Cell death in the Schwann cell lineage and its regulation by neuregulin.

The development of Schwann cells, the myelin-forming glial cells of the vertebrate peripheral nervous system, involves a neonatal phase of proliferation in which cells migrate along and segregate newly formed axons. Withdrawal from the cell cycle, around postnatal days 2-4 in rodents, initiates terminal differentiation to the myelinating state. During this time, Schwann cell number is subject to stringent regulation such that within the first postnatal week, axons and myelinating Schwann cells attain the one-to-one relationship characteristic of the mature nerve. The mechanisms that underly this developmental control remain largely undefined. In this report, we examine the role of apoptosis in the determination of postnatal Schwann cell number. We find that Schwann cells isolated from postnatal day 3 rat sciatic nerve undergo apoptosis in vitro upon serum withdrawal and that Schwann cell death can be prevented by beta forms of neuregulin (NRG-beta) but not by fibroblast growth factor 2 or platelet-derived growth factors AA and BB. This NRG-beta-mediated Schwann cell survival is apparently transduced through an ErbB2/ErbB3 receptor heterodimer. We also provide evidence that postnatal Schwann cells undergo developmentally regulated apoptosis in vivo. Together with other recent findings, these results suggest that Schwann cell apoptosis may play an important role in peripheral nerve development and that Schwann cell survival may be regulated by access to axonally derived NRG.

Rfc5, a small subunit of replication factor C complex, couples DNA replication and mitosis in budding yeast.

The inhibition of DNA synthesis prevents mitotic entry through the action of the S phase checkpoint. In the yeast Saccharomyces cerevisiae, an essential protein kinase, Spk1/Mec2/Rad53/Sad1, controls the coupling of S phase to mitosis. In an attempt to identify genes that genetically interact with Spk1, we have isolated a temperature-sensitive mutation, rfc5-1, that can be suppressed by overexpression of SPK1. The RFC5 gene encodes a small subunit of replication factor C complex. At the restrictive temperature, rfc5-1 mutant cells entered mitosis with unevenly separated or fragmented chromosomes, resulting in loss of viability. Thus, the rfc5 mutation defective for DNA replication is also impaired in the S phase checkpoint. Overexpression of POL30, which encodes the proliferating cell nuclear antigen, suppressed the replication defect of the rfc5 mutant but not its checkpoint defect. Taken together, these results suggested that replication factor C has a direct role in sensing the state of DNA replication and transmitting the signal to the checkpoint machinery.

G1 arrest and down-regulation of cyclin E/cyclin-dependent kinase 2 by the protein kinase inhibitor staurosporine are dependent on the retinoblastoma protein in the bladder carcinoma cell line 5637.

The protein kinase inhibitor staurosporine has been shown to induce G1 phase arrest in normal cells but not in most transformed cells. Staurosporine did not induce G1 phase arrest in the bladder carcinoma cell line 5637 that lacks a functional retinoblastoma protein (pRB-). However, when infected with a pRB-expressing retrovirus [Goodrich, D. W., Chen, Y., Scully, P. & Lee, W.-H. (1992) Cancer Res. 52, 1968-1973], these cells, now pRB+, were arrested by staurosporine in G1 phase. This arrest was accompanied by the accumulation of hypophosphorylated pRB. In both the pRB+ and pRB- cells, cyclin D1-associated kinase activities were reduced on staurosporine treatment. In contrast, cyclin-dependent kinase (CDK) 2 and cyclin E/CDK2 activities were inhibited only in pRB+ cells. Staurosporine treatment did not cause reductions in the protein levels of CDK4, cyclin D1, CDK2, or cyclin E. The CDK inhibitor proteins p21(Waf1/Cip1) and p27 (Kip1) levels increased in staurosporine-treated cells. Immunoprecipitation of CDK2, cyclin E, and p2l from staurosporine-treated pRB+ cells revealed a 2.5- to 3-fold higher ratio of p2l bound to CDK2 compared with staurosporine-treated pRB- cells. In pRB+ cells, p2l was preferentially associated with Thrl6O phosphorylated active CDK2. In pRB- cells, however, p2l was bound preferentially to the unphosphorylated, inactive form of CDK2 even though the phosphorylated form was abundant. This is the first evidence suggesting that G1 arrest by 4 nM staurosporine is dependent on a functional pRB protein. Cell cycle arrest at the pRB- dependent checkpoint may prevent activation of cyclin E/CDK2 by stabilizing its interaction with inhibitor proteins p2l and p27.

Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America.

The silver-haired bat variant of rabies virus (SHBRV) has been identified as the etiological agent of a number of recent human rabies cases in the United States that are unusual in not having been associated with any known history of conventional exposure. Comparison of the different biological and biochemical properties of isolates of this virus with those of a coyote street rabies virus (COSRV) revealed that there are unique features associated with SHBRV. In vitro studies showed that, while the susceptibility of neuroblastoma cells to infection by both viruses was similar, the infectivity of SHBRV was much higher than that of COSRV in fibroblasts (BHK-21) and epithelial cells (MA-104), particularly when these cells were kept at 34 degrees C. At this temperature, low pH-dependent fusion and cell-to-cell spread of virus is seen in BHK-21 cells infected with SHBRV but not with COSRV. It appears that SHBRV may possess an unique cellular tropism and the ability to replicate at lower temperature, allowing a more effective local replication in the dermis. This hypothesis is supported by in vivo results which showed that while SHBRV is less neurovirulent than COSRV when administered via the intramuscular or intranasal routes, both viruses are equally neuroinvasive if injected intracranially or intradermally. Consistent with the above findings, the amino acid sequences of the glycoproteins of SHBRV and COSRV were found to have substantial differences, particularly in the region that contains the putative toxic loop, which are reflected in marked differences in their antigenic composition. Nevertheless, an experimental rabies vaccine based on the Pittman Moore vaccine strain protected mice equally well from lethal doses of SHBRV and COSRV, suggesting that currently used vaccines should be effective in the postexposure prophylaxis of rabies due to SHBRV.

Object-related activity revealed by functional magnetic resonance imaging in human occipital cortex.

The stages of integration leading from local feature analysis to object recognition were explored in human visual cortex by using the technique of functional magnetic resonance imaging. Here we report evidence for object-related activation. Such activation was located at the lateral-posterior aspect of the occipital lobe, just abutting the posterior aspect of the motion-sensitive area MT/V5, in a region termed the lateral occipital complex (LO). LO showed preferential activation to images of objects, compared to a wide range of texture patterns. This activation was not caused by a global difference in the Fourier spatial frequency content of objects versus texture images, since object images produced enhanced LO activation compared to textures matched in power spectra but randomized in phase. The preferential activation to objects also could not be explained by different patterns of eye movements: similar levels of activation were observed when subjects fixated on the objects and when they scanned the objects with their eyes. Additional manipulations such as spatial frequency filtering and a 4-fold change in visual size did not affect LO activation. These results suggest that the enhanced responses to objects were not a manifestation of low-level visual processing. A striking demonstration that activity in LO is uniquely correlated to object detectability was produced by the "Lincoln" illusion, in which blurring of objects digitized into large blocks paradoxically increases their recognizability. Such blurring led to significant enhancement of LO activation. Despite the preferential activation to objects, LO did not seem to be involved in the final, "semantic," stages of the recognition process. Thus, objects varying widely in their recognizability (e.g., famous faces, common objects, and unfamiliar three-dimensional abstract sculptures) activated it to a similar degree. These results are thus evidence for an intermediate link in the chain of processing stages leading to object recognition in human visual cortex.

Fermi-edge singularities in linear and nonlinear ultrafast spectroscopy

We discuss Fermi-edge singularity effects on the linear and nonlinear transient response of an electron gas in a doped semiconductor. We use a bosonization scheme to describe the low-energy excitations, which allows us to compute the time and temperature dependence of the response functions. Coherent control of the energy absorption at resonance is analyzed in the linear regime. It is shown that a phase shift appears in the coherent control oscillations, which is not present in the excitonic case. The nonlinear response is calculated analytically and used to predict that four wave-mixing experiments would present a Fermi-edge singularity when the exciting energy is varied. A new dephasing mechanism is predicted in doped samples that depends linearly on temperature and is produced by the low-energy bosonic excitations in the conduction band.

Isotopic study of ceria-catalyzed soot oxidation in the presence of NOx

The ceria-catalyzed soot oxidation mechanism has been studied by a pulse technique with labeled O2 in the absence and presence of NO, using ceria–soot mixtures prepared in the loose contact mode. In the absence of soot, the ceria-catalyzed oxidation of NO to NO2 takes place with ceria oxygen and not with gas-phase O2. However, the oxygen exchange process between gas-phase O2 and ceria oxygen (to yield back O2, but with oxygen atoms coming from ceria) prevailed with regard to the ceria-catalyzed oxidation of NO to NO2. Gas-phase O2 did not react directly with soot when pulsed to a soot–ceria loose contact mixture. Instead, ceria oxygen is transferred to soot (this step does not require gas-phase molecular oxygen to be present), and gas-phase O2 fills up the vacancies created on the oxide in a further step. The transfer of oxygen between ceria and soot occurred directly in the absence of NO. However, in the presence of NO, NO2 is expected to be additionally generated by ceria oxygen oxidation, which also reacts with soot. The main reaction products of the ceria-catalyzed soot oxidation reaction with NO/O2 were CO2 and NO. Additionally, evidence of the reduction of NOx to N2 was found.

A catalogue of books [donated by Jasper Mauduit] in the library of Harvard College [at]: Cambridge in New England, 1765

This leatherbound volume lists books donated to the Harvard College Library by Jasper Mauduit, who served as an agent in London on behalf of the Province of the Massachusetts Bay. Entries are arranged alphabetically and by format; i.e. the first page lists all folios whose author, title, or keyword begin with "A," the next page lists all quartos beginning with "A," and the following page lists all "octavo &ca" volumes beginning with "A." The volume continues in a similar manner for each letter of the alphabet. Following a devastating fire in 1764 which destroyed most of the books in the Harvard College Library, Mauduit donated books, as well as money for the purchase of books, to the College. He also acted as an agent of the Society for Propagating the Gospel in New England and Parts Adjacent, using the £300 they donated for the rebuilding of the College library to select and purchase a large number of books. It is not known if the books listed in this catalog are those donated by Mauduit himself, or if they are the donations he purchased on behalf of the Society. The creator of this volume is unknown; although all entries are made in the same hand, the identity of the writer has not been determined. The label attached to the front cover, which refers to the Lime Street address of Mauduit's business in London, suggests that the list might have been prepared by Mauduit himself.

Meeting Competition: Why it is not an Abuse under Article 82. Research Papers in Law, 3/2004.

Introduction. Meeting competition occurs when an undertaking lowers its prices in response to the entry of a competitor. Despite accepting that meeting competition can be compatible with Article 82, the Commission2 and the Court of justice3 have repeatedly condemned the practice due to the modalities of implementation or “particular circumstances”.4 However, existing precedent on the subject remains obscurely reasoned and contradictory, such that it is at the present time impossible to give clear advice to undertakings on the circumstances in which meeting competition is compatible with Article 82. Not only is such legal uncertainty in itself damaging but, in so far as it discourages meeting competition, it appears to us to be harmful to competition. As concerns the latter point, it will be seen that some of the most powerful arguments against prohibiting meeting competition are based on the counterproductive nature of the remedies. The present article does not, however, aim to propose a simple solution to distinguish abusive and non-abusive meeting competition.5 Nor does the article aim to give a comprehensive overview of the existing case law in this area.6 Instead, it takes a more economic approach and aims to lay out in a (brief but) systematic fashion the competitive concerns that might potentially be raised by the practice of meeting competition and in doing so to try to identify the main flaws in the Court and Commission’s approach.

