Showing papers by "Tohoku University published in 2004"

The worldwide leaf economics spectrum

Abstract: Bringing together leaf trait data spanning 2,548 species and 175 sites we describe, for the first time at global scale, a universal spectrum of leaf economics consisting of key chemical, structural and physiological properties. The spectrum runs from quick to slow return on investments of nutrients and dry mass in leaves, and operates largely independently of growth form, plant functional type or biome. Categories along the spectrum would, in general, describe leaf economic variation at the global scale better than plant functional types, because functional types overlap substantially in their leaf traits. Overall, modulation of leaf traits and trait relationships by climate is surprisingly modest, although some striking and significant patterns can be seen. Reliable quantification of the leaf economics spectrum and its interaction with climate will prove valuable for modelling nutrient fluxes and vegetation boundaries under changing land-use and climate.

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

Abstract: The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Repeated temperature modulation epitaxy for p-type doping and light-emitting diode based on ZnO

Abstract: Since the successful demonstration of a blue light-emitting diode (LED)1, potential materials for making short-wavelength LEDs and diode lasers have been attracting increasing interest as the demands for display, illumination and information storage grow2,3,4. Zinc oxide has substantial advantages including large exciton binding energy, as demonstrated by efficient excitonic lasing on optical excitation5,6. Several groups have postulated the use of p-type ZnO doped with nitrogen, arsenic or phosphorus7,8,9,10, and even p–n junctions11,12,13. However, the choice of dopant and growth technique remains controversial and the reliability of p-type ZnO is still under debate14. If ZnO is ever to produce long-lasting and robust devices, the quality of epitaxial layers has to be improved as has been the protocol in other compound semiconductors15. Here we report high-quality undoped films with electron mobility exceeding that in the bulk. We have used a new technique to fabricate p-type ZnO reproducibly. Violet electroluminescence from homostructural p–i–n junctions is demonstrated at room-temperature.

IAWA list of microscopic features for softwood identification

Abstract: Pieter Baas – Leiden, The Netherlands Nadezhda Blokhina – Vladivostok, Russia Tomoyuki Fujii – Ibaraki, Japan Peter Gasson – Kew, UK Dietger Grosser – Munich, Germany Immo Heinz – Munich, Germany Jugo Ilic – South Clayton, Australia Jiang Xiaomei – Beijing, China Regis Miller – Madison, WI, USA Lee Ann Newsom – University Park, PA, USA Shuichi Noshiro – Ibaraki, Japan Hans Georg Richter – Hamburg, Germany Mitsuo Suzuki – Sendai, Japan Teresa Terrazas – Montecillo, Mexico Elisabeth Wheeler – Raleigh, NC, USA Alex Wiedenhoeft – Madison, WI, USA

Chiral Brønsted acid-catalyzed direct Mannich reactions via electrophilic activation.

Abstract: It was found that the phosphoric acid derivatives of general structure 1 serve as highly effective catalysts for the direct addition of acetyl acetone to N-Boc-protected arylimines. The beneficial effects of the 3,3‘-bisaryl substituents of the catalysts on the enantioselectivity are greatly appreciated, and thus 1d functions as an excellent catalyst. The Bronsted acid-catalyzed direct Mannich reactions presented herein provide an attractive way to construct β-aminoketones under extremely mild conditions. The stereochemical course of this reaction was established through the synthesis of Boc-(S)-phenylglycine methylester. The transformation thus demonstrated is applicable to a useful method for the synthesis of various phenylglycine derivatives.

High Efficiency of Dye-Sensitized Solar Cells Based on Metal-Free Indoline Dyes

Abstract: We now report metal-free organic dyes having a new type of indoline structure, which exhibits high efficiencies in dye-sensitized solar cells. The solar energy to current conversion efficiencies with the new indoline dye was 6.51%. Under the same conditions, the N3 dye was 7.89% and the N719 dye was 8.26%. The new indoline dye was optimized for the amount of 4-tert-butyl pyridine in the electrolyte and cholic acid as a coadsorbent. Subsequently, the solar energy to current conversion efficiencies reached 8.00%. This value was the highest obtained efficiency for dye-sensitized solar cells based on metal-free organic dyes without an antireflection layer.

