Coupled Dynamics of Iron and Phosphorus in Sediments of an Oligotrophic Coastal Basin and the Impact of Anaerobic Oxidation of Methane

Studies of phosphorus (P) dynamics in surface sediments of lakes and coastal seas typically emphasize the role of coupled iron (Fe), sulfur (S) and P cycling for sediment P burial and release. Here, we show that anaerobic oxidation of methane (AOM) also may impact sediment P cycling in such systems. Using porewater and sediment profiles for sites in an oligotrophic coastal basin (Bothnian Sea), we provide evidence for the formation of Fe-bound P (possibly vivianite; Fe3(PO4)2.8H2O) below the zone of AOM with sulfate. Here, dissolved Fe2+ released from oxides is no longer scavenged by sulfide and high concentrations of both dissolved Fe2+ (>1 mM) and PO4 in the porewater allow supersaturation with respect to vivianite to be reached. Besides formation of Fe(II)-P, preservation of Fe-oxide bound P likely also contributes to permanent burial of P in Bothnian Sea sediments. Preliminary budget calculations suggest that the burial of Fe-bound P allows these sediments to act as a major sink for P from the adjacent eutrophic Baltic Proper

Changes in Proteasome Structure and Function Caused by HAMLET in Tumor Cells

BACKGROUND: Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. METHODOLOGY/PRINCIPAL FINDINGS: HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. CONCLUSIONS/SIGNIFICANCE: The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Genetic Divergence between Freshwater and Marine Morphs of Alewife (Alosa pseudoharengus): A ‘Next-Generation’ Sequencing Analysis

Alewife Alosa pseudoharengus, a small clupeid fish native to Atlantic Ocean, has recently (∼150 years ago) invaded the North American Great Lakes and despite challenges of freshwater environment its populations exploded and disrupted local food web structures. This range expansion has been accompanied by dramatic changes at all levels of organization. Growth rates, size at maturation, or fecundity are only a few of the most distinct morphological and life history traits that contrast the two alewife morphs. A question arises to what extent these rapidly evolving differences between marine and freshwater varieties result from regulatory (including phenotypic plasticity) or structural mutations. To gain insights into expression changes and sequence divergence between marine and freshwater alewives, we sequenced transcriptomes of individuals from Lake Michigan and Atlantic Ocean. Population specific single nucleotide polymorphisms were rare but interestingly occurred in sequences of genes that also tended to show large differences in expression. Our results show that the striking phenotypic divergence between anadromous and lake alewives can be attributed to massive regulatory modifications rather than coding changes

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Bnip3 as a Dual Regulator of Mitochondrial Turnover and Cell Death in the Myocardium

The Bcl-2 adenovirus E1B 19 kDa-interacting protein 3 (Bnip3) is a pro-apoptotic BH3-only protein associated with the pathogenesis of many diseases, including cancer and cardiovascular disease. Studies over the past decade have provided insight into how Bnip3 induces mitochondrial dysfunction and subsequent cell death in cells. More recently, Bnip3 was identified as a potent inducer of autophagy in cells. However, the functional role of Bnip3-mediated autophagy has been difficult to define and remains controversial. New evidence has emerged suggesting that Bnip3 is an important regulator of mitochondrial turnover via autophagy in the myocardium. Also, studies suggest that the induction of Bnip3-dependent mitochondrial autophagy is a separately activated process independent of Bax/Bak and the mitochondrial permeability transition pore (mPTP). This review discusses the current understanding of the functional role that Bnip3 plays in the myocardium. Recent studies suggest that Bnip3 might have a dual function in the myocardium, where it regulates both mitochondrial turnover via autophagy and cell death and that these are two separate processes activated by Bnip3

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Neonatal Androgenization Exacerbates Alcohol-Induced Liver Injury in Adult Rats, an Effect Abrogated by Estrogen

Alcoholic liver disease (ALD) affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2) and ethanol metabolizing enzymes (cytochrome P450, CYP450) are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl), androgenized females (Andro) and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood