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Mitochondria: are they the seat of senescence?   总被引:3,自引:0,他引:3  
Fridovich I 《Aging cell》2004,3(1):13-16
The frequently quoted figure for the fractional univalent reduction of oxygen to superoxide in mitochondria is certainly too high by at least one order of magnitude. This is so because the higher number (2%) was derived from mitochondria whose cytochrome c oxidase was blocked with cyanide. Nevertheless, even the more correct number (0.1%) means that the production of O(2)(-) and H(2)O(2) in mitochondria is large and apt to result in damage to macromolecules in spite of such defensive enzymes as superoxide dismutases and glutathione peroxidase. The data available for nematodes and flies provide a compelling case for the view that the accumulation of oxidative damage to specific mitochondrial proteins leads to the progressive dysfunction that we see as senescence. The data available from work with mammals are much weaker and do not yet allow a strong position to be taken.  相似文献   

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Plant hormone interactions: how complex are they?   总被引:4,自引:0,他引:4  
Models describing plant hormone interactions are often complex and web-like. Here we assess several suggested interactions within one experimental system, elongating pea internodes. Results from this system indicate that at least some suggested interactions between auxin, gibberellins (GAs), brassinosteroids (BRs), abscisic acid (ABA) and ethylene do not occur in this system or occur in the reverse direction to that suggested. Furthermore, some of the interactions are relatively weak and may be of little physiological relevance. This is especially true if plant hormones are assumed to show a log-linear response curve as many empirical results suggest. Although there is strong evidence to support some interactions between hormones (e.g. auxin stimulating ethylene and bioactive GA levels), at least some of the web-like complexities do not appear to be justified or are overstated. Simpler and more targeted models may be developed by dissecting out key interactions with major physiological effects.  相似文献   

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The concept of ecosystem health is derived from analogies with human health, which subsequently leads to the implication that the ecosystem has organismal properties, a 'superorganism' in the Clementsian sense. Its application and usefulness has been the subject of a contentious debate; yet, the term 'ecosystem health' has captured the public's imagination and woven its way into the current lexicon, even incorporated into public policy. However, the application of parasites as bioindicators of ecosystem health poses a curious conundrum. Perceptions of parasites range from mild distaste to sheer disgust among the general public, the media, environmental managers and non-parasitologists in the scientific community. Nevertheless, the biological nature of parasitism incorporates natural characteristics that are informative and useful for environmental management. The helminths in particular have evolved elegant means to ensure their transmission, often relying on complex life cycle interactions that include a variety of invertebrate and vertebrate hosts. The assemblage of these diverse parasites within a host organism potentially reflect that host's trophic position within the food web as well as the presence in the ecosystem of any other organisms that participate in the various parasite life cycles. Perturbations in ecosystem structure and function that affect food web topology will also impact upon parasite transmission, thus affecting parasite species abundance and composition. As such, parasite populations and communities are useful indicators of environmental stress, food web structure and biodiversity. In addition, there may be useful other means to utilise parasitic organisms based on their biology and life histories such as suites or guilds that may be effective bioindicators of particular forms of environmental degradation. The challenge for parasitology is to convince resource managers and fellow scientists that parasites are a natural part of all ecosystems, each species being a potentially useful information unit, and that healthy ecosystems have healthy parasites.  相似文献   

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The major classes of molecular chaperones have highly variable sequences, sizes, and shapes, yet they all bind to unfolded proteins, limit their aggregation, and assist in their folding. Despite the central importance of this process to protein homeostasis, it has not been clear exactly how chaperones guide this process or whether the diverse families of chaperones use similar mechanisms. For the first time, recent advances in NMR spectroscopy have enabled detailed studies of how unfolded, “client” proteins interact with both ATP-dependent and ATP-independent classes of chaperones. Here, we review examples from four distinct chaperones, Spy, Trigger Factor, DnaK, and HscA-HscB, highlighting the similarities and differences between their mechanisms. One striking similarity is that the chaperones all bind weakly to their clients, such that the chaperone–client interactions are readily outcompeted by stronger, intra- and intermolecular contacts in the folded state. Thus, the relatively weak affinity of these interactions seems to provide directionality to the folding process. However, there are also key differences, especially in the details of how the chaperones release clients and how ATP cycling impacts that process. For example, Spy releases clients in a largely folded state, while clients seem to be unfolded upon release from Trigger Factor or DnaK. Together, these studies are beginning to uncover the similarities and differences in how chaperones use weak interactions to guide protein folding.  相似文献   

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Spencer  A. N. 《Hydrobiologia》1991,216(1):565-571
A family of peptides with the carboxy-terminus Arg-Phe-amide has been localized to specific subpopulations of neurons in every cnidarian species examined. These neurons are typically sensory in character or are associated with smooth muscle. Although a transmitter role for these peptides has been suggested for anthozoans at neuromuscular synapses, no such evidence is available for hydrozoans. Instead there is evidence that RF-amides can be modulators of neuronal activity which takes the form of a biphasic (inhibitory then excitatory) response in vivo, while in vitro only the inhibitory response is seen. Voltage clamp studies of identified motor neurons showed large, transitory outward currents when Pol-RF-amide peptide was applied.  相似文献   

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Endometriosis is a chronic benign disease characterized by the presence of abnormally located tissue resembling the endometrium with glands and stroma. This disease has a high degree of morbidity due to chronic pelvic pain and infertility. The disease is likely to be polygenic and multifactorial, but the exact pathogenic mechanisms are still not entirely clear. Recently, adult stem cells have been identified in several tissues, including the endometrium. These cells are probably involved in the regenerative ability of the endometrial cycle, and also in the pathogenesis of proliferative gynaecological diseases, such as endometriosis. The identification of stem cells in animal and human tissues is very complex and the putative stem cells are supposed to be found through several assays such as clonogenicity, label-retaining cells, "side-population" cells, undifferentiation markers, and cellular differentiation. Bone marrow-derived stem cells transplanted into humans and animals have also been identified in eutopic endometrium and endometriotic implants. This review evaluates the available evidence regarding stem/progenitor cells in the human endometrium and explores the possible involvement of these cells in the etiology of endometriosis.  相似文献   

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Branchiobdellid annelids and their freshwater crayfish hosts are generally thought to have a commensal relationship. Branchiobdellids of the genus Cambarincola exploit their hosts through a variety of mechanisms; however, an effect of branchiobdellids on crayfish has not been conclusively demonstrated. We investigated whether branchiobdellids positively affect the host crayfish Cambarus chasmodactylus in the New River, North Carolina. In a laboratory experiment, we placed 0, 3, or 6 branchiobdellids on C. chasmodactylus and observed a significant effect of branchiobdellid presence on both growth and mortality of host crayfish; crayfish with branchiobdellids exhibited faster growth and lower mortality with increasing branchiobdellid density. A tracer experiment demonstrated that branchiobdellids feed on items found in the branchial chamber of C. chasmodactylus. We hypothesize that such feeding activity by branchiobdellids reduces fouling of crayfish gills by epibionts and particulate matter and could lead to the reduced mortality and increased growth rates observed in the laboratory experiment. Specifically, Cambarincola may improve the ventilatory and excretory fitness of C. chasmodactylus by cleaning gill filaments. Field data support this hypothesis by demonstrating that branchiobdellids are found disproportionately at sites proximal to the branchial chamber in the New River. This study provides evidence that the relationship between C. chasmodactylus and Cambarincola may be a cleaning symbiosis, at least in environments where gill fouling is a problem for C. chasmodactylus.  相似文献   

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Non-specific interactions in beta- and gamma-crystallins have been studied by solution X-ray scattering and osmotic pressure experiments. Measurements were carried out as a function of protein concentration at two ionic strengths. The effect of temperature was tested between 7 degrees C and 31 degrees C. Two types of interactions were observed. With beta-crystallin solutions, a repulsive coulombic interaction could be inferred from the decrease of the normalized X-ray scattering intensity near the origin with increasing protein concentration and from the fact that the osmotic pressure increases much more rapidly than in the ideal case. As was previously observed with alpha-crystallins, such behaviour is dependent upon ionic strength but is hardly affected by temperature. In contrast, with gamma-crystallin solutions, the normalized X-ray scattering intensity near the origin increases with increasing protein concentration and the osmotic pressure increases less rapidly than in the ideal case. Such behaviour indicates that attractive forces are predominant, although we do not yet know their molecular origin. Under our experimental conditions, the effect of temperature was striking whereas no obvious contribution of the ionic strength could be seen, perhaps owing to masking by the large temperature effect. The relevance of the different types of non-specific interactions for lens function is discussed.  相似文献   

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In this publication a review is presented based on the findings resulting from sleep-wake investigations searching for sleep disorders associated with insomnia in relatively healthy elderly. 44 Relevant journal articles published between 1980-1998 were found. The four most important sleep disorders which can be accompanied by sleeplessness in relatively healthy elderly people are periodic leg movements disorder (PLM), restless legs syndrome (RLS), REM sleep behaviour disorder (RBD) and sleep apnea syndrome (SAS). Of these disorders, sleep apnea and periodic leg movements occur most frequently, in a quarter of the elderly. The latter, however, seldom complain about sleeplessness. Within the category of older people disorders characterized by movements during sleep increase significantly with age, nightly respiration disorders do not. SAS, PLM and RBD appear most frequently in men and RLS in women. The disorders characterized by movements during sleep (especially RLS and RBD) are often accompanied by sleeplessness. SAS, however, is more closely associated with day-time sleepiness than with sleeplessness. No combination of demographic variables and symptoms allows a reliable prediction of these sleep disorders. Fortunately, these disorders are not a major threat to the health of older people.  相似文献   

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Understanding the consequences of elevated CO2 (eCO2; 800 ppm) on terrestrial ecosystems is a central theme in global change biology, but relatively little is known about how altered plant C and N metabolism influences higher levels of biological organization. Here, we investigate the consequences of C and N interactions by genetically modifying the N-assimilation pathway in Arabidopsis and initiating growth chamber and mesocosm competition studies at current CO2 (cCO2; 400 ppm) and eCO2 over multiple generations. Using a suite of ecological, physiological, and molecular genomic tools, we show that a single-gene mutant of a key enzyme (nia2) elicited a highly orchestrated buffering response starting with a fivefold increase in the expression of a gene paralog (nia1) and a 63% increase in the expression of gene network module enriched for N-assimilation genes. The genetic perturbation reduced amino acids, protein, and TCA-cycle intermediate concentrations in the nia2 mutant compared to the wild-type, while eCO2 mainly increased carbohydrate concentrations. The mutant had reduced net photosynthetic rates due to a 27% decrease in carboxylation capacity and an 18% decrease in electron transport rates. The expression of these buffering mechanisms resulted in a penalty that negatively correlated with fitness and population dynamics yet showed only minor alterations in our estimates of population function, including total per unit area biomass, ground cover, and leaf area index. This study provides insight into the consequences of buffering mechanisms that occur post-genetic perturbations in the N pathway and the associated outcomes these buffering systems have on plant populations relative to eCO2.  相似文献   

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Late-onset porphyrias: what are they?   总被引:1,自引:0,他引:1  
Porphyrias are inherited disorders of heme biosynthesis. ALA dehydratase porphyria (ADP) and congenital erythropoietic porphyria (CEP) are autosomal recessive porphyrias, and are typically expressed at birth or in childhood. However, a few cases of late-onset recessive porphyrias have been reported. Recently we encountered a late-onset ADP patient who developed symptoms of acute porphyria when he was 63 years old. This was accompanied by polycythemia vera. It was concluded that he developed the porphyria because an abnormal ALAD allele was clonally expanded by polycythemia vera. Upon reviewing the literature, a few cases of late-onset CEP were found to be also associated with hematologic abnormalities suggestive of myelodysplastic syndrome (MDS), another clonal disorder. These findings suggest that these late-onset porphyrias may be heterozygous for their gene defects, but clinical expression may be elicited if there is a loss of heterozygosity, either by a clonal expansion of the porphyric allele or by a loss of function mutation in the other allele.  相似文献   

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The essence (living or nonliving entities) of viruses has today become an aporia, i.e. a difficulty inherent in reasoning because they shared four fundamental characteristics with livings (multiplication, genetic information, mutation and evolution) without having the capacity to have an independent life. For much time, however, they were considered minuscule pathogenetic micro-organisms in observance of Koch and Pasteur's 'germ theory' albeit no microbiologist could show their existence except their filterability and pathogenetic action. Only some voices based on experimental results raised against this dogmatic view, in particular those of Beijerinck, Baur and Mrowka, without dipping effectively into the dominant theory. The discovery relative to their nucleoprotein nature made between 1934 and 1936 (Schlesinger as for the phage, and Bawden and co-operators as for Tobacco mosaic virus; TMV), together with the first demonstrations of their structures thanks to electron microscopy (from 1939 onwards) started on casting a new light on their true identity, which could be more clearly identified when, from 1955 onwards, phage and TMV proved to be decisive factors to understand the strategies of replication of the genetic material. Following the new knowledge, the theoretical view relative to viruses changed rather radically and the current view looks on these pathogenetic agents as nonliving aggregates of macromolecules provided with biological properties. There is, however, a current of thought, made explicitly by Lwoff that places viruses as compromise between living and non living and, perhaps, as primitive forms of life which have had great importance for the evolution of cellular life. At any rate, viruses are peculiar entities whose importance cannot be unacknowledged.  相似文献   

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Technological developments in municipal lighting are altering the spectral characteristics of artificially lit habitats. Little is yet known of the biological consequences of such changes, although a variety of animal behaviours are dependent on detecting the spectral signature of light reflected from objects. Using previously published wavelengths of peak visual pigment absorbance, we compared how four alternative street lamp technologies affect the visual abilities of 213 species of arachnid, insect, bird, reptile and mammal by producing different wavelength ranges of light to which they are visually sensitive. The proportion of the visually detectable region of the light spectrum emitted by each lamp was compared to provide an indication of how different technologies are likely to facilitate visually guided behaviours such as detecting objects in the environment. Compared to narrow spectrum lamps, broad spectrum technologies enable animals to detect objects that reflect light over more of the spectrum to which they are sensitive and, importantly, create greater disparities in this ability between major taxonomic groups. The introduction of broad spectrum street lamps could therefore alter the balance of species interactions in the artificially lit environment.  相似文献   

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