bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive milling of graphite with lithium: Application to lithium batteries
Authors: Azaı̈s P. , Duclaux L. , Faugère A.-M. , Béguin F.
Published: July 2002

Reactive milling of graphite with lithium has been performed in order to develop bonding between carbon and lithium atoms and thus to prepare insertion compounds with C/Li molar ratios lower than 6 (C/Li=6, 4 and 2). A test of these new compounds as anodes of Li batteries has shown higher reversible capacities than graphite (372 mA h/g), weaker hysteresis, and smaller irreversible capacities than milled graphite under the same conditions. This is explained by the formation of a lithiated surface.
Metallic ordered double-perovskite Sr2CrReO6 with maximal Curie temperature of 635 K
Authors: Kato H. , Okuda T. , Okimoto Y. , Tomioka Y. , Takenoya Y. , Ohkubo A. , Kawasaki M. , Tokura Y.
Published: July 2002

Electric, thermal, optical, and magnetic properties have been investigated for ferromagnetic (ferrimagnetic) ordered double perovskites, A2CrReO6 (A=Sr and Ca). Sr2CrReO6 is found to be a metallic ferromagnet with a high Curie temperature (TC=635 K), possibly the highest-TC half metal among the perovskite family. By contrast, Ca2CrReO6 is a ferromagnetic Mott insulator with TC of 360 K.
Optical second order nonlinearity of transparent Ba2TiGe2O8 crystallized glasses
Authors: Takahashi Yoshihiro , Benino Yasuhiko , Fujiwara Takumi , Komatsu Takayuki
Published: July 2002

Optical second-order nonlinearity of ferroelastic Ba2TiGe2O8 crystal in transparent crystallized glasses was estimated by means of the Maker fringe technique. Transparent crystallized glasses were fabricated by crystallization of a glass with the composition of 30 BaO.15 TiO2.55 GeO2. The crystalline layer consisting of highly oriented Ba2TiGe2O8 crystals was formed at the surface of about 9 μm thickness, and a clear second-harmonic generation was observed. The optical second-order nonlinearity of d33 for Ba2TiGe2O8 crystal was found to be ∼10 pm/V, being comparable to d22 and d31 of LiNbO3, and demonstrating that Ba2TiGe2O8 crystal is an excellent candidate for nonlinear optical crystals.
Thermistor ceramic with negative temperature coefficient based on Zn7Sb2O12: An inverse spinel-type phase
Authors: Nobre M. A. L. , Lanfredi S.
Published: July 2002

The electric properties of the semiconductor ceramic Zn7Sb2O12 were investigated by impedance spectroscopy. The grain resistance exhibits a thermistor behavior with negative temperature coefficient. Two regions on the resistance curve were identified. Each region shows a different thermistor characteristic parameter (β), which is equal to 3170 and 3845 °C, at measurement temperatures up to 350 °C and above 450 °C, respectively. The temperature coefficient of the resistance (α) was derived being equal to −2.59×10−2 °C−1 and −1.89×10−2 °C−1, at 350 and 450 °C, respectively. The anomalous behavior of the resistance is further evidence of phase transition phenomenon.
Bias effect on the growth of carbon nanotips using microwave plasma chemical vapor deposition
Authors: Tsai C. L. , Chen C. F. , Wu L. K.
Published: July 2002

Carbon nanotips with a high-aspect ratio were directly grown on Pt films. Carbon nanotips grew up to 5.4 μm length and 64 nm diameter under a −120 V bias. Compared to the hollow structure of carbon nanotubes, transmission electron microscopy images indicate its solid body, which is made of graphite. Carbon nanotips possess good field emission characteristics, that is, a turn-on field of 1.5 V/μm and 761 μA/cm2 under 2.2 V/μm. The Pt films provide a good conduction path for electron transport from the cathode to the emission site and do not act as catalysts.
Current-spreading-induced bistability in bipolar cascade vertical-cavity surface-emitting lasers
Authors: Knödl T. , Michalzik R. , Golling M. , Ebeling K. J.
Published: July 2002

We present experimental evidence that current spreading in the cavity of two-stage bipolar cascade vertical-cavity surface-emitting lasers is responsible for the formation of bistability loops in the light versus current characteristics. The bistable behavior strongly varies with the detuning between cavity resonance and gain maximum and is attributed to the wavelength and carrier density dependent absorption coefficient. In order to explain the measured dependencies, an analytical model is presented that very well matches the light output characteristics.
Nanorheology measurement on a single polymer chain
Authors: Sakai Yasuhiro , Ikehara Takayuki , Nishi Toshio , Nakajima Ken , Hara Masahiko
Published: July 2002

The mechanical properties of a single chain of a synthesized polystyrene were measured by atomic force microscopy (AFM). In the conventional force-distance curve measurement, the stress-strain behavior of a chain was obtained. We also measured the dynamic sinusoidal response, as in macroscopic rheological studies, repeatedly at several extension lengths before full stretching or rupturing, by a “nanorheology AFM” that we constructed. It enabled us to design any required movements on a z-piezoelectric scanner, especially sinusoidal movements. The rheological properties of a single polymer chain were discussed from the frequency-dependent measurement.
Electrical characterization of nanocontacts fabricated by nanoindentation and electrodeposition
Authors: Carrey J. , Bouzehouane K. , George J. M. , Ceneray C. , Blon T. , Bibes M. , Vaurès A. , Fusil S. , Kenane S. , Vila L. , Piraux L.
Published: July 2002

We report on the electrical characterization of various types of nanocontacts fabricated by nanoindentation and electrodeposition. Arrays of holes with depths ranging from 0 to 20 nm were produced by nanoindenting at different strengths an Al2O3-50 Å/NiFe-150 Å//Si bilayer. NiFe was then electrodeposited, which led to the growth of particles in the holes. The resistance of the particles was measured with a conducting tip atomic force microscope. Depending on the strength used during the nanoindentation, the resistance ranges from less than 5×103 Ω to more than 1012 Ω. The low-resistance constrictions can be used to study ballistic transport in materials. High-resistance contacts presumably correspond to tunnel nanojunctions.
Role of the wetting layer in the carrier relaxation in quantum dots
Authors: Sanguinetti S. , Watanabe K. , Tateno T. , Wakaki M. , Koguchi N. , Kuroda T. , Minami F. , Gurioli M.
Published: July 2002

We present picosecond time resolved photoluminescence measurements of GaAs/AlGaAs quantum dot structures—grown by modified droplet epitaxy—where no wetting layer is connecting the dots. We find a fast carrier relaxation time (30 ps) to the dot ground state, which becomes even faster for increasing the photogenerated carrier injection. This shows that the two–dimensional character of the wetting layer is not relevant in determining the quantum dot capture, in contrast with the conclusions of several models so far presented in literature. We discuss the role of the barrier states as well as the possibility of Auger processes involving the zero-dimensional levels of the quantum dots.
Pulsed field gradient nuclear magnetic resonance study of long–range diffusion in beds of NaX zeolite: Evidence for different apparent tortuosity factors in the Knudsen and bulk regimes
Authors: Geier O. , Vasenkov S. , Kärger J.
Published: July 2002

The pulsed field gradient nuclear magnetic resonance method is applied to study self-diffusion of ethane in beds of zeolite NaX for displacements which are orders of magnitude larger than the size of individual crystals. Comparison of the measured diffusivities with those calculated using simple gas kinetic theory indicates that for the same bed of NaX crystals the apparent tortuosity factor in the Knudsen regime is significantly larger than that in the bulk regime. This finding is tentatively attributed to the more pronounced geometrical trapping by surface imperfections in the Knudsen than in the bulk regime. Tortuosity factors, which are much larger in the Knudsen regime than in the bulk regime, were also recently obtained by dynamic Monte Carlo simulation of gas diffusion in various porous systems.
A mutation that prevents paramutation in maize also reverses
Mutator
transposon methylation and silencing
Authors: Lisch Damon , Carey Charles C. , Dorweiler Jane E. , Chandler Vicki L.
Published: July 2002

Both paramutation and
Mutator
(
Mu
) transposon inactivation involve heritable changes in gene expression without concomitant changes in DNA sequence. The mechanisms by which these shifts in gene activity are achieved are unknown. Here we present evidence that these two phenomena are linked mechanistically. We show that mutation of a gene,
modifier of paramutation 1
(
mop1
), which prevents paramutation at three different loci in maize, can reverse methylation of
Mutator
elements reliably. In
mop1
mutant backgrounds, methylation of nonautonomous
Mu
elements can be reversed even in the absence of the regulatory
MuDR
element. Previously silenced
MuDR
elements are reactivated sporadically after multiple generations of exposure to
mop1
mutations.
MuDR
methylation is separable from
MuDR
silencing, because removal of methylation does not cause immediate reactivation. The
mop1
mutation does not alter the methylation of certain other transposable elements including those just upstream of a paramutable
b1
gene. Our results suggest that the
mop1
gene acts on a subset of epigenetically regulated sequences in the maize genome and paramutation and
Mu
element methylation require a common factor, which we hypothesize influences chromatin structure.
Zinc finger as distance determinant in the flexible linker of intron endonuclease I-
Tev
I
Authors: Dean Amy B. , Stanger Matt J. , Dansereau John T. , Van Roey Patrick , Derbyshire Victoria , Belfort Marlene
Published: July 2002

I-
Tev
I, the phage T4
td
intron-encoded endonuclease, recognizes a lengthy DNA target and initiates intron mobility by introducing a double-strand break in the homing site. The enzyme uses both sequence and distance determinants to cleave the DNA 23–25 bp upstream of the intron insertion site. I-
Tev
I consists of an N-terminal catalytic domain and a C-terminal DNA-binding domain separated by a long, flexible linker. The DNA-binding domain consists of three subdomains: a zinc finger, a minor-groove binding α-helix, and a helix–turn–helix. In this study, a mutational analysis was undertaken to assess the roles of these subdomains in substrate binding and cleavage. Surprisingly, the zinc finger is not required for DNA binding or catalysis. Rather, the zinc finger is a component of the linker and directs the catalytic domain to cleave the homing site at a fixed distance from the intron insertion site. When the cleavage site (CS) is shifted outside a given range, wild-type I-
Tev
I defaults to the fixed distance, whereas zinc-finger mutants have lost the distance determinant and search out the displaced cleavage sequences. Although counterintuitive, a protein containing a 19-aa deletion of the zinc finger can extend further than can wild-type I-
Tev
I to cleave a distant CS sequence, and a Cys-to-Ala mutant of the ligands for zinc, nominally a longer protein, can retract to cleave at a closer CS sequence. Models are presented for the novel function of the zinc finger, as a molecular constraint, whereby intramolecular protein–protein interactions position the catalytic domain by “catalytic clamp” and/or “linker-organizer” mechanisms.
Allometric scaling and maximum efficiency in physiological eigen time
Authors: Andresen Bjarne , Shiner J. S. , Uehlinger Dominik E.
Published: July 2002

General optimization results from physics indicate that maximum efficiency of a process, in the sense of minimum overall entropy production, is achieved when the rate of entropy production is constant over time, however not in ordinary clock time but on an, in general varying, “eigen time” scale, intrinsic to the system. We identify the eigen time of a biological system with “physiological time,” which generally scales with the 1/4 power of body mass,M1/4, over a vast range of species. Since it is equally well established that metabolic rate scales asM3/4, it follows that organisms produce entropy at the same intrinsic rate, fulfilling a necessary condition for maximum efficiency, and are all, furthermore, equally efficient on the physiological eigen time scale.
Sustained stimulation shifts the mechanism of endocytosis from dynamin-1-dependent rapid endocytosis to clathrin- and dynamin-2-mediated slow endocytosis in chromaffin cells
Authors: Artalejo Cristina R. , Elhamdani Abdeladim , Palfrey H. Clive
Published: July 2002

Transient stimulation of secretion in calf chromaffin cells is invariably followed by rapid endocytosis (RE), a clathrin- and K
+
-independent process with a half time of several seconds. Here we show that when exocytosis is triggered in a more sustained manner, a much slower form of endocytosis (SE) replaces RE. SE is complete within 10 min and is abolished when anticlathrin antibodies are introduced into the cell or when intracellular K
+
is removed. RE, but not SE, is blocked by intracellular administration of antidynamin-1 antibodies; the inverse specificity was found for antidynamin-2 antibodies. Replacement of extracellular Ca
2+
by Ba
2+
or Sr
2+
completely blocked RE but had little effect on SE. Thus chromaffin cells exhibit two kinetically and mechanistically distinct forms of endocytosis that are coupled to different extents of exocytosis and are mediated by different isoforms of dynamin. We surmise that RE is associated with the transient fusion (“kiss-and-run”) mechanism of transmitter release and is the prevalent means of vesicle recapture and recycling under normal physiological conditions, whereas the clathrin-based SE mechanism comes into play only at higher levels of stimulation and may be associated with complete fusion of vesicles with the plasma membrane.
Tau is essential to β-amyloid-induced neurotoxicity
Authors: Rapoport Mark , Dawson Hana N. , Binder Lester I. , Vitek Michael P. , Ferreira Adriana
Published: July 2002

Senile plaques and neurofibrillary tangles, the two hallmark lesions of Alzheimer's disease, are the results of the pathological deposition of proteins normally present throughout the brain. Senile plaques are extracellular deposits of fibrillar β-amyloid peptide (Aβ); neurofibrillary tangles represent intracellular bundles of self-assembled hyperphosphorylated tau proteins. Although these two lesions are often present in the same brain areas, a mechanistic link between them has yet to be established. In the present study, we analyzed whether tau plays a key role in fibrillar Aβ-induced neurite degeneration in central neurons. Cultured hippocampal neurons obtained from wild-type, tau knockout, and human tau transgenic mice were treated with fibrillar Aβ. Morphological analysis indicated that neurons expressing either mouse or human tau proteins degenerated in the presence of Aβ. On the other hand, tau-depleted neurons showed no signs of degeneration in the presence of Aβ. These results provide direct evidence supporting a key role for tau in the mechanisms leading to Aβ-induced neurodegeneration in the central nervous system. In addition, the analysis of the composition of the cytoskeleton of tau-depleted neurons suggested that the formation of more dynamic microtubules might confer resistance to Aβ-mediated neurodegeneration.
A target essential for the activity of a nonacidic yeast transcriptional activator
Authors: Lu Zhen , Ansari Aseem Z. , Lu Xiangyang , Ogirala Anuja , Ptashne Mark
Published: July 2002

P201 is a short (eight-residue) nonacidic peptide that comprises a strong transcriptional activating region when tethered to DNA in yeast. Here we identify the mediator protein Gal11 as an essential target of P201. Deletion of Gal11, which modestly decreases activation elicited by the typical acidic yeast activator, abolishes activation by DNA-tethered P201. A point mutation in Gal11, which has no effect on other Gal11 functions, also greatly diminishes activation by DNA-tethered P201. P201 binds to a fragment of Gal11
in vivo
and
in vitro
, and the interaction is diminished by mutations in either component that decrease activation
in vivo
. P201, unlike the typical yeast acidic activating region, does not work in mammalian cells, which is consistent with the notion that the unique target of P201 (Gal11) is absent from mammalian cells.
Population genomics of drug resistance in
Candida albicans
Authors: Cowen Leah E. , Nantel André , Whiteway Malcolm S. , Thomas David Y. , Tessier Daniel C. , Kohn Linda M. , Anderson James B.
Published: July 2002

