Cynocephalid dermopterans from the Palaeogene of South Asia (Thailand, Myanmar and Pakistan): systematic, evolutionary and palaeobiogeographic implications

Cynocephalid dermopterans (flying lemurs) are represented by only two living genera (Cynocephalus and Galeopterus), which inhabit tropical rainforests of South‐East Asia. Despite their very poor diversity and their limited distribution, dermopterans play a critical role in higher‐level eutherian phylogeny inasmuch as they represent together with Scandentia (tree‐shrew) the sister group of the Primates clade (Plesiadapiformes + Euprimates). However, unlike primates, for which the fossil record extends back to the early Palaeogene on all Holarctic continents and in Africa, the evolutionary history of the order Dermoptera sensu stricto (Cynocephalidae) has so far remained undocumented, with the exception of a badly preserved fragment of mandible from the late Eocene of Thailand (Dermotherium major). In this paper, we described newly discovered fossil dermopterans (essentially dental remains) from different regions of South Asia (Thailand, Myanmar, and Pakistan) ranging from the late middle Eocene to the late Oligocene. We performed microtomographic examinations at the European Synchrotron Radiation Facility (ESRF, Grenoble, France) to analyse different morphological aspects of the fossilized jaws. The abundant material from the late Oligocene of Thailand (Nong Ya Plong coal mine) allows us to emend the diagnosis of the genus Dermotherium and to describe a new species: Dermotherium chimaera sp. n. This species exhibits an interesting mosaic of plesiomorphic cynocephalid characters shared with Cynocephalus and Galeopterus, and as such, it probably documents a form close to the ancestral morphotype from which the two extant forms are derived (supported by cladistic assessment of the dental evidence). The discovery of Palaeogene cynocephalids is particularly significant since it attests to the great antiquity of the order Dermoptera in Asia, and besides, it provides the first spatio‐temporal glimpse into the evolutionary history of that enigmatic mammal group. In that respect, these fossils testify to a long history of endemism in South Asia for dermopterans, and demonstrate that their modern geographic restriction in south‐eastern Asia is clearly a relictual distribution. Cynocephalids had a more widespread distribution during the Palaeogene, which extended from the Indian subcontinent (the rafting Greater India) to South‐East Asia. Their subsequent extinction on the Indian subcontinent was probably mediated by the major palaeogeographic and geomorphologic events related to the India‐Eurasia collision (retreat of the Paratethys Sea, formation of orogenic highlands) that have strongly affected the climate of South Asia at the end of the Oligocene.     

Dynamics of a Pig Slurry Microbial Community during Anaerobic Storage and Management

The microbial community of a pig slurry on a farm was monitored for 6 months using both molecular and cultural approaches. Sampling was carried out at all the different stages of effluent handling, from the rearing build-up to slurry spreading. Total DNA of each sample was extracted and analyzed by PCR-single-strand conformation polymorphism (SSCP) analysis using primers targeting the 16S rRNA genes from the archaeal and bacterial domains and also the Eubacterium-Clostridium, Bacillus-Streptococcus-Lactobacillus, and Bacteroides-Prevotella groups. A comparison of the SSCP profiles showed that there were rapid changes in the dominant bacterial community during the first 2 weeks of anaerobic storage and that the community was relatively stable thereafter. Several bacterial populations, identified as populations closely related to uncultured Clostridium and Porphyromonas and to Lactobacillus and Streptococcus cultured species commonly isolated from pig feces, remained present and dominant from the rearing build-up to the time of spreading. Enumeration of fecal indicators (enterococci and Escherichia coli) performed in parallel using cultural methods revealed the same trends. On the other hand, the archaeal community adapted slowly during pig slurry storage, and its diversity increased. A shift between two hydrogenotrophic methanogenic Methanobrevibacter populations from the storage pit to the pond was observed. Microorganisms present in pig slurry at the time of spreading could not be detected in soil after spreading by either molecular or cultural techniques, probably because of the detection limit inherent in the two techniques.     

