Use of weighted reference panels based on empirical estimates of ancestry for capturing untyped variation

Many association methods use a subset of genotyped single nucleotide polymorphisms (SNPs) to capture or infer genotypes at other untyped SNPs. We and others previously showed that tag SNPs selected to capture common variation using data from The International HapMap Consortium (Nature 437:1299–1320, 2005), The International HapMap Consortium (Nature 449:851–861, 2007) could also capture variation in populations of similar ancestry to HapMap reference populations (de Bakker et al. in Nat Genet 38:1298–1303, 2006; González-Neira et al. in Genome Res 16:323–330, 2006; Montpetit et al. in PLoS Genet 2:282–290, 2006; Mueller et al. in Am J Hum Genet 76:387–398, 2005). To capture variation in admixed populations or populations less similar to HapMap panels, a “cosmopolitan approach,” in which all samples from HapMap are used as a single reference panel, was proposed. Here we refine this suggestion and show that use of a “weighted reference panel,” constructed based on empirical estimates of ancestry in the target population (relative to available reference panels), is more efficient than the cosmopolitan approach. Weighted reference panels capture, on average, only slightly fewer common variants (minor allele frequency > 5%) than the cosmopolitan approach (mean r ² = 0.977 vs. 0.989, 94.5% variation captured vs. 96.8% at r ² > 0.8), across the five populations of the Multiethnic Cohort, but entail approximately 25% fewer tag SNPs per panel (average 538 vs. 718). These results extend a recent study in two Indian populations (Pemberton et al. in Ann Hum Genet 72:535–546, 2008). Weighted reference panels are potentially useful for both the selection of tag SNPs in diverse populations and perhaps in the design of reference panels for imputation of untyped genotypes in genome-wide association studies in admixed populations. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A Computational Analysis of Localized Ca<Superscript>2+</Superscript>-Dynamics Generated by Heterogeneous Release Sites

We investigate the role of heterogeneous expression of IP₃R and RyR in generating diverse elementary Ca²⁺ signals. It has been shown empirically (Wojcikiewicz and Luo in Mol. Pharmacol. 53(4):656–662, 1998; Newton et al. in J. Biol. Chem. 269(46):28613–28619, 1994; Smedt et al. in Biochem. J. 322(Pt. 2):575–583, 1997) that tissues express various proportions of IP₃ and RyR isoforms and this expression is dynamically regulated (Parrington et al. in Dev. Biol. 203(2):451–461, 1998; Fissore et al. in Biol. Reprod. 60(1):49–57, 1999; Tovey et al. in J. Cell Sci. 114(Pt. 22):3979–3989, 2001). Although many previous theoretical studies have investigated the dynamics of localized calcium release sites (Swillens et al. in Proc. Natl. Acad. Sci. U.S.A. 96(24):13750–13755, 1999; Shuai and Jung in Proc. Natl. Acad. Sci. U.S.A. 100(2):506–510, 2003a; Shuai and Jung in Phys. Rev. E, Stat. Nonlinear Soft Matter Phys. 67(3 Pt. 1):031905, 2003b; Thul and Falcke in Biophys. J. 86(5):2660–2673, 2004; DeRemigio and Smith in Cell Calcium 38(2):73–86, 2005; Nguyen et al. in Bull. Math. Biol. 67(3):393–432, 2005), so far all such studies focused on release sites consisting of identical channel types. We have extended an existing mathematical model (Nguyen et al. in Bull. Math. Biol. 67(3):393–432, 2005) to release sites with two (or more) receptor types, each with its distinct channel kinetics. Mathematically, the release site is represented by a transition probability matrix for a collection of nonidentical stochastically gating channels coupled through a shared Ca²⁺ domain. We demonstrate that under certain conditions a previously defined mean-field approximation of the coupling strength does not accurately reproduce the release site dynamics. We develop a novel approximation and establish that its performance in these instances is superior. We use this mathematical framework to study the effect of heterogeneity in the Ca²⁺-regulation of two colocalized channel types on the release site dynamics. We consider release sites consisting of channels with both Ca²⁺-activation and inactivation (“four-state channels”) and channels with Ca²⁺-activation only (“two-state channels”) and show that for the appropriate parameter values, synchronous channel openings within a release site with any proportion of two-state to four-state channels are possible, however, the larger the proportion of two-state channels, the more sensitive the dynamics are to the exact spatial positioning of the channels and the distance between channels. Specifically, the clustering of even a small number of two-state channels interferes with puff/spark termination and increases puff durations or leads to a tonic response.     

Cl Anion-Dependent Mg-ATPase

We studied, in the rat brain, the synaptosomal and microsomal membrane fractions of Cl⁻ ion-activated, Mg²⁺-dependent ATPase, satisfying the necessary kinetic peculiarities of transport ATPases, by a novel method of kinetic analysis of the multisite enzyme systems: (1) the [Mg-ATP] complex constitutes the substrate of the enzymic reaction; (2) the V = f(Cl⁻) dependence-reflecting curve is bell-shaped; (3) substrate dependence, V = f(S), curves at a constant concentration of free ligands (Mg_f, ATP_f, Cl⁻); (4) as known from the literature, in the process of reaction a phosphorylated intermediate is formed (Gerencser, Crit Rev Biochem Mol Biol 31:303–337, 1996). We report on the Cl-ATPase molecular mechanism and its place in the “P-type ATPase” classification.     

Traveller or tourist? Jack Kerouac and the commodification of culture

Jack Kerouac, the author of On The Road, was a central figure of the Beat Generation, a generation which rebelled against middle-class conformity in post–World War II America. Kerouac described himself as “a religious wanderer” (Kerouac 2006: 2), but an examination of his texts and life suggest his travels may also be understood as tourism. Viewed through the prism of tourism, this study will argue, for example, that MacCannell’s notion of the tourist’s quest for reality and authenticity (MacCannell 1989: 3) provides some insight into why Kerouac wrote that just south of Macon, Georgia, he and his travelling companion Neal Cassady stopped and got out of the car, “and suddenly both of us were stoned with joy to realize that in the darkness all around us was fragrant green grass and the smell of fresh manure and warm waters” (Kerouac 1957: 115). As Kerouac rebelled against being, as one of his protagonists in The Dharma Bums put it, “imprisoned in a system of work, produce, consume, work, produce, consume” (Kerouac 2006: 73) he travelled across America on a rapidly improving network of highways, turning “mobility into a retreat” (Holladay and Holton 2009: 42). Kerouac alternately identified himself as a hobo (Kerouac 1973: 181) and “not a real hobo” (Kerouac 1973: 173), but this article asks whether Kerouac’s travels were those of the last in a line of wanderers rebelling against conformity and modernization or a precursor of mobile mass tourism in America.     

Interactive Bodies: The Semiosis of Architectural Forms

In this paper architectural forms are presented as symbolic forms issued from the complex semiosis that characterises human cognition (Ferreira (2007, 2010)). Being semiotic objects, these symbolic forms are, consequently, context- dependent_they emerge and have meaning, i.e., they are assigned a functional and/or aesthetic value, in particular physical, social and cultural frameworks. As it happens with all semiotic objects, architectural forms, whatever their nature, are not static but highly interactive. In fact, they act as agents of specific semiotic processes, engaged in a permanent dialectic relationship with the environment they are embedded in. From this dialectics important physical, social, cultural and economic changes frequently arise, redefining this way the original framework for decades to come. As Pallasmaa (2009) points out: “Architecture is existentially rooted, and it expresses fundamental existential experiences, the complex condensation of how it feels to be human being in this world. Architecture grounds and frames existence and creates specific horizons of perception, understanding and identity.” Architecture happens in the context of particular landscapes both natural and man-made, individuating spaces, assigning them an identity, turning the frequently undifferentiated physical environment into “locus”, “place”, “site”, “ort”, definitely contributing to the definition of the mental map that individual minds are able to share collectively. The fundamental role played by architectural forms in the definition of “place” and identity and in the shaping or reshaping of a physical, social and cultural environment is analysed in this paper through a case study that observes the consequences of this dynamics in the development of the social and cultural tissue of a particular city.     

