Oxygen isotope ratios of PO4: An inorganic indicator of enzymatic activity and P metabolism and a new biomarker in the search for life

The distinctive relations between biological activity and isotopic effect recorded in biomarkers (e.g., carbon and sulfur isotope ratios) have allowed scientists to suggest that life originated on this planet nearly 3.8 billion years ago. The existence of life on other planets may be similarly identified by geochemical biomarkers, including the oxygen isotope ratio of phosphate (δ18Op) presented here. At low near-surface temperatures, the exchange of oxygen isotopes between phosphate and water requires enzymatic catalysis. Because enzymes are indicative of cellular activity, the demonstration of enzyme-catalyzed PO4–H2O exchange is indicative of the presence of life. Results of laboratory experiments are presented that clearly show that δ18OP values of inorganic phosphate can be used to detect enzymatic activity and microbial metabolism of phosphate. Applications of δ18Op as a biomarker are presented for two Earth environments relevant to the search for extraterrestrial life: a shallow groundwater reservoir and a marine hydrothermal vent system. With the development of in situ analytical techniques and future planned sample return strategies, δ18Op may provide an important biosignature of the presence of life in extraterrestrial systems such as that on Mars.

Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice

Induction of phase 2 enzymes, which neutralize reactive electrophiles and act as indirect antioxidants, appears to be an effective means for achieving protection against a variety of carcinogens in animals and humans. Transcriptional control of the expression of these enzymes is mediated, at least in part, through the antioxidant response element (ARE) found in the regulatory regions of their genes. The transcription factor Nrf2, which binds to the ARE, appears to be essential for the induction of prototypical phase 2 enzymes such as glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreductase (NQO1). Constitutive hepatic and gastric activities of GST and NQO1 were reduced by 50–80% in nrf2-deficient mice compared with wild-type mice. Moreover, the 2- to 5-fold induction of these enzymes in wild-type mice by the chemoprotective agent oltipraz, which is currently in clinical trials, was almost completely abrogated in the nrf2-deficient mice. In parallel with the enzymatic changes, nrf2-deficient mice had a significantly higher burden of gastric neoplasia after treatment with benzo[a]pyrene than did wild-type mice. Oltipraz significantly reduced multiplicity of gastric neoplasia in wild-type mice by 55%, but had no effect on tumor burden in nrf2-deficient mice. Thus, Nrf2 plays a central role in the regulation of constitutive and inducible expression of phase 2 enzymes in vivo and dramatically influences susceptibility to carcinogenesis. Moreover, the total loss of anticarcinogenic efficacy of oltipraz in the nrf2-disrupted mice highlights the prime importance of elevated phase 2 gene expression in chemoprotection by this and similar enzyme inducers.

Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy meromyosin reveals asymmetry in the interaction between myosin heads and placement of subfragment 2

Regulation of the actin-activated ATPase of smooth muscle myosin II is known to involve an interaction between the two heads that is controlled by phosphorylation of the regulatory light chain. However, the three-dimensional structure of this inactivated form has been unknown. We have used a lipid monolayer to obtain two-dimensional crystalline arrays of the unphosphorylated inactive form of smooth muscle heavy meromyosin suitable for structural studies by electron cryomicroscopy of unstained, frozen-hydrated specimens. The three-dimensional structure reveals an asymmetric interaction between the two myosin heads. The ATPase activity of one head is sterically “blocked” because part of its actin-binding interface is positioned onto the converter domain of the second head. ATPase activity of the second head, which can bind actin, appears to be inhibited through stabilization of converter domain movements needed to release phosphate and achieve strong actin binding. When the subfragment 2 domain of heavy meromyosin is oriented as it would be in an actomyosin filament lattice, the position of the heads is very different from that needed to bind actin, suggesting an additional contribution to ATPase inhibition in situ.

The μ opiate receptor as a candidate gene for pain: Polymorphisms, variations in expression, nociception, and opiate responses

There are differences between human individuals and between mouse strains in levels of μ opiate receptor (μOR) expression, responses to painful stimuli, and responses to opiate drugs. One of the best candidates for contributing to these differences is variation at the μOR gene locus. Support for this idea comes from analyses of the human and murine μOR genes. Assessments of individual differences in human μOR expression add further support. Studies with mice, including knockout-transgenic, quantitative trait locus, and strain-comparison studies, also strongly support the possibility that μOR gene alleles would be strong candidates for contributing to individual differences in human nociception and opiate drug responses. This paper reviews current analyses of the murine and human μOR genes, their important variants, and correlations between these variants and opiate influences on pain.

