52 research outputs found
A 18p11.23-p11.31 microduplication in a boy with psychomotor delay, cerebellar vermis hypoplasia, chorioretinal coloboma, deafness and GH deficiency
Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin Ī±4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin Ī²1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo
Effects of penicillin and erythromycin on adherence of invasive and noninvasive isolates of Streptococcus pyogenes to laminin
The composition of the middle Miocene (15 Ma) Namling paleoflora, South Central Tibet, in the context of other Tibetan and Himalayan Floras
Molecular phylogeneticists often find that a diversification of western Chinese plant taxa took place in the Miocene and link this to the Neogene uplift of the Tibetan Plateau. This link is made despite abundant geological evidence showing that a high but topographically complex Tibet already existed in the Paleogene. To evaluate and constrain molecular phylogenetic trees and better understand Asian plant diversification requires accurate systematic assignment of well-dated plant megafossils. Here, as part of an ongoing programme of absolute dating and taxonomic evaluation of fossil floras across southwestern China and the Himalaya, we present a new and expanded systematic treatment of the late Miocene leaf flora from the Gazhacun Formation near the village of Wang b'dui in Namling County, central southern Tibet. This flora, whose age (15āÆMa) and paleoelevation (~ 5āÆkm) are well constrained, comprises 9 families, 13 genera and 25 species (including 22 new species). The paleoflora represents a typical boreal temperate mostly deciduous broad-leaved forest attesting to a cool humid climate. At the paleolatitude of the site, < 28āÆĀ°N, this is compatible with the high elevation (4700ā5200āÆm) for this part of Tibet quantified by both leaf physiognomy and isotopic analyses. Plant fossil evidence also witnesses a much wetter Tibetan upland environment before a rising Himalaya obstructed northward-moving moist air from the Indian Ocean
Effects of conformational activation of integrin alpha 1I and alpha 2I domains on selective recognition of laminin and collagen subtypes. ā Integrin alpha I domain activation
Collagen receptor integrins alpha 1 beta 1 and alpha 2 beta 1 can selectively recognize different collagen subtypes. Here we show that their alpha I domains can discriminate between laminin isoforms as well: alpha 1I and alpha 2I recognized laminin-111, -211 and -511, whereas their binding to laminin-411 was negligible. Residue Arg-218 in alpha1 was found to be instrumental in high-avidity binding. The gain-of-function mutation E318W makes the alpha 2I domain to adopt the "open" high-affinity conformation, while the wild-type alpha 2I domain favors the "closed" low-affinity conformation. The E318W mutation markedly increased alpha 2I domain binding to the laminins (-111, -211 and -511), leading us to propose that the activation state of the alpha 2 beta 1 integrin defines its role as a laminin receptor. However, neither wild-type nor alpha 2IE318W domain could bind to laminin-411. alpha 2IE318W also bound tighter to all collagens than alpha 2I wild-type, but it showed reduced ability to discriminate between collagens I, IV and IX. The corresponding mutation, E317A, in the alpha 1I domain transformed the domain into a high-avidity binder of collagens I and IV. Thus, our results indicate that conformational activation of integrin alpha 1I and alpha 2I domains leads to high-avidity binding to otherwise disfavored collagen subtypes
Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin Ī±4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin Ī²1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo
Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine.
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any specialized cell type of the human body, and therefore, ESC/iPSC-derived cell types offer great potential for regenerative medicine. However, key to realizing this potential requires a strong understanding of stem cell biology, techniques to maintain stem cells, and strategies to manipulate cells to efficiently direct cell differentiation toward a desired cell type. As nanoscale science and engineering continues to produce novel nanotechnology platforms, which inform, infiltrate, and impinge on many aspects of everyday life, it is no surprise that stem cell research is turning toward developments in nanotechnology to answer research questions and to overcome obstacles in regenerative medicine. Here we discuss recent advances in ESC and iPSC manipulation using nanomaterials and highlight future challenges within this area of research
Culturing functional pancreatic islets on Ī±5-laminins and curative transplantation to diabetic mice
The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on Ī±5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7āÆdays in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16āÆh. Transplantation of 110-150 mouse islets cultured on Ī±5-laminin-coated polydimethylsiloxane membranes for 3-7āÆdays normalized blood glucose already within 3āÆdays in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with Ī±5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes
- ā¦