High-frequency adventitious shoots regeneration from leaf of non-heading Chinese cabbage (<Emphasis Type="Italic">Brassica campestris</Emphasis> ssp. <Emphasis Type="Italic">chinensis</Emphasis>) cultured in vitro

The objective of the present work was selection of cultivar and suitable medium for regenerating shoots from leaf segments of non-heading Chinese cabbage. We evaluated six types of supplemented media with 2.0, 5.0 and 10.0 mg l⁻¹ 6-BA; 1.0 and 2.0 mg l⁻¹ TDZ; 0.1, 0.3, 0.5, 0.8 and 1.0 mg l⁻¹NAA; 3.0, 5.0 and 7.5 mg l⁻¹AgNO₃; 0.01 mg l⁻¹ 2–4, D and 4.0 mg l⁻¹ KT for shoot regeneration and six cultivars “Sanchidaye”, “Liuchuandasuomian”, “Qingyou 4”, “Liangbaiye”, “AiKang 5” and “Hanxiao F3”, furthermore for root formation three types of supplemented media with 0.2, 0.3, 0.5 mg l⁻¹ NAA, and for survival rate two types of base media: turf + vermiculite + manure (1:2:0.2) and soil + vermiculite (1:2). Culturing leaf segments on MS medium supplemented with 2 mg l⁻¹ TDZ; 0.5 mg l⁻¹ NAA and 7.5 mg l⁻¹ AgNO₃ gave the highest number of shoots per leaf segment (66) while roots were best formed on the medium supplemented with 0.2 mg l⁻¹ NAA. Survival rate was highest (61.6%) in the turf: vermiculite: manure (1:2:0.2) medium. The highest percentage of responding leaf segments, number of shoots per leaf segment, rooting percentage and survival rate were observed in “Liuchuandasuomian”. The plantlets were transferred to the soil and grown into mature plants in pots. These results could be used for preliminary selections of cultivars to transfer disease resistance (Bt) gene through agrobacterium in non-heading Chinese cabbage.     

Selenium–Mercury Interactions in Man and Animals

Selenium–mercury interactions were most extensively studied in relation to alleviation of Hg toxicity by added selenium. This presentation considers the influence of mercury on endogenous selenium, on its tissue and cellular “status” after lifelong or acute exposure to mercury vapor (Hg^o). Discussed are data obtained from (1) humans living near or working in a mercury mine, and (2) rats experimentally exposed in the mine. Mercury vapor is unique—or similar to methylmercury—because of its ability to penetrate cell membranes and so invade all cells, where it is oxidized in the biologically active form (Hg⁺⁺) by catalase. Such in situ-generated ions can react with endogenously generated highly reactive Se metabolites, like HSe−, and render a part of the selenium unavailable for selenoprotein synthesis. Data on human populations indicate that in moderate Hg exposure combined with an adequate selenium supply through diet, Se bioavailability can be preserved. On the other hand, the results of an acute exposure study emphasize the dual role of selenium in mercury detoxification. Besides the well-known Se coaccumulation through formation of nontoxic Hg–Se complexes, we observed noticeable Se (co)excretion, at least at the beginning of exposure. The higher Hg accumulation rate in the group of animals with lower basal selenium levels can also point to selenium involvement in mercury excretion. In such conditions there is a higher probability for decreased selenoprotein levels (synthesis) in some tissues or organs, depending on the synthesis hierarchy.     

Climate change and coral reefs: Trojan horse or false prophecy?