Oceanic minerals: Their origin, nature of their environment, and significance

The chemical and isotopic compositions of oceanic biogenic and authigenic minerals contain invaluable information on the evolution of seawater, hence on the history of interaction between tectonics, climate, ocean circulation, and the evolution of life. Important advances and greater understanding of (a) key minor and trace element cycles with various residence times, (b) isotopic sources and sinks and fractionation behaviors, and (c) potential diagenetic problems, as well as developments in high-precision instrumentation, recently have been achieved. These advances provided new compelling evidence that neither gradualism nor uniformitarianism can explain many of the new important discoveries obtained from the chemistry and isotopic compositions of oceanic minerals. Presently, the best-developed geochemical proxies in biogenic carbonates are 18O/16O and Sr/Ca ratios (possibly Mg/Ca) for temperature; 87Sr/86Sr for input sources, Cd/Ca and Ba/Ca ratios for phosphate and alkalinity concentrations, respectively, thus also for ocean circulation; 13C/12C for ocean productivity; B isotopes for seawater pH;, U, Th isotopes, and 14C for dating; and Sr and Mn concentrations for diagenesis. The oceanic authigenic minerals most widely used for chemical paleoceanography are barite, evaporite sulfates, and hydrogenous ferromanganese nodules. Marine barite is an effective alternative monitor of seawater 87Sr/86Sr, especially where carbonates are diagenetically altered or absent. It also provides a high-resolution record of seawater sulfate S isotopes, (evaporite sulfates only carry an episodic record), with new insights on factors affecting the S and C cycles and atmospheric oxygen. High-resolution studies of Sr, Nd, and Pb isotopes of well-dated ferromanganese nodules contain invaluable records on climate driven changes in oceanic circulation.

Mineral surfaces and bioavailability of heavy metals: A molecular-scale perspective

There is a continual influx of heavy metal contaminants and pollutants into the biosphere from both natural and anthropogenic sources. A complex variety of abiotic and biotic processes affects their speciation and distribution, including adsorption onto and desorption from mineral surfaces, incorporation in precipitates or coprecipitates, release through the dissolution of minerals, and interactions with plants and microbes. Some of these processes can effectively isolate heavy metals from the biosphere, whereas others cause their release or transformation to different species that may be more (or less) bioavailable and/or toxic to organisms. Here we focus on abiotic adsorption and precipitation or coprecipitation processes involving the common heavy metal contaminant lead and the metalloids arsenic and selenium in mine tailings and contaminated soils. We have used extremely intense x-rays from synchrotron sources and a structure-sensitive method known as x-ray absorption fine structure (XAFS) spectroscopy to determine the molecular-level speciation of these elements at concentrations of 50 to several thousand ppm in the contaminated environmental samples as well as in synthetic sorption samples. Our XAFS studies of As and Pb in the mine tailings show that up to 50% of these contaminants in the samples studied may be present as adsorbed species on mineral surfaces, which makes them potentially more bioavailable than when present in sparingly soluble solid phases. Our XAFS studies of Se(VI) sorption on Fe2+-containing sulfates show that this element undergoes redox reactions that transform it into less bioavailable and less toxic species. This type of information on molecular-level speciation of heavy metal and metalloid contaminants in various environmental settings is needed to prioritize remediation efforts and to assess their potential hazard to humans and other organisms.

In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.

