bluuebunny/crossref_metadata_2025 huggingface dataset:
Of Mancessions and Hecoveries: Race, Gender, and the Political Construction of Economic Crises and Recoveries
Authors: Strolovitch Dara Z.
Published: March 2013

Through a discussion of the 2008 mortgage crisis and its similarities to the Great Depression of the 1930's and the Great Recession of 2007–09, I argue that the very notions of economic “crisis” and “recovery” are politically and ideologically constructed, and that conditions of vulnerability, often simply taken for granted as part of the normal social landscape when they affect marginalized populations, become regarded as crises when they affect dominant groups. Each of these crises, I argue, reveals different facets of the ways in which the power, normativity, and privilege of those perceived to be affected by economic hard times serve (1) to construct some economic troubles as “normal” and others as “crises;' (2) to prevent economic problems related to structural inequalities from being treated as crises by dominant political actors and institutions; and (3) to shape ideas about the ostensible solutions and ends to economic crises. By calling attention to these features of economic “crisis,” I aim to demonstrate the relevance of scholarship on race, class, gender, and intersectionality to the understanding of fundamental questions of contemporary political economy not often viewed from this perspective.
Theoretical study of interactions of BSA protein in a NaCl aqueous solution
Authors: Pellicane Giuseppe , Cavero Miguel
Published: March 2013

Bovine Serum Albumine (BSA) aqueous solutions in the presence of NaCl are investigated for different protein concentrations and low to intermediate ionic strengths. Protein interactions are modeled via a charge-screened colloidal model, in which the range of the potential is determined by the Debye-Hückel constant. We use Monte Carlo computer simulations to calculate the structure factor, and assume an oblate ellipsoidal form factor for BSA. The theoretical scattered intensities are found in good agreement with the experimental small angle X-ray scattering intensities available in the literature. The performance of well-known integral equation closures to the Ornstein-Zernike equation, namely the mean spherical approximation, the Percus-Yevick, and the hypernetted chain equations, is also assessed with respect to computer simulation.
Laplacian spectra of recursive treelike small-world polymer networks: Analytical solutions and applications
Authors: Liu Hongxiao , Zhang Zhongzhi
Published: March 2013

A central issue in the study of polymer physics is to understand the relation between the geometrical properties of macromolecules and various dynamics, most of which are encoded in the Laplacian spectra of a related graph describing the macrostructural structure. In this paper, we introduce a family of treelike polymer networks with a parameter, which has the same size as the Vicsek fractals modeling regular hyperbranched polymers. We study some relevant properties of the networks and show that they have an exponentially decaying degree distribution and exhibit the small-world behavior. We then study the Laplacian eigenvalues and their corresponding eigenvectors of the networks under consideration, with both quantities being determined through the recursive relations deduced from the network structure. Using the obtained recursive relations we can find all the eigenvalues and eigenvectors for the networks with any size. Finally, as some applications, we use the eigenvalues to study analytically or semi-analytically three dynamical processes occurring in the networks, including random walks, relaxation dynamics in the framework of generalized Gaussian structure, as well as the fluorescence depolarization under quasiresonant energy transfer. Moreover, we compare the results with those corresponding to Vicsek fractals, and show that the dynamics differ greatly for the two network families, which thus enables us to distinguish between them.
B-doping in Ge by excimer laser annealing
Authors: Impellizzeri G. , Napolitani E. , Boninelli S. , Fisicaro G. , Cuscunà M. , Milazzo R. , Magna A. La , Fortunato G. , Priolo F. , Privitera V.
Published: March 2013

An experimental and theoretical study of the effect of excimer laser annealing (ELA) on B redistribution and electrical activation in Ge is reported. We performed detailed structural, chemical, and electrical characterizations of Ge samples implanted with B (20 keV, 1 × 1015, or 1 × 1016 B/cm2) and processed by ELA (λ = 308 nm) with multiple pulses (1, 3, or 10). We also developed a diffusion model, in order to simulate the B redistribution induced by the ELA process. We found an anomalous impurity redistribution in the molten phase, which causes a dopant incorporation during the melt-growth at the maximum melt depth. The investigated samples showed a partial electrical activation of the B dopant. The inactivation of B in the samples implanted with 1 × 1015 B/cm2 was correlated to an oxygen contamination, while the poor electrical activation of B in the samples implanted with 1 × 1016 B/cm2 was related to the precipitation of the dopant, in good agreement with the experimental and theoretical results.
Interface-controlled magnetism and transport of ultrathin manganite films
Authors: Shapoval O. , Hühn S. , Verbeeck J. , Jungbauer M. , Belenchuk A. , Moshnyaga V.
Published: March 2013

We report ferromagnetic, TC=240 K, and metallic, TMI=250 K, behaviors of a three unit cell thick interface engineered lanthanum manganite film, grown by metalorganic aerosol deposition technique on SrTiO3(100) substrates. Atomically resolved electron microscopy and chemical analysis show that ultrathin manganite films start to grow with La-O layer on a strongly Mn/Ti-intermixed interface, engineered by an additional deposition of 2 u.c. of Sr-Mn-O. Such interface engineering results in a hole-doped manganite layer and stabilizes ferromagnetism and metallic conductivity down to the thickness of d = 3 u.c. The films with d = 8 u.c. demonstrate a bulk-like transport behavior with TMI∼TC=310−330 K.
Influence of interface roughness on the exchange bias of Co/CoO multilayers
Authors: Wang J. , Sannomiya T. , Shi J. , Nakamura Y.
Published: March 2013

