Carbon isotope ratioss of coccolith-associated polysaccharides of Emiliania huxleyi as a function of growth rate and CO2 concentration

The calcite plates, or coccoliths, of haptophyte algae including Emiliania huxleyi are formed in intracellular vesicles in association with water–soluble acidic polysaccharides. These coccolith–associated polysaccharides (CAPs) are involved in regulating coccolith formation and have been recovered from sediment samples dating back to ∼180 Ma. Paired measurements of the carbon isotopic compositions of CAPs and coccolith calcite have been proposed as a novel paleo–pCO2 barometer, but additional proxy validation and development are still required. Here we present culture results quantifying carbon isotopic offsets between CAPs and other cellular components: bulk organic biomass, alkenones, and calcite. E. huxleyi was grown in nitrate–limited chemostat experiments at growth rates (µ) of 0.20–0.62/d and carbon dioxide concentrations of 10.7–17.6 µmol/kg. We find that CAPs are isotopically enriched by 4.5–10.1‰ relative to bulk organic carbon, exhibiting smaller isotopic offsets at faster growth rates and lower CO2 concentrations. This variability suggests that CAPs record a complementary signature of past growth conditions with different sensitivity than alkenones or coccolith calcite. By measuring the isotopic compositions of all three molecules and minerals of self-consistent origin, the ratio µ/[CO2(aq)] may be reconstructed with fewer assumptions than current approaches

Reply to Morel : cadmium as a micronutrient and macrotoxin in the oceans

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 110 (2013): E1878, doi:10.1073/pnas.1305068110.We thank François Morel for his interest in our study. Morel states that our conclusions are based on the approximate match between the Cd-isotope composition of cultured bacteria and the fractionation of Cd isotopes seen in seawater (1). This match is only a minor component of our argument, and we welcome the opportunity to reiterate our case

The role of Rubisco kinetics and pyrenoid morphology in shaping the CCM of haptophyte microalgae

The haptophyte algae are a cosmopolitan group of primary producers that contribute significantly to the marine carbon cycle and play a major role in paleo-climate studies. Despite their global importance, little is known about carbon assimilation in haptophytes, in particular the kinetics of their Form 1D CO2-fixing enzyme, Rubisco. Here we examine Rubisco properties of three haptophytes with a range of pyrenoid morphologies (Pleurochrysis carterae, Tisochrysis lutea, and Pavlova lutheri) and the diatom Phaeodactylum tricornutum that exhibit contrasting sensitivities to the trade-offs between substrate affinity (Km) and turnover rate (kcat) for both CO2 and O2. The pyrenoid-containing T. lutea and P. carterae showed lower Rubisco content and carboxylation properties (KC and kCcat) comparable with those of Form 1D-containing non-green algae. In contrast, the pyrenoid-lacking P. lutheri produced Rubisco in 3-fold higher amounts, and displayed a Form 1B Rubisco kCcat–KC relationship and increased CO2/O2 specificity that, when modeled in the context of a C3 leaf, supported equivalent rates of photosynthesis to higher plant Rubisco. Correlation between the differing Rubisco properties and the occurrence and localization of pyrenoids with differing intracellular CO2:O2 microenvironments has probably influenced the divergent evolution of Form 1B and 1D Rubisco kinetics

Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT), 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder). Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.Boryana S Stamova, Michelle Apperson, Wynn L Walker, Yingfang Tian, Huichun Xu, Peter Adamczy, Xinhua Zhan, Da-Zhi Liu, Bradley P Ander, Isaac H Liao, Jeffrey P Gregg, Renee J Turner, Glen Jickling, Lisa Lit and Frank R Shar

Perception of isolated chords: Examining frequency of occurrence, instrumental timbre, acoustic descriptors and musical training

