Weidenreich,Coon, and multiregional evolution

Many theories of human evolution emphasie that there was significant geographic variation. They may have little else in common, though, and the idea that Coon provided the evolutionary basis for Weidenreich’s polycentrism, while multiregionalism cleansed Coon’s writings of racism has been misleading. Coon and Weidenreich were as different as polygenism and monogenism, and in the basis of their differences lies the genesis of multiregionalism.     

Parametric Procedures in the Analysis of Replicated Pairwise Interaction Point Patterns

A parametric approach fits particular classes of parametric models to the data, uses the model parameter estimates as summaries and tests for differences between groups by comparing fits with and without the assumption of common parameter values across groups. The paper discusses how a parametric approach can be implemented in the specific context of a single‐factor replicated spatial experiment and uses simulations to show when the parametric approach can be efficient or potentially misleading. An analysis of the spatial distribution of pyramidal neurons in human patients is also shown.     

Age and sex bias in the reconstruction of past population structures

Palaeodemographical studies are founded on the assumption that the sex and age distribution of the skeletal sample reflects the constitution of the original population. It is becoming increasingly clear, however, that the type and amount of information that may be derived from osteoarchaeological collections are related to the state of preservation of remains. This work proposes a new method to evaluate bone preservation, to identify age and sex biases in the preservation of human skeletal remains, and to assess whether differences in preservation patterns are more dependent on factors intrinsic or extrinsic to anatomical features of human bones. Three osteological collections and over 600 skeletons were observed. The state of preservation of human bones was assessed using three preservation indexes: the anatomical preservation index (API), the bone representation index (BRI), and the qualitative bone index (QBI). The results suggest that subadult skeletons are generally more poorly preserved and with bones less well-represented than adult skeletons. Among subadults, female and male skeletons have different patterns of preservation according to their age. This pattern of preservation depends on intrinsic anatomical properties of bones themselves, while external factors can only increase these differences in the state of preservation and representation of osseous remains. It is concluded from this that failure to recognize these differences may lead to misleading interpretations of paleodemography of past human populations.     

False cell lines: The problem and a solution

Hundreds of misleading reports are published every year containing data on human cancer cell lines that are derived from some other species, tissue or individual to that claimed. In consequence, millions of dollars provided for cancer research are being spent on the production of misleading data. This review describes how cross-contamination occurs, catalogues the use of false cell lines in leading biomedical journals, and suggests ways to resolve the problem. This revised version was published online in August 2006 with corrections to the Cover Date.     

Has the "Equal Environments" assumption been tested in twin studies?

A recurring criticism of the twin method for quantifying genetic and environmental components of human differences is the necessity of the so-called "equal environments assumption" (EEA) (i.e., that monozygotic and dizygotic twins experience equally correlated environments). It has been proposed to test the EEA by stratifying twin correlations by indices of the amount of shared environment. However, relevant environments may also be influenced by genetic differences. We present a model for the role of genetic factors in niche selection by twins that may account for variation in indices of the shared twin environment (e.g., contact between members of twin pairs). Simulations reveal that stratification of twin correlations by amount of contact can yield spurious evidence of large shared environmental effects in some strata and even give false indications of genotype x environment interaction. The stratification approach to testing the equal environments assumption may be misleading and the results of such tests may actually be consistent with a simpler theory of the role of genetic factors in niche selection.     

MEASURING THE PLASTICITY OF DEVELOPMENTAL RATE ACROSS INSECT POPULATIONS: COMMENT ON ROCHA AND KLACZKO (2012)

Rocha and Klaczko emphasize the general complexity of reaction norm shape and caution that ignoring such complexity can be misleading when forcing nonlinear reaction norms into linear shapes. They refer to our article on differences in plasticity of Drosophila serrata populations along a latitudinal gradient as an example of a misleading simplifying approach. However, their claim that an artifact is introduced into our analyses by calculating developmental rate as the reciprocal of development time (rate = time^?1) is based on a misunderstanding of the mathematical properties of the thermal developmental rate reaction norm. Here we discuss why developmental rate is a suitable measure for our study and under which circumstances it is appropriate to describe developmental rate by a linear model.     

Reduction of misleading ("false") positive results in mammalian cell genotoxicity assays. I. Choice of cell type

Current in vitro mammalian cell genotoxicity assays show a high rate of positive results, many of which are misleading when compared with in vivo genotoxicity or rodent carcinogenicity data. P53-deficiency in many of the rodent cell lines may be a key factor in this poor predictivity. As part of an European Cosmetics Industry Association initiative for improvement of in vitro mammalian cell assays, we have compared several rodent cell lines (V79, CHL, CHO) with p53-competent human peripheral blood lymphocytes (HuLy), TK6 human lymphoblastoid cells, and the human liver cell line, HepG2. We have compared in vitro micronucleus (MN) induction following treatment with 19 compounds that were accepted as producing misleading or "false" positive results in in vitro mammalian cell assays [6]. Of these, six chemicals (2-ethyl-1,3-hexandiol, benzyl alcohol, urea, sodium saccharin, sulfisoxazole and isobutyraldehyde) were not toxic and did not induce any MN at concentrations up to 10mM. d,l-Menthol and ethionamide induced cytotoxicity, but did not induce MN. o-Anthranilic acid was not toxic and did not induce MN in V79, CHL, CHO, HuLy and HepG2 cells up to 10mM. Toxicity was induced in TK6 cells, although there were no increases in MN frequency up to and above the 55% toxicity level. The other 10 chemicals (1,3-dihydroxybenzene, curcumin, propyl gallate, p-nitrophenol, ethyl acrylate, eugenol, tert-butylhydroquinone, 2,4-dichlorophenol, sodium xylene sulfonate and phthalic anhydride) produced cytotoxicity in at least one cell type, and were evaluated further for MN induction in most or all of the cell types listed above. All these chemicals induced MN at concentrations <10mM, with levels of cytotoxicity below 60% (measured as the replication index) in at least one cell type. The rodent cell lines (V79, CHO and CHL) were consistently more susceptible to cytotoxicity and MN induction than p53-competent cells, and are therefore more susceptible to giving misleading positive results. These data suggest that a reduction in the frequency of misleading positive results can be achieved by careful selection of the mammalian cell type for genotoxicity testing.     

Targeted tissue proteomic analysis of human astrocytomas

Complicating proteomic analysis of whole tissues is the obvious problem of cell heterogeneity in tissues, which often results in misleading or confusing molecular findings. Thus, the coupling of tissue microdissection for tumor cell enrichment with capillary isotachophoresis-based selective analyte concentration not only serves as a synergistic strategy to characterize low abundance proteins, but it can also be employed to conduct comparative proteomic studies of human astrocytomas. A set of fresh frozen brain biopsies were selectively microdissected to provide an enriched, high quality, and reproducible sample of tumor cells. Despite sharing many common proteins, there are significant differences in the protein expression level among different grades of astrocytomas. A large number of proteins, such as plasma membrane proteins EGFR and Erbb2, are up-regulated in glioblastoma. Besides facilitating the prioritization of follow-on biomarker selection and validation, comparative proteomics involving measurements in changes of pathways are expected to reveal the molecular relationships among different pathological grades of gliomas and potential molecular mechanisms that drive gliomagenesis.     

Chlorophyll,glycerolipid and protein ratios in spinach chloroplast grana and stroma lamellae

The relative molar amounts of glycerolipids are similar in grana and stroma lamellae, as are the ratios of total glycerolipid to weight of membrane protein. However the chlorophyll content relative to protein of grana lamellae is about 40% higher than that of stroma lamellae from the same preparation. Previous reports of chemical composition or enzyme activity based on chlorophyll alone can be highly misleading. The large functional and conformational differences between these two membranes may be related to these differences in pigment content, but are likely to result primarily from qualitative protein differences. The data are in accord with a membrane model in which nonpolar regions of membrane protein bind lipid in fairly constant amounts.     

Model misspecification and probabilistic tests of topology: evidence from empirical data sets

Probabilistic tests of topology offer a powerful means of evaluating competing phylogenetic hypotheses. The performance of the nonparametric Shimodaira-Hasegawa (SH) test, the parametric Swofford-Olsen-Waddell-Hillis (SOWH) test, and Bayesian posterior probabilities were explored for five data sets for which all the phylogenetic relationships are known with a very high degree of certainty. These results are consistent with previous simulation studies that have indicated a tendency for the SOWH test to be prone to generating Type 1 errors because of model misspecification coupled with branch length heterogeneity. These results also suggest that the SOWH test may accord overconfidence in the true topology when the null hypothesis is in fact correct. In contrast, the SH test was observed to be much more conservative, even under high substitution rates and branch length heterogeneity. For some of those data sets where the SOWH test proved misleading, the Bayesian posterior probabilities were also misleading. The results of all tests were strongly influenced by the exact substitution model assumptions. Simple models, especially those that assume rate homogeneity among sites, had a higher Type 1 error rate and were more likely to generate misleading posterior probabilities. For some of these data sets, the commonly used substitution models appear to be inadequate for estimating appropriate levels of uncertainty with the SOWH test and Bayesian methods. Reasons for the differences in statistical power between the two maximum likelihood tests are discussed and are contrasted with the Bayesian approach.     

