the organism against conditions far beyond those experienced in nature.     

Causes and consequences of monodominance in tropical lowland forests

Tropical canopy dominance in lowland, well-drained forests by one plant species is a long-standing conundrum in tropical biology. Research now shows that dominance is not the result of one trait or mechanism. We suggest that the striking dominance of Gilbertiodendron dewevrei in the Ituri Forest of northeastern Congo is the result of a number of traits in adult trees that significantly modify the understory environment, making it difficult for other species to regenerate there. Adults cast deep shade that reduces light levels in the understory of the Gilbertiodendron forest to levels significantly lower than in the mixed-species forest. Moreover, the monodominant forest has deep leaf litter that could inhibit the establishment of small-seeded species, and the leaf litter is slow to decompose, potentially causing the low availability of nitrogen. We expect that juveniles of Gilbertiodendron may have an advantage in this environment over other species. In general, it appears that all tropical monodominant species share a similar suite of traits.     

Causes and consequences of tumour acidity and implications for treatment

Tumour cells have a lower extracellular pH (pHe) than normal cells; this is an intrinsic feature of the tumour phenotype, caused by alterations either in acid export from the tumour cells or in clearance of extracellular acid. Low pHe benefits tumour cells because it promotes invasiveness, whereas a high intracellular pH (pHi) gives them a competitive advantage over normal cells for growth. Molecular genetic approaches have revealed hypoxia-induced coordinated upregulation of glycolysis, a potentially important mechanism for establishing the metabolic phenotype of tumours. Understanding tumour acidity opens up new opportunities for therapy.