Showing papers by "Hokkaido University published in 1998"
TL;DR: A structural basis for the hypothesis that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics is demonstrated.
Abstract: Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.
1,010 citations
TL;DR: It is demonstrated that hepatocyte growth factor/scatter factor is present in muscle, can be released upon injury, and has the ability to activate quiescent satellite cells in vivo.
697 citations
TL;DR: This article provided empirical support for the theory of trust that emhasizes the role of general trust (trust in others in general) in emancipating people from the confines of safe, but closed relationships.
Abstract: A theory of trust proposed by Yamagishi and Yamagishi provides the basis for the prediction that (1) social uncertainty promotes commitment formation between particular partners and (2) high trusters tend to form committed relations less frequently than would low trusters when facing social uncertainty. These predictions receive support in two experiments conducted in the United States and Japan. The findings provide empirical support for the theory of trust that emhasizes the role of general trust (trust in others in general) in emancipating people fromt the confines of safe, but closed relationships. The results also offer a theoretical explanation for what have been viewed in the past as cultural differences.
658 citations
TL;DR: The analysis of the antigenic and biological properties of the H5N1 influenza viruses isolated from chickens, ducks, and geese from farms and poultry markets in Hong Kong during 1997 and compares them with those of virus isolated from the index human case revealed limited antigenic drift in 15 years.
580 citations
TL;DR: In this paper, unique electrical, thermal, and chemical responses of polymer gels are described and recently observed frictional specificities of gels were also briefly introduced, showing that a polymer gel shows a variety of stimuli-responsive actions, responding to external environmental changes.
Abstract: A polymer gel is a soft and wet material capable of undergoing large deformation A deformed gel, in turn, changes its chemical potential, behaving as an energy transducer Thus, a polymer gel shows a variety of stimuli-responsive actions, responding to external environmental changes In this article unique electrical, thermal, and chemical responses of polymer gels are described Recently observed frictional specificities of gels are also briefly introduced
506 citations
TL;DR: A novel cadherin-related neuronal receptor (Cnr) gene family is found by studying Fyn-binding activity in mouse brain by finding the expression patterns of each member of this novel family were grossly similar to each other but restricted to subpopulations of neurons of the same type.
458 citations
TL;DR: Results indicate that the geometry of the interconnected porous structure in PPHAP and coral-HAP create spaces for vasculature that lead to osteogenesis while the smooth structure and close contact of particles in SPHAP inhibit vascular formation and proliferation of mesenchymal cells, preventing bone and cartilage formation.
Abstract: Bone morphogenetic protein (BMP) is known to require a suitable carrier to induce ectopic bone formation in vivo. Hydroxyapatite ceramics have been reported to be effective in some forms but ineffective in others as a carrier of BMP-induced bone formation. In this study we compare three geometrically different forms of hydroxyapatite to examine their functions as carriers of BMP-induced bone formation. A fraction containing all the active BMPs (BMP cocktail) was partially purified from a 4M guanidine extract from bovine bone by a three-step chromatographic procedure. The BMP cocktail was combined with each of three forms of hydroxyapatite--solid particles (SPHAP), porous particles (PPHAP), and coral-replicated porous tablets (coral-HAP)--and implanted subcutaneously into rats. Both the PPHAP and coral-HAP systems induced osteogenesis 2 weeks after implantation, as evidenced by morphological and biochemical observations. Details of the osteogenetic process were followed by double-fluorescence labeling in the coral-HAP system to confirm bone formation on the surface of hydroxyapatite. However, there was no evidence of osteogenesis or chondrogenesis in the SPHAP system. The results indicate that the geometry of the interconnected porous structure in PPHAP and coral-HAP create spaces for vasculature that lead to osteogenesis while the smooth structure and close contact of particles in SPHAP inhibit vascular formation and proliferation of mesenchymal cells, preventing bone and cartilage formation. It was concluded that the geometrical structure in hydroxyapatite ceramics that induces vasculature is crucial as a carrier for BMP-induced bone formation.
442 citations
TL;DR: Results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic Cerebellar damage after acute brain injury.
Abstract: To study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST-deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.
416 citations
TL;DR: It is demonstrated that a chlorophyll a oxygenase is involved inchlorophyll b formation and that an overlapping region of a nuclear genome was deleted in all mutants and that this encodes a protein whose sequence is similar to those of methyl monooxygenases.
Abstract: Chlorophyll b is an ubiquitous accessory pigment in land plants, green algae, and prochlorophytes. Its biosynthesis plays a key role in the adaptation to various light environments. We isolated six chlorophyll b-less mutants by insertional mutagenesis by using the nitrate reductase or argininosuccinate lyase genes as tags and examined the rearrangement of mutant genomes. We found that an overlapping region of a nuclear genome was deleted in all mutants and that this encodes a protein whose sequence is similar to those of methyl monooxygenases. This coding sequence also contains putative binding domains for a [2Fe-2S] Rieske center and for a mononuclear iron. The results demonstrate that a chlorophyll a oxygenase is involved in chlorophyll b formation. The reaction mechanism of chlorophyll b formation is discussed.
396 citations
TL;DR: The results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.
Abstract: Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid β protein (Aβ), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but Aβ negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.
366 citations
TL;DR: The findings suggest that target P300s are not influenced by the nontarget stimulus configuration, whereas the nontTarget P300 outcomes are determined directly by the stimulus context.
Abstract: P300 differences for target (.10), nontarget (.10), and standard tones (.80) were assessed using a three-stimulus oddball paradigm in which participants responded only to the target (n = 12). Target/standard (easy or difficult) and nontarget/standard (large or small) pitch differences were manipulated orthogonally. In all conditions, target tones elicited a parietal P300, which was affected only by the target/standard discrimination ease. Nontarget in the easy/large and difficult/small conditions elicited a parietal but smaller P300 than the target but in the easy/small condition elicited similar ERPs to the standard. However, nontarget stimuli in the difficult/large condition elicited an anterior maximum and earlier P300 (P3a) component. The findings suggest that target P300s are not influenced by the nontarget stimulus configuration, whereas the nontarget P300 outcomes are determined directly by the stimulus context. The theoretical implications are discussed.
TL;DR: Highly inert to ionic additions to aldehydes, aryl- and 1-alkenylboronic acids succumb to a catalytic variant mediated by a [Rh(acac)(CO)2 ]-diphosphane complex in aqueous phase at 80-95°C to yield secondary alcohols.
Abstract: Highly inert to ionic additions to aldehydes, aryl- and 1-alkenylboronic acids succumb to a catalytic variant mediated by a [Rh(acac)(CO)2]–diphosphane complex in aqueous phase at 80–95°C to yield secondary alcohols [Eq. (a)]. A key step in the catalytic cycle is the transmetalation between the boron reagent and the rhodium complex. Ln=diphosphane (e.g. 1,1′-bis(diphenylphosphanyl)ferrocene); R=aryl, 1-alkenyl; R′=alkyl, aryl; acac=acetylacetonate.
TL;DR: The results indicate that direct infection of epithelial cells by EBV may occur naturally in vivo, and this could be mediated by an unidentified, epithelium-specific binding receptor for EBV.
Abstract: We show clear evidence for direct infection of various human epithelial cells by Epstein-Barr virus (EBV) in vitro. The successful infection was achieved by using recombinant EBV (Akata strain) carrying a selective marker gene but without any other artificial operations, such as introduction of the known EBV receptor (CD21) gene or addition of polymeric immunoglobulin A against viral gp350 in culture. Of 21 human epithelial cell lines examined, 18 became infected by EBV, as ascertained by the detection of EBV-determined nuclear antigen (EBNA) 1 expression in the early period after virus exposure, and the following selection culture easily yielded a number of EBV-infected clones from 15 cell lines. None of the human fibroblasts and five nonhuman-derived cell lines examined was susceptible to the infection. By comparison, cocultivation with virus producers showed approximately 800-fold-higher efficiency of infection than cell-free infection did, suggesting the significance of direct cell-to-cell contact as a mode of virus spread in vivo. Most of the epithelial cell lines infectable with EBV were negative for CD21 expression at the protein and mRNA levels. The majority of EBV-infected clones established from each cell line invariably expressed EBNA1, EBV-encoded small RNAs, rightward transcripts from the BamHI-A region of the virus genome, and latent membrane protein (LMP) 2A, but not the other EBNAs or LMP1. This restricted form of latent viral gene expression, which is a central issue for understanding epithelial oncogenesis by EBV, resembled that seen in EBV-associated gastric carcinoma and LMP1-negative nasopharyngeal carcinoma. The results indicate that direct infection of epithelial cells by EBV may occur naturally in vivo, and this could be mediated by an unidentified, epithelium-specific binding receptor for EBV. The EBV convertants are viewed, at least in terms of viral gene expression, as in vitro analogs of EBV-associated epithelial tumor cells, thus facilitating analysis of an oncogenic role(s) for EBV in epithelial cells.
TL;DR: In this article, a two-dimensional micron-sized honeycomb structure was formed when a chloroform solution of an amphiphilic polymer was cast on solid surfaces at high atmospheric humidity.
TL;DR: Production of antigenic peptides that serve as MHC class I ligands is essential for initiation of cell‐mediated immunity, suggesting that modifications and renewal of pre‐existing non‐immune genes were instrumental in the emergence of adaptive immunity.
Abstract: Production of antigenic peptides that serve as MHC class I ligands is essential for initiation of cell-mediated immunity. Accumulating evidence indicates that the proteasome, a large multisubunit protein deg radative machine in eukaryotes, functions as a processing enzyme responsible for the generation of MHC class I ligands. This processing system is elaborately regulated by various immunomodulatory cytokines. In particular, interferon-gamma induces the formation of immunoproteasomes and a recently identified proteasomal regulatory factor. PA28, which in concert contribute to efficient production of MHC class I ligands. Many of the MHC-encoded genes including LMP appear to have emerged by an ancient chromosomal duplication, suggesting that modifications and renewal of pre-existing non-immune genes were instrumental in the emergence of adaptive immunity.
TL;DR: Kullback-Leibler discrimination information and the Chernoff information measure are developed for the multivariate non-Gaussian case for discrimination between different classes of multivariate time series.
Abstract: Minimum discrimination information provides a useful generalization of likelihood methodology for classification and clustering of multivariate time series. Discrimination between different classes of multivariate time series that can be characterized by differing covariance or spectral structures is of importance in applications occurring in the analysis of geophysical and medical time series data. For discrimination between such multivariate series, Kullback-Leibler discrimination information and the Chernoff information measure are developed for the multivariate non-Gaussian case. Asymptotic error rates and limiting distributions are given for a generalized spectral disparity measure that includes the foregoing criteria as special cases. Applications to problems of clustering and classifying earthquakes and mining explosions are given.
TL;DR: In this paper, the dispersion relations of the surface modes are calculated for circular cylinders of AlAs which form a square lattice in a GaAs matrix, and the folding and anisotropy of surface wave branches, as well as the existence of pseudosurface waves, are found.
Abstract: Acoustic waves localized at the surface of two-dimensional (2D) periodic elastic structures, or 2D phononic crystals, are studied theoretically by taking account of the elastic anisotropy of constituent materials. The surface considered is perpendicular to the axis of a periodic array of cylinders embedded in a background material. The dispersion relations of the surface modes are calculated for circular cylinders of AlAs which form a square lattice in a GaAs matrix. The folding and anisotropy of the surface wave branches, as well as the existence of pseudosurface waves, are found. The stop band distributions of the surface, pseudosurface, and bulk waves are plotted in a form relevant for comparison with ultrasound imaging experiments.
TL;DR: The selective scarcity of theseNMDA receptor subunits in the stratum lucidum suggests that a different synaptic targeting mechanism exerts within a single CA3 pyramidal neurone in vivo, which would explain contrasting significance of the NMDA receptor channel in LTP induction mechanisms between the mossy fibre‐CA3 synapse and other hippocampal synapses.
Abstract: Hippocampal synapses express two distinct forms of the long-term potentiation (LTP), i.e. NMDA receptor-dependent and -independent LTPs. To understand its molecular-anatomical basis, we produced affinity-purified antibodies against the GluRepsilon1 (NR2A), GluRepsilon2 (NR2B), and GluRzeta1 (NR1) subunits of the N-methyl-D-aspartate (NMDA) receptor channel, and determined their distributions in the mouse hippocampus. Using NMDA receptor subunit-deficient mice as the specificity controls, section pretreatment with proteases (pepsin and proteinase K) was found to be very effective to detect authentic NMDA receptor subunits. As the result of modified immunohistochemistry, all three subunits were detected at the highest level in the strata oriens and radiatum of the CA1 subfield, and high levels were also seen in most other neuropil layers of the CA1 and CA3 subfields and of the dentate gyrus. However, the stratum lucidum, a mossy fibre-recipient layer of the CA3 subfield, contained low levels of the GluRepsilon1 and GluRzeta1 subunits and almost excluded the GluRepsilon2 subunit. Double immunofluorescence with the AMPA receptor GluRalpha1 (GluR1 or GluR-A) subunit further demonstrated that the GluRepsilon1 subunit was colocalized in a subset, not all, of GluRalpha1-immunopositive structures in the stratum lucidum. Therefore, the selective scarcity of these NMDA receptor subunits in the stratum lucidum suggests that a different synaptic targeting mechanism exerts within a single CA3 pyramidal neurone in vivo, which would explain contrasting significance of the NMDA receptor channel in LTP induction mechanisms between the mossy fibre-CA3 synapse and other hippocampal synapses.
TL;DR: In this article, the potential-dependent reorientation of a water molecule, adsorption of sulfate, and interactions between water and sulfate on a highly ordered Au(111) electrode surface in sulfuric acid solutions have been investigated in situ as a function of applied potential by means of surface-enhanced infrared absorption spectroscopy.
Abstract: Potential-dependent reorientation of a water molecule, adsorption of sulfate, and interactions between water and sulfate on a highly ordered Au(111) electrode surface in sulfuric acid solutions have been investigated in situ as a function of applied potential by means of surface-enhanced infrared absorption spectroscopy. The spectrum of the water layer at the interface changes in both intensity and frequency as the applied potential changes due to the reorientation of water molecules. The orientations deduced from infrared spectra are in good agreement with the predictions made by molecular dynamics simulations at potentials below and around the potential of zero charge (pzc) of the electrode where sulfate adsorption is negligible. At potentials above the pzc, sulfate anion is adsorbed at 3-fold hollow sites on the (111) surface via three oxygen atoms. When the potential is increased and the fractional coverage of sulfate reaches to about one-half of full coverage, adsorbed sulfate anions start to form sh...
TL;DR: As segmental spinal instrumentation progresses from one level to three levels, the overall torsional and flexural rigidity of the system increases, however, segmental displacement at the site of simulated instability becomes more obvious.
Abstract: Study design An in vitro biomechanical analysis of three anterior instability patterns was performed using calf lumbosacral spines. Stiffness of the constructs was compared, and segmental motion analyses were performed. Objectives To clarify the factors that alter the stability of the spinal instrumentation and to evaluate the influence of instrumentation on the residual intact motion segments. Summary of background data Recently, many adverse effects have been reported in fusion augmented with rigid instrumentation. Only few reports are available regarding biomechanical effects of stability provided by spinal instrumentation and its effects on residual adjacent motion segments in the lumbar-lumbosacral spine. Methods Eighteen calf lumbosacral spine specimens were divided into three groups according to instability patterns--one-level, two-level, and three-level disc dissections. Six constructs were cyclically tested in rotation, flexion-extension, and lateral bending of intact spines, of destabilized spine, and of spines with four segmental posterior instrumentation systems used to extend the levels of instability (Cotrel-Dubousset compression hook and three transpedicular screw fixation systems). During each test, stiffness values and segmental displacements were measured. Results The rigidity of the instrumented construct increased as the fixation range became more extensive. Although application of the instrumentation effectively reduced the segmental motion of the destabilized vertebral level, the motion at the destabilized level tended to increase as the number of unstable vertebral levels increased, and the fixation range of the instrumentation became more extensive. Instrumented constructs produced higher segmental displacement values at the upper residual intact motion segment when compared with those of the intact spine. In contrast, the instrumented constructs decreased their segmental displacement values at the lower residual intact motion segment with higher magnitude of the translational (shear) motion taking place compared with the intact spine in flexion-extension and lateral bending. These changes in the motion pattern became more distinct as the fixation range became more extensive. Conclusions As segmental spinal instrumentation progresses from one level to three levels, the overall torsional and flexural rigidity of the system increases. However, segmental displacement at the site of simulated instability becomes more obvious. Application of segmental instrumentation changes the motion pattern of the residual intact motion segments, and the changes in the motion pattern become more distinct as the fixation range becomes more extensive and as the rigidity of the construct increases.
TL;DR: Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.
Abstract: Objective The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of subarachnoid hemorrhage was evaluated in a multicenter placebo-controlled double-blind clinical trial. Methods Patients who suffered aneurysmal subarachnoid hemorrhages of Hunt and Kosnik Grades II through IV at admission and were able to start drug treatment within 96 hours of the ictus were enrolled. Early surgery was performed whenever possible. Oral administration of ebselen granules suspended in water (150 mg, twice a day) or placebo was started immediately after admission and continued for 2 weeks. The major end points were the Glasgow Outcome Scale at 2 weeks, 1 month, and 3 months after the start of treatment. The incidence of delayed ischemic neurological deficits clinically diagnosed as resulting from vasospasm and the incidence and extent of low-density areas on postoperative computed tomographic scans were also studied as secondary outcome measures. Results Intent-to-treat analysis of the 286 patients enrolled in the trial (145 patients administered ebselen and 141 administered placebo) revealed that the incidence of clinically diagnosed delayed ischemic neurological deficits was unaltered. There were 52 (receiving ebselen) and 58 (receiving placebo) patients with delayed deficits; however, a significantly better outcome was observed after ebselen treatment than after placebo (P = 0.005, chi2 test). There was a corresponding decrease in the incidence and extent of low-density areas (P = 0.032, Wilcoxon rank sum test). Conclusion Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.
TL;DR: In this article, the carbonylative cross-coupling reaction of arylboronic acids with aryls electrophiles to yield unsymmetrical biaryl ketones was carried out in anisole at 80 °C in the presence of a palladium catalyst and a base.
Abstract: The carbonylative cross-coupling reaction of arylboronic acids with aryl electrophiles (ArI, ArBr, and ArOTf) to yield unsymmetrical biaryl ketones was carried out in anisole at 80 °C in the presence of a palladium catalyst and a base. The reaction selectively proceeded under an atmospheric pressure of carbon monoxide when PdCl2(PPh3)2 (3 mol %)/K2CO3 (3 equiv) were used for aryl iodides and PdCl2(dppf) (3 mol %)/K2CO3 (3 equiv)/KI (3 equiv) for the bromides or the triflates. The carbonylation of arylboronic acids with benzyl halides gave aryl benzyl ketones.
TL;DR: Examination of the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos suggests that xTAK1 and xTAB1 function in the BMP signal transduction pathway in xenopus embryos in a cooperative manner.
Abstract: Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.
TL;DR: A possible contribution of EGF to the pathophysiology of bronchial asthma, including airway remodeling, is suggested.
Abstract: Chronic airway inflammation, one of the pathophysiologic features of bronchial asthma, is suspected to be responsible for irreversible pathological changes of airways, called airway remodeling. To examine the mechanisms of airway remodeling in asthma, we investigated the expression of epidermal growth factor (EGF) and its receptor immunohistochemically in asthmatic human airways. Airway specimens from seven patients with asthma were obtained from autopsied and surgically resected lungs. Control specimens were obtained from lungs of eight subjects without asthma and other pulmonary complications at autopsy. We stained those specimens by the avidin-biotin-peroxidase complex (ABC) method with anti-human polyclonal EGF antibody and monoclonal EGF receptor antibodies. Three different portions of airways-large bronchi (about 1 cm in diameter), small bronchi (about 3 mm in diameter), and peripheral airways (less than 2 mm in diameter)-were examined. The thickness of the bronchial smooth muscle and basement membrane was significantly greater in the asthmatic airways than in controls. Clear immunoreactivities of EGF were widely observed on bronchial epithelium, glands, and smooth muscle in asthmatic airways. In the controls, the bronchial epithelium and the bronchial glands partially expressed faint EGF immunoreactivity. For the EGF receptor, clear immunoreactivities were also observed on bronchial epithelium, glands, smooth muscle, and basement membrane in asthmatic airways. In control airways, only part of the bronchial epithelium and smooth muscle weakly expressed EGF receptor immunoreactivity. These results suggest a possible contribution of EGF to the pathophysiology of bronchial asthma, including airway remodeling.
TL;DR: The authors examined available circum-Antarctic glacial history archives on land, related to developments after the Last Glacial Maximum (LGM), and concluded that Holocene environmental development in Antarctica differed from that in the Northern Hemisphere.
