bluuebunny/crossref_metadata_2025 huggingface dataset:
RasMutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes
Authors: Mullin James M. , Leatherman James M. , Valenzano Mary Carmen , Huerta Erika Rendon , Verrechio Jon , Smith David M. , Snetselaar Karen , Liu Mantao , Francis Mary Kay , Sell Christian
Published: September 2005

Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK1renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of d-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to d-mannitol (Mr182), polyethylene glycol (Mr4000), and 10,000-Mrmethylated dextran but not to 2,000,000-Mrmethylated dextran. This implies a “ceiling” on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier.
The Mitotic Exit Network Mob1p-Dbf2p Kinase Complex Localizes to the Nucleus and Regulates Passenger Protein Localization
Authors: Stoepel Jan , Ottey Michelle A. , Kurischko Cornelia , Hieter Philip , Luca Francis C.
Published: September 2005

The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved signaling network that coordinates CDK inactivation, cytokinesis and G1 gene transcription. The MEN Cdc14p phosphatase is sequestered in the nucleolus and transiently released in early anaphase and telophase. Cdc14p mediates mitotic exit by dephosphorylating Cdk1p substrates and promoting Cdk1p inactivation. Cdc14p also regulates the localization of chromosomal passenger proteins, which redistribute from kinetochores to the mitotic spindle during anaphase. Here we present evidence that the MEN protein kinase complex Mob1p-Dbf2p localizes to mitotic nuclei and partially colocalizes with Cdc14p and kinetochore proteins. Chromatin immunoprecipitation (ChIP) experiments reveal that Mob1p, Dbf2p, and Cdc14p associate with centromere DNA and require the centromere binding protein Ndc10p for this association. We establish that Mob1p is essential for maintaining the localization of Aurora, INCENP, and Survivin chromosomal passenger proteins on anaphase spindles, whereas Cdc14p and the Mob1p-Dbf2p-activating kinase Cdc15p are required for establishing passenger protein localization on the spindle. Moreover, Mob1p, but not Cdc15p, is required for dissociating Aurora from the kinetochore region. These findings reveal kinetochores as sites for MEN signaling and implicate MEN in coordinating chromosome segregation and/or spindle integrity with mitotic exit and cytokinesis via regulation of chromosome passenger proteins.
Irrwege Der Orthographie – und Ein Ausweg
Authors: Ickler Theodor
Published: September 2005

An einem breiten Querschnitt aus allen wesentlichen Bereichen wird gezeigt, daß die Rechtschreibreform zu einer flächendeckenden Qualitätsminderung deutscher Texte geführt hat. Dafür verantwortlich sind nicht nur die allerdings auffallend häufigen Fehlinterpretationen der neuen Regeln, sondern gerade auch bei deren ‘korrekter’ Anwendung kommt es zu elementaren Verstößen gegen die Grammatik. Es waren die Verfasser der Reform selbst, die aufgrund dieser Erfahrung schon Ende 1997 eine Korrektur des Regelwerks für unumgänglich notwendig erklärten. Die Unstimmigkeiten der Regeln sowie die seither inoffiziell vorgenommenen Änderungen haben bei Journalisten und Autoren den folgenreichen Eindruck entstehen lassen, daß nunmehr beinahe alles möglich sei. Es wird gezeigt, daß auf der Grundlage einer derart verwirrenden Vorlage keine sprachrichtige Einheitsorthographie wiederhergestellt werden kann. Die einfachste Lösung wäre ein Moratorium über 2005 hinaus, d. h. ein Weitergeltenlassen der alten Regelung, verbunden mit der gleitenden Beendigung des verfehlten Reformexperiments.
Multiple metastatic tuberculosis abscesses in a patient with Pott disease and lung tuberculosis: a case report
Authors: Saral Yunus , Coskun Başak Kandi , Ozturk Perihan , Bulut Yasemin , Çobanoglu Bengu
Published: September 2005

Abstract:  The incidence of tuberculosis in Western countries is rising, and continued vigilance together with an awareness of its protean manifestations is essential. Cutaneous tuberculosis is a relatively rare manifestation of the disease, accounting for only 1% of extrapulmonary cases of tuberculosis and 0.14% of all reported cases of tuberculosis. A 19‐year‐old male patient was admitted to our clinic with skin lesions both at the front and at the back of his body. With clinical findings, histopathology, polymerase chain reaction, PA lung graph, and computerised tomography, the patient was diagnosed with metastatic tuberculosis abscess associated with lung tuberculosis and Pott's disease. Antituberculosis drugs were administered. An increased awareness of the re‐emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasing common skin disorder.
Inflammatory dermatoses of the vulva
Authors: Hammock Lauren A. , Barrett Terry L.
Published: September 2005

Abstract:  Inflammatory, non‐neoplastic epidermal alterations of the vulva can be correctly diagnosed using classification schemes applied to skin elsewhere on the body. A wide range of inflammatory disorders may occur on the vulva, and they may have a similar clinical presentation to HPV lesions. However, HPV is incurable and often is treated surgically. Accordingly, as inflammatory dermatoses commonly occur on the vulva and are often curable with topical therapy, an awareness of these entities and an ability to distinguish them from HPV are imperative.
Scleromyxedema‐like lesions of patients in renal failure contain hyaluronan: a possible pathophysiological mechanism
Authors: Neudecker Birgit A. , Stern Robert , Mark Leslie A. , Steinberg Steven
Published: September 2005

Background:  Patients with renal failure have been identified recently, some on dialysis, others with renal transplants, who have scleromyxedema‐like skin changes. These lesions are characterized grossly by extensive thickening of skin, brawny pigmentation, papules, and subcutaneous nodules. Mucinous deposits are observed histologically that resemble those in scleromyxedema.

