Is it functional?

This report describes the first scientific meeting of the British Society for Proteome Research (BSPR), which was organised jointly with the European Bioinformatics Institute (EBI) and held in July 2004. The focus of the conference was functional proteomics with an emphasis on possible clinical application. The main subjects described here are: the need to simplify samples, the use of biological fluids versus tissue, consideration of biological and experimental variation and the creation of databases to achieve meaningful functional analysis.     

Telomerase in T lymphocytes: use it and lose it?

The enzyme telomerase counteracts telomere loss in proliferating cells and extends their capacity for replication. The importance of telomerase is highlighted by the award of the 2006 Albert Lasker Prize for Basic Medical Research for its discovery. Malignant cells subvert telomerase induction to their advantage, and up-regulation of this enzyme confers these populations with unlimited proliferative potential with obvious detrimental consequences. However this enzyme is also essential for the lifelong maintenance of normal cell populations that have a high rate of turnover. Thymic involution in early adulthood dictates that memory T cell populations have to be maintained by continuous proliferation. This highlights the inherent paradox that telomerase down-regulation in T cells may protect against malignancy yet also lead to replicative exhaustion of repeatedly activated memory T cells. In this article, we review the data on telomerase regulation in T lymphocytes and the implications this has for the maintenance of T cell memory.     

Implications of exercise training in mtDNA defects--use it or lose it?

Whether regular exercise is beneficial or should be avoided is a question currently unsettled in patients with heteroplasmic mitochondrial DNA (mtDNA) disorders of skeletal muscle. Deleterious effects of habitual physical inactivity superimposed upon impaired mitochondrial oxidative phosphorylation may contribute to varying degrees of exercise intolerance in these patients. Endurance exercise training is widely known to improve exercise capacity in healthy subjects and various chronic-disease patient populations. Although we have shown that beneficial physiological and biochemical responses to training increase exercise tolerance in patients with mtDNA defects, knowledge of the muscle adaptive response to endurance training within the setting of mitochondrial heteroplasmy remains limited. In order to determine advisability of endurance training as therapy, it remains to be established whether potential endurance training-induced increases in mutant mtDNA levels may be offset by increases in absolute wild-type mtDNA levels, and whether chronic inactivity leads to a selective down-regulation of wild-type mtDNA. Resistance training utilizes a different adaptive exercise approach to induce the transfer of normal mitochondrial templates from satellite cells to mature muscle fibers of patients with sporadic mtDNA disorders. The efficacy and safety of this approach needs to be further established. Our current inability to clearly advise patients to "use it or lose it" underscores the immediate urgency of studying the effects of exercise on skeletal muscle of patients with heteroplasmic mtDNA defects.     

Diagnosing smallpox: would you know it if you saw it?

The intentional release of anthrax in the United States in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. Little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. During December 2002 and January 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the diagnosis and management of patients who present with vesicular rash illness. In addition to demographic and training-related questions, the questionnaire included items about perceived comfort in diagnosing and evaluating rashes, knowledge of the key differential diagnostic characteristics of chickenpox and smallpox, and the diagnostic interpretation of color photographs of patients with smallpox or chickenpox. Responses were summarized as a perceived comfort score, a differential diagnosis score, and a picture score. Of 266 eligible physicians, 178 (67%) responded. Of these, 95% thought clinicians need more education about bioterrorism; only 17% reported comfort in diagnosing smallpox. Although most physicians recognized pictures of smallpox and chickenpox, only 36% correctly answered 3 of 4 questions regarding differential diagnosis, an important aspect of identifying cases early. Those who were comfortable diagnosing rash illnesses had higher differential diagnosis scores. Strategies for bioterrorism-related training could take advantage of physicians' awareness of their own knowledge deficits.     

Single-molecule biology: what is it and how does it work?

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, we have tried to study subtle and complex biological processes by crude in vitro techniques, looking at average behaviors of vast numbers of molecules under conditions usually remote from those existing in the cell. Researchers have realized the limitations of this approach, but none other has been available. Now, we can not only observe the nuances of the behaviors of individual molecules but prod and probe them as well. Perhaps most important is the emerging ability to carry out such observations and manipulations within the living cell. The long-awaited leap to an in vivo biochemistry is at last underway.     

Wildlife utilization: use it or lose it — a Kenyan perspective

The history, present status, plans for the future and constraints of consumptive utilization of wildlife in Kenya are discussed. Such utilization is considered to be a viable development option and has positive aspects for conservation of the environment and animals. It is proposed that illegal consumptive utilization is at such a level in the country that if it is not brought under control the wildlife population will decline catastrophically. There are numerous constraints of a legal and infrastructural nature which will reduce the potential of wildlife utilization, especially in the short term. Community knowledge of sustainable utilization methods is lacking as is, to a large extent, governmental and non-governmental support for such activities. The Kenya Wildlife Service is the body empowered to act in this area and it is funded to carry a community programme forward but implementation will require a massive locally-driven initiative without bureaucratic interference. Game ranching and farming are developing but involve only a small sector of the community and at a relatively low level compared with Southern Africa. Some practical and veterinary aspects are briefly discussed.     

Is it a revolution?

Jablonka and Lamb's claim that evolutionary biology is undergoing a ‘revolution’ is queried. But the very concept of revolutionary change has uncertain application to a field organized in the manner of contemporary biology. The explanatory primacy of sequence properties is also discussed.

The human chin revisited: what is it and who has it?

Although the presence of a "chin" has long been recognized as unique to Homo sapiens among mammals, both the ontogeny and the morphological details of this structure have been largely overlooked. Here we point out the essential features of symphyseal morphology in H. sapiens, which are present and well-defined in the fetus at least as early as the fifth gestational month. Differences among adults in expression of these structures, particularly in the prominence of the mental tuberosity, are developmental epiphenomena and serve to emphasize the importance of studying this region in juveniles whenever possible. A survey of various middle to late Pleistocene fossil hominids for which juveniles are known reveals that these features are present in some late Pleistocene specimens assigned to H. sapiens, but not in all of the presumed anatomically modern H. sapiens (i.e., Qafzeh 8, 9, and 11). The adult specimens from Skhūl, as well as the adult Qafzeh 7 specimen, are similarly distinctive in symphyseal morphology. Neanderthals are quite variable in their own right, and they as well as other middle to late Pleistocene fossils lack the symphyseal features of H. sapiens. Some of the latter are, however, seen in the Tighenif (Ternifine) mandibles.