Statistical properties of bootstrap estimation of phylogenetic variability from nucleotide sequences: II. Four taxa without a molecular clock

Summary The statistical properties of sample estimation and bootstrap estimation of phylogenetic variability from a sample of nucleotide sequences were studied by considering model trees of three taxa with an outgroup. The cases of constant and varying rates of nucleotide substitution were compared. From sequences obtained by simulation, phylogenetic trees were constructed by using the maximum parsimony (MP) and neighbor joining (NJ) methods. The effectiveness and consistency of the MP method were studied in terms of proportions of informative sites. The results of simulation showed that bootstrap estimation of the confidence level for an inferred phylogeny can be used even under unequal rates of evolution if the rate differences are not large so that the MP method is not misleading. The condition under which the MP method becomes misleading (inconsistent) is more stringent for slowly evolving sequences than for rapidly evolving ones, and it also depends on the length of the internal branch. If the rate differences are large so that the MP method becomes consistently misleading, then bootstrap estimation will reinforce an erroneous conclusion on topology. Similar conclusions apply to the NJ method with uncorrected distances. The NJ method with corrected distances performs poorly when the sequence length is short but can avoid the inconsistency problem if the sequence length is long and if the distances can be estimated accurately.Offprint requests to: W.-H. Li     

Uncertainty in identifying local extinctions: the distribution of missing data and its effects on biodiversity measures

Identifying local extinctions is integral to estimating species richness and geographic range changes and informing extinction risk assessments. However, the species occurrence records underpinning these estimates are frequently compromised by a lack of recorded species absences making it impossible to distinguish between local extinction and lack of survey effort—for a rigorously compiled database of European and Asian Galliformes, approximately 40% of half-degree cells contain records from before but not after 1980. We investigate the distribution of these cells, finding differences between the Palaearctic (forests, low mean human influence index (HII), outside protected areas (PAs)) and Indo-Malaya (grassland, high mean HII, outside PAs). Such cells also occur more in less peaceful countries. We show that different interpretations of these cells can lead to large over/under-estimations of species richness and extent of occurrences, potentially misleading prioritization and extinction risk assessment schemes. To avoid mistakes, local extinctions inferred from sightings records need to account for the history of survey effort in a locality.     

The specificity enigma: from mechanics to poems.

Biological specificity is usually described in terms of the lock-and-key metaphor. However, this metaphor is to a certain extent misleading and does not grasp the complexity underlying biological specificity. The failure of the lock-and-key metaphor makes it difficult to understand immune recognition. This is the reason why immune specificity has been described as the "Specificity Enigma." In this article, I point at three important differences between biological specificity and mechanical specificity, and suggest an alternative lens through which immune specificity can be considered.     

Epstein-Barr virus-induced transformation of B cells for the diagnosis of genetic metabolic disorders--enumerative conditions for cryopreservation

Epstein-Barr virus (EBV) infection in vitro causes transformation of B cells and generates B lymphoblastoid cell lines (LCLs). These LCLs have been widely used for the diagnostic of several genetic metabolic disorders. However, up to now, efficiency of LCL generation has been based on misleading subjective analysis. In this study, quantitative analyses have been performed to indicate efficiency of B-cell transformation to measuring human lysosomal acid hydrolases associated with: GM1-gangliosidosis type I, Gaucher disease and mucopolysaccharidosis type I. Peripheral blood mononuclear cells were isolated from 13 subjects, and LCLs were produced by culturing them with EBV for 12 days. Activities of the enzymes beta-galactosidase, beta-glucosidase and alpha-iduronidase were measured before and after cryopreservation in liquid nitrogen for 30 days. Efficiency of the B-cell transformation was screened every 4 days by the enumeration of cell proliferation, cell counts and changes in granularity estimated by flow cytometry. We observed the generation of 13 LCLs. Cell transformation was confirmed by the gradual increase of cellular clusters, cell size and granularity. In addition, we determined that the activity of the enzymes mentioned above did not change following cryopreservation. These data suggest that our enumerative approach for screening of EBV-LCLs is efficient for the enzymatic determination of human lysosomal acid hydrolases and may thus replace misleading subjective analyses.     

Going the distance: human population genetics in a clinal world

Global human genetic variation is greatly influenced by geography, with genetic differentiation between populations increasing with geographic distance and within-population diversity decreasing with distance from Africa. In fact, these 'clines' can explain most of the variation in human populations. Despite this, population genetics inferences often rely on models that do not take geography into account, which could result in misleading conclusions when working at global geographic scales. Geographically explicit approaches have great potential for the study of human population genetics. Here, we discuss the most promising avenues of research in the context of human settlement history and the detection of genomic elements under natural selection. We also review recent technical advances and address the challenges of integrating geography and genetics.     