Methods:  Biopsies of these lesions were stained with a biotinylated hyaluronan (HA)‐binding protein coupled to an avidin‐peroxidase reaction.

Results:  These lesions are associated with marked deposition of HA in the papillary dermis.

Conclusions:  HA turnover is cleared rapidly in the circulation by both liver and kidney. Evidence suggests that high molecular size HA chains, which are anti‐inflammatory, antiangiogenic, and immuno‐suppressive are cleared by the liver. By contrast, intermediate‐size fragments, which are highly angiogenic, inflammatory, and a stimulus for fibrous deposition, are cleared by the kidney. The accumulation of such fragments in renal failure can account for HA deposition in the dermis and may be a mechanism for the nephrogenic fibrosing dermopathy that can accompany these lesions.
Evaluating investment projects in the presence of sectoral linkages1
Authors: Matouschek Niko , Venables Anthony J.
Published: September 2005

In this paper we develop a framework to assess the economic impact of foreign investment projects. If investment projects interact with other industries in the host economy, either by buying inputs locally or by selling their own product to local downstream firms, they can create sectoral linkages. The expansion of upstream and downstream industries can feed back to the project's own industry leading to a further expansion of the local industry. We study the circumstances under which investment projects lead to the creation of sectoral linkages and characterize the factors that determine the project's welfare impact. We link analytical findings to case studies undertaken for the EBRD.
Effect of amniotic fluid on coagulation and platelet function in pregnancy: an evaluation using thromboelastography*
Authors: Harnett M. J. P. , Hepner D L. , Datta S. , Kodali B. S.
Published: September 2005

Amniotic fluid embolism is a rare obstetric complication. The exact pathogenesis of this syndrome remains unknown and significant controversy exists whether coagulopathy should always be present. We used thromboelastography to assess the effect of amniotic fluid on coagulation and platelet function in pregnant women. Different volumes of amniotic fluid (10–60 μl) were added to blood (330 μl) from pregnant women and thromboelastography variables determined. There were three important findings. R time, reflecting time to first clot formation, was significantly decreased with the addition of 10 μl amniotic fluid; platelet function, as determined by Reopro‐TEG technique, was increased with the addition of 30 μl of amniotic fluid; and there was no evidence of fibrinolysis in any samples studied. In conclusion, our study substantiates the hypothesis that coagulation profile changes are invariable accompaniments of amniotic fluid embolism.
Platelet transfusion prophylaxis for patients with haematological malignancies: where to now?
Authors: Stanworth S. J. , Hyde C. , Brunskill S. , Murphy M. F.
Published: September 2005

National guidelines for platelet transfusion in many countries recommend that the general platelet transfusion trigger for prophylaxis is 10 × 109/l. This annotation reviews the evidence for this threshold level and discusses other current unresolved issues relevant to platelet transfusion practice such as the optimal dose and the clinical benefit of a strategy for the prophylactic use of platelet transfusions when the platelet count falls below a given threshold.
The use of a fixed high sensitivity to evaluate five D‐dimer assays’ ability to rule out deep venous thrombosis: a novel approach
Authors: Stevens Scott M. , Gregory Elliott C. , Woller Scott C. , Li Liang , Bennett Sterling T. , Egger Marlene , Snow Gregory L.
Published: September 2005

Suspected deep venous thrombosis (DVT) is difficult to refute without complex diagnostic algorithms and expensive testing. We analysed five d‐dimer assays’ utility for exclusion of suspected DVT during a prospective clinical cohort trial, choosing a highly sensitive cut‐off value at which to compare the assays. Assays were performed on 436 consecutive patients who were referred with symptoms that suggested a first episode of DVT. Venous thromboembolism (VTE) was defined as positive findings on comprehensive duplex ultrasonography or any episode, or complication of VTE detected during 3 months of clinical follow‐up. All five assays were performed in 377 patients. At a highly sensitive cut‐off value, all five assays reliably excluded DVT in the study population. While the choice of a highly sensitive cut‐off value reduced the specificity of all the assays, the change in specificity differed between tests. Our findings suggest that a second‐generation d‐dimer assay could be used as a stand‐alone test to rule out suspected DVT when a highly sensitive cut‐off value is chosen. These findings should be subjected to a prospective management study, as a small reduction in sensitivity from our findings could result in a clinically relevant decrease in negative predictive value.
Transient overexpression of γ interferon promotesAspergillusclearance in invasive pulmonary aspergillosis
Authors: Shao C , Qu J , He L , Zhang Y , Wang J , Wang Y , Zhou H , Liu X
Published: September 2005