We followed adaptation in experimental microbial populations to inhibitory concentrations of an antimicrobial drug. The evolution of drug resistance was accompanied in all cases by changes in gene expression that persisted in the absence of the drug; the new patterns of gene expression were constitutive. The changes in gene expression occurred in four replicate populations of the pathogenic fungus
Candida albicans
during 330 generations of evolution in the presence of the antifungal drug fluconazole. Genome-wide expression profiling of over 5,000 ORFs identified 301 whose expression was significantly modulated. Cluster analysis identified three distinct patterns of gene expression underlying adaptation to the drug. One pattern was unique to one population and included up-regulation of the multidrug ATP-binding cassette transporter gene,
CDR2
. A second pattern occurred at a late stage of adaptation in three populations; for two of these populations profiled earlier in their evolution, a different pattern was observed at an early stage of adaptation. The succession of early- and late-stage patterns of gene expression, both of which include up-regulation of the multidrug major facilitator transporter gene,
MDR1
, must represent a common program of adaptation to this antifungal drug. The three patterns of gene expression were also identified in fluconazole-resistant clinical isolates, providing further evidence that these patterns represent common programs of adaptation to fluconazole.
Chaotic mixing deep in the lung
Authors: Tsuda Akira , Rogers Rick A. , Hydon Peter E. , Butler James P.
Published: July 2002

Our current understanding of the transport and deposition of aerosols (viruses, bacteria, air pollutants, aerosolized drugs) deep in the lung has been grounded in dispersive theories based on untested assumptions about the nature of acinar airflow fields. Traditionally, these have been taken to be simple and kinematically reversible. In this article, we apply the recently discovered fluid mechanical phenomenon of irreversible low-Reynolds number flow to the lung. We demonstrate, through flow visualization studies in rhythmically ventilated rat lungs, that such a foundation is false, and that chaotic mixing may be key to aerosol transport. We found substantial alveolar flow irreversibility with stretched and folded fractal patterns, which lead to a sudden increase in mixing. These findings support our theory that chaotic alveolar flow—characterized by stagnation saddle points associated with alveolar vortices—governs gas kinematics in the lung periphery, and hence the transport, mixing, and ultimately the deposition of fine aerosols. This mechanism calls for a rethinking of the relationship of exposure and deposition of fine inhaled particles.
Polyproline II structure in a sequence of seven alanine residues
Authors: Shi Zhengshuang , Olson C. Anders , Rose George D. , Baldwin Robert L. , Kallenbach Neville R.
Published: July 2002

A sequence of seven alanine residues—too short to form an α-helix and whose side chains do not interact with each other—is a particularly simple model for testing the common description of denatured proteins as structureless random coils. The3JHNαcoupling constants of individual alanine residues have been measured from 2 to 56°C by using isotopically labeled samples. The results display a thermal transition between different backbone conformations, which is confirmed by CD spectra. The NMR results suggest that polyproline II is the dominant conformation at 2°C and the content of β strand is increased by approximately 10% at 55°C relative to that at 2°C. The polyproline II conformation is consistent with recent studies of short alanine peptides, including structure prediction byab initioquantum mechanics and solution structures for both a blocked alanine dipeptide and an alanine tripeptide. CD and other optical spectroscopies have found structure in longer “random coil” peptides and have implicated polyproline II, which is a major backbone conformation in residues within loop regions of protein structures. Our result suggests that the backbone conformational entropy in alanine peptides is considerably smaller than estimated by the random coil model. New thermodynamic data confirm this suggestion: the entropy loss on alanine helix formation is only 2.2 entropy units per residue.
trilogy
: Discovery of sequence–structure patterns across diverse proteins
Authors: Bradley Philip , Kim Peter S. , Berger Bonnie
Published: July 2002

We describe a new computer program,
trilogy
, for the automated discovery of sequence–structure patterns in proteins.
trilogy
implements a pattern discovery algorithm that begins with an exhaustive analysis of flexible three-residue patterns; a subset of these patterns are selected as seeds for an extension process in which longer patterns are identified. A key feature of the method is explicit treatment of both the sequence and structure components of these motifs: each
trilogy
pattern is a pair consisting of a sequence pattern and a structure pattern. Matches to both these component patterns are identified independently, allowing the program to assign a significance score to each sequence–structure pattern that assesses the degree of correlation between the corresponding sequence and structure motifs.
trilogy
identifies several thousand high-scoring patterns that occur across protein families. These include both previously identified and potentially novel motifs. We expect that these sequence–structure patterns will be useful in predicting protein structure from sequence, annotating newly determined protein structures, and identifying novel motifs of potential functional or structural significance. Further details on 7,768 significant patterns identified by
trilogy
can be found at
http://theory.lcs.mit.edu/trilogy
.
Inverting dynamic force microscopy: From signals to time-resolved interaction forces
Authors: Stark Martin , Stark Robert W. , Heckl Wolfgang M. , Guckenberger Reinhard
Published: July 2002

