bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the ferroelectric-relaxor transition in PbMg1/3Nb2/3O3–PbTiO3 ceramics by piezoresponse force microscopy
Authors: Shvartsman V. V. , Kholkin A. L.
Published: August 2010

The spontaneous transition between the ferroelectric and relaxor states was investigated in 0.86PbMg1/3Nb2/3O3–0.14PbTiO3 ceramics using piezoresponse force microscopy (PFM). Macroscopically, the transition from the ferroelectric to relaxor phases manifests itself by an anomaly in the temperature dependences of the dielectric permittivity and by a sharp decline of the remanent polarization. Alternatively, PFM reveals a decay of the ferroelectric micron-size domains at the macroscopic Curie temperature, TC. Simultaneously, smaller domains of submicron sizes are observed at temperatures appreciably above TC, being concentrated near grain boundaries. It is argued that the particular mechanical and electrical conditions at the grain boundaries promote nucleation of the ferroelectric phase.
Ferroelectric microdomains and microdomain arrays recorded in strontium–barium niobate crystals in the field of atomic force microscope
Authors: Volk Tatiana R. , Simagina Liliya V. , Gainutdinov Radmir V. , Tolstikhina Alla L. , Ivleva Lyudmila I.
Published: August 2010

Microdomains and various one-dimensional (1D)- and two-dimensional (2D)-microdomain arrays were formed under dc-voltages applied to the tip of an atomic force microscope (AFM) in ferroelectric SrxBa1−xNb2O6 crystals. Detailed studies of the characteristics of the AFM—recording and decay kinetics of the written arrays have shown that the crucial factors of the stability of a domain array are its dimensionality and discreteness (described by a distance Δ between the recorded point domains forming the array). The dependence of the stability on the discreteness of domain ensembles is analyzed. With decreasing Δ, the decay times of the domain ensembles increases. The stability of 2D arrays (domain squares, complex-shaped arrays composed of the domain ensembles of opposite polarity) by orders of magnitude exceeds that of 1D-arrays (domain chains and lines) provided all factors of recording being the same. As an illustration, the decay time of individual (spatially separated) domains and quasicontinuous domain lines are tens of minutes and about 20 h, respectively, whereas a quasicontionuous domain square persists within at least ten days. We assume the existence of cooperative interactions in microdomain ensembles, which reveal themselves even in arrays consisting of spatially separated point domain.
Are Al2O3 and MgO tunnel barriers suitable for spin injection in graphene?
Authors: Dlubak B. , Seneor P. , Anane A. , Barraud C. , Deranlot C. , Deneuve D. , Servet B. , Mattana R. , Petroff F. , Fert A.
Published: August 2010

We report on the structural impact on graphene and multi-layers graphene of the growth by sputtering of tunnel barriers. Sputtered Al2O3 and MgO barriers were chosen for their well-known efficiency as spin injectors in spintronics devices. The impact of the growth on the structure of graphene and up to 4-layer flakes was analyzed by Raman spectroscopy. This study reveals that for Al2O3 growth, the impact is moderate for a monolayer and decreases sharply for bilayers and above. In the case of MgO all the flakes underwent a strong amorphization. Moreover, this reveals that while single layer graphene is believed to offer the best spin transport properties, the better robustness of multilayer graphene may ultimately make it a better choice for spintronics devices.
A transform of complementary aspects with applications to entropic uncertainty relations
Authors: Mandayam Prabha , Wehner Stephanie , Balachandran Niranjan
Published: August 2010

Even though mutually unbiased bases and entropic uncertainty relations play an important role in quantum cryptographic protocols, they remain ill understood. Here, we construct special sets of up to 2n+1 mutually unbiased bases (MUBs) in dimension d=2n, which have particularly beautiful symmetry properties derived from the Clifford algebra. More precisely, we show that there exists a unitary transformation that cyclically permutes such bases. This unitary can be understood as a generalization of the Fourier transform, which exchanges two MUBs, to multiple complementary aspects. We proceed to prove a lower bound for min-entropic entropic uncertainty relations for any set of MUBs and show that symmetry plays a central role in obtaining tight bounds. For example, we obtain for the first time a tight bound for four MUBs in dimension d=4, which is attained by an eigenstate of our complementarity transform. Finally, we discuss the relation to other symmetries obtained by transformations in discrete phase space and note that the extrema of discrete Wigner functions are directly related to min-entropic uncertainty relations for MUBs.
The van der Waals potential of the magnesium dimer
Authors: Li P. , Xie W. , Tang K. T.
Published: August 2010

The ground state van der Waals potential of the magnesium dimer is described by the Tang–Toennies potential model, which requires five essential parameters. Among them, the three dispersion coefficients C6, C8, and C10 are available from accurate ab initio calculations. The other two are the Born–Mayer parameters in A exp(−bR). In this paper, we show that A and b can be determined from the self-consistent Hartree–Fock calculations and the experimental dissociation energy D0. The predicted well depth De and equilibrium distance Re are in nearly perfect agreement with the experiment. In fact, the entire potential energy curve, which is given by a single analytic function, is in excellent agreement with the pointwise potential energies constructed from the spectroscopic measurements in the interval of 6a0–14a0 and in good agreement with the experimental repulsive potential determined from Franck–Condon factors of the bound-free transitions for R less than 6a0. The reduced potential of Mg2 is analyzed in terms of its components, and the number of terms in the dispersion series necessary for convergence is investigated.
Strong critical current density enhancement in NiCu/NbN superconducting nanostripes for optical detection
Authors: Marrocco N. , Pepe G. P. , Capretti A. , Parlato L. , Pagliarulo V. , Peluso G. , Barone A. , Cristiano R. , Ejrnaes M. , Casaburi A. , Kashiwazaki N. , Taino T. , Myoren H. , Sobolewski Roman
Published: August 2010