The effect of interface roughness on the magnetic properties of ferromagnetic/antiferromagnetic multilayer has been studied by comparing the interfaces within identical multilayer (lower vs. upper) or from different Co/CoO multilayers (different deposition sequence). It has been found that for identical multilayer, the upper Co/CoO interfaces grow rougher and show stronger exchange bias than the lower Co/CoO interfaces. Structural analyses indicate that the successive layer deposition gives rise to a cumulative roughness at the upper interface, which affects the magnetic properties of ferromagnetic layer and its coupling to the antiferromagnetic layers. The interface roughness strengthens the interfacial exchange coupling by the increase of defect-generated uncompensated antiferromagnetic spins; such spins form coupling with the spins from Co layer at the interface. Due to the different coupling strength of each Co layer to the neighboring CoO layers, the multilayer showed distinct switching fields during the magnetization reversal process. Our results imply the possibility to control the strength of exchange bias, coercivity, and related magnetic properties by tuning the interface roughness.
Broadband wide-angle dispersion measurements: Instrumental setup, alignment, and pitfalls
Authors: Farhang A. , Abasahl B. , Dutta-Gupta S. , Lovera A. , Mandracci P. , Descrovi E. , Martin O. J. F.
Published: March 2013

The construction, alignment, and performance of a setup for broadband wide-angle dispersion measurements, with emphasis on surface plasmon resonance (SPR) measurements, are presented in comprehensive detail. In contrast with most SPR instruments working with a monochromatic source, this setup takes advantage of a broadband/white light source and has full capability for automated angle vs. wavelength dispersion measurements for any arbitrary nanostructure array. A cylindrical prism is used rather than a triangular one in order to mitigate refraction induced effects and allow for such measurements. Although seemingly simple, this instrument requires use of many non-trivial methods in order to achieve proper alignment over all angles of incidence. Here we describe the alignment procedure for such a setup, the pitfalls introduced from the finite beam width incident onto the cylindrical prism, and deviations in the reflected/transmitted beam resulting from the finite thickness of the sample substrate. We address every one of these issues and provide experimental evidences on the success of this instrument and the alignment procedure used.
Note: Rapid offset reduction of impedance bridges taking into account instrumental damping and phase shifting
Authors: van der Wel C. M. , Kortschot R. J. , Bakelaar I. A. , Erné B. H. , Kuipers B. W. M.
Published: March 2013

The sensitivity of an imperfectly balanced impedance bridge is limited by the remaining offset voltage. Here, we present a procedure for offset reduction in impedance measurements using a lock-in amplifier, by applying a complex compensating voltage external to the bridge. This procedure takes into account instrumental damping and phase shifting, which generally occur at the high end of the operational frequency range. Measurements demonstrate that the output of the circuit rapidly converges to the instrumentally limited noise at any frequency.
Selective area growth and characterization of InGaN nanocolumns for phosphor-free white light emission
Authors: Albert S. , Bengoechea-Encabo A. , Sanchez-Garcia M. A. , Calleja E. , Jahn U.
Published: March 2013

This work reports on the morphology and light emission characteristics of ordered InGaN nanocolumns grown by plasma-assisted molecular beam epitaxy. Within the growth temperature range of 750 to 650 °C, the In incorporation can be modified either by the growth temperature, the In/Ga ratio, or the III/V ratio, following different mechanisms. Control of these factors allows the optimization of the InGaN nanocolumns light emission wavelength and line-shape. Furthermore, yellow-white emission is obtained at room temperature from nanostructures with a composition-graded active InGaN region obtained by temperature gradients during growth.
Contact resistance improvement by dielectric breakdown in semiconductor-dielectric-metal contact
Authors: Majumdar Kausik , Hobbs Chris , Matthews Ken , Chen Chien-Hao , Ngai Tat , Yong Kang Chang , Bersuker Gennadi , Vivekanand Saikumar , Rodgers Martin , Gausepohl Steven , Kirsch Paul D. , Jammy Raj
Published: March 2013

We propose an approach for reduction of the contact resistance by inducing dielectric breakdown in a Si-dielectric-metal contact stack. We observe a 36% reduction in the contact resistance as well as an improvement in the uniformity in the distribution after dielectric breakdown. The results open up interesting device applications in complementary metal oxide semiconductor technology.
Investigation on origin of Z1/2 center in SiC by deep level transient spectroscopy and electron paramagnetic resonance
Authors: Kawahara Koutarou , Thang Trinh Xuan , Tien Son Nguyen , Janzén Erik , Suda Jun , Kimoto Tsunenobu
Published: March 2013

The Z1/2 center in n-type 4H-SiC epilayers—a dominant deep level limiting the carrier lifetime—has been investigated. Using capacitance versus voltage (C-V) measurements and deep level transient spectroscopy (DLTS), we show that the Z1/2 center is responsible for the carrier compensation in n-type 4H-SiC epilayers irradiated by low-energy (250 keV) electrons. The concentration of the Z1/2 defect obtained by C-V and DLTS correlates well with that of the carbon vacancy (VC) determined by electron paramagnetic resonance, suggesting that the Z1/2 deep level originates from VC.
A route for efficient non-resonance cloaking by using multilayer dielectric coating
Authors: Wang Xiaohui , Semouchkina Elena
Published: March 2013

An approach for designing transmission cloaks by using ordinary dielectrics instead of meta- and plasmonic materials is proposed and demonstrated by the development of a multi-layer cloak for hiding cylindrical objects larger than the wavelengths of incident radiation. The parameters of the cloak layers were found by using the Genetic Algorithm-based optimization procedure, which employed the reciprocal of total scattering cross width of the cloaked target, derived from the solution of the Helmholtz equation, as the fitness function. The proposed cloak demonstrated better cloaking efficiency than did a similarly sized metamaterial cloak designed by using the transformation optics relations.
The importance of iron supply during repetitive harvesting of Aster tripolium
Authors: Ventura Yvonne , Myrzabayeva Malika , Alikulov Zerekbay , Cohen Shabtai , Shemer Zion , Sagi Moshe
Published: March 2013

Aster tripolium L. is a salt marsh halophyte that has recently gained interest as a cash crop vegetable. Leaf yield and quality were investigated in plants grown with salinity in experiments with Perlite in pots and in plots on dune sand. Plants were repetitively harvested in a 14-day cycle. A. tripolium irrigated with 50 mM NaCl exhibited the highest yield when grown in pots, whereas in the plot experiment no significant differences in biomass accumulation occurred up to 80 mM NaCl in the irrigation water. Chemical leaf composition changed with salinity, exhibiting higher levels of electrical conductivity, total soluble solutes and the non-enzymatic antioxidant compounds ascorbic acid and polyphenols compared with control plants grown without NaCl supplementation. Using the repetitive harvest regime, leaf chlorosis occurred, a symptom shared by deficiencies in either nitrogen or iron. Comparative applications of five iron chelate formulations in plants grown with 50 mM NaCl in pots revealed improved leaf colour and chlorophyll content for only two of the applied Fe-chelates. Concomitantly with leaf colour restoration, the activity of nitrate reductase, the first enzyme during nitrate assimilation, which requires heme-iron for its proper function, increased 3-fold as a result of the iron treatment in the plot experiment. Importantly, the enhancement of nitrate reductase activity was associated with a considerable decrease in the leaf nitrate concentration. Therefore, we concluded that iron deficiency, in addition to leaf chlorosis, reduces A. tripolium leaf quality as a vegetable by increasing the leaf nitrate content. Furthermore, nitrate reductase (NR) activity levels in A. tripolium leaves may act as an indicator of iron deficiency that manifests itself as reduced nitrate content owing to the higher NR activity upon proper iron nutrition. These results demonstrate the importance of salinity level and the application of an appropriate iron-chelating formulation to generate marketable yields of Aster tripolium leafy vegetable when grown commercially on dune sand.
Do mosquitoes influence bat activity in coastal habitats?
Authors: Gonsalves Leroy , Lamb Susan , Webb Cameron , Law Bradley , Monamy Vaughan
Published: March 2013

Context Conservation of insectivorous bat populations requires appropriate management of foraging habitats and the prey resources they sustain. Endangered coastal saltmarsh communities support a diverse range of aquatic and terrestrial arthropods, including the saltmarsh mosquito (Aedes vigilax Skuse), an important vector of mosquito-borne viruses and a potentially important prey resource for insectivorous bats. Prey detectability by bats is considered to be limited with low-frequency echolocation, particularly in cluttered habitats, that may render abundant Ae. vigilax populations unavailable to some bat species. Aims To investigate relationships between availability of Ae. vigilax and non-mosquito prey, and the activity of foraging insectivorous bats in a range of coastal habitats. Methods We measured nightly bat activity and the abundance of prey (mosquito and non-mosquito) concurrently during neap and spring tides in saltmarsh, urban and forest habitats. Comparisons were made between tidal cycle and habitats, and relationships between bat activity and the abundance of prey were examined. Key results Whereas prey abundances were generally greatest in saltmarsh and forest habitats, bat activity was greatest in the forest habitat. However, proportional feeding activity was greatest in saltmarsh. Prey abundance was positively correlated with total bat activity only in the open saltmarsh, where an absence of clutter would maximise prey detectability and thus availability. Positive correlations between Ae. vigilax abundance and bat activity, across all habitats, were restricted to bats of the Vespadelus genus, which are small-sized bats that employ high-frequency echolocation suitable for detection of small prey along edges. Conclusions These findings suggest that Ae. vigilax may be an important prey resource for small, high-frequency echolocating bats capable of discerning small prey within cluttered forest as well as exploiting abundant prey in the open saltmarsh. Implications Small, high-frequency echolocating bats should be the focus of future studies investigating the importance of small prey, such as Ae. vigilax, to the diets of foraging bats.
Direct interaction of the major light-harvesting complex II and PsbS in nonphotochemical quenching
Authors: Wilk Laura , Grunwald Matthias , Liao Pen-Nan , Walla Peter Jomo , Kühlbrandt Werner
Published: March 2013

