bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased efficiency of oligonucleotide-mediated gene repair through slowing replication fork progression
Authors: Wu Xue-Song , Xin Li , Yin Wen-Xuan , Shang Xi-Ying , Lu Lu , Watt Rory M. , Cheah Kathryn S. E. , Huang Jian-Dong , Liu De-Pei , Liang Chih-Chuan
Published: February 2005

Targeted gene modification mediated by single-stranded oligonucleotides (SSOs) holds great potential for widespread use in a number of biological and biomedical fields, including functional genomics and gene therapy. By using this approach, specific genetic changes have been created in a number of prokaryotic and eukaryotic systems. In mammalian cells, the precise mechanism of SSO-mediated chromosome alteration remains to be established, and there have been problems in obtaining reproducible targeting efficiencies. It has previously been suggested that the chromatin structure, which changes throughout the cell cycle, may be a key factor underlying these variations in efficiency. This hypothesis prompted us to systematically investigate SSO-mediated gene repair at various phases of the cell cycle in a mammalian cell line. We found that the efficiency of SSO-mediated gene repair was elevated by ≈10-fold in thymidine-treated S-phase cells. The increase in repair frequency correlated positively with the duration of SSO/thymidine coincubation with host cells after transfection. We supply evidence suggesting that these increased repair frequencies arise from a thymidine-induced slowdown of replication fork progression. Our studies provide fresh insight into the mechanism of SSO-mediated gene repair in mammalian cells and demonstrate how its efficiency may be reliably and substantially increased.
Indirect reciprocity, image scoring, and moral hazard
Authors: Brandt Hannelore , Sigmund Karl
Published: February 2005

Whether one-shot interactions can stably sustain mutual cooperation if they are based on a minimal form of reputation building has been the subject of considerable debate. We show by mathematical modeling that the answer is positive if we assume an individual's social network evolves in time. In this case, a stable mixture of discriminating and undiscriminating altruists can be proof against invasion by defectors. This sheds light on current discussions about the merits of different types of moral assessment, an issue where theoretical arguments and experimental findings seem at odds.Unexpectedly, our approach also relates to the proverbial observation that people tend to become more tightfisted with age.
Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease
Authors: Georganopoulou Dimitra G. , Chang Lei , Nam Jwa-Min , Thaxton C. Shad , Mufson Elliott J. , Klein William L. , Mirkin Chad A.
Published: February 2005

The recently developed ultrasensitive bio-barcode assay was used to measure the concentration of amyloid-β-derived diffusible ligands (ADDLs), a potential soluble pathogenic Alzheimer's disease (AD) marker, in the cerebrospinal fluid (CSF) of 30 individuals. ADDL concentrations for the subjects diagnosed with AD were consistently higher than the levels in the CSF taken from nondemented age-matched controls. Studies of ADDLs or for any other potential pathogenic AD markers in CSF have not been possible because of their low concentration in CSF (<1 pM). This study is a step toward a diagnostic tool, based on soluble pathogenic markers for the debilitating disease.
Profiling early infection responses:Pseudomonas aeruginosaeludes host defenses by suppressing antimicrobial peptide gene expression
Authors: Apidianakis Yiorgos , Mindrinos Michael N. , Xiao Wenzhong , Lau Gee W. , Baldini Regina L. , Davis Ronald W. , Rahme Laurence G.
Published: February 2005

Insights into the host factors and mechanisms mediating the primary host responses after pathogen presentation remain limited, due in part to the complexity and genetic intractability of host systems. Here, we employ the modelDrosophila melanogasterto dissect and identify early host responses that function in the initiation and progression ofPseudomonas aeruginosapathogenesis. First, we use immune potentiation and genetic studies to demonstrate that flies mount a heightened defense against the highly virulentP. aeruginosastrain PA14 when first inoculated with strain CF5, which is avirulent in flies; this effect is mediated via the Imd and Toll signaling pathways. Second, we use whole-genome expression profiling to assess and compare theDrosophilaearly defense responses triggered by the PA14 vs. CF5 strains to identify genes whose expression patterns are different in susceptible vs. resistant host–pathogen interactions, respectively. Our results identify pathogenesis- and defense-specific genes and uncover a previously undescribed mechanism used byP. aeruginosain the initial stages of its host interaction: suppression ofDrosophiladefense responses by limiting antimicrobial peptide gene expression. These results provide insights into the genetic factors that mediate or restrict pathogenesis during the early stages of the bacterial–host interaction to advance our understanding ofP. aeruginosa-human infections.
Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human
Authors: Song Huai-Dong , Tu Chang-Chun , Zhang Guo-Wei , Wang Sheng-Yue , Zheng Kui , Lei Lian-Cheng , Chen Qiu-Xia , Gao Yu-Wei , Zhou Hui-Qiong , Xiang Hua , Zheng Hua-Jun , Chern Shur-Wern Wang , Cheng Feng , Pan Chun-Ming , Xuan Hua , Chen Sai-Juan , Luo Hui-Ming , Zhou Duan-Hua , Liu Yu-Fei , He Jian-Feng , Qin Peng-Zhe , Li Ling-Hui , Ren Yu-Qi , Liang Wen-Jia , Yu Ye-Dong , Anderson Larry , Wang Ming , Xu Rui-Heng , Wu Xin-Wei , Zheng Huan-Ying , Chen Jin-Ding , Liang Guodong , Gao Yang , Liao Ming , Fang Ling , Jiang Li-Yun , Li Hui , Chen Fang , Di Biao , He Li-Juan , Lin Jin-Yan , Tong Suxiang , Kong Xiangang , Du Lin , Hao Pei , Tang Hua , Bernini Andrea , Yu Xiao-Jing , Spiga Ottavia , Guo Zong-Ming , Pan Hai-Yan , He Wei-Zhong , Manuguerra Jean-Claude , Fontanet Arnaud , Danchin Antoine , Niccolai Neri , Li Yi-Xue , Wu Chung-I , Zhao Guo-Ping
Published: February 2005

The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the
Spike
gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.
TGF-β and the Smad Signaling Pathway Support Transcriptomic Reprogramming during Epithelial-Mesenchymal Cell Transition
Authors: Valcourt Ulrich , Kowanetz Marcin , Niimi Hideki , Heldin Carl-Henrik , Moustakas Aristidis
Published: February 2005

Epithelial-mesenchymal transition (EMT) contributes to normal tissue patterning and carcinoma invasiveness. We show that transforming growth factor (TGF)-β/activin members, but not bone morphogenetic protein (BMP) members, can induce EMT in normal human and mouse epithelial cells. EMT correlates with the ability of these ligands to induce growth arrest. Ectopic expression of all type I receptors of the TGF-β superfamily establishes that TGF-β but not BMP pathways can elicit EMT. Ectopic Smad2 or Smad3 together with Smad4 enhanced, whereas dominant-negative forms of Smad2, Smad3, or Smad4, and wild-type inhibitory Smad7, blocked TGF-β–induced EMT. Transcriptomic analysis of EMT kinetics identified novel TGF-β target genes with ligand-specific responses. Using a TGF-β type I receptor that cannot activate Smads nor induce EMT, we found that Smad signaling is critical for regulation of all tested gene targets during EMT. One such gene, Id2, whose expression is repressed by TGF-β1 but induced by BMP-7 is critical for regulation of at least one important myoepithelial marker, α-smooth muscle actin, during EMT. Thus, based on ligand-specific responsiveness and evolutionary conservation of the gene expression patterns, we begin deciphering a genetic network downstream of TGF-β and predict functional links to the control of cell proliferation and EMT.
From Sorting Endosomes to Exocytosis: Association of Rab4 and Rab11 GTPases with the Fc Receptor, FcRn, during Recycling
Authors: Ward E. Sally , Martinez Cruz , Vaccaro Carlos , Zhou Jinchun , Tang Qing , Ober Raimund J.
Published: February 2005

A longstanding question in cell biology is how is the routing of intracellular organelles within cells regulated? Although data support the involvement of Rab4 and Rab11 GTPases in the recycling pathway, the function of Rab11 in particular is uncertain. Here we have analyzed the association of these two Rab GTPases with the Fc receptor, FcRn, during intracellular trafficking. This Fc receptor is both functionally and structurally distinct from the classical Fcγ receptors and transports immunoglobulin G (IgG) within cells. FcRn is therefore a recycling receptor that sorts bound IgG from unbound IgG in sorting endosomes. In the current study we have used dual color total internal reflection fluorescence microscopy (TIRFM) and wide-field imaging of live cells to analyze the events in human endothelial cells that are involved in the trafficking of FcRn positive (FcRn+) recycling compartments from sorting endosomes to exocytic sites at the plasma membrane. Our data are consistent with the following model for this pathway: FcRn leaves sorting endosomes in Rab4+Rab11+or Rab11+compartments. For Rab4+Rab11+compartments, Rab4 depletion occurs by segregation of the two Rab proteins into discrete domains that can separate. The Rab11+FcRn+vesicle or tubule subsequently fuses with the plasma membrane in an exocytic event. In contrast to Rab11, Rab4 is not involved in exocytosis.
Rab11 in Recycling Endosomes Regulates the Sorting and Basolateral Transport of E-Cadherin
Authors: Lock John G. , Stow Jennifer L.
Published: February 2005

E-cadherin plays an essential role in cell polarity and cell-cell adhesion; however, the pathway for delivery of E-cadherin to the basolateral membrane of epithelial cells has not been fully characterized. We first traced the post-Golgi, exocytic transport of GFP-tagged E-cadherin (Ecad-GFP) in unpolarized cells. In live cells, Ecad-GFP was found to exit the Golgi complex in pleiomorphic tubulovesicular carriers, which, instead of moving directly to the cell surface, most frequently fused with an intermediate compartment, subsequently identified as a Rab11-positive recycling endosome. In MDCK cells, basolateral targeting of E-cadherin relies on a dileucine motif. Both E-cadherin and a targeting mutant, ΔS1-E-cadherin, colocalized with Rab11 and fused with the recycling endosome before diverging to basolateral or apical membranes, respectively. In polarized and unpolarized cells, coexpression of Rab11 mutants disrupted the cell surface delivery of E-cadherin and caused its mistargeting to the apical membrane, whereas apical ΔS1-E-cadherin was unaffected. We thus demonstrate a novel pathway for Rab11 dependent, dileucine-mediated, μ1B-independent sorting and basolateral trafficking, exemplified by E-cadherin. The recycling endosome is identified as an intermediate compartment for the post-Golgi trafficking and exocytosis of E-cadherin, with a potentially important role in establishing and maintaining cadherin-based adhesion.
Meiotic S-Phase Damage Activates Recombination without Checkpoint Arrest
Authors: Pankratz Daniel G. , Forsburg Susan L.
Published: February 2005

Checkpoints operate during meiosis to ensure the completion of DNA synthesis and programmed recombination before the initiation of meiotic divisions. Studies in the fission yeast Schizosaccharomyces pombe suggest that the meiotic response to DNA damage due to a failed replication checkpoint response differs substantially from the vegetative response, and may be influenced by the presence of homologous chromosomes. The checkpoint responses to DNA damage during fission yeast meiosis are not well characterized. Here we report that DNA damage induced during meiotic S-phase does not activate checkpoint arrest. We also find that in wild-type cells, markers for DNA breaks can persist at least to the first meiotic division. We also observe increased spontaneous S-phase damage in checkpoint mutants, which is repaired by recombination without activating checkpoint arrest. Our results suggest that fission yeast meiosis is exceptionally tolerant of DNA damage, and that some forms of spontaneous S-phase damage can be repaired by recombination without activating checkpoint arrest.
The Yeast Ubiquitin Ligase SCFMet30Regulates Heavy Metal Response
Authors: Yen James L. , Su Ning-Yuan , Kaiser Peter
Published: February 2005

Cells have developed a variety of mechanisms to respond to heavy metal exposure. Here, we show that the yeast ubiquitin ligase SCFMet30plays a central role in the response to two of the most toxic environmental heavy metal contaminants, namely, cadmium and arsenic. SCFMet30inactivates the transcription factor Met4 by proteolysis-independent polyubiquitination. Exposure of yeast cells to heavy metals led to activation of Met4 as indicated by a complete loss of ubiquitinated Met4 species. The association of Met30 with Skp1 but not with its substrate Met4 was inhibited in cells treated with cadmium. Cadmium-activated Met4 induced glutathione biosynthesis as well as genes involved in sulfuramino acid synthesis. Met4 activation was important for the cellular response to cadmium because mutations in various components of the Met4-transcription complex were hypersensitive to cadmium. In addition, cell cycle analyses revealed that cadmium induced a delay in the transition from G1to S phase of the cell cycle and slow progression through S phase. Both cadmium and arsenic induced phosphorylation of the cell cycle checkpoint protein Rad53. Genetic analyses demonstrated a complex effect of cadmium on cell cycle regulation that might be important to safeguard cellular and genetic integrity when cells are exposed to heavy metals.
Availability of short amino acid sequences in proteins
Authors: Otaki Joji M. , Ienaka Shunsuke , Gotoh Tomonori , Yamamoto Haruhiko
Published: February 2005

Much attention is being paid to protein databases as an important information source for proteome research. Although used extensively for similarity searches, protein databases themselves have not fully been characterized. In a systematic attempt to reveal protein‐database characters that could contribute to revealing how protein chains are constructed, frequency distributions of all possible combinatorial sets of three, four, and five amino acids (“triplets,” “quartets,” and “pentats”; collectively called constituent sequences) have been examined in the nonredundant (nr) protein database, demonstrating the existence of nonrandom bias in their “availability” at the population level. Nonexistent short sequences of pentats were found that showed low availability in biological proteins against their expected probabilities of occurrence. Among them, six representative ones were successfully synthesized as peptides with reasonably high yields in a conventional Fmoc method, excluding the possibility that a putative physicochemical energy barrier in forming them could be a direct cause for the low availability. They were also expressed as soluble fusion proteins in a conventional Escherichia coli BL21Star(DE3) system with reasonably high yield, again excluding a possible difficulty in their biological synthesis. Together, these results suggest that information on three‐dimensional structures and functions of proteins exists in the context of connections of short constituent sequences, and that proteins are composed of evolutionarily selected constituent sequences, which are reflected in their availability differences in the database. These results may have biological implications for protein structural studies.
Crystallization of bacteriorhodopsin from bicelle formulations at room temperature
Authors: Faham Salem , Boulting Gabriella L. , Massey Elizabeth A. , Yohannan Sarah , Yang Dawn , Bowie James U.
Published: February 2005

We showed previously that high‐quality crystals of bacteriorhodopsin (bR) from Halobacterium salinarum can be obtained from bicelle‐forming DMPC/CHAPSO mixtures at 37°C. As many membrane proteins are not sufficiently stable for crystallization at this high temperature, we tested whether the bicelle method could be applied at a lower temperature. Here we show that bR can be crystallized at room temperature using two different bicelle‐forming compositions: DMPC/CHAPSO and DTPC/CHAPSO. The DTPC/CHAPSO crystals grown at room temperature are essentially identical to the previous, twinned crystals: space group P21 with unit cell dimensions of a = 44.7 Å, b = 108.7 Å, c = 55.8 Å, β = 113.6°. The room‐temperature DMPC/CHAPSO crystals are untwinned, however, and belong to space group C2221 with the following unit cell dimensions: a = 44.7 Å, b = 102.5 Å, c = 128.2 Å. The bR protein packs into almost identical layers in the two crystal forms, but the layers stack differently. The new untwinned crystal form yielded clear density for a previously unresolved CHAPSO molecule inserted between protein subunits within the layers. The ability to grow crystals at room temperature significantly expands the applicability of bicelle crystallization.
A THEORY OF MONEY AND MARKETPLACES*
Authors: Matsui Akihiko , Shimizu Takashi
Published: February 2005

This article considers an infinitely repeated economy with divisible fiat money. The economy has many marketplaces that agents choose to visit. In each marketplace, agents are randomly matched to trade goods. There exist a variety of stationary equilibria. In some equilibrium, each good is traded at a single price, whereas in another, every good is traded at two different prices. There is a continuum of such equilibria, which differ from each other in price and welfare levels. However, it is shown that only the efficient single‐price equilibrium is evolutionarily stable.
INTERTEMPORAL COMPLEMENTARITY AND OPTIMALITY: A STUDY OF A TWO‐DIMENSIONAL DYNAMICAL SYSTEM*
Authors: Mitra Tapan , Nishimura Kazuo
Published: February 2005

We study the underlying structure of the two‐dimensional dynamical system generated by a class of dynamic optimization models that allow for intertemporal complementarity between adjacent periods, but preserve the time‐additively separable framework of Ramsey models. Specifically, we identify conditions under which the results of the traditional Ramsey‐type theory are preserved even when the intertemporal independence assumption is relaxed. Local analysis of this theme has been presented by Samuelson (Western Economic Journal 9 (1971), 21–26). We establish global convergence results and relate them to the local analysis, by using the mathematical theory of two‐dimensional dynamical systems. We also relate the local stability property of the stationary optimal stock to the differentiability of the optimal policy function near the stationary optimal stock, by using the Stable Manifold Theorem.
OPTIMAL CARTEL PRICING IN THE PRESENCE OF AN ANTITRUST AUTHORITY*
Authors: Harrington Joseph E.
Published: February 2005

The dynamic behavior of a price‐fixing cartel is explored when it is concerned about creating suspicions that a cartel has formed. Consistent with preceding static theories, the cartel's steady‐state price is decreasing in the damage multiple and the probability of detection. However, contrary to those theories, it is independent of the level of fixed fines. It is also shown that the cartel prices higher when a more competitive benchmark price is used in calculating damages.
ON THE IMPACT OF HETEROGENEITY ON INDETERMINACY*
Authors: Ghiglino Christian , Olszak‐Duquenne Marielle
Published: February 2005

Some recent research indicates that the occurrence of indeterminacy in models with externalities may be overstated because these models ignore agents' heterogeneity. We consider a neoclassical two‐sector growth model with technological externalities. Agents are heterogeneous with respect to their shares of the initial stock of capital and in labor endowments. We find that the sign of the effect of inequality on indeterminacy is not pinned down by the standard properties of preferences. However, when the inverse of absolute risk aversion is a convex (respectively concave) function, homogeneity (heterogeneity) tends to neutralize the external effects and eliminate indeterminacy.
Inclusiveness and ICT in education: a focus on gender, ethnicity and social class
Authors: Heemskerk Irma , Brink Anouk , Volman Monique , Ten Dam Geert
Published: February 2005

Abstract
This paper presents the results of a literature review on gender, ethnic and socioeconomic status differences related to ICT in primary and secondary education. The review was conducted in order to develop an index for analysing the inclusiveness of educational ICT applications. The research question was: ‘How and to what extent do the characteristics of educational ICT tools enhance or inhibit learning for different groups of students?’ A discussion of both research‐ and practice‐oriented literature results in a proposal for such an index. The paper concludes with a discussion of various dilemmas associated with the idea of the index, and of the ways in which it may be used in research and educational practice.
Hypermedia learning and prior knowledge: domain expertise vs. system expertise
Authors: Mitchell Timothy J. F. , Chen Sherry Y. , Macredie Robert D.
Published: February 2005

Abstract Prior knowledge is often argued to be an important determinant in hypermedia learning, and may be thought of as including two important elements: domain expertise and system expertise. However, there has been a lack of research considering these issues together. In an attempt to address this shortcoming, this paper presents a study that examines how domain expertise and system expertise influence students' learning performance in, and perceptions of, a hypermedia system. The results indicate that participants with lower domain knowledge show a greater improvement in their learning performance than those with higher domain knowledge. Furthermore, those who enjoy using the Web more are likely to have positive perceptions of non‐linear interaction. Discussions on how to accommodate the different needs of students with varying levels of prior knowledge are provided based on the results.
Seismic stratigraphy, buried beach ridges and contourite drifts: the Late Quaternary history of the closed Lago Cardiel basin, Argentina (49°S)
Authors: Gilli Adrian , Anselmetti Flavio S. , Ariztegui Daniel , Beres Milan , McKenzie Judith A. , Markgraf Vera
Published: February 2005

The results of a seismic stratigraphic analysis of a closed lake basin, Lago Cardiel, in southernmost South America are reported. Very few high‐resolution, continental records spanning the Late Quaternary have been obtained from this region. Seismic sequence stratigraphic analysis allows a reconstruction of lake level variations. Two major hiatuses of unknown age occurred during the early evolution of the basin with the deposition of an alluvial fan in a restricted area in the intervening time period. Following the development of a relatively shallow lake during the late Pleistocene and a short desiccation pulse around 11 220 14C yr BP, a transgression of over 135 m occurred at the beginning of the Holocene. The transgression was associated with the formation of beach ridges preserved in the lake stratigraphy on the floor of the modern Lago Cardiel at four different elevations. The preservation of largely unreworked beach ridges indicates a stepwise rise in the lake level. There is no seismic evidence of a major lowering of the lake below modern level during the entire Holocene. Deposition since the mid‐Holocene is marked by strong lateral differences in sediment accumulation with a depocentre slightly to the north of the basin midpoint and a pronounced mounded distribution. Seismic reflection geometries, as well as sedimentological characteristics indicate a lacustrine contourite drift covering an area of 80–100 km2. As Lago Cardiel is under the influence of westerly winds, these most likely drove lake circulation. The identification of drowned beach ridges and of contourite drifts illustrates that high‐resolution seismic stratigraphy is not only a powerful tool in reconstructing past lake level elevations for closed lake basins, but it can also provide information about the rate of lake level changes and the presence and strength of lake currents.
Morphology and facies architecture of a falling sea level strandplain, Umiujaq, Hudson Bay, Canada
Authors: FRASER CHRISTIAN , HILL PHILIP R. , ALLARD MICHEL
Published: February 2005

Coastal strandplain deposits near Umiujaq, eastern Hudson Bay, Canada, were formed under falling relative sea level conditions resulting from postglacial isostatic uplift. Ground‐probing radar profiles across the strandplain reveal a lower progradational unit (LPU) discordantly overlain by an upper progradational unit (UPU), which were correlated with stratigraphic sections exposed in incised valley walls. The discordance is a wave erosion surface (WES) that separates fine shoreface sands of the LPU from coarse‐sand and gravel of the UPU. Major basal downlap surfaces can be traced updip into marine terraces and define downstepping wedges. The downstepping is interpreted as representing ‘autocyclic’ morphological reconfiguration rather than a response to changes in the rate of sea level fall. The internal architecture is strongly dependent on the accommodation and thus on antecedent topography. A conceptual model for strandplain deposition under falling sea level incorporates a bipartite shallowing‐upward sandy succession when sufficient accommodation is available. Where accommodation space is limited, a sharp‐based bar‐and‐beach sandbody directly overlies muddy deeper water deposits and the WES resembles a regressive surface of erosion.
Microtextures, geochemistry and geochronology of authigenic xenotime: constraining the cementation history of a Palaeoproterozoic metasedimentary sequence
Authors: VALLINI DANIELA A. , RASMUSSEN BIRGER , KRAPEŽ BRYAN , FLETCHER IAN R. , MCNAUGHTON NEAL J.
Published: February 2005

An ≈ 26 m thick unit of phosphatic sandstone and black shale (the Phosphatic Unit) in the Palaeoproterozoic Mount Barren Group of south‐western Australia contains abundant authigenic xenotime crystals showing well‐preserved diagenetic textures. Despite extensive regional deformation and thermal metamorphism, the peak of which occurred at ≈ 1205 Ma, the Phosphatic Unit was preserved as a low‐strain envelope because of its pre‐compaction carbonate and phosphate cementation. In situ U–Pb geochronology of xenotime reveals four discrete age populations at 1693 ± 4, 1645 ± 3, 1578 ± 10 and 1481 ± 21 Ma. When integrated with petrography, the age data place a timeframe on: (i) sediment deposition; (ii) phosphogenesis; (iii) diagenetic cement infilling; (iv) diagenetic pyrite formation; (v) secondary porosity generation; (vi) hydrocarbon migration; (vii) burial compaction; and (viii) hydrothermal alteration, up until peak thermal metamorphism. Xenotime growth at ≈ 1693 Ma occurred prior to compaction, whereas xenotime growth at ≈ 1645 Ma occurred during burial. Xenotime growth at ≈ 1580 Ma and at ≈ 1480 Ma appears to be the far‐field record of thermotectonic events associated with intracontinental extension and magmatism recorded elsewhere in Australia. Geochemical analysis, integrated with geochronology, shows a systematic increase in MREE/HREE in xenotime crystals with decreasing age and with increasing stratigraphic depth. Coupled with a decrease in xenotime abundance and age with depth, it suggests that: (i) the main focus of porosity infilling was at the top of the Phosphatic Unit and progressed downwards over the > 200 Myr period of porosity infilling, and (ii) the changes in xenotime REE chemistry may be due to an influx of MREE from increasing amounts of dissolved apatite or changes, with respect to REE solubility, in the physiochemical nature of the fluids with burial depth.
Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2
Authors: Zankl A , Bonafé L , Calcaterra V , Di Rocco M , Superti‐Furga A
Published: February 2005

The inherited osteolysis syndromes are a heterogeneous group of skeletal disorders whose classification is still uncertain. Three osteolysis syndromes show autosomal recessive inheritance and multicentric involvement: Torg syndrome (OMIM 259600), Winchester syndrome (OMIM 277950) and Nodulosis–Arthropathy–Osteolysis syndrome (NAO; OMIM 605156). The 2001 Nosology of the International Skeletal Dysplasia Society (Hall CM, Am J Med Genet 2002: 113: 65) classifies NAO as a variant of Torg syndrome, while Winchester syndrome is considered as a separate disorder. Recently, mutations in the matrix metalloproteinase 2 (MMP2) gene were identified in affected individuals with a clinical diagnosis of NAO in two Arab families. We report a homozygous missense mutation (E404K) in the active site of MMP2 in a 21‐year‐old woman with a severe form of osteolysis best compatible with a diagnosis of Winchester syndrome. The clinical and molecular findings suggest that Torg, NAO and Winchester syndromes are allelic disorders that form a clinical spectrum.
Hospitalizations for childhood asthma in Athens, Greece, from 1978 to 2000
Authors: Priftis K. , Panagiotopoulou‐ Gartagani P. , Tapratzi‐Potamianou P. , Zachariadi‐Xypolita A. , Sagriotis A. , Saxoni‐Papageorgiou P.
Published: February 2005

Trends in rates of asthma admissions among children have shown a variety of patterns in different countries in the last decades. We undertook the present study to determine the time trends in asthma admissions and readmissions of children in Athens, Greece. Data were obtained retrospectively from hospital registries of the three main children's hospitals in Athens from 1978 to 2000. Children admitted with the diagnoses of asthma, asthmatic bronchitis or wheezy bronchitis were included. Hospital admission rate for asthma among children 0–14 yr from 1978 to 2000 rose by 271% (p < 0.001). The rise in rates among those aged 0–4 and 5–15 yr were 250% and 276%, respectively. The mean annual increase in admission rate was 12.2% for 1978–1987, 4.7% for 1988–1993 and 0.6% for 1994–2000. The readmission rate among children 0–14 yr was increased from 15.3% to 23.3%. A positive correlation between admission and readmission rates in all age groups was observed. In conclusion, our findings show an increase in the childhood asthma admission rate in Athens in late 1970's and during the 1980’s, which has decelerated in the 1990’s, particularly in the second‐half of the decade. The readmission rate paralleled that of admissions over the entire study period.
Clinical and laboratory aspects of chronic granulomatous disease in description of eighteen patients
Authors: Carnide Eugénia Grilo , Jacob Cristina Abe , Castro Ana Moschione , Pastorino Antonio Carlos
Published: February 2005

To describe the epidemiological, clinical, laboratory, and evolution characteristics of 18 patients with chronic granulomatous disease (CGD). In this retrospective study, clinical, laboratory, and epidemiological data were obtained from the medical records of all patients with CGD seen at the Allergy and Immunology Unit of the Pediatrics Department (School of Medicine, University of Sao Paulo) from January 1979 to December 2001. Medical history and physical examination data, personal and family history, presence of consanguinity, weight and height data, presence of hepatosplenomegaly, adenomegaly, or other relevant alterations at the time of admission were obtained for all patients. We reviewed 18 patients (male:female, 8:1) with a median duration of symptoms of 1.25 months and with a median time since diagnosis of 13 months. A family history of death as a result of infection was reported by three patients and five other patients had a common relative with CGD who was included in the series. The clinical manifestations observed were: failure to thrive, adenomegaly, hepatosplenomegaly, pneumonia, and abscesses. Relevant laboratory data were hypergammaglobulinemia and nitroblue tetrazolium reduction test of 0% in 14 patients. Seven patients received IFN‐γ and 11 sulfamethoxazole–trimethoprim. Six patients died of suppurative pulmonary infections. Age at the onset of symptoms was early, although diagnosis was late in some patients. Pulmonary involvement was the most prevalent clinical manifestation in the different phases of the disease and the major cause of death. Hypergammaglobulinemia, anemia, and leukocytosis were relevant laboratory data.
Markers of eosinophilic inflammation and tissue re‐modelling in children before clinically diagnosed bronchial asthma
Authors: Pohunek P. , Warner J. O. , Turzíková J. , Kudrmann J. , Roche W. R.
Published: February 2005

Chronic inflammatory changes in the bronchial mucosa have been well documented in patients with established asthma. Much less is known of the changes, which occur in the airways of children early in the evolution of their disease with most of the information based on indirect markers of inflammation only. We evaluated markers of inflammation and tissue re‐modelling in bronchial biopsies from children with early respiratory symptoms before a clear clinical diagnosis of bronchial asthma could be made. We examined bronchial biopsies performed in 27 children between the ages of 1.2 and 11.7 yr who were bronchoscoped for a clinical indication because of recurrent or chronic respiratory symptoms. The patients were re‐evaluated 22–80 months after the original bronchoscopy to determine whether or not they had subsequently developed bronchial asthma. There were more eosinophils in the bronchial mucosa (129.4 vs. 19.1 cells/mm2 of lamina propria, p < 0.001) and the thickness of the subepithelial lamina reticularis was greater (4.65 vs. 3.72 μm, p = 0.044) in children with bronchial asthma diagnosed at follow‐up, compared with the children who did not progress to asthma. Eosinophilic inflammation and airway re‐modelling occur early in the natural history of bronchial asthma and are present even before asthma would be diagnosed based on clinical symptoms. Recognition of these changes and their significance for clinical disease should emphasize the need for timely detection and diagnosis of asthma in children to facilitate the early introduction of anti‐asthma therapy.
Contrasting Patch Residence Strategy in Two Species of Sit‐and‐Wait Foragers Under the Same Environment: A Constraint by Life History?
Authors: Miyashita Tadashi
Published: February 2005

The present study explored the significance of life history constraints on patch residence strategy by using two congeneric web spider species living in the same habitat. Nephila maculata had a large body size but had a shorter developmental period compared with N. clavata, indicating that N. maculata should have a greater foraging efficiency to reach maturity and reproduce. Residence time at web‐sites in N. maculata was shorter than that in N. clavata, irrespective of the season. However, supplementation of food to N. maculata increased residence time, suggesting that it searches web‐sites with higher prey intake. Investment of web materials, an important trait influencing web relocation frequency, was not greater in N. maculata. In addition, microhabitat and prey size did not differ significantly after controlling for the effect of body size. Because N. maculata needs to attain a large body size in a shorter period of time, this species appears to take a risk of moving patches to seek high quality web‐sites.
Comparison of Sugar Beet Cropping Systems with Dead and Living Mulch using a Glyphosate‐resistant Hybrid
Authors: Petersen J. , Röver A.
Published: February 2005

The aim of this study was to evaluate new options for sugar beet mulch systems, using a glyphosate‐resistant hybrid. In four field trials – conducted in 2002 and 2003 at two sites in a major sugar beet‐growing region in the central Germany – three different mulch systems (straw, non‐winterhardy and winterhardy cover crop) and an alternative seedbed preparation method (rotary band tillage) have been tested in comparison with a control treatment (plough, no mulch, broadcast seedbed preparation) representing the common German practice. In all systems, a set of eight different weed control programmes, including two reference treatments, one with selective conventional herbicides and five exclusively using glyphosate, has been evaluated for efficacy. It could be shown that the integration of winterhardy cover crops into sugar beet mulch systems reduced the risk of nitrogen loss by leaching. The changes in the nitrogen dynamics neither influence the yield nor the technical quality of the sugar beet. The field emergence of sugar beet decreased while using a winterhardy cover crop, but was not altered by the seedbed preparation method. Compared with the conventional broadcast seedbed preparation, the rotary band tillage did reduce the weed density. The lowest weed density was observed in the straw mulch system. It was not possible to control the remaining plants of the winterhardy cover crops completely with selective herbicides. If glyphosate was used until the four‐leaf stage of the sugar beet, a regulation of the winterhardy cover crop was achievable. With glyphosate it was also feasible to control older weeds together with the newly emerging ones with post‐emergence applications only. For most of the mulch systems tested, the sugar beet was very sensitive to weed competition between the four‐ and 10‐leaf stage. If the weeds within the sugar beet rows were controlled during this sensitive period with an early glyphosate band application, the remaining weeds between the rows could be left uncontrolled until the 10‐leaf stage of the sugar beet without any yield loss. Only in the combination of winterhardy cover crop × rotary band seedbed preparation, the weeds and cover crop had to be controlled directly after emergence of the sugar beet.
Evaluation of Five Most Commonly Grown Cotton Cultivars (Gossypium hirsutum L.) Under Mediterranean Conditions: Productivity and Fibre Quality
Authors: Avgoulas C. , Bouza L. , Koutrou A. , Papadopoulou S. , Kosmas S. , Makridou E. , Papastylianou P. , Bilalis D.
Published: February 2005

Studies were conducted in four regions of central Greece (Larisa, Karditsa, Livadia, Thiva), to evaluate the productivity and fibre properties (fibre strength and fibre length) of the five most commonly grown cotton cultivars in these regions. The experiments lasted for 6 years (1995–2000). All the characteristics tested were strongly influenced by the factors ‘year’, ‘cultivar’ and ‘region’. Significant cultivar × region, year × cultivar, region × year and cultivar × region × year interactions occurred for all the characteristics studied. The cultivar Alegria had the highest seed‐cotton and lint yield, while Aria had the lowest ones. Both cultivars gave the highest mean lint percentage but the lowest mean boll weight (MBW). Alegria had the lowest fibre strength, while Aria had the highest. The Acala‐type cultivars, Acala SJ2 and Zeta 2, had intermediate seed‐cotton and lint yield, while Vered 171 had high seed‐cotton and satisfactory lint yield. The three cultivars mentioned above had the highest MBW and very good fibre strength. Positive correlation was observed between fibre strength and length. In spite of the fact that mean fibre length was statistically the same in all cultivars, it was influenced by the factor ‘year’, as a result of different weather conditions. The year 1996 was the most unfavourable one for seed‐cotton yield and MBW, because it was characterized by lower than average air temperatures and rather dry conditions for all study sites. The factor ‘region’, a combination of different climatic conditions and cultural practices, influenced significantly all the parameters studied.
Diffuse panbronchiolitis in China
Authors: CHEN Yu , KANG Jian , LI Shengqi
Published: February 2005

Objective:  Diffuse panbronchiolitis (DPB) is a progressive inflammatory disease, well recognized in Japan, that is characterized by chronic sinusitis and obstructive small airway disease. A total of 40 patients with DPB in mainland China were reviewed in order to describe the epidemiology of DPB in China and to compare their clinical characteristics with those of cases reported in Japan.

Methodology:  A systematic search was conducted of the Chinese language literature published in mainland China from 1996 to 2003. The 40 subjects who fulfilled the diagnostic criteria for DPB were retrospectively analysed for clinical, physiological, radiological, and pathological features and their geographic distribution.

Results:  The 40 patients included in this study (31 male and nine female) were distributed in 12 provinces and three other cities in China. All presented with chronic cough, sputum production, and 32 had exertional dyspnoea. All but three had a history of sinusitis. Lung function assessment showed a mixed obstructive‐restrictive pattern in 30 cases. CXR revealed diffuse fine nodular shadows in all patients. Human leukocyte antigen‐B54 was positive in five patients (n = 12). A total of 30 (75%) patients had been misdiagnosed prior to their diagnosis of DPB being made.

Conclusions:  DPB is not rare in China but its incidence is relatively low. Poor recognition and/or genetic factors may be the reason. The clinical, radiographic and histological features of Chinese patients resemble those described in Japanese patients.
Potential involvement of subclinical Sjögren's syndrome in various lung diseases
Authors: KURUMAGAWA Toshikazu , KOBAYASHI Hideo , MOTOYOSHI Kazuo
Published: February 2005

Objectives:  Sjögren's syndrome (SS) affects the respiratory system, but previous studies have not assessed the role of subclinical SS in lung disease. The aim of this investigation was to explore the potential role of subclinical SS as a factor in the pathogenesis of various diffuse lung diseases.

Methodology:  This single‐cohort prospective study was performed over a 5‐year period in 313 consecutive patients with diffuse lung disease, who had neither primary xerosis nor a diagnosis of SS. They were referred for the Saxon test and underwent additional tests for SS when decreased saliva production was detected.

Results:  The subjects included 109 patients with sarcoidosis, 77 with various interstitial pneumonias, 49 with bronchiectasis, and 78 with other diseases. The incidence of decreased saliva production was 17.3% (54 out of 313). A total of 40 of the 54 patients completed further examinations, and definite or probable SS was diagnosed in 29 (9.3% of the original 313). Definite SS was diagnosed in six patients with interstitial pneumonia, three with bronchiolitis, three with sarcoidosis, and five with other diseases.

Conclusions:  The prevalence of decreased saliva production and SS without obvious symptoms of dryness was high among patients with diffuse lung disease. In these patients, it is important to screen for SS, even if symptoms are not apparent.
Metered dose inhalers: A need for dose counters
Authors: HOLT Shaun , HOLT Avrille , WEATHERALL Mark , MASOLI Matthew , BEASLEY Richard
Published: February 2005

Objectives:  This study investigated the ability of patients to assess when a metered dose inhaler (MDI) is empty.

Methodology:  A total of 17 patients assessed, by shaking, the number of doses remaining in a salbutamol MDI that had been partially emptied. Another 100 patients were asked to collect all salbutamol MDIs they considered to be empty and would have thrown away. These MDI canisters were weighed and the number of doses that had been used was estimated.

Results:  Using the ‘shaking method’, patients overestimated the amount remaining by around 40 doses. The mean number of doses delivered from an MDI labelled to contain 200 doses before it was discarded was 224 (range, 155–289).

Conclusions:  These findings confirm that patients are unable to determine when an MDI should be discarded, resulting in insufficient drug delivery at the end of the life of an MDI for the majority of patients, and wastage of the drug for others.
Different roles of interleukin‐10 in onset and resolution of asthmatic responses in allergen‐challenged mice
Authors: MATSUMOTO Koichiro , INOUE Hiromasa , TSUDA Miyuki , HONDA Yasuko , KIBE Atsuko , MACHIDA Kentaro , YOSHIURA Yuki , NAKANISHI Yoichi
Published: February 2005

Objective:  Although interleukin (IL)‐10 is an immunoregulatory cytokine produced by various cells including T cells, its precise role in asthma remains uncertain. The aim of this study was to investigate the role of IL‐10 in experimental asthma using ovalbumin (OVA)‐sensitized mice.

Methodology:  Mice were challenged with OVA aerosol, and airway responsiveness and inflammation were measured. OVA‐specific IL‐10‐producing CD4+ T cells were counted from lung cells collected by enzymatic digestion and stimulated ex vivo with OVA. The effects of an anti‐IL‐10 antibody on airway responsiveness and inflammation were also evaluated.

Results:  The OVA challenge caused airway hyperresponsiveness and eosinophilic inflammation. A significant increase in IL‐10‐producing CD4+ T cells was observed, mainly in the CD45RBlow subset, for several days after the OVA challenge. Anti‐IL‐10 antibody treatment before the OVA challenge did not affect eosinophilic inflammation but significantly inhibited airway hyperresponsiveness 24 h after the OVA challenge. However, anti‐IL‐10 antibody treatment just before the last OVA challenge significantly attenuated the resolution of eosinophilic inflammation without affecting airway responsiveness 2 weeks after the OVA challenge.

Conclusions:  Intrinsic IL‐10 may have a distinct role in the early and late phases of asthmatic responses. In the early phase, IL‐10 induces airway hyperresponsiveness, while in the late phase IL‐10 contributes to the resolution of eosinophilic inflammation.
Clinicopathological differences between acute and chronic eosinophilic pneumonia
Authors: MOCHIMARU Hiroshi , KAWAMOTO Masashi , FUKUDA Yuh , KUDOH Shoji
Published: February 2005

Objective:  Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). Furthermore, there are no reports describing the clinicopathological differences between the various forms of eosinophilic pneumonias.

Methodology:  The histological findings in acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) were examined and the clinical and radiological features were contrasted with them.

Results:  Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases, while air space consolidation was seen in all CEP cases. Histologically, interstitial oedema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, although the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls.

Conclusions:  An essential histological difference between AEP and CEP is the severity of basal lamina damage and the amount of subsequent intraluminal fibrosis. In AEP particularly, these findings explain the radiographical findings, as well as the rapid and complete improvement noted in such cases.