bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis
Authors: Ford P. J. , Gemmell E. , Hamlet S. M. , Hasan A. , Walker P. J. , West M. J. , Cullinan M. P. , Seymour G. J.
Published: August 2005

Background/aims:  Chronic infections such as those caused by Chlamydia pneumoniae and periodontopathic bacteria such as Porphyromonas gingivalis have been associated with atherosclerosis, possibly due to cross‐reactivity of the immune response to bacterial GroEL with human heat shock protein (hHSP) 60.

Methods:  We examined the cross‐reactivity of anti‐GroEL and anti‐P. gingivalis antibodies with hHSP60 in atherosclerosis patients and quantified a panel of six pathogens in atheromas.

Results:  After absorption of plasma samples with hHSP60, there were variable reductions in the levels of anti‐GroEL and anti‐P. gingivalis antibodies, suggesting that these antibodies cross‐reacted with hHSP60. All of the artery specimens were positive for P. gingivalis. Fusobacterium nucleatum, Tannerella forsythia, C. pneumoniae, Helicobacter pylori, and Haemophilus influenzae were found in 84%, 48%, 28%, 4%, and 4% of arteries, respectively. The prevalence of the three periodontopathic microorganisms, P. gingivalis, F. nucleatum and T. forsythia, was significantly higher than that of the remaining three microorganisms.

Conclusions:  These results support the hypothesis that in some patients, cross‐reactivity of the immune response to bacterial HSPs including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may be a possible mechanism for the association between atherosclerosis and periodontal infection.
Molecular analysis of the genes involved in the biosynthesis of serotype specific polysaccharide in the novel serotype k strains of Streptococcus mutans
Authors: Nomura R. , Nakano K. , Ooshima T.
Published: August 2005

We previously reported the new serotype k of Streptococcus mutans, which, compared to serotypes c, e, and f, features a drastic reduction in the length of the glucose side chain linked to the rhamnose backbone of the serotype specific polysaccharide. The 5′ region of the rgpF gene of serotype k strains contains a distinctive nucleotide sequence, which suggests that an alteration of the rgpF gene in serotype k strains may explain the shortened glucose side chain. However, in the present study, expression of the rgpF gene of MT8148 (serotype c) in serotype k isolates was not found to lead to serotype conversion. Furthermore, mRNA expression of rgpE, known to be associated with glucose side chain formation, was not detected in any of the tested serotype k isolates with an RT‐PCR method. The nucleotide alignment of all genes known to be involved in the biosynthesis of serotype specific polysaccharide in serotype k strains was shown to be quite similar to that of serotype c strains, as compared to serotype e and f strains, especially in the region downstream of rgpF. Our results indicate that the common characteristics of serotype k isolates may be caused by a lack of expression of the gene involved in glucose side chain formation.
Secondary myelodysplastic syndrome after small cell lung cancer and esophageal cancer
Authors: OTSUKA YUICHI , KONISHI TOSHIRO , NARA SATOSHI , FURUSHIMA KAORU , NAKAJIMA KENTARO , SHIMADA HIROSHI
Published: August 2005

Abstract  A 50‐year‐old man was referred to our department with esophageal cancer. He had past history of small cell lung cancer treated with chemoradiation therapy 10 years prior. The disease was evaluated as complete remission after chemoradiation therapy and no recurrence had been observed. Esophagectomy accompanying postoperative chemotherapy was applied, but he died of secondary myelodysplastic syndrome with its acute myeloblastic transformation. Risk evaluation revealed a high incidence of esophageal cancer after radiation therapy and hematological malignancies after chemoradiation therapy in usual regimen with topoisomerase inhibitor or alkylating agents. Chemoradiation therapy is thought to be one of a few highly effective therapeutic alternatives and many complete remission cases have been reported in small cell lung cancer or esophageal cancer. In post‐therapeutic follow up of patients with such past therapeutic histories, we should be cautious about secondary malignancies even if primary malignant disease was evaluated as complete remission in long past history.
Results of alcohol and albendazole injections in hepatic hydatidosis: Experimental study
Authors: YETIM IBRAHIM , ERZURUMLU KENAN , HOKELEK MURAT , BARIS SANCAR , DERVISOGLU ADEM , POLAT CAFER , BELET UMIT , BUYUKKARABACAK YALÇIN , GUVENLI ABDULLAH
Published: August 2005

Background:  Percutaneous drainage with alcohol injection for hydatid cysts has been commonly used in the last two decades. Albendazole is the drug of choice in the medical treatment of hydatidosis, and has also been used as an intraoperative scolicidal solution. The side‐effects of its local application are not well known and have not been investigated. The purpose of the present study was to investigate the effects of the intracystic injections of alcohol and albendazole solutions on the hydatid cysts and hepatobiliary system of rabbits.

Methods:  There were three groups of eight rabbits: a control group, an alcohol group and an albendazole group. In all groups hepatic hydatidosis was obtained. The control group received no therapeutic procedure. Cyst liquid was aspirated, and alcohol or albendazole solutions were injected in the other two study groups. alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ‐glutamyl transferase (GGT) levels, echinococcus indirect hemagglutination (IHA) tests, and the size and volume of the residual cysts were investigated. Liver was histopathologically evaluated.

Results:  The ALT, AST, GGT, and alkaline phosphatase (ALP) levels were significantly higher in the alcohol group, whereas echinococcus IHA level was highest in the control group than in the study groups. Albendazole had similar effects but of a lesser degree (P < 0.01). After therapy, the cyst volume was greater in the control than in the albendazole group (P < 0.01). In histopathological evaluation hepatocellular necrosis, portal inflammation and fibrosis were most severe in the alcohol group (P < 0.01).

