Neanderthal hand and foot remains from Moula‐Guercy,Ardèche,France

The hand and foot remains from Moula‐Guercy cave (Ardèche, France) comprise 24 specimens of Eemian age (ca. 120 ka). The specimens include primarily complete elements, which are rare among the Moula‐Guercy postcrania. The hand remains have several characteristic Neanderthal traits including a laterally facing (parasagittally oriented) second metacarpal‐capitate articulation, a short styloid process, a wide proximal articular surface on the third metacarpal, and absolutely expanded apical tuberosities on the distal hand phalanges relative to modern humans. The foot remains include several incomplete elements along with an antimeric pair of naviculars, a medial cuneiform and cuboid, and a single complete element from each of the distal segments (one each: metatarsal, proximal foot phalanx, intermediate foot phalanx, distal foot phalanx). Consistent among the specimens are relatively wide diaphyses for length in the metatarsals and phalanges and large and prominent muscle attachments, both consistent with previously published Neanderthal morphology. The hand and foot collection from Moula‐Guercy is an important dataset for future studies of Neanderthal functional morphology, dexterity, and behavior as it represents a previously undersampled time period for European Neanderthals. Am J Phys Anthropol 152:516–529, 2013. © 2013 Wiley Periodicals, Inc.     

The Effect of Nonindependent Mate Pairing on the Effective Population Size

The effective population size (N_e) quantifies the effectiveness of genetic drift in finite populations. When generations overlap, theoretical expectations for N_e typically assume that the sampling of offspring genotypes from a given individual is independent among successive breeding events, even though this is not true in many species, including humans. To explore the effects on N_e of nonindependent mate pairing across breeding events, we simulated the genetic drift of mitochondrial DNA, autosomal DNA, and sex chromosome DNA under three mating systems. Nonindependent mate pairing across breeding seasons has no effect when all adults mate pair for life, a small or moderate effect when females reuse stored sperm, and a large effect when there is intense male–male competition for reproduction in a harem social system. If adult females reproduce at a constant rate irrespective of the type of mate pairing, the general effect of nonindependent mate pairing is to decrease N_e for paternally inherited components of the genome. These findings have significant implications for the relative N_e values of different genomic regions, and hence for the expected levels of DNA sequence diversity in these regions.THE effective population size (N_e) is a fundamental parameter of population genetics, which quantifies the effect of genetic drift, the stochastic change in allele frequencies over time in a population of finite size (Wright 1931). The magnitude of N_e affects both the level of genetic variability within a population and the efficiency with which populations retain mildly beneficial mutations and purge mildly deleterious ones. This influences a myriad of genetic phenomena, such as the level of DNA sequence polymorphism, the rate of substitution of nonsynonymous and functional noncoding nucleotide positions, the abundance of transposable elements, levels of variation, and the rate of evolution of gene expression, the persistence of duplicate genes, and genome size and organization (Lynch 2007; Charlesworth 2009). There are a variety of definitions of N_e; here we use the definition in terms of the mean coalescence time of a pair of neutral alleles, which is given by 2N_e (Charlesworth 2009). This definition has the useful feature that the expected pairwise nucleotide site diversity under the widely used infinite sites model is equal to 4N_eμ, where μ is the neutral mutation rate (Kimura 1971).As a result of differences in their ploidy level and mode of inheritance, autosomal DNA (aDNA), the X chromosome (xDNA), the Y chromosome (yDNA), and maternally transmitted organelle DNA such as mitochondrial DNA (mtDNA) generally have a different N_e values. Under certain conditions, such as constant population size, discrete generations, a Poisson distribution of reproductive success, and a sex ratio equal to one, the relative N_e values of these genomic regions (N_e-a, N_e-x, N_e-mt, and N_e-y) are expected to be 4:3:1:1 (Charlesworth 2009). This is because aDNA is biparentally inherited and diploid; xDNA is biparentally inherited, diploid in females, and haploid in males (with female heterogamety, the reverse applies to the Z chromosome), and yDNA (the W chromosome, with female heterogamety) and mtDNA are both effectively uniparentally inherited and haploid in most species.However, several characteristics of natural populations, such as unequal numbers of males and females and nonrandom variation in reproductive success, can affect the value of N_e, even for populations with discrete generations (reviewed in Caballero 1994; Hedrick 2007; Charlesworth 2009). In addition, natural selection at sites linked to neutral markers also has the potential to increase N_e (under balancing selection) (Charlesworth 2006) or to decrease N_e (with background selection or selective sweeps) (Hudson and Kaplan 1988; Charlesworth et al. 1993). Because the nature of natural selection varies in different genomic regions, especially in relation to the rate of recombination, N_e may also vary among unlinked regions with the same ploidy and mode of inheritance, for example, different portions of an autosomal chromosome (Gossmann et al. 2011). In natural populations, these factors can skew the relative N_e values away from the 4:3:1:1 expectation. Even when the effects of natural selection and “nonideal” demography are ignored, the 4:3:1:1 relation still has a large variance when applied to individual loci (Hudson and Turelli 2003).When generations overlap, an additional source of possible deviations from these idealized relations arises from variation among individuals in survival and reproductive success among breeding seasons (Felsenstein 1971; Hill 1972, 1979; Johnson 1977) and from sex differences in demographic parameters and stochastic changes in population size (Engen et al. 2007). In contrast, the effect of a high variance in reproductive success caused by male–male competition is lessened when generations overlap for many breeding seasons (Nunney 1993; Charlesworth 2001). Conversely, overlapping generations with nonindependent mate pairing across breeding seasons could increase the variance in reproductive success. For example, in humans, paternity is correlated with paternal confidence in paternity (Anderson 2006), and married individuals tend to repeatedly produce offspring with each other more frequently than expected by chance. Nonindependent mate pairing among breeding seasons occurs in many other species as well—for example, long-term pair bonding in prairie voles (DeVries et al. 1995), harems in gorillas (Gatti et al. 2004), and sperm storage in fruit flies (Neubaum and Wolfner 1999).Current theoretical models that allow calculation of the effective population size with overlapping generations and age structure make several simplifying assumptions, notably constant sizes of each age class, sufficiently large numbers of individuals in each age class that second-order terms in their reciprocals can be neglected, and independent sampling of offspring genotypes from the same individual reproducing at different times (Hill 1972; Nunney 1991, 1993; Caballero 1994; Charlesworth 1994, 2001). The latter assumption in particular makes it difficult to provide accurate expressions for species such as humans and Drosophila, which reproduce nonindependently because of long-term pair bonds and sperm storage, respectively (Charlesworth 2001).The goal of this study is therefore to explore the consequences of nonindependence of reproductive events across time in different social systems and with different age structures, using simulations of genetic drift in two types of age-structured populations, under different scenarios of independent and nonindependent mate pairing among breeding events. We have explored how these scenarios affect the relative values of N_e-a, N_e-x, N_e-mt, and N_e-y using the infinite alleles model of mutation (Kimura and Crow 1964), with particular emphasis on comparisons of similar mating systems that differ in the extent of nonindependence among breeding events.     

Discovery and SAR of PF-4693627, a potent,selective and orally bioavailable mPGES-1 inhibitor for the potential treatment of inflammation

Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new therapeutic target for safe and effective anti-inflammatory drugs. The discovery of a novel series of orally active, selective benzoxazole piperidinecarboxamides as mPGES-1 inhibitors is described. Structure–activity optimization of lead 5 with cyclohexyl carbinols resulted in compound 12, which showed excellent in vitro potency and selectivity against COX-2, and reasonable pharmacokinetic properties. Further SAR studies of the benzoxazole ring substituents lead to a novel series of highly potent compounds with improved PK profile, including 23, 26, and 29, which were effective in a carrageenan-stimulated guinea pig air pouch model of inflammation. Based on its excellent in vitro and in vivo pharmacological, pharmacokinetic and safety profile and ease of synthesis, compound 26 (PF-4693627) was advanced to clinical studies.     

New bioactive dihydrofuranocoumarins from the roots of the Tunisian Ferula lutea (Poir.) Maire

A phytochemical investigation of the roots of Ferula lutea (Poir.) Maire led to the isolation of new dihydrofuranocoumarins as two inseparable isomers, (?)-5-hydroxyprantschimgin 1 and (?)-5-hydroxydeltoin 2, together with eight known compounds, (?)-prantschimgin 3, (?)-deltoin 4, psoralen 5, xanthotoxin 6, umbelliferone 7, caffeic acid 8, β-sitosterol 9 and stigmasterol 10. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR experiments and mass spectroscopy analysis, as well as by comparison with literature data. The anti-acetylcholinesterase and cytotoxic effects of the isolates and antioxidant activities of the mixture (1+2) were also evaluated in this work. Results showed that the mixture (1+2) has the most cytotoxic activity with IC₅₀ values 0.29 ± 0.05 and 1.61 ± 0.57 μM against the cell lines HT-29 and HCT 116, respectively. The greatest acetylcholinesterase inhibitory activity (IC₅₀ = 0.76 ± 0.03) was exhibited by the xanthotoxin 6. In addition, the mixture (1+2) was investigated for its antioxidant activity and showed IC₅₀ values 18.56, 13.06, 7.59, and 4.81 μM towards DPPH free radical scavenging, ABTS radical monocation, singlet oxygen and hydrogen peroxide, respectively.     

Partitioning of genetic variation across the genome using multimarker methods in a wild bird population

The underlying basis of genetic variation in quantitative traits, in terms of the number of causal variants and the size of their effects, is largely unknown in natural populations. The expectation is that complex quantitative trait variation is attributable to many, possibly interacting, causal variants, whose effects may depend upon the sex, age and the environment in which they are expressed. A recently developed methodology in animal breeding derives a value of relatedness among individuals from high‐density genomic marker data, to estimate additive genetic variance within livestock populations. Here, we adapt and test the effectiveness of these methods to partition genetic variation for complex traits across genomic regions within ecological study populations where individuals have varying degrees of relatedness. We then apply this approach for the first time to a natural population and demonstrate that genetic variation in wing length in the great tit (Parus major) reflects contributions from multiple genomic regions. We show that a polygenic additive mode of gene action best describes the patterns observed, and we find no evidence of dosage compensation for the sex chromosome. Our results suggest that most of the genomic regions that influence wing length have the same effects in both sexes. We found a limited amount of genetic variance in males that is attributed to regions that have no effects in females, which could facilitate the sexual dimorphism observed for this trait. Although this exploratory work focuses on one complex trait, the methodology is generally applicable to any trait for any laboratory or wild population, paving the way for investigating sex‐, age‐ and environment‐specific genetic effects and thus the underlying genetic architecture of phenotype in biological study systems.     

