Bithorax Complex genes control alary muscle patterning along the cardiac tube of Drosophila

Cardiac specification models are widely utilized to provide insight into the expression and function of homologous genes and structures in humans. In Drosophila, contractions of the alary muscles control hemolymph inflow and support the cardiac tube, however embryonic development of these muscles remain largely understudied. We found that alary muscles in Drosophila embryos appear as segmental pairs, attaching dorsally at the seven-up (svp) expressing pericardial cells along the cardiac dorsal vessel, and laterally to the body wall. Normal patterning of alary muscles along the dorsal vessel was found to be a function of the Bithorax Complex genes abdominal-A (abd-A) and Ultrabithorax (Ubx) but not of the orphan nuclear receptor gene svp. Ectopic expression of either abd-A or Ubx resulted in an increase in the number of alary muscle pairs from seven to 10, and also produced a general elongation of the dorsal vessel. A single knockout of Ubx resulted in a reduced number of alary muscles. Double knockouts of both Ubx and abd-A prevented alary muscles from developing normally and from attaching to the dorsal vessel. These studies demonstrate an additional facet of muscle development that depends upon the Hox genes, and define for the first time mechanisms that impact development of this important subset of muscles.     

Genetic heterogeneity in regional populations of Quebec—Parental lineages in the Gaspe Peninsula

Stable colonization of the Gaspe Peninsula by Europeans started in the middle of the 18th century at the time of the British conquest of New France. The earliest settlers were Acadians, escaping British deportation policies, followed by Loyalists from the US, who preferred to remain under British rule after the Declaration of Independence. In the 19th century, the developing fishing industry attracted French Canadians from the St. Lawrence Valley and newcomers from Europe including Channel Islanders from Jersey and Guernsey. We analyzed parental lineages of the self‐declared descendants of these four groups of settlers by mtDNA D‐loop sequencing and Y‐chromosome genotyping and compared them with French, British, and Irish samples. Their representation in terms of haplotype frequency classes reveals different signatures of founder effects, such as a loss of rare haplotypes, modification of intermediate frequency haplotypes, reduction in genetic diversity (seen in Acadians), but also enrichment by admixture. Parental lineages correlate with group identity. Descendants of early settlers, Acadians and Loyalists, preserved their identity more than those of French Canadian and Channel Islander “latecomers.” Although overall genetic diversity among Gaspesians is comparable with their European source populations, F_ST analysis indicated their greater differentiation. Distinct settlement history, a limited number of founders and relative genetic isolation contributed to the regionalization of the Quebec gene pool that appears less homogenous than usually anticipated. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

Functional conservation between mammalian MGRN1 and plant LOG2 ubiquitin ligases

Plant LOSS OF GDU 2 (LOG2) and Mammalian Mahogunin Ring Finger 1 (MGRN1) proteins are RING-type E3 ligases sharing similarity N-terminal to the RING domain. Deletion of this region disrupts the interaction of LOG2 with the plant membrane protein GLUTAMINE DUMPER1 (GDU1). Phylogenetic analysis identified two clades of LOG2/MGRN1-like proteins in vertebrates and plants. The ability of MGRN1 to functionally replace LOG2 was tested. MGRN1 ubiquitylates GDU1 in vitro and can partially substitute for LOG2 in the plant, partially restoring amino acid resistance to a GDU1-myc over-expression, log2-2 background. Altogether, these results suggest a conserved function for the N-terminal domain in evolution.     

Geographical Variation in Body Size and Sexual Size Dimorphism in an Australian Lizard,Boulenger's Skink (Morethia boulengeri)

Ecogeographical rules help explain spatial and temporal patterns in intraspecific body size. However, many of these rules, when applied to ectothermic organisms such as reptiles, are controversial and require further investigation. To explore factors that influence body size in reptiles, we performed a heuristic study to examine body size variation in an Australian lizard, Boulenger''s Skink Morethia boulengeri from agricultural landscapes in southern New South Wales, south-eastern Australia. We collected tissue and morphological data on 337 adult lizards across a broad elevation and climate gradient. We used a model-selection procedure to determine if environmental or ecological variables best explained body size variation. We explored the relationship between morphology and phylogenetic structure before modeling candidate variables from four broad domains: (1) geography (latitude, longitude and elevation), (2) climate (temperature and rainfall), (3) habitat (vegetation type, number of logs and ground cover attributes), and (4) management (land use and grazing history). Broad phylogenetic structure was evident, but on a scale larger than our study area. Lizards were sexually dimorphic, whereby females had longer snout-vent length than males, providing support for the fecundity selection hypothesis. Body size variation in M. boulengeri was correlated with temperature and rainfall, a pattern consistent with larger individuals occupying cooler and more productive parts of the landscape. Climate change forecasts, which predict warmer temperature and increased aridity, may result in reduced lizard biomass and decoupling of trophic interactions with potential implications for community organization and ecosystem function.     

