bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafast plasmonics using transparent conductive oxide hybrids in the epsilon-near-zero regime
Authors: Traviss Daniel , Bruck Roman , Mills Ben , Abb Martina , Muskens Otto L.
Published: March 2013

The dielectric response of transparent conductive oxides near the bulk plasmon frequency is characterized by a refractive index less than vacuum. In analogy with x-ray optics, it is shown that this regime results in total external reflection and air-guiding of light. In addition, the strong reduction of the wavevector in the indium-tin oxide below that of free space enables a new surface plasmon polariton mode which can be excited without requiring a prism or grating coupler. Ultrafast control of the surface plasmon polariton mode is achieved with a modulation amplitude reaching 20%.
Preparation, structural and magnetic studies on BiFe1-xCrxO3 (x = 0.0, 0.05 and 0.1) multiferroic nanoparticles
Authors: Layek Samar , Saha Santanu , Verma H. C.
Published: March 2013

BiFe1-xCrxO3 (x = 0.0, 0.05 and 0.1) nanoparticles are prepared by the combustion method without using any solvent. All the synthesized nanoparticles are single phase in nature, nearly spherical in shape and crystallize in distorted perovskite structure (space group R3c) with an average crystallite size of the order of 40 nm. The room temperature magnetization observed in BiFeO3 nanoparticles is larger than that in the bulk. Saturation magnetization and coercive field increase with increasing Cr-doping. Strong superexchange interaction between Fe3+ and Cr3+ atoms is likely to give rise to such increase in magnetization with Cr-doping. Mössbauer data of these nanoparticles show ordered magnetic state in which Fe atoms are in 3+ oxidation states.
The puckering free-energy surface of proline
Authors: Wu Di
Published: March 2013

Proline has two preferred puckering states, which are often characterized by the pseudorotation phase angle and amplitude. Although proline's five endocyclic torsion angles can be utilized to calculate the phase angle and amplitude, it is not clear if there is any direct correlation between each torsion angle and the proline-puckering pathway. Here we have designed five proline puckering pathways utilizing each torsion angle χj (j = 1∼5) as the reaction coordinate. By examining the free-energy surfaces of the five puckering pathways, we find they can be categorized into two groups. The χ2 pathway (χ2 is about the Cβ—Cγ bond) is especially meaningful in describing proline puckering: it changes linearly with the puckering amplitude and symmetrically with the phase angle. Our results show that this conclusion applies to both trans and cis proline conformations. We have also analyzed the correlations of proline puckering and its backbone torsion angles ϕ and ψ. We show proline has preferred puckering states at the specific regions of ϕ, ψ angles. Interestingly, the shapes of ψ-χ2 free-energy surfaces are similar among the trans proline in water, cis proline in water and cis proline in the gas phase, but they differ substantially from that of the trans proline in the gas phase. Our calculations are conducted using molecular simulations; we also verify our results using the proline conformations selected from the Protein Data Bank. In addition, we have compared our results with those calculated by the quantum mechanical methods.
RDTM solution of Caputo time fractional-order hyperbolic telegraph equation
Authors: Srivastava Vineet K. , Awasthi Mukesh K. , Tamsir Mohammad
Published: March 2013

In this study, a mathematical model has been developed for the second order hyperbolic one-dimensional time fractional Telegraph equation (TFTE). The fractional derivative has been described in the Caputo sense. The governing equations have been solved by a recent reliable semi-analytic method known as the reduced differential transformation method (RDTM). The method is a powerful mathematical technique for solving wide range of problems. Using RDTM method, it is possible to find exact solution as well as closed approximate solution of any ordinary or partial differential equation. Three numerical examples of TFTE have been provided in order to check the effectiveness, accuracy and convergence of the method. The computed results are also depicted graphically.
A ring test of a wireless in vitro gas production system
Authors: Cornou Cécile , Storm Ida M. L. Drejer , Hindrichsen Ida K. , Worgan Hilary , Bakewell Eleanor , Ruiz David R. Yáñez , Abecia Leticia , Tagliapietra Franco , Cattani Mirko , Ritz Christian , Hansen Hanne H.
Published: March 2013

The in vitro gas production (GP) technique has been widely used for feed evaluation. However, variability in results limits useful comparisons. Results from a ring test undertaken in four laboratories (Italy – IT, Spain – SP, Wales – WA and Denmark – DK) using the same wireless equipment (ANKOM Technology), same substrates and same laboratory protocol are presented, including calculation of repeatability and reproducibility according to ISO 5725-2. Hay, maize starch and straw samples and units without sample (blanks) were incubated in five repetitions using rumen inoculum from cows (DK, IT and WA) or sheep (SP). Curves, corrected for blanks, were fitted using an exponential regression model with a lag time. The following variables were considered: (i) GP24 and GP48: raw values at 24 and 48 h (mL/g DM), corrected for blanks; (ii) A: asymptotic GP (mL/g DM); (iii) T1/2: time when half A is produced (h); (iv) GPMR: maximum predicted GP rate (mL/h); (v) L: lag time (h). A mixed model including laboratories as random effect was used. A significant interaction between substrate and laboratories was found for all variables except A. The most repeatable and reproducible results were observed for A and GP48. The results from this ring test suggest the need for more standardisation, particularly in the procedures that occur outside the laboratory.
TRPV4 channels stimulate Ca
2
+
-induced Ca
2+
release in astrocytic endfeet and amplify neurovascular coupling responses
Authors: Dunn Kathryn M. , Hill-Eubanks David C. , Liedtke Wolfgang B. , Nelson Mark T.
Published: March 2013

In the CNS, astrocytes are sensory and regulatory hubs that play important roles in cerebral homeostatic processes, including matching local cerebral blood flow to neuronal metabolism (neurovascular coupling). These cells possess a highly branched network of processes that project from the soma to neuronal synapses as well as to arterioles and capillaries, where they terminate in “endfeet” that encase the blood vessels. Ca
2+
signaling within the endfoot mediates neurovascular coupling; thus, these functional microdomains control vascular tone and local perfusion in the brain. Transient receptor potential vanilloid 4 (TRPV4) channels—nonselective cation channels with considerable Ca
2+
conductance—have been identified in astrocytes, but their function is largely unknown. We sought to characterize the influence of TRPV4 channels on Ca
2+
dynamics in the astrocytic endfoot microdomain and assess their role in neurovascular coupling. We identified local TRPV4-mediated Ca
2+
oscillations in endfeet and further found that TRPV4 Ca
2+
signals are amplified and propagated by Ca
2+
-induced Ca
2+
release from inositol trisphosphate receptors (IP
3
Rs). Moreover, TRPV4-mediated Ca
2+
influx contributes to the endfoot Ca
2+
response to neuronal activation, enhancing the accompanying vasodilation. Our results identify a dynamic synergy between TRPV4 channels and IP
3
Rs in astrocyte endfeet and demonstrate that TRPV4 channels are engaged in and contribute to neurovascular coupling.
Hsp70 nucleotide exchange factor Fes1 is essential for ubiquitin-dependent degradation of misfolded cytosolic proteins
Authors: Gowda Naveen Kumar Chandappa , Kandasamy Ganapathi , Froehlich Marceli S. , Dohmen R. Jürgen , Andréasson Claes
Published: March 2013

Protein quality control systems protect cells against the accumulation of toxic misfolded proteins by promoting their selective degradation. Malfunctions of quality control systems are linked to aging and neurodegenerative disease. Folding of polypeptides is facilitated by the association of 70 kDa Heat shock protein (Hsp70) molecular chaperones. If folding cannot be achieved, Hsp70 interacts with ubiquitylation enzymes that promote the proteasomal degradation of the misfolded protein. However, the factors that direct Hsp70 substrates toward the degradation machinery have remained unknown. Here, we identify Fes1, an Hsp70 nucleotide exchange factor of hitherto unclear physiological function, as a cytosolic triaging factor that promotes proteasomal degradation of misfolded proteins. Fes1 selectively interacts with misfolded proteins bound by Hsp70 and triggers their release from the chaperone. In the absence of Fes1, misfolded proteins fail to undergo polyubiquitylation, aggregate, and induce a strong heat shock response. Our findings reveal that Hsp70 direct proteins toward either folding or degradation by using distinct nucleotide exchange factors.
M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation
Authors: Morgan Hugh P. , O’Reilly Francis J. , Wear Martin A. , O’Neill J. Robert , Fothergill-Gilmore Linda A. , Hupp Ted , Walkinshaw Malcolm D.
Published: March 2013

We show that the M2 isoform of pyruvate kinase (M2PYK) exists in equilibrium between monomers and tetramers regulated by allosteric binding of naturally occurring small-molecule metabolites. Phenylalanine stabilizes an inactive T-state tetrameric conformer and inhibits M2PYK with an IC
50
value of 0.24 mM, whereas thyroid hormone (triiodo-
l
-thyronine, T3) stabilizes an inactive monomeric form of M2PYK with an IC
50
of 78 nM. The allosteric activator fructose-1,6-bisphosphate [F16BP, AC
50
(concentration that gives 50% activation) of 7 μM] shifts the equilibrium to the tetrameric active R-state, which has a similar activity to that of the constitutively fully active isoform M1PYK. Proliferation assays using HCT-116 cells showed that addition of inhibitors phenylalanine and T3 both increased cell proliferation, whereas addition of the activator F16BP reduced proliferation. F16BP abrogates the inhibitory effect of both phenylalanine and T3, highlighting a dominant role of M2PYK allosteric activation in the regulation of cancer proliferation. X-ray structures show constitutively fully active M1PYK and F16BP-bound M2PYK in an R-state conformation with a lysine at the dimer-interface acting as a peg in a hole, locking the active tetramer conformation. Binding of phenylalanine in an allosteric pocket induces a 13° rotation of the protomers, destroying the peg-in-hole R-state interface. This distinct T-state tetramer is stabilized by flipped out Trp/Arg side chains that stack across the dimer interface. X-ray structures and biophysical binding data of M2PYK complexes explain how, at a molecular level, fluctuations in concentrations of amino acids, thyroid hormone, and glucose metabolites switch M2PYK on and off to provide the cell with a nutrient sensing and growth signaling mechanism.
Turnover of microbial lipids in the deep biosphere and growth of benthic archaeal populations
Authors: Xie Sitan , Lipp Julius S. , Wegener Gunter , Ferdelman Timothy G. , Hinrichs Kai-Uwe
Published: March 2013