Bimodal loop-loop interactions increase the affinity of RNA aptamers for HIV-1 RNA structures

Multiple loop-loop interactions between adjacent RNA hairpins regulate gene expression in different organisms. To demonstrate that such natural interactions could be mimicked for generating RNA ligands that are able to recognize simultaneously at least two structured RNA targets, a double kissing complex model was designed. The target consisted of two HIV-1 transactivating responsive (TAR) RNA variants, BRU and MAL, connected by a non-nucleotidic linker. The double ligand was generated by combining the corresponding hairpin aptamers, R06BRU and R06MAL, identified previously by in vitro selection [Ducongé, F., and Toulmé, J. J (1999) RNA 5, 1605-1614]. The resulting interaction was analyzed by thermal denaturation monitored by UV spectroscopy, electrophoretic mobility shift assays (EMSAs), and surface plasmon resonance (SPR) experiments. The bimodal complex was characterized by a binding equilibrium constant increased by at least 1 order of magnitude compared to that of the complexes between the individual parent hairpins. This resulted from a slower dissociation rate. We then made use of such a strategy for targeting two structured functional motifs of the folded 5' untranslated region (5'UTR) of HIV-1. Two bivalent RNA ligands were designed that targeted simultaneously the TAR and dimerization initiation site (DIS) hairpins or the TAR and poly(A) ones. The results show that these ligands also displayed enhanced affinity for their target compared to the individual molecules. The work reported here suggests that bimodal structured RNA ligands might provide a way of increasing the affinity of aptamers for folded RNA targets.     

An RpoH-like heat shock sigma factor is involved in stress response and virulence in Brucella melitensis 16M

B. melitensis 16M genome analysis revealed the presence of six putative sigma factor-encoding genes: rpoD, rpoH1, rpoH2, rpoE1, rpoE2, and rpoN. We mutated all these genes except rpoD. Phenotypic analysis of the mutants reveals that a strain carrying an rpoH2 null mutation (DeltarpoH2) is impaired for growth at 21 and 42 degrees C and shows increased sensitivity to hydrogen peroxide. Compared to the wild-type strain, the DeltarpoH2 mutant is attenuated in all virulence models tested. Three other null mutants (DeltarpoH1, DeltarpoE1, and DeltarpoE2 mutants) are also defective for survival in mice at 4 weeks postinfection. We also demonstrated that rpoH2 deletion strongly reduces the expression of two major virulence factors in B. melitensis, the type IV secretion system and the flagellum.     

Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation

A renewed interest in tricarboxylic acid cycle enzymopathies has resulted from the report that, in addition to devastating encephalopathies, these can result in various types of tumors in human. We first review the major features of the cycle that may underlie this surprising variety of clinical features. After discussing the rare cases of encephalopathies associated with specific deficiencies of some of the tricarboxylic acid cycle enzyme, we finally examine the mechanism possibly causing tumor/cancer formation in the cases of mutations affecting fumarase or succinate dehydrogenase genes. mitochondria; fumarase; succinate dehydrogenase; cancer; encephalopathy     

A new primate from the Eocene Pondaung Formation of Myanmar and the monophyly of Burmese amphipithecids

The family Amphipithecidae is one of the two fossil primate taxa from Asia that appear to be early members of the anthropoid clade. Ganlea megacanina, gen. et sp. nov., is a new amphipithecid from the late middle Eocene Pondaung Formation of central Myanmar. The holotype of Ganlea is distinctive in having a relatively enormous lower canine showing heavy apical wear, indicating an important functional role of the lower canine in food preparation and ingestion. A phylogenetic analysis of amphipithecid relationships suggests that Ganlea is the sister taxon of Myanmarpithecus, a relatively small-bodied taxon that has often, but not always, been included in Amphipithecidae. Pondaungia is the sister taxon of the Ganlea + Myanmarpithecus clade. All three Pondaung amphipithecid genera are monophyletic with respect to Siamopithecus, which is the most basal amphipithecid currently known. The inclusion of Myanmarpithecus in Amphipithecidae diminishes the likelihood that amphipithecids are specially related to adapiform primates. Extremely heavy apical wear has been documented on the lower canines of all three genera of Burmese amphipithecids. This distinctive wear pattern suggests that Burmese amphipithecids were an endemic radiation of hard object feeders that may have been ecological analogues of living New World pitheciin monkeys.     