Conclusions:  Alcohol and albendazole solutions are effective as scolicidal solutions. Higher scolicidal effect and lesser side‐effects on hepatobiliary system are the advantages of albendazole solution.

© 2005 Blackwell Publishing Asia Pty Ltd
Helicobacter pylorieradication decreases the expression of glycosylphosphatidylinositol‐anchored complement regulators, decay‐accelerating factor and homologous restriction factor 20, in human gastric epithelium
Authors: JOH TAKASHI , SASAKI MAKOTO , KATAOKA HIROMI , TANIDA SATOSHI , ITOH KEISUKE , KONDO YUTAKA , OGASAWARA NAOTAKA , OSHIMA TADAYUKI , OKADA NORIKO , OHARA HIROTAKA , SANO HITOSHI , NAKAO HARUKI , SOBUE SATOSHI , ITOH MAKOTO
Published: August 2005

Background:It has previously been reported that there is a strong correlation between the expression of glycosylphosphatidylinositol (GPI)‐anchored complement membrane inhibitor in gastric epithelium and the severity of inflammation of gastric mucosa. To investigate the regulation of complement activity in gastric epithelium duringHelicobacter pylori(H. pylori)‐associated gastritis, the expression of GPI‐anchored complement membrane inhibitors, decay‐accelerating factor (DAF) and 20‐kDa homologous restriction factor 20 (HRF20), and membrane cofactor protein (MCP), which is a transmembrane protein, were evaluated after removal of theH. pyloristimulus. Furthermore, the expression of the complement fragment, C3c, was also investigated.

Methods:Forty‐six patients with epigastric symptoms and endoscopically confirmed peptic ulcer or gastritis who hadH. pyloriinfection of the gastric mucosa were enrolled in the present study. Biopsy specimens were obtained from the gastric antrum and corpus 1 month before and after eradication.Helicobacter pyloriinfection was determined by the rapid urease test, histology, and culture before eradication, and by histology, culture, and urea breath test after eradication. Gastric biopsy specimens obtained before and after eradication were evaluated for infiltration by neutrophils and mononuclear cells. The expression of complement membrane inhibitors, DAF, HRF20, and MCP and that of the main complement fragment, C3c, was immunohistochemically evaluated.

Results:One month after the eradication ofH. pylori, the infiltration by neutrophils and mononuclear cells in the gastric mucosa decreased significantly (P < 0.0001) as compared with that before eradication. The expression of DAF, HRF20, and C3c on gastric mucosal epithelium also significantly decreased in both the antrum and the corpus (P < 0.05) 1 month after eradication. However, no change was observed in the expression of MCP.

Conclusions:The decrease in the expression of GPI‐anchored complement regulator and the complement after removal of a chronic microbial stimulus suggests that the gastric epithelium appears to undergo an aggressive stress of complement duringH. pyloriinfection. Conclusively, DAF and HRF20 may play an important protective role against complement‐mediated damage induced by chronic microbial stimuli in such a pathological condition.
Effects of HFE gene mutations and alcohol on iron status, liver biochemistry and morbidity
Authors: OLYNYK JOHN K , KNUIMAN MATTHEW W , DIVITINI MARK L , BARTHOLOMEW HELEN C , CULLEN DIGBY J , POWELL LAWRIE W
Published: August 2005

Background and Aims:  The aims of the present study were to determine: (i) whether alcohol consumption is greater in individuals with HFE mutations; and (ii) whether common HFE mutations modify the effects of alcohol on serum iron and liver biochemistry or morbidity.

Methods:  The residents of the town of Busselton in Western Australia were subject to cross‐sectional health surveys between 1966 and 1983. In 1994/1995 all surviving participants of the earlier surveys were invited to take part in a follow‐up survey. Logistic, linear and Poisson log‐linear regression analyses were performed in 1490 men and 1452 women from the 1994/1995 survey to assess the relationships between HFE mutations, alcohol, iron levels, liver biochemistry and morbidity.

Results:  Heavy or moderate alcohol consumption was present in 7% or 36% of men and 0.5% or 12% of women, respectively. Alcohol consumption strongly influenced levels of serum ferritin and gamma glutamyl transpeptidase (GGT) and mean cell volume (MCV) in men and women but only alanine aminotransferase (ALT) levels in women. These effects were independent of HFE gene mutations. Hospital admission rates for respiratory disorders were higher in men with the C282Y mutation.

Conclusions:  Alcohol consumption strongly influences serum ferritin and GGT levels and MCV in men and women but only ALT levels in women, and these effects are independent of HFE mutations. HFE gene mutations do not predispose to moderate or heavy alcohol consumption. The C282Y mutation is associated with increased respiratory admission rates in men.

© 2005 Blackwell Publishing Asia Pty Ltd
Prevalence of gastric cancer decreases with age in long‐living elderly in Japan, possibly due to changes in Helicobacter pylori infection status
Authors: KAWADE MASAYA , JOH TAKASHI , OSHIMA TADAYUKI , TAKAHASHI NOBUO , OGAWA KUMIKO , OHARA HIROTAKA , NOMURA TOMOYUKI , ITOH MAKOTO
Published: August 2005

Objectives:  The prevalence of Helicobacter pylori (Hp) infection and the development of gastric cancer are both believed to increase with age in Japan. However, no studies have investigated people older than 65 years in detail. In this study, we investigated the prevalence of Hp infection and gastric cancer in the elderly, and analyzed the influence of both factors on longevity.

