BackgroundThe Azadirachta indica (neem) tree is a source of a wide number of natural products, including the potent biopesticide azadirachtin. In spite of its widespread applications in agriculture and medicine, the molecular aspects of the biosynthesis of neem terpenoids remain largely unexplored. The current report describes the draft genome and four transcriptomes of A. indica and attempts to contextualise the sequence information in terms of its molecular phylogeny, transcript expression and terpenoid biosynthesis pathways. A. indica is the first member of the family Meliaceae to be sequenced using next generation sequencing approach.ResultsThe genome and transcriptomes of A. indica were sequenced using multiple sequencing platforms and libraries. The A. indica genome is AT-rich, bears few repetitive DNA elements and comprises about 20,000 genes. The molecular phylogenetic analyses grouped A. indica together with Citrus sinensis from the Rutaceae family validating its conventional taxonomic classification. Comparative transcript expression analysis showed either exclusive or enhanced expression of known genes involved in neem terpenoid biosynthesis pathways compared to other sequenced angiosperms. Genome and transcriptome analyses in A. indica led to the identification of repeat elements, nucleotide composition and expression profiles of genes in various organs.ConclusionsThis study on A. indica genome and transcriptomes will provide a model for characterization of metabolic pathways involved in synthesis of bioactive compounds, comparative evolutionary studies among various Meliaceae family members and help annotate their genomes. A better understanding of molecular pathways involved in the azadirachtin synthesis in A. indica will pave ways for bulk production of environment friendly biopesticides.

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Purpose Laparoscopic nephrectomy with autotransplantation is a viable option when renal preservation is required or ureteral reconstruction is impossible. In this study we report on our long-term experience with laparoscopic nephrectomy with autotransplantation. Materials and Methods A retrospective review of data from all patients who underwent laparoscopic nephrectomy with autotransplantation since 2000 revealed data for 52 of 59 patients after study exclusions. Indications for laparoscopic nephrectomy with autotransplantation included ureteral stricture disease (41), renal malignancy (7), ptotic kidney (1), chronic flank pain (1), renal artery aneurysm (1) and renovascular hypertension (1). Followup included ultrasonography, nuclear renography and computerized tomography. Complications analyzed were Clavien-Dindo grade III or higher. Results A total of 52 patients (30 women, 57.6%) underwent laparoscopic nephrectomy with autotransplantation at a median age of 48 years (range 12 to 76). At a median followup of 73.5 months 47 patients (90.3%) had long-term function of the autotransplanted renal unit including 3 of 4 (75%) solitary kidneys. There were 5 patients (9.7%) who experienced renal unit failure at a median of 15 months. Of these patients 3 required nephrectomy of autotransplant unit secondary to renal vein thrombosis (1 day), pseudoaneurysm (15 months) and chronic pain (48 months). Overall 4 patients had early complications and 8 had late complications. In the tumor group 4 patients had disease progression and all are alive. Conclusions Laparoscopic nephrectomy with autotransplantation is an excellent long-term surgical option (greater than 90% success rate with longer than 6-year median followup) for complex ureteral and renal conditions that necessitate preservation of renal parenchyma. However, tumor progression is possible after ex vivo tumor excision. Therefore, careful patient selection and followup are mandatory. This report supports the safety, efficacy and durability of laparoscopic nephrectomy with autotransplantation in experienced hands.

Background: Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in eukaryotic cellular function. However, the effects mitochondrial DNA (mtDNA) levels have on the nuclear transcriptome have not been defined under physiological conditions. In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted ρ 0 counterparts grown in culture and as tumor xenografts in immune-deficient mice.

I. IntroductionTHE PURPOSE of this paper is to examine the effects of tax-induced investor clienteles on capital asset prices. In their seminal work on corporate dividend policy, Miller and Modigliani (1961) argued that in a world where dividend income is taxed at a higher rate than capital gains, and tax rates vary across investors, corporations would adjust their dividend policies until, in equilibrium, such policies coincided with the desires of shareholders. That is, tax-induced shareholder clienteles would form, with low (high) yielding stocks being held by investors in high (low) marginal tax brackets. Black and Scholes (1974) argue for a 'supply effect', such that in equilibrium, a marginal change in a corporation's dividend distribution would leave its stock price unaffected. Brennan (1970) was the first to derive an After-Tax Capital Asset Pricing Model (CAPM) that accounted for the differential taxation of dividend and capital gains, and for a progressive tax scheme. The model was later extended by Litzenberger and Ramaswamy (1979) to account for restrictions on investors' borrowing. While in both models investors' tax brackets do influence their portfolio choices, it turns out that in equilibrium the expected return per unit of dividend yield is a constant across securities and independent of dividend yield. It is shown in the present study that this result obtains only in the absence of any restrictions on short sales. While Brennan took corporate dividend policies as exogenous, his analysis under pure exchange indicates that an equilibrium where corporations are paying positive dividends is inconsistent with the required return per unit of dividend yield being zero. Put another way, the weighted average (using investors' global risk tolerances as weights) of investors' marginal tax brackets determines the expected return per unit of dividend yield. Since corporations1 and tax-exempt investors would be indifferent between dividends and capital gains while other investors have a preference for capital gains, this weightedaverage tax rate would be positive. Litzenberger and Ramaswamy (1979) demonstrate that an equilibrium where corporations are paying positive dividends is consistent with the expected return per unit of yield being zero, if there are dividend related * Stanford University and Columbia University, respectively. We are grateful for helpful discussions with George Constantinides and Stephen Schaefer. 'Dividend income and short term capital gains are eligible for the 85 percent dividend exclusion. Corporations have the option of realizing all gains short term; therefore, the common assertion that corporations' (as investors) preference for dividends cannot be based solely on the existence of the 85 percent dividend exclusion and the corporate tax rates of long-term capital gains. 469 470 The Journal of Finance constraints on either borrowing or on the tax deductibility of interest on margin borrowing.Recently, Miller and Scholes (1979) have argued that investors can escape the penalty tax ...

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BackgroundIt has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism.ResultsDespite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes.ConclusionWe identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.