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31.
The L RNA of three Lassa virus strains originating from Nigeria, Ghana/Ivory Coast, and Sierra Leone was sequenced and the data subjected to structure predictions and phylogenetic analyses. The L gene products had 2218-2221 residues, diverged by 18% at the amino acid level, and contained several conserved regions. Only one region of 504 residues (positions 1043-1546) could be assigned a function, namely that of an RNA polymerase. Secondary structure predictions suggest that this domain is very similar to RNA-dependent RNA polymerases of known structure encoded by plus-strand RNA viruses, permitting a model to be built. Outside the polymerase region, there is little structural data, except for regions of strong alpha-helical content and probably a coiled-coil domain at the N terminus. No evidence for reassortment or recombination during Lassa virus evolution was found. The secondary structure-assisted alignment of the RNA polymerase region permitted a reliable reconstruction of the phylogeny of all negative-strand RNA viruses, indicating that Arenaviridae are most closely related to Nairoviruses. In conclusion, the data provide a basis for structural and functional characterization of the Lassa virus L protein and reveal new insights into the phylogeny of negative-strand RNA viruses. 相似文献
32.
Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS 总被引:18,自引:0,他引:18
Storkebaum E Lambrechts D Dewerchin M Moreno-Murciano MP Appelmans S Oh H Van Damme P Rutten B Man WY De Mol M Wyns S Manka D Vermeulen K Van Den Bosch L Mertens N Schmitz C Robberecht W Conway EM Collen D Moons L Carmeliet P 《Nature neuroscience》2005,8(1):85-92
Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general. 相似文献
33.
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35.
Hubacek JA Stüber F Fröhlich D Book M Wetegrove S Rothe G Schmitz G 《Genes and immunity》2000,1(6):405-407
Sepsis is characterised by a systemic inflammatory response to bacterial products during infection, which interestingly both in humans and animal models is gender associated with a higher susceptibility of males than females. The CD14 receptor is involved in activation of cells by lipopolysaccharides released from Gram-negative bacteria and, as recently shown, also by products of Gram-positive bacteria (e.g., peptidoglycans and lipoteichoic acid). The functional relevance of a C(-159)T CD14 polymorphism recently has been shown based on correlation of the T allele to higher plasma levels of soluble CD14, and higher membrane expression on monocytes. We, therefore, now analysed this CD14 polymorphism in 204 patients with severe sepsis and 247 controls. No significant difference of allele frequencies was observed between sepsis patients and controls neither for males nor females. Mortality also was not associated with the polymorphism studied. This may suggest that other mechanisms for lipopolysaccharide recognition, such as the recently described Toll-like receptors are important for inflammatory cell activation in sepsis. 相似文献
36.
The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. 相似文献
37.
The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation 总被引:5,自引:0,他引:5
Wetzels AM; Bastiaans BA; Hendriks JC; Goverde HJ; Punt-van der Zalm AP; Verbeet JG; Braat DD 《Human reproduction (Oxford, England)》1998,13(5):1325-1330
In a human in-vitro fertilization (IVF) programme, the effect of co-
culture of embryos with human fibroblasts was evaluated with respect to
pregnancy rate and embryo development. Patients were included in the study
after giving informed written consent. The IVF treatments were randomly
assigned by stratification of both age (<36 versus > or =36 years)
and previous IVF attempts (yes versus no). After fertilization was
established, the zygotes were transferred to a 4-well dish with or without
fibroblasts and cultured for 2 days. On the third day after ovum pick-up
(OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were
scored and a maximum of three embryos was transferred. Supernumerary
embryos of good quality were cryopreserved. The design of this study was a
group sequential trial with the objective of detecting differences between
pregnancy rates following IVF with conventional incubation or incubation in
co-culture with fibroblasts. This design included one evaluation at
half-way data collection. In the study, 148 patients had an OPU, of whom 77
were allocated to the co-culture group. There was no statistically
significant difference in pregnancy rate, cell number and embryo quality
between the two groups. The ongoing pregnancy rate per embryo transfer was
27% in co-culture and 30% in the conventional culture group. The
implantation rates per transferred embryo were 17 and 18% respectively.
Using a multivariate logistic regression model for the probability of
ongoing pregnancies, the odds ratio of co-culture, adjusted for age and
previous IVF attempts, was not statistically significant. In conclusion,
co-culture with human fibroblasts does not contribute to an improvement of
embryo quality nor to a higher pregnancy rate after IVF in an unselected
group of patients.
相似文献
38.