We present measurements of ferromagnet/superconductor (NiCu/NbN) and plain superconducting (NbN) nanostripes with the linewidth ranging from 150 to 300 nm. The NiCu (3 nm)/NbN (8 nm) bilayers, as compared to NbN (8 nm), showed a up to six times increase in their critical current density, reaching at 4.2 K the values of 5.5 MA/cm2 for a 150 nm wide nanostripe meander and 12.1 MA/cm2 for a 300 nm one. We also observed six-time sensitivity enhancement when the 150 nm wide NiCu/NbN nanostripe was used as an optical detector. The strong critical current enhancement is explained by the vortex pinning strength and density increase in NiCu/NbN bilayers and confirmed by approximately tenfold increase in the vortex polarizability factor.
Corrugated interfaces in multiphase core-annular flow
Authors: Shum Ho Cheung , Sauret Alban , Fernandez-Nieves Alberto , Stone Howard A. , Weitz David A.
Published: August 2010

Microfluidic devices can be used to produce highly controlled and monodisperse double or multiple emulsions. The presence of inner drops inside a jet of the middle phase introduces deformations in the jet, which leads to breakup into monodisperse double emulsions. However, the ability to generate double emulsions can be compromised when the interfacial tension between the middle and outer phases is low, leading to flow with high capillary and Weber numbers. In this case, the interface between the fluids is initially deformed by the inner drops but the jet does not break into drops. Instead, the jet becomes highly corrugated, which prevents formation of controlled double emulsions. We show using numerical calculations that the corrugations are caused by the inner drops perturbing the interface and the perturbations are then advected by the flow into complex shapes.
Effect of SNP origin on analyses of genetic diversity in cattle
Authors: Neto Laercio R. Porto , Barendse William
Published: August 2010

The methods of single nucleotide polymorphism (SNP) identification can lead to ascertainment bias, which will affect population genetic analyses based on those data. In livestock species, the methods of SNP identification through genome sequencing are likely to suffer from this ascertainment bias. In the present study, a subset of data from the Bovine HapMap Project was re-analysed to quantify the effects of ascertainment bias on a range of common analyses and statistics. Data from 189 animals of the zebu breeds Brahman, Nelore and Gir, taurine beef Angus, Limousin and Hereford and taurine dairy Holstein, Jersey and Brown Swiss were analysed. There were 141 SNPs each of Angus, Brahman and Holstein origin, giving a total of 423 SNPs organised in 141 triplets. Each triplet consisted of one SNP of each breed, separated on average by 0.75 Mb within each triplet and where triplets were separated by 14.96 Mb to ensure that each triplet was unaffected by linkage disequilibrium. The minor allele frequency distribution, estimates of the F-statistic, FST, the partitioning of variance and population substructure were relatively unaffected by breed of origin of the SNPs. Estimates of heterozygosity were significantly affected by breed of origin of the SNPs. The clustering of animals of closely related breeds varied in the principal component analyses (PCA). However, in the PCA the effect of breed of origin of 141 SNPs was similar to the effect of using different panels of 141 SNPs of all three breeds, so the differences found in the PCA may not be all due to bias by the origin of the SNPs. Based on these results, analyses that depend on FST, including signatures of selection, gene flow and effective population size are unlikely to be strongly affected by SNP origin. Analyses that partition genetic variance and some analyses of population substructure will also be largely unaffected. However, analyses that are dependent on locus heterozygosity, which can be used for studying population bottlenecks, or those that study selection using extended haplotype homozygosity may be significantly affected by breed of origin of the SNPs.
Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking
Authors: Koduru Suresh , Kumar Lalit , Massaad Michel J. , Ramesh Narayanaswamy , Le Bras Séverine , Ozcan Esra , Oyoshi Michiko K. , Kaku Mayumi , Fujiwara Yuko , Kremer Leonor , King Sandra , Fuhlbrigge Robert , Rodig Scott , Sage Peter , Carman Chris , Alcaide Pilar , Luscinskas Francis W. , Geha Raif S.
Published: August 2010

The F-BAR domain containing protein CIP4 (Cdc42 interacting protein 4) interacts with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of filamentous actin. CIP4−/−mice had normal T- and B-lymphocyte development but impaired T cell-dependent antibody production, IgG antibody affinity maturation, and germinal center (GC) formation, despite an intact CD40L–CD40 axis. CIP4−/−mice also had impaired contact hypersensitivity (CHS) to haptens, and their T cells failed to adoptively transfer CHS. Ovalbumin-activated CD4+effector T cells from CIP4−/−/OT-II mice migrated poorly to antigen-challenged skin. Activated CIP4−/−T cells exhibited impaired adhesion and polarization on immobilized VCAM-1 and ICAM-1 and defective arrest and transmigration across murine endothelial cell monolayers under shear flow conditions. These results demonstrate an important role for CIP4 in integrin-dependent T cell-dependent antibody responses and GC formation and in integrin-mediated recruitment of effector T cells to cutaneous sites of antigen-driven immune reactions.
Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein
Authors: Järås Marcus , Johnels Petra , Hansen Nils , Ågerstam Helena , Tsapogas Panagiotis , Rissler Marianne , Lassen Carin , Olofsson Tor , Bjerrum Ole Weis , Richter Johan , Fioretos Thoas
Published: August 2010

Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9 and 22 and giving rise to the constitutively active tyrosine kinase P210 BCR/ABL1. Therapeutic strategies aiming for a cure of CML will require full eradication of Ph chromosome-positive (Ph+) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34+cells and also in cord blood CD34+cells as a consequence of retroviralBCR/ABL1expression. To test whether IL1RAP expression distinguishes normal (Ph−) and leukemic (Ph+) cells within the CML CD34+CD38−cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate their Ph-chromosome status. Interestingly, we found that the CML CD34+CD38−IL1RAP+cells were Ph+, whereas CML CD34+CD38−IL1RAP−cells were almost exclusively Ph−. By performing long-term culture-initiating cell assays on the two cell populations, we found that Ph+and Ph−candidate CML stem cells could be prospectively separated. In addition, by generating an anti-IL1RAP antibody, we provide proof of concept that IL1RAP can be used as a target on CML CD34+CD38−cells to induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies IL1RAP as a unique cell surface biomarker distinguishing Ph+from Ph−candidate CML stem cells and opens up a previously unexplored avenue for therapy of CML.
Chk1 promotes replication fork progression by controlling replication initiation
Authors: Petermann Eva , Woodcock Mick , Helleday Thomas
Published: August 2010

DNA replication starts at initiation sites termed replication origins. Metazoan cells contain many more potential origins than are activated (fired) during each S phase. Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which suppresses origin firing in response to replication blocks and during normal S phase by inhibiting the cyclin-dependent kinase Cdk2. In addition to increased origin activation, cells deficient in Chk1 activity display reduced rates of replication fork progression. Here we investigate the causal relationship between increased origin firing and reduced replication fork progression. We use the Cdk inhibitor roscovitine or RNAi depletion of Cdc7 to inhibit origin firing in Chk1-inhibited or RNAi-depleted cells. We report that Cdk inhibition and depletion of Cdc7 can alleviate the slow replication fork speeds in Chk1-deficient cells. Our data suggest that increased replication initiation leads to slow replication fork progression and that Chk1 promotes replication fork progression during normal S phase by controlling replication origin activity.
Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo
Authors: Rimoin Anne W. , Mulembakani Prime M. , Johnston Sara C. , Lloyd Smith James O. , Kisalu Neville K. , Kinkela Timothee L. , Blumberg Seth , Thomassen Henri A. , Pike Brian L. , Fair Joseph N. , Wolfe Nathan D. , Shongo Robert L. , Graham Barney S. , Formenty Pierre , Okitolonda Emile , Hensley Lisa E. , Meyer Hermann , Wright Linda L. , Muyembe Jean-Jacques
Published: August 2010

Studies on the burden of human monkeypox in the Democratic Republic of the Congo (DRC) were last conducted from 1981 to 1986. Since then, the population that is immunologically naïve to orthopoxviruses has increased significantly due to cessation of mass smallpox vaccination campaigns. To assess the current risk of infection, we analyzed human monkeypox incidence trends in a monkeypox-enzootic region. Active, population-based surveillance was conducted in nine health zones in central DRC. Epidemiologic data and biological samples were obtained from suspected cases. Cumulative incidence (per 10,000 population) and major determinants of infection were compared with data from active surveillance in similar regions from 1981 to 1986. Between November 2005 and November 2007, 760 laboratory-confirmed human monkeypox cases were identified in participating health zones. The average annual cumulative incidence across zones was 5.53 per 10,000 (2.18–14.42). Factors associated with increased risk of infection included: living in forested areas, male gender, age < 15, and no prior smallpox vaccination. Vaccinated persons had a 5.2-fold lower risk of monkeypox than unvaccinated persons (0.78 vs. 4.05 per 10,000). Comparison of active surveillance data in the same health zone from the 1980s (0.72 per 10,000) and 2006–07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox incidence. Thirty years after mass smallpox vaccination campaigns ceased, human monkeypox incidence has dramatically increased in rural DRC. Improved surveillance and epidemiological analysis is needed to better assess the public health burden and develop strategies for reducing the risk of wider spread of infection.
Catalytic and chaperone-like functions in an intrinsically disordered protein associated with desiccation tolerance
Authors: Chakrabortee Sohini , Meersman Filip , Kaminski Schierle Gabriele S. , Bertoncini Carlos W. , McGee Brian , Kaminski Clemens F. , Tunnacliffe Alan
Published: August 2010

Intrinsically disordered proteins (IDPs) lack well-defined structure but are widely represented in eukaryotic proteomes. Although the functions of most IDPs are not understood, some have been shown to have molecular recognition and/or regulatory roles where their disordered nature might be advantageous. Anhydrin is an uncharacterized IDP induced by dehydration in an anhydrobiotic nematode,
Aphelenchus avenae
. We show here that anhydrin is a moonlighting protein with two novel, independent functions relating to desiccation tolerance. First, it has a chaperone-like activity that can reduce desiccation-induced enzyme aggregation and inactivation in vitro. When expressed in a human cell line, anhydrin localizes to the nucleus and reduces the propensity of a polyalanine expansion protein associated with oculopharyngeal muscular dystrophy to form aggregates. This in vivo activity is distinguished by a loose association of anhydrin with its client protein, consistent with a role as a molecular shield. In addition, anhydrin exhibits a second function as an endonuclease whose substrates include supercoiled, linear, and chromatin linker DNA. This nuclease activity could be involved in either repair of desiccation-induced DNA damage incurred during anhydrobiosis or in apoptotic or necrotic processes, for example, but it is particularly unexpected for anhydrin because IDP functions defined to date anticorrelate with enzyme activity. Enzymes usually require precise three-dimensional positioning of residues at the active site, but our results suggest this need not be the case. Anhydrin therefore extends the range of IDP functional categories to include catalysis and highlights the potential for the discovery of new functions in disordered proteomes.
The liquid-liquid phase transition in silicon revealed by snapshots of valence electrons
Authors: Beye Martin , Sorgenfrei Florian , Schlotter William F. , Wurth Wilfried , Föhlisch Alexander
Published: August 2010