The photosystem II (PSII) subunit S (PsbS) plays a key role in nonphotochemical quenching, a photoprotective mechanism for dissipation of excess excitation energy in plants. The precise function of PsbS in nonphotochemical quenching is unknown. By reconstituting PsbS together with the major light-harvesting complex of PSII (LHC-II) and the xanthophyll zeaxanthin (Zea) into proteoliposomes, we have tested the individual contributions of PSII complexes and Zea to chlorophyll (Chl) fluorescence quenching in a membrane environment. We demonstrate that PsbS is stable in the absence of pigments in vitro. Significant Chl fluorescence quenching of reconstituted LHC-II was observed in the presence of PsbS and Zea, although neither Zea nor PsbS alone was sufficient to induce the same quenching. Coreconstitution with PsbS resulted in the formation of LHC-II/PsbS heterodimers, indicating their direct interaction in the lipid bilayer. Two-photon excitation measurements on liposomes containing LHC-II, PsbS, and Zea showed an increase of electronic interactions between carotenoid S
1
and Chl states,

, that correlated directly with Chl fluorescence quenching. These findings are in agreement with a carotenoid-dependent Chl fluorescence quenching by direct interactions of LHCs of PSII with PsbS monomers.
Early cercopithecid monkeys from the Tugen Hills, Kenya
Authors: Rossie James B. , Gilbert Christopher C. , Hill Andrew
Published: March 2013

The modern Old World Monkeys (Superfamily Cercopithecoidea, Family Cercopithecidae) can be traced back into the late Miocene, but their origin and subsequent diversification is obscured by the scarcity of terrestrial fossil sites in Africa between 15 and 6 Ma. Here, we document the presence of cercopithecids at 12.5 Ma in the Tugen Hills of Kenya. These fossils add 3 My to the known antiquity of crown Cercopithecidae. The two specimens represent one or possibly two species of early colobine, and their morphology suggests that they were less folivorous than their modern relatives.
Neonatal antibody responses are attenuated by interferon-γ produced by NK and T cells during RSV infection
Authors: Tregoning John S. , Wang Belinda Lei , McDonald Jacqueline U. , Yamaguchi Yuko , Harker James A. , Goritzka Michelle , Johansson Cecilia , Bukreyev Alexander , Collins Peter L. , Openshaw Peter J.
Published: March 2013

Respiratory syncytial virus (RSV) infects most children in the first year of life and is a major single cause of hospitalization in infants and young children. There is no effective vaccine, and antibody generated by primary neonatal infection is poorly protective against reinfection even with antigenically homologous viral strains. Studying the immunological basis of these observations in neonatal mice, we found that antibody responses to infection were low and unaffected by CD4 depletion, in contrast with adult mice, which had stronger CD4-dependent antibody responses. Natural killer cell depletion or codepletion of CD4+and CD8+cells during neonatal RSV infection caused a striking increase in anti-RSV antibody titer. These cells are major sources of the cytokine IFN-γ, and blocking IFN-γ also enhanced RSV-specific antibody responses in neonates. In addition, infection with a recombinant RSV engineered to produce IFN-γ reduced antibody titer, confirming that IFN-γ plays a pivotal role in inhibition of antibody responses after neonatal infection. These unexpected findings show that the induction of a strong cellular immune response may limit antibody responses in early life and that vaccines that induce IFN-γ–secreting cells might, in some situations, be less protective than those that do not.
Time-lapse electrical recordings of single neurons from the mouse neocortex
Authors: Cohen Lior , Koffman Noa , Meiri Hanoch , Yarom Yosef , Lampl Ilan , Mizrahi Adi
Published: March 2013

The ability of the brain to adapt to environmental demands implies that neurons can change throughout life. The extent to which single neurons actually change remains largely unstudied, however. To evaluate how functional properties of single neurons change over time, we devised a way to perform in vivo time-lapse electrophysiological recordings from the exact same neuron. We monitored the contralateral and ipsilateral sensory-evoked spiking activity of individual L2/3 neurons from the somatosensory cortex of mice. At the end of the first recording session, we electroporated the neuron with a DNA plasmid to drive GFP expression. Then, 2 wk later, we visually guided a recording electrode in vivo to the GFP-expressing neuron for the second time. We found that contralateral and ipsilateral evoked responses (i.e., probability to respond, latency, and preference), and spontaneous activity of individual L2/3 pyramidal neurons are stable under control conditions, but that this stability could be rapidly disrupted. Contralateral whisker deprivation induced robust changes in sensory-evoked response profiles of single neurons. Our experiments provide a framework for studying the stability and plasticity of single neurons over long time scales using electrophysiology.
Pheromone sensing regulates
Caenorhabditis elegans
lifespan and stress resistance via the deacetylase SIR-2.1
Authors: Ludewig Andreas H. , Izrayelit Yevgeniy , Park Donha , Malik Rabia U. , Zimmermann Anna , Mahanti Parag , Fox Bennett W. , Bethke Axel , Doering Frank , Riddle Donald L. , Schroeder Frank C.
Published: March 2013

Lifespan in
Caenorhabditis elegans
,
Drosophila
, and mice is regulated by conserved signaling networks, including the insulin/insulin-like growth factor 1 (IGF-1) signaling cascade and pathways depending on sirtuins, a family of NAD
+
-dependent deacetylases. Small molecules such as resveratrol are of great interest because they increase lifespan in many species in a sirtuin-dependent manner. However, no endogenous small molecules that regulate lifespan via sirtuins have been identified, and the mechanisms underlying sirtuin-dependent longevity are not well understood. Here, we show that in
C. elegans
, two endogenously produced small molecules, the dauer-inducing ascarosides ascr#2 and ascr#3, regulate lifespan and stress resistance through chemosensory pathways and the sirtuin SIR-2.1. Ascarosides extend adult lifespan and stress resistance without reducing fecundity or feeding rate, and these effects are reduced or abolished when nutrients are restricted. We found that ascaroside-mediated longevity is fully abolished by loss of SIR-2.1 and that the effect of ascr#2 requires expression of the G protein-coupled receptor DAF-37 in specific chemosensory neurons. In contrast to many other lifespan-modulating factors, ascaroside-mediated lifespan increases do not require insulin signaling via the FOXO homolog DAF-16 or the insulin/IGF-1-receptor homolog DAF-2. Our study demonstrates that
C. elegans
produces specific small molecules to control adult lifespan in a sirtuin-dependent manner, supporting the hypothesis that endogenous regulation of metazoan lifespan functions, in part, via sirtuins. These findings strengthen the link between chemosensory inputs and conserved mechanisms of lifespan regulation in metazoans and suggest a model for communal lifespan regulation in
C. elegans
.
Plant elicitor peptides are conserved signals regulating direct and indirect antiherbivore defense
Authors: Huffaker Alisa , Pearce Gregory , Veyrat Nathalie , Erb Matthias , Turlings Ted C. J. , Sartor Ryan , Shen Zhouxin , Briggs Steven P. , Vaughan Martha M. , Alborn Hans T. , Teal Peter E. A. , Schmelz Eric A.
Published: March 2013

Insect-induced defenses occur in nearly all plants and are regulated by conserved signaling pathways. As the first described plant peptide signal, systemin regulates antiherbivore defenses in the Solanaceae, but in other plant families, peptides with analogous activity have remained elusive. In the current study, we demonstrate that a member of the maize (
Zea mays
) plant elicitor peptide (Pep) family, ZmPep3, regulates responses against herbivores. Consistent with being a signal, expression of the
ZmPROPEP3
precursor gene is rapidly induced by
Spodoptera exigua
oral secretions. At concentrations starting at 5 pmol per leaf, ZmPep3 stimulates production of jasmonic acid, ethylene, and increased expression of genes encoding proteins associated with herbivory defense. These include proteinase inhibitors and biosynthetic enzymes for production of volatile terpenes and benzoxazinoids. In accordance with gene expression data, plants treated with ZmPep3 emit volatiles similar to those from plants subjected to herbivory. ZmPep3-treated plants also exhibit induced accumulation of the benzoxazinoid phytoalexin 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside. Direct and indirect defenses induced by ZmPep3 contribute to resistance against
S. exigua
through significant reduction of larval growth and attraction of
Cotesia marginiventris
parasitoids. ZmPep3 activity is specific to Poaceous species; however, peptides derived from PROPEP orthologs identified in Solanaceous and Fabaceous plants also induce herbivory-associated volatiles in their respective species. These studies demonstrate that Peps are conserved signals across diverse plant families regulating antiherbivore defenses and are likely to be the missing functional homologs of systemin outside of the Solanaceae.
Fossil slabs attached to unsubducted fragments of the Farallon plate
Authors: Wang Yun , Forsyth Donald W. , Rau Christina J. , Carriero Nina , Schmandt Brandon , Gaherty James B. , Savage Brian
Published: March 2013

As the Pacific–Farallon spreading center approached North America, the Farallon plate fragmented into a number of small plates. Some of the microplate fragments ceased subducting before the spreading center reached the trench. Most tectonic models have assumed that the subducting oceanic slab detached from these microplates close to the trench, but recent seismic tomography studies have revealed a high-velocity anomaly beneath Baja California that appears to be a fossil slab still attached to the Guadalupe and Magdalena microplates. Here, using surface wave tomography, we establish the lateral extent of this fossil slab and show that it is correlated with the distribution of high-Mg andesites thought to derive from partial melting of the subducted oceanic crust. We also reinterpret the high seismic velocity anomaly beneath the southern central valley of California as another fossil slab extending to a depth of 200 km or more that is attached to the former Monterey microplate. The existence of these fossil slabs may force a reexamination of models of the tectonic evolution of western North America over the last 30 My.
CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells
Authors: Arndt Kathrin , Grinenko Tatyana , Mende Nicole , Reichert Doreen , Portz Melanie , Ripich Tatsiana , Carmeliet Peter , Corbeil Denis , Waskow Claudia
Published: March 2013