Deep subseafloor sediments host a microbial biosphere with unknown impact on global biogeochemical cycles. This study tests previous evidence based on microbial intact polar lipids (IPLs) as proxies of live biomass, suggesting that Archaea dominate the marine sedimentary biosphere. We devised a sensitive radiotracer assay to measure the decay rate of ([
14
C]glucosyl)-diphytanylglyceroldiether (GlcDGD) as an analog of archaeal IPLs in continental margin sediments. The degradation kinetics were incorporated in model simulations that constrained the fossil fraction of subseafloor IPLs and rates of archaeal turnover. Simulating the top 1 km in a generic continental margin sediment column, we estimated degradation rate constants of GlcDGD being one to two orders of magnitude lower than those of bacterial IPLs, with half-lives of GlcDGD increasing with depth to 310 ky. Given estimated microbial community turnover times of 1.6–73 ky in sediments deeper than 1 m, 50–96% of archaeal IPLs represent fossil signals. Consequently, previous lipid-based estimates of global subseafloor biomass probably are too high, and the widely observed dominance of archaeal IPLs does not rule out a deep biosphere dominated by Bacteria. Reverse modeling of existing concentration profiles suggest that archaeal IPL synthesis rates decline from around 1,000 pg⋅mL
−1
sediment⋅y
−1
at the surface to 0.2 pg⋅mL
−1
⋅y
−1
at 1 km depth, equivalent to production of 7 × 10
5
to 140 archaeal cells⋅mL
−1
sediment⋅y
−1
, respectively. These constraints on microbial growth are an important step toward understanding the relationship between the deep biosphere and the carbon cycle.
EJC core component MLN51 interacts with eIF3 and activates translation
Authors: Chazal Pierre-Etienne , Daguenet Elisabeth , Wendling Corinne , Ulryck Nathalie , Tomasetto Catherine , Sargueil Bruno , Le Hir Hervé
Published: March 2013

The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonucleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.
The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway
Authors: Rauthan Manish , Ranji Parmida , Aguilera Pradenas Nataly , Pitot Christophe , Pilon Marc
Published: March 2013

Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the synthesis of cholesterol via the mevalonate pathway. This pathway also produces coenzyme Q (a component of the respiratory chain), dolichols (important for protein glycosylation), and isoprenoids (lipid moieties responsible for the membrane association of small GTPases). We previously showed that the nematode
Caenorhabditis elegans
is useful to study the noncholesterol effects of statins because its mevalonate pathway lacks the sterol synthesis branch but retains all other branches. Here, from a screen of 150,000 mutagenized genomes, we isolated four
C. elegans
mutants resistant to statins by virtue of gain-of-function mutations within the first six amino acids of the protein ATFS-1, the key regulator of the mitochondrial unfolded protein response that includes activation of the chaperones HSP-6 and HSP-60. The
atfs-1
gain-of-function mutants are also resistant to ibandronate, an inhibitor of an enzyme downstream of HMG-CoA reductase, and to gliotoxin, an inhibitor acting on a subbranch of the pathway important for protein prenylation, and showed improved mitochondrial function and protein prenylation in the presence of statins. Additionally, preinduction of the mitochondrial unfolded protein response in wild-type worms using ethidium bromide or paraquat triggered statin resistance, and similar observations were made in
Schizosaccharomyces pombe
and in a mammalian cell line. We conclude that statin resistance through maintenance of mitochondrial homeostasis is conserved across species, and that the cell-lethal effects of statins are caused primarily through impaired protein prenylation that results in mitochondria dysfunction.
Structural foundations of resting-state and task-based functional connectivity in the human brain
Authors: Hermundstad Ann M. , Bassett Danielle S. , Brown Kevin S. , Aminoff Elissa M. , Clewett David , Freeman Scott , Frithsen Amy , Johnson Arianne , Tipper Christine M. , Miller Michael B. , Grafton Scott T. , Carlson Jean M.
Published: March 2013

Magnetic resonance imaging enables the noninvasive mapping of both anatomical white matter connectivity and dynamic patterns of neural activity in the human brain. We examine the relationship between the structural properties of white matter streamlines (structural connectivity) and the functional properties of correlations in neural activity (functional connectivity) within 84 healthy human subjects both at rest and during the performance of attention- and memory-demanding tasks. We show that structural properties, including the length, number, and spatial location of white matter streamlines, are indicative of and can be inferred from the strength of resting-state and task-based functional correlations between brain regions. These results, which are both representative of the entire set of subjects and consistently observed within individual subjects, uncover robust links between structural and functional connectivity in the human brain.
Anticipating land surface change
Authors: Streeter Richard , Dugmore Andrew J.
Published: March 2013

The interplay of human actions and natural processes over varied spatial and temporal scales can result in abrupt transitions between contrasting land surface states. Understanding these transitions is a key goal of sustainability science because they can represent abrupt losses of natural capital. This paper recognizes flickering between alternate land surface states in advance of threshold change and critical slowing down in advance of both threshold changes and noncritical transformation. The early warning signals we observe are rises in autocorrelation, variance, and skewness within millimeter-resolution thickness measurements of tephra layers deposited in A.D. 2010 and A.D. 2011. These signals reflect changing patterns of surface vegetation, which are known to provide early warning signals of critical transformations. They were observed toward migrating soil erosion fronts, cryoturbation limits, and expanding deflation zones, thus providing potential early warning signals of land surface change. The record of the spatial patterning of vegetation contained in contemporary tephra layers shows how proximity to land surface change could be assessed in the widespread regions affected by shallow layers of volcanic fallout (those that can be subsumed within the existing vegetation cover). This insight shows how we could use tephra layers in the stratigraphic record to identify “near misses,” close encounters with thresholds that did not lead to tipping points, and thus provide additional tools for archaeology, sustainability science, and contemporary land management.
Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium
Authors: Ryan Zachary C. , Ketha Hemamalini , McNulty Melissa S. , McGee-Lawrence Meghan , Craig Theodore A. , Grande Joseph P. , Westendorf Jennifer J. , Singh Ravinder J. , Kumar Rajiv
Published: March 2013

Inactivating mutations of the
SOST
(sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (
sost
) gene was replaced by the β-D-galactosidase (
lacZ
) gene in the germ line. Knockout (KO) (
sost
−/−
) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of
sost
KO mice but was undetectable in WT mice. Eight-week-old, male
sost
KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (
cyp27B1
) mRNA was increased in kidneys of
sost
KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased
cyp27B1
mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in
sost
KO mice compared with WT mice.
Sost
KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.
Exploiting microbial hyperthermophilicity to produce an industrial chemical, using hydrogen and carbon dioxide
Authors: Keller Matthew W. , Schut Gerrit J. , Lipscomb Gina L. , Menon Angeli L. , Iwuchukwu Ifeyinwa J. , Leuko Therese T. , Thorgersen Michael P. , Nixon William J. , Hawkins Aaron S. , Kelly Robert M. , Adams Michael W. W.
Published: March 2013

Microorganisms can be engineered to produce useful products, including chemicals and fuels from sugars derived from renewable feedstocks, such as plant biomass. An alternative method is to use low potential reducing power from nonbiomass sources, such as hydrogen gas or electricity, to reduce carbon dioxide directly into products. This approach circumvents the overall low efficiency of photosynthesis and the production of sugar intermediates. Although significant advances have been made in manipulating microorganisms to produce useful products from organic substrates, engineering them to use carbon dioxide and hydrogen gas has not been reported. Herein, we describe a unique temperature-dependent approach that confers on a microorganism (the archaeon
Pyrococcus furiosus,
which grows optimally on carbohydrates at 100°C) the capacity to use carbon dioxide, a reaction that it does not accomplish naturally. This was achieved by the heterologous expression of five genes of the carbon fixation cycle of the archaeon
Metallosphaera sedula,
which grows autotrophically at 73°C. The engineered
P. furiosus
strain is able to use hydrogen gas and incorporate carbon dioxide into 3-hydroxypropionic acid, one of the top 12 industrial chemical building blocks. The reaction can be accomplished by cell-free extracts and by whole cells of the recombinant
P. furiosus
strain. Moreover, it is carried out some 30°C below the optimal growth temperature of the organism in conditions that support only minimal growth but maintain sufficient metabolic activity to sustain the production of 3-hydroxypropionate. The approach described here can be expanded to produce important organic chemicals, all through biological activation of carbon dioxide.
New World cattle show ancestry from multiple independent domestication events
Authors: McTavish Emily Jane , Decker Jared E. , Schnabel Robert D. , Taylor Jeremy F. , Hillis David M.
Published: March 2013

