Research in the exercise sciences: where do we go from here?

The goal of this article is to provide a perspective on how research involving the acute and chronic effects of exercise (referred to as "exercise sciences") on the structure and function of organs systems will evolve in the next century. Within the last 30 years, exercise-related research has rapidly transitioned from an organ to a subcellular/molecular focus. Thus future research will continue to be heavily influenced by molecular biology tools, fueled by both emerging technologies (e.g., "gene-chip microarrays") designed to dissect gene function on a macro scale as well as by the completion of the human genome project in which the approximately 80,000 genes comprising humans will be completely sequenced. These successes will drive the emerging fields of functional genomics (the dissecting of a gene's identity and function) and proteomics (the study of the properties of proteins). Funding levels at the National Institutes of Health will likely increase in order to expand these emerging fields as well as provide avenues for translating fundamental knowledge into solving the complexities of a number of degenerative diseases influenced heavily by activity/inactivity factors such as cardiopulmonary disease, diabetes, obesity, and the debilitating disorders associated with aging. Thus there are many challenges facing future exercise scientists who must harness the new technologies and take an aggressive stance in bringing this important field to the forefront.     

The sylvatic cycle of Neospora caninum: where do we go from here?

Bovine abortions due to Neospora caninum infection are a major cattle-production problem worldwide. The parasite is readily maintained in cattle populations by vertical transmission. The domestic dog excretes oocysts in its feces and, after sporulation, these oocysts are infectious to cattle. Current control measures are aimed at culling infected cows and limiting the access of cattle to infective oocysts. The recent revelations that coyotes (Canis latrans) can excrete N. caninum oocysts in their feces and that white-tailed deer (Odocoileus virginianus) are natural intermediate hosts of the parasite demonstrate the existence of a sylvatic cycle of neosporosis in North America. This complicates parasite-prevention programs but opens many new and exciting avenues of research. Similar canid-ruminant sylvatic cycles might exist in other countries and, if so, need to be investigated.     

Human infectious diseases in the genomics era: where do we go from here?

Ripudaman K Bains is the editor of the Genome Biology special issue content on the ‘genomics of infectious diseases’, and introduces the collection in this editorial.     

Survey‐gap analysis in expeditionary research: where do we go from here?

Research expeditions into remote areas to collect biological specimens provide vital information for understanding biodiversity. However, major expeditions to little‐known areas are expensive and time consuming, time is short, and well‐trained people are difficult to find. In addition, processing the collections and obtaining accurate identifications takes time and money. In order to get the maximum return for the investment, we need to determine the location of the collecting expeditions carefully. In this study we used environmental variables and information on existing collecting localities to help determine the sites of future expeditions. Results from other studies were used to aid in the selection of the environmental variables, including variables relating to temperature, rainfall, lithology and distance between sites. A survey gap analysis tool based on ‘ED complementarity’ was employed to select the sites that would most likely contribute the most new taxa. The tool does not evaluate how well collected a previously visited site survey site might be; however, collecting effort was estimated based on species accumulation curves. We used the number of collections and/or number of species at each collecting site to eliminate those we deemed poorly collected. Plants, birds, and insects from Guyana were examined using the survey gap analysis tool, and sites for future collecting expeditions were determined. The south‐east section of Guyana had virtually no collecting information available. It has been inaccessible for many years for political reasons and as a result, eight of the first ten sites selected were in that area. In order to evaluate the remainder of the country, and because there are no immediate plans by the Government of Guyana to open that area to exploration, that section of the country was not included in the remainder of the study. The range of the ED complementarity values dropped sharply after the first ten sites were selected. For plants, the group for which we had the most records, areas selected included several localities in the Pakaraima Mountains, the border with the south‐east, and one site in the north‐west. For birds, a moderately collected group, the strongest need was in the north‐west followed by the east. Insects had the smallest data set and the largest range of ED complementarity values; the results gave strong emphasis to the southern parts of the country, but most of the locations appeared to be equidistant from one another, most likely because of insufficient data. Results demonstrate that the use of a survey gap analysis tool designed to solve a locational problem using continuous environmental data can help maximize our resources for gathering new information on biodiversity. © 2005 The Linnean Society of London, Biological Journal of the Linnean Society, 2005, 85 , 549–567.     

NMR-based plant metabolomics: where do we stand, where do we go?

NMR-based metabolomics is an important tool for studying biological systems and has been applied in various organisms, including animals, plants and microbes. NMR is able to provide a 'holistic view' of the metabolites under certain conditions, and thus is advantageous for metabolomic studies. To maximize the use of the information obtained, it is also important to create a platform to measure, store and share data. Public databases for storing and sharing information are still lacking for NMR-based metabolomic analysis in plants. Such databases are urgently needed to make metabolic profiling a real omics technology. In addition, to understand metabolic processes in depth, single-cell analysis and the turnover of metabolites in pathways (fluxomics) should be measured.     

Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here?

The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline.     

Transgenerational plasticity and climate change experiments: Where do we go from here?