Sex steroids,ANGELS and osteoporosis

Osteoporosis is characterized by reduced bone density and strength. Bone mass peaks between age 30 and 40 and then declines. This can be accelerated by factors including menopause and insufficient dietary calcium. Hormone replacement therapy (HRT) is currently the standard treatment for osteoporosis. However, growing concern over potential side effects of HRT has driven a search for alternative therapies. A recent report 1 reveals a potential alternative to HRT: a gender-neutral synthetic steroid that increases bone mass and strength without affecting reproductive organs. This compound acts via a novel extranuclear sex steroid receptor signaling mechanism that has important implications for nuclear receptor biology and human health.     

Differences between rats and mice in induction of 4S beta-naphthoflavone-binding protein expression by treatment with beta-naphthoflavone

Sprague-Dawley rats and several inbred strains of mice were compared with respect to the induction of 4S BNF-binding protein expression by treatment with beta-naphthoflavone (BNF), an aryl hydrocarbon receptor (AhR) ligand. Inbred strains of mice chosen for the study encompassed 3 allelic forms of AhR found in Mus musculus so far. As it was reported by us earlier, treating rats with BNF caused a significant induction of BNF-binding protein expression. By contrast, no BNF-binding protein was detected in mice treated with BNF in corn oil as a vehicle or with corn oil itself.     

The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells

The dual oxidase-thiocyanate-lactoperoxidase (Duox/SCN(-)/LPO) system generates the microbicidal oxidant hypothiocyanite in the airway surface liquid by using LPO, thiocyanate, and Duox-derived hydrogen peroxide released from the apical surface of the airway epithelium. This system is effective against several microorganisms that infect airways of cystic fibrosis and other immunocompromised patients. We show herein that exposure of airway epithelial cells to Pseudomonas aeruginosa obtained from long-term cultures inhibits Duox1-dependent hydrogen peroxide release, suggesting that some microbial factor suppresses Duox activity. These inhibitory effects are not seen with the pyocyanin-deficient P. aeruginosa strain PA14 Phz1/2. We show that purified pyocyanin, a redox-active virulence factor produced by P. aeruginosa, inhibits human airway cell Duox activity by depleting intracellular stores of NADPH, as it generates intracellular superoxide. Long-term exposure of human airway (primary normal human bronchial and NCI-H292) cells to pyocyanin also blocks induction of Duox1 by Th2 cytokines (IL-4, IL-13), which was prevented by the antioxidants glutathione and N-acetylcysteine. Furthermore, we showed that low concentrations of pyocyanin blocked killing of wild-type P. aeruginosa by the Duox/SCN(-)/LPO system on primary normal human bronchial epithelial cells. Thus, pyocyanin can subvert Pseudomonas killing by the Duox-based system as it imposes oxidative stress on the host. We also show that lactoperoxidase can oxidize pyocyanin, thereby diminishing its cytotoxicity. These data establish a novel role for pyocyanin in the survival of P. aeruginosa in human airways through competitive redox-based reactions between the pathogen and host.     

Acute in vitro hypoxia and high-altitude (4,559 m) exposure decreases leukocyte oxygen consumption

Hypoxia impairs metabolic functions by decreasing activity and expression of ATP-consuming processes. To separate hypoxia from systemic effects, we tested whether hypoxia at high altitude affects basal and PMA-stimulated leukocyte metabolism and how this compares to acute (15 min) and 24 h of in vitro hypoxia. Leukocytes were prepared at low altitude and ～24 h after arrival at 4559 m. Mitochondrial oxygen consumption (JO?) was measured by respirometry, oxygen radicals by electron spin resonance spectroscopy, both at a Po? = 100 mmHg (JO?,???) and 20 mmHg (JO?,??). Acute hypoxia of leukocytes decreased JO? at low altitude. Exposure to high altitude decreased JO?,???, whereas JO?,?? was not affected. Acute hypoxia of low-altitude samples decreased the activity of complexes I, II, and III. At high altitude, activity of complexes I and III were decreased when measured in normoxia. Stimulation of leukocytes with PMA increased JO?,??? at low (twofold) and high altitude (five-fold). At both locations, PMA-stimulated JO? was decreased by acute hypoxia. Basal and PMA-stimulated reactive oxygen species (ROS) production were unchanged at high altitude. Separate in vitro experiments performed at low altitude show that ～75% of PMA-induced increase in JO? was due to increased extra-mitochondrial JO? (JO?(,res); in the presence of rotenone and antimycin A). JO?(,res) was doubled by PMA. Acute hypoxia decreased basal JO?(,res) by ～70% and PMA-stimulated JO?(,res) by about 50% in cells cultured in normoxia and hypoxia (1.5% O?; 24 h). Conversely, 24 h in vitro hypoxia decreased mitochondrial JO?,??? and JO?,??, extra-mitochondrial, basal, and PMA-stimulated JO? were not affected. These results show that 24 h of high altitude but not 24 h in vitro hypoxia decreased basal leukocyte metabolism, whereas PMA-induced JO? and ROS formation were not affected, indicating that prolonged high-altitude hypoxia impairs mitochondrial metabolism but does not impair respiratory burst. In contrast, acute hypoxia impairs respiratory burst at either altitude.