Impairment of a cortical event-related desynchronisation during a bimanual load-lifting task in children with autistic disorder 总被引:1,自引:0,他引:1
In autism, the abilities of communication are affected, associated with abnormalities of cognitive, sensorial and motor development. In a previous study based on a load-lifting task, we showed impairment of anticipation in children with autism as evidenced by kinematics and eletromyographic recordings [Neurosci. Lett. 348 (2003) 17]. In the present study, we assessed the cortical counterparts of the use of anticipatory postural adjustments in a group of control children and in a group of children with autism. The tasks required maintaining a stable forearm position despite imposed or voluntary lifting of an object placed either on the controlateral forearm or on a support. We investigated the differences between the two groups of children on the Event-Related Desynchronisation (ERD) which precedes movement onset in adults [Electroencephalogr. Clin. Neurophysiol. 46 (1979) 138]. Electroencephalogram (EEG) power evolution of a 6-8-Hz frequency band was averaged before and after imposed or voluntary movement onset. EEG reactivity of control and autistic children did not differ during the imposed unloading condition, but significant differences appeared in the voluntary unloading situations. Before lifting the object, control children showed an ERD above the left motor areas. An ERD also occurred above the right motor areas when the object was placed on their forearm. This indicates that the ERD can also translate the use of anticipatory postural adjustments. By contrast, children with autism did not show an ERD in the two voluntary situations. This suggests a central deficit of anticipation in both postural and motor control in children with autism. 相似文献
39.
Endothelin receptor expression in human decidua 总被引:3,自引:1,他引:3
Kohnen G; Campbell S; Irvine GA; Church HJ; MacLachlan F; Titterington M; Cameron IT 《Molecular human reproduction》1998,4(2):185-193
The endothelins are signalling peptides that act via two receptors, ET(A)
and ET(B). In the human endometrium, endothelin receptors have been
demonstrated in glands and stroma and have been shown to vary during the
course of the menstrual cycle. The present study was undertaken to
determine whether or not expression of endothelin receptors changes during
pregnancy or after administration of exogenous progestagens. The expression
of the receptors was correlated with the appearance of basement membrane
components during decidualization of the endometrial stroma. Decidual
specimens (n = 15) were obtained during the first trimester of pregnancy
and 10 at term. Sixteen pairs of endometrial biopsies were obtained from
women with menorrhagia before and after exposure to exogenous progestagens.
A total of 15 hysterectomy specimens were used as controls for the
expression of stromal basement membrane proteins in the absence of
decidualization. Autoradiography was carried out with selective ligands for
ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of
ligand binding was then compared with the distribution of laminin alpha2
light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and
collagen IV were expressed in stromal decidual cells in the first trimester
of pregnancy. ET(B) was also found on endometrial glandular epithelium.
Quantitative macro-autoradiography and multiple regression analysis
demonstrated a highly significant positive correlation (P < 0.001)
between expression of ET(B) and laminin alpha2 light chain. In the third
trimester qualitative examination suggested a reduction of ET(A) in the
stroma. Progestagen-induced decidua exhibited a similar pattern to that
found in first trimester decidua. This study has demonstrated up-regulation
of ET(B) during the progesterone- dependent process of decidualization and
suggests a paracrine or autocrine role for endothelins in the decidua.
相似文献
40.
Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice 总被引:6,自引:0,他引:6 下载免费PDF全文
Rutten BP Van der Kolk NM Schafer S van Zandvoort MA Bayer TA Steinbusch HW Schmitz C 《The American journal of pathology》2005,167(1):161-173
Neuron and synapse loss are important features of the neuropathology of Alzheimer's disease (AD). Recently, we observed substantial age-related hippocampal neuron loss in APP751SL/PS1M146L transgenic mice but not in PS1M146L mice. Here, we investigated APP751SL mice, PS1M146L mice, and APP751SL/PS1M146L mice for age-related alterations in synaptic integrity within hippocampal stratum moleculare of the dentate gyrus (SM), stratum lucidum of area CA3 (SL), and stratum radiatum of area CA1-2 (SR) by analyzing densities and numbers of synaptophysin-immunoreactive presynaptic boutons (SIPBs). Wild-type mice, APP751SL mice and PS1M146L mice showed similar amounts of age-related SIPB loss within SM, and no SIPB loss within SL. Both APP751SL mice and PS1M146L mice showed age-related SIPB loss within SR. Importantly, APP751SL/PS1M146L) mice displayed the severest age-related SIPB loss within SM, SL, and SR, even in regions free of extracellular Abeta deposits. Together, these mouse models offer a unique framework to study the impact of several molecular and cellular events caused by mutant APP and/or mutant PS1 on age-related alterations in synaptic integrity. The observation of age-related SIPB loss within SR of PS1M146L mice supports a role of mutant PS1 in neurodegeneration apart from its contribution to alterations in Abeta generation. 相似文献