Recombination or mutational hot spots in human mtDNA?

Awadalla, Eyre-Walker, and Maynard Smith (1999) recently argued that there might be recombination in human mitochondrial DNA (mtDNA). Their claim was based on their observation of decaying linkage disequilibrium (LD) as a function of physical distance. Their study was much criticized, and follow-up studies have failed to find any evidence for recombination. We argue that the criticisms levied, even if correct, could not possibly explain the findings of Awadalla, Eyre-Walker, and Maynard Smith (1999). Nonetheless, the test proposed by Awadalla, Eyre-Walker, and Maynard Smith (1999 ) is not robust because recombination is not the only explanation for decay of LD. We show that such a pattern can be caused by mutational hot spots as well. However, a closer look at the data suggests that the pattern observed was not caused by mutational hot spots but rather by chance. Thus, there appears to be no evidence for recombination in the mtDNA polymorphism data. In conclusion, we discuss the possibility of detecting recombination in mtDNA and the implications of its existence.     

Acral myxoinflammatory fibroblastic sarcoma in FNAB samples: can we distinguish it from other myxoid lesions?

We analysed cytomorphological characteristics of three fine needle aspiration biopsy (FNAB) samples of acral myxoinflammatory fibroblastic sarcoma (AMIFS) as well as the features of a number of other benign and malignant myxoid lesions. The analysis showed that FNAB samples from two cases of AMIFS had similar cytomorphology, containing all the characteristic features described in surgical biopsies: myxoid material, spindle cells with bipolar cytoplasmic extensions, epithelioid cells with globules of extra-cellular material, ganglion-like and lipoblast-like giant cells. Only the inflammatory component was scarce. The third sample did not contain features typical of AMIFS. Samples from other myxoid tumours resembled AMIFS to some extent, however, none of them contained all three tumour components characteristic of AMIFS. Cytomorphology of AMIFS may be characteristic enough to enable a definitive diagnosis from FNAB, provided all the distinctive features are sampled.     

When can we distinguish between neutral and non‐neutral processes in community dynamics under ecological drift?

Determining whether the composition of ecological communities (species presence and abundance), can be predicted from species demographic traits, rather than being a result of neutral drift, is a key ecological question. Here we compare the similarity of community composition, from different community assembly models run under identical environmental conditions, where interspecific competition is assumed to be either neutral or niche-based. In both cases, species colonize a focal patch from a network of neighbouring patches in a metacommunity. We highlight the circumstances (rate and spatial scale of dispersal, and the relative importance of ecological drift) where commonly used community similarity metrics or species rank–abundance relationships are likely to give similar results, regardless of the underlying processes (neutral or non-neural) driving species' dynamics. As drift becomes more important in driving species abundances, deterministic niche structure has a smaller influence. Our ability to discriminate between different underlying processes driving community organization depends on the relative importance of different drift processes that operate on different spatial scales.     

How can we bring together empiricists and modellers in functional biodiversity research?

Improving our understanding of biodiversity and ecosystem functioning and our capacity to inform ecosystem management requires an integrated framework for functional biodiversity research (FBR). However, adequate integration among empirical approaches (monitoring and experimental) and modelling has rarely been achieved in FBR. We offer an appraisal of the issues involved and chart a course towards enhanced integration. A major element of this path is the joint orientation towards the continuous refinement of a theoretical framework for FBR that links theory testing and generalization with applied research oriented towards the conservation of biodiversity and ecosystem functioning. We further emphasize existing decision-making frameworks as suitable instruments to practically merge these different aims of FBR and bring them into application. This integrated framework requires joint research planning, and should improve communication and stimulate collaboration between modellers and empiricists, thereby overcoming existing reservations and prejudices. The implementation of this integrative research agenda for FBR requires an adaptation in most national and international funding schemes in order to accommodate such joint teams and their more complex structures and data needs.     

Linking science and practice in ecological research and management: How can we do it better?