Pentatransmembrane glycoprotein prominin-1 (CD133) is expressed at the cell surface of multiple somatic stem cells, and it is widely used as a cell surface marker for the isolation and characterization of human hematopoietic stem cells (HSCs) and cancer stem cells. CD133 has been linked on a cell biological basis to stem cell-fate decisions in human HSCs and emerges as an important physiological regulator of stem cell maintenance and expansion. Its expression and physiological relevance in the murine hematopoietic system is nevertheless elusive. We show here that CD133 is expressed by bone marrow-resident murine HSCs and myeloid precursor cells with the developmental propensity to give rise to granulocytes and monocytes. However, CD133 is dispensable for the pool size and function of HSCs during steady-state hematopoiesis and after transplantation, demonstrating a substantial species difference between mouse and man. Blood cell numbers in the periphery are normal; however, CD133 appears to be a modifier for the development of growth-factor responsive myeloerythroid precursor cells in the bone marrow under steady state and mature red blood cells after hematopoietic stress. Taken together, these studies show that CD133 is not a critical regulator of hematopoietic stem cell function in mouse but that it modifies frequencies of growth-factor responsive hematopoietic progenitor cells during steady state and after myelotoxic stress in vivo.
Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability
Authors: Wang Donglai , Zhou Jingyi , Liu Xiangyu , Lu Danyu , Shen Changchun , Du Yipeng , Wei Fu-Zheng , Song Boyan , Lu Xiaopeng , Yu Yu , Wang Lina , Zhao Ying , Wang Haiying , Yang Yang , Akiyama Yoshimitsu , Zhang Hongquan , Zhu Wei-Guo
Published: March 2013

Suppressor of variegation 3–9 homolog 1 (SUV39H1), a histone methyltransferase, catalyzes histone 3 lysine 9 trimethylation and is involved in heterochromatin organization and genome stability. However, the mechanism for regulation of the enzymatic activity of SUV39H1 in cancer cells is not yet well known. In this study, we identified SET domain-containing protein 7 (SET7/9), a protein methyltransferase, as a unique regulator of SUV39H1 activity. In response to treatment with adriamycin, a DNA damage inducer, SET7/9 interacted with SUV39H1 in vivo, and a GST pull-down assay confirmed that the chromodomain-containing region of SUV39H1 bound to SET7/9. Western blot using antibodies specific for antimethylated SUV39H1 and mass spectrometry demonstrated that SUV39H1 was specifically methylated at lysines 105 and 123 by SET7/9. Although the half-life and localization of methylated SUV39H1 were not noticeably changed, the methyltransferase activity of SUV39H1 was dramatically down-regulated when SUV39H1 was methylated by SET7/9. Consequently, H3K9 trimethylation in the heterochromatin decreased significantly, which, in turn, led to a significant increase in the expression of
satellite 2
(
Sat2
) and
α-satellite
(
α-Sat
), indicators of heterochromatin relaxation. Furthermore, a micrococcal nuclease sensitivity assay and an immunofluorescence assay demonstrated that methylation of SUV39H1 facilitated genome instability and ultimately inhibited cell proliferation. Together, our data reveal a unique interplay between SET7/9 and SUV39H1—two histone methyltransferases—that results in heterochromatin relaxation and genome instability in response to DNA damage in cancer cells.
Deciphering mutant ELOVL4 activity in autosomal-dominant Stargardt macular dystrophy
Authors: Logan Sreemathi , Agbaga Martin-Paul , Chan Michael D. , Kabir Nabila , Mandal Nawajes A. , Brush Richard S. , Anderson Robert E.
Published: March 2013

Autosomal-dominant Stargardt-like macular dystrophy [Stargardt3 (STGD3)] results from single allelic mutations in the elongation of very-long–chain fatty acids-like 4 (
ELOVL4
), whereas recessive mutations lead to skin and brain dysfunction. ELOVL4 protein localizes to the endoplasmic reticulum, where it mediates the condensation reaction catalyzing the formation of very-long–chain (VLC) (C-28 to C-40) fatty acids, saturated and polyunsaturated (PUFA). The defective gene product is truncated at the C terminus, leading to mislocalization and aggregation in other organelles. We hypothesized that the STGD3 truncated mutant may generate mislocalized, and therefore toxic, keto intermediates of fatty acid elongation, thereby contributing to the disease process. Using cell-based and cell-free microsome assays, we found that the truncated protein lacked innate condensation activity. Coexpression of different forms of wild-type and mutant ELOVL4 revealed a large dominant-negative effect of mutant protein on ELOVL4 localization and enzymatic activity, resulting in reduced VLC-PUFA synthesis. The reduction in VLC-PUFA levels in STGD3 and age-related macular degeneration may be a contributing factor to their retinal pathology.
Structure-based ligand discovery for the Large-neutral Amino Acid Transporter 1, LAT-1
Authors: Geier Ethan G. , Schlessinger Avner , Fan Hao , Gable Jonathan E. , Irwin John J. , Sali Andrej , Giacomini Kathleen M.
Published: March 2013