The activity of glycogen synthase (GSase; EC 2.4.1.11) is regulated by covalent phosphorylation. Because of this regulation, GSase has generally been considered to control the rate of glycogen synthesis. This hypothesis is examined in light of recent in vivo NMR experiments on rat and human muscle and is found to be quantitatively inconsistent with the data under conditions of glycogen synthesis. Our first experiments showed that muscle glycogen synthesis was slower in non-insulin-dependent diabetics compared to normals and that their defect was in the glucose transporter/hexokinase (GT/HK) part of the pathway. From these and other in vivo NMR results a quantitative model is proposed in which the GT/HK steps control the rate of glycogen synthesis in normal humans and rat muscle. The flux through GSase is regulated to match the proximal steps by "feed forward" to glucose 6-phosphate, which is a positive allosteric effector of all forms of GSase. Recent in vivo NMR experiments specifically designed to test the model are analyzed by metabolic control theory and it is shown quantitatively that the GT/HK step controls the rate of glycogen synthesis. Preliminary evidence favors the transporter step. Several conclusions are significant: (i) glucose transport/hexokinase controls the glycogen synthesis flux; (ii) the role of covalent phosphorylation of GSase is to adapt the activity of the enzyme to the flux and to control the metabolite levels not the flux; (iii) the quantitative data needed for inferring and testing the present model of flux control depended upon advances of in vivo NMR methods that accurately measured the concentration of glucose 6-phosphate and the rate of glycogen synthesis.

Rates of decomposition of ribose and other sugars: implications for chemical evolution.

The existence of the RNA world, in which RNA acted as a catalyst as well as an informational macromolecule, assumes a large prebiotic source of ribose or the existence of pre-RNA molecules with backbones different from ribose-phosphate. The generally accepted prebiotic synthesis of ribose, the formose reaction, yields numerous sugars without any selectivity. Even if there were a selective synthesis of ribose, there is still the problem of stability. Sugars are known to be unstable in strong acid or base, but there are few data for neutral solutions. Therefore, we have measured the rate of decomposition of ribose between pH 4 and pH 8 from 40 degrees C to 120 degrees C. The ribose half-lives are very short (73 min at pH 7.0 and 100 degrees C and 44 years at pH 7.0 and 0 degrees C). The other aldopentoses and aldohexoses have half-lives within an order of magnitude of these values, as do 2-deoxyribose, ribose 5-phosphate, and ribose 2,4-bisphosphate. These results suggest that the backbone of the first genetic material could not have contained ribose or other sugars because of their instability.

The International Human Rights Policies of New Democracies: Brazil and Chile in Comparative Perspective

Since the beginning of the 1990s, the majority of Latin American states have attempted to incorporate in some way or another human rights concern into their respective foreign policies, highlighting a history of human rights abuses and the return of democratic political rule as a trigger for galvanizing a commitment to assist in preventing such violations in other countries. Yet, while human rights have come to play a non-trivial role in the contemporary foreign policy of many Latin American states, there is great diversity in the ways and the extent to which they go about incorporating human rights concerns into their foreign policies. Explaining the diversity of human rights foreign policies of new Latin American democracies is at the heat of this project. The main research questions are the following: Why do new democracies incorporate human rights into their foreign policies? And what explains the different international human rights policies of new democracies? To answer these questions, this research compares the human rights foreign policies of Chile and Brazil for over two decades starting from their respective transitions to democracy. The study argues that states commitment to international human rights is the result of the intersection of domestic and international influences. At the international level, the search for international legitimacy and the desire for recognition and credibility affected the adoption of international human rights in both cases but with different degrees of impact. International values and pressures by themselves, while necessary, are an insufficient condition for human rights initiatives perceived to have not insubstantial political, economic or strategic costs. New democracies will be more or less likely to actively include human rights in their international policies depending on the following four domestic conditions: political leadership legitimizing the inclusion of human rights into a state's policies, civil society groups connected to international human rights advocacy networks with a capacity to influencing the foreign policy decisions of their government, and the Foreign Ministry's attitudes towards international human rights and the degree of influence it exercises over the outcome of the foreign policy process.

Challenges and Opportunities in Managing the Aging Workforce: An Investigation of the Federal Emergency Management Agency

The aging workforce is becoming the majority of the working population in the United States. Although the literature on the aging workforce is sizable, little exists on how public agencies use the older workers. This capstone project examines the challenges and opportunities related to the employment of older workers as seen through a case study of the Federal Emergency Management Agency (FEMA). Knowledge gained from a synthesis of the literature review with survey data collected and analyzed will enable HR professionals to better understand the demographic, economic, regulatory, and intellectual influences of the aging workforce. The results from the survey of FEMA employees suggest a basis to plan and implement successful hiring and retention policies related to the aging workforce.

