Les néandertaliens de la Caverna delle Fate (Finale Ligure,Italie). I - Chronostratigraphie,restes squelettiques

The new excavations derived by the French-Italian team in the Caverna delle Fate, Finale Ligure (Italy) between 1983 and 1987 have permitted the digging up neandertalian remains in a chronostratigraphic and paleoenvironmental accurate context. They increased the bones identified in the old collection of the Father Amerano's excavations. Actually 16 humain remains including frontal elements, zygomatique, occipital fragment, hemimandible, mandible and 10 isolated teeth can be attributed to one adult and one child 8–10 years old. This assemblage shows two interesting topics: these human remains have affinities with other neandertalian elements discovered in the occidental European Mediterranean area, so that we propose the existence of a gracile neandertalian population in this region; their chronological attribution to the MIS 5.1 suggests that at this stage the neandertalian apomorphies are not wholly integrated.     

Les restes humains du Pliocène final et du début du Pléistocène inférieur de Dmanissi, Géorgie (1991-2000). I - Les crânes, D 2280, D 2282, D 2700

Since 1991, several human remains: 5 skulls, 4 mandibles and numerous postcranial fragments have been discovered on the Dmanissi prehistoric open site. It is an exceptional discovery due to the stratigraphical, paleontological and cultural context, which is well known and accurately well dated (Upper Pliocene-Early Pleistocene). Most of the hominids discovered in the level V and VI are dated between 1.81 My (level V) and 1.77 My (level VI) corresponding to a 40,000 years period. The assemblage of fossil human remains is peculiar due to (1) the quality of bone representation (distinct parts of the skeleton are preserved: skull, thorax, upper and lower limbs, belt), (2) the high degree of bone preservation (skulls and long bones are entire, rarely broken or crushed), (3) the diversity age at death estimated for each of the 5 individuals (3 adults, 1 young adult, 1 adolescent of both sexes). The study dealing with the first discovered mandibles and skulls has begun with Leo Gabounia since 1991 and represents several interests: 1) a paleoanthropological interest: the Dmanissi skulls are characterized by their small size; they are short, narrow and low. The skullcaps are less elevated than those of the Homo erectus group and even those of Homo ergaster. They are more elevated than those of Homo habilis and very close to Homo rudolfensis. The elevation and the transversal development of the middle part of the skull in the parietotemporal region are more significant: the Dmanissi specimens are intermediate between Homo habilis and Homo ergaster. In term of cranial capacity, a similar trend is observed. Generally speaking, the skull is slender. The vault is more flat than in Homo erectus, the frontal bone is less developed, divergent and the postorbital constriction is strong. The temporal bone is long, flat and the mastoid part is short. The upper part of the occipital bone is low and narrow. Crests are thin, less developed than in the Homo erectus group. The superior temporal crests are in a high position and a torus angularis is present on the adult-male specimen. The glenoid cavity is large with strong edges. The petrotympanic region is slender with a tympanic circle individualized and it shows a horizontal rotation in a posterior position, which is distinct from Homo erectus. The orthognathic trend of the face distinguishes the Dmanissi specimens from the early Pleistocene hominids (Homo habilis, Homo ergaster) and from the first Eurasian Homo erectus. Nevertheless, the subnasal region of the face is projected. The morphology of the mid-face, showing a developed pillar of the canine, an inframalar incurvation and an anterior position of the root of the zygomaticomaxillary crest, suggests strong masticatory stress. Considering the overall morphology, cranial and metrical features, the Dmanissi fossil skulls are intermediate to the Homo habilis-rudolfensis group and Homo ergaster while they are closer to the former and peculiarly to Homo rudolfensis (ER 1470). However, the Dmanissi fossil skulls are distinct from Homo rudolfensis by numerous features and among them: by their large maximum cranial width (Euryon-Euryon), the posterior rotation of their petrotympanic structure and the strong development of the pillar of their canine. Due to the gracility of their face, the narrowness of their occipital bone, and their cranial base pattern (mastoid region and petrotympanic structure), the Dmanissi fossil skulls are different from the Homo erectus group: 2) the abundance of the human fossils discovered in Dmanissi site provides information about the biodiversity of these hominids with the establishment of the morphological features related to either growth or sexual patterns: 3) compared to modern humans, the Dmanissi fossil skulls seem to follow a different growth pattern. The present study of the fossil skulls discovered is a pioneer step. Indeed, the Dmanissi site has yielded the oldest evidences of the first settlements in Eurasia, which were, until now, attributed to Homo erectus. The Dmanissi fossil skulls are close to the Homo habilis-rudolfensis African group. We attribute these hominids to Homo georgicus.     

The sensitivity and specificity of markers for event times

The statistical literature on assessing the accuracy of risk factors or disease markers as diagnostic tests deals almost exclusively with settings where the test, Y, is measured concurrently with disease status D. In practice, however, disease status may vary over time and there is often a time lag between when the marker is measured and the occurrence of disease. One example concerns the Framingham risk score (FR-score) as a marker for the future risk of cardiovascular events, events that occur after the score is ascertained. To evaluate such a marker, one needs to take the time lag into account since the predictive accuracy may be higher when the marker is measured closer to the time of disease occurrence. We therefore consider inference for sensitivity and specificity functions that are defined as functions of time. Semiparametric regression models are proposed. Data from a cohort study are used to estimate model parameters. One issue that arises in practice is that event times may be censored. In this research, we extend in several respects the work by Leisenring et al. (1997) that dealt only with parametric models for binary tests and uncensored data. We propose semiparametric models that accommodate continuous tests and censoring. Asymptotic distribution theory for parameter estimates is developed and procedures for making statistical inference are evaluated with simulation studies. We illustrate our methods with data from the Cardiovascular Health Study, relating the FR-score measured at enrollment to subsequent risk of cardiovascular events.     

New embedding medium for sectioning undecalcified bone

Methylmethacrylate (MMA) is the most commonly used embedding medium for sectioning undecalcified bone; however, a number of problems exist with its use in a research laboratory. MMA requires a long infiltration time and temperature control, and it reacts with many polymers. We used Kleer Set resin? as an alternative embedding medium for sectioning undecalcified bone specimens. Fluorochrome labeled bone specimens were sectioned transversely using a ground section technique and longitudinally on a sledge macrotome. The slides were viewed using both transmitted light and epifluorescence microscopy. High quality sections were obtained using Kleer Set resin? for both sectioning techniques. We have shown that this new embedding medium is simpler, safer, quicker to use and does not interfere with visualization of fluorochromes.     

Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5×10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4×10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10⁻¹²) and DPA (p = 1×10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1×10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.     

Synthesis and pharmacological evaluation of novel Amino-prostanoids: potent and orally effective thromboxane A2 receptor antagonists

Modification of the thromboxane receptor antagonists, GR 32191, has led to a series of readily synthesized amino-prostanoids. The most effective compound is GR 70067, an orally active agent that may be useful in the treatment of thrombotic disease.     

Blood groups and protein polymorphisms in five goat breeds (Capra hircus)

Data on allele frequencies at six red cell blood group systems and three blood protein polymorphic loci in five goat breeds are reported. Two blood proteins, albumin and carbonic anhy-drase, were not found to be polymorphic. The B blood group system of goats, like its homologue in cattle and sheep, is highly complex. At least 44 B phenogroups (haplotypes) have been distinguished in this study. Based on the variation in allele frequencies between breeds, genetic distances were calculated. The distances estimated by four different methods were in close agreement with data from the history and geographic origins of the breeds examined.