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Institution

Laboratory of Molecular Biology

FacilityCambridge, Cambridgeshire, United Kingdom
About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.
Topics: Gene, RNA, DNA, Population, Transcription (biology)


Papers
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Journal ArticleDOI
TL;DR: Findings indicate that the PEI/DNA complexes pass the capillary barrier in the lung, and linear PEI has promise as a vector for intravenous transfer of therapeutic genes.
Abstract: Generally, cationic vector-based intravenous delivery of DNA is hindered by interactions of positively charged complexes with serum proteins. However, if optimally formulated, cationic vectors can provide reasonable levels of transfection in the lung either by intravenous or intrapulmonary routes. We investigated the in vivo transfection capacity of a cationic polymer: linear, 22 kDa polyethylenimine. PEI/DNA complexes were formulated in 5% glucose and delivered into adult mice through the tail vein. Two marker genes were used, β-galactosidase and luciferase. High levels of luciferase expression (107 RLU/mg protein) were found in the lung when DNA was complexed with PEI at a ratio of 4 nitrogen equivalents per DNA phosphate. Lower levels of transfection were found in the heart, spleen, liver and kidney. Expression was dose- and time-dependent in all tissues examined. In the lung, β-galactosidase staining showed transgene expression in clusters of 10 or more pulmonary cells including the alveolar endothelium, squamous and great alveolar epithelial cells (type I and II pneumocytes) and septal cells. These findings indicate that the complexes pass the capillary barrier in the lung. Although the delivery mechanism requires elucidation, linear PEI has promise as a vector for intravenous transfer of therapeutic genes.

369 citations

Journal ArticleDOI
17 Oct 1996-Nature
TL;DR: It is found that overexpression of either construct mimics wingless phenotypes, thereby uncoupling changes in adhesion from signalling effects, and it is demonstrated that both constructs titrate Armadillo from a 'signalling' pool which is functionally distinct from the junctional pool.
Abstract: THE Wnt genes encode secreted glycoproteins used in intercellular communication at multiple steps during development. Signalling by Wingless, the Drosophila Wnt-1 homologue, requires the activity of Armadillo1,2, the homologue of vertebrate β-catenin3, which is a component of the cadherin/catenin complex at adherens junctions4,5. The genetic link between wingless and armadillo suggests that cell fate specification and cell–cell adhesion might be controlled concurrently. For instance, in one extreme view, Wingless could specify cell fate entirely by modulating cell adhesion. Alternatively, it might signal independently of adherens junctions. To distinguish between these alternatives, we have expressed two polypeptides that have opposite effects on cad-herin-dependent adhesion: full-length Drosophila E-cadherin and a dominant-negative truncated form. We found that overexpression of either construct mimics wingless phenotypes, thereby uncoupling changes in adhesion from signalling effects. We demonstrate that both constructs titrate Armadillo from a 'signalling' pool which is functionally distinct from the junctional pool.

369 citations

Journal ArticleDOI
TL;DR: It is demonstrated that, unlike wild-type and IL-4-/- mice, the IL-13-/- animals failed to clear N. brasiliensis infections efficiently, despite developing a robust Th2-like cytokine response to infection, and this observation may linkIL-13 with the production of intestinal mucus which is believed to facilitate worm expulsion.

369 citations

Journal ArticleDOI
TL;DR: In this review, the basis for an emerging consensus on how dynamin functions is presented, and three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamIn oligomer constricts in the presence of GTP; and third, dynam in catalyzes membrane fission upon GTP hydrolysis.
Abstract: The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion.

369 citations

Journal ArticleDOI
TL;DR: Observations indicate that entirely in vitro-generated neural precursors are able to respond to environmental signals guiding cell migration and differentiation and have the potential to reconstitute neuronal and glial lineages in the central nervous system.
Abstract: During embryogenesis, pluripotent stem cells segregate into daughter lineages of progressively restricted developmental potential. In vitro, this process has been mimicked by the controlled differentiation of embryonic stem cells into neural precursors. To explore the developmental potential of these cell-culture-derived precursors in vivo, we have implanted them into the ventricles of embryonic rats. The transplanted cells formed intraventricular neuroepithelial structures and migrated in large numbers into the brain tissue. Embryonic-stem-cell-derived neurons, astrocytes, and oligodendrocytes incorporated into telencephalic, diencephalic, and mesencephalic regions and assumed phenotypes indistinguishable from neighboring host cells. These observations indicate that entirely in vitro-generated neural precursors are able to respond to environmental signals guiding cell migration and differentiation and have the potential to reconstitute neuronal and glial lineages in the central nervous system.

368 citations


Authors

Showing all 19431 results

NameH-indexPapersCitations
Robert J. Lefkowitz214860147995
Ronald M. Evans199708166722
Tony Hunter175593124726
Marc G. Caron17367499802
Mark Gerstein168751149578
Timothy A. Springer167669122421
Harvey F. Lodish165782101124
Ira Pastan1601286110069
Bruce N. Ames158506129010
Philip Cohen154555110856
Gerald M. Rubin152382115248
Ashok Kumar1515654164086
Kim Nasmyth14229459231
Kenneth M. Yamada13944672136
Harold E. Varmus13749676320
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20239
202265
20211,222
20201,165
20191,082
2018945