The Second Data Release of the Sloan Digital Sky Survey

Abstract: The Sloan Digital Sky Survey (SDSS) has validated and made publicly available its Second Data Release. This data release consists of 3324 deg2 of five-band (ugriz) imaging data with photometry for over 88 million unique objects, 367,360 spectra of galaxies, quasars, stars, and calibrating blank sky patches selected over 2627 deg2 of this area, and tables of measured parameters from these data. The imaging data reach a depth of r ≈ 22.2 (95% completeness limit for point sources) and are photometrically and astrometrically calibrated to 2% rms and 100 mas rms per coordinate, respectively. The imaging data have all been processed through a new version of the SDSS imaging pipeline, in which the most important improvement since the last data release is fixing an error in the model fits to each object. The result is that model magnitudes are now a good proxy for point-spread function magnitudes for point sources, and Petrosian magnitudes for extended sources. The spectroscopy extends from 3800 to 9200 A at a resolution of 2000. The spectroscopic software now repairs a systematic error in the radial velocities of certain types of stars and has substantially improved spectrophotometry. All data included in the SDSS Early Data Release and First Data Release are reprocessed with the improved pipelines and included in the Second Data Release. Further characteristics of the data are described, as are the data products themselves and the tools for accessing them.

An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms

Abstract: Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.

Control of carrier density by self-assembled monolayers in organic field-effect transistors

Abstract: Organic thin-film transistors are attracting a great deal of attention due to the relatively high field-effect mobility in several organic materials. In these organic semiconductors, however, researchers have not established a reliable method of doping at a very low density level, although this has been crucial for the technological development of inorganic semiconductors. In the field-effect device structures, the conduction channel exists at the interface between organic thin films and SiO2 gate insulators. Here, we discuss a new technique that enables us to control the charge density in the channel by using organosilane self-assembled monolayers (SAMs) on SiO2 gate insulators. SAMs with fluorine and amino groups have been shown to accumulate holes and electrons, respectively, in the transistor channel: these properties are understood in terms of the effects of electric dipoles of the SAMs molecules, and weak charge transfer between organic films and SAMs.

Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis

Abstract: Costimulatory signals are required for activation of immune cells, but it is not known whether they contribute to other biological systems. The development and homeostasis of the skeletal system depend on the balance between bone formation and resorption. Receptor activator of NF-kappaB ligand (RANKL) regulates the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor (M-CSF). But it remains unclear how RANKL activates the calcium signals that lead to induction of nuclear factor of activated T cells c1, a key transcription factor for osteoclastogenesis. Here we show that mice lacking immunoreceptor tyrosine-based activation motif (ITAM)-harbouring adaptors, Fc receptor common gamma subunit (FcRgamma) and DNAX-activating protein (DAP)12, exhibit severe osteopetrosis owing to impaired osteoclast differentiation. In osteoclast precursor cells, FcRgamma and DAP12 associate with multiple immunoreceptors and activate calcium signalling through phospholipase Cgamma. Thus, ITAM-dependent costimulatory signals activated by multiple immunoreceptors are essential for the maintenance of bone homeostasis. These results reveal that RANKL and M-CSF are not sufficient to activate the signals required for osteoclastogenesis.

A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells

Abstract: The stability of c-Myc is regulated by multiple Ras effector pathways. Phosphorylation at Ser 62 stabilizes c-Myc, whereas subsequent phosphorylation at Thr 58 is required for its degradation. Here we show that Ser 62 is dephosphorylated by protein phosphatase 2A (PP2A) before ubiquitination of c-Myc, and that PP2A activity is regulated by the Pin1 prolyl isomerase. Furthermore, the absence of Pin1 or inhibition of PP2A stabilizes c-Myc. A stable c-Myc(T58A) mutant that cannot bind Pin1 or be dephosphorylated by PP2A replaces SV40 small T antigen in human cell transformation and tumorigenesis assays. Therefore, small T antigen, which inactivates PP2A, exerts its oncogenic potential by preventing dephosphorylation of c-Myc, resulting in c-Myc stabilization. Thus, Ras-dependent signalling cascades ensure transient and self-limiting accumulation of c-Myc, disruption of which contributes to human cell oncogenesis.

Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7.

Abstract: The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain. However, the turnover of c-Myc is largely dependent on phosphorylation of threonine-58 and serine-62 in MB1, residues that are often mutated in cancer. We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1. Whereas wild-type Fbw7 promoted c-Myc turnover in cells, an Fbw7 mutant lacking the F-box domain delayed it. Furthermore, depletion of Fbw7 by RNA interference increased both the abundance and transactivation activity of c-Myc. Accumulation of c-Myc was also apparent in mouse Fbw7−/− embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively.