The basis for the anomalies of water is still mysterious. Quite generally tetrahedrally coordinated systems, also silicon, show similar thermodynamic behavior but lack—like water—a thorough explanation. Proposed models—controversially discussed—explain the anomalies as a remainder of a first-order phase transition between high and low density liquid phases, buried deeply in the “no man’s land”—a part of the supercooled liquid region where rapid crystallization prohibits any experimental access. Other explanations doubt the existence of the phase transition and its first-order nature. Here, we provide experimental evidence for the first-order-phase transition in silicon. With ultrashort optical pulses of femtosecond duration we instantaneously heat the electronic system of silicon while the atomic structure as defined by the much heavier nuclear system remains initially unchanged. Only on a picosecond time scale the energy is transferred into the atomic lattice providing the energy to drive the phase transitions. With femtosecond X-ray pulses from FLASH, the free-electron laser at Hamburg, we follow the evolution of the valence electronic structure during this process. As the relevant phases are easily distinguishable in their electronic structure, we track how silicon melts into the low-density-liquid phase while a second phase transition into the high-density-liquid phase only occurs after the latent heat for the first-order phase transition has been transferred to the atomic structure. Proving the existence of the liquid-liquid phase transition in silicon, the hypothesized liquid-liquid scenario for water is strongly supported.
Repression of Wnt signaling by a Fer-type nonreceptor tyrosine kinase
Authors: Putzke Aaron P. , Rothman Joel H.
Published: August 2010

The Wnt signaling pathway must be properly modulated to ensure an appropriate output: pathological conditions result from either insufficient or excessive levels of Wnt signal. For example, hyperactivation of the Wnt pathway is associated with various cancers and subnormal Wnt signaling can lead to increased invasiveness of tumor cells. We found that the
Caenorhabditis elegans
ortholog of the Fer nonreceptor tyrosine kinase, FRK-1, limits Wnt signaling by preventing the adhesion complex-associated β-catenin, HMP-2, from participating in Wnt-dependent specification of the endoderm during embryogenesis. Removal of FRK-1 function results in relocalization of HMP-2 to the nucleus of epidermal cells, and allows it to substitute for WRM-1, the nuclear β-catenin that normally transduces the Wnt signal during endoderm development. APR-1, the
C. elegans
APC ortholog, is similarly required to prevent HMP-2 relocalization and keeps it from participating in Wnt signal transduction; this finding partially explains the paradoxical observation that APR-1 acts either negatively or positively in Wnt signaling, depending on context. The apparent hyperactivation of the Wnt response in the absence of FRK-1 leads to hyperproliferation in the endoderm, as is also seen when WRM-1 is overexpressed in wild-type embryos. The specification and proliferation activities of Wnt signaling are separable: although the Tcf/Lef factor POP-1 acts in Wnt-dependent endoderm specification, it is not apparently required for hyperproliferation resulting from excessive Wnt signaling. These findings highlight a role for a Fer-type kinase in setting the proper levels of Wnt signaling and demonstrate the importance of this modulation in ensuring appropriate cell division.
Mechanism of
Trypanosoma brucei gambiense
(group 1) resistance to human trypanosome lytic factor
Authors: Kieft Rudo , Capewell Paul , Turner C. Michael R. , Veitch Nicola J. , MacLeod Annette , Hajduk Stephen
Published: August 2010

Human innate immunity against most African trypanosomes, including
Trypanosoma brucei brucei
, is mediated by a minor subclass of toxic serum HDL, called trypanosome lytic factor-1 (TLF-1). This HDL contains two primate specific proteins, apolipoprotein L-1 and haptoglobin (Hp)-related protein, as well as apolipoprotein A-1. These assembled proteins provide a powerful defense against trypanosome infection.
Trypanosoma brucei rhodesiense
causes human African sleeping sickness because it has evolved an inhibitor of TLF-1, serum resistance-associated (SRA) protein.
Trypanosoma brucei gambiense
lacks the
SRA
gene, yet it infects humans. As transfection of
T. b. gambiense
(group 1) is not possible, we initially used in vitro-selected TLF-1–resistant
T. b. brucei
to examine SRA-independent mechanisms of TLF-1 resistance. Here we show that TLF-1 resistance in
T. b. brucei
is caused by reduced expression of the Hp/Hb receptor gene (
TbbHpHbR
). Importantly,
T. b. gambiense
(group 1) also showed a marked reduction in uptake of TLF-1 and a corresponding decrease in expression of
T. b. gambiense
Hp/Hb receptor (
TbgHpHbR
). Ectopic expression of
TbbHpHbR
in TLF-1–resistant
T. b. brucei
rescued TLF-1 uptake, demonstrating that decreased
TbbHpHbR
expression conferred TLF-1 resistance. Ectopic expression of
TbgHpHbR
in TLF-1–resistant
T. b. brucei
failed to rescue TLF-1 killing, suggesting that coding sequence changes altered Hp/Hb receptor binding affinity for TLF-1. We propose that the combination of coding sequence mutations and decreased expression of
TbgHpHbR
directly contribute to parasite evasion of human innate immunity and infectivity of group 1
T. b. gambiense
.
A transmembrane formin nucleates subapical actin assembly and controls tip-focused growth in pollen tubes
Authors: Cheung Alice Y. , Niroomand Shahriar , Zou Yanjiao , Wu Hen-Ming
Published: August 2010