Coverage and invariability in fuzzy systems

This paper presents a new complex system systemic. Here, we are working in a fuzzy environment, so we have to adapt all the previous concepts and results that were obtained in a non-fuzzy environment, for this fuzzy case. The direct and indirect influences between variables will provide the basis for obtaining fuzzy and/or non-fuzzy relationships, so that the concepts of coverage and invariability between sets of variables will appear naturally. These two concepts and their interconnections will be analyzed from the viewpoint of algebraic properties of inclusion, union and intersection (fuzzy and non-fuzzy), and also for the loop concept, which, as we shall see, will be of special importance.

Ukraine, Belarus and Moldova and the Chinese economic expansion in Eastern Europe. OSW Commentary No. 79, 2012-05-28

The countries of Eastern European and China have been increasingly interested in deepening bilateral contacts over the past few years. In the case of Ukraine, Belarus and Moldova this has been caused by the bad economic situation which was in part caused by the consequences of the global economic crisis of 2008 and the desire to establish closer political relations with a country whose significance on the international arena is continually growing. Each of these countries has different expectations regarding the scale and the nature of co-operation with China. Chisinau wishes only to boost trade, whereas in Minsk and Kyiv, Beijing is also presented as a strategic partner whose investments may not only help the indebted economies recover but also strengthen the position of these countries in their dealings with the EU, and especially with Russia. Beijing sees co-operation with these countries in differently, and its offer is much more modest than Belarus and Ukraine are expecting. Eastern Europe is one of the last parts of the world with which China is activating its co-operation. This is not a priority region for Beijing. China wants to derive economic benefits and to diversify the markets on which it invests its financial surplus, and it does not intend to extend its political dialogue with Ukraine, Belarus and Moldova beyond the framework which determines its economic interests. The main reason for this is the nature of relations between Russia and China. Beijing sees its partnership with Moscow as more beneficial, and will not offer these countries support in their relations with Russia since in its opinion they belong to Russia’s sphere of influence. Minsk and Kyiv are pinning too much hope on their co-operation with Beijing, while China offers no real counterbalance to the Russian and EU influences in these countries. Nevertheless, it should be expected that China will capitalise on the beneficial political climate in Ukraine, Belarus and Moldova to reinforce its influence in a region whose location will facilitate its expansion to the EU and the Customs Union markets. In the medium term, Beijing may become a major economic player in Eastern Europe. In a decade’s time this may translate into political influence. Meanwhile, in the short term, China’s financial engagement in Ukraine, Belarus and Moldova will contribute to increasing the debts and deepening the foreign trade deficits of these countries.

Perspectives in Resource Management and Climate Change Adaptation in the Southern and Eastern Mediterranean. MEDPRO Policy Paper No. 6, March 2013

This policy paper focuses on the sustainable management of some key natural resources in southern and eastern Mediterranean countries (SEMCs) under climate change and anthropogenic pressures. In a business-as-usual and even more so in a failed cooperation scenario, water resources, ecosystems and biodiversity in the region are under stress, with negative consequences for agriculture, food security, tourism and development. However, proper adaptation strategies are shown to be effective in reconciling resource conservation with GDP, trade and population growth. These need be implemented in different ways: technological, institutional, behavioural; and at different levels: regional, national and international. There is ample room for fruitful cooperation between the EU and SEMCs in this area, which can take the form of EU direct financial and technical support when resources in SEMCs are scarce, and of multilateral and bilateral cooperation programmes to improve resource efficiency. The EU could also take on the role of coordinating these different bilateral actions and, at the same time, support SEMCs to establish a structured programme focused on the communication and dissemination of emerging best practices.

Social Capital and Individual Happiness in Europe. Bruges European Economic Research (BEER) Papers 25/December 2012

This paper explores the relationship between social capital and happiness both in Europe as a whole, as well as in its four main geographical macro-regions – North, South, East and West – separately. We test the hypothesis of whether social capital, in its three-fold definition established by Coleman (1988) – trust, social interaction, and norms and sanctions – influences individual happiness across European countries and regions. The concept of social capital is further enriched by incorporating Putnam- (1993) and Olson- (1982) type variables on associational activity. Using ordinal logistic regression analysis on data for 48,583 individuals from 25 European countries, we reach three main findings. First, social capital matters for happiness across the three dimensions considered. Second, the main drivers of the effects of social capital on happiness appear to be informal social interaction and general social, as well as institutional trust. And third, there are significant differences in how social capital interacts with happiness across different areas of Europe, with the connection being at is weakest in the Nordic countries.