Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis. Indeed, data obtained from genetic and genome association studies have implicated interactive contributions of genes controlling protein quality control and metabolism. For example, loss of key proteins that are responsible for clearance of dysfunctional mitochondria through a process called mitophagy has been found to cause PD, and a significant proportion of genes associated with PD encode proteins involved in the autophagy‐lysosomal pathway. In this review, we highlight the evidence for the targeting of mitochondria by proteotoxic, redox and metabolic stress, and the role autophagic surveillance in maintenance of mitochondrial quality. Furthermore, we summarize the role of α‐synuclein, leucine‐rich repeat kinase 2, and tau in modulating mitochondrial function and autophagy. Among the stressors that can overwhelm the mitochondrial quality control mechanisms, we will discuss 4‐hydroxynonenal and nitric oxide. The impact of autophagy is context depend and as such can have both beneficial and detrimental effects. Furthermore, we highlight the potential of targeting mitochondria and autophagic function as an integrated therapeutic strategy and the emerging contribution of the microbiome to PD susceptibility.
Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured
populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour
of a pest-controlling money spider,Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous
environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail,
in a process termed 'ballooning'. 相似文献
Summary In this collaborative European study, a total of 4871 cystic fibrosis (CF) chromosomes and 3539 normal chromosomes have been
characterized for the haplotypes defined by the 2 extragenic polymorphic sequences revealed by XV2c and KM19. The association
between one of these haplotypes (B haplotype) and the most frequent CF mutation, ΔF508, suggests for the latter a single origin
and a subsequent diffusion according to a South East-North West gradient. The linkage disequilibrium data between CF and the
B haplotype in different European populations are compatible with a relatively more recent appearance of the mutation in Northern
Europe whereas in Southern Europe a longer history of the same mutation would have allowed time for recombination with other
haplotypes. This model is also compatible with a selective advantage of carriers but does not account for (1) the excess of
B haplotypes observed among both normal and non-ΔF508 CF chromosomes; (2) the correlation between the B haplotype and the
severity of the phenotypic effect caused by CF mutations, as measured by pancreatic insufficiency and meconium ileus. 相似文献
Aqueous acetic acid was used to fix and store specimens of tissue prior to dissociation into nuclear suspensions for flow cytometric quantitation of DNA. The optimum concentration was 20 volumes of glacial acetic acid in 80 volumes of distilled water. Both neoplastic and benign nuclei were easily released from the fixed tissue blocks by slicing and shaking. Residual undissociated tissue was suitable for microscopic examination to confirm its identity. The nuclei fluoresced brightly after staining with propidium iodide, and yielded histograms similar to those from unfixed samples. Acetic-acid fixation resulted in slightly broader G1 and G0 peaks in the DNA histograms in comparison to unfixed cells, but fluorescent debris was less and correlation between the flow cytometric S-phase fraction (SPF) and in vitro thymidine labelling index (TLI) was better than with unfixed cells. Twenty-one of thirty-nine acetic-acid-fixed breast carcinomas had DNA indices in excess of 1.0 (increased nuclear DNA content in comparison to benign cells), and eighteen had DNA indices of 1.0 (normal or near-normal). The SPF was usually in excess of the TLI, but the two were significantly correlated (r = 0.72, P less than 0.0001). However, a significant correlation of SPF with TLI held only for the group with DNA index greater than 1.0. DNA indices greater than 1.0 were associated with high SPF and TLI, and high SPF and TLI each associated with low content of estrogen receptor. 相似文献
Citrus canker is a disease caused by Xantomonas citri subsp.citri (Xac), and has emerged as one of the major threats to the worldwide citrus crop because it affects all commercial citrus varieties,
decreases the production and quality of the fruits and can spread rapidly in citrus growing areas. In this work, the first
proteome of Xac was analyzed using two methodologies, two-dimensional liquid chromatography (2D LC) and tandem mass spectrometry (MS/MS). 相似文献
Mating plugs that males place onto the female genital tract are generally assumed to prevent remating with other males. Mating plugs are usually explained as a consequence of male-male competition in multiply mating species. Here, we investigated whether mating plugs also have collateral effects on female fitness. These effects are negative when plugging reduces female mating rate below an optimum. However, plugging may also be positive when plugging prevents excessive forced mating and keeps mating rate closer to a females' optimum. Here, we studied these consequences in the gonochoristic nematode Caenorhabditis remanei. We employed a new CO2-sedation technique to interrupt matings before or after the production of a plug. We then measured mating rate, attractiveness and offspring number.
Results
The presence of a mating plug did not affect mating rate or attractiveness to roving males. Instead, females with mating plugs produced more offspring than females without copulatory plugs.
Conclusions
Our experiment suggests that plugging might have evolved under male-male competition but represents a poor protection against competing males in our experiment. Even if plugging does not reduce mating rate, our results indicate that females may benefit from being plugged in a different sense than remating prevention. 相似文献
Interspecific comparisons of microsatellite loci have repeatedly shown that
the loci are longer and more variable in the species from which they are
derived (the focal species) than are homologous loci in other (nonfocal)
species. There is debate as to whether this is due to directional evolution
or to an ascertainment bias during the cloning and locus selection
processes. This study tests these hypotheses by performing a reciprocal
study. Eighteen perfect dinucleotide microsatellite loci identified from a
Drosophila simulans library screen and 18 previously identified in an
identical Drosophila melanogaster library screen were used to survey
natural populations of each species. No difference between focal and
nonfocal species was observed for mean PCR fragment length. However,
heterozygosity and number of alleles were significantly higher in the focal
species than in the nonfocal species. The most common allele in the
Zimbabwe population of both species was sequenced for 31 of the 36 loci.
The length of the longest stretch of perfect repeat units is, on average,
longer in the focal species than in the non-focal species. There is a
positive correlation between the length of the longest stretch of perfect
repeats and heterozygosity. The difference in heterozygosity can thus be
explained by a reduction in the length of the longest stretch of perfect
repeats in the nonfocal species. Furthermore, flanking-sequence length
difference was noted between the two species at 58% of the loci sequenced.
These data do not support the predictions of the directional-evolution
hypothesis; however, consistent with the ascertainment bias hypothesis, the
lower variability in nonfocal species is an artifact of the microsatellite
cloning and isolation process. Our results also suggest that the magnitude
of ascertainment bias for repeat unit length is a function of the
microsatellite size distribution in the genomes of different species.
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