Maynard et al. (Coral Reefs 27:745–749, 2008a) claim that much of the concern about the impacts of climate change on coral reefs has been “based on essentially untested assumptions regarding reefs and their capacity to cope with future climate change”. If correct, this claim has important implications for whether or not climate change represents the largest long-term threat to the sustainability of coral reefs, especially given their ad hominem argument that many coral reef scientists are guilty of “popularising worst-case scenarios” at the expense of truth. This article looks critically at the claims made by Maynard et al. (Coral Reefs 27:745–749, 2008a) and comes to a very different conclusion, with the thrust and veracity of their argument being called into question. Contrary to the fears of Grigg (Coral Reefs 11:183–186, 1992), who originally made reference to the Cassandra syndrome due to his concern about the sensationalisation of science, the proposition that coral reefs face enormous challenges from climate change and ocean acidification has and is being established through “careful experimentation, long-term monitoring and objective interpretation”. While this is reassuring, coral reef ecosystems continue to face major challenges from ocean warming and acidification. Given this, it is an imperative that scientists continue to maintain the rigour of their research and to communicate their conclusions as widely and clearly as possible. Given the shortage of time and the magnitude of the problem, there is little time to spare.     

Interactions of mercury in rat brain

In order to study the metabolism of mercury (Hg), its affinity to metallothionein (MT), and its influence on levels of the essential metals copper and zinc in the brain tissue of rats exposed to elemental mercury (Hg^O) vapor was investigated. The major findings were:

Spatial clustering property and its self-similarity in membrane potentials of hippocampal CA1 pyramidal neurons for a spatio-temporal input sequence

To clarify how the information of spatiotemporal sequence of the hippocampal CA3 affects the postsynaptic membrane potentials of single pyramidal cells in the hippocampal CA1, the spatio-temporal stimuli was delivered to Schaffer collaterals of the CA3 through a pair of electrodes and the post-synaptic membrane potentials were recorded using the patch-clamp recording method. The input–output relations were sequentially analyzed by applying two measures; “spatial clustering” and its “self-similarity” index. The membrane potentials were hierarchically clustered in a self-similar manner to the input sequences. The property was significantly observed at two and three time-history steps. In addition, the properties were maintained under two different stimulus conditions, weak and strong current stimulation. The experimental results are discussed in relation to theoretical results of Cantor coding, reported by Tsuda (Behav Brain Sci 24(5):793–847, 2001) and Tsuda and Kuroda (Jpn J Indust Appl Math 18:249–258, 2001; Cortical dynamics, pp 129–139, Springer-Verlag, 2004).     

An amplified surface plasmon resonance "turn-on" sensor for mercury ion using gold nanoparticles

Inorganic mercury ion (Hg²⁺) has been shown to coordinate to DNA duplexes that feature thymine–thymine (T–T) base pair mismatches. This observation suggests that an Hg²⁺-induced conformational change in a single-stranded DNA molecule can be used to detect aqueous Hg²⁺. Here, we have developed an analytical method using surface plasmon resonance (SPR) to develop a highly selective and sensitive detection technique for Hg²⁺ that takes advantage of T–Hg²⁺–T coordination chemistry. The general concept used in this approach is that the “turn-on” reaction of a hairpin probe via coordination of Hg²⁺ by the T–T base pair results in a substantial increase in the SPR response, followed by specific hybridization with a gold nanoparticle probe to amplify the sensor performance. Meanwhile, the limit of detection is 1 nM, which is lower than other recently developed techniques. A linear correlation is observed between the measured SPR reflectivity and the logarithm of the Hg²⁺ concentration over the concentration range of 5–5000 nM. Additionally, the SPR system provides high selectivity for Hg²⁺ in the presence of other divalent metal ions up to micromolar concentration levels. The proposed approach is also successfully utilized for the determination of Hg²⁺ in water samples.     

Use of sugarcane molasses “B” as an alternative for ethanol production with wild-type yeast <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> ITV-01 at high sugar concentrations