Methods:  All patients investigated were 65 years old and over. A total of 1877 autopsy cases were used to investigate the prevalence of gastric cancer and colonic cancer. Serum samples were obtained from 644 patients with dyspepsia and analyzed for Hp‐IgG antibodies. Of these 644 patients, 63 underwent upper gastrointestinal endoscopies. Five biopsies were obtained and evaluated for the following morphological variables: neutrophils, mononuclear cell, atrophy, and intestinal metaplasia. Hp infection was evaluated histologically and with the 13C‐urea breath test.

Results:  The prevalence of gastric cancer was significantly lower in subjects older than 85 years. The positive rate of serum Hp‐IgG, and Hp infection as detected histologically and by the 13C‐urea breath test, also decreased with age. In Hp(+) patients, the neutrophil score significantly decreased with age. In Hp(–) patients, however, the intestinal metaplasia score significantly increased with age.

Conclusions:  The non‐infection of Hp itself is not related to longevity in Japanese elderly, because even Hp(–) patients appear to have been infected previously with Hp. The lower prevalence of gastric cancer in the elderly may be due to the disappearance of Hp colonization, which may contribute to longevity in Japanese elderly.

© 2005 Blackwell Publishing Asia Pty Ltd
Should Orbscan pachometry be performed before or after Goldmann applanation tonometry?
Authors: Huang Ronnie Y. C. , Lam Andrew K. C. , Chan Rufina , Young Shui‐ming
Published: August 2005

Purpose:  To compare the Orbscan central corneal thickness (CCT) values before and after intraocular pressure (IOP) measurement with Goldmann applanation tonometry in young normal adults.

Materials and Methods:  Fifty‐three eyes of 53 subjects who were free from any ocular problems were studied. The measurements included optical pachometry by the Orbscan II system, followed by Goldmann applanation tonometry, and finally Orbscan optical pachometry again. Standard Goldmann technique was adopted with the application of one drop of 0.4% benoxinate and fluorescein sodium prior to the measurement. The same operator was involved in the Orbscan pachometry before and after Goldmann tonometry. Another investigator was responsible for Goldmann tonometry. Three readings were obtained in each case, and the means were used for analysis.

Results:  The mean IOP of the sample was 14.6 ± 2.6 mmHg. There was no significant difference (paired t‐test: p = 0.50) in the mean CCT values before and after the Goldmann tonometry (551 ± 32 and 552 ± 35 μm respectively).

Conclusion:  Standard Goldmann applanation tonometry does not affect the Orbscan CCT values. Measurement of CCT for the adjustment of true IOP can be carried out either before or after Goldmann tonometry.
SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques
Authors: Boyer Jean D. , Robinson Tara M. , Kutzler Michele A. , Parkinson R. , Calarota Sandra A. , Sidhu Maninder K. , Muthumani Karuppiah , Lewis Mark , Pavlakis George , Felber Barbara , Weiner David
Published: August 2005

Abstract:  Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV‐1)‐specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co‐delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)‐12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL‐12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL‐12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co‐injected with the IL‐12 molecular adjuvant. The IL‐12 expanded antigen‐specific IFN‐γ positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL‐12 enhances a CD8 vaccine immune response, however, different cellular profiles.
Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS
Authors: Nichole Cline A. , Bess Julian W. , Piatak Michael, Jr , Lifson Jeffrey D.
Published: August 2005

Abstract:  As new assay methods for quantitative reverse transcription‐polymerase chain reaction (RT‐PCR), such as real time RT‐PCR techniques, approach theoretical limits of per reaction sensitivity, further increments in the sensitivity of measurements of viral load can only be achieved by increasing the amount of input RNA per reaction. We describe a robust, convenient, rapid integrated approach for specimen preparation and real time RT‐PCR assay for plasma simian immunodeficiency virus (SIV) RNA viral load that provides a threshold sensitivity of 10 copy Eq/ml, and tolerates less than optimally processed specimens. The method provides accurate quantitation of viral load for the SIV virus isolates in common use for non‐human primate studies. We demonstrate the utility of the method in sensitively tracking viral load in an animal showing effective control of viral replication to levels below the threshold for quantitation in conventional assays.
Intercellular Gamma‐Herpesvirus Dissemination Involves Co‐Ordinated Intracellular Membrane Protein Transport
Authors: May Janet S. , de Lima Brigitte D. , Colaco Susanna , Stevenson Philip G.
Published: August 2005

The murine gamma‐herpesvirus‐68 (MHV‐68) ORF27 encodes gp48, a type 2 transmembrane glycoprotein that contributes to intercellular viral spread. Gp48 is expressed on the surface of infected cells but is retained intracellularly after transfection. In this study, we show that the multimembrane spanning ORF58 gene product is both necessary and sufficient for gp48 to reach the cell surface. ORF58‐deficient MHV‐68 expressed ORF27 in normal amounts, but retained it in the endoplasmic reticulum (ER). Transfected ORF27 also remained in ER, whereas green fluorescent protein‐tagged ORF58 localized to the ER and trans‐Golgi network. When ORF27 and ORF58 were co‐transfected, they formed a protein complex and reached the cell surface. Surprisingly, ORF58 rather than ORF27 mediated cell binding via a small extracellular loop. The heavily glycosylated ORF27 component of the complex may, therefore, act mainly to protect this loop against antibody. The interdependent transport of ORF27 and ORF58 transport ensures that such protection is always present.
A second novel dye‐linked L‐proline dehydrogenase complex is present in the hyperthermophilic archaeon Pyrococcus horikoshii OT‐3
Authors: Kawakami Ryushi , Sakuraba Haruhiko , Tsuge Hideaki , Goda Shuichiro , Katunuma Nobuhiko , Ohshima Toshihisa
Published: August 2005