Significance

Cattle were independently domesticated from the aurochs, a wild bovine species, in the vicinity of the current countries of Turkey and Pakistan ∼10,000 y ago. Cattle have since spread with humans across the world, including to regions where these two distinct lineages have hybridized. Using genomic tools, we investigated the ancestry of cattle from across the world. We determined that the descendants of the cattle brought to the New World by the Spanish in the late 1400s show ancestry from multiple domesticated lineages. This pattern resulted from pre-Columbian introgression of genes from African cattle into southern Europe.
Evolutionary mix-and-match with MFS transporters
Authors: Madej M. Gregor , Dang Shangyu , Yan Nieng , Kaback H. Ronald
Published: March 2013

Major facilitator superfamily (MFS) transport proteins are ubiquitous in the membranes of all living cells, and ∼25% of prokaryotic membrane transport proteins belong to this superfamily. The MFS represents the largest and most diverse group of transporters and includes members that are clinically important. A wide range of substrates is transported in many instances actively by transduction of the energy stored in an H
+
electrochemical gradient into a concentration gradient of substrate. MFS transporters are characterized by a deep central hydrophilic cavity surrounded by 12 mostly irregular transmembrane helices. An alternating inverted triple-helix structural symmetry within the N- and C-terminal six-helix bundles suggests that the proteins arose by intragenic multiplication. However, despite similar features, MFS transporters share only weak sequence homology. Here, we show that rearrangement of the structural symmetry motifs in the
Escherichia coli
fucose permease (FucP) results in remarkable homology to lactose permease (LacY). The finding is supported by comparing the location of 34 point mutations in FucP to the location of mutants in LacY. Furthermore, in contrast to the conventional, linear sequence alignment, homologies between sugar- and H
+
-binding sites in the two proteins are observed. Thus, LacY and FucP likely evolved from primordial helix-triplets that formed functional transporters; however, the functional segments assembled in a different consecutive order. The idea suggests a simple, parsimonious chain of events that may have led to the enormous sequence diversity within the MFS.
Regional control of histone H3 lysine 27 methylation in
Neurospora
Authors: Jamieson Kirsty , Rountree Michael R. , Lewis Zachary A. , Stajich Jason E. , Selker Eric U.
Published: March 2013

Trimethylated lysine 27 on histone H3 (H3K27me3) is present in
Drosophila, Arabidopsis
, worms, and mammals, but is absent from yeasts that have been examined. We identified and analyzed H3K27me3 in the filamentous fungus
Neurospora crassa
and in other
Neurospora
species. H3K27me3 covers 6.8% of the
N. crassa
genome, encompassing 223 domains, including 774 genes, all of which are transcriptionally silent.
N. crassa
H3K27me3-marked genes are less conserved than unmarked genes and only ∼35% of genes marked by H3K27me3 in
N. crassa
are also H3K27me3-marked in
Neurospora discreta
and
Neurospora tetrasperma
. We found that three components of the
Neurospora
Polycomb repressive complex 2 (PRC2)—[Su-(var)3–9; E(z); Trithorax] (SET)-7, embryonic ectoderm development (EED), and SU(Z)12 (suppressor of zeste12)—are required for H3K27me3, whereas the fourth component,
Neurospora
protein 55 (an
N. crassa
homolog of p55/RbAp48), is critical for H3K27me3 only at subtelomeric domains. Loss of H3K27me3, caused by deletion of the gene encoding the catalytic PRC2 subunit,
set-7
, resulted in up-regulation of 130 genes, including genes in both H3K27me3-marked and unmarked regions.
Generation of induced neurons via direct conversion in vivo
Authors: Torper Olof , Pfisterer Ulrich , Wolf Daniel A. , Pereira Maria , Lau Shong , Jakobsson Johan , Björklund Anders , Grealish Shane , Parmar Malin
Published: March 2013

Cellular reprogramming is a new and rapidly emerging field in which somatic cells can be turned into pluripotent stem cells or other somatic cell types simply by the expression of specific combinations of genes. By viral expression of neural fate determinants, it is possible to directly reprogram mouse and human fibroblasts into functional neurons, also known as induced neurons. The resulting cells are nonproliferating and present an alternative to induced pluripotent stem cells for obtaining patient- and disease-specific neurons to be used for disease modeling and for development of cell therapy. In addition, because the cells do not pass a stem cell intermediate, direct neural conversion has the potential to be performed in vivo. In this study, we show that transplanted human fibroblasts and human astrocytes, which are engineered to express inducible forms of neural reprogramming genes, convert into neurons when reprogramming genes are activated after transplantation. Using a transgenic mouse model to specifically direct expression of reprogramming genes to parenchymal astrocytes residing in the striatum, we also show that endogenous mouse astrocytes can be directly converted into neural nuclei (NeuN)-expressing neurons in situ. Taken together, our data provide proof of principle that direct neural conversion can take place in the adult rodent brain when using transplanted human cells or endogenous mouse cells as a starting cell for neural conversion.
Abrogation of IL-4 receptor-α-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing Th2 response
Authors: Müller Uwe , Stenzel Werner , Piehler Daniel , Grahnert Andreas , Protschka Martina , Köhler Gabriele , Frey Oliver , Held Josephin , Richter Tina , Eschke Maria , Kamradt Thomas , Brombacher Frank , Alber Gottfried
Published: March 2013

In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor α (IL-4Rα)-dependent polyfunctional Th2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4Rα-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4Rα expression on macrophages (LysMCreIL-4Rα–/lox mice) and IL-4Rα–/lox littermates. LysMCreIL-4Rα–/lox mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysMCreIL-4Rα–/lox mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysMCreIL-4Rα–/lox and IL-4Rα–/lox control mice, but macrophages from LysMCreIL-4Rα–/lox mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary Th2 responses were similar in infected LysMCreIL-4Rα–/lox and IL-4Rα–/lox mice with each mouse strain harboring polyfunctional Th2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysMCreIL-4Rα–/lox and IL-4Rα–/lox mice. Our results demonstrate that, despite residual IL-4Rα-independent alternative macrophage activation and ongoing Th2-dependent allergic inflammation, abrogation of IL-4Rα-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4Rα+/– background indicating a key contribution of macrophage IL-4Rα expression to susceptibility in allergic bronchopulmonary mycosis.
Three new stable L5 Mars Trojans
Authors: de la Fuente Marcos C. , de la Fuente Marcos R.
Published: March 2013

Mars was second to Jupiter in being recognized as the host of a population of Trojan minor bodies. Since 1990, five asteroids – 5261 Eureka, (101429) 1998 VF31, (121514) 1999 UJ7, 2001 DH47 and (311999) 2007 NS2 – have been identified as Mars Trojans, one L4 and four L5. Dynamical and spectroscopic evidence suggests that some Mars Trojans may be remnants of the original planetesimal population that formed in the terrestrial planets region. Here, we revisit the long-term dynamical evolution of the previously known Mars Trojans and show that 2011 SC191, 2011 SL25 and 2011 UN63 are also trailing (L5) Mars Trojans. They appear to be as stable as Eureka and may have been Trojans over the age of the Solar system. The fact that five Trojans move in similar orbits and one of them is a binary may point to the disruption of a larger body early in the history of the Solar system. Such a catastrophic event may also explain the apparently strong asymmetry in terms of number of objects (one versus seven) between the L4 and L5 regions. Future spectroscopic observations should be able to reject or confirm a putative common chemical signature that may lend further support to a collisional scenario.
Speculation and Risk Sharing with New Financial Assets*
Authors: Simsek Alp
Published: March 2013

I investigate the effect of financial innovation on portfolio risks when traders have belief disagreements. I decompose traders’ average portfolio risks into two components: the uninsurable variance, defined as portfolio risks that would obtain without belief disagreements, and the speculative variance, defined as portfolio risks that result from speculation. My main result shows that financial innovation always increases the speculative variance through two distinct channels: by generating new bets and by amplifying traders’ existing bets. When disagreements are large, these effects are sufficiently strong that financial innovation increases average portfolio risks, decreases average portfolio comovements, and generates greater speculative trading volume relative to risk-sharing volume. Moreover, a profit-seeking market maker endogenously introduces speculative assets that increase average portfolio risks.
Aminosilane functionalizations of mesoporous oxidized silicon for oligonucleotide synthesis and detection
Authors: De Stefano Luca , Oliviero Giorgia , Amato Jussara , Borbone Nicola , Piccialli Gennaro , Mayol Luciano , Rendina Ivo , Terracciano Monica , Rea Ilaria
Published: March 2013

Direct solid phase synthesis of peptides and oligonucleotides (ONs) requires high chemical stability of the support material. In this work, we have investigated the passivation ability of porous oxidized silicon multilayered structures by two aminosilane compounds, 3-aminopropyltriethoxysilane and 3-aminopropyldimethylethoxysilane (APDMES), for optical label-free ON biosensor fabrication. We have also studied by spectroscopic reflectometry the hybridization between a 13 bases ON, directly grown on the aminosilane modified porous oxidized silicon by
in situ
synthesis, and its complementary sequence. Even if the results show that both devices are stable to the chemicals (carbonate/methanol) used, the porous silica structure passivated by APDMES reveals higher functionalization degree due to less steric hindrance of pores.
On receiving a first copy of
Notes and Records
: George Sarton to A. V. Hill, 24 February 1942
Authors: Fox Robert
Published: March 2013

George Sarton, often regarded as the founder of the discipline of the history of science, appears to have first seen
Notes and Records of the Royal Society
in 1942. His letter of acknowledgement to A. V. Hill conveys both his pleasure at the publication (which the Royal Society had launched in 1938) and his frustration in trying to persuade scientists and ‘humanists’ of the value of his work. The letter also records Sarton's sadness at the death of his Harvard colleague L. J. Henderson, a fellow-worker in his campaign to ‘humanize science’.
Dislocations and inclusions in prestressed metals
Authors: Argani Luca , Bigoni Davide , Mishuris Gennady
Published: March 2013

The effect of prestress on dislocation (and inclusion) fields in nonlinear elastic solids is analysed by extending previous solutions by Eshelby and Willis. Using a plane-strain constitutive model (for incompressible incremental nonlinear elasticity) to describe the behaviour of ductile metals (
J
2
-deformation theory of plasticity), we show that when the level of prestress is high enough that shear band formation is approached, strongly localized strain patterns emerge, when a dislocation dipole is emitted by a source. These may explain cascade activation of dislocation clustering along slip band directions.
Large-scale phylogeny of chameleons suggests African origins and Eocene diversification
Authors: Tolley Krystal A. , Townsend Ted M. , Vences Miguel
Published: March 2013

Oceanic dispersal has emerged as an important factor contributing to biogeographic patterns in numerous taxa. Chameleons are a clear example of this, as they are primarily found in Africa and Madagascar, but the age of the family is post-Gondwanan break-up. A Malagasy origin for the family has been suggested, yet this hypothesis has not been tested using modern biogeographic methods with a dated phylogeny. To examine competing hypotheses of African and Malagasy origins, we generated a dated phylogeny using between six and 13 genetic markers, for up to 174 taxa representing greater than 90 per cent of all named species. Using three different ancestral-state reconstruction methods (Bayesian and likelihood approaches), we show that the family most probably originated in Africa, with two separate oceanic dispersals to Madagascar during the Palaeocene and the Oligocene, when prevailing oceanic currents would have favoured eastward dispersal. Diversification of genus-level clades took place in the Eocene, and species-level diversification occurred primarily in the Oligocene. Plio-Pleistocene speciation is rare, resulting in a phylogeny dominated by palaeo-endemic species. We suggest that contraction and fragmentation of the Pan-African forest coupled to an increase in open habitats (savannah, grassland, heathland), since the Oligocene played a key role in diversification of this group through vicariance.
Inferred L/M cone opsin polymorphism of ancestral tarsiers sheds dim light on the origin of anthropoid primates
Authors: Melin Amanda D. , Matsushita Yuka , Moritz Gillian L. , Dominy Nathaniel J. , Kawamura Shoji
Published: March 2013

Tarsiers are small nocturnal primates with a long history of fuelling debate on the origin and evolution of anthropoid primates. Recently, the discovery of M and L opsin genes in two sister species,Tarsius bancanus(Bornean tarsier) andTarsius syrichta(Philippine tarsier), respectively, was interpreted as evidence of an ancestral long-to-middle (L/M) opsin polymorphism, which, in turn, suggested a diurnal or cathemeral (arrhythmic) activity pattern. This view is compatible with the hypothesis that stem tarsiers were diurnal; however, a reversion to nocturnality during the Middle Eocene, as evidenced by hyper-enlarged orbits, predates the divergence ofT. bancanusandT. syrichtain the Late Miocene. Taken together, these findings suggest that some nocturnal tarsiers possessed high-acuity trichromatic vision, a concept that challenges prevailing views on the adaptive origins of the anthropoid visual system. It is, therefore, important to explore the plausibility and antiquity of trichromatic vision in the genusTarsius. Here, we show that Sulawesi tarsiers (Tarsius tarsier), a phylogenetic out-group of Philippine and Bornean tarsiers, have an L opsin gene that is more similar to the L opsin gene ofT. syrichtathan to the M opsin gene ofT. bancanusin non-synonymous nucleotide sequence. This result suggests that an L/M opsin polymorphism is the ancestral character state of crown tarsiers and raises the possibility that many hallmarks of the anthropoid visual system evolved under dim (mesopic) light conditions. This interpretation challenges the persistent nocturnal–diurnal dichotomy that has long informed debate on the origin of anthropoid primates.
Antlers on the Arctic Refuge: capturing multi-generational patterns of calving ground use from bones on the landscape
Authors: Miller Joshua H. , Druckenmiller Patrick , Bahn Volker
Published: March 2013

Bone accumulations faithfully record historical ecological data on animal communities, and owing to millennial-scale bone survival on high-latitude landscapes, have exceptional potential for extending records on arctic ecosystems. For the Porcupine Caribou Herd, maintaining access to calving grounds on the Arctic National Wildlife Refuge (ANWR, Alaska) is a central management concern. However, variability in calving ground geography over the 30+ years of monitoring suggests establishing the impacts of climate change and potential petroleum development on future calving success could benefit from extended temporal perspectives. Using accumulations of female antlers (shed within days of calving) and neonatal skeletons, we test if caribou calving grounds develop measureable and characteristic bone accumulations and if skeletal data may be helpful in establishing a fuller, historically integrated understanding of landscape and habitat needs. Bone surveys of an important ANWR calving area reveal abundant shed antlers (reaching 103km–2) and high proportional abundance of newborn skeletal individuals (up to 60% neonate). Openly vegetated riparian terraces, which compose less than 10 per cent of ANWR calving grounds, yield significantly higher antler concentrations than more abundant habitats traditionally viewed as primary calving terrain. Differences between habitats appear robust to potential differences in bone visibility. The distribution of antler weathering stages mirrors known multi-decadal calving histories and highlights portions of the antler accumulation that probably significantly extends records of calving activity. Death assemblages offer historically integrated ecological data valuable for the management and conservation of faunas across polar latitudes.
Integrative analysis of C. elegans modENCODE ChIP-seq data sets to infer gene regulatory interactions
Authors: Van Nostrand Eric L. , Kim Stuart K.
Published: March 2013