Molasses “B” is a rich co-product of the sugarcane process. It is obtained from the second step of crystallization and is richer in fermentable sugars (50–65%) than the final molasses, with a lower non-sugar solid content (18–33%); this co-product also contains good vitamin and mineral levels. The use of molasses “B” for ethanol production could be a good option for the sugarcane industry when cane sugar prices diminish in the market. In a complex medium like molasses, osmotolerance is a desirable characteristic for ethanol producing strains. The aim of this work was to evaluate the use of molasses “B” for ethanol production using Saccharomyces cerevisiae ITV-01 (a wild-type yeast isolated from sugarcane molasses) using different initial sugar concentrations (70–291 g L⁻¹), two inoculum sizes and the addition of nutrients such as yeast extract, urea, and ammonium sulphate to the culture medium. The results obtained showed that the strain was able to grow at 291 g L⁻¹ total sugars in molasses “B” medium; the addition of nutrients to the culture medium did not produce a statistically significant difference. This yeast exhibits high osmotolerance in this medium, producing high ethanol yields (0.41 g g⁻¹). The best conditions for ethanol production were 220 g L⁻¹ initial total sugars in molasses “B” medium, pH 5.5, using an inoculum size of 6 × 10⁶ cell mL⁻¹; ethanol production was 85 g L⁻¹, productivity 3.8 g L⁻¹ h⁻¹ with 90% preserved cell viability.     

Atmospheric culturable bacteria associated with meteorological conditions at a summer-time site in the mid-Willamette Valley,Oregon

A set of simultaneously collected quantitative measurements of 12 meteorological and 6 culturable atmospheric bacterial (CAB) variables was made over a grass seed field during several early, mid, and late summer days. The observation site was located between the Cascade and Coastal Mountain Ranges near Corvallis in the Willamette Valley, Oregon. Principal component analysis identified those meteorological variables that had the highest loadings in six eigenvectors that account for 95.9% of variation in the data factors, i.e., temperature @ 6.3 m above ground level (AGL), wind velocity @ 10.0 m AGL, wind velocity difference @ 1.7–10.0 m, barometric pressure, wind direction standard deviation, and wind direction. When these variables were used in a cluster analysis, they formed three statistically distinct meteorological variable clusters with means at ca. “midnight”, ca. “midday”, and ca. “evening.” The highest mean density of CAB (i.e., 153.4 ± 162.5 CFU/m³) was associated with the “midday” meteorological Cluster-1 that had warm, dry “gentle breezes” from the southeast, in the relatively bacteria loaded Willamette Valley air. The lowest mean density of CAB (i.e., 35.5 ± 24.1 CFU/m³) was associated with meteorological Cluster-3 in the late afternoon and “evening” occurring during the hottest and driest part of the day with “fresh breezes” coming from the north northwest in air off the Pacific Ocean. Finally, the last cluster, Cluster-2 occurred about midnight and had an intermediate density of CAB (74.2 ± 76.2 CFU/m³) in “light air” coming from the northwest, perhaps off the Pacific Ocean. The CAB associated with each of the three meteorological clusters was only partially statistically distinct. Partially because the CAB in both the Pacific Ocean derived air masses of the “evening” Cluster-3 and “midnight” Cluster-2 were not statically separable, though both were statistically separable from the midday, Willamette Valley derived Cluster-1. Further indicating their common source, both Pacific Ocean derived air masses had very similar percentages of pigmented bacteria, which were dissimilar to the pigmented bacterial population density in the Willamette Valley air masses. In short, it is speculated that “midnight” atmosphere may simply contain the settling concentrated residual bacterial particles in the abated fresh Pacific Ocean breezes after sundown. It is clearly shown that with the methods employed, it is possible to associate the uniqueness of the quantity, and to a lesser extent the quality, of the CAB population with the atmospheric conditions reported herein. From this project comes speculation that the strategies relating the quasi-conservative bacterial populations associated with distinct but nonconservative air mass properties can help to better understand more of the bacterial dynamics found in such situations. And to a further extent, molecular biological methods could be applied to identify bacterial taxa in specific air masses.     

