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281.
Tagging and tracking individual networks within a complex mitochondrial web with photoactivatable GFP 总被引:5,自引:0,他引:5
Twig G Graf SA Wikstrom JD Mohamed H Haigh SE Elorza A Deutsch M Zurgil N Reynolds N Shirihai OS 《American journal of physiology. Cell physiology》2006,291(1):C176-C184
Assembly of mitochondria into networks supports fuel metabolism and calcium transport and is involved in the cellular response to apoptotic stimuli. A mitochondrial network is defined as a continuous matrix lumen whose boundaries limit molecular diffusion. Observation of individual networks has proven challenging in live cells that possess dense populations of mitochondria. Investigation into the electrical and morphological properties of mitochondrial networks has therefore not yielded consistent conclusions. In this study we used matrix-targeted, photoactivatable green fluorescent protein to tag single mitochondrial networks. This approach, coupled with real-time monitoring of mitochondrial membrane potential, permitted the examination of matrix lumen continuity and fusion and fission events over time. We found that adjacent and intertwined mitochondrial structures often represent a collection of distinct networks. We additionally found that all areas of a single network are invariably equipotential, suggesting that a heterogeneous pattern of membrane potential within a cell's mitochondria represents differences between discrete networks. Interestingly, fission events frequently occurred without any gross morphological changes and particularly without fragmentation. These events, which are invisible under standard confocal microscopy, redefine the mitochondrial network boundaries and result in electrically disconnected daughter units. membrane potential; fusion; fission; heterogeneity; green fluorescent protein; tetramethylrhodamine ethyl ester perchlorate 相似文献
282.
The spread of a contagious disease is often accompanied by a rise in awareness of those in the social vicinity of infected individuals, and a subsequent change in behaviour. Such reactions can manifest themselves in lower susceptibility as people try to prevent themselves from catching the disease, but also in lower infectivity because of self-imposed quarantine or better hygiene, shorter durations of infectiousness or longer immunity. We here focus on the scenario of an endemic disease of which members of the population can be either aware or unaware, and consider a broad set of possible reactions. We quantify the impact on the endemicity of a disease in a well-mixed population under the variation of different disease parameters as a consequence of growing awareness in the population. Applying a pair-closure scheme allows us to analyse the effect of local correlations if aware individuals tend to occur near infected cases, and to link this to the amount of overlap between the networks underlying the spread of awareness and disease, respectively. Lastly, we study the consequences on the dynamics when the pathogen and awareness spread at different velocities. 相似文献
283.
Genomic-level analyses of DNA from non-invasive sources would facilitate powerful conservation and evolutionary studies in natural populations of endangered and otherwise elusive species. However, the typical low quantity and poor quality of DNA that is extracted from non-invasive samples have generally precluded such work. Here we apply a modified DNA capture protocol that, when used in combination with massively-parallel sequencing technology, facilitates efficient and highly-accurate resequencing of megabases of specified nuclear genomic regions from fecal DNA samples. We validated our approach by comparing genetic variants identified from corresponding fecal and blood DNA samples of six western chimpanzees (Pan troglodytes verus) across more than 1.5 megabases of chromosome 21, chromosome X, and the complete mitochondrial genome. Our results suggest that it is now feasible to conduct genomic studies in natural populations for which constraints on invasive sampling have otherwise long been a barrier. The data we collected also provided an opportunity to examine western chimpanzee genetic diversity at unprecedented scale. Despite high mitochondrial genome diversity (π = 0.585%), western chimpanzees have a low ratio (0.42) of X chromosomal (π = 0.034%) to autosomal (chromosome 21 π = 0.081%) sequence diversity, a pattern that may reflect an unusual demographic history of this subspecies. 相似文献
284.
Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases. 相似文献
285.
Ori Segev Naomi Hill Alan R. Templeton Leon Blaustein 《Journal for Nature Conservation》2010,18(3):189-195
The fire salamander, Salamandra infraimmaculata, is listed as an endangered species in Israel and Israeli populations represent the genus’ worldwide southern-most limit. This endangered classification was based largely on limited mark-recapture data and on using the Lincoln index whose assumptions of equal catchability, time homogeneity and a closed population are unlikely kept for salamander populations. We estimated population size at five breeding sites in northern Israel – two permanent and three temporary breeding sites – for up to three years using a non-parametric procedure that allows the probabilities of recapture to vary both with time and with individual animal. We also compared breeding phenology and population size structure at these same sites. Population estimates at some breeding sites were larger than previously thought. Adult population size was not correlated with the size of the water body, but instead, sites with permanent water bodies had significantly larger populations. First arrival date to the breeding site of individuals on consecutive years was positively correlated at all sites suggesting that some individuals breed consistently early while others breed consistently late. Activity abundance was correlated with daily rainfall at a permanent site but not at an adjacent temporary site. Instead, activity abundance at the temporary breeding site was synchronised with pool inundation, which did not occur during the first rains. Males remained longer than females at all breeding sites. This study provides clear management implications both in terms of determining the vulnerability of specific populations, and in suggesting that permanent breeding sites are much more likely to support larger populations. 相似文献
286.
