The response of runners to arduous triathlon competition

As very few of the competitors in a triathlon are truly specialist in more than one of the three disciplines, high levels of physical (and mental) stress may result during the course of the event. We investigated some of the physiological responses occurring in runners participating in an "Iron Man" triathlon consisting of canoeing (20 km), cycling (90 km) and running (42 km), in that sequence. Twenty-one male entrants volunteered as subjects for the study. Prior to the competition, maximal oxygen consumption (VO2max) was determined. Basal venous blood samples were collected on the day prior to the competition and post-exercise venous blood samples were collected within 5 minutes of completion of the race. Serum iron was significantly reduced from a mean basal value of 20.6 mumol X l-1 to a mean value of 8.4 mumol X l-1 after the race. Cortisol levels showed a 3 fold increase after the race. Gross VO2max (l X min-1) and mass standardised VO2max (ml X min-1 X kg-1) were both negatively correlated to cortisol levels after the race (p less than 0.05). Total performance time was not related to gross VO2max (l X min-1) but was well correlated to mass corrected VO2max (ml X min-1 X kg-1). The marked fall in serum iron may have been related to heavy sweating or prelatent iron deficiency. Chronic iron deficiency (without frank anaemia) can impair physical performance, although we were unable to show any significant correlation between serum iron level after the race and time taken to complete the event.(ABSTRACT TRUNCATED AT 250 WORDS)     

The long road to engineering durable disease resistance in wheat

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The long road to understanding the baculovirus P10 protein

The baculovirus P 10 protein has always represented a mystery in the feld of insect virology. Like the baculovirus polyhedrin protein it is expressed at high levels very late in infection. Homologues of the Autographa californica nucleopolyhedrovirus plO gene are conserved in all Alphabaculoviruses and in other viruses of lepidopteran hosts yet is completely dispensable for virus replication and transmission. P10 is a microtubule interacting protein whose expression has been associated with the formation of a variety of complex and extensive cytoplasmic and nuclear structures. P10 has been associated with a number of roles during infection ranging from the formation of virus occlusion bodies, to affecting the rate of cellular and/or nuclear lysis during the final stages of the virus replication cycle. In this article we review recent work aimed at understanding the role of this enigmatic protein, putting them into context with recent advances in understanding of protein structure and function. We look back at a number of historical studies and observations, reanalysing their conclusions based on recent data and our own observations. The role of the P 10 protein during baculovirus replication remains elusive, however, novel avenues of investigation have been identified that will, we are sure, eventually lead to an understanding of this protein.     

The long road to recombinase‐mediated plant transformation

The use of site‐specific recombinases to manipulate eukaryotic genomes began nearly three decades ago. Although seemingly parallel efforts were being made in animal and plant systems, the motivation for its development in plants was unique to, at least at the time, crop bioengineering issues. The impetus behind site‐specific deletion in plants was to remove antibiotic resistance genes used during transformation but unnecessary in commercial products. Site‐specific integration in plants was more than academic curiosity of position effects on gene expression, but a necessary step towards developing the serial stacking of DNA to the same chromosome locus – to insure that bioengineered crops can be improved over time through transgene additions without inflating the number of segregating loci. This article is not a review of the literature on site‐specific recombination, but a first person account of the series of events leading to the development of a gene stacking transformation system in plants.     

The long hard road to a completed Candida albicans genome

After almost a decade of work, the sequencing, assembly, and annotation of the genome of the fungal pathogen Candida albicans is finally close at hand. This review covers the early history of the C. albicans genome project, from the release of early assemblies that provided the impetus for an explosion in functional genomics research, to a community-based annotation and a preview of the work that was necessary for the production of a final genome assembly.     

Assembling chromatin: The long and winding road

It has been over 35years since the acceptance of the "chromatin subunit" hypothesis, and the recognition that nucleosomes are the fundamental repeating units of chromatin fibers. Major subjects of inquiry in the intervening years have included the steps involved in chromatin assembly, and the chaperones that escort histones to DNA. The following commentary offers an historical perspective on inquiries into the processes by which nucleosomes are assembled on replicating and nonreplicating chromatin. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.     

ERAD: the long road to destruction

Endoplasmic reticulum (ER)-associated protein degradation (ERAD) eliminates misfolded or unassembled proteins from the ER. ERAD targets are selected by a quality control system within the ER lumen and are ultimately destroyed by the cytoplasmic ubiquitin-proteasome system (UPS). The spatial separation between substrate selection and degradation in ERAD requires substrate transport from the ER to the cytoplasm by a process termed dislocation. In this review, we will summarize advances in various aspects of ERAD and discuss new findings on how substrate dislocation is achieved.     

The long unwinding road of RNA helicases

RNA helicases comprise a large family of enzymes that are thought to utilize the energy of NTP binding and hydrolysis to remodel RNA or RNA-protein complexes, resulting in RNA duplex strand separation, displacement of proteins from RNA molecules, or both. These functions of RNA helicases are required for all aspects of cellular RNA metabolism, from bacteria to humans. We provide a brief overview of the functions of RNA helicases and highlight some of the recent key advances that have contributed to our current understanding of their biological function and mechanism of action.     

Microbicides: still a long road to success

The development of efficient microbicides, the topically applied compounds that protect uninfected individuals from acquiring HIV-1, is a promising strategy to contain HIV-1 epidemics. Such microbicides should of course possess anti-HIV-1 activity, but they should also act against other genital pathogens, which facilitate HIV-1 transmission. The new trend in microbicide strategy is to use drugs currently used in HIV-1 therapy. The success of this strategy is mixed so far and is impaired by our limited knowledge of the basic mechanisms of HIV-1 transmission as well as by the inadequacy of the systems in which microbicides are tested in preclinical studies.     

Post-translational control of the long and winding road to cholesterol

The synthesis of cholesterol requires more than 20 enzymes, many of which are intricately regulated. Post-translational control of these enzymes provides a rapid means for modifying flux through the pathway. So far, several enzymes have been shown to be rapidly degraded through the ubiquitin–proteasome pathway in response to cholesterol and other sterol intermediates. Additionally, several enzymes have their activity altered through phosphorylation mechanisms. Most work has focused on the two rate-limiting enzymes: 3-hydroxy-3-methylglutaryl CoA reductase and squalene monooxygenase. Here, we review current literature in the area to define some common themes in the regulation of the entire cholesterol synthesis pathway. We highlight the rich variety of inputs controlling each enzyme, discuss the interplay that exists between regulatory mechanisms, and summarize findings that reveal an intricately coordinated network of regulation along the cholesterol synthesis pathway. We provide a roadmap for future research into the post-translational control of cholesterol synthesis, and no doubt the road ahead will reveal further twists and turns for this fascinating pathway crucial for human health and disease.