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1.
Mehnert KI Beramendi A Elghazali F Negro P Kyriacou CP Cantera R 《Developmental neurobiology》2007,67(4):415-421
In Drosophila melanogaster, as in most other higher organisms, a circadian clock controls the rhythmic distribution of rest/sleep and locomotor activity. Here we report that the morphology of Drosophila flight neuromuscular terminals changes between day and night, with a rhythm in synaptic bouton size that continues in constant darkness, but is abolished during aging. Furthermore, arrhythmic mutations in the clock genes timeless and period also disrupt this circadian rhythm. Finally, these clock mutants also have an opposing effect on the nonrhythmic phenotype of neuronal branching, with tim mutants showing a dramatic hyperbranching morphology and per mutants having fewer branches than wild-type flies. These unexpected results reveal further circadian as well as nonclock related pleiotropic effects for these classic behavioral mutants. 相似文献
2.
Much of the information about the function of D. melanogaster genes has come from P-element mutagenesis. The major drawback of the P element, however, is its strong bias for insertion into some genes (hotspots) and against insertion into others (coldspots). Within genes, 5′-UTRs are preferential targets. For the successful completion of the Drosophila Genome Disruption Project, the use of transposon vectors other than P will be necessary. We examined here the suitability of the Minos element from Drosophila hydei as a tool for Drosophila genomics. Previous work has shown that Minos, a member of the Tc1/mariner family of transposable elements, is active in diverse organisms and cultured cells; it produces stable integrants in the germ line of several insect species, in the mouse, and in human cells. We generated and analyzed 96 Minos integrations into the Drosophila genome and devised an efficient “jump-starting” scheme for production of single insertions. The ratio of insertions into genes vs. intergenic DNA is consistent with a random distribution. Within genes, there is a statistically significant preference for insertion into introns rather than into exons. About 30% of all insertions were in introns and ~55% of insertions were into or next to genes that have so far not been hit by the P element. The insertion sites exhibit, in contrast to other transposons, little sequence requirement beyond the TA dinucleotide insertion target. We further demonstrate that induced remobilization of Minos insertions can delete nearby sequences. Our results suggest that Minos is a useful tool complementing the P element for insertional mutagenesis and genomic analysis in Drosophila. 相似文献
3.
Pozidis C Chalkiadaki A Gomez-Serrano A Stahlberg H Brown I Tampakaki AP Lustig A Sianidis G Politou AS Engel A Panopoulos NJ Mansfield J Pugsley AP Karamanou S Economou A 《The Journal of biological chemistry》2003,278(28):25816-25824
Type III protein secretion (TTS) is catalyzed by translocases that span both membranes of Gram-negative bacteria. A hydrophilic TTS component homologous to F1/V1-ATPases is ubiquitous and essential for secretion. We show that hrcN encodes the putative TTS ATPase of Pseudomonas syringae pathovar phaseolicola and that HrcN is a peripheral protein that assembles in clusters at the membrane. A decahistidinyl HrcN derivative was overexpressed in Escherichia coli and purified to homogeneity in a folded state. Hydrodynamic analysis, cross-linking, and electron microscopy revealed four distinct HrcN forms: I, 48 kDa (monomer); II, approximately 300 kDa (putative hexamer); III, 575 kDa (dodecamer); and IV, approximately 3.5 MDa. Form III is the predominant form of HrcN at the membrane, and its ATPase activity is dramatically stimulated (>700-fold) over the basal activity of Form I. We propose that TTS ATPases catalyze protein translocation as activated homo-oligomers at the plasma membrane. 相似文献
4.
Kozower BD Christofidou-Solomidou M Sweitzer TD Muro S Buerk DG Solomides CC Albelda SM Patterson GA Muzykantov VR 《Nature biotechnology》2003,21(4):392-398
Vascular immunotargeting may facilitate the rapid and specific delivery of therapeutic agents to endothelial cells. We investigated whether targeting of an antioxidant enzyme, catalase, to the pulmonary endothelium alleviates oxidative stress in an in vivo model of lung transplantation. Intravenously injected enzymes, conjugated with an antibody to platelet-endothelial cell adhesion molecule-1, accumulate in the pulmonary vasculature and retain their activity during prolonged cold storage and transplantation. Immunotargeting of catalase to donor rats augments the antioxidant capacity of the pulmonary endothelium, reduces oxidative stress, ameliorates ischemia-reperfusion injury, prolongs the acceptable cold ischemia period of lung grafts, and improves the function of transplanted lung grafts. These findings validate the therapeutic potential of vascular immunotargeting as a drug delivery strategy to reduce endothelial injury. Potential applications of this strategy include improving the outcome of clinical lung transplantation and treating a wide variety of endothelial disorders. 相似文献
5.
BACKGROUND: Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. CASE PRESENTATION: A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. CONCLUSIONS: Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment. 相似文献
6.
In the light of experimental results showing significant forward centre of mass (CoM) displacements within the base of support,
this study investigated if whole body reaching movements can be executed whilst keeping the CoM fixed in the horizontal axis.
Using kinematic simulation techniques, angular configurations were recreated from experimental data imposing two constraints:
a constant horizontal position of the CoM and an identical trajectory of the hand to grasp an object. The comparison between
recorded and simulated trials showed that stabilisation of the CoM was associated with greater backward hip displacements,
which became more marked with increasing object distance. This was in contrast to recorded trials showing reductions in backward
hip displacements with increasing distance. Results also showed that modifications to angular displacements were necessary
only at the shoulder and hip joints, but that these modifications were within the limits of joint mobility. The analysis of
individual joint torques revealed that the pattern and timing of simulated trials were similar to those recorded experimentally.