Cytokines are critical molecules necessary for normal lung pathogen host defences. Gamma interferon (IFN-γ) and T1-phenotype immune responses are important components of host defence against Aspergillus. Therefore, we hypothesized that transient overexpression of IFN-γ within the lung could augment host immunity against Aspergillus. Here it was showed that intranasal administration of 5 × 107 colony-forming units (CFU) of Aspergillus fumigatus (Af ) induced the expression of IFN-γ. Mice were intranasally (i.n) administrated with 5 × 108 PFU of a recombinant adenovirus vector containing the murine IFN-γ cDNA (AdmIFN-γ), and challenged 24 h later with Af. We observed that i.n. administration of AdmIFN-γ resulted in about a fourfold increase in levels of IFN-γ and IL-12 within the lung, about a 75% reduction in lung fungal contents at day 2 and a more than threefold higher survival rate in the AdmIFN-γ-treated group compared to the controls (P < 0·01). This protection effect was not found when AdmIFN-γ was i.p. administrated. Alveolar macrophages and lung leucocytes isolated from i.n. AdmIFN-γ-treated animals displayed enhanced killing of intracellular Aspergillus organisms ex vivo. These results demonstrate that transient overexpression of IFN-γ could augment host defence against Aspergillus.
Vaginal vault smears –‘know more – do less’: a questionnaire survey of primary health care practitioners
Authors: Stokes‐Lampard H. , Wilson S. , Allan T. , Waddell C. , Kehoe S.
Published: September 2005

Background:  The vaginal vault smear is a test for cellular atypia in women who have undergone a hysterectomy. In asymptomatic women the test has poor sensitivity and specificity. Current guidelines recommend: vault smears should not be used after hysterectomy for benign pathology; two vault smears (6 and 12 months postsurgery) should be taken when there is evidence of completely excised CIN II/III in the specimen.

Aim:  To describe primary health care professionals’ self‐reported knowledge and behaviour relating to the use of vault smears.

Design of Study:  Questionnaire.

Setting:  South Birmingham.

Methods:  Postal questionnaire survey to primary health care professionals (general practitioners and practice nurses, n = 424).

Results:  Response rate 80.0%, completed response rate 68.9%. Mean knowledge score was 7.3 out of possible 12 (SD 1.9); range 0–10. No significant differences were observed between GPs and practice nurses in knowledge scores, although differences were noted in the frequency of performing vault smears. An inverse relationship was observed between frequency of performing vault smears and level of knowledge about the test. There was a positive association between requesting further information and the ‘knowledge score’. Only 11% correctly answered a question based on current guidelines.

Conclusions:  Knowledge of current guidelines was poor. Those who undertook fewest vault smears appeared best informed. This suggests that if all primary care professionals practised according to current guidelines, the number of vault smears performed may be reduced. Unnecessary vault smears may cause additional anxiety in women and have financial consequences for the NHS.
[13C] phenylalanine breath test and hepatic phenylalanine metabolism enzymes in cirrhotic rats
Authors: Yan W. , Sun D. , Lin X. , Jiang Y. , Sun X.
Published: September 2005

Background  Stable isotope 13C‐labelled phenylalanine breath test has been applied to enable the quantitative evaluation of hepatic functional reserve, but the mechanism underlying the changes in function has not been resolved. This study evaluated the correlation between expression of the mRNA of key enzymes mediating phenylalanine metabolism and the metabolism of L‐[1‐13C] phenylalanine (13C‐phe) assessed by the excretion of 13C‐CO2 in the breath of rats with, and without, chronic hepatic injury induced by administration of carbon tetrachloride (CCl4).

Materials and methods  Male Sprague‐Dawley (SD) rats (n = 29) were given subcutaneous injections of CCl4 to induce chronic hepatic injury. L‐[1‐13C] phenylalanine breath tests (PheBT) were then applied to the rats to assess hepatic function. Expression of phenylalanine hydroxylase (PHH) and tyrosine transaminase (TYT) mRNA in liver was detected by real‐time fluorescence quantification RT‐PCR, using TaqMan as the probe. It was then determined whether the PheBT results correlated with PHH and/or TYT mRNA expression. In addition, immunohistochemical labelling was used to visualize PHH protein expression in the control and injured liver tissue.

Results  There were significant decreases in PheBT and PHH mRNA expression in the cirrhotic rats relative to the uninjured controls and these two measures of liver function were correlated. However, TYT mRNA expression was not changed by CCl4‐induced liver injury. The immunohistochemical analysis revealed that PHH protein was expressed predominantly in the cytoplasm of liver cells.

Conclusions  The results of the PheBT were consistent with the changes in PHH gene expression following liver injury. The present findings indicate that decreased expression of the rate‐limiting enzyme PHH, but not of TYT, might underlie the functional deficits detected as decreased PheBT. The 13C excretion rate constant per mass liver (PheBT‐k/LW) was the most sensitive index that could be used to evaluate the PHH mRNA expression in the liver.
Plant nitrogen concentration, use efficiency, and contents in a tallgrass prairie ecosystem under experimental warming
Authors: An Yuan , Wan Shiqiang , Zhou Xuhui , Subedar Afzal A. , Wallace Linda L. , Luo Yiqi
Published: September 2005