Two distinguishable activity bands for dye‐linked l‐proline dehydrogenase (PDH1 and PDH2) were detected when crude extract of the hyperthermophilic archaeon Pyrococcus horikoshii OT‐3 was run on a polyacrylamide gel. After purification, PDH1 was found to be composed of two different subunits with molecular masses of 56 and 43 kDa, whereas PDH2 was composed of four different subunits with molecular masses of 52, 46, 20 and 8 kDa. The native molecular masses of PDH1 and PDH2 were 440 and 101 kDa, respectively, indicating that PDH1 has an α4β4 structure, while PDH2 has an αβγδ structure. PDH2 was found to be similar to the dye‐linked l‐proline dehydrogenase complex from Thermococcus profundus, but PDH1 is a different type of enzyme. After production of the enzyme in Escherichia coli, high‐performance liquid chromatography showed the PDH1 complex to contain the flavins FMN and FAD as well as ATP. Gene expression and biochemical analyses of each subunit revealed that the β subunit bound FAD and exhibited proline dehydrogenase activity, while the α subunit bound ATP, but unlike the corresponding subunit in the T. profundus enzyme, it exhibited neither proline dehydrogenase nor NADH dehydrogenase activity. FMN was not bound to either subunit, suggesting it is situated at the interface between the α and β subunits. A comparison of the amino‐acid sequences showed that the ADP‐binding motif in the α subunit of PDH1 clearly differs from that in the α subunit of PDH2. It thus appears that a second novel dye‐linked l‐proline dehydrogenase complex is produced in P. horikoshii.
Quantitative analysis of ultrasensitive responses
Authors: Legewie Stefan , Blüthgen Nils , Herzel Hanspeter
Published: August 2005

Ultrasensitive responses are common in cellular information transfer because they allow cells to decode extracellular stimuli in an all‐or‐none manner. Biochemical responses are usually analyzed by fitting the Hill equation, and the estimated Hill coefficient is taken as a measure of sensitivity. However, this approach is not appropriate if the response under consideration significantly deviates from the best‐fit Hill equation. In addition, Hill coefficients greater than unity do not necessarily imply ultrasensitive behaviour if basal activation is significant. In order to circumvent these problems we propose a general method for the quantitative analysis of sensitivity, the relative amplification plot, which is based on the response coefficient defined in metabolic control analysis. To quantify sensitivity globally (i.e. over the whole stimulus range) we introduce the integral‐based relative amplification coefficient. Our relative amplification approach can easily be extended to monotonically decreasing, bell‐shaped or nonsaturated responses.
Molecular and functional characterization of a novel splice variant of ANKHD1 that lacks the KH domain and its role in cell survival and apoptosisc
Authors: Miles Melissa C. , Janket Michelle L. , Wheeler Elizabeth D. A. , Chattopadhyay Ansuman , Majumder Biswanath , DeRicco Jeremy , Schafer Elizabeth A. , Ayyavoo Velpandi
Published: August 2005

Multiple ankyrin repeat motif‐containing proteins play an important role in protein–protein interactions. ANKHD1 proteins are known to possess multiple ankyrin repeat domains and a single KH domain with no known function. Using yeast two‐hybrid system analysis, we identified a novel splice variant of ANKHD1. This splice variant of ANKHD1, which we designated as HIV‐1 Vpr‐binding ankyrin repeat protein (VBARP), does not contain the signature KH domain, and codes for only a single ankyrin repeat motif. We characterized VBARP by molecular and functional analysis, revealing that VBARP is ubiquitously expressed in different tissues as well as cell lines of different lineage. In addition, blast searches indicated that orthologs and homologs to VBARP exist in different phyla, suggesting that VBARP might be evolutionarily conserved, and thus may be involved in basic cellular function(s). Furthermore, biochemical analysis revealed the presence of two VBARP isoforms coding for 69 and 49 kDa polypeptides, respectively, that are primarily localized in the cytoplasm. Functional analysis using short interfering RNA approaches indicate that this gene product is essential for cell survival through its regulation of caspases. Taken together, these results indicate that VBARP is a novel splice variant of ANKHD1 and may play a role in cellular apoptosis (antiapoptotic) and cell survival pathway(s).
cAMP inhibits CSF‐1‐stimulated tyrosine phosphorylation but augments CSF‐1R‐mediated macrophage differentiation and ERK activation
Authors: Wilson Nicholas J. , Cross Maddalena , Nguyen Thao , Hamilton John A.
Published: August 2005

Macrophage colony stimulating factor (M‐CSF) or CSF‐1 controls the development of the macrophage lineage through its receptor tyrosine kinase, c‐Fms. cAMP has been shown to influence proliferation and differentiation in many cell types, including macrophages. In addition, modulation of cellular ERK activity often occurs when cAMP levels are raised. We have shown previously that agents that increase cellular cAMP inhibited CSF‐1‐dependent proliferation in murine bone marrow‐derived macrophages (BMM) which was associated with an enhanced extracellular signal‐regulated kinase (ERK) activity. We report here that increasing cAMP levels, by addition of either 8‐bromo cAMP (8BrcAMP) or prostaglandin E1 (PGE1), can induce macrophage differentiation in M1 myeloid cells engineered to express the CSF‐1 receptor (M1/WT cells) and can potentiate CSF‐1‐induced differentiation in the same cells. The enhanced CSF‐1‐dependent differentiation induced by raising cAMP levels correlated with enhanced ERK activity. Thus, elevated cAMP can promote either CSF‐1‐induced differentiation or inhibit CSF‐1‐induced proliferation depending on the cellular context. The mitogen‐activated protein kinase/extracellular signal‐related protein kinase kinase (MEK) inhibitor, PD98059, inhibited both the cAMP‐ and the CSF‐1R‐dependent macrophage differentiation of M1/WT cells suggesting that ERK activity might be important for differentiation in the M1/WT cells. Surprisingly, addition of 8BrcAMP or PGE1 to either CSF‐1‐treated M1/WT or BMM cells suppressed the CSF‐1R‐dependent tyrosine phosphorylation of cellular substrates, including that of the CSF‐1R itself. It appears that there are at least two CSF‐1‐dependent pathway(s), one MEK/ERK dependent pathway and another controlling the bulk of the tyrosine phosphorylation, and that cAMP can modulate signalling through both of these pathways.
Spectroscopic characterization of the isolated heme‐bound PAS‐B domain of neuronal PAS domain protein 2 associated with circadian rhythms
Authors: Koudo Ryoji , Kurokawa Hirofumi , Sato Emiko , Igarashi Jotaro , Uchida Takeshi , Sagami Ikuko , Kitagawa Teizo , Shimizu Toru
Published: August 2005

Neuronal PAS domain protein 2 (NPAS2) is an important transcription factor associated with circadian rhythms. This protein forms a heterodimer with BMAL1, which binds to the E‐box sequence to mediate circadian rhythm‐regulated transcription. NPAS2 has two PAS domains with heme‐binding sites in the N‐terminal portion. In this study, we overexpressed wild‐type and His mutants of the PAS‐B domain (residues 241–416) of mouse NPAS2 and then purified and characterized the isolated heme‐bound proteins. Optical absorption spectra of the wild‐type protein showed that the Fe(III), Fe(II) and Fe(II)–CO complexes are 6‐co‐ordinated low‐spin complexes. On the other hand, resonance Raman spectra indicated that both the Fe(III) and Fe(II) complexes contain mixtures of 5‐co‐ordinated high‐spin and 6‐co‐ordinated low‐spin complexes. Based on inverse correlation between νFe‐CO and νC‐O of the resonance Raman spectra, it appeared that the axial ligand trans to CO of the heme‐bound PAS‐B is His. Six His mutants (His266Ala, His289Ala, His300Ala, His302Ala, His329Ala, and His335Ala) were generated, and their optical absorption spectra were compared. The spectrum of the His335Ala mutant indicated that its Fe(III) complex is the 5‐co‐ordinated high‐spin complex, whereas, like the wild‐type, the complexes for the five other His mutants were 6‐co‐ordinated low‐spin complexes. Thus, our results suggest that one of the axial ligands of Fe(III) in PAS‐B is His335. Also, binding kinetics suggest that heme binding to the PAS‐B domain of NPAS2 is relatively weak compared with that of sperm whale myoglobin.
Characterization of D‐amino‐acid‐containing excitatory conotoxins and redefinition of the I‐conotoxin superfamily
Authors: Buczek Olga , Yoshikami Doju , Watkins Maren , Bulaj Grzegorz , Jimenez Elsie C. , Olivera Baldomero M.
Published: August 2005

Post‐translational isomerization of l‐amino acids to d‐amino acids is a subtle modification, not detectable by standard techniques such as Edman sequencing or MS. Accurate predictions require more sequences of modified polypeptides. A 46‐amino‐acid‐long conotoxin, r11a, belonging to the I‐superfamily was previously shown to have a d‐Phe residue at position 44. In this report, we characterize two related peptides, r11b and r11c, with d‐Phe and d‐Leu, respectively, at the homologous position. Electrophysiological tests show that all three peptides induce repetitive activity in frog motor nerve, and epimerization of the single amino acid at the third position from the C‐terminus attenuates the potency of r11a and r11b, but not that of r11c. Furthermore, r11c (but neither r11a nor r11b) also acts on skeletal muscle. We identified more cDNA clones encoding conopeptide precursors with Cys patterns similar to r11a/b/c. Although the predicted mature toxins have the same cysteine patterns, they belong to two different gene superfamilies. A potential correlation between the identity of the gene superfamily to which the I‐conotoxin belongs and the presence or absence of a d‐amino acid in the primary sequence is discussed. The great diversity of I‐conopeptide sequences provides a rare opportunity for defining parameters that may be important for this most stealthy of all post‐translational modifications. Our results indicate that neither the chemical nature of the side chain nor the precise vicinal sequence around the modified residue seem to be critical, but there may be favored loci for isomerization to a d‐amino acid.
Ecology of an Improbable Association: The Pseudomyrmecine Plant‐antTetraponera tessmanniand the Myrmecophytic LianaVitex thyrsiflora(Lamiaceae) in Cameroon1
Authors: Djiéto‐Lordon Champlain , Dejean Alain , Ring Richard A. , Nkongmeneck Bernard Aloys , Lauga Jacques , McKey Doyle
Published: August 2005