287.
Direct interaction between a myosin V motor and the Rab GTPases Ypt31/32 is required for polarized secretion 总被引:1,自引:1,他引:0
Lipatova Z Tokarev AA Jin Y Mulholland J Weisman LS Segev N 《Molecular biology of the cell》2008,19(10):4177-4187
Rab GTPases recruit myosin motors to endocytic compartments, which in turn are required for their motility. However, no Ypt/Rab GTPase has been shown to regulate the motility of exocytic compartments. In yeast, the Ypt31/32 functional pair is required for the formation of trans-Golgi vesicles. The myosin V motor Myo2 attaches to these vesicles through its globular-tail domain (GTD) and mediates their polarized delivery to sites of cell growth. Here, we identify Myo2 as an effector of Ypt31/32 and show that the Ypt31/32–Myo2 interaction is required for polarized secretion. Using the yeast-two hybrid system and coprecipitation of recombinant proteins, we show that Ypt31/32 in their guanosine triphosphate (GTP)-bound form interact directly with Myo2-GTD. The physiological relevance of this interaction is shown by colocalization of the proteins, genetic interactions between their genes, and rescue of the lethality caused by a mutation in the Ypt31/32-binding site of Myo2-GTD through fusion with Ypt32. Furthermore, microscopic analyses show a defective Myo2 intracellular localization in ypt31Δ/32ts and in Ypt31/32-interaction–deficient myo2 mutant cells, as well as accumulation of unpolarized secretory vesicles in the latter mutant cells. Together, these results indicate that Ypt31/32 play roles in both the formation of trans-Golgi vesicles and their subsequent Myo2-dependent motility. 相似文献
288.
Recovery of Streptococcus iniae from Diseased Fish Previously Vaccinated with a Streptococcus Vaccine 总被引:1,自引:0,他引:1
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Gilad Bachrach Amir Zlotkin Avshalom Hurvitz Donald L. Evans Avi Eldar 《Applied microbiology》2001,67(8):3756-3758
Streptococcus iniae was recovered from diseased rainbow trout (Oncorhynchus mykiss, Walbaum) previously vaccinated against streptococcosis. PCR and serological methods indicate the presence of a new serotype in the diseased fish. 相似文献
289.
Peter B. Johansen Yael Segev Daniel Landau Moshe Phillip Allan Flyvbjerg 《Experimental diabetes research》2003,4(2):73-81
The growth hormone (GH) and insulin-like growth factor
I (IGF-I) axis were studied in streptozotocin (STZ) diabetic
and nondiabetic female mice following intravenous
(IV) injection of the GH secretagogue (GHS) ipamorelin or
saline. On day 14, blood samples were obtained before and
10 minutes after the injection. Livers were removed and
frozen for determination of the mRNA expressions of the
GH receptor, GH-binding protein, and IGF-I, and hepatic
IGF-I peptide. Serum samples were analyzed for GH and
IGF-I. Following ipamorelin injection, the GH levels were
found to be 150 ± 35 μg/L and 62 ± 11 μg/L in the diabetic
compared to the nondiabetic mice (P < .05). Serum IGF-I
levels were lower in diabetic than in nondiabetic animals,
and rose after stimulation only in the nondiabetic animals.
Furthermore, hepatic GH resistance and IGF-I mRNA levels
and IGF-I peptide were increased in nondiabetic animals
in response to GH stimulation, whereas the low levels per se
of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial
part of the clinical features of type 1 diabetes in humans,
including GH hypersecretion and GH resistance. Accordingly,
it is proposed that STZ diabetic mice may be a better
model of the perturbations of the GH/IGF-I axis in diabetes
than STZ diabetic rats. 相似文献
290.
Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy
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Magen D Georgopoulos C Bross P Ang D Segev Y Goldsher D Nemirovski A Shahar E Ravid S Luder A Heno B Gershoni-Baruch R Skorecki K Mandel H 《American journal of human genetics》2008,83(1):30-42
Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration. 相似文献