Plant nitrogen (N) relationship has the potential to regulate plant and ecosystem responses strongly to global warming but has not been carefully examined under warmed environments. This study was conducted to examine responses of plant N relationship (i.e. leaf N concentration, N use efficiency, and plant N content in this study) to a 4‐year experimental warming in a tallgrass prairie in the central Great Plains in USA. We measured mass‐based N and carbon (C) concentrations of stem, green, and senescent leaves, and calculated N resorption efficiency, N use efficiency, plant N content, and C : N ratios of five dominant species (two C4 grasses, one C3 grass, and two C3 forbs). The results showed that warming decreased N concentration of both green and senescent leaves, and N resorption efficiency for all species. N use efficiencies and C : N ratios were accordingly higher under warming than control. Total plant N content increased under warming because of warming‐induced increases in biomass production that are larger than the warming‐induced decreases in tissue N concentration. The increases in N contents in both green and senescent plant tissues suggest that warming enhanced both plant N uptake and return through litterfall in the tallgrass ecosystem. Our results also suggest that the increased N use efficiency in C4 grasses is a primary mechanism leading to increased biomass production under warming in the grassland ecosystem.
Hepatitis C virus free‐virion and immune‐complex dynamics during interferon therapy with and without ribavirin in genotype‐1b chronic hepatitis C patients
Authors: Fujita N. , Kaito M. , Tanaka H. , Horiike S. , Urawa N. , Sugimoto R. , Konishi M. , Watanabe S. , Adachi Y.
Published: September 2005

Summary. The Synergistic effect of interferon (IFN) and ribavirin for patients with chronic hepatitis C has been demonstrated, but ribavirin has no apparent direct antiviral effect against hepatitis C virus (HCV) when used as monotherapy. To elucidate the mechanism of ribavirin on enhanced HCV eradication when used in combination therapy, we investigated the serum HCV dynamics of free‐virions (FV) and immune‐complexes (IC) in genotype‐1b infected patients treated with IFN‐α2b alone (n = 11) or in combination with ribavirin (n = 15). Serum FV‐ and IC‐HCV RNA were separated by immunoprecipitation using anti‐human immunoglobulin and quantified serially using real‐time detection polymerase chain reaction. At the first phase (day 0–2), the decline of FV‐ and IC‐HCV RNA was similar between the two treatment groups. At the second phase (day 2–28), the decline of IC was significantly faster in patients treated with IFN plus ribavirin compared with IFN alone [exponential decay slope = 0.079 ± 0.036vs0.048 ± 0.027 log10/day,P = 0.0248; half‐life = 81.1 ± 21.4vs135.1 ± 61.4 h,P = 0.0053], although the second phase FV‐decline was not significantly different between the two treatment groups. The fast second phase decline of IC was associated with sustained virological response to therapy. These results suggest that ribavirin may modulate the humoral immune response against HCV and trigger a favourable response to IFN. In conclusion, analysis of early IC‐HCV dynamics is useful for predicting the response to therapy and for understanding the mechanism of action of antiviral drugs in chronic hepatitis C patients.
Evolutionary processes in a continental island system: molecular phylogeography of the AegeanNigella arvensisalliance (Ranunculaceae) inferred from chloroplast DNA
Authors: BITTKAU C. , COMES H. P.
Published: September 2005

Continental shelf island systems, created by rising sea levels, provide a premier setting for studying the effects of past fragmentation, dispersal, and genetic drift on taxon diversification. We used phylogeographical (nested clade) and population genetic analyses to elucidate the relative roles of these processes in the evolutionary history of the AegeanNigella arvensisalliance (= ‘coenospecies’). We surveyed chloroplast DNA (cpDNA) variation in 455 individuals from 47 populations (nine taxa) of the alliance throughout its core range in the Aegean Archipelago and surrounding mainland areas of Greece and Turkey. The study revealed the presence of three major lineages, with largely nonoverlapping distributions in the Western, Central, and Eastern Aegean. There is evidence supporting the idea that these major lineages evolvedin situfrom a widespread (pan‐Aegean) ancestral stock as a result of multiple fragmentation events, possibly due to the influence of post‐Messinian sea flooding, Pleistocene eustatic changes and corresponding climate fluctuations. Over‐sea dispersal and founder events appear to have played a rather insignificant role in the group's history. Rather, all analytical approaches identified the alliance as an organism group with poor seed dispersal capabilities and a susceptibility to genetic drift. In particular, we inferred that the observed level of cpDNA differentiation between Kikladian island populations ofNigella degeniilargely reflects population history, (viz. Holocene island fragmentation) and genetic drift in the near absence of seed flow since their time of common ancestry. Overall, our cpDNA data for theN.arvensisalliance in general, andN.degeniiin particular, indicate that historical events were important in determining the phylogeographical patterns seen, and that genetic drift has historically been relatively more influential on population structure than has cytoplasmic gene flow.
Functional genomics of Buchnera and the ecology of aphid hosts
Authors: MORAN NANCY A. , DEGNAN PATRICK H.
Published: September 2005