Pollen tubes are highly polarized plant cells specialized in delivering sperm for fertilization. Pollen tube growth is rapid, occurs exclusively at the tip, and can reach distances thousands of times the diameter of the pollen grain without cell division, thus representing an excellent model system for studying asymmetric cell growth. In flowering plants, pollen tube growth is dependent on the actin cytoskeleton, which supports an efficient vesicle trafficking system to deliver membrane and cell-wall materials to the tube tip. A highly dynamic subapical actin structure and an apical vesicular zone are known to be critical for the tip-growth process. How this apical organization is maintained, how the subapical actin structure is assembled, and direct evidence for its functional coupling with tip growth remain to be established. Here, we show that a tip-located, cell membrane-anchored actin-nucleating protein, the
Arabidopsis
formin homology5 (FH5), stimulates actin assembly from the subapical membrane, provides actin filaments for vesicular trafficking to the apical dome, and mediates assembly of the subapical actin structure. Moreover, FH5-expressing pollen tubes provided a unique opportunity to demonstrate that assembly of the subapical actin structure is concomitant with the acquisition of rapid tip growth, providing further support for their functional coupling. Together, our results show that FH5 plays a pivotal role in establishing the subapical actin and apical vesicular organization critical for tip-focused growth in pollen tubes.
Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides
Authors: Claesen Jan , Bibb Mervyn
Published: August 2010

Posttranslational modification of amino acids confers a range of structural features and activities on ribosomally synthesized peptides, many of which have potent antimicrobial or other biological activities. Cypemycin is an extensively modified linear peptide produced by
Streptomyces sp.
OH-4156 with potent in vitro activity against mouse leukemia cells. Cypemycin does not contain lanthionine bridges but exhibits some of the structural features of lantibiotics, notably dehydrated threonines (dehydrobutyrines) and a C-terminal
S
-[(Z)-2-aminovinyl]-
d
-cysteine. Consequently it was classified as a member of the lantibiotic family of posttranslationally modified peptides. Cypemycin also possesses two
l
-
allo
-isoleucine residues and an N-terminal
N
,
N
-dimethylalanine, both unique amino acid modifications. We identified and heterologously expressed the cypemycin biosynthetic gene cluster and performed a mutational analysis of each individual gene. We show that even the previously described modifications are carried out by unusual enzymes or via a modification pathway unrelated to lantibiotic biosynthesis. Bioinformatic analysis revealed the widespread occurrence of cypemycin-like gene clusters within the bacterial kingdom and in the Archaea. Cypemycin is the founding member of an unusual class of posttranslationally modified ribosomally synthesized peptides, the linaridins.
Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating
Authors: Shi Yun , Suh Young Ho , Milstein Aaron D. , Isozaki Kaname , Schmid Sabine M. , Roche Katherine W. , Nicoll Roger A.
Published: August 2010

Glutamate receptors of the AMPA subtype (AMPARs) mediate fast synaptic transmission in the brain. These ionotropic receptors rely on auxiliary subunits known as transmembrane AMPAR regulatory proteins (TARPs) for both trafficking and gating. Recently, a second family of AMPAR binding proteins, referred to as cornichons, were identified and also proposed to function as auxiliary subunits. Cornichons are transmembrane proteins that modulate AMPAR function in expression systems much like TARPs. In the present study we compare the role of cornichons in controlling AMPA receptor function in neurons and HEK cells to that of TARPs. Cornichons mimic some, but not all, of the actions of TARPs in HEK cells; their role in neurons, however, is more limited. Although expressed cornichons can affect the trafficking of AMPARs, they were not detected on the surface of neurons and failed to alter the kinetics of endogenous AMPARs. This neuronal role is more consistent with that of an endoplasmic reticulum (ER) chaperone rather than a bona fide auxiliary subunit.
The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage
Authors: Larsen Dorthe Helena , Poinsignon Catherine , Gudjonsson Thorkell , Dinant Christoffel , Payne Mark R. , Hari Flurina J. , Rendtlew Danielsen Jannie M. , Menard Patrice , Sand Jette Christensen , Stucki Manuel , Lukas Claudia , Bartek Jiri , Andersen Jens S. , Lukas Jiri
Published: August 2010

In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination are not fully understood. In a mass spectrometry screen, we identified the adenosine triphosphate–dependent chromatin-remodeling protein CHD4 (chromodomain helicase DNA-binding protein 4) as a factor that becomes transiently immobilized on chromatin after IR. Knockdown of CHD4 triggers enhanced Cdc25A degradation and p21Cip1 accumulation, which lead to more pronounced cyclin-dependent kinase inhibition and extended cell cycle delay. At DNA double-strand breaks, depletion of CHD4 disrupts the chromatin response at the level of the RNF168 ubiquitin ligase, which in turn impairs local ubiquitylation and BRCA1 assembly. These cell cycle and chromatin defects are accompanied by elevated spontaneous and IR-induced DNA breakage, reduced efficiency of DNA repair, and decreased clonogenic survival. Thus, CHD4 emerges as a novel genome caretaker and a factor that facilitates both checkpoint signaling and repair events after DNA damage.
A testis-specific regulator of complex and hybrid N-glycan synthesis
Authors: Huang Hung-Hsiang , Stanley Pamela
Published: August 2010