Transient forces between nanoscale objects on surfaces govern friction, viscous flow, and plastic deformation, occur during manipulation of matter, or mediate the local wetting behavior of thin films. To resolve transient forces on the (sub) microsecond time and nanometer length scale, dynamic atomic force microscopy (AFM) offers largely unexploited potential. Full spectral analysis of the AFM signal completes dynamic AFM. Inverting the signal formation process, we measure the time course of the force effective at the sensing tip. This approach yields rich insight into processes at the tip and dispenses with
a priori
assumptions about the interaction, as it relies solely on measured data. Force measurements on silicon under ambient conditions demonstrate the distinct signature of the interaction and reveal that peak forces exceeding 200 nN are applied to the sample in a typical imaging situation. These forces are 2 orders of magnitude higher than those in covalent bonds.
Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy
Authors: Özcelik Cemil , Erdmann Bettina , Pilz Bernhard , Wettschureck Nina , Britsch Stefan , Hübner Norbert , Chien Kenneth R. , Birchmeier Carmen , Garratt Alistair N.
Published: July 2002

The
ErbB2
(
Her2
) proto-oncogene encodes a receptor tyrosine kinase, which is frequently amplified and overexpressed in human tumors. ErbB2 provides the target for a novel and effective antibody-based therapy (Trastuzumab/Herceptin) used for the treatment of mammary carcinomas. However, cardiomyopathies develop in a proportion of patients treated with Trastuzumab, and the incidence of such complications is increased by combination with standard chemotherapy. Gene ablation studies have previously demonstrated that the ErbB2 receptor, together with its coreceptor ErbB4 and the ligand Neuregulin-1, are essential for normal development of the heart ventricle. We use here Cre-
lox
P technology to mutate
ErbB2
specifically in ventricular cardiomyocytes. Conditional mutant mice develop a severe dilated cardiomyopathy, with signs of cardiac dysfunction generally appearing by the second postnatal month. We infer that signaling from the ErbB2 receptor, which is enriched in T-tubules in cardiomyocytes, is crucial for adult heart function. Conditional
ErbB2
mutant mice provide a model of dilated cardiomyopathy. In particular, they will allow a rigorous assessment of the role of ErbB2 in the heart and provide insight into the molecular mechanisms that underlie the adverse effects of anti-ErbB2 antibodies.
Polynucleotide phosphorylase is a global regulator of virulence and persistency in
Salmonella enterica
Authors: Clements Mark O. , Eriksson Sofia , Thompson Arthur , Lucchini Sacha , Hinton Jay C. D. , Normark Staffan , Rhen Mikael
Published: July 2002

For many pathogens, the ability to regulate their replication in host cells is a key element in establishing persistency. Here, we identified a single point mutation in the gene for polynucleotide phosphorylase (PNPase) as a factor affecting bacterial invasion and intracellular replication, and which determines the alternation between acute or persistent infection in a mouse model for
Salmonella
enterica
infection. In parallel, with microarray analysis, PNPase was found to affect the mRNA levels of a subset of virulence genes, in particular those contained in
Salmonella
pathogenicity islands 1 and 2. The results demonstrate a connection between PNPase and
Salmonella
virulence and show that alterations in PNPase activity could represent a strategy for the establishment of persistency.
Deciphering peripheral nerve myelination by using Schwann cell expression profiling
Authors: Nagarajan Rakesh , Le Nam , Mahoney Heather , Araki Toshiyuki , Milbrandt Jeffrey
Published: July 2002

Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs,
MASR
(myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.
Leukemia inhibitory factor inhibits neuronal terminal differentiation through STAT3 activation
Authors: Moon Cheil , Yoo Joo-Yeon , Matarazzo Valéry , Sung Young Kwan , Kim Esther J. , Ronnett Gabriele V.
Published: July 2002

The discovery of stem cells in the adult central nervous system raises questions concerning the neurotrophic factors that regulate postnatal neuronal development. Olfactory receptor neurons (ORNs) are a useful model, because they are capable of robust neurogenesis throughout adulthood. We have investigated the role of leukemia inhibitory factor (LIF) in postnatal neuronal development by using ORNs as a model. LIF is a multifunctional cytokine implicated in various aspects of neuronal development, including phenotype determination, survival, and in response to nerve injury. LIF-deficient mice display significant increases, both in the absolute amount and in the number of cells expressing olfactory marker protein, a marker of mature ORNs. The maturation of ORNs was significantly inhibited by LIF
in vitro
. LIF activated the STAT3 pathway in ORNs, and transfection of ORNs with a dominant negative form of STAT3 abolished the effect of LIF. These findings demonstrate that LIF negatively regulates ORN maturation via the STAT3 pathway. Thus, LIF plays a critical role in controlling the transition of ORNs to maturity. Consequently, a population of ORNs is maintained in an immature state to facilitate the rapid repopulation of the olfactory epithelium with mature neurons during normal cell turnover or after injury.
Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone
Authors: Horwitz Edwin M. , Gordon Patricia L. , Koo Winston K. K. , Marx Jeffrey C. , Neel Michael D. , McNall Rene Y. , Muul Linda , Hofmann Ted
Published: July 2002

Treatment with isolated allogeneic mesenchymal cells has the potential to enhance the therapeutic effects of conventional bone marrow transplantation in patients with genetic disorders affecting mesenchymal tissues, including bone, cartilage, and muscle. To demonstrate the feasibility of mesenchymal cell therapy and to gain insight into the transplant biology of these cells, we used gene-marked, donor marrow-derived mesenchymal cells to treat six children who had undergone standard bone marrow transplantation for severe osteogenesis imperfecta. Each child received two infusions of the allogeneic cells. Five of six patients showed engraftment in one or more sites, including bone, skin, and marrow stroma, and had an acceleration of growth velocity during the first 6 mo postinfusion. This improvement ranged from 60% to 94% (median, 70%) of the predicted median values for age- and sex-matched unaffected children, compared with 0% to 40% (median, 20%) over the 6 mo immediately preceding the infusions. There was no clinically significant toxicity except for an urticarial rash in one patient just after the second infusion. Failure to detect engraftment of cells expressing the neomycin phosphotransferase marker gene suggested the potential for immune attack against therapeutic cells expressing a foreign protein. Thus, allogeneic mesenchymal cells offer feasible posttransplantation therapy for osteogenesis imperfecta and likely other disorders originating in mesenchymal precursors.
The structures of the active center in dark-adapted bacteriorhodopsin by solution-state NMR spectroscopy
Authors: Patzelt Heiko , Simon Bernd , terLaak Antonius , Kessler Brigitte , Kühne Ronald , Schmieder Peter , Oesterhelt Dieter , Oschkinat Hartmut
Published: July 2002

The two forms of bacteriorhodopsin present in the dark-adapted state, containing either
all-trans
or 13-
cis
,15-
syn
retinal, were examined by using solution state NMR, and their structures were determined. Comparison of the
all-trans
and the 13-
cis
,15-
syn
forms shows a shift in position of about 0.25 Å within the pocket of the protein. Comparing this to the 13-
cis
,15-
anti
chromophore of the catalytic cycle M-intermediate structure, the 13-
cis
,15-
syn
form demonstrates a less pronounced up-tilt of the retinal C12—C14 region, while leaving W182 and T178 essentially unchanged. The N—H dipole of the Schiff base orients toward the extracellular side in both forms, however, it reorients toward the intracellular side in the 13-
cis
,15-
anti
configuration to form the catalytic M-intermediate. Thus, the change of the N—H dipole is considered primarily responsible for energy storage, conformation changes of the protein, and the deprotonation of the Schiff base. The structural similarity of the
all-trans
and 13-
cis
,15-
syn
forms is taken as strong evidence for the ion dipole dragging model by which proton (hydroxide ion) translocation follows the change of the dipole.
Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis
Authors: Bäcklund Johan , Carlsen Stefan , Höger Torsten , Holm Björn , Fugger Lars , Kihlberg Jan , Burkhardt Harald , Holmdahl Rikard
Published: July 2002

Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263–270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n= 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients.
Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model
Authors: Su Hua , Arakawa-Hoyt Janice , Kan Yuet Wai
Published: July 2002

Intramyocardial injection of genes encoding angiogenic factors could provide a useful approach for the treatment of ischemic heart disease. However, uncontrolled expression of angiogenic factors
in vivo
may cause some unwanted side effects, such as hemangioma formation, retinopathy, and arthritis. It may also induce occult tumor growth and artherosclerotic plaque progression. Because hypoxia-inducible factor 1 is up-regulated in a variety of hypoxic conditions and it regulates gene expression by binding to a cis-acting hypoxia-responsive element (HRE), we propose to use HRE, found in the 3′ end of the erythropoietin gene to control gene expression in ischemic myocardium. A concatemer of nine copies of the consensus sequence of HRE isolated from the erythropoietin enhancer was used to mediate hypoxia induction. We constructed two adeno-associated viral vectors in which LacZ and vascular endothelial growth factor (VEGF) expressions were controlled by this HRE concatemer and a minimal simian virus 40 promoter. Both LacZ and VEGF expression were induced by hypoxia and/or anoxia in several cell lines transduced with these vectors. The functions of these vectors in ischemic myocardium were tested by injecting them into normal and ischemic mouse myocardium created by occlusion of the left anterior descending coronary artery. The expression of LacZ gene was induced eight times and of VEGF 20 times in ischemic myocardium compared with normal myocardium after the viral vector transduction. Hence, HRE is a good candidate for the control of angiogenic factor gene expression in ischemic myocardium.
Diffuse fluid flux through orogenic belts: Implications for the world ocean
Authors: Ingebritsen Steven E. , Manning Craig E.
Published: July 2002

Fifty years ago a classic paper by W. W. Rubey [(1951)
Geol. Soc. Am. Bull.
62, 1111–1148] examined various hypotheses regarding the origin of sea water and concluded that the most likely hypothesis was volcanic outgassing, a view that was generally accepted by earth scientists for the next several decades. More recent work suggests that the rate of subduction of water is much larger than the volcanic outgassing rate, lending support to hypotheses that either ocean volume has decreased with time, or that the imbalance is offset by continuous replenishment of water by cometary impacts. These alternatives are required in the absence of additional mechanisms for the return of water from subducting lithosphere to the Earth's surface. Our recent work on crustal permeability suggests a large capacity for water upflow through tectonically active continental crust, resulting in a heretofore unrecognized degassing pathway that can accommodate the water subduction rate. Escape of recycled water via delivery from the mantle through zones of active metamorphism eliminates the mass-balance argument for the loss of ocean volume or extraterrestrial sources.
Altered accumbens neural response to prediction of reward associated with place in dopamine D2 receptor knockout mice
Authors: Tran Anh Hai , Tamura Ryoi , Uwano Teruko , Kobayashi Tsuneyuki , Katsuki Motoya , Matsumoto Gen , Ono Taketoshi
Published: July 2002

Midbrain dopaminergic activity seems to be important in forming the prediction of future events such as rewards. The nucleus accumbens (NAc) plays an important role in the integration of reward with motor function, and it receives dense dopamine innervation and extensive limbic and cortical afferents. Here, we examined the specific role of the dopamine D2 receptor (D2R) in mediating associative learning, locomotor activity, and regulating NAc neural responses by using D2R-knockout (KO) mice and their wild-type littermates. D2R-KO mice displayed reduced locomotor activity and slower acquisition of a place-learning task. D2R-KO eliminated the prereward inhibitory response of neurons in the NAc. In contrast, an increased number of neurons in D2R-KO mice displayed place-related activity. These results provide evidence that D2R in the NAc participates in coding for a specific type of neural response to incentive contingencies and partly in spatial learning.
An ectopic human
XIST
gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells
Authors: Hall Lisa L. , Byron Meg , Sakai Kosuke , Carrel Laura , Willard Huntington F. , Lawrence Jeanne B.
Published: July 2002

It has been believed that XIST RNA requires a discrete window in early development to initiate the series of chromatin-remodeling events that form the heterochromatic inactive X chromosome. Here we investigate four adult male HT-1080 fibrosarcoma cell lines expressing ectopic human XIST and demonstrate that these postdifferentiation cells can undergo chromosomal inactivation outside of any normal developmental context. All four clonal lines inactivated the transgene-containing autosome to varying degrees and with variable stability. One clone in particular consistently localized the ectopic XIST RNA to a discrete chromosome territory that exhibited striking hallmarks of inactivation, including long-range transcriptional inactivation. Results suggest that some postdifferentiation cell lines are capable of
de novo
chromosomal inactivation; however, long-term retention of autosomal inactivation was less common, which suggests that autosomal inactivation may confer a selective disadvantage. These results have fundamental significance for understanding genomic programming in early development.
Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure
Authors: Rokosh D. Gregg , Simpson Paul C.
Published: July 2002

α1-adrenergic receptors (ARs) play a major role in blood pressure regulation. The three α1-AR subtypes (A/C, B, and D) stimulate contraction of isolated arteries, but it is uncertain how different subtypes contribute to blood pressure regulation in the intact animal. We studied the role of the α1A/C subtype by using gene knockout. α1A/C knockout (KO) mice were viable and overtly normal. The LacZ reporter gene replaced α1A/C coding sequence in the KO, and β-galactosidase staining was present in resistance arteries and arterioles, but not in the thoracic aorta or its main branches. By tail cuff manometer and arterial catheter in conscious mice, α1A/C KO mice were hypotensive at rest, with an 8–12% reduction of blood pressure dependent on α1A/C gene copy number. A61603, an α1A/C-selective agonist, caused a pressor response that was lost in the KO and reduced but significant in heterozygous mice with a single copy of the α1A/C. A subtype-nonselective agonist [phenylephrine (PE)] caused a pressor response in KO mice, but the final arterial pressure was only 85% of wild type. The baroreflex was reset in the KO, and heart rate variability was decreased. After baroreflex blockade with atropine, PE increased blood pressure but did not change heart rate. Cardiac and vascular responses to the β-AR agonist isoproterenol were unchanged, and the arterial lumen area was not altered. We conclude that the α1A/C-AR subtype is a vasopressor expressed in resistance arteries and is required for normal arterial blood pressure regulation. α1A/C-selective antagonists might be desirable antihypertensive agents.
Second- and third-hand chloroplasts in dinoflagellates: Phylogeny of oxygen-evolving enhancer 1 (PsbO) protein reveals replacement of a nuclear-encoded plastid gene by that of a haptophyte tertiary endosymbiont
Authors: Ishida Ken-ichiro , Green Beverley R.
Published: July 2002