Synchronized changes to relative neuron populations in postnatal human neocortical development

Mammalian prenatal neocortical development is dominated by the synchronized formation of the laminae and migration of neurons. Postnatal development likewise contains “sensitive periods” during which functions such as ocular dominance emerge. Here we introduce a novel neuroinformatics approach to identify and study these periods of active development. Although many aspects of the approach can be used in other studies, some specific techniques were chosen because of a legacy dataset of human histological data (Conel in The postnatal development of the human cerebral cortex, vol 1–8. Harvard University Press, Cambridge, 1939–1967). Our method calculates normalized change vectors from the raw histological data, and then employs k-means cluster analysis of the change vectors to explore the population dynamics of neurons from 37 neocortical areas across eight postnatal developmental stages from birth to 72 months in 54 subjects. We show that the cortical “address” (Brodmann area/sub-area and layer) provides the necessary resolution to segregate neuron population changes into seven correlated “k-clusters” in k-means cluster analysis. The members in each k-cluster share a single change interval where the relative share of the cortex by the members undergoes its maximum change. The maximum change occurs in a different change interval for each k-cluster. Each k-cluster has at least one totally connected maximal “clique” which appears to correspond to cortical function.     

A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside

The small alkylating molecule, 3-bromopyruvate (3BP), is a potent and specific anticancer agent. 3BP is different in its action from most currently available chemo-drugs. Thus, 3BP targets cancer cells’ energy metabolism, both its high glycolysis (“Warburg Effect”) and mitochondrial oxidative phosphorylation. This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an “Energy Blocker”, is very rapid in killing such cells. This is in sharp contrast to most commonly used anticancer agents that usually take longer to show a noticeable effect. In addition, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells. Therefore, 3BP can be considered a member, perhaps one of the first, of a new class of anticancer agents. Following 3BP’s discovery as a novel anticancer agent in vitro in the Year 2000 (Published in Ko et al. Can Lett 173:83–91, 2001), and also as a highly effective and rapid anticancer agent in vivo shortly thereafter (Ko et al. Biochem Biophys Res Commun 324:269–275, 2004), its efficacy as a potent anticancer agent in humans was demonstrated. Here, based on translational research, we report results of a case study in a young adult cancer patient with fibrolamellar hepatocellular carcinoma. Thus, a bench side discovery in the Department of Biological Chemistry at Johns Hopkins University, School of Medicine was taken effectively to bedside treatment at Johann Wolfgang Goethe University Frankfurt/Main Hospital, Germany. The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly.     

The carbon footprint measurement toolkit for the EU Ecolabel

Background, aim and scope  

Established in 1992, the European Union Ecolabel, that is briefly called “the Flower” because of the mark, is a voluntary ecological product award issued by the 1980/2000 Regulation (EC 2000). Adopting the ISO classification, the EU Ecolabel belongs to the “Type I environmental labelling” (ISO 14024:1999). The possibility to include GreenHouse Gases (GHG) emissions (as of CO₂ equivalents) among the EU Ecolabel criteria is a news that is justified to the consideration that, in the last 30 years, their management and limitation assumed a relevant and strategic importance for greenhouse effect control. This paper introduces results of a project for the European Commission that aimed at developing and checking a carbon footprint calculator procedure suitable for the inclusion of the GHG emission issue in the EU Ecolabel criteria. The output tool is primarily aimed at the policy maker, i.e. the European Commission, the European Union Ecolabel Board and the Ad Hoc Working Group (AHWG, created to develop a transparent and wide discussion with reference stakeholders, see Fig. 2 for more details), but, in this step, not directly to the applicant yet.     

The Poetics of Purpose

Hackles have been raised in biosemiotic circles by T. L. Short’s assertion that semiosis, as defined by Peirce, entails “acting for purposes” and therefore is not found below the level of the organism (2007a:174–177). This paper examines Short’s teleology and theory of purposeful behavior and offers a remedy to the disagreement. Remediation becomes possible when the issue is reframed in the terms of the complexity sciences, which allows intentionality to be understood as the interplay between local and global aspects of a system within a system. What is called “acting for purposes” is not itself a type of behavior so much as a relationship between a dynamic system that “exists for a purpose” and its microprocesses that “serve purposes.” The “intentional object” of philosophy is recast here as the holistic self-organized dynamics of a system, which exists for the purpose of self-maintenance, and that constrains the parts’ behaviors, which serve the purpose of forming the system. (A “system” can be any emergent, e.g. an abiotic form, an adapted species, a self, a conditioned response, thought, or a set of ideas.) The self-organized whole, which is represented to the parts in their own constrained behaviors, assumes the guiding function so long attributed to the mysterious “intentional object.” If emergent self-causation is not disallowed, creative originality, as well as directionality, becomes part of the definition of purposeful behavior. Thus, key tools used here, required for understanding emergence, come from poetics rather than semoitics. In the microprocesses of self-organization, I find what I call “accidental” indices and icons — which are poetic in the sense that they involve mere metonymic contiguity and metaphoric similarity — and which are preferentially selected under constrained conditions allowing radically new connections to habituate into an “intentional” self-organized system that, not coincidentally, has some of the emergent characteristics of a conventional symbolic system.

