1,721,007 research outputs found
Nek2 localises to the distal portion of the mother centriole/basal body and is required for timely cilium disassembly at the G2/M transition
No full textThe NIMA-related kinase Nek2 promotes centrosome separation at the G2/M transition and, consistent with this role, is known to be concentrated at the proximal ends of centrioles. Here, we show by immunofluorescence microscopy that Nek2 also localises to the distal portion of the mother centriole. Its accumulation at this site is cell cycle-dependent and appears to peak in late G2. These findings are consistent with previous data implicating Nek2 in promoting reorganisation of centrosome-anchored microtubules at the G2/M transition, given that microtubules are anchored at the subdistal appendages of the mother centriole in interphase. In addition, we report that siRNA-mediated depletion of Nek2 compromises the ability of cells to resorb primary cilia before the onset of mitosis, while overexpression of catalytically active Nek2A reduces ciliation and cilium length in serum-starved cells. Based on these findings, we propose that Nek2 has a role in promoting cilium disassembly at the onset of mitosis. We also present evidence that recruitment of Nek2 to the proximal ends of centrioles is dependent on one of its substrates, the centrosome cohesion protein C-Nap
Human embryo and early fetus research
No full textStudies of human embryos and fetuses have highlighted developmental differences between humans and model organisms. In addition to describing the normal biology of our own species, a justification in itself, studies of early human development have aided identification of candidate disease genes mapped by positional cloning strategies, understanding pathophysiology, where human disorders are not faithfully reproduced by models in other species, and, more recently, potential therapies based on human embryonic stem and embryonic germ cells. In this article, we review these applications. We also discuss when and how to study human embryo and early fetuses and some of the regulations of this researc
Developmental plasticity of human foetal femur-derived cells in pellet culture: self assembly of an osteoid shell around a cartilaginous core
Full text linkThis study has examined the osteogenic and chondrogenic differentiation of human foetal femur-derived cells in 3-dimensional pellet cultures. After culture for 21-28 days in osteogenic media, the pellets acquired a unique configuration that consisted of an outer fibrous layer, an osteoid-like shell surrounding a cellular and cartilaginous region. This configuration is typical to the cross section of the foetal femurs at the same age and was not observed in pellets derived from adult human bone marrow stromal cells. Time course study showed that after 7-14 days, the cells of the inner cellular region were viable, proliferated rapidly, and were immuno-positive for c-myc, as well as for bone sialoprotein and type I collagen. After 21-28 days, the cells accumulated at the inner edge of the osteoid shell. The direction of osteoid formation thus differed from that of periosteal bone formation. Following micro-dissection of the human foetal femurs into epiphyses, bone cylinder and hypertrophic cartilage, epiphyseal chondrocytes and osteoblasts both gave rise to osteoid-shell forming cells. These studies demonstrate the developmental plasticity of human foetal skeletal and epiphyseal chondrocytes and suggest that the microenvironment modulates lineage commitment and matrix formation. Furthermore, this ex vivo model offers a new approach to delineate human bone development as well as a model with potential application for evaluation of therapeutic compounds for bone formation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Characterisation of a novel gene on distal 11q as a potential candidate for Hypoplastic Left Heart Syndrome
No full textChronological expression of ciliated bronchial epithelim 1 in mouse and human pulmonary differentiation
No full textADAM33 in embryonic lungs
No full textRationale: ADAM33 is an asthma susceptibility gene with polymorphic variation that is strongly associated with asthma and bronchial hyperresponsiveness ( Van Eerdewegh et al. Nature 2002;418:426–30[CrossRef][Medline]). Single nucleotide polymorphisms (SNPs) in ADAM33 also predict impaired lung function in COPD ( van Diemen et al. Am J Respir Crit Care Med 2005;172:329–33[Abstract/Free Full Text]) and in young children ( Simpson et al. Am J Respir Crit Care Med 2005;172:55–60[Abstract/Free Full Text]). To study the link between maternal atopy and development of asthma, we postulated that ADAM33 is expressed during embryonic lung development and is affected by Th2 cytokines.Methods: Mouse lungs were harvested at embryonic day (ED) 11–19 and human embryonic lungs (HEL) (7–10 weeks) were collected following the Polkinghorne Committee guidelines after informed consent and ethical approval. Lung explants were cultured in vitro for 3–18 days±interleukin (IL)-13. Samples were processed for mRNA, protein, and image analysis.Results: ADAM33 mRNA increased during embryonic development in mouse and human lungs. ADAM33 splice variants were detected in HELs but the ß-isoform and the metalloprotease domain were rare. Western blotting confirmed the presence of multiple isoforms of ADAM33. Immunomicroscopy showed ADAM33 around alpha smooth muscle actin ({alpha}SMA) positive tubular structures within the undifferentiated mesenchyme. In vitro, ADAM33 and {alpha}SMA mRNA expression in ED12 lung explants cultured with IL-13 were increased after 48 hours (p = 0.015) and 72 hours (p = 0.026) compared with lungs cultured in medium alone. HELs cultured for 6, 12, and 18 days in the presence of IL-13 showed cystic phenotypic changes compared with medium alone.Conclusion: The expression of ADAM33 in developing embryonic lungs and its interaction with IL-13 suggests a key role in airway modelling that may contribute to the pathogenesis of chronic lung disease
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