Current-induced domain-wall switching in a ferromagnetic semiconductor structure

Abstract: Magnetic information storage relies on external magnetic fields to encode logical bits through magnetization reversal. But because the magnetic fields needed to operate ultradense storage devices are too high to generate, magnetization reversal by electrical currents is attracting much interest as a promising alternative encoding method. Indeed, spin-polarized currents can reverse the magnetization direction of nanometre-sized metallic structures through torque; however, the high current densities of 10(7)-10(8) A cm(-2) that are at present required exceed the threshold values tolerated by the metal interconnects of integrated circuits. Encoding magnetic information in metallic systems has also been achieved by manipulating the domain walls at the boundary between regions with different magnetization directions, but the approach again requires high current densities of about 10(7) A cm(-2). Here we demonstrate that, in a ferromagnetic semiconductor structure, magnetization reversal through domain-wall switching can be induced in the absence of a magnetic field using current pulses with densities below 10(5) A cm(-2). The slow switching speed and low ferromagnetic transition temperature of our current system are impractical. But provided these problems can be addressed, magnetic reversal through electric pulses with reduced current densities could provide a route to magnetic information storage applications.

Atomic-scale imaging of nanoengineered oxygen vacancy profiles in SrTiO3

Abstract: At the heart of modern oxide chemistry lies the recognition that beneficial (as well as deleterious) materials properties can be obtained by deliberate deviations of oxygen atom occupancy from the ideal stoichiometry. Conversely, the capability to control and confine oxygen vacancies will be important to realize the full potential of perovskite ferroelectric materials, varistors and field-effect devices. In transition metal oxides, oxygen vacancies are generally electron donors, and in strontium titanate (SrTiO3) thin films, oxygen vacancies (unlike impurity dopants) are particularly important because they tend to retain high carrier mobilities, even at high carrier densities. Here we report the successful fabrication, using a pulsed laser deposition technique, of SrTiO3 superlattice films with oxygen doping profiles that exhibit subnanometre abruptness. We profile the vacancy concentrations on an atomic scale using annular-dark-field electron microscopy and core-level spectroscopy, and demonstrate absolute detection sensitivities of one to four oxygen vacancies. Our findings open a pathway to the microscopic study of individual vacancies and their clustering, not only in oxides, but in crystalline materials more generally.

COPD in Japan : the Nippon COPD Epidemiology study

Abstract: Objectives: Despite high smoking rates, few prevalence studies of COPD have been performed in Asia. The Nippon COPD Epidemiology (NICE) Study used spirometry to measure prevalence of airflow limitation in Japanese adults. Methodology: Clinical, spirometric, and risk factor exposure data were collected on 2343 subjects aged ≥ 40 years who were demographically similar to the Japanese population. Airflow limitation was defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC < 70%). Results: Prevalence of airflow limitation was 10.9%. Based upon GOLD severity criteria, 56% of these cases were found to be mild, 38% moderate, 5% severe, and 1% very severe. Airflow limitation was significantly more prevalent in males than females (16.4% vs. 5.0%; P 70 years; P < 0.001). Of note, airflow limitation was also found in 5.8% of non-smokers and 4.6% of those younger than age 60 years. Only 9.4% of cases with airflow limitation reported a previous diagnosis of COPD. Conclusions: Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.

Atomic disorder effects on half-metallicity of the full-Heusler alloys Co 2 ( Cr 1 − x Fe x ) Al : A first-principles study

Abstract: We investigate the atomic disorder effects on the half-metallicity of the full-Heusler alloy ${\mathrm{Co}}_{2}({\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x})\mathrm{Al}$ from first principles by using the Korringa-Kohn-Rostoker method with the coherent potential approximation. Our results show that disorder between Cr and Al does not significantly reduce the spin polarization of the parent alloy ${\mathrm{Co}}_{2}\mathrm{CrAl},$ while disorder between Co and Cr makes a considerable reduction of the spin polarization. It is observed that the spin polarization of ${\mathrm{Co}}_{2}({\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x})\mathrm{Al}$ decreases with increasing Fe concentration x in both the ordered ${L2}_{1}$ and the disordered $B2$ structures, and that the effects of the disorder on the spin polarization is significant at low Fe concentrations. The results suggest that a highly spin-polarized ferromagnet with high Curie temperature will be obtained if a ${\mathrm{Co}}_{2}({\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x})\mathrm{Al}$ with the ordered ${L2}_{1}$ structure can be fabricated at low Fe concentrations.

