CCR5 Revisited: How Mechanisms of HIV Entry Govern AIDS Pathogenesis

The chemokine receptor CCR5 has been the focus of intensive studies since its role as a coreceptor for HIV entry was discovered in 1996. These studies lead to the development of small molecular drugs targeting CCR5, with maraviroc becoming in 2007 the first clinically approved chemokine receptor inhibitor. More recently, the apparent HIV cure in a patient transplanted with hematopoietic stem cells devoid of functional CCR5 rekindled the interest for inactivating CCR5 through gene therapy and pharmacological approaches. Fundamental research on CCR5 has also been boosted by key advances in the field of G-protein coupled receptor research, with the realization that CCR5 adopts a variety of conformations, and that only a subset of these conformations may be targeted by chemokine ligands. In addition, recent genetic and pathogenesis studies have emphasized the central role of CCR5 expression levels in determining the risk of HIV and SIV acquisition and disease progression. In this article, we propose to review the key properties of CCR5 that account for its central role in HIV pathogenesis, with a focus on mechanisms that regulate CCR5 expression, conformation, and interaction with HIV envelope glycoproteins.     

The potency of lemon (Citrus limon L.) essential oil to control some fungal diseases of grapevine wood

This study aimed to evaluate the in vitro antifungal activity (AA) of the essential oil (EO) of lemon (Citrus limon L.) against three pathogenic fungi attacking grapevine wood. The composition of the EO was also studied. Ten volatile components were identified by gas chromatography–mass spectrometry. The results showed that the EO consists of volatile components where monoterpene hydrocarbons are the most abundant ones. Four major components were identified, which represent 99.9% of the total EO (limonene, neral, ß-pinene, and ?-terpinene). The AA of the EO was evaluated against three pathogenic fungi attacking grapevine wood (Eutypa sp., Botryosphaeria dothidea, and Fomitiporia mediterranea). The results showed that the EO exerts AA against all tested fungi and significantly inhibits their growth. Eutypa sp. is the most sensitive fungus. These results show, for the first time, a new use for the EO of lemon (C. limon L.) to control fungal diseases of grapevine wood.     

Étude craniométrique du complexe d’espèces Meriones shawii–grandis (Mammalia : Rodentia) au Maroc,en Algérie et en Tunisie

In North Africa, the rodents of the species complex Meriones shawii–grandis have a considerable ecological, economic and epidemiological importance. Until now, the systematics of these species was subject to discussion due to the presence of populations displaying high morphological variability. By means of an approach of traditional morphometrics based on cranial distances and by using the method of the log shape-ratio, we attempt to characterize morphologically these two taxa. The results show significant differences in size and shape between the specimens of Morocco, on the one hand, and those of Algeria and Tunisia, on the other hand. The samples of Morocco that have been molecularly typed and attributed to M. grandis have larger tooth rows and narrower skulls, as well as relatively small tympanic bullae. On the other hand, those of Algeria and Tunisia assigned to M. shawii are characterized by small tooth rows and wide skulls with well-developed tympanic bullae. The morphological distance is relatively strong between both clades (79.5%), which corresponds to the molecular distance. However, the discriminant analysis performed after molecularly-typed specimens allows the correct classification of only 91.8% of the individuals.     

Occurrence of the Lower Cambrian anemone-style trace fossils in the Zabuk Formation (Mardin–Derik,SE Turkey)

The Zabuk Formation of the Derik Group exposed over much of south-eastern Turkey presents a succession composed of shallow marine and fluvial siliciclastic sedimentary rocks. The Lower Cambrian assemblages containing abundant anemone-style trace fossils are known from most major palaeocontinents such as Laurentia, Baltica, and Gondwana. These have possible affinities with semi-infaunal dwelling anemones on siliciclastic mid-latitude shelves of West Gondwana in early Fortunian deposits. Among them is Bergaueria, characterized by plug-shaped burrows as exemplified by Bergaueria perata, that is, a characteristic trace fossil of the Cambrian globally.     

Regulation of phospholipase D by phosphorylation-dependent mechanisms

The rapid production of phosphatidic acid following receptor stimulation has been demonstrated in a wide range of mammalian cells. Virtually every cell uses phosphatidylcholine as substrate to produce phosphatidic acid in a controlled reaction catalyzed by specific PLD isoforms. Considerable effort has been directed at studying the regulation of PLD activities and subsequent work has characterized a family of proteins including PLD1 and PLD2. Whereas both PLD enzymes are dependent on phosphatidylinositol 4,5-bisphosphate for activity only the PLD1 isoform was strongly stimulated by the small GTPases ARF and RhoA and by protein kinase Cα as well. A role for tyrosine kinase activities in the membrane recruitment of small GTPases, in the synthesis of phosphatidylinositol 4,5-bisphosphate and tyrosine phosphorylation of PLD1 and PLD2 has been uncovered. However, it still not clear exactly how tyrosine phosphorylation of proteins contributes to PLD activation in cells. Here we review the data linking tyrosine phosphorylation of proteins to the activation of PLD and describe recent finding on the sites and possible mechanisms of action of tyrosine kinases in receptor-mediated PLD activation. Finally, a model illustrating the potential complex interplay linking these signaling events with the activation of PLD is presented.     