Database analyses identified 4933434I20Rik as a glycosyltransferase-like gene expressed mainly in testicular germ cells and regulated during spermatogenesis. Expression of a membrane-bound form of the protein resulted in a marked and specific reduction in N-acetylglucosaminyltransferase I (GlcNAcT-I) activity and complex and hybrid N-glycan synthesis. Thus, the novel activity was termed GlcNAcT-I inhibitory protein (GnT1IP). Membrane-bound GnT1IP localizes to the ER, the ER-Golgi intermediate compartment (ERGIC), and the cis-Golgi. Coexpression of membrane-anchored GnT1IP with GlcNAcT-I causes association of the two proteins, inactivation of GlcNAcT-I, and mislocalization of GlcNAcT-I from the medial-Golgi to earlier compartments. Therefore, GnT1IP is a regulator of GlcNAcT-I and complex and hybrid N-glycan production. Importantly, the formation of high mannose N-glycans resulting from inhibition of GlcNAcT-I by GnT1IP markedly increases the adhesion of CHO cells to TM4 Sertoli cells. Testicular germ cells might use GnT1IP to induce the expression of high mannose N-glycans on glycoproteins, thereby facilitating Sertoli–germ cell attachment at a particular stage of spermatogenesis.
IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages
Authors: Smallie Tim , Ricchetti Giuseppe , Horwood Nicole J. , Feldmann Marc , Clark Andrew R. , Williams Lynn M.
Published: August 2010

IL-10 plays a central nonredundant role in limiting inflammation in vivo. However, the mechanisms involved remain to be resolved. Using primary human macrophages, we found that IL-10 inhibits selected inflammatory genes, primarily at a level of transcription. At the TNF gene, this occurs not through an inhibition of RNA polymerase II (Pol II) recruitment and transcription initiation but through a mechanism targeting the stimulation of transcription elongation by cyclin-dependent kinase (CDK) 9. We demonstrated an unanticipated requirement for a region downstream of the TNF 3′ untranslated region (UTR) that contains the nuclear factor κB (NF-κB) binding motif (κB4) both for induction of transcription by lipopolysaccharide (LPS) and its inhibition by IL-10. IL-10 not only inhibits the recruitment of RelA to regions containing κB sites at the TNF gene but also to those found at other LPS-induced genes. We show that although IL-10 elicits a general block in RelA recruitment to its genomic targets, the gene-specific nature of IL-10’s actions are defined through the differential recruitment of CDK9 and the control of transcription elongation. At TNF, but not NFKBIA, the consequence of RelA recruitment inhibition is a loss of CDK9 recruitment, preventing the stimulation of transcription elongation.
Revised SHEA Position Paper: Influenza Vaccination of Healthcare Personnel
Authors: Talbot Thomas R. , Babcock Hilary , Caplan Arthur L. , Cotton Deborah , Maragakis Lisa L. , Poland Gregory A. , Septimus Edward J. , Tapper Michael L. , Weber David J.
Published: August 2010

Executive Summary

This document serves as an update and companion piece to the 2005 Society for Healthcare Epidemiology of America (SHEA) Position Paper entitled “Influenza Vaccination of Healthcare Workers and Vaccine Allocation for Healthcare Workers During Vaccine Shortages.” In large part, the discussion about the rationale for influenza vaccination of healthcare personnel (HCP), the strategies designed to improve influenza vaccination rates in this population, and the recommendations made in the 2005 paper still stand. This position paper notes new evidence released since publication of the 2005 paper and strengthens SHEA's position on the importance of influenza vaccination of HCP. This document does not discuss vaccine allocation during times of vaccine shortage, because the 2005 SHEA Position Paper still serves as the Society's official statement on that issue.
A MedievalScholasticusand Renaissance Choirmaster: A Portrait of John Hothby at Lucca*
Authors: Brand Benjamin
Published: August 2010

John Hothby's career as cathedral choirmaster at Lucca is one of the longest, best documented, and most exceptional of any Northern musician active in fifteenth-century Italy. As director of the cathedral school and choir, this Englishman embodied two models of music master: a scholastic trained in the old Trivium and Quadrivium, and a professional maestro di cappella. Fulfilling this double role was but one way in which Hothby differed from his fellow oltremontani by ingratiating himself with his Lucchese patrons, colleagues, and citizens at large. Another was the integration into his curriculum of older pedagogies of local and regional origin, ones designed to appeal to his Italian students. The most important example of such appropriation were the laude that formed a basis for his students’ exercises in two-voice mensural counterpoint. The latter appear in I-Lc, Enti religiosi soppressi, 3086, one of only two examples of student work to survive from before 1500. These newly discovered exercises thus illuminate not only Hothby's career, but also a hitherto obscure stage of learning by which aspiring singers progressed from strict, note-against-note discant to complex, florid polyphony.
Prophets, Saints, and Matriarchs: Portraits of Old Women in Early Modern Italy*
Authors: Campbell Erin J.
Published: August 2010