In many animal groups, mutualistic bacterial symbionts play a central role in host ecology, by provisioning rare nutrients and thus enabling specialization on restricted diets. Among such symbionts, genomic studies are most advanced for Buchnera, the obligate symbiont of aphids, which feed on phloem sap. The contents of the highly reduced Buchnera genomes have verified its role in aphid nutrition. Comparisons of Buchnera gene sets indicate ongoing, irreversible gene losses that are expected to affect aphid nutritional needs. Furthermore, almost all regulatory genes have been eliminated, raising the question of whether and how gene expression responds to environmental change. Microarray studies on genome‐wide expression indicate that Buchnera has evolved some constitutive changes in gene expression: homologues of heat stress genes have elevated transcript levels in Buchnera (relative to other bacteria) even in the absence of stress. Additionally, the microarray results indicate that responses to heat stress and to amino acid availability are both few and modest. Observed responses are consistent with control by the few ancestral regulators retained in the genome. Initial studies on the role of host genes in mediating the symbiosis reveal distinctive expression patterns in host cells harbouring Buchnera. In the near future, a complete genome of pea aphid will accelerate progress in understanding the functional integration of aphid and Buchnera genomes. Although information for other insect symbioses is relatively limited, studies on symbionts of carpenter ants and tsetse flies indicate many similarities to Buchnera.
Host immunity modulates transcriptional changes in a multigene family (yir) of rodent malaria
Authors: Cunningham Deirdre A. , Jarra William , Koernig Sandra , Fonager Jannik , Fernandez‐Reyes Delmiro , Blythe Jane E. , Waller Cecilia , Preiser Peter R. , Langhorne Jean
Published: September 2005

Variant antigens, encoded by multigene families, and expressed at the surface of erythrocytes infected with the human malaria parasite Plasmodium falciparum and the simian parasite Plasmodium knowlesi, are important in evasion of host immunity. The vir multigene family, encoding a very large number of variant antigens, has been identified in the human parasite Plasmodium vivax and homologues (yir) of this family exist in the rodent parasite Plasmodium yoelii. These genes are part of a superfamily (pir) which are found in Plasmodium species infecting rodents, monkeys and humans (P. yoelii, P. berghei, P. chabaudi, P. knowlesi and P. vivax). Here, we show that YIR proteins are expressed on the surface of erythrocytes infected with late‐stage asexual parasites, and that host immunity modulates transcription of yir genes. The surface location and expression pattern of YIR is consistent with a role in antigenic variation. This provides a unique opportunity to study the regulation and expression of the pir superfamily, and its role in both protective immunity and antigenic variation, in an easily accessible animal model system.
Linking structural assembly to gene expression: a novel mechanism for regulating the activity of a σ54 transcription factor
Authors: Dutton Rachel J. , Xu Zhaohui , Gober James W.
Published: September 2005

In Caulobacter crescentus, the temporal and spatial expression of late flagellar genes is regulated by the σ54 transcriptional activator, FlbD. Genetic experiments have indicated that the trans‐acting factor FliX regulates FlbD in response to the progression of flagellar assembly, repressing FlbD activity until an early flagellar basal body structure is assembled. Following assembly of this structure, FliX is thought to function as an activator of FlbD. Here we have investigated the mechanism of FliX‐mediated regulation of FlbD activity. In vitro transcription experiments showed that purified FliX could function as a repressor of FlbD‐activated transcription. Transcription activated by a gain‐of‐function mutant of FlbD (FlbD‐1204) that is active in vivo in the absence of an early flagellar structure, was resistant to the repressive effects of FliX. DNA binding studies showed that FliX inhibited the interaction of wild‐type FlbD with enhancer DNA but did not effect FlbD‐catalysed ATPase activity. DNA binding activity of FlbD‐1204 was relatively unaffected by FliX indicating that this mutant protein bypasses the transcriptional requirement for early flagellar assembly by escaping FliX‐mediated negative regulation. Gel filtration and co‐immunoprecipitation experiments indicated that FliX formed a stable complex with FlbD. These experiments demonstrate that regulation of FlbD activity is unusual among the well‐studied σ54 transcriptional activators, apparently combining a two‐component receiver domain with additional control imposed via interaction with a partner protein, FliX.
Tus‐mediated arrest of DNA replication in Escherichia coli is modulated by DNA supercoiling
Authors: Valjavec‐Gratian Majda , Henderson Thomas A. , Hill Thomas M.
Published: September 2005

In the absence of RecA, expression of the Tus protein of Escherichia coli is lethal when ectopic Ter sites are inserted into the chromosome in an orientation that blocks completion of chromosome replication. Using this observation as a basis for genetic selection, an extragenic suppressor of Tus‐mediated arrest of DNA replication was isolated with diminished ability of Tus to halt DNA replication. Resistance to tus expression mapped to a mutation in the stop codon of the topA gene (topA869), generating an elongated topoisomerase I protein with a marked reduction in activity. Other alleles of topA with mutations in the carboxyl‐terminal domain of topoisomerase I, topA10 and topA66, also rendered recA strains with blocking Ter sites insensitive to tus expression. Thus, increased negative supercoiling in the DNA of these mutants reduced the ability of Tus–Ter complexes to arrest DNA replication. The increase in superhelical density did not diminish replication arrest by disrupting Tus–Ter interactions, as Tus binding to Ter sites was essentially unaffected by the topA mutations. The topA869 mutation also relieved the requirement for recombination functions other than recA to restart replication, such as recC, ruvA and ruvC, indicating that the primary effect of the increased negative supercoiling was to interfere with Tus blockage of DNA replication. Introduction of gyrB mutations in combination with the topA869 mutation restored supercoiling density to normal values and also restored replication arrest at Ter sites, suggesting that supercoiling alone modulated Tus activity. We propose that increased negative supercoiling enhances DnaB unwinding activity, thereby reducing the duration of the Tus–DnaB interaction and leading to decreased Tus activity.
Hyperosmotic stress induces metacaspase‐ and mitochondria‐dependent apoptosis in Saccharomyces cerevisiae
Authors: Silva Rui D. , Sotoca Roberto , Johansson Björn , Ludovico Paula , Sansonetty Filipe , Silva Manuel T. , Peinado José M. , Côrte‐Real Manuela
Published: September 2005