Evidence for an Oscillatory Signature in Atmospheric Neutrino Oscillations

Abstract: Muon neutrino disappearance probability as a function of neutrino flight length $L$ over neutrino energy $E$ was studied. A dip in the $L/E$ distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed $L/E$ distribution constrained ${\ensuremath{ u}}_{\ensuremath{\mu}}\ensuremath{\leftrightarrow}{\ensuremath{ u}}_{\ensuremath{\tau}}$ neutrino oscillation parameters; $1.9\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}l\ensuremath{\Delta}{m}^{2}l3.0\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}\text{ }\text{ }{\mathrm{e}\mathrm{V}}^{2}$ and ${sin }^{2}2\ensuremath{\theta}g0.90$ at 90% confidence level.

Quantum magnetic excitations from stripes in copper oxide superconductors

Abstract: In the copper oxide parent compounds of the high-transition-temperature superconductors the valence electrons are localized--one per copper site--by strong intra-atomic Coulomb repulsion. A symptom of this localization is antiferromagnetism, where the spins of localized electrons alternate between up and down. Superconductivity appears when mobile 'holes' are doped into this insulating state, and it coexists with antiferromagnetic fluctuations. In one approach to describing the coexistence, the holes are believed to self-organize into 'stripes' that alternate with antiferromagnetic (insulating) regions within copper oxide planes, which would necessitate an unconventional mechanism of superconductivity. There is an apparent problem with this picture, however: measurements of magnetic excitations in superconducting YBa2Cu3O6+x near optimum doping are incompatible with the naive expectations for a material with stripes. Here we report neutron scattering measurements on stripe-ordered La1.875Ba0.125CuO4. We show that the measured excitations are, surprisingly, quite similar to those in YBa2Cu3O6+x (refs 9, 10) (that is, the predicted spectrum of magnetic excitations is wrong). We find instead that the observed spectrum can be understood within a stripe model by taking account of quantum excitations. Our results support the concept that stripe correlations are essential to high-transition-temperature superconductivity.

Intermolecular and supramolecular photoinduced electron transfer processes of fullerene–porphyrin/phthalocyanine systems

Abstract: The attainment of a better understanding of the dependence of photoinduced electron transfer reaction rates on the molecular structures of the donor and acceptor entities results in improving the capture and storage of solar energy. Here, the intermolecular and supramolecular electron transfer processes from electron donors (porphyrins (P), chlorophylls (Chl), phthalocyanines (Pc) and naphthalocyanines (Nc)) and their metal derivatives to electron acceptors (fullerenes such as C 60 and C 70 ) studied by nanosecond and picosecond laser flash photolysis techniques in polar and nonpolar solvents are reviewed. For intermolecular systems in polar solvents, photoinduced electron transfer takes place via the excited triplet states of C 60 /C 70 or via the excited triplet states of P/Pc/Nc, yielding solvated radical ions in polar solvents; thus, the back electron transfer rates are generally slow. In the case of the supramolecular dyads and triads formed by axial coordination, hydrogen bonding, crown ether complexation, or rotaxane formation, the photoinduced charge separation takes place mainly from the excited singlet state of the donor; however, the back electron transfer rates are generally quite fast. The relations between structures and photochemical reactivities of these novel supramolecular systems are discussed in relation to the efficiency of charge separation and charge recombination.

Infrared spectroscopic evidence for protonated water clusters forming nanoscale cages.

Abstract: Size-dependent development of the hydrogen bond network structure in largesized clusters of protonated water, H+(H2O)n (n = 4 to 27), was probed by infrared spectroscopy of OH stretches. Spectral changes with cluster size demonstrate that the chain structures at small sizes (n ≲ 10) develop into two-dimensional net structures (∼10

Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus.

Abstract: The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.

Ultra-stable nanoparticles of CdSe revealed from mass spectrometry

Abstract: Nanoparticles under a few nanometres in size have structures and material functions that differ from the bulk because of their distinct geometrical shapes and strong quantum confinement. These qualities could lead to unique device applications. Our mass spectral analysis of CdSe nanoparticles reveals that (CdSe)(33) and (CdSe)(34) are extremely stable: with a simple solution method, they grow in preference to any other chemical compositions to produce macroscopic quantities. First-principles calculations predict that these are puckered (CdSe)(28)-cages, with four- and six-membered rings based on the highly symmetric octahedral analogues of fullerenes, accommodating either (CdSe)(5) or (CdSe)(6) inside to form a three-dimensional network with essentially heteropolar sp(3)-bonding. This is in accordance with our X-ray and optical analyses. We have found similar mass spectra and atomic structures in CdS, CdTe, ZnS and ZnSe, demonstrating that mass-specified and macroscopically produced nanoparticles, which have been practically limited so far to elemental carbon, can now be extended to a vast variety of compound systems.