In young individuals of the obligate myrmecophytic lianaVitex thyrsiflora, several species of ants and other arthropods compete for resources offered by the plant. In mature individuals, the only inhabitant is the ant speciesTetraponera tessmanni, which is completely restricted toVitexlianas as its sole host. Established colonies of this ant provide effective defense against herbivores. The association betweenV. thyrsifloraandT. tessmanniis unusual in two respects. First, the climbing life form is rare among myrmecophytes. Secondly, it is surprising that a pseudomyrmecine should be the obligate associate of a liana. Pseudomyrmecine plant‐ants often prune vegetation contacting their host plant. This behavior functions in part to protect against invasion of the host by ecologically dominant ants. In contrast,T. tessmannidoes not prune and is associated with a plant whose success, and thus that of its resident ant colony, depends on contacts with many other plants. Several traits ofV. thyrsifloraandT. tessmannicombine to make the colonization of host plants by potential competitors very difficult. These include behavioral and morphological filters restricting entrance into the plant and exploitation of the resources it can supply; plant anatomical organization that enablesT. tessmanniworkers to carry out all activities, except leaf patrolling, within a single, branched private nesting space within which all food resources offered by the plant are produced; and polygyny, permitting the colony to monopolize a large, rapidly growing and long‐lived territory.
Frugivory and Seed Fate in Bursera inversa (Burseraceae) at Tinigua Park, Colombia: Implications for Primate Conservation1
Authors: Stevenson Pablo R. , Link Andrés , Ramírez Beatriz H.
Published: August 2005

The large ateline primates are efficient seed dispersers in Neotropical forests and hunting is driving their populations to extinction, but we do not know whether other frugivores could substitute primates in their ecological role as seed dispersers. In this study we test this possibility using a potential keystone species (Bursera inversa) at Tinigua Park, Colombia. This plant species allows us to compare seed removal rates between emergent, isolated trees, without primate visitors and trees with connected crowns. We used traps to estimate fruit production and seed removal rates in six different trees, and fruiting trees were observed during 2 yr to quantify the number of seeds manipulated by different animal species. We carried out seed predation experiments to test if seed removal by predators was affected by distance or density effects. We found that the most productive trees attracted more visiting species and seed removal rates differed among trees, the lowest corresponding to trees without primate access. Seed removal rates from the ground by predators were not higher below parental trees than away from them, but the distribution of saplings in the forest suggests that seed dispersal is advantageous. Although it is likely that the effect of primate extinctions will vary depending on tree species traits, conserving the populations of primate seed dispersers is critical to maintain the ecological processes in this forest.
Long‐term effects of streptozotocin‐induced diabetes on the electrocardiogram, physical activity and body temperature in rats
Authors: Howarth F. C. , Jacobson M. , Shafiullah M. , Adeghate E.
Published: August 2005

In vivo biotelemetry studies have demonstrated that short‐term streptozotocin (STZ)‐induced diabetes is associated with a reduction in heart rate (HR) and heart rate variability (HRV) and prolongation of QT and QRS intervals. This study investigates the long‐term effects of STZ‐induced diabetes on the electrocardiogram (ECG), physical activity and body temperature. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. ECG, physical activity and body temperature data were continuously recorded with a telemetry system before and following the administration of STZ (60 mg kg−1) for a period of 22 weeks. HR, physical activity and body temperature declined rapidly 3–5 days after the administration of STZ. The effects became conspicuous with time reaching a new steady state approximately 1–2 weeks after STZ treatment. HR at 4 weeks was 268 ± 5 beats min−1 in diabetic rats compared to 347 ± 12 beats min−1 in age‐matched controls. HRV at 4 weeks was also significantly reduced after STZ treatment (18 ± 3 beats min−1) compared to controls (33 ± 3 beats min−1). HR and HRV were not additionally altered in either diabetic rats (266 ± 5 and 20 ± 4 beats min−1) or age‐matched controls (316 ± 6 and 25 ± 4 beats min−1) at 22 weeks. Reduced physical activity and/or body temperature may partly underlie the reductions in HR and HRV. In addition, the increased power spectral low frequency/high frequency ratio from 4 weeks after STZ treatment may indicate an accompanying disturbance in sympathovagal balance.
New dimensions in tissue engineering: possible models for human physiology
Authors: Baar Keith
Published: August 2005

Tissue engineering is a discipline of great promise. In some areas, such as the cornea, tissues engineered in the laboratory are already in clinical use. In other areas, where the tissue architecture is more complex, there are a number of obstacles to manoeuvre before clinically relevant tissues can be produced. However, even in areas where clinically relevant tissues are decades away, the tissues being produced at the moment provide powerful new models to aid the understanding of complex physiological processes. This article provides a personal view of the role of tissue engineering in advancing our understanding of physiology, with specific attention being paid to musculoskeletal tissues.
CONSTRAINTS ON THE NEUTRINO PARAMETERS FROM THE "RISE-UP" IN THE BORON NEUTRINO SPECTRUM AT LOW ENERGIES
Authors: DEV S. , KUMAR SANJEEV
Published: August 2005

The rise-up in boron neutrino spectrum at low energies has been studied within the framework of "pure LMA" scenario. Indirect bounds on the spectral "upturn" have been obtained from the available solar neutrino data. These bounds have been used to demonstrate the efficacy of the precision measurements of the "upturn" for further constraining the neutrino parameter space allowed by SNO salt phase data. The sterile neutrino flux has been constrained in the light of the recent 766.3 Ty KamLAND spectral data.
LOW SCALE INFLATION AND THE IMMEDIATE HEAVY CURVATON DECAY
Authors: RODRÍGUEZ YEINZON
Published: August 2005