During the last years, several reports described an apoptosis‐like programmed cell death process in yeast in response to different environmental aggressions. Here, evidence is presented that hyperosmotic stress caused by high glucose or sorbitol concentrations in culture medium induces in Saccharomyces cerevisiae a cell death process accompanied by morphological and biochemical indicators of apoptotic programmed cell death, namely chromatin condensation along the nuclear envelope, mitochondrial swelling and reduction of cristae number, production of reactive oxygen species and DNA strand breaks, with maintenance of plasma membrane integrity. Disruption of AIF1 had no effect on cell survival, but lack of Yca1p drastically reduced metacaspase activation and decreased cell death indicating that this death process was associated to activation of this protease. Supporting the involvement of mitochondria and cytochrome c in caspase activation, the mutant strains cyc1Δcyc7Δ and cyc3Δ, both lacking mature cytochrome c, displayed a decrease in caspase activation associated to increased cell survival when exposed to hyperosmotic stress. These findings indicate that hyperosmotic stress triggers S. cerevisiae into an apoptosis‐like programmed cell death that is mediated by a caspase‐dependent mitochondrial pathway partially dependent on cytochrome c.
Structure and mechanism of Escherichia coli RecA ATPase
Authors: Bell Charles E.
Published: September 2005

RecA protein catalyses an ATP‐dependent DNA strand‐exchange reaction that is the central step in the repair of dsDNA breaks by homologous recombination. Although much is known about the structure of RecA protein itself, we do not at present have a detailed picture of how RecA binds to ssDNA and dsDNA substrates, and how these interactions are controlled by the binding and hydrolysis of the ATP cofactor. Recent studies from electron microscopy and X‐ray crystallography have revealed important ATP‐mediated conformational changes that occur within the protein, providing new insights into how RecA catalyses DNA strand‐exchange. A unifying theme is emerging for RecA and related ATPase enzymes in which the binding of ATP at a subunit interface results in large conformational changes that are coupled to interactions with the substrates in such a way as to promote the desired reactions.
Endocardial Schwannomas in the Wistar Rat
Authors: Teredesai A. , Wöhrmann T.
Published: September 2005

Endocardial neoplasms were observed in 13 Wistar rats, 15–30 months old, from a 30‐month inhalation study. Eight of the rats were dissected at 30 months and the other five between 15 and 29 months. Histologically, the lesions in the heart were diagnosed as endocardial schwannomas. Two of the 13 schwannomas were malignant, while the rest were benign. One malignant schwannoma metastasized to the thymus and the other metastasized to the aorta, oesophagus, liver and spleen. Some schwannomas appeared as early lesions limited to the endocardium consisting of round to ovoid cells interspersed with spindle cells, while other schwannomas appeared as advanced lesions consisting of a thin superficial layer of round to ovoid cells and a deeper layer of spindle cells characteristic of endocardial schwannomas. The histological appearance of the metastases was identical to that of the primary tumour. The diagnosis was confirmed by positive immunostaining for S‐100 protein. The incidence of endocardial schwannomas in the Wistar rat strain was 1.8%.
Effect of 5‐hydroxytryptamine on neurogenic vasoconstriction in the isolated, autoperfused hindquarters of the rat
Authors: Calama E , Ortíz de Urbina AV , Morán A , Martín ML , San Román L
Published: September 2005

1. In the present study, we analysed the effect of different doses of 5‐hydroxytryptamine (5‐HT; intravenous infusions of 0.001–40 µg/kg per min) in the autoperfused hindquarters of the rat subjected to electrical stimulation (frequencies of 0.5–20 Hz) of the lumbar chains, investigating the relationship between the adrenergic and serotonergic systems in this vascular bed.

2. Because we observed that 5‐HT inhibited the increases in perfusion pressure induced by electrical stimulation of the lumbar chains, we used different agonists and antagonists to analyse the mechanism of action of 5‐HT.

3. The effect of 5‐HT was inhibited by methiothepin (a non‐specific 5‐HT receptor antagonist), but not by ritanserin (a selective 5‐HT2 receptor antagonist). The effects of 5‐HT were mimicked by 5‐carboxamidotryptamine (a 5‐HT1 receptor agonist) and L‐694 247 (a selective 5‐HT1D receptor agonist), but not by 8‐hydroxy‐2‐dipropylaminotetralin (a 5‐HT1A receptor agonist), CGS‐12066B (a 5‐HT1B receptor agonist), α‐methyl‐5‐HT (a 5‐HT2 receptor agonist), 1‐(3‐chlorophenyl) piperazine (a 5‐HT2C receptor agonist) or 1‐phenylbiguanide (a 5‐HT3 receptor agonist). The selective 5‐HT1D/1B receptor antagonist BRL 15572 inhibited the effect of the agonist L‐694 247.

4. Our data suggest that 5‐HT inhibits the increases in perfusion pressure induced by the electrical stimulation of the lumbar chains, acting on presynaptic 5‐HT1D receptors and decreasing the release of noradrenaline from the sympathetic nerves in the hindquarter vascular bed of the rat.
Left–right asymmetry in the alimentary canal of the Drosophila embryo
Authors: Hayashi Makoto , Aono Hikomaru , Ishihara Junichi , Oshima Sadaaki , Yamamoto Hideaki , Nakazato Yu‐ichi , Kobayashi Satoru
Published: September 2005

In many animal groups, left–right (LR) asymmetry within the body is observed. The left and right sides of the body are generally defined with reference to the anterior–posterior (AP) and dorsal–ventral (DV) axes. In this study, we investigated whether LR asymmetry is solely dependent on the AP and DV polarities in Drosophila embryos. We focused on the proventriculus, a posterior part of the foregut, and the hindgut because LR asymmetry in these body parts is highly stable in normal embryos. In embryos with a fully reversed AP polarity, LR asymmetry in both the proventriculus and the hindgut was re‐oriented in relation to the reversed AP polarity. This demonstrates that inversion of AP polarity does not affect LR asymmetry of these tissues, and implies that LR asymmetry is specified in relation to the AP and DV polarities. Our findings were not consistent with the alternative hypothesis that LR asymmetry is predetermined by maternal signals that localize asymmetrically along the LR axis in the oocyte and/or early embryo.
Effect of phase limited inhibition of MyoD expression on the terminal differentiation of bovine myoblasts: No alteration of Myf5 or myogenin expression
Authors: Muroya Susumu , Nakajima Ikuyo , Oe Mika , Chikuni Koichi
Published: September 2005

To investigate the roles played by MyoD in the terminal differentiation of satellite cell‐derived myoblasts, the effect of antisense inhibition of MyoD expression was examined in bovine adult myoblast culture, in which inhibition treatment was limited to the terminal differentiation phase. MyoD antisense oligonucleotide DNA (AS‐mD) suppressed the formation of multinucleated myotubes in the cell culture. Myotube formation was suppressed even when AS‐mD treatment was limited to the period preceding the onset of myotube formation. Reverse transcriptase–polymerase chain reaction (RT–PCR) analysis revealed that treatment with AS‐mD suppressed the expression of myosin heavy chain embryonic isoform and troponin T isoforms at 4 days after the induction of differentiation. AS‐mD also suppressed the expression of MRF4, but did not alter the expression of either Myf5 or myogenin, in contrast to previous results using mouse cells possessing MyoD(–/–) genetic background. These findings suggest that MyoD controls myogenesis but not Myf5 or myogenin mRNA expression during the terminal differentiation phase. Furthermore, among the α4, α5, α6, and α7 integrins, α4, α5, and α7 integrin expression was suppressed by AS‐mD treatment, in parallel with the suppression of myotube formation, which suggests that MyoD controls myotube formation by regulating the expression of α4, α5, and α7 integrins.
DNA methylation differences in human p14.5 gene promoter region in normal and proliferating cells
Authors: Pozdniakovaite Natalija , Popendikyte Violeta
Published: September 2005

Methylation status of cytosines and its changes during cell proliferation was analyzed in the 5′‐flanking region of the human p14.5 gene, which encodes a member of the YER057c/YIL051c/YjgF protein family. We describe evidence of dramatic DNA methylation differences revealed in the study, and present detailed mapping of methylated cytosines (metC) at the 5′‐flanking region of the p14.5 gene in several human normal tissues and tumor cells lines. DNA methylation profiles demonstrated aberrant distribution of metC positions with the different degree of methylation along all analyzed 5′‐flanking regions of the p14.5 gene in cancer cells. We investigated DNA methylation changes in p14.5 5′‐flanking region during cell differentiation by using DNA samples of freshly isolated monocytes and macrophages. According to our data, cellular differentiation processes from monocytes to macrophages are related to the elevated degree of DNA methylation of the p14.5 gene at the putative binding motifs for several transcription factors. The present findings indicate that some cytosines in the promoter region may have some significance in the degree of expression of the p14.5 gene during cell proliferation and cancerogenesis.
Photodynamic therapy in the management of juxtapapillary capillary haemangiomas
Authors: Golshevsky Jonathan R , O'Day Justin
Published: September 2005

Abstract

Capillary haemangiomas occurring on or adjacent to the optic disc pose unique therapeutic problems. Their natural history is highly variable, but has a propensity to lead to the development of progressive exudate with marked deterioration in visual acuity, often culminating in retinal detachment and vitreal haemorrhages. On reviewing the literature, no therapeutic modality has demonstrated an efficacy in treating the lesion and providing an acceptable visual acuity result. A case of a 61‐year‐old man with a left‐sided juxtapapillary capillary haemangioma treated with verteporfin photodynamic therapy is described. The patient's visual acuity improved from 6/36 to 6/12 initially, with an appreciable reduction in exudate and lesion size. Subsequent treatments failed to eradicate the lesion, with visual acuity stabilizing at 6/60. With larger cohorts of patients and variable treatment parameters, the true efficacy of photodynamic therapy to treat these lesions may be determined.
Glial heterotopia of the orbit and extranasal region: an unusual entity
Authors: Bajaj Mandeep S , Kashyap Seema , Wagh Vijay B , Pathak Harish , Shrey Dinesh
Published: September 2005

Abstract

Glial heterotopia or the occurrence of isolated non‐teratomatous extracranial glial tissue is rare. Most of the reported cases of this entity arise in the nose. Herein a rare case of heterotopic glial tissue in the orbit and extranasal region without bony defect is described.
Bruch's membrane and the vascular intima: is there a common basis for age‐related changes and disease?
Authors: Sivaprasad Sobha , Bailey Tracey A , Chong Victor NH
Published: September 2005