Several dinoflagellate species have plastids that more closely resemble those of an unrelated algal group, the haptophytes, suggesting these plastids have been obtained by tertiary endosymbiosis. Because both groups are photosynthetic, all of the genes for nuclear-encoded plastid proteins might be supplied by the dinoflagellate host or some of them might have been replaced by haptophyte genes. Sequences of the conserved nuclear
psb
O gene were obtained from the haptophyte
Isochrysis galbana
, the peridinin-containing dinoflagellate
Heterocapsa triquetra
, and the 19′hexanoyloxy-fucoxanthin-containing dinoflagellate
Karenia brevis
. Phylogenetic analysis of the oxygen-evolving-enhancer (PsbO) proteins confirmed that in
K. brevis
the original peridinin-type plastid was replaced by that of a haptophyte, an alga which had previously acquired a red algal chloroplast by secondary endosymbiosis. It showed clearly that during this tertiary symbiogenesis the original
psb
O gene in the dinoflagellate nucleus was replaced by a
psb
O gene from the haptophyte nucleus. The phylogenetic analysis also confirmed that the origin of the peridinin-type dinoflagellate plastid was indeed a red alga.
Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles
Authors: Schoch Claudia , Kohlmann Alexander , Schnittger Susanne , Brors Benedikt , Dugas Martin , Mergenthaler Susanne , Kern Wolfgang , Hiddemann Wolfgang , Eils Roland , Haferlach Torsten
Published: July 2002

Acute myeloid leukemia (AML) is a heterogeneous group of genetically defined diseases. Their classification is important with regard to prognosis and treatment. We performed microarray analyses for gene expression profiling on bone marrow samples of 37 patients with newly diagnosed AML. All cases had either of the distinct subtypes AML M2 with t(8;21), AML M3 or M3v with t(15;17), or AML M4eo with inv(16). Diagnosis was established by cytomorphology, cytogenetics, fluorescence
in situ
hybridization, and reverse transcriptase–PCR in every sample. By using two different strategies for microarray data analyses, this study revealed a unique correlation between AML-specific cytogenetic aberrations and gene expression profiles.
A ribozyme that ligates RNA to protein
Authors: Baskerville Scott , Bartel David P.
Published: July 2002

We have used a combination of
in vitro
selection and rational design to generate ribozymes that form a stable phosphoamide bond between the 5′ terminus of an RNA and a specific polypeptide. This reaction differs from that of previously identified ribozymes, although the product is analogous to the enzyme–nucleotidyl intermediates isolated during the reactions of certain proteinaceous enzymes, such as guanyltransferase, DNA ligase, and RNA ligase. Comparative sequence analysis of the isolated ribozymes revealed that they share a compact secondary structure containing six stems arranged in a four-helix junction and branched pseudoknot. An optimized version of the ribozyme reacts with substrate-fusion proteins, allowing it to be used to attach RNA tags to proteins both
in vitro
and within bacterial cells, suggesting a simple way to tag a specific protein with amplifiable information.
Beyond the Rayleigh instability limit for multicharged finite systems: From fission to Coulomb explosion
Authors: Last Isidore , Levy Yaakov , Jortner Joshua
Published: July 2002

We address the stability of multicharged finite systems driven by Coulomb forces beyond the Rayleigh instability limit. Our exploration of the nuclear dynamics of heavily charged Morse clusters enabled us to vary the range of the pair potential and of the fissibility parameter, which results in distinct fragmentation patterns and in the angular distributions of the fragments. The Rayleigh instability limit separates between nearly binary (or tertiary) spatially unisotropic fission and spatially isotropic Coulomb explosion into a large number of small, ionic fragments. Implications are addressed for a broad spectrum of dynamics in chemical physics, radiation physics of ultracold gases, and biophysics, involving the fission of clusters and droplets, the realization of Coulomb explosion of molecular clusters, the isotropic expansion of optical molasses, and the Coulomb instability of “isolated” proteins.
Randomized controlled trial of a treatment for anorexia and bulimia nervosa
Authors: Bergh Cecilia , Brodin Ulf , Lindberg Greger , Södersten Per
Published: July 2002

Evidence for the effectiveness of existing treatments of patients with eating disorders is weak. Here we describe and evaluate a method of treatment in a randomized controlled trial. Sixteen patients, randomly selected out of a group composed of 19 patients with anorexia nervosa and 13 with bulimia nervosa, were trained to eat and recognize satiety by using computer support. They rested in a warm room after eating, and their physical activity was restricted. The patients in the control group (
n
= 16) received no treatment. Remission was defined by normal body weight (anorexia), cessation of binge eating and purging (bulimia), a normal psychiatric profile, normal laboratory test values, normal eating behavior, and resumption of social activities. Fourteen patients went into remission after a median of 14.4 months (range 4.9–26.5) of treatment, but only one patient went into remission while waiting for treatment (
P
= 0.0057). Relapse is considered a major problem in patients who have been treated to remission. We therefore report results on a total of 168 patients who have entered our treatment program. The estimated rate of remission was 75%, and estimated time to remission was 14.7 months (quartile range 9.6 ≥ 32). Six patients (7%) of 83 who were treated to remission relapsed, but the others (93%) have remained in remission for 12 months (quartile range 6–36). Because the risk of relapse is maximal in the first year after remission, we suggest that most patients treated with this method recover.