The C. elegans modENCODE Consortium has defined in vivo binding sites for a large array of transcription factors by ChIP-seq. In this article, we present examples that illustrate how this compendium of ChIP-seq data can drive biological insights not possible with analysis of individual factors. First, we analyze the number of independent factors bound to the same locus, termed transcription factor complexity, and find that low-complexity sites are more likely to respond to altered expression of a single bound transcription factor. Next, we show that comparison of binding sites for the same factor across developmental stages can reveal insight into the regulatory network of that factor, as we find that the transcription factor UNC-62 has distinct binding profiles at different stages due to distinct cofactor co-association as well as tissue-specific alternative splicing. Finally, we describe an approach to infer potential regulators of gene expression changes found in profiling experiments (such as DNA microarrays) by screening these altered genes to identify significant enrichment for targets of a transcription factor identified in ChIP-seq data sets. After confirming that this approach can correctly identify the upstream regulator on expression data sets for which the regulator was previously known, we applied this approach to identify novel candidate regulators of transcriptional changes with age. The analysis revealed nine candidate aging regulators, of which three were previously known to have a role in longevity. We experimentally showed that two of the new candidate aging regulators can extend lifespan when overexpressed, indicating that this approach can identify novel functional regulators of complex processes.
Barley MLA Immune Receptors Directly Interfere with Antagonistically Acting Transcription Factors to Initiate Disease Resistance Signaling
Authors: Chang Cheng , Yu Deshui , Jiao Jian , Jing Shaojuan , Schulze-Lefert Paul , Shen Qian-Hua
Published: March 2013

The nucleotide binding domain and Leucine-rich repeat (NLR)–containing proteins in plants and animals mediate pathogen sensing inside host cells and mount innate immune responses against microbial pathogens. The barley (Hordeum vulgare) mildew A (MLA) locus encodes coiled-coil (CC)–type NLRs mediating disease resistance against the powdery mildew pathogen Blumeria graminis. Here, we report direct interactions between MLA and two antagonistically acting transcription factors, MYB6 and WRKY1. The N-terminal CC signaling domain of MLA interacts with MYB6 to stimulate its DNA binding activity. MYB6 functions as a positive regulator of basal and MLA-mediated immunity responses to B. graminis. MYB6 DNA binding is antagonized by direct association with WRKY1 repressor, which in turn also interacts with the MLA CC domain. The activated form of full-length MLA10 receptor is needed to release MYB6 activator from WRKY1 repression and to stimulate MYB6-dependent gene expression. This implies that, while sequestered by the WRKY1 repressor in the presence of the resting immune receptor, MYB6 acts as an immediate and positive postactivation signaling component of the active state of MLA during transcriptional reprogramming for innate immune responses.
Segmenting Greek tomato consumers: policy and marketing insights towards a healthy diet
Authors: Alamanos Eleftherios , Bourlakis Michael , Tzimitra‐Kalogianni Irini
Published: March 2013

Purpose

The study aims to examine consumer behaviour towards fresh tomatoes and to reveal the factors that influence consumption leading to an adoption of a healthy diet.

Design/methodology/approach

A consumer survey was carried out in Thessaloniki (Greece) and 337 self‐reported questionnaires from tomato consumers were used in the analysis. The major consumer segments are illustrated and interventions to promote tomato consumption are suggested.

Findings

The findings from principal component analysis indicate that the main factors that influence consumption of fresh tomatoes are: “nutrition value”, “organoleptic characteristics” of tomatoes and “eating habits” of consumers. A two‐step cluster analysis revealed three segments of tomato consumers labelled as “Tomato‐loyals”, “Sensorialists” and “Health‐conscious”.

Practical implications

The findings reveal the consumption characteristics of each consumer segment where tailored social marketing plans can be developed based on this work. The findings will be of interest to food marketers and food policy makers, as they can contribute to addressing obesity problems in Europe in general and Mediterranean countries in particular.

Originality/value

The paper identifies the underlying reasons for eating fresh tomatoes, which can lead to the adoption of a healthy diet and can support policies towards that. It also reveals new consumer segments and highlights differences between them. In addition, it highlights the interventions to increase tomato consumption of each segment. Finally, it employs a cluster analysis technique, two‐step cluster analysis, which has not been widely used in marketing research.