This study investigated the perception of isolated chords using a combination of experimental manipulation and exploratory analysis. Twelve types of chord (five triads and seven tetrads) were presented in two instrumental timbres (piano and organ) to listeners who rated the chords for consonance, pleasantness, stability and relaxation. Listener ratings varied by chord, by timbre, and according to musical expertise, and revealed that musicians distinguished consonance from the other variables in a way that other listeners did not. To further explain the data, a principal component analysis and linear regression examined three potential predictors of the listener ratings. First, each chord’s frequency of occurrence was obtained by counting its appearances in selected works of music. Second, listeners rated their familiarity with the instrumental timbre in which the chord was played. Third, chords were described using a set of acoustic features derived using the Timbre Toolbox and MIR Toolbox. Results of the study indicated that listeners’ ratings of both consonance and stability were influenced by the degree of musical training and knowledge of tonal hierarchy. Listeners’ ratings of pleasantness and relaxation, on the other hand, depended more on the instrumental timbre and other acoustic descriptions of the chord

Parthenogenic Blastocysts Derived from Cumulus-Free In Vitro Matured Human Oocytes

Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis..Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer

Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa

<p>Abstract</p> <p>Background</p> <p>African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade.</p> <p>Results</p> <p>Several published studies indicate high prostate cancer burden in Nigeria and Ghana. There was no published literature for the countries Benin, Gambia and Senegal that met our review criteria. Prostate cancer morbidity and/or mortality data from the Caribbean Islands and the United Kingdom also provided comparable or worse prostate cancer burden to that of US Blacks.</p> <p>Conclusion</p> <p>The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group.</p

Influenza Virus Non-Structural Protein 1 (NS1) Disrupts Interferon Signaling

Type I interferons (IFNs) function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1) encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1-, STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non-tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1 virus infection of human monocyte-derived macrophages led to inhibition of both ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo human lung tissues with IFN-α results in the up-regulation of a number of IFN-stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data suggest that NS1 can directly interfere with IFN signaling to enhance viral replication, but that treatment with IFN can nevertheless override these inhibitory effects to block H5N1 and H1N1 virus infections

Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

Our understanding of the underlying molecular mechanism of Parkinson’s disease (PD) is hampered by a lack of access to affected human dopaminergic (DA) neurons on which to base experimental research. Fortunately, the recent development of a PD disease model using induced pluripotent stem cells (iPSCs) provides access to cell types that were previously unobtainable in sufficient quantity or quality, and presents exciting promises for the elucidation of PD etiology and the development of potential therapeutics. To more effectively model PD, we generated two patient-derived iPSC lines: a line carrying a homozygous p.G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene and another carrying a full gene triplication of the α-synuclein encoding gene, SNCA. We demonstrated that these PD-linked pluripotent lines were able to differentiate into DA neurons and that these neurons exhibited increased expression of key oxidative stress response genes and α-synuclein protein. Moreover, when compared to wild-type DA neurons, LRRK2-G2019S iPSC-derived DA neurons were more sensitive to caspase-3 activation caused by exposure to hydrogen peroxide, MG-132, and 6-hydroxydopamine. In addition, SNCA-triplication iPSC-derived DA neurons formed early ubiquitin-positive puncta and were more sensitive to peak toxicity from hydrogen peroxide-induced stress. These aforementioned findings suggest that LRRK2-G2019S and SNCA-triplication iPSC-derived DA neurons exhibit early phenotypes linked to PD. Given the high penetrance of the homozygous LRRK2 mutation, the expression of wild-type α-synuclein protein in the SNCA-triplication line, and the clinical resemblance of patients afflicted with these familial disorders to sporadic PD patients, these iPSC-derived neurons may be unique and valuable models for disease diagnostics and development of novel pharmacological agents for alleviation of relevant disease phenotypes

EMF1 and PRC2 Cooperate to Repress Key Regulators of Arabidopsis Development

EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis vegetative development. Loss of function mutants in the EMF1 gene mimic the phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode epigenetic repressors that regulate many aspects of eukaryotic development. In Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins, EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG mechanism is unclear. To study the EMF1 functions and its mechanism of action, we performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3 modification on the chromosomal and genic level. ChIPOTLe peak finding and clustering analyses both show that the highly trimethylated genes also have high enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with regulatory genes, which are silenced to allow vegetative growth, and with genes specifying cell fates during growth and differentiation. H3K27me3 marks not only these genes but also some genes that are involved in endosperm development and maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene activities via diverse mechanisms and plays a novel role in the PcG mechanism