Self-assembly of a silica–surfactant nanocomposite in a porous alumina membrane

Abstract: A mesoporous membrane composed of nanochannels with a uniform diameter has a potential use for precise size-exclusive separation of molecules. Here, we report a novel method to form a hybrid membrane composed of silica-surfactant nanocomposite and a porous alumina membrane, by which size-selective transport of molecules across the membrane becomes possible. The nanocomposite formed inside each columnar alumina pore was an assembly of surfactant-templated silica-nanochannels with a channel diameter of 3.4 nm; the channel direction being predominantly oriented along the wall of the columnar alumina pore. Molecules could be transported across the membrane including the silica-surfactant nanocomposite with a capability of nanometre-order size-exclusive separation. Our proposed membrane system has a potential use not only for separation science, but also catalysis and chip technologies.

Role of Arginine in Protein Refolding, Solubilization, and Purification

Abstract: Recombinant proteins are often expressed in the form of insoluble inclusion bodies in bacteria. To facilitate refolding of recombinant proteins obtained from inclusion bodies, 0.1 to 1 M arginine is customarily included in solvents used for refolding the proteins by dialysis or dilution. In addition, arginine at higher concentrations, e.g., 0.5-2 M, can be used to extract active, folded proteins from insoluble pellets obtained after lysing Escherichia coli cells. Moreover, arginine increases the yield of proteins secreted to the periplasm, enhances elution of antibodies from Protein-A columns, and stabilizes proteins during storage. All these arginine effects are apparently due to suppression of protein aggregation. Little is known, however, about the mechanism. Various effects of solvent additives on proteins have been attributed to their preferential interaction with the protein, effects on surface tension, or effects on amino acid solubility. The suppression of protein aggregation by arginine cannot be readily explained by either surface tension effects or preferential interactions. In this review we show that interactions between the guanidinium group of arginine and tryptophan side chains may be responsible for suppression of protein aggregation by arginine.

Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation

Abstract: Imprinted genes are expressed from only one of the parental chromosomes and are marked epigenetically by DNA methylation and histone modifications1,2,3,4,5,6,7,8,9. The imprinting center 2 (IC2) on mouse distal chromosome 7 is flanked by several paternally repressed genes, with the more distant ones imprinted exclusively in the placenta. We found that most of these genes lack parent-specific DNA methylation, and genetic ablation of methylation does not lead to loss of their imprinting in the trophoblast (placenta). The silent paternal alleles of the genes are marked in the trophoblast by repressive histone modifications (dimethylation at Lys9 of histone H3 and trimethylation at Lys27 of histone H3), which are disrupted when IC2 is deleted, leading to reactivation of the paternal alleles. Thus, repressive histone methylation is recruited by IC2 (potentially through a noncoding antisense RNA) to the paternal chromosome in a region of at least 700 kb and maintains imprinting in this cluster in the placenta, independently of DNA methylation. We propose that an evolutionarily older imprinting mechanism limited to extraembryonic tissues was based on histone modifications, and that this mechanism was subsequently made more stable for use in embryonic lineages by the recruitment of DNA methylation.

Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase

Abstract: The cyclin-dependent kinase inhibitor p27(Kip1) is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCF(Skp2) is implicated in p27(Kip1) degradation, proteolysis of p27(Kip1) at the G0-G1 transition proceeds normally in Skp2(-/-) cells. Moreover, p27(Kip1) is exported from the nucleus to the cytoplasm at G0-G1 (refs 9-11). These data suggest the existence of a Skp2-independent pathway for the degradation of p27(Kip1) at G1 phase. We now describe a previously unidentified E3 complex: KPC (Kip1 ubiquitination-promoting complex), consisting of KPC1 and KPC2. KPC1 contains a RING-finger domain, and KPC2 contains a ubiquitin-like domain and two ubiquitin-associated domains. KPC interacts with and ubiquitinates p27(Kip1) and is localized to the cytoplasm. Overexpression of KPC promoted the degradation of p27(Kip1), whereas a dominant-negative mutant of KPC1 delayed p27(Kip1) degradation. The nuclear export of p27(Kip1) by CRM1 seems to be necessary for KPC-mediated proteolysis. Depletion of KPC1 by RNA interference also inhibited p27(Kip1) degradation. KPC thus probably controls degradation of p27(Kip1) in G1 phase after export of the latter from the nucleus.