The end of a thermal inflation era, driven by the rolling of a flaton field coupled to the curvaton, cause a huge increase in the curvaton mass and decay rate while the curvaton is still frozen. It is shown that, if this increase is enough for the curvaton to immediately decay, low scale inflation with Hubble parameter H* ~ 103 GeV is achieved for more natural values of the flaton-curvaton coupling constant λ (10-10≲λ≲ 10-4) and the curvaton bare mass mσ (mσ ≲ 1 GeV ).
n-QUASI-ISOTOPY I: QUESTIONS OF NILPOTENCE
Authors: MELIKHOV SERGEY A. , REPOVŠ DUŠAN
Published: August 2005

It is well-known that no knot can be cancelled in a connected sum with another knot, whereas every link can be cancelled up to link homotopy in a (componentwise) connected sum with another link. In this paper we address the question whether the noncancellation property of knots holds for (piecewise-linear) links up to some stronger analogue of link homotopy, which still does not distinguish between sufficiently close C0-approximations of a topological link. We introduce a sequence of such increasingly stronger equivalence relations under the name of k-quasi-isotopy, k∈ℕ; all of them are weaker than isotopy (in the sense of Milnor). We prove that every link can be cancelled up to peripheral structure preserving isomorphism of any quotient of the fundamental group, functorially invariant under k-quasi-isotopy; functoriality means that the isomorphism between the quotients for links related by any allowable crossing change fits in the commutative diagram with the fundamental group of the complement to the intermediate singular link. The proof invokes Baer's theorem on the join of subnormal locally nilpotent subgroups. On the other hand, the integral generalized ( lk ≠ 0) Sato–Levine invariant [Formula: see text] is invariant under 1-quasi-isotopy, but is not determined by any quotient of the fundamental group (endowed with the peripheral structure), functorially invariant under 1-quasi-isotopy — in contrast to Waldhausen's theorem.

As a byproduct, we use [Formula: see text] to determine the image of the Kirk–Koschorke invariant [Formula: see text] of fibered link maps.
n-QUASI-ISOTOPY II: COMPARISON
Authors: MELIKHOV SERGEY A. , REPOVŠ DUŠAN
Published: August 2005

Geometric aspects of the filtration on classical links by k-quasi-isotopy are discussed, including the effect of Whitehead doubling, relations with Smythe's n-splitting and Kobayashi's k-contractibility. One observation is: ω-quasi-isotopy is equivalent to PL isotopy for links in a homotopy 3-sphere (respectively, contractible open 3-manifold) M if and only if M is homeomorphic to S3(respectively, ℝ3). As a byproduct of the proof of the "if" part, we obtain that every compact subset of an acyclic open set in a compact orientable 3-manifold M is contained in a PL homology 3-ball in M.

We show that k-quasi-isotopy implies (k + 1)-cobordism of Cochran and Orr. If zm-1(c0+c1z2+⋯+cnz2n) denotes the Conway polynomial of an m-component link, it follows that the residue class of ckmodulo gcd (c0,…,ck-1) is invariant under k-quasi-isotopy. Another corollary is that each Cochran's derived invariant βkis also invariant under k-quasi-isotopy, and therefore assumes the same value on all PL links, sufficiently C0-close to a given topological link. This overcomes an algebraic obstacle encountered by Kojima and Yamasaki, who "became aware of impossibility to define" for wild links what for PL links is equivalent to the formal power series ∑βnznby a change of variable.
TOROIDAL DEHN SURGERIES ON KNOTS IN S1 × S2
Authors: LEE SANGYOP
Published: August 2005

Given a simple manifold, we investigate two Dehn fillings, one of which contains a non-separating sphere and the other contains an essential torus.
ALGEBRAIC STRUCTURES ON GRAPH COHOMOLOGY
Authors: CATTANEO ALBERTO S. , COTTA-RAMUSINO PAOLO , LONGONI RICCARDO
Published: August 2005

We define algebraic structures on graph cohomology and prove that they correspond to algebraic structures on the cohomology of the spaces of imbeddings of S1 or ℝ into ℝn. As a corollary, we deduce the existence of an infinite number of nontrivial cohomology classes in Imb (S1, ℝn) when n is even and greater than 3. Finally, we give a new interpretation of the anomaly term for the Vassiliev invariants in ℝ3.
DISSIPATIVE SOLITON PULSATIONS WITH PERIODS BEYOND THE LASER CAVITY ROUND TRIP TIME
Authors: AKHMEDIEV N. , SOTO-CRESPO J. M. , GRAPINET M. , GRELU Ph.
Published: August 2005

We review recent results on periodic pulsations of the soliton parameters in a passively mode-locked fiber laser. Solitons change their shape, amplitude, width and velocity periodically in time. These pulsations are limit cycles of a dissipative nonlinear system in an infinite-dimensional phase space. Pulsation periods can vary from a few to hundreds of round trips. We present a continuous model of a laser as well as a model with parameter management. The results of the modeling are supported with experimental results obtained using a fiber laser.
TRANSFORMATION OF DIRECTIONAL COUPLERS TO MULTI-MODE INTERFEROMETERS BASED ON RIDGE WAVEGUIDES AND ITS APPLICATIONS
Authors: DARMAWAN S. , LEE S. Y. , LEE C. W. , CHIN M. K.
Published: August 2005