Phenotypic plasticity, both within and across generations, is an important mechanism that organisms use to cope with rapid climate change. While an increasing number of studies show that plasticity across generations (transgenerational plasticity or TGP) may occur, we have limited understanding of key aspects of TGP, such as the environmental conditions that may promote it, its relationship to within‐generation plasticity (WGP) and its role in evolutionary potential. In this review, we consider how the detection of TGP in climate change experiments is affected by the predictability of environmental variation, as well as the timing and magnitude of environmental change cues applied. We also discuss the need to design experiments that are able to distinguish TGP from selection and TGP from WGP in multigenerational experiments. We conclude by suggesting future research directions that build on the knowledge to date and admit the limitations that exist, which will depend on the way environmental change is simulated and the type of experimental design used. Such an approach will open up this burgeoning area of research to a wider variety of organisms and allow better predictive capacity of the role of TGP in the response of organisms to future climate change.     

Vascular endothelial growth factor receptors and the therapeutic targeting of angiogenesis in cancer: where do we go from here?

Abstract Vascular Endothelial Growth Factor receptors (VEGFRs), the interactions with their ligands and the subsequent signalling pathways are known to play a vital role in tumour angiogenesis. Initial clinical trials of VEGFR inhibitors were disappointing but over the past decade some therapies have been successfully brought to market. At present, VEGFR inhibitors appear to be most promising as adjuvants to conventional chemotherapy. However, several interacting signalling molecules and downstream pathways have recently been shown to interact with VEGFR signalling and provide promising novel targets, such as the platelet-derived growth factor (PDGF), epithelial growth factor (EGF), human epithelial receptor-2, (HER-2) Tie-2 and oestrogen receptors. Elucidation of this web of signalling pathways may identify new therapeutic strategies which may be used in combination with VEGFR inhibitors to augment the efficacy of anti-angiogenic cancer treatments. This review assesses the role of modulating VEGFR activity in cancer and systematically examines current evidence and trials in this area.     

Vascular endothelial growth factor receptors and the therapeutic targeting of angiogenesis in cancer: where do we go from here?

Abstract

Vascular Endothelial Growth Factor receptors (VEGFRs), the interactions with their ligands and the subsequent signalling pathways are known to play a vital role in tumour angiogenesis. Initial clinical trials of VEGFR inhibitors were disappointing but over the past decade some therapies have been successfully brought to market. At present, VEGFR inhibitors appear to be most promising as adjuvants to conventional chemotherapy. However, several interacting signalling molecules and downstream pathways have recently been shown to interact with VEGFR signalling and provide promising novel targets, such as the platelet-derived growth factor (PDGF), epithelial growth factor (EGF), human epithelial receptor-2, (HER-2) Tie-2 and oestrogen receptors. Elucidation of this web of signalling pathways may identify new therapeutic strategies which may be used in combination with VEGFR inhibitors to augment the efficacy of anti-angiogenic cancer treatments. This review assesses the role of modulating VEGFR activity in cancer and systematically examines current evidence and trials in this area.     

Shift-work research: Where do we stand,where should we go?

Sleep and Biological Rhythms - Shift-work seriously affects the health and well-being of millions of people worldwide, and the number of shift workers is constantly rising (currently approximately...     

25 years of recombinant proteins from reactor-grown cells - Where do we go from here?

The purpose of this review is to describe the current status and to highlight several emerging trends in the manufacture of recombinant therapeutic proteins in cultivated mammalian cells, focusing on Chinese hamster ovary cells as the major production host. Over the past 25 years, specific and volumetric productivities for recombinant cell lines have increased about 20-fold as the result of improvements in media and bioprocess design. Future yield increases are expected to come from further developments in gene delivery and genetic selection for more efficient recovery of high-producing cell lines and in high-throughput cultivation systems to simplify medium design and bioprocess development. Other emerging trends in protein manufacturing that are discussed include the use of disposal bioreactors and transient gene expression. We specifically highlight current research in our own laboratories.     

Modifications of symbionts during ectomycorrhiza formation what do we know and where do we go?

Abstract

Ectomycorrhizas are subterranean organs resulting from the alteration in root structure by soil-inhabiting symbiotic fungi. Hyphae of the mycobiont have to contact the root surface, become attached to the root, and subsequently enter the root by growing between epidermal cells (and in some species, cortical cells) to form the Hartig net. A chemotropic stimulus might be involved in early hypha-root contact and recognition-adhesion may involve a polysaccharide-lectin interaction, but further research is needed to confirm this. Fungal hyphae adhering to the root surface change their mode of growth from apical, extension growth to a loss of this pattern resulting in a multi-branched mycelium. A similar change in pattern of branching occurs as hyphae form the Hartig net. In both cases, a change in the cytoskeleton might precede the change in branching. The ingress of hyphae between epidermal cells in angiosperm roots triggers radial rather than axial elongation of these cells; a reorientation of the cytoskeleton and subsequently the cellulose microfibrils is hypothesized to be involved in this process. Wall changes in root cells contiguous to Hartig net hyphae also occur, and these might facilitate nutrient exchange between the symbionts.