Substrate specificities and properties of human phospholipases A2 in a mixed vesicle model.

Studies of the specificity of phospholipases A2 (PLA2s) for different substrates have usually been carried out in vesicles or mixed micelles, where differences in shape, size, or charge of vesicles formed with different phospholipids may give misleading results. Another factor is binding of the enzyme to the phospholipid surface, which has recently been addressed using vesicles of an anionic phospholipid, dimyristoyl-sn-glycero-3-phosphomethanol (DMPM) to which some extracellular PLA2s were shown to bind with a very high affinity (Jain, M. K., and Berg, O. G. (1989) Biochem. Biophys. Acta 1002, 127-156). In the present report we have used a similar system to study the substrate preferences of two human PLA2s that are thought to be physiologically relevant in the metabolism of arachidonic acid: a recombinant form of the human synovial fluid (14 kDa) PLA2 and the cytosolic (85 kDa) PLA2 found in monocytic cells. It is shown that both human enzymes bind tightly to DMPM vesicles and follow the basic characteristics of processive hydrolysis in this model using analysis of progress curves and substrate competition experiments. Mixed vesicles containing DMPM with small amounts (3-5 mol%) of other phospholipids have been used to study the substrate selectivity of the two human isoenzymes. The synovial fluid PLA2 shows a clear preference (approximately 7-fold) for sn-glycero-3-phosphoethanolamine over sn-glycero-3-phosphocholine. Within glycerophosphocholines, this enzyme displays little preference for the sn-2 fatty acyl group, and a slight preference for phospholipids with sn-1-acyl versus sn-1-alkyl substituents. In contrast, the cytosolic PLA2 shows a marked selectivity for arachidonoyl in the sn-2 position and only minor differences in selectivity for the polar head group in the sn-3 position. This enzyme does not distinguish between sn-1-acyl and sn-1-alkyl subclasses of glycerophosphocholines.     

Parameter estimation in approximate enzyme kinetics models

Enzyme kinetic modeling is based on a very specific approximation to a more detailed model; this approximation is often called the Michaelis-Menten approximation. Its success lies not only in an initial concentration difference that is set experimentally, but also in a certain difference among kinetic rate constants. Other differences among these constants lead to additional model approximations, often much simpler than the Michaelis-Menten approximation. Under the conditions where these alternate approximations apply, the Michaelis-Menten approximation would give misleading parameter estimates.     

Is It Human? Discriminating between Real Tracks and Track-Like Structures

Some human footprints-like hollows in the tuffaceous ground of an ancient quarry and of a recent anthropic path, created by the inhabitants no more than 30 years ago near the small village of Carangi (Caserta province, Southern Italy), allowed scientists to study some of the most misleading alteration processes of the volcanic tuff formations. The closeness of this site to the “Ciampate del Diavolo” ichnosite, bearing some of the oldest human fossil footprints, and the common stratigraphical and sedimentological background permitted accurate comparisons between actual human fossil footprints and footprint-like depressions, which can be easily mistaken for actual fossil evidence. This comparative study has permitted the reporting of some useful features and advice on distinguishing actual fossil footprints from natural and/or anthropic pseudo-tracks.     

On the WILCOXON-MANN-WHITNEY-Test as Nonparametric Analogue and Extension of t-Test

In the present paper some basic aspects of the WILCOXON -MANN -WHITNEY -test under various assumptions concerning the underlying distributions are studied. Starting with a formal analogy to Student's t-test its specific sensibility is worked out and the connexion to the problem of testing differences in location is discussed in detail as well as to the model with ordered alternatives. Further a counter example is given showing that the common verbal formulation the WILCOXON -MANN -WHITNEY -test being a test on ‘differences in distribution’ in general is misleading. As an example of an extended application of the WILCOXON -MANN -WHITNEY -statistic the test of POTT-HOFF (1963) on differences in medians of symmetric distributions is treated together with a discussion on suitable variance estimators to guarantee appropriate asymptotic distribution.     

Population differences in spatial learning in three-spined sticklebacks

In a changing environment, learning and memory are essential for an animal''s survival and reproduction. The role played by the environment in shaping learning and memory is now attracting considerable attention. Until now, studies have tended to compare the behaviour of two, or at best a few species but interspecific comparisons can be misleading as many life history variables other than environment may differ between species. Here we report on an experiment designed to determine how learning varies between different populations of the same species, the three-spined stickleback. We found differences between the populations in their ability to solve a spatial task and also in the spatial strategies they used. A second simple learning task showed that these differences were not the result of gross differences in learning ability or adaptation to laboratory conditions. We discuss these results and suggest that the behavioural differences may relate to features of the respective habitats from which the fish were sampled.