This essay examines portraits of old women that were produced for the households of the professional and elite classes in Emilia-Romagna, Lombardy, and the Veneto during the second half of the sixteenth century, when, as a result of religious and social reform, women's lives came under increasing scrutiny. By interpreting the portraits within the context of prescriptive texts on the stages of women's lives, this study argues that the portraits provide evidence for the pivotal role of old women within the moral and symbolic order of the family, as well as in the wider community beyond the home.
EURObservational Research Programme: The Heart Failure Pilot Survey (ESC‐HF Pilot)
Authors: Maggioni Aldo P. , Dahlström Ulf , Filippatos Gerasimos , Chioncel Ovidiu , Leiro Marisa Crespo , Drozdz Jaroslaw , Fruhwald Friedrich , Gullestad Lars , Logeart Damien , Metra Marco , Parissis John , Persson Hans , Ponikowski Piotr , Rauchhaus Mathias , Voors Adriaan , Nielsen Olav Wendelboe , Zannad Faiez , Tavazzi Luigi ,   on behalf of the Heart Failure Association of the ESC (HFA)
Published: August 2010

Aims

The primary objective of the new ESC‐HF Pilot Survey was to describe the clinical epidemiology of outpatients and inpatients with heart failure (HF) and the diagnostic/therapeutic processes applied across 12 participating European countries. This pilot study was specifically aimed at validating the structure, performance, and quality of the data set, for continuing the survey into a permanent registry.

Methods and results

The ESC‐HF Pilot study is a prospective, multicentre, observational survey conducted in 136 cardiology centres from 12 European countries selected to represent the different health systems and care attitudes across Europe. All outpatients with HF and patients admitted for acute HF were included during the enrolment period (1 day per week for 8 consecutive months). From October 2009 to May 2010, 5118 patients were included in this pilot survey, of which 1892 (37%) were admitted for acute HF and 3226 (63%) for chronic HF. Ischaemic aetiology was reported in about half of the patients. In patients admitted for acute HF, the most frequent clinical profile was decompensated HF (75% of cases), whereas pulmonary oedema and cardiogenic shock were reported, respectively, in 13.3 and 2.3% of the cases. The total in‐hospital mortality rate was 3.8% and was cardiovascular in 90.1% of the cases. Lowest and highest mortality rates were observed in hypertensive HF and in cardiogenic shock, respectively. More than 80% of patients with chronic HF were treated with renin–angiotensin–aldosterone system blockers and β‐adrenergic blockers. However, target doses of such drugs were reached in one‐third to one‐fourth of the patients only.

Conclusion

The ESC‐HF Pilot Survey is an example of the possibility of utilizing an observational methodology to get insights into the current clinical practice in Europe, whose picture will be completed by the 1‐year follow‐up. Moreover, this study offered the opportunity to refine the organizational structure of a long‐term, extended European network.
Delayed Time to Defibrillation after Intraoperative and Periprocedural Cardiac Arrest
Authors: Mhyre Jill M. , Ramachandran Satya Krishna , Kheterpal Sachin , Morris Michelle , Chan Paul S.
Published: August 2010

Background

Delay in defibrillation (more than 2 min) is associated with worse survival in patients with a cardiac arrest because of ventricular fibrillation or pulseless ventricular tachycardia in intensive care units and inpatient wards.

Methods

We tested the relationship between delayed defibrillation and survival from intraoperative or periprocedural cardiac arrest, adjusting for baseline patient characteristics. The analysis was based on data from 865 patients who had intraoperative or periprocedural cardiac arrest caused by ventricular fibrillation or pulseless ventricular tachycardia in 259 hospitals participating in the National Registry of Cardiopulmonary Resuscitation.

Results

The median time to defibrillation was less than 1 min (interquartile range, <1 to 1 min). Delays in defibrillation occurred in 119 patients (13.8%). Characteristics associated with delayed defibrillation included pulseless ventricular tachycardia and noncardiac admitting diagnosis. The association between delayed defibrillation and survival to hospital discharge differed for periprocedural and intraoperative cardiac arrests (P value for interaction = 0.003). For patients arresting outside the operating room, delayed defibrillation was associated with a lower probability of surviving to hospital discharge (31.6% vs. 62.1%, adjusted odds ratio 0.49; 95% CI 0.27, 0.88; P = 0.018). In contrast, delayed defibrillation was not associated with survival for cardiac arrests in the operating room (46.8% vs. 39.6%, adjusted odds ratio 1.23, 95% CI 0.70, 2.19, P = 0.47).

Conclusions

Delays in defibrillation occurred in one of seven cardiac arrests in the intraoperative and periprocedural arenas. Although delayed defibrillation was associated with lower rates of survival after cardiac arrests in periprocedural areas, there was no association with survival for cardiac arrests in the operating room.
Serum Levels of CK18 M30 and Leptin Are Useful Predictors of Steatohepatitis and Fibrosis in Paediatric NAFLD
Authors: Fitzpatrick Emer , Mitry Ragai R , Quaglia Alberto , Hussain Munther J , deBruyne Ruth , Dhawan Anil
Published: August 2010

Background:

With the alarming growth in prevalence of paediatric nonalcoholic fatty liver disease (NAFLD), there is a need for noninvasive methods of stratifying disease severity. Our aim was to evaluate a combination of serum biomarkers as a measure of disease activity in paediatric NAFLD.

Patients and Methods:

Forty‐five children with biopsy‐proven NAFLD were enrolled. Caspase‐cleaved CK18 fragments (CK18 M30), hyaluronic acid, leptin, and adiponectin were measured in serum using enzyme‐linked immunosorbent assays and high‐sensitivity C‐reactive protein using a colorimetric assay.