Anthropoid versus strepsirhine status of the African Eocene primates Algeripithecus and Azibius: craniodental evidence

Recent fossil discoveries have demonstrated that Africa and Asia were epicentres for the origin and/or early diversification of the major living primate lineages, including both anthropoids (monkeys, apes and humans) and crown strepsirhine primates (lemurs, lorises and galagos). Competing hypotheses favouring either an African or Asian origin for anthropoids rank among the most hotly contested issues in paleoprimatology. The Afrocentric model for anthropoid origins rests heavily on the >45 Myr old fossil Algeripithecus minutus from Algeria, which is widely acknowledged to be one of the oldest known anthropoids. However, the phylogenetic position of Algeripithecus with respect to other primates has been tenuous because of the highly fragmentary fossils that have documented this primate until now. Recently recovered and more nearly complete fossils of Algeripithecus and contemporaneous relatives reveal that they are not anthropoids. New data support the idea that Algeripithecus and its sister genus Azibius are the earliest offshoots of an Afro–Arabian strepsirhine clade that embraces extant toothcombed primates and their fossil relatives. Azibius exhibits anatomical evidence for nocturnality. Algeripithecus has a long, thin and forwardly inclined lower canine alveolus, a feature that is entirely compatible with the long and procumbent lower canine included in the toothcomb of crown strepsirhines. These results strengthen an ancient African origin for crown strepsirhines and, in turn, strongly challenge the role of Africa as the ancestral homeland for anthropoids.     

TGFβ-induced GRK2 expression attenuates AngII-regulated vascular smooth muscle cell proliferation and migration

Through diametric actions, the transforming growth factor β (TGFβ) and Angiotensin II (AngII) play important roles in regulating various biological responses such as cell proliferation and migration. Signaling initiated by TGFβ and AngII occurs through two structurally and functionally distinct receptor super families, the serine/threonine kinase and G protein-coupled receptors (GPCRs). Previously, we identified the G protein-coupled receptor kinase-2 (GRK2), a key regulatory factor in the desensitization of GPCRs, as a direct downstream target of the TGFβ signaling cascade. GRK2 acts through a negative feed-back loop mechanism to terminate TGFβ-induced smad signaling. To investigate the impact of TGFβ-induced GRK2 expression on GPCR signaling, we examined its effect on AngII signaling in vascular smooth muscle cells (VSMCs). In this study, we show that activation of the TGFβ signaling cascade in VSMCs results in increased GRK2 expression levels, which consequently inhibits AngII-induced ERK phosphorylation and antagonizes AngII-induced VSMC proliferation and migration. Moreover, the inhibitory effect of TGFβ on AngII signaling occurs at the Mek-Erk interface and is abrogated when an anti-sense oligonucleotide directed against GRK2 is used. Thus, we conclude that TGFβ signaling antagonizes AngII-induced VSMC proliferation and migration through the inhibition of ERK phosphorylation and that GRK2 is a key factor mediating the cross-talk between these two receptor super families.     

Bacterial monitoring by molecular tools of a continuous stirred tank reactor treating textile wastewater

This study was performed to examine the effect of the bacterial diversity changes on the performances of a continuously stirred tank reactor (CSTR) treating textile wastewater. The molecular fingerprint established using polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) methods showed that bacterial community profiles changed simultaneously with the increase of the wastewater loading rates (WLR). For the two WLR of 0.28 g l(-1)d(-1) and 0.37 g l(-1)d(-1), the reactor maintained good performances, suggesting that the large bacterial community present a high specific activity. The increase of the WLR from 0.37 to 1.12 g l(-1)d(-1) decreased the colour and the chemical oxygen demand (COD) removal efficiencies from 90% to 55% and from 85% to 30%, respectively, explained by the decrease of the bacterial diversity and activity. The changes of the bacterial dominance had no affect on the reactor performances. However, the decrease of the bacterial diversity significantly affected the colour and the COD removal efficiencies. It should conclude that indigo dye-containing textile wastewater treatment required the concerted activity of multiple bacterial populations.