Summary In conservation management, ensuring that the most appropriate research is conducted and results are actually put into practice is a complex and challenging process. While there are success stories, many hurdles can reduce the likelihood of appropriate research being initiated and its findings communicated and implemented. This article describes the ideal research–management cycle, summarizes the major factors that impede it and draws on the experiences of the authors to provide a series of examples of successful approaches to help keep the cycle going. We consider that the major impediments to a functioning research–management cycle relate to a lack of collaboration, poor communication, inappropriate funding and political timelines, change inertia and a lack of capacity. Although addressing structural difficulties such as matching funding timelines to those required for ecological research is a fundamental challenge, we can make incremental improvements to the way in which we operate that will improve the chances that research is both useful and used. The principles underpinning our success stories are (i) strategic development of capacity, (ii) increased breadth and depth of collaborations between researchers and managers and (iii) improved communications. Participants in the research–management cycle must seek to involve stakeholders through all project stages from project conception, to implementation, evaluation and knowledge updating. Finally, we should only see the first iteration of the research process as complete when new knowledge is applied operationally with monitoring and ongoing evaluation in place.     

How can we conserve cold stenotherm communities in warming Alpine ponds?

Freshwater biodiversity has shown to be highly vulnerable to climate warming, alpine cold stenotherm populations being especially at risk of getting extinct. This paper aims at identifying the environmental factors favouring cold stenotherm species in alpine ponds. This information is required to provide management recommendations for habitats restoration or creation, needed for the mitigation of the effects of climate warming on alpine freshwater biodiversity. Cold stenotherm species richness as well as total (i.e. stenotherm and eurytherm) richness were analyzed for aquatic plants, Coleoptera and Odonata in 26 subalpine and alpine ponds from Switzerland and were related to environmental factors ecologically relevant for pond biodiversity. Our results confirmed that the set of environmental variables governing pond biodiversity in alpine or subalpine ponds is specific to altitude. Altitude and macrophyte presence were important drivers of cold stenotherm and total species richness, whereas connectivity did not show any significant relation. Therefore, the management of pond biodiversity has to be ‘altitude-specific’. Nevertheless, cold stenotherm species from the investigated alpine ponds do not show some specific requirements if compared to the other species inhabiting these ponds. Therefore, both total and cold stenotherm species richness could be favoured by the same management measures.     

How can we deliver the large plant genomes? Strategies and perspectives

The first sequenced plant genome, from the small mustard plant Arabidopsis thaliana, was published at the end of 2000. The sequencing of the rice genome is well under way. The sizes of plant genomes vary by a factor of up to 1000, and many important crop plants have genomes that are several times larger than the human genome. To gain insight into the gene toolbox of plant species, numerous large-scale EST sequencing projects have been launched successfully, and analysis procedures are constantly being refined to add maximum value to the sequence data. In addition, an alternative approach to exclude repetitive noncoding DNA and to enrich sequence libraries for gene-containing genomic regions has been developed. This strategy has the potential to deliver information about both genes and regulatory regions outside the transcribed regions.     

How accurately can we control the FDR in analyzing microarray data?

SUMMARY: We want to evaluate the performance of two FDR-based multiple testing procedures by Benjamini and Hochberg (1995, J. R. Stat. Soc. Ser. B, 57, 289-300) and Storey (2002, J. R. Stat. Soc. Ser. B, 64, 479-498) in analyzing real microarray data. These procedures commonly require independence or weak dependence of the test statistics. However, expression levels of different genes from each array are usually correlated due to coexpressing genes and various sources of errors from experiment-specific and subject-specific conditions that are not adjusted for in data analysis. Because of high dimensionality of microarray data, it is usually impossible to check whether the weak dependence condition is met for a given dataset or not. We propose to generate a large number of test statistics from a simulation model which has asymptotically (in terms of the number of arrays) the same correlation structure as the test statistics that will be calculated from the given data and to investigate how accurately the FDR-based testing procedures control the FDR on the simulated data. Our approach is to directly check the performance of these procedures for a given dataset, rather than to check the weak dependency requirement. We illustrate the proposed method with real microarray datasets, one where the clinical endpoint is disease group and another where it is survival.     

