Species Survival in Fragmented Landscapes: Where to From Here?

We summarise the contributions of empiricists, modellers, and practitioners in this issue of Biodiversity and Conservation, and highlight the most important areas for future research on species survival in fragmented landscapes. Under the theme uncertainty in research and management, we highlight five areas for future research. First, we know little about the effects of density dependence on the viability of metapopulations, a requirement for fragmented landscapes. Second, successful early attempts suggest that it is worth developing more rigorous calibration methods for population viability analysis with spatially explicit, individual-based models. In particular, the balance between model complexity, ease of calibration, and precision, needs to be addressed. Third, we need to improve methods to discriminate between models, including alternatives to time-series approaches. Fourth, when our ability to reduce model uncertainty is weak, we need to incorporate this uncertainty in population viability analysis. Fifth, population viability analysis and decision analysis can be integrated to make uncertainty an explicit part of the decision process. An important future direction is extending the decision framework to adaptive management. Under the theme tools for quantifying risk and predicting species sensitivity to fragmentation, we highlight three areas for future research. First, we need to develop tools to support comparative approaches to population viability analysis. Second, population modelling can be used to find rules of thumb to support conservation decisions when very little is known about a species. Rules of thumb need to be extended to the problem of managing for multiple species. Third, species traits might be useful for predicting sensitivity but predictions could be further refined by considering the relative importance of population processes at different scales. Under the theme tools for reassembling fragmented landscapes, we consider the focal species approach, and highlight aspects of the approach that require more rigorous testing. Finally, we highlight two important areas for future research not presented in the previous themes or papers in this volume. First, we need to incorporate the deterministic effects of habitat modification into the modelling framework of population viability analysis. Second, an avenue of research that remains largely unexplored is the combination of landscape-scale experiments and population modelling, especially using data from existing fragmentation experiments and from experiments designed to test the effects of defragmenting landscapes.     

Where Are We Now? Bergmann's Rule Sensu Lato in Insects

Abstract Bergmann's rule states that individuals of a species/clade at higher altitudes or latitudes will be larger than those at lower ones. A systemic review of the known literature on inter- and intraspecific variation in insect size along latitudinal or altitudinal clines was done to see how often such clines appeared and whether they reflected classwide, species-specific, or experimentally biased tendencies. Nearly even numbers of studies showed Bergmann clines and converse-Bergmann clines, where insects get smaller as latitude/altitude increases. In fact, the majority of studies suggested no clines at all. Small ranges may have obscured certain clines, while giant ranges may have introduced artifacts. Researchers examining interspecific patterns found clines less frequently than those examining intraspecific patterns because of variation among species within the clades, which renders interspecific studies unhelpful. Bergmann's rule does not apply to hexapods with nearly the same consistency as it does to endothermic vertebrates. The validity of Bergmann's rule for any group and range of insects is highly idiosyncratic and partially depends on the study design. I conclude that studies of Bergmann's rule should focus within species and look at widespread but contiguous populations to account for all sources of variation while minimizing error.     

Risk Sensitivity in Behavior: Where Are We Now? Introduction to the Symposium

Risk-sensitive behavior is the phenomenon of animals exhibitingpreferences when offered choices whose outcomes differ in theirdegree of variance. It is now well demonstrated that many animalsare sensitive to differences in the magnitude of variance inrewards. A considerable body of literature on risk sensitivityhas been generated in recent years, encompassing theoreticaland empirical work, from both functional and mechanistic approaches.Nevertheless, it is less than clear how animal preferences forvariability are determined. It is therefore timely to look broadlyat what has been accomplished, and to identify the most promisingsynthetic approaches for future work.     

Antibiotic Use in Animal Agriculture: What Have We Learned and Where are We Going?

Antibiotics are enormously important for the humane and efficient production of food animals. These benefits are somewhat offset by the human and animal health antibiotic resistance risks posed by their use in animals. This article provides an overview of what we have learned about antibiotic resistance as an issue in animal agriculture and where that knowledge could lead us in the future. To preserve the effectiveness of antibiotics, more action is needed to ensure their prudent use, particularly in the case of antibiotic growth promoters and antibiotics deemed critically important for human and animal health.     

Vitiligo: Where Do We Stand?

Vitiligo is a puzzling disorder characterized by a disappearance of epidermal and/or follicular melanocytes by unknown mechanisms. This very common disorder involving 1–4% of the world population is thus of great importance for the practicing dermatologist. The cellular and molecular mechanisms leading to the destruction of melanocytes in this disorder have not yet been elucidated, making it of major interest for the cell biologist involved in melanocyte research. Recent advances in this field, due largely to the availability of techniques for culturing normal human melanocytes, opened new perspectives in the understanding of vitiligo. Although vitiligo has long been considered a disorder confined to the skin, there is now good evidence that it also involves the extracutaneous compartment of the “melanocyte organ.” It is also clear that vitiligo is not only a melanocyte disorder, but that it also involves cells, such as keratinocytes and Langerhans cells, found in the epidermis and follicular epithelium. The three prevailing theories of the pathogenesis of vitiligo are the immune hypothesis, the neural hypothesis, and the self-destruct hypothesis. New hypotheses suggest that vitiligo may be due to (1) a deficiency in an unidentified melanocyte growth factor, (2) an intrinsic defect of the structure and function of the rough endoplasmic reticulum in vitiligo melanocytes, (3) abnormalities in a putative melatonin receptor on melanocytes and (4) a breakdown in free radical defense in the epidermis. None of these hypotheses has been demonstrated, and according to the available data, it is likely that the loss of epidermal and follicular melanocytes in vitiligo may be the result of several different pathogenetic mechanisms.     

