Plasma Leptin Levels and Incidence of Heart Failure, Cardiovascular Disease, and Total Mortality in Elderly Individuals

OBJECTIVE: Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals. RESEARCH DESIGN AND METHODS: We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed. RESULTS: Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03–1.55] and 1.28 [1.09–1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75–1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00–1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels. CONCLUSIONS: In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.National Institutes of Health's National Heart, Lung, and Blood Institute (N01-HC25195, N01-HV28178, K24-HL04334, R01-DK080739

An ovary transcriptome for all maturational stages of the striped bass (Morone saxatilis), a highly advanced perciform fish

<p>Abstract</p> <p>Background</p> <p>The striped bass and its relatives (genus <it>Morone</it>) are important fisheries and aquaculture species native to estuaries and rivers of the Atlantic coast and Gulf of Mexico in North America. To open avenues of gene expression research on reproduction and breeding of striped bass, we generated a collection of expressed sequence tags (ESTs) from a complementary DNA (cDNA) library representative of their ovarian transcriptome.</p> <p>Results</p> <p>Sequences of a total of 230,151 ESTs (51,259,448 bp) were acquired by Roche 454 pyrosequencing of cDNA pooled from ovarian tissues obtained at all stages of oocyte growth, at ovulation (eggs), and during preovulatory atresia. Quality filtering of ESTs allowed assembly of 11,208 high-quality contigs ≥ 100 bp, including 2,984 contigs 500 bp or longer (average length 895 bp). Blastx comparisons revealed 5,482 gene orthologues (E-value < 10^-3), of which 4,120 (36.7% of total contigs) were annotated with Gene Ontology terms (E-value < 10^-6). There were 5,726 remaining unknown unique sequences (51.1% of total contigs). All of the high-quality EST sequences are available in the National Center for Biotechnology Information (NCBI) Short Read Archive (GenBank: <ext-link ext-link-id="SRX007394" ext-link-type="gen">SRX007394</ext-link>). Informative contigs were considered to be abundant if they were assembled from groups of ESTs comprising ≥ 0.15% of the total short read sequences (≥ 345 reads/contig). Approximately 52.5% of these abundant contigs were predicted to have predominant ovary expression through digital differential display <it>in silico </it>comparisons to zebrafish (<it>Danio rerio</it>) UniGene orthologues. Over 1,300 Gene Ontology terms from Biological Process classes of Reproduction, Reproductive process, and Developmental process were assigned to this collection of annotated contigs.</p> <p>Conclusions</p> <p>This first large reference sequence database available for the ecologically and economically important temperate basses (genus <it>Morone</it>) provides a foundation for gene expression studies in these species. The predicted predominance of ovary gene expression and assignment of directly relevant Gene Ontology classes suggests a powerful utility of this dataset for analysis of ovarian gene expression related to fundamental questions of oogenesis. Additionally, a high definition Agilent 60-mer oligo ovary 'UniClone' microarray with 8 × 15,000 probe format has been designed based on this striped bass transcriptome (eArray Group: Striper Group, Design ID: 029004).</p

Assessing Nutrient Limitation in Complex Forested Ecosystems : Alternatives to Large-Scale Fertilization Experiments

Quantifying nutrient limitation of primary productivity is a fundamental task of terrestrial ecosystem ecology, but in a high carbon dioxide environment it is even more critical that we understand potential nutrient constraints on plant growth. Ecologists often manipulate nutrients with fertilizer to assess nutrient limitation, yet for a variety of reasons, nutrient fertilization experiments are either impractical or incapable of resolving ecosystem responses to some global changes. The challenges of conducting large, in situ fertilization experiments are magnified in forests, especially the high-diversity forests common throughout the lowland tropics. A number of methods, including fertilization experiments, could be seen as tools in a toolbox that ecologists may use to attempt to assess nutrient limitation, but there has been no compilation or synthetic discussion of those methods in the literature. Here, we group these methods into one of three categories (indicators of soil nutrient supply, organismal indicators of nutrient limitation, and lab-based experiments and nutrient depletions), and discuss some of the strengths and limitations of each. Next, using a case study, we compare nutrient limitation assessed using these methods to results obtained using large-scale fertilizations across the Hawaiian Archipelago. We then explore the application of these methods in high-diversity tropical forests. In the end, we suggest that, although no single method is likely to predict nutrient limitation in all ecosystems and at all scales, by simultaneously utilizing a number of the methods we describe, investigators may begin to understand nutrient limitation in complex and diverse ecosystems such as tropical forests. In combination, these methods represent our best hope for understanding nutrient constraints on the global carbon cycle, especially in tropical forest ecosystems