When less can be better: How can we make genomic selection more cost-effective and accurate in barley?

Key message

We were able to obtain good prediction accuracy in genomic selection with ~?2000 GBS-derived SNPs. SNPs in genic regions did not improve prediction accuracy compared to SNPs in intergenic regions.

Abstract

Since genotyping can represent an important cost in genomic selection, it is important to minimize it without compromising the accuracy of predictions. The objectives of the present study were to explore how a decrease in the unit cost of genotyping impacted: (1) the number of single nucleotide polymorphism (SNP) markers; (2) the accuracy of the resulting genotypic data; (3) the extent of coverage on both physical and genetic maps; and (4) the prediction accuracy (PA) for six important traits in barley. Variations on the genotyping by sequencing protocol were used to generate 16 SNP sets ranging from ~?500 to ~?35,000 SNPs. The accuracy of SNP genotypes fluctuated between 95 and 99%. Marker distribution on the physical map was highly skewed toward the terminal regions, whereas a fairly uniform coverage of the genetic map was achieved with all but the smallest set of SNPs. We estimated the PA using three statistical models capturing (or not) the epistatic effect; the one modeling both additivity and epistasis was selected as the best model. The PA obtained with the different SNP sets was measured and found to remain stable, except with the smallest set, where a significant decrease was observed. Finally, we examined if the localization of SNP loci (genic vs. intergenic) affected the PA. No gain in PA was observed using SNPs located in genic regions. In summary, we found that there is considerable scope for decreasing the cost of genotyping in barley (to capture ~?2000 SNPs) without loss of PA.

     

The ecogenetic link between demography and evolution: can we bridge the gap between theory and data?

Calls to understand the links between ecology and evolution have been common for decades. Population dynamics, i.e. the demographic changes in populations, arise from life history decisions of individuals and thus are a product of selection, and selection, on the contrary, can be modified by such dynamical properties of the population as density and stability. It follows that generating predictions and testing them correctly requires considering this ecogenetic feedback loop whenever traits have demographic consequences, mediated via density dependence (or frequency dependence). This is not an easy challenge, and arguably theory has advanced at a greater pace than empirical research. However, theory would benefit from more interaction between related fields, as is evident in the many near-synonymous names that the ecogenetic loop has attracted. We also list encouraging examples where empiricists have shown feasible ways of addressing the question, ranging from advanced data analysis to experiments and comparative analyses of phylogenetic data.     

How can human pluripotent stem cells help decipher and cure Huntington's disease?

Pluripotent stem cell (PSC) technologies are becoming a key asset for deciphering pathological cascades and for developing new treatments against many neurodegenerative disorders, including Huntington's disease (HD). This perspective discusses the challenges and opportunities facing the use of PSCs for treating HD, focusing on four major applications: namely, the use of PSCs as a substitute source of human striatal cells for current HD cell therapy, as a cellular model of HD for the validation of human-specific gene therapies, for deciphering molecular mechanisms underlying HD, and in drug discovery.     

How can we improve information delivery to support conservation and restoration decisions?

Incorporating science into resource conservation and management is becoming increasingly important, but it is not yet clear how to provide information to decision makers most effectively. To evaluate sources of information used to support the management and conservation of California’s riparian bird habitat, we distributed a questionnaire to restoration practitioners and public and private land managers. We asked respondents to rate the importance and availability of different sources of information they use to inform their decisions. Synthetic reviews and peer-reviewed publications both received high importance and availability ratings. Web-based tools received low importance and availability ratings. One-on-one interactions between ecologists and decision makers received high importance ratings, similar to those of peer-reviewed publications and synthetic reviews, but their availability was rated lower than any other method of decision support. Our results suggest that the decision makers we surveyed are already using a wide variety of information, but that prioritizing one-on-one interactions between scientists and decision makers will enhance the delivery of all sources of information.     

How can we improve tracking of transplanted tissue in the United States?

