How many alleles per locus should be used to estimate genetic distances?

As more microsatellite loci become available for use in genetic surveys of population structure, population geneticists are able to select loci to use in population structure surveys. This study used computer simulations to investigate how the number of alleles at loci affects the precision of estimates of four common genetic distances. This showed that equivalent results could be achieved by examining either a few loci with many alleles or many loci with a few alleles. More specifically, the total number of independent alleles appears to be a good indicator of how precise estimates of genetic distance will be.     

How should pathogen transmission be modelled?

Host-pathogen models are essential for designing strategies for managing disease threats to humans, wild animals and domestic animals. The behaviour of these models is greatly affected by the way in which transmission between infected and susceptible hosts is modelled. Since host-pathogen models were first developed at the beginning of the 20th century, the 'mass action' assumption has almost always been used for transmission. Recently, however, it has been suggested that mass action has often been modelled wrongly. Alternative models of transmission are beginning to appear, as are empirical tests of transmission dynamics.     

How should dysplastic human hips be evaluated?

Dysplasia of the human hip is characterised by insufficient anterolateral covering of femoral head by the acetabulum. In our study, we evaluated dysplastic human hip joints using biomechanical parameters (the peak contact stress in the weight-bearing area of the hip - pmax) and X-ray image parameters (the centre-edge angle - thetaCE, the transverse acetabular inclination angle - thetaUS, the acetabular index of the weight-bearing zone - thetaAC, the ACM angle - thetaACM, and the hip value - HV). The purpose of this study is to make use of X-ray and biomechanical parameters to evaluate hips diagnosed with "hip dysplasia", and to establish whether or not there is a correlation between the two. Our results show a statistically significant correlation between pmax and thetaCE, thetaUS and thetaAC. The correlation between pmax and thetaACM and HV is not statistically significant.     

In vitro activity of the echinocandins. How should it be evaluated?

Echinocandins are a novel class of antifungal drugs. They have good activity against Candida spp and Aspergillus spp. Their low selective toxicity allows their administration at high doses with few secondary side effects. We have reviewed the available data on the endpoints for these drugs in their in vitro susceptibility testing on yeasts and moulds. The microdilution broth method is the most commonly used technique and MIC-1 (80% of growth inhibition) seems to be the most reliable endpoint when yeasts are tested. This endpoint also seems to be the most appropriate for the different drugs when they are combined with echinocandins using the checkerboard method for testing yeasts. By contrast, in the case of moulds, the minimum effective concentration (MEC) correlates better with the in vivo activity than the MIC when echinocandins are tested, and when these drugs are combined with other antifungals, MIC-2 (50% of growth inhibition) seems the most appropriate endpoint. Criteria based on drug pharmacodynamics is the most useful to define the echinocandin endpoints that best correlate with their in vivo efficacy.     

How should xanthine oxidase-generated superoxide yields be measured?

The rate of formation of superoxide measured by its reduction of tetranitromethane (TNM) and by its reduction of ferric cytochrome c (Fe(III) cc) are in excellent agreement when the superoxide is generated from a simple chemical precursor. In contrast, the rate of formation of superoxide generated in the reaction of xanthine oxidase with acetaldehyde is much higher (up to a factor of 6) when measured with TNM and compared with Fe(III) cc. It is shown that Fe(III) cc measures superoxide that has diffused from the enzyme, and that TNM probably scavenges all the dioxygen that is reduced by one electron by the enzyme. The TNM traps enzyme-bound superoxide in competition with the second-electron transfer and proton transfer, which normally yield hydrogen peroxide. The proton transfer is probably rate determining, k(p) 相似文献   

How should we be selecting our graduate students?

We use many quantitative undergraduate metrics to help select our graduate students, but which of these usefully discriminate successful from underperforming students and which should be ignored? Almost everyone has his or her own pet theory of the most predictive criteria, but I hoped to address this question in a more unbiased manner. I conducted a retrospective analysis of the highest- and lowest-ranked graduate students over the past 20 years in the Tetrad program at the University of California at San Francisco to identify undergraduate metrics that significantly differed between these groups. Only the number of years of research experience and subject graduate record exams (GREs) were strong discriminators between the highest- and lowest-ranked students, whereas many other commonly used admissions metrics (analytical, verbal, and quantitative GREs, grade point average, and ranking of undergraduate institution) showed no correlation with graduate performance. These are not necessarily the same criteria that matter at other graduate programs, but I would urge faculty elsewhere to conduct similar analyses to improve the admissions process and to minimize the use of useless metrics in selecting our students.     

How many biological replicates are needed in an RNA-seq experiment and which differential expression tool should you use?

RNA-seq is now the technology of choice for genome-wide differential gene expression experiments, but it is not clear how many biological replicates are needed to ensure valid biological interpretation of the results or which statistical tools are best for analyzing the data. An RNA-seq experiment with 48 biological replicates in each of two conditions was performed to answer these questions and provide guidelines for experimental design. With three biological replicates, nine of the 11 tools evaluated found only 20%–40% of the significantly differentially expressed (SDE) genes identified with the full set of 42 clean replicates. This rises to >85% for the subset of SDE genes changing in expression by more than fourfold. To achieve >85% for all SDE genes regardless of fold change requires more than 20 biological replicates. The same nine tools successfully control their false discovery rate at ≲5% for all numbers of replicates, while the remaining two tools fail to control their FDR adequately, particularly for low numbers of replicates. For future RNA-seq experiments, these results suggest that at least six biological replicates should be used, rising to at least 12 when it is important to identify SDE genes for all fold changes. If fewer than 12 replicates are used, a superior combination of true positive and false positive performances makes edgeR and DESeq2 the leading tools. For higher replicate numbers, minimizing false positives is more important and DESeq marginally outperforms the other tools.     

How many eggs should be laid in one's own nest and others’ in intra-specific brood parasitism?

Recent field studies have demonstrated that many bird species practice intra-specific brood parasitism. They lay eggs in the nests of other individuals of the same species, let the foster parents rear their offspring and avoid the cost of parental care. It has been shown that many birds, including starlings, swallows and geese, practice intra-specific brood parasitism in various forms. Intra-specific brood parasitism can be viewed in terms of optimal resource allocation: how many eggs should be put in the nests of other individuals under the risk of being parasitized by others. The situation here is a game, because the fitness of a parasitic individual depends on how other individuals behave (how many individuals practice parasitism and to what extent). The ecology of intra-specific brood parasitism has been investigated extensively by field ornithologists recently and it is full of material for modeling population/evolutionary biology. In this paper, I present a simple individual-based model to challenge the resource allocation problem in intra-specific brood parasitism. Previous theoretical studies of intra-specific brood parasitism have been based on ESS or quantitative genetics models, where a population is implicitly assumed to be homogeneous and the distribution form of the trait being studied (the allocation rate or the number of eggs laid parasitically) is inherently monomorphic. This paper aims to explore the evolution of intra-specific brood parasitism without these restrictions. In the model, an individual is assigned a strategy, an allocation ratio of eggs that are laid parasitically in the nests of other individuals, and the strategy is inherited by offspring either asexually or sexually. Based on the simulation analysis, the evolution of the allocation rate (the extent of intra-specific brood parasitism) is discussed. The extension of this model to a tractable analytical model is also discussed.     

How should the optical tweezers experiment be used to characterize the red blood cell membrane mechanics?

Stretching red blood cells using optical tweezers is a way to characterize the mechanical properties of their membrane by measuring the size of the cell in the direction of the stretching (axial diameter) and perpendicularly (transverse diameter). Recently, such data have been used in numerous publications to validate solvers dedicated to the computation of red blood cell dynamics under flow. In the present study, different mechanical models are used to simulate the stretching of red blood cells by optical tweezers. Results first show that the mechanical moduli of the membranes have to be adjusted as a function of the model used. In addition, by assessing the area dilation of the cells, the axial and transverse diameters measured in optical tweezers experiments are found to be insufficient to discriminate between models relevant to red blood cells or not. At last, it is shown that other quantities such as the height or the profile of the cell should be preferred for validation purposes since they are more sensitive to the membrane model.