Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lecture”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources
PubMed1999

Colworth Medal Lecture. Enzymes in the quantum world.

Studies on those enzymes and electron-transfer proteins involved in the catabolism of 'C1' substrates in methylotrophic bacteria have provided a wealth of information concerning the transfer of electrons and hydrogen by quantum tunnelling mechanisms. With regard to H-transfer, studies with MADH have provided the first example of ground-state tunnelling of hydrogen driven by the natural, thermally activated, low-frequency motions of the enzyme molecule. Subsequent studies with related enzymes (e.g. TMADH and bacterial sarcosine oxidase) and with thermophilic alcohol dehydrogenase suggest that vibrationally assisted tunnelling of hydrogen may be more widespread than originally assumed. Our studies of electron transfer in TMADH and ETF have established a role for large-scale protein dynamics in interprotein electron transfer, and have made a contribution to the ongoing debate concerning the mechanism of amine oxidation by enzymes. Moreover, our work has identified a hitherto unknown mechanism for the control of electron density in reduced flavin that influences the rate of electron transfer between redox centres within a protein molecule. Despite this progress, however, many questions still remain to be resolved. With the development of more sophisticated experimental techniques (and also continued financial support from the funding agencies!), the mechanistic uncertainties surrounding the quantum mechanical transfer of electrons and hydrogen in biological molecules should be transmogrified into the certainties one more readily acquaints with the classical world.

Catalytic Domain↗
PubMed2002

Novartis Medal Lecture. Antibodies: a paradigm for the evolution of molecular recognition.

Novel proteins have been elaborated over evolutionary time by an iterative alternation of mutation and selection. In a similar way, the humoral immune system also uses an iterative alternation of mutation and selection to generate novel antibodies that display a high affinity for their cognate antigen -- but this is achieved in a matter of a days. Gene rearrangement is used to produce a primary repertoire of antibodies and, on entering the body, antigen triggers the clonal expansion of those B lymphocytes that express a cognate antibody, albeit one of low affinity. Rapid and specific affinity maturation is then achieved by subjecting the immunoglobulin genes in the rapidly expanding B cells to a period of intense mutation. The intensity of this mutational assault is tolerated because it is targeted specifically to the immunoglobulin genes, causing relatively little damage to other loci. Antigen-mediated selection then allows the preferential expansion of those mutants expressing antibodies displaying improved binding characteristics. Here, studies are described that have been performed to glean insight into the mechanisms of the hypermutation and selection processes. Experiments are also described in which an attempt has been made to recapitulate aspects of physiological antibody generation in vitro, allowing the development of novel approaches to the generation of proteins with high-affinity binding sites.

Antibodies↗
PubMed2003

Biochemical Society Special Lecture. Nitrate- and nitrite-responsive sensors NarX and NarQ of proteobacteria.

Nitrate and nitrite are efficient respiratory oxidants for anaerobic growth. In Escherichia coli, the homologous nitrate reductase (Nar) two-component regulatory systems NarX-NarL and NarQ-NarP collaborate to control anaerobic respiratory gene expression in response to nitrate and nitrite. Several other species classified in the gamma and beta subdivisions of the proteobacteria contain only a single Nar two-component regulatory pair. This raises questions concerning the physiology of anaerobic respiration as well as the evolution, function and cross-regulation of two-component regulatory systems. Here, I focus on the sensor histidine kinases NarX and NarQ, and present a comparison of the deduced NarX and NarQ primary sequences from a broad sampling of proteobacteria. This comparison defines shared features, including a large central region of unknown function that appears to be unique to this family of sensor kinases. I then consider the phylogenetic distribution of narX and narQ genes in relation to anaerobic respiratory enzyme repertoire and physiological function. One noteworthy observation is that narXL genes are specifically associated with the structural genes for membrane-bound nitrate reductase, narGHJI, whereas organization and linkage of the narQ and narP genes is quite variable. I conclude with some speculative thoughts on the evolutionary and functional divergence of the NarX-NarL and NarQ-NarP regulatory systems. Overall, this analysis aims to provide a basis for future hypothesis and experimentation in this area.

Amino Acid Sequence↗
PubMed2003

Morton Medal Lecture. New insights into the roles of phosphoinositides and inositol polyphosphates in yeast.

During the past half century, we have progressed from simply viewing myo -inositol-containing glycerophospholipids as quantitatively minor membrane constituents to the present, very striking, situation in which more and more important cellular functions are being assigned to a plethora of phosphorylated derivatives of inositol and phosphatidylinositol. Two such examples are discussed briefly: the activation by environmental stresses of the single phosphoinositidase C of yeast, which is related to the phospholipase C delta s of other eukaryotes, and the involvement of PtdIns(3,5) P (2) in endomembrane trafficking.

Enzyme Activation↗
PubMed2003

Wellcome Trust Award Lecture. Chromatin-modifying enzymes in transcription and cancer.

In recent years, our view of how gene expression is controlled has changed dramatically. The discovery of enzymes that modify histones has revealed that transcription is an enzymically driven process. Such modifications can recruit specific proteins and mediate chromatin changes that affect transcription either positively or negatively. Important biological pathways leading to cell proliferation are under the control of these enzymes, and several of them are found deregulated in cancer. The hope is that chromatin-modifying enzymes will be a rich source of targets for drug discovery.

Acetylesterase↗
PubMed1998

Why do people change addictive behavior? The 1996 H. David Archibald Lecture.

Although there are specialty journals and professions focusing on addictions treatment, the reasons why people change addictive behaviors are still not well understood. The simplistic account that people change because they receive treatment is wanting in many ways. Many people who recover do so without formal treatment. Even relatively brief interventions seem to trigger change, and the dose of treatment delivered is surprisingly unrelated to outcomes. Client compliance with many different approaches, including placebo medication, has been linked to better outcomes. Client outcomes also vary widely depending upon the therapist who delivers treatment. Various models are briefly considered that may help in understanding this intriguing puzzle of change.

Behavior, Addictive↗
PubMed1999

Drug anticipation and drug addiction. The 1998 H. David Archibald Lecture.

Environmental cues associated with drug use become capable of eliciting withdrawal symptoms, craving and relapse to drug self-administration. The phenomenon, although noted almost 150 years ago, has repeatedly been confirmed in epidemiological and experimental studies. Drug tolerance, which is closely correlated with withdrawal symptoms and craving, is also modulated by drug-associated environmental cues. The contribution of predrug cues to withdrawal and tolerance is emphasized in a Pavlovian conditioning analysis of drug administration. Drug-induced disturbances are modulated by homeostatic responses elicited by pharmacological stimulation. According to the conditioning analysis, we learn to anticipate the drug effect; corrective response (conditional compensatory responses) occur in the presence of situations and events that have been associated with the drug in the past. These conditional responses, seen in anticipation of drugs, importantly contribute to drug tolerance, failures of tolerance (enigmatic overdoses), and withdrawal symptoms. I review evidence indicating that a complete analysis of drug withdrawal and tolerance requires an appreciation of the contribution of Pavlovian conditioning.

Conditioning, Classical↗
PubMed2003

The Neil Smith Memorial Lecture: John Laws Milton. The Founder of St John's Hospital for Diseases of the Skin.

John Laws Milton, a 19th-Century surgeon, founded the St John's Hospital for Diseases of the Skin close to Leicester Square in London in 1863. This article reviews his single-minded effort to establish dermatology as a medical subspeciality and to create a proper skin diseases hospital. The review also details his many contributions to the medical and dermatological literature, including his insightful description of the pregnancy dermatosis, herpes (pemphigoid) gestationis.

Dermatology↗