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排序方式: 共有129条查询结果,搜索用时 15 毫秒
81.
Ediriweera PS Chandana Yasuhiro Maeda Akihiko Ueda Hiroshi Kiyonari Naoko Oshima Mako Yamamoto Shunya Kondo Junseo Oh Rei Takahashi Yoko Yoshida Satoshi Kawashima David B Alexander Hitoshi Kitayama Chiaki Takahashi Yasuhiko Tabata Tomoko Matsuzaki Makoto Noda 《BMC developmental biology》2010,10(1):1-13
Background
The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood.Results
We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region.Conclusion
We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution. 相似文献82.
René J van der Schaaf Bimmer E Claessen Loes P Hoebers Niels J Verouden Jacques J Koolen Maarten J Suttorp Emanuele Barbato Matthijs Bax Bradley H Strauss Göran K Olivecrona Vegard Tuseth Dietmar Glogar Truls Råmunddal Jan G Tijssen Jan J Piek José PS Henriques 《Trials》2010,11(1):1-9
Background
Hypothyroidism is a prevalent endocrine condition. Individuals with this disease are commonly managed through supplementation with synthetic thyroid hormone, with the aim of alleviating symptoms and restoring normal thyroid stimulating hormone levels. Generally this management strategy is effective and well tolerated. However, there is research to suggest that a significant proportion of hypothyroid sufferers are being inadequately managed. Furthermore, hypothyroid patients are more likely to have a decreased sense of well-being and more commonly experience constitutional and neuropsychiatric complaints, even with pharmacological intervention. The current management of hypothyroidism follows a biomedical model. Little consideration has been given to a biopsychosocial approach to this condition. Within the chiropractic profession there is growing support for the use of a biopsychosocial-based intervention called Neuro-Emotional Technique (NET) for this population.Methods/Design
A placebo-controlled, single-blinded, randomised clinical pilot-trial has been designed to assess the influence of Neuro-Emotional Technique on a population with primary overt hypothyroidism. A sample of 102 adults (≥18 years) who meet the inclusion criteria will be randomised to either a treatment group or a placebo group. Each group will receive ten treatments (NET or placebo) over a six week period, and will be monitored for six months. The primary outcome will involve the measurement of depression using the Depression, Anxiety and Stress Scale (DASS). The secondary outcome measures to be used are; serum thyroid stimulating hormone, serum free-thyroxine, serum free-triiodothyronine, serum thyroid peroxidase auto-antibodies, serum thyroglobulin auto-antibodies as well as the measurement of functional health and well-being using the Short-Form-36 Version 2. The emotional states of anxiety and stress will be measured using the DASS. Self-measurement of basal heart rate and basal temperature will also be included among the secondary outcome measures. The primary and secondary measures will be obtained at commencement, six weeks and six months. Measures of basal heart rate and basal temperature will be obtained daily for the six month trial period, with recording to commence one week prior to the intervention.Discussion
The study will provide information on the influence of NET when added to existing management regimens in individuals with primary overt hypothyroidism.Trial Registration
ANZCTR Number: 12607000040460 相似文献83.
Background
The human menstrual cycle is known to exhibit a significant amount of unexplained variability. This variation is typically dismissed as random fluctuations in an otherwise periodic and predictable system. Given the many delayed nonlinear feedbacks in the multiple levels of the reproductive endocrine system, however, the menstrual cycle can properly be construed as the output of a nonlinear dynamical system, and such a system has the possibility of being in a chaotic trajectory. We hypothesize that this is in fact the case and that it accounts for the observed variability. 相似文献84.
Gerry T. M. Wagenaar Pavel Uhrin Klara Weipoltshammer Marlene Almeder Pieter S. Hiemstra Margarethe Geiger Joost C. M. Meijers Christian Schöfer 《Journal of molecular histology》2010,41(1):27-37
Proteolysis of extracellular matrix is an important requirement for embryonic development and is instrumental in processes
such as morphogenesis, angiogenesis, and cell migration. Efficient remodeling requires controlled spatio-temporal expression
of both the proteases and their inhibitors. Protein C inhibitor (PCI) effectively blocks a range of serine proteases, and
recently has been suggested to play a role in cell differentiation and angiogenesis. In this study, we mapped the expression
pattern of PCI throughout mouse development using in situ hybridization and immunohistochemistry. We detected a wide-spread,
yet distinct expression pattern with prominent PCI levels in skin including vibrissae, and in fore- and hindgut. Further sites
of PCI expression were choroid plexus of brain ventricles, heart, skeletal muscles, urogenital tract, and cartilages. A strong
and stage-dependent PCI expression was observed in the developing lung. In the pseudoglandular stage, PCI expression was present
in distal branching tubules whereas proximal tubules did not express PCI. Later in development, in the saccular stage, PCI
expression was restricted to distal bronchioli whereas sacculi did not express PCI. PCI expression declined in postnatal stages
and was not detected in adult lungs. In general, embryonic PCI expression indicates multifunctional roles of PCI during mouse
development. The expression pattern of PCI during lung development suggests its possible involvement in lung morphogenesis
and angiogenesis. 相似文献
85.
Heemskerk B van Vreeswijk T Veltrop-Duits LA Sombroek CC Franken K Verhoosel RM Hiemstra PS van Leeuwen D Ressing ME Toes RE van Tol MJ Schilham MW 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(12):8851-8859
Human adenovirus (HAdV) infection is a frequent and potentially severe complication following allogeneic stem cell transplantation in children. Because treatment with antiviral drugs is often ineffective, adoptive transfer of donor-derived HAdV-specific T cells able to control viral replication of HAdV of multiple serotypes may be an option for therapy. In healthy donors, predominantly HAdV-specific T cells expressing CD4 are detected. In this study, a preclinical in vitro model was used to measure the antiviral effect of HAdV-specific CD4+ T cells. CD4+ HAdV-specific T cell clones restricted by HLA class II molecules were generated and most of these clones recognized conserved peptides derived from the hexon protein. These cross-reactive T cell clones were able to control viral replication of multiple serotypes of HAdV in EBV-transformed B cells (B-LCL), melanoma cells (MJS) and primary bronchial epithelial cells through cognate interaction. The HAdV-specific CD4+ T cell clones were able to specifically lyse infected target cells using a perforin-dependent mechanism. Antigenic peptides were also presented to the CD4+ T cell clones when derived from endogenously produced hexon protein. Together, these results show that cross-reactive HAdV-specific CD4+ T cells can control replication of HAdV in vitro and provide a rationale for the use of HAdV-specific T cells in adoptive immunotherapy protocols for control of life-threatening HAdV-infections in immunocompromised patients. 相似文献
86.
Nell MJ Tjabringa GS Wafelman AR Verrijk R Hiemstra PS Drijfhout JW Grote JJ 《Peptides》2006,27(4):649-660
New peptides for lipopolysaccharide (LPS) and lipoteichoic acid (LTA) neutralization in upper respiratory tract infections were developed and evaluated in terms of efficacy and safety for application in humans. Based on the sequence of the human antimicrobial peptide LL-37 we developed and investigated length variants, substitution analogues and modifications to stabilize the peptides to prevent enzymatic degradation and to improve efficacy. The most promising peptide appears P60.4, a 24 amino acid peptide with similar efficacy as LL-37 in terms of LPS and LTA neutralization and lower pro-inflammatory activity. In addition, the acetylated and amidated version of this peptide shows no toxicity and displays higher or equal antimicrobial activity compared to LL-37. 相似文献
87.
Julie A. Long Phillip H. Purdy Kees Zuidberg Sipke-Joost Hiemstra Sandra G. Velleman Henri Woelders 《Cryobiology》2014
Cryopreservation methods for poultry semen are not reliable for germplasm preservation, especially for turkeys, where fertility rates from frozen/thawed semen are particularly low. The objective was to evaluate cryopreservation methods for effectiveness in promoting cryosurvival and post-thaw function of sperm from five turkey lines: one commercial line and four research (RBC1; E; RBC2; F) lines from Ohio State University (OSU). The model for cryopreservation was set up as a 2 × 2 × 2 × 5 design for cryoprotectant (glycerol or dimethylacetamide (DMA)), cryopreservation medium (Lake or ASG), method of dilution (fixed dilution volume versus fixed sperm concentration) and turkey line, respectively. The final cryoprotectant concentrations were 11% glycerol or 6% DMA. Thawed sperm were evaluated for plasma membrane integrity and quality, motility, acrosome integrity and, after artificial insemination, for egg fertility and hatchability. Commercial turkey hens were used for all fertility trials, regardless of semen source. Turkey sperm frozen with glycerol exhibited higher membrane integrity and membrane quality upon thawing than turkey sperm frozen with DMA although no differences in total motility, and only minimal differences in progressive motility, were detected among the eight cryopreservation treatments. Within line, fertility was affected by cryoprotectant, medium and dilution method, where the overall highest percentages of fertile, viable embryos (Day 7) occurred for the DMA/ASG/fixed sperm concentration method, while high percentages (15.8–31.5%) of fertile, non-viable embryos (Day 1–6) were observed for multiple cryopreservation methods, including two glycerol treatments. From a single insemination, the duration of true and viable fertility in all lines was 10–13 weeks and 9–10 weeks, respectively. The duration of hatchability was 4–6 weeks after insemination for four of the turkey lines. The highest percentage of viable embryos was observed for the commercial line (9.5 ± 2.4%), followed by the E line (5.3 ± 1.3%), F line (3.7 ± 2.0%) and RBC2 line (2.6 ± 0.8%). For the RBC1 line, there was 100% embryonic death by Day 6 of incubation. Overall, better fertility results were obtained with the cryoprotectant DMA, the ASG diluent and fixed sperm concentration. However, the applicability of this method for preserving semen from research populations may be line dependent. 相似文献
88.
89.
Background
Identification of DNA-binding proteins is one of the major challenges in the field of genome annotation, as these proteins play a crucial role in gene-regulation. In this paper, we developed various SVM modules for predicting DNA-binding domains and proteins. All models were trained and tested on multiple datasets of non-redundant proteins. 相似文献90.
Núbia Boechat Alcione S Carvalho Kelly Salom?o Solange L de Castro Carlos F Araujo-Lima Francisco VC Mello Israel Felzenszwalb Claudia AF Aiub Taline Ramos Conde Helena PS Zamith Rolf Skupin Günter Haufe 《Memórias do Instituto Oswaldo Cruz》2015,110(4):492-499
Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and
cytotoxic properties have been attributed to the presence of the nitro group.
However, we synthesised nitroimidazoles with activity against the trypomastigotes of
Trypanosoma cruzi, but that were not genotoxic. Herein,
nitroimidazoles (11-19) bearing different substituent groups were investigated for
their potential induction of genotoxicity (comet assay) and mutagenicity
(Salmonella/Microsome assay) and the correlations of these
effects with their trypanocidal effect and with megazol were investigated. The
compounds were designed to analyse the role played by the position of the nitro group
in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable
groups at N-1 as an anion receptor group and the role of a methyl group at C-2.
Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to
those bearing NO2 at C-5. However, when there was a CH3
at C-2, the position of the NO2 group had no influence on the genotoxic activity.
Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3
at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl)
and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on
genotoxicity. This study contributes to the future search for new and safer
prototypes and provide. 相似文献