Abstract

Several clinical and epidemiological studies have concurrently illuminated established cardiovascular risk factors in age‐related macular degeneration (AMD), raising the possibility that cardiovascular disease and AMD may share a similar pathogenic process. The vascular intima and the Bruch's membrane share several age‐related changes and are the seat of many common molecules. Diseases of these structures may represent parallel responses to the tissue injury induced by multiple intercalated factors such as genetic variations, oxidative stress, inappropriately directed immune response or inflammatory disease complex. However, there are marked differences in the age‐related changes in these two structures. The strategic location of the Bruch's membrane between the retinal pigment epithelium and the choriocapillaris can at least partially explain the differential susceptibility of AMD to cardiovascular risk factors. Unlike the vascular wall that is exposed to changes from the endothelium, the Bruch's membrane is subject to changes from both the endothelium (choriocapillaris) and epithelium (retinal pigment epithelium). Moreover, although both the vascular wall and Bruch's membrane become lipid laden with age, the lipid composition is characteristically different. This review examines the morphological and biochemical alterations in the senescent Bruch's membrane and its analogy to the vascular wall to evaluate the concurrence of atherosclerosis and AMD.
Fascicular keratitis in children: can corneal phlycten be mobile?
Authors: Taherian Kasra , Shekarchian Mina , Taylor Robert H
Published: September 2005

Abstract

Phlyctenulosis is an uncommon condition that usually affects children's cornea or conjunctiva. Although its exact aetiology is unknown, it is thought to be a non‐specific delayed hypersensitivity reaction to staphylococci or other bacterial, fungal or parasitic antigens. Herein a case of a 3.5‐year‐old boy with corneal phlyctenulosis is described in whom the phlycten appears to have has migrated from its origin at the limbus to the central cornea (fascicular keratitis) and become visually disabling. At his last follow up he was asymptomatic. Some stromal scarring of the right cornea remained and his visual acuity improved in both eyes following treatment.
Skew deviation: a precursor to basilar artery thrombosis
Authors: Mennel Stefan , Hergan Klaus , Peter Silvia
Published: September 2005

Abstract

The aim of this study was to describe skew deviation and vertical nystagmus as the initial signs for basilar artery thrombosis, a life‐threatening disease. A 51‐year‐old woman complained of vertical diplopia for more than 20 h. A computed tomography of the brain was normal, but subsequently the patient developed additional symptoms including nausea, ventilation problems (dyspnoea) and somnolence. Neuro‐ophthalmological evaluation revealed a skew deviation and a vertical nystagmus. Magnetic resonance imaging allowed the diagnosis of basilar artery occlusion. An emergency intervention with cerebral catheter angiography and local intra‐arterial thrombolysis was performed. Total recanalization of the basilar artery was achieved resulting in a complete neurological recovery, including the skew deviation and nystagmus. This rare case of skew deviation associated with basilar artery occlusion was a diagnostic challenge and highlights adequate differential diagnosis. Skew deviation is an important clinical sign. In this patient it was the key to a correct diagnosis enabling an immediate and successful intervention.
Priming Effects in Explicit and Implicit Memory for Textual Advertisements
Authors: Finlay Karen , Marmurek Harvey H.C. , Morton Rachel
Published: September 2005

Les effets d’une amorce sur les mémoires implicite et explicite à propos d’un produit placé dans un texte ont été mis à l’épreuve sous deux conditions, l’une où l’attention était orientée vers (encodage intentionnel) ou détournée du produit (encodage incident). Dans la première expérience, les caractéristiques positives d’un produit avaient plus de chances que les négatives d’être restituées, ce qui a conduit à un effet d’assimilation dans une condition témoin. Par contre, lorsque les particularités du produit étaient en amorec, le rappel explicite des caractéristiques négatives augmentait, débouchant sur un effet de contraste. L’impact de l’amorce était limitéà la condition d’encodage intentionnel, ce qui signifiait un effacement de l’information incompatible avec l’amorce. Dans la deuxième expérience, les épreuves de mémoires implicites perceptuelle et sémantique ont montré des effets d’amorce équivalents suite à l’encodage du produit, qu’il soit intentionnel ou incident. Par suite et contrairement à la mémoire explicite, la mémoire implicite du produit n’était pas conditionnée par l’attention. L’identification de ces limites de l’amorçage est utile aux gens de marketing qui envisagent ce consevoir une publicité exploitant les mémoires explicite et implicite d’un produit.

The effects of priming on explicit and implicit memory about a product placed within a narrative were tested under conditions in which attention was drawn to (intentional encoding) or away from (incidental encoding) the product. In Experiment 1, positive features of a product were more likely to be recalled than negative features leading to an assimilation effect in a baseline condition. When the product characteristic was primed, however, explicit recall of the negative features increased resulting in a contrast effect. The impact of priming was restricted to the intentional encoding condition reflecting resolution of information incongruent with the prime. In Experiment 2, perceptual and semantic implicit memory tests revealed equivalent priming effects following both intentional and incidental encoding of the product. Thus, unlike explicit memory, implicit memory for the product was not limited by attention. Recognition of these boundary conditions of priming informs marketers intending to design advertising that taps explicit and implicit memory for a product.