The Large-neutral Amino Acid Transporter 1 (LAT-1)—a sodium-independent exchanger of amino acids, thyroid hormones, and prescription drugs—is highly expressed in the blood–brain barrier and various types of cancer. LAT-1 plays an important role in cancer development as well as in mediating drug and nutrient delivery across the blood–brain barrier, making it a key drug target. Here, we identify four LAT-1 ligands, including one chemically novel substrate, by comparative modeling, virtual screening, and experimental validation. These results may rationalize the enhanced brain permeability of two drugs, including the anticancer agent acivicin. Finally, two of our hits inhibited proliferation of a cancer cell line by distinct mechanisms, providing useful chemical tools to characterize the role of LAT-1 in cancer metabolism.
Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest inXenopusembryos
Authors: Milet Cécile , Maczkowiak Frédérique , Roche Daniel D. , Monsoro-Burq Anne Hélène
Published: March 2013

Defining which key factors control commitment of an embryonic lineage among a myriad of candidates is a longstanding challenge in developmental biology and an essential prerequisite for developing stem cell-based therapies. Commitment implies that the induced cells not only express early lineage markers but further undergo an autonomous differentiation into the lineage. The embryonic neural crest generates a highly diverse array of derivatives, including melanocytes, neurons, glia, cartilage, mesenchyme, and bone. A complex gene regulatory network has recently classified genes involved in the many steps of neural crest induction, specification, migration, and differentiation. However, which factor or combination of factors is sufficient to trigger full commitment of this multipotent lineage remains unknown. Here, we show that, in contrast to other potential combinations of candidate factors, coactivating transcription factors Pax3 and Zic1 not only initiate neural crest specification from various early embryonic lineages inXenopusand chicken embryos but also trigger full neural crest determination. These two factors are sufficient to drive migration and differentiation of several neural crest derivatives in minimal culture conditions in vitro or ectopic locations in vivo. After transplantation, the induced cells migrate to and integrate into normal neural crest craniofacial target territories, indicating an efficient spatial recognition in vivo. Thus, Pax3 and Zic1 cooperate and execute a transcriptional switch sufficient to activate full multipotent neural crest development and differentiation.
Rescue of fragile X syndrome phenotypes in
Fmr1
KO mice by the small-molecule PAK inhibitor FRAX486
Authors: Dolan Bridget M. , Duron Sergio G. , Campbell David A. , Vollrath Benedikt , Rao B. S. Shankaranarayana , Ko Hui-Yeon , Lin Gregory G. , Govindarajan Arvind , Choi Se-Young , Tonegawa Susumu
Published: March 2013

Fragile X syndrome (FXS) is the most common inherited form of autism and intellectual disability and is caused by the silencing of a single gene, fragile X mental retardation 1 (
Fmr1
). The
Fmr1
KO mouse displays phenotypes similar to symptoms in the human condition—including hyperactivity, repetitive behaviors, and seizures—as well as analogous abnormalities in the density of dendritic spines. Here we take a hypothesis-driven, mechanism-based approach to the search for an effective therapy for FXS. We hypothesize that a treatment that rescues the dendritic spine defect in
Fmr1
KO mice may also ameliorate autism-like behavioral symptoms. Thus, we targeted a protein that regulates spines through modulation of actin cytoskeleton dynamics: p21-activated kinase (PAK). Our results demonstrate that a potent small molecule inhibitor of group I PAKs reverses dendritic spine phenotypes in
Fmr1
KO mice. Moreover, this PAK inhibitor—which we call FRAX486—also rescues seizures and behavioral abnormalities such as hyperactivity and repetitive movements, thereby supporting the hypothesis that a drug treatment that reverses the spine abnormalities can also treat neurological and behavioral symptoms. Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult
Fmr1
KO mice, demonstrating the potential for rapid, postdiagnostic therapy in adults with FXS.
Northern Hemisphere summer monsoon intensified by mega-El Niño/southern oscillation and Atlantic multidecadal oscillation
Authors: Wang Bin , Liu Jian , Kim Hyung-Jin , Webster Peter J. , Yim So-Young , Xiang Baoqiang
Published: March 2013

Prediction of monsoon changes in the coming decades is important for infrastructure planning and sustainable economic development. The decadal prediction involves both natural decadal variability and anthropogenic forcing. Hitherto, the causes of the decadal variability of Northern Hemisphere summer monsoon (NHSM) are largely unknown because the monsoons over Asia, West Africa, and North America have been studied primarily on a regional basis, which is unable to identify coherent decadal changes and the overriding controls on planetary scales. Here, we show that, during the recent global warming of about 0.4 °C since the late 1970s, a coherent decadal change of precipitation and circulation emerges in the entirety of the NHSM system. Surprisingly, the NHSM as well as the Hadley and Walker circulations have all shown substantial intensification, with a striking increase of NHSM rainfall by 9.5% per degree of global warming. This is unexpected from recent theoretical prediction and model projections of the 21st century. The intensification is primarily attributed to a mega-El Niño/Southern Oscillation (a leading mode of interannual-to-interdecadal variation of global sea surface temperature) and the Atlantic Multidecadal Oscillation, and further influenced by hemispherical asymmetric global warming. These factors driving the present changes of the NHSM system are instrumental for understanding and predicting future decadal changes and determining the proportions of climate change that are attributable to anthropogenic effects and long-term internal variability in the complex climate system.
Independent divergence of 13- and 17-y life cycles among three periodical cicada lineages
Authors: Sota Teiji , Yamamoto Satoshi , Cooley John R. , Hill Kathy B. R. , Simon Chris , Yoshimura Jin
Published: March 2013