A comparison of plot-based satellite and Earth system model estimates of tropical forest net primary production

Net primary production (NPP) by plants represents the largest annual flux of carbon dioxide (CO2) from the atmosphere to the terrestrial biosphere, playing a critical role in the global carbon (C) cycle and the Earth’s climate. Rates of NPP in tropical forests are thought to be among the highest on Earth, but debates about the magnitude, patterns, and controls of NPP in the tropics highlight uncertainty in our understanding of how tropical forests may respond to environmental change. Here, we compared tropical NPP estimates generated using three common approaches: (1) field-based methods scaled from plot-level measurements of plant biomass, (2) radiation-based methods that model NPP from satellite-derived radiation absorption by plants, (3) and biogeochemical model-based methods. For undisturbed tropical forests as a whole, the three methods produced similar NPP estimates (i.e. about 10 Pg C yr1). However, the three different approaches produced vastly different patterns of NPP both in space and through time, suggesting that our understanding of tropical NPP is poor and that our ability to predict the response of NPP in the tropics to environmental change is limited. To address this shortcoming, we suggest the development of an expanded, high-density, permanent network of sites where NPP is continuously evaluated using multiple approaches. Well-designed NPP megatransects that include a high-density plot network would significantly increase the accuracy and certainty in the observed rates and patterns of tropical NPP and improve the reliability of Earth system models used to predict NPP–carbon cycle–climate interactions into the futur

The 3’-5’ exoribonuclease Dis3 regulates the expression of specific microRNAs in Drosophila wing imaginal discs

Dis3 is a highly conserved exoribonuclease which degrades RNAs in the 3'-5' direction. Mutations in Dis3 are associated with a number of human cancers including multiple myeloma and acute myeloid leukaemia. In this work, we have assessed the effect of a Dis3 knockdown on Drosophila imaginal disc development and on expression of mature microRNAs. We find that Dis3 knockdown severely disrupts the development of wing imaginal discs in that the flies have a "no wing" phenotype. Use of RNA-seq to quantify the effect of Dis3 knockdown on microRNA expression shows that Dis3 normally regulates a small subset of microRNAs, with only 11 (10.1%) increasing in level > 2-fold and 6 (5.5%) decreasing in level >2-fold. Of these microRNAs, miR-252-5p is increased 2.1-fold in Dis3-depleted cells compared to controls while the level of the miR-252 precursor is unchanged, suggesting that Dis3 can act in the cytoplasm to specifically degrade this mature miRNA. Furthermore, our experiments suggest that Dis3 normally interacts with the exosomal subunit Rrp40 in the cytoplasm to target miR-252-5p for degradation during normal wing development. Another microRNA, miR-982-5p, is expressed at lower levels in Dis3 knockdown cells, while the miR-982 precursor remains unchanged, indicating that Dis3 is involved in its processing. Our study therefore reveals an unexpected specificity for this ribonuclease towards microRNA regulation, which is likely to be conserved in other eukaryotes and may be relevant to understanding its role in human disease

Resource limitation modulates the fate of dissimilated nitrogen in a dual-pathway Actinobacterium

Respiratory ammonification and denitrification are two evolutionarily unrelated dissimilatory nitrogen (N) processes central to the global N cycle, the activity of which is thought to be controlled by carbon (C) to nitrate (NO₃⁻) ratio. Here we find that Intrasporangium calvum C5, a novel menaquinone-based dual-pathway denitrifier/respiratory ammonifier, disproportionately utilizes ammonification rather than denitrification when grown under carbon or nitrate limitation, not C:NO3- ratio. Instead, C:NO₃⁻ ratio is a confounding variable for resource limitation. We find that the protein atomic composition for denitrification modules (NirK) are significantly cost minimized for C and N compared to ammonification modules (NrfA), indicating that resource limitation is a major selective pressure imprinted in the architecture of these proteins. The evolutionary precedent for these findings suggests ecological and biogeochemical importance as evidenced by higher growth rates when I. calvum grows predominantly using its ammonification pathway and by assimilating its end-product (ammonium) for growth under ammonium-deplete conditions. Genomic analysis of I. calvum further reveals a versatile ecophysiology to cope with nutrient stress and redox conditions. Metabolite and transcriptional profiles during growth indicate that transcript abundances encoding for its nitrite reducing enzyme modules, NrfAH and NirK, significantly increase in response to nitrite production. Mechanistically, our results suggest that pathway selection is driven by intracellular redox potential (redox poise), which may be lowered during resource limitation, thereby decreasing catalytic activity of upstream electron transport steps needed for denitrification enzymes. Our work advances our understanding of the biogeochemical flexibility of N-cycling organisms, pathway evolution, and ecological food-webs