Déficience dans la réparation par excision de nucléotides en phase S induite par la séquestration du facteur de réplication RPA

Introduction Les lésions induites par les rayons UV peuvent causer des blocages dans la réplication de l'ADN. Ces dommages sont éliminés par le processus moléculaire très conservé de réparation par excision de nucléotides (NER). Nous avons précédemment démontré que la protéine ATR, une kinase majeure impliquée dans le stress réplicatif, est requise pour une NER efficace, et ce exclusivement durant la phase S. Des résultats subséquents ont suggéré que ce prérequis n’était pas lié à la réponse induite par ATR, mais plutôt d’une conséquence globale causée par la présence de stress réplicatif. En ce sens, nous mettons l’emphase qu’après irradiation UV, le complexe RPA joue un rôle crucial dans l'activation des mécanismes de NER ainsi que dans le redémarrage des fourches de réplication bloquées. Hypothèses: En général, les mutations qui confèrent une augmentation du stress réplicatif engendrent une séquestration excessive du facteur RPA aux fourches de réplication bloquées ce qui réduit son accessibilité pour le NER. Méthodes et résultats: Le modèle de la levure a été choisi pour vérifier cette hypothèse. Nous avons développé un essai de NER spécifique à chacune des phases du cycle cellulaire pour démontrer que les cellules déficientes en Mec1, l’homologue d’ATR, sont défectives dans la réparation par excision de nucléotides spécifiquement en phase S. De plus, plusieurs autres mutants de levure, caractérisés par un niveau de dommages spontanés élevé, ont aussi exhibé un défaut similaire. Ces mutants ont démontré une fréquence et une intensité de formation de foyers de RPA plus élevée. Finalement, une diminution partielle de RPA dans les levures a induit un défaut significatif dans le NER spécifiquement durant la phase S. Conclusion: Nos résultats supportent la notion que la séquestration de RPA aux fourches de réplication endommagées durant la phase S prévient son utilisation pour la réparation par excision de nucléotides ce qui inhibe fortement l'efficacité de réparation. Cette étude chez la levure facilite l’élucidation du phénomène analogue chez l’humain et, ultimement, comprend des implications majeures dans la compréhension du mécanisme de développement des cancers UV-dépendants.

Weishenme Zhongguo zai diyi ci shijie dazhan zhong juyou zhongyao zuoyong 为什么中国在第一次世界大战中具有重要作用 (Why China Played an Important Role in the First World War)

Aufbauend auf dem analytischen Tool des Totalen Krieges (vgl. den Artikel des Autors zu Controversy Total War in 1914-1918-Online) werden im vorliegenden Beitrag die Anstrengungen Chinas im Ersten Weltkrieg zu denjenigen anderer nicht europäischer Länder wie Australien, Südafrika oder Indien in Bezug gesetzt. Dabei wird das Ziel verfolgt, den globalen Charakter eines Konfliktes deutlich zu machen, der zurecht als erster Weltkrieg bezeichnet wird und in welchem China sicherlich eine weit bedeutsamere Rolle spielte, als es gemeinhin in der Historiographie dargestellt wird. Ursprünglich wurde der Beitrag als Antwort auf die Frage konzipiert, warum nicht nur China für eine Globalgeschichte des Ersten Weltkrieges von Bedeutung war. Im Verlauf der Übersetzung wurde der Titel dahingehend angepasst, dass stärker die Bedeutung von Chinas Rolle im Ersten Weltkrieg betont wurde.

Endosymbiotic bacteria in honey bees: Arsenophonus spp. are not transmitted transovarially

Intracellular endosymbiotic bacteria are common and can play a crucial role for insect pathology. Therefore, such bacteria could be a potential key to our understanding of major losses of Western honey bees (Apis mellifera) colonies. However, the transmission and potential effects of endosymbiotic bacteria in A. mellifera and other Apis spp. are poorly understood. Here, we explore the prevalence and transmission of the genera Arsenophonus, Wolbachia, Spiroplasma and Rickettsia in Apis spp. Colonies of A. mellifera (N = 33, with 20 eggs from worker brood cells and 100 adult workers each) as well as mated honey bee queens of A. cerana, A. dorsata and A. florea (N = 12 each) were screened using PCR. While Wolbachia, Spiroplasma and Rickettsia were not detected, Arsenophonus spp. were found in 24.2% of A. mellifera colonies and respective queens as well as in queens of A. dorsata (8.3%) and A. florea (8.3%), but not in A. cerana. The absence of Arsenophonus spp. from reproductive organs of A. mellifera queens and surface-sterilized eggs does not support transovarial vertical transmission. Instead, horizontal transmission is most likely.

Mineralogy of ODP Hole 117-722B (Appendix)

Bulk mineralogy of the terrigenous fraction of 99 samples from ODP Site 722 on the Owen Ridge, western Arabian Sea, has been determined by x-ray diffraction, using an internal standard method. The sampling interval, approximately 4.3 k.y., provides a detailed mineralogic record for the past 500 k.y. Previous studies have identified important modern continental sediment sources and the mineral assemblages presently derived from each. These studies have also demonstrated that most of this material is supplied by southwest and northwest winds during the summer monsoon. A variety of marine and terrestrial records and general circulation model (GCM) simulations have indicated the importance of monsoonal circulation during the Pleistocene and Holocene and have demonstrated increased aridity during glacial times and increased humidity during inter glacials. The mineralogic data generated here were used to investigate variations in source area weathering conditions during these environmental changes. Terrigenous minerals present include smectite, illite, palygorskite, kaolinite, chlorite, quartz, plagioclase feldspar, and dolomite. This mineralogy is consistent with the compositions of source areas presently supplying sediment to the Arabian Sea. An R-mode factor analysis has identified four mineral assemblages present throughout the past 500 k.y.: quartz/chlorite/dolomite (Factor 1), kaolinite/plagioclase/illite (Factor 2), smectite (Factor 3), and palygorskite/dolomite (Factor 4). Chlorite, illite, and palygorskite are extremely susceptible to chemical weathering, and a spectral comparison of these factors with the eolian mass accumulation rate (MAR) record from Hole 722B (an index of dust source area aridity) indicates that Factors 1, 2, and 4 are directly related to changes in aridity. Because of these characteristics, Factors 1,2, and 4 are interpreted to originate from arid source regions. Factor 3 is interpreted to record more humid source conditions. Time-series of scores for the four factors are dominated by short-term (10-100 k.y.) variability, and do not correlate well to glacial/interglacial fluctuations in the time domain. These characteristics suggest that local climatic shifts were complex, and that equilibrium weathering assemblages did not develop immediately after climatic change. Spectral analysis of factor scores identifies peaks at or near the primary Milankovitch frequencies for all factors. Factor 1 (quartz/chlorite/dolomite), Factor 2 (kaolinite/plagioclase/illite), and Factor 4 (illite/palygorskite) are coherent and in phase with the MAR record over the 23, 41, and 100 k.y. bands, respectively. The reasons for coherency at single Milankovitch frequencies are not known, but may include differences in the susceptibilities of minerals to varying time scales of weathering and/or preferential development of suitable continental source environments by climatic changes at the various Milankovitch frequencies.

230Th, 231Pa, and 10Be in particle size fractions of an opal-rich sediment of the Atlantic Southern Ocean

This study centers on the question: How sensitive are 231Pa/230Th and 10Be/230Th to sediment composition and redistribution? The natural radionuclides 231Pa, 230Th and 10Be recorded in deep sea sediments are tracers for water mass advection and particle fluxes. We investigate the influence of oceanic particle composition on the element adsorption in order to improve our understanding of sedimentary isotope records. We present new data on particle size specific 231Pa and 10Be concentrations. An additional separation step, based on settling velocities, led to the isolation of a very opal-rich phase. We find that opal-rich particles contain the highest 231Pa and 10Be concentrations, and higher 231Pa/230Th and 10Be/230Th isotope ratios than opal-poor particles. The fractionation relative to 230Th induced by the adsorption to opal-rich particles is more pronounced for 231Pa than for 10Be. We conclude that bulk 231Pa/230Th in Southern Ocean sediments is most suitable as a proxy for past opal fluxes. The comparison between two neighboring cores with rapid and slow accumulation rates reveals that these isotope ratios are not influenced significantly by the intensity of sediment focusing at these two study sites. However, a simulation shows that particle sorting by selective removal of sediment (winnowing) could change the isotope ratios. Consequently, 231Pa/230Th should not be used as paleocirculation proxy in cases where a strong loss of opal-rich material due to bottom currents occurred.

A history of military government in newly acquired territory of the United States ...

Published also as Studies in history, economics and public law, vol. 20, no. 2.