Results:

Median age was 12.7 years (55% boys). Median body mass index z score was 1.7. CK18 M30 levels were significantly higher in patients with NAFLD versus controls, median 288 IU/L versus 172 IU/L (P < 0.001), and in those with steatohepatitis, median 347 IU/L versus simple steatosis (NAFLD activity score < 3), median 191 IU/L (P = 0.006). Significant fibrosis (≥F2) could be differentiated from no/minimal fibrosis (<F2), median 393 IU/L versus 243 IU/L (P = 0.03). Leptin could distinguish <F2 from ≥F2; 28.9 ng/mL versus 70.1 ng/mL (P = 0.037). Adiponectin, hyaluronic acid, and high‐sensitivity C‐reactive protein did not achieve significance in predicting steatohepatitis nor significant fibrosis.

Conclusions:

The present study combines use of markers for different processes in the development of steatohepatitis. Serum biomarkers, especially CK18 M30, are useful in stratifying disease severity in paediatric NAFLD.
Role of Intestinal Transporters in Neonatal Nutrition: Carbohydrates, Proteins, Lipids, Minerals, and Vitamins
Authors: Boudry Gaëlle , David Elmer S , Douard Véronique , Monteiro Iona M , Le Huërou‐Luron Isabelle , Ferraris Ronaldo P
Published: August 2010

To support rapid growth and a high metabolic rate, infants require enormous amounts of nutrients. The small intestine must have the complete array of transporters that absorb the nutrients released from digested food. Failure of intestinal transporters to function properly often presents symptoms as “failure to thrive” because nutrients are not absorbed and as diarrhea because unabsorbed nutrients upset luminal osmolality or become substrates of intestinal bacteria. We enumerate the nutrients that constitute human milk and various infant milk formulas, explain their importance in neonatal nutrition, then describe for each nutrient the transporter(s) that absorbs it from the intestinal lumen into the enterocyte cytosol and from the cytosol to the portal blood. More than 100 membrane and cytosolic transporters are now thought to facilitate absorption of minerals and vitamins as well as products of digestion of the macronutrients carbohydrates, proteins, and lipids. We highlight research areas that should yield information needed to better understand the important role of these transporters during normal development.
WAVY LEAF1, an Ortholog of Arabidopsis HEN1, Regulates Shoot Development by Maintaining MicroRNA and Trans-Acting Small Interfering RNA Accumulation in Rice
Authors: Abe Masashi , Yoshikawa Takanori , Nosaka Misuzu , Sakakibara Hitoshi , Sato Yutaka , Nagato Yasuo , Itoh Jun-ichi
Published: August 2010

In rice (Oryza sativa), trans-acting small interfering RNA (ta-siRNA) is essential for shoot development, including shoot apical meristem (SAM) formation and leaf morphogenesis. The rice wavy leaf1 (waf1) mutant has been identified as an embryonic mutant resembling shoot organization1 (sho1) and sho2, homologs of a loss-of-function mutant of DICER-LIKE4 and a hypomorphic mutant of ARGONAUTE7, respectively, which both act in the ta-siRNA production pathway. About half of the waf1 mutants showed seedling lethality due to defects in SAM maintenance, but the rest survived to the reproductive phase and exhibited pleiotropic phenotypes in leaf morphology and floral development. Map-based cloning of WAF1 revealed that it encodes an RNA methyltransferase, a homolog of Arabidopsis (Arabidopsis thaliana) HUA ENHANCER1. The reduced accumulation of small RNAs in waf1 indicated that the stability of the small RNA was decreased. Despite the greatly reduced level of microRNAs and ta-siRNA, microarray and reverse transcription-polymerase chain reaction experiments revealed that the expression levels of their target genes were not always enhanced. A double mutant between sho and waf1 showed an enhanced SAM defect, suggesting that the amount and/or quality of ta-siRNA is crucial for SAM maintenance. Our results indicate that stabilization of small RNAs by WAF1 is indispensable for rice development, especially for SAM maintenance and leaf morphogenesis governed by the ta-siRNA pathway. In addition, the inconsistent relationship between the amount of small RNAs and the level of the target mRNA in waf1 suggest that there is a complex regulatory mechanism that modifies the effects of microRNA/ta-siRNA on the expression of the target gene.
Expression, purification and crystallization of Swi5 and the Swi5–Sfr1 complex from fission yeast
Authors: Kuwabara Naoyuki , Hashimoto Hiroshi , Yamada Noriyo , Unzai Satoru , Ikeguchi Mitsunori , Sato Mamoru , Murayama Yasuto , Iwasaki Hiroshi , Shimizu Toshiyuki
Published: August 2010

The assembly of the presynaptic filament of recombinases represents the most important step in homologous recombination. The formation of the filament requires assistance from mediator proteins. Swi5 and Sfr1 have been identified as mediators in fission yeast and these proteins form a complex that stimulates strand exchange. Here, the expression, purification and crystallization of Swi5 and its complex with an N-terminally truncated form of Sfr1 (ΔN180Sfr1) are presented. Analytical ultracentrifugation of the purified samples showed that Swi5 and the protein complex exist as tetramers and heterodimers in solution, respectively. Swi5 was crystallized in two forms belonging to space groupsC2 andR3 and the crystals diffracted to 2.7 Å resolution. Swi5–ΔN180Sfr1 was crystallized in space groupP21212 and the crystals diffracted to 2.3 Å resolution. The crystals of Swi5 and Swi5–ΔN180Sfr1 are likely to contain one tetramer and two heterodimers in the asymmetric unit, respectively.