Roveacrinids (Crinoidea,Roveacrinida) from the Cenomanian-Turonian of southwest Algeria (Saharan Atlas and Guir Basin)

In the southwestern part of Algeria, the Cenomanian-Turonian marine deposits build up a prominent ledge in a perched syncline (Ksour Mountains, western Saharan Atlas) or at high radius of curvature (Guir Basin). The petrographical analysis of the Cenomanian-Turonian deposits of the Ksour Mountains and of the Guir Basin reveals unexpected assemblages of roveacrinoidal ossicles comparable with those formerly reported from the Tinrhert area. For the first time, isolated ossicles of genuine and undisputable Roveacrinidae are illustrated. Three sections, Djebel Rhoundjaia (western Saharan Atlas), Berridel and Kénadsa (Guir Basin), were scrutinized to recognize the microcrinoidal sections within the carbonate microfacies and to compile the successive occurrence of respective roveacrinid taxa (besides the classical search for standard index microfossils) in an attempt to pinpoint more precisely the position of the Cenomanian-Turonian boundary (C/T B). These assemblages are particularly morphologically and taxonomically diverse with three species of genus Roveacrinus and one of genus Orthogonocrinus. The presence of Saccocomidae (Applinocrinus) is especially unusual in such stratigraphic levels. The relative abundance and diversity of Roveacrinidae evidence a peak when approaching the C/T B. Such an event is recurring in the latest Cenomanian in various Tethyan and Atlantic areas. These fluctuations are consistent with a high surface-water productivity just before the C/T B.     

Adaptation to bipedal gait and fifth metatarsal structural properties in Australopithecus,Paranthropus, and Homo

Humans, unlike African apes, have relatively robust fifth metatarsals (Mt5) presumably reflecting substantial weight-bearing and stability function in the lateral column of the former. When this morphological difference emerged during hominin evolution is debated. Here we investigate internal diaphyseal structure of Mt5s attributed to Australopithecus (from Sterkfontein), Paranthropus (from Swartkrans), and Homo (from Olduvai, Dmanisi, and Dinaledi) placed in the context of human and African ape Mt5 internal diaphyseal structure. ‘Whole-shaft’ properties were evaluated from 17 cross sections sampling 25% to 75% diaphyseal length using computed tomography. To assess structural patterns, scaled cortical bone thicknesses (sCBT) and scaled second moments of area (sSMA) were visualized and evaluated through penalized discriminant analyses. While the majority of fossil hominin Mt5s exhibited ape-like sCBT, their sSMA were comparatively more human-like. Human-like functional loading of the lateral column existed in at least some fossil hominins, although perhaps surprisingly not in hominins from Dmanisi or Dinaledi.     

Endocrine disruptors (EDs) and hormone-dependent cancers: Correlation or causal relationship?

The selective increase in the incidence of hormone-dependent cancers (breast, prostate, testicular) in industrialized countries is associated with the increasing number of endocrine disruptors (EDs) in the environment and raises questions about the role of EDs in mammary carcinogenesis. Answering these questions is difficult because the number of EDs is large and varies with time. Moreover hormonal carcinogenesis is multifactorial and progresses slowly and in stages. This discussion will be limited to breast cancer and three EDs: distilbene, bisphenol A (BPA), and dichlorodiphenyltrichloroethane (DDT). All these three EDs bind estrogen receptors, albeit with widely different affinities. Several complementary approaches have been used: French cancer records, epidemiological studies on cohorts followed over several decades, numerous in vitro experimental studies using cell cultures and in vivo animal studies. These approaches all converge to the same result, strongly suggesting a causal relationship between EDs and precancerous lesions. Except for distilbene, the mechanisms and molecular targets involved are still unclear, which makes it difficult to look for substitute products that are just as efficient, but less toxic.     

Dorsal rib histology of dinosaurs and a crocodylomorph from western Portugal: Skeletochronological implications on age determination and life history traits

Bone histology is an important tool for uncovering life history traits of extinct animals, particularly those that lack modern analogs, such as the non-avian dinosaurs. In most studies, histological analyses preferentially focus on long bones for understanding growth rates and determining age. Here we show, by analyzing ornithischians (a stegosaur and an ornithopod), saurischians (a sauropod and a theropod), and a crocodile, rib histology is a suitable alternative. The estimated age for all sampled taxa ranges between 14 to 17 years for Lourinhanosaurus antunesi and 27 to 31 years estimated for Draconyx loureiroi. The theropod Baryonyx was skeletally mature around 23–25 years of age but showed unfused neurocentral sutures, a paedomorphic feature possibly related to aquatic locomotion. Our results show that ribs can contain a nearly complete growth record, and reveal important information about individual age, point of sexual maturity, and, in some cases, sex. Because ribs are more available than long bones, this method opens new possibilities for studying rare and incomplete fossils, including holotypes.     

Trophic ecology of the pikeperch (Sander lucioperca) in its introduced areas: a stable isotope approach in southwestern France

During the last decades, non-native predatory fish species have been largely introduced in European lakes and rivers, calling for detailed information on the trophic ecology of co-existing native and non-native predators. The present study describes the trophic ecology of the introduced pikeperch (Sander lucioperca) in two southwestern French rivers, using stable isotope analysis. Pikeperch could be categorized as a top-predator, and had a significantly higher trophic position (TP, mean±SE=4.2±0.1) compared to other predatory fish such as the native pike (Esox lucius, TP=3.7±0.1) and the introduced European catfish (Silurus glanis, TP=3.8±0.1). Most studies of resource use in freshwaters consider predatory fish as ecologically equivalent; however, this study showed that the pikeperch occupied a higher trophic niche compared to other predatory species in the Lot and Tarn rivers (Garonne River basin). This apparent specialization may thus have consequences upon interspecific relationships within the predatory guild and upon the functional organization of biological communities. To cite this article: D. Kopp et al., C. R. Biologies 332 (2009).