Currently an estimated two million tissues are distributed for transplantation annually. With increasing use of recovered tissue, clusters of transplant-transmitted infection have shown the difficulty of tracking tissues from an infected donor to the recipient. The challenge of tissue tracking to multiple transplant recipients was illustrated in a recent investigation of transmission of hepatitis C virus infection from a donor of organs and tissues. When a tissue bank issued a recall of the donated tissue, the Centers for Disease Control and Prevention was notified to assist public health authorities; the mean time to locate and notify the physicians who had transplanted the tissue was 13 days, while the mean time to notify, inform, and test the patients was 29 days. Lack of common coding and nomenclature was one of the key challenges in tracking tissue to the recipient. Some changes that could improve timeliness in the event of a recall includes: (1) standardized tissue nomenclature and coding through unique donor identifiers; (2) tissue traceability requirements using systems similar to that used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level.     

How well can we predict native contacts in proteins based on decoy structures and their energies?

One strategy for ab initio protein structure prediction is to generate a large number of possible structures (decoys) and select the most fitting ones based on a scoring or free energy function. The conformational space of a protein is huge, and chances are rare that any heuristically generated structure will directly fall in the neighborhood of the native structure. It is desirable that, instead of being thrown away, the unfitting decoy structures can provide insights into native structures so prediction can be made progressively. First, we demonstrate that a recently parameterized physics-based effective free energy function based on the GROMOS96 force field and a generalized Born/surface area solvent model is, as several other physics-based and knowledge-based models, capable of distinguishing native structures from decoy structures for a number of widely used decoy databases. Second, we observe a substantial increase in correlations of the effective free energies with the degree of similarity between the decoys and the native structure, if the similarity is measured by the content of native inter-residue contacts in a decoy structure rather than its root-mean-square deviation from the native structure. Finally, we investigate the possibility of predicting native contacts based on the frequency of occurrence of contacts in decoy structures. For most proteins contained in the decoy databases, a meaningful amount of native contacts can be predicted based on plain frequencies of occurrence at a relatively high level of accuracy. Relative to using plain frequencies, overwhelming improvements in sensitivity of the predictions are observed for the 4_state_reduced decoy sets by applying energy-dependent weighting of decoy structures in determining the frequency. There, approximately 80% native contacts can be predicted at an accuracy of approximately 80% using energy-weighted frequencies. The sensitivity of the plain frequency approach is much lower (20% to 40%). Such improvements are, however, not observed for the other decoy databases. The rationalization and implications of the results are discussed.     

Leptin in farm animals: where are we and where can we go?

Fat affects meat quality, value and production efficiency as well as providing energy reserves for pregnancy and lactation in farm livestock. Leptin, the adipocyte product of the obese (ob) gene, was quickly seen as a predictor of body fat content in animals approaching slaughter and an aid to assessing reproductive readiness in females. Its participation in inflammation and immune responses that help animals survive infection and trauma has clear additional relevance to meat and milk production. Furthermore, almost a decade of discoveries of nucleotide polymorphisms in the leptin and leptin receptor genes has suggested useful applications relating to feed intake regulation, the efficiency of feed use, the composition of growth, the timing of puberty, mammogenesis and mammary gland function and fertility in cattle, pigs and poultry. The current review attempts to summarise where research has taken us in each of these aspects and speculates on where future research might lead.     

How similar are protein folding and protein binding nuclei? Examination of vibrational motions of energy hot spots and conserved residues

The underlying physico-chemical principles of the interactions between domains in protein folding are similar to those between protein molecules in binding. Here we show that conserved residues and experimental hot spots at intermolecular binding interfaces overlap residues that vibrate with high frequencies. Similarly, conserved residues and hot spots are found in protein cores and are also observed to vibrate with high frequencies. In both cases, these residues contribute significantly to the stability. Hence, these observations validate the proposition that binding and folding are similar processes. In both packing plays a critical role, rationalizing the residue conservation and the experimental alanine scanning hot spots. We further show that high-frequency vibrating residues distinguish between protein binding sites and the remainder of the protein surface.