Mhc‐linked survival and lifetime reproductive success in a wild population of great tits

Major histocompatibility complex (Mhc) genes are frequently used as a model for adaptive genetic diversity. Although associations between Mhc and disease resistance are frequently documented, little is known about the fitness consequences of Mhc variation in wild populations. Further, most work to date has involved testing associations between Mhc genotypes and fitness components. However, the functional diversity of the Mhc, and hence the mechanism by which selection on Mhc acts, depends on how genotypes map to the functional properties of Mhc molecules. Here, we test three hypotheses that relate Mhc diversity to fitness: (i) the maximal diversity hypothesis, (ii) the optimal diversity hypothesis and (iii) effect of specific Mhc types. We combine mark–recapture methods with analysis of long‐term breeding data to investigate the effects of Mhc class I functional diversity (Mhc supertypes) on individual fitness in a wild great tit (Parus major) population. We found that the presence of three different Mhc supertypes was associated with three different components of individual fitness: survival, annual recruitment and lifetime reproductive success (LRS). Great tits possessing Mhc supertype 3 experienced higher survival rates than those that did not, whereas individuals with Mhc supertype 6 experienced higher LRS and were more likely to recruit offspring each year. Conversely, great tits that possessed Mhc supertype 5 had reduced LRS. We found no evidence for a selective advantage of Mhc diversity, in terms of either maximal or optimal supertype diversity. Our results support the suggestion that specific Mhc types are an important determinant of individual fitness.     

The impact of strain diversity and mixed infections on the evolution of resistance to Bacillus thuringiensis

Pesticide mixtures can reduce the rate at which insects evolve pesticide resistance. However, with live biopesticides such as the naturally abundant pathogen Bacillus thuringiensis (Bt), a range of additional biological considerations might affect the evolution of resistance. These can include ecological interactions in mixed infections, the different rates of transmission post-application and the impact of the native biodiversity on the frequency of mixed infections. Using multi-generation selection experiments, we tested how applications of single and mixed strains of Bt from diverse sources (natural isolates and biopesticides) affected the evolution of resistance in the diamondback moth, Plutella xylostella, to a focal strain. There was no significant difference in the rate of evolution of resistance between single and mixed-strain applications although the latter did result in lower insect populations. The relative survivorship of Bt-resistant genotypes was higher in the mixed-strain treatment, in part owing to elevated mortality of susceptible larvae in mixtures. Resistance evolved more quickly with treatments that contained natural isolates, and biological differences in transmission rate may have contributed to this. Our data indicate that the use of mixtures can have unexpected consequences on the fitness of resistant and susceptible insects.     

Chilo partellus (Swinhoe) (Lepidoptera: Pyralidae) a new invasive species in Israel

Chilo partellus, the spotted stem borer (SSB), is reported for the first time from the fields of sorghum and corn in Israel. Spotted stem borer larvae were first discovered in July 2010 on sorghum and corn plants in the Western Galilee. The new pest had spread all over northern Israel by the end of 2011. The identity of the new pest was confirmed using the morphology of the dissected male genitalia and its attraction to SSB sex pheromone.     

Intérêt de l’imagerie hybride TEMP/TDM dans la localisation des glandes parathyroïdes ectopiques : à propos de 3 cas

The presence of a parathyroid gland in ectopic position constitutes one of the leading causes of surgery failure. For this purpose, scintigraphy takes a major place in the anatomical localization of pathological parathyroid and so facilitates its treatment. The advent of hybrid cameras combining single photon emission tomography to CT (SPECT/CT) has further strengthened the contribution of this imaging modality in the precise localization of ectopic parathyroid and its anatomical relationships. The objective of our work is to illustrate the interest of hybrid imaging SPECT/CT, compared to planar scintigraphy and ultrasounds within the framework of primary hyperparathyroidism, particularly ectopic situation through three cases.     

Intérêt de la scintigraphie pulmonaire de perfusion dans les dilatations des bronches de l’enfant

IntroductionBronchiectasis is a chronic disease of the lungs by repeated respiratory infection. An early and adequate diagnosis and management reduce the morbidity and mortality of this disease. The aim of this study is to emphasize the importance of the combination of Computer Tomography (CT) and lung perfusion scan (SPP) in the diagnosis and therapeutic approach.Materials and methodsForty-three children were referred in the nuclear medicine department with a clinical diagnosis of bronchiectasis; they underwent a CT and a SPP.Results and conclusionBy analyzing the results of the SPP and CT separately, we conclude that there is no significant difference between the two investigations. The combination of the two explorations provides a gain in most surgical therapeutic orientation.