Abstract: This overview examines available circum-Antarctic glacial history archives on land, related to developments after the Last Glacial Maximum (LGM). It considers the glacial-stratigraphic and morphologic records and also biostratigraphical information from moss banks, lake sediments and penguin rookeries, with some reference to relevant glacial marine records. It is concluded that Holocene environmental development in Antarctica differed from that in the Northern Hemisphere. The initial deglaciation of the shelf areas surrounding Antarctica took place before 10 000 14C yrs before present(BP), and was controlled by rising global sea level. This was followed by the deglaciation of some presently ice-free inner shelf and land areas between 10 000 and 8000 yr BP. Continued deglaciation occurred gradually between 8000 yr BP and 5000 yr BP. Mid-Holocene glacial readvances are recorded from various sites around Antarctica. There are strong indications of a circum-Antarctic climate warmer than today 4700–2000 yr BP. The best dated records from the Antarctic Peninsula and coastal Victoria Land suggest climatic optimums there from 4000–3000 yr BP and 3600–2600 yr BP, respectively. Thereafter Neoglacial readvances are recorded. Relatively limited glacial expansions in Antarctica during the past few hundred years correlate with the Little Ice Age in the Northern Hemisphere.
TL;DR: It is suggested that the initial epigenetic changes in germ cells of male and female embryos are similar and the methylation status of both alleles of a number of loci in EG cells was similar to that of the paternal allele in normal somatic cells.
Abstract: Expression of imprinted genes is dependent on their parental origin. This is reflected in the heritable differential methylation of parental alleles. The gametic imprints are however reversible as they do not endure for more than one generation. To investigate if the epigenetic changes in male and female germ line are similar or not, we derived embryonic germ (EG) cells from primordial germ cells (PGCs) of day 11.5 and 12.5 male and female embryos. The results demonstrate that they have an equivalent epigenotype. First, chimeras made with EG cells derived from both male and female embryos showed comparable fetal overgrowth and skeletal abnormalities, which are similar to but less severe than those induced by androgenetic embryonic stem (ES) cells. Thus, EG cells derived from female embryos resemble androgenetic ES cells more than parthenogenetic cells. Furthermore, the methylation status of both alleles of a number of loci in EG cells was similar to that of the paternal allele in normal somatic cells. Hence, both alleles of Igf2r region 2, Peg1/Mest, Peg3, Nnat were consistently unmethylated in EG cells as well as in the primary embryonic fibroblasts (PEFs) rescued from chimeras. More strikingly, both alleles of p57kip2 that were also unmethylated in EG cells, underwent de novo methylation in PEFs to resemble a paternal allele in somatic cells. The exceptions were the H19 and Igf2 genes that retained the methylation pattern in PEFs as seen in normal somatic tissues. These studies suggest that the initial epigenetic changes in germ cells of male and female embryos are similar.
TL;DR: Ets‐1 and Ets‐2 provide the link connecting EGF stimuli with activation of uPA and 92 kDa type IV collagenase promoters and may contribute to invasion phenotypes.
Abstract: Urokinase plasminogen activator (uPA) has been associated with invasion and metastasis in breast cancer. The expression of uPA and 92 kDa type IV collagenase (gelatinase B/MMP-9) is regulated by growth factors, receptor-type tyrosine kinases and cytoplasmic oncoproteins. Here, we have identified transcriptional requirements for the induction of uPA and 92 kDa type IV collagenase by epidermal growth factor (EGF). EGF stimulates the motile and invasive activities specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of extracellular matrix-degrading proteases including type I collagenase/MMP-1, 92 kDa type IV collagenase/MMP-9, uPA and uPA receptor were induced. EGF also transiently stimulated expression of the transcription factors Ets-1 and Ets-2. Reporter transfection assays revealed the activation of uPA and MMP-9 collagenase promoters by EGF and the requirement of each of the composite Ets and AP-1 transcription factor binding sites for an EGF response. Most notably, transfections with the Ets-1 and Ets-2 expression vectors potentiated uPA and MMP-9 promoter activation in response to EGF. Mutation of the threonine 75 residue of chicken Ets-2 conserved in the Pointed group of the Ets family proteins abrogated the ability of Ets-2 to collaborate with EGF. Ets-1 and Ets-2 were highly expressed in invasive breast tumor cell lines. Our results suggest that Ets-1 and Ets-2 provide the link connecting EGF stimuli with activation of uPA and 92 kDa type IV collagenase promoters and may contribute to invasion phenotypes.