Enzymatic capacities of metabolic fuel use in cuttlefish (Sepia officinalis) and responses to food deprivation: insight into the metabolic organization and starvation survival strategy of cephalopods

Food limitation is a common challenge for animals. Cephalopods are sensitive to starvation because of high metabolic rates and growth rates related to their "live fast, die young" life history. We investigated how enzymatic capacities of key metabolic pathways are modulated during starvation in the common cuttlefish (Sepia officinalis) to gain insight into the metabolic organization of cephalopods and their strategies for coping with food limitation. In particular, lipids have traditionally been considered unimportant fuels in cephalopods, yet, puzzlingly, many species (including cuttlefish) mobilize the lipid stores in their digestive gland during starvation. Using a comprehensive multi-tissue assay of enzymatic capacities for energy metabolism, we show that, during long-term starvation (12 days), glycolytic capacity for glucose use is decreased in cuttlefish tissues, while capacities for use of lipid-based fuels (fatty acids and ketone bodies) and amino acid fuels are retained or increased. Specifically, the capacity to use the ketone body acetoacetate as fuel is widespread across tissues and gill has a previously unrecognized capacity for fatty acid catabolism, albeit at low rates. The capacity for de novo glucose synthesis (gluconeogenesis), important for glucose homeostasis, likely is restricted to the digestive gland, contrary to previous reports of widespread gluconeogenesis among cephalopod tissues. Short-term starvation (3-5 days) had few effects on enzymatic capacities. Similar to vertebrates, lipid-based fuels, putatively mobilized from fat stores in the digestive gland, appear to be important energy sources for cephalopods, especially during starvation when glycolytic capacity is decreased perhaps to conserve available glucose

European Sea Bass (Dicentrarchus labrax) immune status and disease resistance are impaired by arginine dietary supplementation

Infectious diseases and fish feeds management are probably the major expenses in the aquaculture business. Hence, it is a priority to define sustainable strategies which simultaneously avoid therapeutic procedures and reinforce fish immunity. Currently, one preferred approach is the use of immunostimulants which can be supplemented to the fish diets. Arginine is a versatile amino acid with important mechanisms closely related to the immune response. Aiming at finding out how arginine affects the innate immune status or improve disease resistance of European seabass (Dicentrarchus labrax) against vibriosis, fish were fed two arginine-supplemented diets (1% and 2% arginine supplementation). A third diet meeting arginine requirement level for seabass served as control diet. Following 15 or 29 days of feeding, fish were sampled for blood, spleen and gut to assess cell-mediated immune parameters and immune-related gene expression. At the same time, fish from each dietary group were challenged against Vibrio anguillarum and survival was monitored. Cell-mediated immune parameters such as the extracellular superoxide and nitric oxide decreased in fish fed arginine-supplemented diets. Interleukins and immune-cell marker transcripts were down-regulated by the highest supplementation level. Disease resistance data were in accordance with a generally depressed immune status, with increased susceptibility to vibriosis in fish fed arginine supplemented diets. Altogether, these results suggest a general inhibitory effect of arginine on the immune defences and disease resistance of European seabass. Still, further research will certainly clarify arginine immunomodulation pathways thereby allowing the validation of its potential as a prophylactic strategy.European Union's Seventh Framework Programme AQUAEXCEL (Aquaculture Infrastructures for Excellence in European Fish Research) [262336]; AQUAIMPROV [NORTE-07-0124-FEDER-000038]; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte) , under the National Strategic Reference Framework, through the European Regional Development Fund; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte), under the National Strategic Reference Framework through the COMPETE - Operational Competitiveness Programme; Fundacao para a Ciencia e Tecnologia; Fundacao para a Ciencia e Tecnologia [SFRH/BD/89457/2012, SFRH/BPD/77210/2011]; Generalitat Valenciana through the project REVIDPAQUA [ISIC/2012/003]; [PEst-C/MAR/LA0015/2013]; [UID/Multi/04423/2013]info:eu-repo/semantics/publishedVersio

Resolving the ancestry of Austronesian-speaking populations

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The “out-of-Taiwan” model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR)

BACKGROUND: Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia. METHODS: A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ≥ 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety. RESULTS: Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or renal insufficiency were recorded. CONCLUSION: In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated

Exposure to fluctuating salinity enhances free amino acid accumulation in Tigriopus californicus (Copepoda)

Intracellular concentrations of free amino acids (FAA) in the intertidal copepod Tigriopus californicus increase in response to hyperosmotic stress and decrease in response to hypo-osmotic stress. The purpose of this study was to determine if exposure to repeated bouts of osmotic stress resulted in changes in FAA accumulation or the degree of FAA retention in subsequent episodes. Five groups of T. californicus were exposed for 22 days to a fluctuating salinity regime which consisted of 24 h at 100% seawater followed by 24 h at either 90, 80, 70, 60 or 50% seawater (11 cycles). After the tenth exposure to 100% seawater, individuals from each treatment group were analyzed for alanine and proline concentration. Alanine and proline accumulation generally increased in proportion to the osmotic stress up to 60–100% seawater — additional osmotic stress failed to increase total accumulation. Prior exposure to fluctuating salinity increased the extent of alanine and proline retention observed upon transfer to a hypo-osmotic medium. The treatment group which had experienced the most extreme fluctuation (50–100% seawater) retained alanine and proline levels approximately 10- and 20-fold higher, respectively, than controls. A less severe salinity fluctuation was required to elicit this response for alanine (90–100% seawater) than for proline (60–100% seawater). Previous exposure to fluctuating salinity also resulted in increased alanine and proline accumulation in subsequent episodes of hyperosmotic stress. 24 h after transfer from 50 to 100% seawater, alanine and proline levels in the conditioned copepods were approximately 3- and 7-fold higher, respectively, than in copepods which had not been cycled. This facilitation in alanine and proline accumulation occurred after 10 and 11 cycles, respectively. Of the increased accumulation in alanine and proline, 7.0% and 22.5%, respectively, could be accounted for by the higher degree of FAA retention while under hypo-osmotic conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47130/1/360_2004_Article_BF00692733.pd

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

Mechanical cleaning of graphene using in situ electron microscopy

Avoiding and removing surface contamination is a crucial task when handling specimens in any scientific experiment. This is especially true for two-dimensional materials such as graphene, which are extraordinarily affected by contamination due to their large surface area. While many efforts have been made to reduce and remove contamination from such surfaces, the issue is far from resolved. Here we report on an in situ mechanical cleaning method that enables the site-specific removal of contamination from both sides of two dimensional membranes down to atomic-scale cleanliness. Further, mechanisms of re-contamination are discussed, finding surface-diffusion to be the major factor for contamination in electron microscopy. Finally the targeted, electron-beam assisted synthesis of a nanocrystalline graphene layer by supplying a precursor molecule to cleaned areas is demonstrated

Multi-Ethnic Analysis of Lipid-Associated Loci: The NHLBI CARe Project

Background: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings: We tested a set of $\sim$50,000 polymorphisms from $\sim$2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans