Gene Expression in a Drosophila Model of Mitochondrial Disease

Background A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings Here, we describe a transcriptome-wide analysis of gene expression in tko25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stress-response genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified. Conclusions/Significance These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.Public Library of Scienc

Evolutionary diversification of new caledonian Araucaria

New Caledonia is a global biodiversity hotspot. Hypotheses for its biotic richness suggest either that the island is a ‘museum’ for an old Gondwana biota or alternatively it has developed following relatively recent long distance dispersal and in situ radiation. The conifer genus Araucaria (Araucariaceae) comprises 19 species globally with 13 endemic to this island. With a typically Gondwanan distribution, Araucaria is particularly well suited to testing alternative biogeographic hypotheses concerning the origins of New Caledonian biota. We derived phylogenetic estimates using 11 plastid and rDNA ITS2 sequence data for a complete sampling of Araucaria (including multiple accessions of each of the 13 New Caledonian Araucaria species). In addition, we developed a dataset comprising 4 plastid regions for a wider taxon sample to facilitate fossil based molecular dating. Following statistical analyses to identify a credible and internally consistent set of fossil constraints, divergence times estimated using a Bayesian relaxed clock approach were contrasted with geological scenarios to explore the biogeographic history of Araucaria. The phylogenetic data resolve relationships within Araucariaceae and among the main lineages in Araucaria, but provide limited resolution within the monophyletic New Caledonian species group. Divergence time estimates suggest a Late Cretaceous-Cenozoic radiation of extant Araucaria and a Neogene radiation of the New Caledonian lineage. A molecular timescale for the evolution of Araucariaceae supports a relatively recent radiation, and suggests that earlier (pre-Cenozoic) fossil types assigned to Araucaria may have affinities elsewhere in Araucariaceae. While additional data will be required to adequately resolve relationships among the New Caledonian species, their recent origin is consistent with overwater dispersal following Eocene emersion of New Caledonia but is too old to support a single dispersal from Australia to Norfolk Island for the radiation of the Pacific Araucaria sect. Eutacta clade.Mai Lan Kranitz, Edward Biffin, Alexandra Clark, Michelle L. Hollingsworth, Markus Ruhsam, Martin F. Gardner, Philip Thomas, Robert R. Mill, Richard A. Ennos, Myriam Gaudeul, Andrew J. Lowe, Peter M. Hollingswort

Inventory of current EU paediatric vision and hearing screening programmes

Background: We examined the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes relevant for comparison of screening programmes were derived from literature and used to compile three questionnaires on vision, hearing and public-health screening. Tests used, professions involved, age and frequency of testing seem to influence sensitivity, specificity and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists and audiologists involved in paediatric screening in all EU fullmember, candidate and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% more than once. First measurement of VA varies from three to seven years of age, but is usually before the age of five. At age three and four picture charts, including Lea Hyvarinen are used most, in children over four Tumbling-E and Snellen. As first hearing screening test otoacoustic emission (OAE) is used most in healthy neonates, and auditory brainstem response (ABR) in premature newborns. The majority of hearing testing programmes are staged; children are referred after one to four abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1-4) and funding sources (8)

Climate-driven palaeofloral fluctuations on a volcanic slope from the low latitudes of the Palaeotethys (early Permian, West Sumatra)

The present paper focuses on plant diversity fluctuations within three ecosystems from a volcanic slope in the sequence analytical context of three superimposed cyclicities. This analysis was possible thanks to the isotopic age evaluation of the volcanic Merangin section that bracketed the Mengkarang Formation on West Sumatra between 296.77 ± 0.04 and 296.14 ± 0.09 Ma (Asselian, Lower Permian). The Merangin section consists of a 490 m long fining and thinning tuffaceous aggregational sequence composed of eight short-eccentricity fining and thinning upwards parasequences. The palaeoflora along the sequence varies from tropical wet taxa, comprising cordaitalean and ferns, to mesic-xeric taxa, typified by seed ferns and early conifers. Herein the palaeofloral content of 14 consecutive lahars from a single volcanic accretion wedge in the seventh parasequence is described in detail. It displays a gradual increase in the ratios of (seed) ferns (Macralethopteris hallei, Sphenopteris sp. and gigantopterids) and early conifers (Dicranophyllum molle, Tobleria bicuspis), reaching a 100% in the 6th bed, and returning to 100% cordaitalean and ferns. The high ratio of seed ferns and early conifers in the 6th lahar is interpreted as reflecting a temporary lowering of the tree line caused by a glacial maximum from a high order cycle (obliquity or precession), superimposed on a short-eccentricity cycle, which in turn is superimposed on our third-order cycle palaeofloral transition described earlier for the whole sequence. Along this lower Permian section from the low latitudes from the Palaeotethys, glacial-interglacial cycles are seen to affect the fluctuations of the vegetation line in a chiefly similar way as during the Quaternary. The diversity fluctuations for three ecosystems (wetlands, lower and upper slope) are modelled for two of the three or more superimposed cycles. Emphasis is put on the appearance of a glacial palaeoflora on top of the sequence

Climate-driven palaeofloral fluctuations on a volcanic slope from the low latitudes of the Palaeotethys (early Permian, West Sumatra)

The present paper focuses on plant diversity fluctuations within three ecosystems from a volcanic slope in the sequence analytical context of three superimposed cyclicities. This analysis was possible thanks to the isotopic age evaluation of the volcanic Merangin section that bracketed the Mengkarang Formation on West Sumatra between 296.77 ± 0.04 and 296.14 ± 0.09 Ma (Asselian, Lower Permian). The Merangin section consists of a 490 m long fining and thinning tuffaceous aggregational sequence composed of eight short-eccentricity fining and thinning upwards parasequences. The palaeoflora along the sequence varies from tropical wet taxa, comprising cordaitalean and ferns, to mesic-xeric taxa, typified by seed ferns and early conifers. Herein the palaeofloral content of 14 consecutive lahars from a single volcanic accretion wedge in the seventh parasequence is described in detail. It displays a gradual increase in the ratios of (seed) ferns (Macralethopteris hallei, Sphenopteris sp. and gigantopterids) and early conifers (Dicranophyllum molle, Tobleria bicuspis), reaching a 100% in the 6th bed, and returning to 100% cordaitalean and ferns. The high ratio of seed ferns and early conifers in the 6th lahar is interpreted as reflecting a temporary lowering of the tree line caused by a glacial maximum from a high order cycle (obliquity or precession), superimposed on a short-eccentricity cycle, which in turn is superimposed on our third-order cycle palaeofloral transition described earlier for the whole sequence. Along this lower Permian section from the low latitudes from the Palaeotethys, glacial-interglacial cycles are seen to affect the fluctuations of the vegetation line in a chiefly similar way as during the Quaternary. The diversity fluctuations for three ecosystems (wetlands, lower and upper slope) are modelled for two of the three or more superimposed cycles. Emphasis is put on the appearance of a glacial palaeoflora on top of the sequence