Genetic research in osteoporosis: Where are we? Where should we go next?

Fractures resulting from low bone mass and excessive skeletal fragility (osteoporosis) are common worldwide both in males and females, particularly in later years of life. Both fractures, and the most important predictor of fractures, bone mass, are now known to be strongly heritable. This fact, plus the current growth in genetic science, has led to a surge of genetic research in osteoporosis, mostly in the search for genes and their polymorphisms that are responsible for variation in bone mass. Finding the genetic basis underlying variation in bone mass will lead us to deeper understanding of the biology of bone mass accumulation, maintenance and adaptation to load. This, plus finding the genetic basis for overall variation in fracture risk per se, will facilitate the development of interventions, both pharmaceutical and non-pharmaceutical, to prevent and/or treat osteoporosis successfully. This research has produced a rather large number of gene loci that seem to influence bone mass. The challenge now is to refine the statistical genetics and the phenotypes involved so that we can confidently identify those gene loci that truly influence bone mass, and to find ways to study the genetic basis for the most direct disease outcome of interest, fracture.     

TRPM2 Cation Channels,Oxidative Stress and Neurological Diseases: Where Are We Now?

The Na+ and Ca²⁺-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca²⁺ or by hydrogen peroxide (H₂O₂), an experimental model for oxidative stress, binding to the channel’s enzymatic Nudix domain. Since the mechanisms that lead to TRPM2 gating in response to ADPR and H₂O₂ are not understood in neuronal cells, I summarized previous findings and important recent advances in the understanding of Ca²⁺ influx via TRPM2 channels in different neuronal cell types and disease processes. Considering that TRPM2 is activated by oxidative stress, mediated cell death and inflammation, and is highly expressed in brain, the channel has been investigated in the context of central nervous system. TRPM2 plays a role in H₂O₂ and amyloid β-peptide induced striatal cell death. Genetic variants of the TRPM2 gene confer a risk of developing Western Pacific amyotropic lateral sclerosis and parkinsonism-dementia complex and bipolar disorders. TRPM2 also contributes to traumatic brain injury processes such as oxidative stress, inflammation and neuronal death. There are a limited number of TRPM2 channel blockers and they seem to be cell specific. For example, ADPR-induced Ca²⁺ influx in rat hippocampal cells was not blocked by N-(p-amylcinnomoyl)anthralic acid (ACA), the IP₃ receptor inhibitor 2-aminoethoxydiphenyl borate or PLC inhibitor flufenamic acid (FFA). However, the Ca²⁺ entry in rat primary striatal cells was blocked by ACA and FFA. In conclusion TRPM2 channels in neuronal cells can be gated by either ADPR or H₂O₂. It seems to that the exact relationship between TRPM2 channels activation and neuronal cell death still remains to be determined.     

Nematode Memory: Now,Where Was I?

The nematode Caenorhabditis elegans is able to use tastes, smells and temperature to locate food. New data show that worms can also detect the level of oxygen in the environment and migrate towards an oxygen level associated with food.     

Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.     

Where are the pseudogenes in bacterial genomes?

Most bacterial genomes have very few pseudogenes; notable exceptions include the genomes of the intracellular parasites Rickettsia prowazekii and Mycobacterium leprae. As DNA can be introduced into microbial genomes in many ways, the compact nature of these genomes suggests that the rate of DNA influx is balanced by the rate of DNA deletion. We propose that the influx of dangerous genetic elements such as transposons and bacteriophages selects for the maintenance of relatively high deletion rates in most bacteria; the sheltered lifestyle of intracellular parasites removes this threat, leading to reduced deletion rates and larger pseudogene loads.     

Comparative Modelling Techniques: Where are we?

The enormous increase in data availability brought about by genomic projects is paralleled by an equally unprecedented increase in the expectations for new medical, pharmacological, environmental and biotechnological discoveries. Whether or not we will be able to meet (at least partially) these expectations will depend on how well we will be able to interpret the data and translate the mono-dimensional information encrypted in genomes into a detailed understanding of its biological meaning at the phenotypic level. The process is far from being trivial, and the obstacles along the road are formidable: even the problem of identifying coding regions in eukaryotic genomes is not completely solved. Far more complex is identification of the function of the encoded proteins, and this will probably represent the most challenging problem for the next generations of scientists.     

Molecular targeted therapies in breast cancer: Where are we now?

Targeted therapies, in cancer treatment, represent a new generation of drugs that interfere with specific molecular targets (typically proteins) having critical roles to play in tumour growth or progression. The principle of targeted therapy is certainly not new: tamoxifen, a hormonal agent targeted at the estrogen receptor, has been in use for more than 30 years. However, this principle has re-gained significant emphasis with the recent development of new biological agents, such as trastuzumab, which was first approved for the treatment of advanced breast cancer (BC) in 1998. Presently, there are at least three different targeted therapies with well documented activity in advanced BC and all three are now being studied in the adjuvant setting; trastuzumab and bevacizumab are monoclonal antibodies, and lapatinib is a dual inhibitor of HER-1 and HER-2. This paper will review the increasing role of molecular targeted therapies in BC, with a particular focus on those drugs currently being tested in early BC, as well as, on future perspectives.