Resistance to carbon dioxide,an anoxic stress inDrosophila melanogaster

Résumé Des lignées deD. melanogaster formées à partir d'une femelle fécondée naturellement, sont polymorphiques par raport au degré de mortalité résultant de leur maintient prolongé dans une atmosphère de CO₂. Il est établi que ces différences proviennent de variations dans les gènes additifs. On observe que la réaction au CO₂ est presque identique à celle que provoque le N₂, un gaz biologiquement inerte, causant l'asphyxie. L'auteur conclut que le CO₂ entraîne l'asphyxie lorsqu'on l'administre durant des périodes prolongées et que les populations naturelles deD. melanogaster sont polymorphiques quant à leur résistance à l'asphyxie.

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Supported by Commonwealth of Australia Postgraduate Award.

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Advice and criticism by Prof.P. A. Parsons is gratefully acknowledged.     

Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.     

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1)

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.     

Demonstration of a sexual dimorphism in the olfactory pathways of the drones ofApis mellifica L. (Hymenoptera,Apidae)

Summary An important sexual dimorphism is demonstrated in the drone at the level of the first central relay of the antennal olfactory pathway (antennal lobe of the deutocerebrum), represented by large and easily identifiable glomerular complexes. This preparation seems to be an excellent model for a functional study of the olfactory system.     

Vascular normalization in Rgs5-deficient tumours promotes immune destruction

The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture. Constant vessel remodelling leads to spontaneous haemorrhages and increased interstitial fluid pressure in the tumour environment. Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma. The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.     

Reduction and selective oxo group silylation of the uranyl dication

Uranium occurs in the environment predominantly as the uranyl dication [UO2]2+. Its solubility renders this species a problematic contaminant which is, moreover, chemically extraordinarily robust owing to strongly covalent U-O bonds. This feature manifests itself in the uranyl dication showing little propensity to partake in the many oxo group functionalizations and redox reactions typically seen with [CrO2]2+, [MoO2]2+ and other transition metal analogues. As a result, only a few examples of [UO2]2+ with functionalized oxo groups are known. Similarly, it is only very recently that the isolation and characterization of the singly reduced, pentavalent uranyl cation [UO2]+ has been reported. Here we show that placing the uranyl dication within a rigid and well-defined molecular framework while keeping the environment anaerobic allows simultaneous single-electron reduction and selective covalent bond formation at one of the two uranyl oxo groups. The product of this reaction is a pentavalent and monofunctionalized [O = U...OR]+ cation that can be isolated in the presence of transition metal cations. This finding demonstrates that under appropriate reaction conditions, the uranyl oxo group will readily undergo radical reactions commonly associated only with transition metal oxo groups. We expect that this work might also prove useful in probing the chemistry of the related but highly radioactive plutonyl and neptunyl analogues found in nuclear waste.     

Reconstructing the early evolution of Fungi using a six-gene phylogeny

The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore flagellum, leading to the diversification of terrestrial fungi. Here we develop phylogenetic hypotheses for Fungi using data from six gene regions and nearly 200 species. Our results indicate that there may have been at least four independent losses of the flagellum in the kingdom Fungi. These losses of swimming spores coincided with the evolution of new mechanisms of spore dispersal, such as aerial dispersal in mycelial groups and polar tube eversion in the microsporidia (unicellular forms that lack mitochondria). The enigmatic microsporidia seem to be derived from an endoparasitic chytrid ancestor similar to Rozella allomycis, on the earliest diverging branch of the fungal phylogenetic tree.