Peak joint torque values showed particularly that keeping the CoM at a constant horizontal position resulted in significantly
smaller ankle peak flexor and extensor torques. It may be concluded from this study that `stabilising' the CoM during human
whole body reaching represents a feasible strategy, but not the one chosen by subjects under experimental conditions. Our
results also do not support the idea of the CoM as the stabilised reference value for the coordination between posture and
goal-directed movements.
Received: 22 September 1998 / Accepted in revised form: 2 June 1999 相似文献
7.
Renia Coghlan Elizabeth Gardiner Farhana Amanullah Chikwe Ihekweazu Rina Triasih Malgorzata Grzemska Charalambos Sismanidis 《PloS one》2015,10(10)
MethodologyExploratory assessments were carried out in Indonesia, Nigeria and Pakistan, reaching a range of facility types in two selected areas of each country. Record reviews and interviews of healthcare providers were carried out to assess numbers of unreported paediatric TB cases, diagnostic pathways followed and treatment regimens prescribed.
Main Findings
A total of 985 unreported diagnosed paediatric TB cases were identified over a three month period in 2013 in Indonesia from 64 facilities, 463 in Pakistan from 35 facilities and 24 in Nigeria from 20 facilities. These represent an absolute additional annualised yield to 2013 notifications reported to WHO of 15% for Indonesia, 2% for Nigeria and 7% for Pakistan. Only 12% of all facilities provided age and sex-disaggregated data. Findings highlight the challenges of confirming childhood TB. Diagnosis patterns in Nigeria highlight a very low suspicion for childhood TB. Providers note the need for paediatric medicines aligned to WHO recommendations.Conclusion: How Market Data Can Support Better Public Health Interventions
This study emphasises the impact of incomplete reporting on the estimation of disease burden and potential market size of paediatric TB medicines. Further studies on “hubs” (facilities treating large numbers of childhood TB cases) will improve our understanding of the epidemic, support introduction efforts for new treatments and better measure markets for new paediatric medicines. 相似文献8.
Developments in insect transgenesis using transposons combined with available mass rearing technology for insects such as
the Medfly, Ceratitis capitata, provide opportunity for the production of protein for industrial, agricultural and healthcare purposes on a very large scale.
In this study, we report the germ-line transformation and expression of a cDNA encoding human growth hormone (hGH) in transgenic
Drosophila using the Minos transposon. Production and secretion of a bioactive hGH into the haemolymph of transgenic larvae was demonstrated by immunoblot
analysis, ELISA and a proliferation bioassay. Stable expression of hGH was observed over 50 generations. The results indicate
that mass reared transgenic diptera with a rapid period of larval growth could provide cost effective production systems for
the manufacture of therapeutic and other high value proteins. 相似文献
9.
Codd V Dolezel D Stehlik J Piccin A Garner KJ Racey SN Straatman KR Louis EJ Costa R Sauman I Kyriacou CP Rosato E 《Genetics》2007,177(3):1539-1551
The circadian mechanism appears remarkably conserved between Drosophila and mammals, with basic underlying negative and positive feedback loops, cycling gene products, and temporally regulated nuclear transport involving a few key proteins. One of these negative regulators is PERIOD, which in Drosophila shows very similar temporal and spatial regulation to TIMELESS. Surprisingly, we observe that in the housefly, Musca domestica, PER does not cycle in Western blots of head extracts, in contrast to the TIM protein. Furthermore, immunocytochemical (ICC) localization using enzymatic staining procedures reveals that PER is not localized to the nucleus of any neurons within the brain at any circadian time, as recently observed for several nondipteran insects. However, with confocal analysis, immunofluorescence reveals a very different picture and provides an initial comparison of PER/TIM-containing cells in Musca and Drosophila, which shows some significant differences, but many similarities. Thus, even in closely related Diptera, there is considerable evolutionary flexibility in the number and spatial organization of clock cells and, indeed, in the expression patterns of clock products in these cells, although the underlying framework is similar. 相似文献
10.
Charalambos Litos Despina Hatzipanayioti Alexandra Lymberopoulou-Karaliota 《Inorganica chimica acta》2007,360(7):2321-2330
The gradual release of the ligand 3,4-dihydroxybenzoic acid (3,4-DHBA) from its molybdenum complex in the presence of ascorbic acid (AscA) in a weakly acidic aqueous solution (pH ∼ 3.5) is described. We observed that the formation of the 3,4-DHBA-semiquinone oxidation state and the semidehydroascorbate is a pre-requisite for the release of the 3,4-DHBA ligand. The interaction of these radicals leads at the same time to the further degradation of AscA resulting in, among other compounds, threonic acid which participates in the reaction with molybdenum. The comparison of the complexing ability indicated that threonic acid competes with protocatechuate, while ascorbic acid is a less good ligand for the Mo(VI). Solution studies on the reaction mechanism were performed by cyclic voltammetry, NMR spectroscopy and UV-Vis spectroscopy. Isolated precipitates were investigated by NMR spectroscopy. The antioxidant properties of 3,4-DHBA and AscA were also compared using the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). 相似文献