We present a comparison of directional couplers and multi-mode interferometers based on the unique properties of high-index contrast ridge waveguides. The two devices are intimately related as the MMI is structurally derived from the DC. For the first time, the continuous evolution from the two-mode coupling characteristic of DC to the multi-mode mixing and interference characteristic of MMI is shown. We show that practical directional couplers with reasonable gap size can also be quite compact and have the same coupling length for both TE and TM polarizations. Consequently, the DC can be just as polarization insensitive as the MMI. These features, however, require careful design control involving a large set of design parameters. On top of that, we also show a novel design of polarization splitter based on both DC and MMI. By comparison, the MMI design is more robust and involves fewer design variables.
TRANSPARENT TiO2-PMMA NANOHYBRIDS OF HIGH NANOCRYSTALLINITY AND ENHANCED NONLINEAR OPTICAL PROPERTIES
Authors: YUWONO AKHMAD HERMAN , XUE JUNMIN , WANG JOHN , ELIM HENDRY IZAAC , JI WEI
Published: August 2005

Nanohybrid thin films of titania-polymethyl methacrylate ( TiO2 -PMMA) with varying degrees of nanocrystallinity have been successfully synthesized via an in-situ sol gel-polymerization route, assisted by subsequent thermal and water vapor treatments. Post-hydrothermal treatment by water vapor at relatively low temperatures led to a higher degree of crystallinity for TiO2 nanoparticles than the conventional thermal annealing. The degree of TiO2 crystallinity in the resulting nanohybrid films was studied by using XRD, FTIR, UV-Vis spectroscopies and HRTEM. The resulting nanohybrid thin films are highly transparent in the visible region, with an estimated band gap energies, Eg, close to that of anatase TiO2 (~ 3.20 eV). The nanocrystallinity level of TiO2 phase strongly affects both linear and nonlinear optical properties of the nanohybrids. A significant enhancement in linear refractive index, no, up to 1.780 and a third-order nonlinear optical susceptibility, χ(3) as high as 5.27 × 10-9 esu , were demonstrated with the nanohybrid exhibiting the enhanced TiO2 crystallinity and well-preserved PMMA matrix.
Method for the determination of the arteriovenous muscle protein balance during non-steady-state blood and muscle amino acid concentrations
Authors: Katsanos Christos S. , Chinkes David L. , Sheffield-Moore Melinda , Aarsland Asle , Kobayashi Hisamine , Wolfe Robert R.
Published: August 2005

We describe a method based on the traditional arteriovenous balance technique in conjunction with muscle biopsies for the determination of leg muscle protein balance during the nonsteady state in blood amino acid concentrations. Six young, healthy individuals were studied in the postabsorptive state (pre-Phe) and after a bolus ingestion of ∼0.5 g phenylalanine (post-Phe). Post-Phe free phenylalanine concentrations in blood and muscle increased ( P < 0.05), but the respective concentrations of the amino acid threonine did not change. The average post-Phe leg net balance (NB) for threonine decreased from basal ( P < 0.05), but that for phenylalanine did not change. A volume of distribution for free phenylalanine in the leg was calculated based on the leg lean mass and the relative muscle water content and used to estimate the rate of accumulation of free phenylalanine in the leg. When the post-Phe NB for phenylalanine was corrected for the rate of accumulation of free phenylalanine in the leg, the post-Phe NB for phenylalanine decreased from basal ( P < 0.05). This corrected value was not different ( P > 0.05) from the value predicted for the phenylalanine NB based on the pre- and post-Phe NB responses for threonine. We conclude that the protein NB in non-steady-state blood phenylalanine concentrations can be determined from the arteriovenous phenylalanine NB by accounting for changes in free phenylalanine within its volume of distribution.
Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development
Authors: Gnanalingham M. G. , Mostyn A. , Webb R. , Keisler D. H. , Raver N. , Alves-Guerra M. C. , Pecqueur C. , Miroux B. , Symonds M. E. , Stephenson T.
Published: August 2005

In the neonate, adipose tissue and the lung both undergo a rapid transition after birth, which results in dramatic changes in uncoupling protein abundance and glucocorticoid action. Leptin potentially mediates some of these adaptations and is known to promote the loss of uncoupling protein (UCP)1, but its effects on other mitochondrial proteins or glucocorticoid action are not known. We therefore determined the effects of acute and chronic administration of ovine recombinant leptin on brown adipose tissue (BAT) and/or lung in neonatal sheep. For the acute study, eight pairs of 1-day-old lambs received, sequentially, 10, 100, and 100 μg of leptin or vehicle before tissue sampling 4 h from the start of the study, whereas in the chronic study, nine pairs of 1-day-old lambs received 100 μg of leptin or vehicle daily for 6 days before tissue sampling on day 7. Acute leptin decreased the abundance of UCP2, glucocorticoid receptor, and 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 mRNA and increased 11β-HSD type 2 mRNA abundance in BAT, a pattern that was reversed with chronic leptin administration, which also diminished lung UCP2 protein abundance. In BAT, UCP2 mRNA abundance was positively correlated to plasma leptin and nonesterified fatty acids and negatively correlated to mean colonic temperature in the leptin group at 7 days. In conclusion, leptin administration to the neonatal lambs causes differential effects on UCP2 abundance in BAT and lung. These effects may be important in the development of these tissues, thereby optimizing lung function and fat growth.