The evolution of 13- and 17-y periodical cicadas (Magicicada) is enigmatic because at any given location, up to three distinct species groups (Decim, Cassini, Decula) with synchronized life cycles are involved. Each species group is divided into one 13- and one 17-y species with the exception of the Decim group, which contains two 13-y species—13-y species areMagicicada tredecim,Magicicada neotredecim,Magicicada tredecassini, andMagicicada tredecula; and 17-y species areMagicicada septendecim,Magicicada cassini, andMagicicada septendecula. Here we show that the divergence leading to the present 13- and 17-y populations differs considerably among the species groups despite the fact that each group exhibits strikingly similar phylogeographic patterning. The earliest divergence of extant lineages occurred ∼4 Mya with one branch forming the Decim species group and the other subsequently splitting 2.5 Mya to form the Cassini and Decula species groups. The earliest split of extant lineages into 13- and 17-y life cycles occurred in the Decim lineage 0.5 Mya. All three species groups experienced at least one episode of life cycle divergence since the last glacial maximum. We hypothesize that despite independent origins, the three species groups achieved their current overlapping distributions because life-cycle synchronization of invading congeners to a dominant resident population enabled escape from predation and population persistence. The repeated life-cycle divergences supported by our data suggest the presence of a common genetic basis for the two life cycles in the three species groups.
Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases
Authors: Gil Margaret , Seshadri Mukund , Komorowski Marcin P. , Abrams Scott I. , Kozbor Danuta
Published: March 2013

Significance

Novel advances in viral oncotherapy require effective direct oncolysis and manipulation of the tumor microenvironment, which has proven to be an important target in cancer treatment. The CXCR4 receptor for the CXCL12 chemokine is one of the key stimuli involved in signaling interactions between tumor cells and their microenvironment, suggesting that inhibition of this pathway by oncolytic viruses expressing the CXCR4 antagonist should increase efficacy over that mediated by oncolysis alone. We are unique in demonstrating that targeting CXCR4 signaling through an oncolytic vaccinia virus yields a significant therapeutic impact against primary and metastatic breast cancer.
Activationless charge transport across 4.5 to 22 nm in molecular electronic junctions
Authors: Yan Haijun , Bergren Adam Johan , McCreery Richard , Della Rocca Maria Luisa , Martin Pascal , Lafarge Philippe , Lacroix Jean Christophe
Published: March 2013

In this work, we bridge the gap between short-range tunneling in molecular junctions and activated hopping in bulk organic films, and greatly extend the distance range of charge transport in molecular electronic devices. Three distinct transport mechanisms were observed for 4.5–22-nm-thick oligo(thiophene) layers between carbon contacts, with tunneling operative when
d
 < 8 nm, activated hopping when
d
> 16 nm for high temperatures and low bias, and a third mechanism consistent with field-induced ionization of highest occupied molecular orbitals or interface states to generate charge carriers when
d
= 8–22 nm. Transport in the 8–22-nm range is weakly temperature dependent, with a field-dependent activation barrier that becomes negligible at moderate bias. We thus report here a unique, activationless transport mechanism, operative over 8–22-nm distances without involving hopping, which severely limits carrier mobility and device lifetime in organic semiconductors. Charge transport in molecular electronic junctions can thus be effective for transport distances significantly greater than the 1–5 nm associated with quantum-mechanical tunneling.
Structure of human enterovirus 71 in complex with a capsid-binding inhibitor
Authors: Plevka Pavel , Perera Rushika , Yap Moh Lan , Cardosa Jane , Kuhn Richard J. , Rossmann Michael G.
Published: March 2013

Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-Å-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs.
Effects of cochlear loading on the motility of active outer hair cells
Authors: Ó Maoiléidigh Dáibhid , Hudspeth A. J.
Published: March 2013

Outer hair cells (OHCs) power the amplification of sound-induced vibrations in the mammalian inner ear through an active process that involves hair-bundle motility and somatic motility. It is unclear, though, how either mechanism can be effective at high frequencies, especially when OHCs are mechanically loaded by other structures in the cochlea. We address this issue by developing a model of an active OHC on the basis of observations from isolated cells, then we use the model to predict the response of an active OHC in the intact cochlea. We find that active hair-bundle motility amplifies the receptor potential that drives somatic motility. Inertial loading of a hair bundle by the tectorial membrane reduces the bundle’s reactive load, allowing the OHC’s active motility to influence the motion of the cochlear partition. The system exhibits enhanced sensitivity and tuning only when it operates near a dynamical instability, a Hopf bifurcation. This analysis clarifies the roles of cochlear structures and shows how the two mechanisms of motility function synergistically to create the cochlear amplifier. The results suggest that somatic motility evolved to enhance a preexisting amplifier based on active hair-bundle motility, thus allowing mammals to hear high-frequency sounds.