“Chelatable iron pool”: inositol 1,2,3-trisphosphate fulfils the conditions required to be a safe cellular iron ligand

Mammalian cells contain a pool of iron that is not strongly bound to proteins, which can be detected with fluorescent chelating probes. The cellular ligands of this biologically important “chelatable”, “labile” or “transit” iron are not known. Proposed ligands are problematic, because they are saturated by magnesium under cellular conditions and/or because they are not “safe”, i.e. they allow iron to catalyse hydroxyl radical formation. Among small cellular molecules, certain inositol phosphates (InsPs) excel at complexing Fe³⁺ in such a “safe” manner in vitro. However, we previously calculated that the most abundant InsP, inositol hexakisphosphate, cannot interact with Fe³⁺ in the presence of cellular concentrations of Mg²⁺. In this work, we study the metal complexation behaviour of inositol 1,2,3-trisphosphate [Ins(1,2,3)P ₃], a cellular constituent of unknown function and the simplest InsP to display high-affinity, “safe”, iron complexation. We report thermodynamic constants for the interaction of Ins(1,2,3)P ₃ with Na⁺, K⁺, Mg²⁺, Ca²⁺, Cu²⁺, Fe²⁺ and Fe³⁺. Our calculations indicate that Ins(1,2,3)P ₃ can be expected to complex all available Fe³⁺ in a quantitative, 1:1 reaction, both in cytosol/nucleus and in acidic compartments, in which an important labile iron subpool is thought to exist. In addition, we calculate that the fluorescent iron probe calcein would strip Fe³⁺ from Ins(1,2,3)P ₃ under cellular conditions, and hence labile iron detected using this probe may include iron bound to Ins(1,2,3)P ₃. Therefore Ins(1,2,3)P ₃ is the first viable proposal for a transit iron ligand. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation

An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3 and reduce Fe3 to Fe2 , demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the β-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more acces- sible to degradation.     

The Role of Organic Acids in the Domestication of <Emphasis Type="Italic">Oxalis tuberosa</Emphasis>: A New Model for Studying Domestication Resulting in Opposing Crop Phenotypes<Superscript>1</Superscript>

The Role of Organic Acids in the Domestication of Oxalis tuberosa: A New Model for Studying Domestication Resulting in Opposing Crop Phenotypes. Though few crops display directly opposing domesticated phenotypes, these crops may be the key to understanding domestication processes that address conflicting selective pressures in the agricultural ecosystem. Two relatively well-known examples are cassava (Manihot esculenta Crantz), which has high-cyanide and low-cyanide varieties, and potato (Solanum section Petota). Among the potatoes are several species, including the common potato (Solanum tuberosum L.), that have low levels of glycoalkaloids and there are other species of “bitter potato” with elevated levels of glycoalkaloids. We propose that Oxalis tuberosa Molina, “oca,” may represent a third example of such a crop system, with opposing high organic acid and low organic acid cultivars. Each cultivar set has different cultural food preparation practices (“use-categories”), similar to the “use-categories” that have been described for potatoes in the Andes (Brush et al. Economic Botany 35;70–88, 1981; Zimmerer Journal of Biogeography 18;165–178, 1991). Our initial analyses suggest that organic acids in tubers may be an important biochemical difference between use-categories, based on both oxalic acid and pH data. Here, we review our understanding of organic acids in oca tubers, while highlighting areas that merit further investigation.