David Long

Bio: David Long is an academic researcher from University College London. The author has contributed to research in topics: Physics & Coronal mass ejection. The author has an hindex of 49, co-authored 286 publications receiving 9270 citations. Previous affiliations of David Long include Wayne State University & Penn State Milton S. Hershey Medical Center.

A Seven-Transmembrane Domain Receptor Involved in Fusion and Entry of T-cell-tropic Human Immunodeficiency Virus Type 1 Strains

Abstract: Entry of human immunodeficiency virus type 1 (HIV-1) into cells requires binding to CD4 and fusion with a cellular membrane. Fusion does not occur in most nonhuman cells even when they express human CD4, indicating that one or more human accessory factors are required for virus infection. Recently, a seven-transmembrane domain protein has been shown to serve as an accessory factor for T-cell-tropic (T-tropic) HIV-1 isolates (Y. Feng, C. C. Broder, P. E. Kennedy, and E. A. Berger, Science 272:872-877, 1996). Here we show that expression of this glycoprotein, termed fusin, in murine, feline, simian, and quail cell lines, in conjunction with human CD4, rendered these cells fully permissive for HIV-1 envelope glycoprotein (Env)-mediated membrane fusion. Expression of CD4 or fusin alone did not permit fusion. In addition, introduction of fusin and CD4 into a human cell line, U87MG, that is resistant to HIV-1 induced syncytium formation and to infection by HIV-1 when expressing CD4 alone made this cell line permissive for Env-mediated cell-cell fusion. Fusion was observed only with T-tropic Env proteins. Macrophage-tropic (M-tropic) Env proteins from the SF162, ADA, and Ba-L HIV-1 strains did not fuse with cells expressing fusin and CD4, suggesting that M-tropic viruses utilize an accessory molecule other than fusin. Finally, coexpression of fusin and CD4 made both a murine and feline cell line susceptible to virus infection by T-tropic, but not M-tropic, HIV-1 strains.

Linking continental-slope failures and climate change: Testing the clathrate gun hypothesis

Abstract: It has been suggested that the release of clathrates rather than expansion of wetlands is the primary cause of the rapid increases observed in the ice-core atmospheric methane record during the Pleistocene. Because submarine sediment failures can involve as much as 5000 Gt of sediment and have the capacity to release vast quantities of methane hydrates, one of the major tests of the clathrate gun hypothesis is determining whether the periods of enhanced continental-slope failure and atmospheric methane correlate. To test the clathrate gun hypothesis, we have collated published dates for submarine sediment failures in the North Atlantic sector and correlated them with climatic change for the past 45 k.y. More than 70% by volume of continental-slope failures during the past 45 k.y. was displaced in two periods, between 15 and 13 ka and between 11 and 8 ka. Both these intervals correlate with rising sea level and peaks in the methane record during the Bolling-Allerod and Preboreal periods. These data support the clathrate gun hypothesis for glacial-interglacial transitions. The data do not, however, support the clathrate gun hypothesis for glacial millennial-scale climate cycles, because the occurrence of sediment failures correlates with Heinrich events, i.e., lows in sea level and atmospheric methane. A secondary use of this data set is the insight into the possible cause of continental-slope failures. Glacial-period slope failures occur mainly in the low latitudes and are associated with lowering sea level. This finding suggests that reduced hydrostatic pressure and the associated destabilization of gas hydrates may be the primary cause. The Bolling-Allerod sediment failures were predominantly low latitude, suggesting an early tropical response to deglaciation, e.g., enhanced precipitation and sediment load to the continental shelf or warming of intermediate waters. In contrast, sediment failures during the Preboreal period and the majority of the Holocene occurred in the high latitudes, suggesting either isostatic rebound–related earthquake activity or reduced hydrostatic pressure caused by isostatic rebound, causing destabilization of gas hydrates.

Cancer nanomedicine: progress, challenges and opportunities.

Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Membrane Technology and Applications

Abstract: Overview of membrane science and technology membrane transport theory membrane and modules concentration polarization reverse osmosis ultrafiltration microfiltration gas separation pervaporation ion exchange membrane processes - electrodialysis carrier facilitated transport medical applications of membranes other membranes processed.

Strategies in the design of nanoparticles for therapeutic applications

Abstract: Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

Abstract: The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells. There is evidence for another class of oncogenes, in which tumour-predisposing mutations are recessive to wild-type alleles. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb, assigned to the q14 band of human chromosome 13. Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours, almost half of which are osteosarcomas believed to be caused by the same mutation. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13q14, all or part of which is frequently deleted in retinoblastomas and osteosarcomas.

New methods of drug delivery.

Abstract: Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered.