bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection by and protective immune responses against Plasmodium berghei ANKA are not affected in macrophage scavenger receptors A deficient mice
Authors: Cunha-Rodrigues Margarida , Portugal Sílvia , Febbraio Maria , Mota Maria M
Published: August 2006

Background

Scavenger receptors (SRs) recognize endogenous molecules modified by pathological processes as well as components of diverse microorganisms. Mice deficient for both SR-AI and II are more susceptible to infections by a variety of bacterial and viral pathogens.

Results

Here we show that SR-A deficient mice and wild type mice are equally susceptible to malaria infection both during liver and blood stages. Moreover, like wild type mice, SR-A deficient mice are able to mount a protective immune response against radiation attenuated sporozoites.

Conclusion

Our results do not reveal a function of SR-A I and II receptors in the Plasmodium berghei ANKA infection, both in the development of CM and parasitemia control. Moreover, these receptors appear not to be required for the establishment of a protective immune response against the malaria liver stages.
Water incident related hospital activity across England between 1997/8 and 2003/4: a retrospective descriptive study
Authors: Henderson Holly , Wilson Richard C
Published: August 2006

Background

No one has ever reported or investigated the number of people who have been admitted to hospital for a water related incident. The purpose of this paper is to examine, the hospital activity resulting from such incidents including to length of stay, gender, age and cause.

Methods

The data was extracted from the Hospital Episode Statistics (HES) for episodes with a mention of ICD 10 (V90–94, W15–16, W65–74, X38, X92, Y21) for the years 1997/8 to 2003/4. Population based rates and relative risk were calculated using the most recent Census data for England (2001).

Results

The 6,793 episodes resulted in a total of 32,520 bed days with an average of length of stay of 5.0 days. Males made up 73.7% (n = 5,006) of episodes and females 26.1% (n = 1,787). Annual trends peaked in 1999–2000 at a rate of 2.4 per 100,000 and have fluctuated on alternate years there after. In terms of relative risk males are at a 2.3 to 3.0 increased annual risk of being admitted compared to females, relating to a water event. The highest annual rates were observed within the 0 – 14 age group, ranging from 3.1 to 4.2 episodes per 100,000.

Conclusion

Based on these findings, for every one drowning that occurs per year there are three hospital episodes. Each of the age groups identified within the study reported an increase in hospital episodes between 2002 – 2003 and 2003 – 2004, when considering the fatality information available it would appear that although fatalities are decreasing in the similar time period, hospital episodes are increasing.

For the 0–14 age group, the cause of the injury had changed over the years, moving away from bath tub and swimming pool, to watercraft incidents (V91 – 93). For the 15 – 59 age group there had been a decline in the frequency of watercraft and water transport episodes, however, an increase in diving and jumping injury and incidents. In the over 60 age group water transport episodes remained the most frequent, with swimming pool related episodes declining and other specified drowning and submersion increasing.

More work needs to be undertaken in regard to who is admitted to hospital, when where, and how to fill gaps in knowledge and highlight information that is critical to prevention strategies.
Anticancer activity of extracts derived from the mature roots of Scutellaria baicalensis on human malignant brain tumor cells
Authors: Scheck Adrienne C , Perry Krya , Hank Nicole C , Clark W Dennis
Published: August 2006

Background

Flavonoid-rich extracts from the mature roots of Scutellaria baicalensis have been shown to exhibit antiproliferative effects on various cancer cell lines. We assessed the ability of an ethanolic extract of S. baicalensis root to inhibit the proliferation of malignant glioma cells.

Methods

Cell lines derived from primary and recurrent brain tumors from the same patient and cells selected for resistance to the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were used to identify antiproliferative effects of this extract when used alone and in conjunction with BCNU.

Results and discussion

Results indicated that Scutellaria baicalensis not only inhibits cellular growth in recurrent and drug resistant brain tumor cell lines, but also demonstrates an increased inhibitory effect when used in conjunction with BCNU.

Conclusion

The results of this study support the efficacy of S. baicalensis as an anticancer agent for glioblastomas multiforme and a potential adjuvant treatment to current chemotherapeutic agents used in the treatment of both primary and recurrent GBMs. Further studies of the effects of individual flavonoids alone and in combination with each other and with currently used therapies are needed.
The influence of completing a health-related questionnaire on primary care consultation behaviour
Authors: Jeffery Amanda , Jinks Clare , Jordan Kelvin
Published: August 2006

Background

Surveys of the population are commonly used to obtain information on health status. Increasingly, researchers are linking self-reported health status information to primary care consultation data. However, it is not known how participating in a health-related survey affects consultation behaviour. The objective of this study was to assess whether completion of a health-related questionnaire changes primary care consultation behaviour.

Methods

Participants were 3402 adults aged 50 and over from the general population in North Staffordshire, UK, who completed a health-related postal survey received in April 2003. The survey was predominantly about occurrence and severity of knee pain in the last year. Primary care attendance for the three months following response was compared to three control periods: i) the three months prior to the survey, ii) the same time period in the previous year and iii) the same time period in the following year. Comparisons were made on consultations for any problem, consultations for musculoskeletal disorders and consultations for knee problems.

Results

The percentage of subjects consulting for any condition was marginally higher for the three months directly after receipt of the questionnaire but the difference was only statistically significant in comparison to the three months before the survey (64% v. 62%, p = 0.05). There was little difference in consultation prevalence for musculoskeletal problems immediately after the survey compared to the three control periods. There was an increase of 37% in knee disorder consultations for the three months after the survey compared to the three months directly before the survey (p = 0.02). However, consultation prevalence for knee problems was identical for the three months after the survey to the same time periods in the years prior to and following the survey (both p = 0.94).

Conclusion

The results from this study suggests that questionnaires related to physical health do not affect the standard consulting behaviour of patients, even for the symptom under investigation. This should reassure researchers who wish to link self-reported health status and medical care utilisation and clinicians whose patients are involved in such research.
Identifying conditions for inducible protein production in E. coli: combining a fed-batch and multiple induction approach
Authors: Aucoin Marc G , McMurray-Beaulieu Virginie , Poulin Frédéric , Boivin Eric B , Chen Jingkui , Ardelean Francisc M , Cloutier Mathieu , Choi Young J , Miguez Carlos B , Jolicoeur Mario
Published: August 2006

Background

In the interest of generating large amounts of recombinant protein, inducible systems have been studied to maximize both the growth of the culture and the production of foreign proteins. Even though thermo-inducible systems were developed in the late 1970's, the number of studies that focus on strategies for the implementation at bioreactor scale is limited. In this work, the bacteriophage lambda PL promoter is once again investigated as an inducible element but for the production of green fluorescent protein (GFP). Culture temperature, induction point, induction duration and number of inductions were considered as factors to maximize GFP production in a 20-L bioreactor.

Results

It was found that cultures carried out at 37°C resulted in a growth-associated production of GFP without the need of an induction at 42°C. Specific production was similar to what was achieved when separating the growth and production phases. Shake flask cultures were used to screen for desirable operating conditions. It was found that multiple inductions increased the production of GFP. Induction decreased the growth rate and substrate yield coefficients; therefore, two time domains (before and after induction) having different kinetic parameters were created to fit a model to the data collected.

Conclusion

Based on two batch runs and the simulation of culture dynamics, a pre-defined feeding and induction strategy was developed to increase the volumetric yield of a temperature regulated expression system and was successfully implemented in a 20-L bioreactor. An overall cell density of 5.95 g DW l-1 was achieved without detriment to the cell specific production of GFP; however, the production of GFP was underestimated in the simulations due to a significant contribution of non-growth associated product formation under limiting nutrient conditions.
Adenoid basal carcinoma of the cervix in a 20-year-old female: a case report
Authors: DePond William David , Flauta Victor Santos , Lingamfelter Daniel Christian , Schnee David Mark , Menendez Kristyn Poncy
Published: August 2006

Background

Adenoid basal carcinoma of the cervix is a rare condition mostly occurring among postmenopausal women. Although it can be confused with adenoid cystic carcinoma of the cervix, adenoid basal carcinoma has several clinicopathologic features that will allow distinction from adenoid cystic carcinoma.

Case presentation

This is the case of a twenty-year old African-American female who initially presented with a high-grade squamous intraepithelial lesion on Pap smear, with a subsequent cervical LEEP specimen revealing adenoid basal carcinoma. The lesion showed the characteristic histologic features of adenoid basal carcinoma and was positive for the immunohistochemical marker EMA and negative for collagen IV, further defining the tumor while helping to rule out the possibility of adenoid cystic carcinoma. As far as the authors are aware, this is the youngest reported case of adenoid basal carcinoma to date.

Conclusion

This case shows that adenoid basal carcinoma can deviate markedly from its typical postmenopausal demographics to affect women as young as 20 years of age. In addition, adenoid basal carcinoma has several identifiable features that will differentiate it from adenoid cystic carcinoma including histologic and cellular morphologies, as well as immunohistochemistry. Treatment for most patients involves hysterectomy, LEEP, or a conization procedure which provides a favorable prognosis because of this lesion's low potential for recurrence and metastasis.
Role of gp120 in dendritic cell dysfunction in HIV infection
Authors: Chougnet Claire , Gessani Sandra
Published: August 2006

Only a limited fraction of circulating virions are demonstrably infectious; therefore, exposure to inactivated viruses may mimic the most frequent type of CD4-HIV interactions that occur in vivo. Several studies have recently underscored the crucial role that those noninfectious viruses could play in defective immune function in HIV-infected individuals and in particular, in the dysregulation of dendritic cell (DC) function. In this review, we discuss how interactions between DC and HIV gp120 or inactivated virus, which harbor intact surface gp120, lead to impaired DC function through direct (direct contact) or indirect mechanisms (as a consequence of primary CD4+ T cell dysregulation, followed by defective CD4-DC interactions). It is important that these functionally impaired DCs fail to give optimal signal to T cells but appear to favor the emergence of regulatory T cells. gp120-mediated impairment of DC function could therefore play an important role in the pathogenesis of HIV disease.
The glutamate-glutamine cycle as an inducible, protective face of macrophage activation
Authors: Gras Gabriel , Porcheray Fabrice , Samah Boubekeur , Leone Cathie
Published: August 2006

Neuronal damage in HIV infection results mainly from chronic activation of brain tissue and involves inflammation, oxidative stress, and glutamate-related neurotoxicity. Glutamate toxicity acts via two distinct pathways: an excitotoxic one, in which glutamate receptors are hyperactivated, and an oxidative one, in which cystine uptake is inhibited, resulting in glutathione depletion, oxidative stress, and cell degeneration. A number of studies have shown that astrocytes normally take up glutamate, keeping extracellular glutamate concentration low in the brain and preventing excitotoxicity. They, in turn, provide the trophic amino acid glutamine via their expression of glutamine synthetase. These protective and trophic actions are inhibited in HIV infection, probably as a result of the effects of inflammatory mediators and viral proteins. In vitro and in vivo studies have demonstrated that activated microglia and brain macrophages (AMM) express the transporters and enzymes of the glutamate cycle. This suggests that in addition to their recognized neurotoxic properties in HIV infection, these cells exhibit some neuroprotective properties, which may partly compensate for the inhibited astrocytic function. This hypothesis might explain the discrepancy between microglial activation, which occurs early in the disease, and neuronal apoptosis and neuronal loss, which are late events. In this review, we discuss the possible neuroprotective and neurotrophic roles of AMM and their relationships with inflammation and oxidative stress.
Cathepsin K in Adipocyte Differentiation and Its Potential Role in the Pathogenesis of Obesity
Authors: Xiao Yin , Junfeng Han , Tianhong Luo , Lu Wang , Shulin Chen , Yu Zhao , Xiaohua Li , Weixia Jian , Sheng Zheng , Yanyun Gu , Guo Li , Min Luo
Published: August 2006

Context: The alteration of protein expression in white adipose tissue (WAT) may contribute to the pathogenesis of obesity.

Objective: The aim of the present study was to uncover proteins differentially expressed in the WAT of overweight/obese subjects and study the role of the identified proteins in adipocyte differentiation.

Design and Setting: Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry were used to identify proteins differentially expressed in WAT between obese/overweight and control groups. Cathepsin K (CTSK), one of the proteins identified by the above methods, was highlighted to assess its effects on adipocyte differentiation through 3T3-L1 cell line.

Results: Human visceral adipose tissue of overweight/obese subjects displayed a differential protein expression profile, compared with that of normal-weight controls. CTSK was up-regulated in the WAT of overweight/obese subjects, and it had a significant positive correlation with body mass index. In vitro study showed that CTSK expression and its enzyme activity gradually increased in the process of adipocyte differentiation. Moreover, E-64, an inhibitor of CTSK, could prevent adipocyte differentiation in a dose-dependent manner, which was characterized by the absence of triglyceride accumulation and glycerol contents.

Conclusions: CTSK, a cysteine protease involved in extracellular matrix remodeling, could be one of the determinants of adipocyte differentiation. CTSK may be involved in the pathogenesis of obesity by promoting adipocyte differentiation.
Differences in the Apparent Metabolic Clearance Rate of Testosterone in Young and Older Men with Gonadotropin Suppression Receiving Graded Doses of Testosterone
Authors: Coviello Andrea D. , Lakshman Kishore , Mazer Norman A. , Bhasin Shalender
Published: August 2006

Background: Recently we found that testosterone levels are higher in older men than young men receiving exogenous testosterone. We hypothesized that older men have lower apparent testosterone metabolic clearance rates (aMCR-T) that contribute to higher testosterone levels.

Objective: The objective of the study was to compare aMCR-T in older and young men and identify predictors of aMCR-T.

Methods: Sixty-one younger (19–35 yr) and 60 older (59–75 yr) men were given a monthly GnRH agonist and weekly testosterone enanthate (TE) (25, 50, 125, 300, or 600 mg) for 5 months. Estimated aMCR-T was calculated from the amount of TE delivered weekly and trough serum testosterone concentrations, corrected for real-time absorption kinetics from the im testosterone depot.

Results: Older men had lower total (316 ± 13 vs. 585 ± 26 ng/dl, P < 0.00001) and free testosterone (4 ± 0.1 vs. 6 ± 0.3 ng/dl, P < 0.00001) and higher SHBG (52 ± 3 vs. 33 ± 2 nmol/liter, P < 0.00001) than younger men at baseline. Total and free testosterones increased with TE dose and were higher in older men than young men in the 125-, 300-, and 600-mg dose groups. aMCR-T was lower in older men than young men (1390 ± 69 vs. 1821 ± 102 liter/d, P = 0.006). aMCR-T correlated negatively with age (P = 0.0007), SHBG (P = 0.046), and total testosterone during treatment (P = 0.02) and percent body fat at baseline (P = 0.01) and during treatment (P = 0.004). aMCR-T correlated positively with lean body mass at baseline (P = 0.03) and during treatment (P = 0.01). In multiple regression models, significant predictors of aMCR-T included lean body mass (P = 0.008), percent fat mass (P = 0.009), and SHBG (P = 0.001).

Conclusions: Higher testosterone levels in older men receiving TE were associated with an age-related decrease in apparent testosterone metabolic clearance rates. Body composition and SHBG were significant predictors of aMCR-T.
Longitudinal Changes in Insulin-Like Growth Factor-I, Insulin Sensitivity, and Secretion from Birth to Age Three Years in Small-for-Gestational-Age Children
Authors: Iñiguez Germán , Ong Ken , Bazaes Rodrigo , Avila Alejandra , Salazar Teresa , Dunger David , Mericq Verónica
Published: August 2006

Introduction: Insulin resistance (IR) develops as early as age 1 to 3 yr in small for gestational age (SGA) infants who show rapid catch-up postnatal weight gain. In contrast, greater insulin secretion is related to infancy height gains. We hypothesized that IGF-I levels could be differentially related to gains in length and weight and also differentially related to IR and insulin secretion.

Methods: In a prospective study of 50 SGA (birth weight < 5th percentile) and 14 normal birth weight [appropriate for gestational age (AGA)] newborns, we measured serum IGF-I levels at birth, 1 yr, and 3 yr. IR (by homeostasis model assessment) and insulin secretion (by short iv glucose tolerance test) were also measured at 1 yr and 3 yr.

Results: SGA infants had similar mean length and weight at 3 yr compared with AGA infants. SGA infants had lower IGF-I levels at birth (P < 0.0001), but conversely they had higher IGF-I levels at 3 yr (P = 0.003) than AGA infants. Within the SGA group, at 1 yr IGF-I was associated with length gain from birth and insulin secretion (P < 0.0001); in contrast at 3 yr IGF-I was positively related to weight, body mass index, and IR.

Conclusions: IGF-I levels increased rapidly from birth in SGA, but not AGA children. During the key first-year growth period, IGF-I levels were related to β-cell function and longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed, IGF-I levels were related to body mass index and IR, and these higher IGF-I levels in SGA infants might indicate the presence of relative IGF-I resistance.
Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity: Associations with Insulin Resistance, Adiponectin, and Visceral Fat
Authors: Burgert Tania S. , Taksali Sara E. , Dziura James , Goodman T. Robin , Yeckel Catherine W. , Papademetris Xenophon , Constable R. Todd , Weiss Ram , Tamborlane William V. , Savoye Mary , Seyal Aisha A. , Caprio Sonia
Published: August 2006

Background: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established.

Methods: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging.

Findings: Elevated ALT (>35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18–35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver.

Interpretation: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.
Nonclassical 21-Hydroxylase Deficiency
Authors: New Maria I.
Published: August 2006

Context: Nonclassical congenital adrenal hyperplasia (CAH) owing to steroid 21-hydroxylase deficiency (NC21OHD) is the most frequent of all autosomal recessive genetic diseases, occurring in one in 100 persons in the heterogeneous New York City population. NC21OHD occurs with increased frequency in certain ethnic groups, such as Ashkenazi Jews, in whom one in 27 express the disease. NC21OHD is underdiagnosed in both male and female patients with hyperandrogenic symptoms because hormonal abnormalities in NC21OHD are only mild to moderate, not severe as in the classical form of CAH. Unlike classical CAH, NC21OHD is not associated with ambiguous genitalia of the newborn female.

Main Outcome Measures: The hyperandrogenic symptoms include advanced bone age, early pubic hair, precocious puberty, tall stature, and early arrest of growth in children; infertility, cystic acne, and short stature in both adult males and females; hirsutism, frontal balding, polycystic ovaries, and irregular menstrual periods in females; and testicular adrenal rest tissue in males.

Conclusions: The signs and symptoms of hyperandrogenism are reversed with dexamethasone treatment.
Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer of the epidermis
Authors: Sur Inderpreet , Rozell Björn , Jaks Viljar , Bergström Åsa , Toftgård Rune
Published: August 2006

Krüppel-like factor5 (Klf5) is a zinc-finger transcription factor normally expressed in the skin. Here, we show that overexpression of Klf5 in the basal layer of the epidermis during embryogenesis affects epidermal development and disrupts epithelial-mesenchymal interactions necessary for skin adnexae formation as well as craniofacial morphogenesis. The transgenic mice exhibited exencephaly, craniofacial defects, persistent abdominal herniation and ectodermal dysplasia. Moreover, the epidermis was hypoplastic and underwent abnormal differentiation with expression of keratin8, a marker for single-layered epithelia, in the stratified epidermis. Correspondingly, we observed a downregulation of ΔNp63 expression in the skin. Overexpression of Klf5 in adult mice led to hyperkeratosis, follicle occlusion and epidermal erosions. Further, we observed decrease and even loss of the stem cell population of bulge keratinocytes, as characterized by the expression pattern of α6 integrin and CD34 markers. Our data suggest a new role of Klf5 as a modulator of p63 expression and the differentiation program of epidermal cells relevant for regenerative potential of the epidermis and epithelial-mesenchymal interactions.
An Ins(1,4,5)P3 receptor in Paramecium is associated with the osmoregulatory system
Authors: Ladenburger Eva-Maria , Korn Iris , Kasielke Nicole , Wassmer Thomas , Plattner Helmut
Published: August 2006

In the ciliate Paramecium, a variety of well characterized processes are regulated by Ca2+, e.g. exocytosis, endocytosis and ciliary beat. Therefore, among protozoa, Paramecium is considered a model organism for Ca2+ signaling, although the molecular identity of the channels responsible for the Ca2+ signals remains largely unknown. We have cloned - for the first time in a protozoan - the full sequence of the gene encoding a putative inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) receptor from Paramecium tetraurelia cells showing molecular characteristics of higher eukaryotic cells. The homologously expressed Ins(1,4,5)P3-binding domain binds [3H]Ins(1,4,5)P3, whereas antibodies unexpectedly localize this protein to the osmoregulatory system. The level of Ins(1,4,5)P3-receptor expression was reduced, as shown on a transcriptional level and by immuno-staining, by decreasing the concentration of extracellular Ca2+ (Paramecium cells rapidly adjust their Ca2+ level to that in the outside medium). Fluorochromes reveal spontaneous fluctuations in cytosolic Ca2+ levels along the osmoregulatory system and these signals change upon activation of caged Ins(1,4,5)P3. Considering the ongoing expulsion of substantial amounts of Ca2+ by the osmoregulatory system, we propose here that Ins(1,4,5)P3 receptors serve a new function, i.e. a latent, graded reflux of Ca2+ to fine-tune [Ca2+] homeostasis.
Validating Aurora B as an anti-cancer drug target
Authors: Girdler Fiona , Gascoigne Karen E. , Eyers Patrick A. , Hartmuth Sonya , Crafter Claire , Foote Kevin M. , Keen Nicholas J. , Taylor Stephen S.
Published: August 2006

The Aurora kinases, a family of mitotic regulators, have received much attention as potential targets for novel anti-cancer therapeutics. Several Aurora kinase inhibitors have been described including ZM447439, which prevents chromosome alignment, spindle checkpoint function and cytokinesis. Subsequently, ZM447439-treated cells exit mitosis without dividing and lose viability. Because ZM447439 inhibits both Aurora A and B, we set out to determine which phenotypes are due to inhibition of which kinase. Using molecular genetic approaches, we show that inhibition of Aurora B kinase activity phenocopies ZM447439. Furthermore, a novel ZM compound, which is 100 times more selective for Aurora B over Aurora A in vitro, induces identical phenotypes. Importantly, inhibition of Aurora B kinase activity induces a penetrant anti-proliferative phenotype, indicating that Aurora B is an attractive anti-cancer drug target. Using molecular genetic and chemical-genetic approaches, we also probe the role of Aurora A kinase activity. We show that simultaneous repression of Aurora A plus induction of a catalytic mutant induces a monopolar phenotype. Consistently, another novel ZM-related inhibitor, which is 20 times as potent against Aurora A compared with ZM447439, induces a monopolar phenotype. Expression of a drug-resistant Aurora A mutant reverts this phenotype, demonstrating that Aurora A kinase activity is required for spindle bipolarity in human cells. Because small molecule-mediated inhibition of Aurora A and Aurora B yields distinct phenotypes, our observations indicate that the Auroras may present two avenues for anti-cancer drug discovery.
Architecture of the vimentin cytoskeleton is modified by perturbation of the GTPase ARF1
Authors: Styers Melanie L. , Kowalczyk Andrew P. , Faundez Victor
Published: August 2006

Intermediate filaments are required for proper membrane protein trafficking. However, it remains unclear whether perturbations in vesicular membrane transport result in changes in the architecture of the vimentin cytoskeleton. We find that treatment of cells with Brefeldin A, an inhibitor of specific stages of membrane transport, causes changes in the organization of vimentin filaments. These changes arise from movement of pre-existing filaments. Brefeldin A treatment also leads to alterations in the microtubule cytoskeleton. However, this effect is not observed in cells lacking intermediate filaments, indicating that microtubule bundling is downstream of perturbations in the vimentin cytoskeleton. Brefeldin A-induced changes in vimentin architecture are probably mediated through its effects on ADP-ribosylation factor 1 (ARF1). Expression of a dominant-negative mutant of ARF1 induces BFA-like modifications in vimentin morphology. The BFA-dependent changes in vimentin architecture occurred concurrently with the release of the ARF1-regulated adaptor complexes AP-3 and AP-1 from membranes and adaptor redistribution to vimentin networks. These observations indicate that perturbation of the vesicular membrane transport machinery lead to reciprocal changes in the architecture of vimentin networks.
Benzocrown Ether Hydrazones as Extractants for Alkali Metal Ions
Authors: Sakamoto Hidefumi , Goto Hiroki , Yokoshima Makoto , Dobashi Makoto , Ishikawa Junichi , Doi Kunio , Otomo Makoto
Published: August 2006

Four types of benzo-15-crown-5 and benzo-18-crown-6 derivatives bearing a substituted hydrazone moiety as a proton-dissociable chromogenic group were synthesized and the solvent extraction behaviors of these compounds for alkali metal ions were evaluated spectrophotometrically. Benzo-15-crown-5 and -18-crown-6 hydrazones with 2,4-dinitro-6-(trifluoromethyl)phenyl or 2,6-dinitro-4-(trifluoromethyl)phenyl groups extracted alkali metal ions predominantly as 2 : 1 and 1 : 1 (crown ether : metal ion) complexes, respectively, from an aqueous alkaline solution into 1,2-dichloroethane and these ligands exhibited high K+-selectivity. The composition of the extracted species and the K+-selectivity depended on the polarity of the extraction solvent used. In particular, 2 : 2 complexes of several alkali metal ions with benzo-15-crown-5 and -18-crown-6 hydrazones bearing a 2,4-dinitro-6-(trifluoromethyl)phenyl group were readily extracted from an aqueous solution into chloroform.
Synthesis of Barnase Site-Specifically Labelled with Two 13C Atoms Using Partially Protected Peptide Thioester Building Blocks
Authors: Hojo Hironobu , Aimoto Saburo
Published: August 2006

Barnase, site-specifically labelled with two 13C atoms, was synthesized using partially protected peptide thioesters as building blocks. Four partially protected peptide segments (Boc–[Lys(Boc)19,27]–barnase(1—34)–SC(CH3)2CH2CO–Nle–NH2, iNoc–[Lys(Boc)39,49]–barnase(35—52)–SC(CH3)2CH2CO–Nle–NH2, iNoc–[Lys(Boc)62,66]–barnase(53—81)–SC(CH3)2CH2CO–Nle–NH2, [Lys(Boc)98,108]–barnase(82—110)) were successively condensed in the presence of silver ions and N-hydroxysuccinimide (HONSu). Finally, barnase with full ribonuclease activity was obtained in a yield of 11% based on the carboxyl terminal peptide segment.
Convenient Synthesis of Biphenyl-2-carboxylic Acids via the Nucleophilic Aromatic Substitution Reaction of 2-Methoxybenzoates by Aryl Grignard Reagents
Authors: Hattori Tetsutaro , Suzuki Takatsugu , Hayashizaka Noriyuki , Koike Nobuyuki , Miyano Sotaro
Published: August 2006

Nucleophilic aromatic substitution (SNAr) of 2-methoxybenzoic esters derived from 2,6-dialkylphenols by aryl Grignard reagents affords 1,1′-biphenyl-2-carboxylates in excellent yields by proper choice of the bulk of the 2,6-dialkyl-substituents. The phenoxyl protecting groups can be easily removed from the resulting biphenyl-2-carboxylates to the free acids by treatment with potassium hydroxide in aqueous ethanol (2,4,6-trimethylphenyl and 2,6-diisopropylphenyl esters) or sodium methoxide in toluene–hexamethylphosphoric triamide (2,6-di-t-butyl-4-methylphenyl esters). The regioselective biphenyl coupling reaction via the SNAr process is utilized for the key-step construction of the biphenyl skeleton in a formal synthesis of cannabinol.
Studies on Nickel-Containing Ziegler-Type Catalysts. III. Dimerization of Propylene to 2,3-Dimethylbutenes. Part-I
Authors: Sato Hiroshi , Noguchi Takanobu , Yasui Seimei
Published: August 2006

A new selective catalyst was developed for the dimerization of propylene to 2,3-dimethylbutenes (DMBS). It comprises five components: nickel naphthenate (Ni(naph)2)/AlEt3/PR3/diene/chlorinated phenol. Among them, chlorinated phenol is an essential component for activating the catalyst. Both the dimerization of propylene and the isomerization of the produced 2,3-dimethyl-1-butene (DMB-1) to 2,3-dimethyl-2-butene (DMB-2) are accelerated in proportion to the content of the chlorinated phenol as well as to the number of chlorine atoms on the chlorinated phenol. These effects are attributed to the Lewis acidity of the reaction product between AlEt3 and the chlorinated phenol. Thus, either DMB-1 or DMB-2 can be produced selectively by controlling the composition of the catalyst.

The content of DMBS mainly depends upon the phosphine ligand; this ligand effect is discussed in terms of the 31P NMR chemical shift. A high content of DMBS of up to 85% in propylene dimers was attained when phosphines with chemical shifts between 0 and −30 ppm were used.
Effect of the Poly(oxyethylene) Chain Length of Ionic Surfactants on the Extraction of Alkali Metal Ions
Authors: Sakai Yukio , Nabeki Kumiko , Uehara Eisaku , Hiraishi Michinori , Takagi Makoto
Published: August 2006

The following three extractants were synthesized: (n = 3, 6, 9). The extraction constants for alkali metal ions were also determined. The extractability with an extractant having three oxyethylene units decreases in the order Li+ > K+ > Na+ > Cs+   Rb+; for other extractants, K+ > Rb+ > Cs+ > Na+ > Li+.
CD Spectra and Cyclization of Linear Pentapeptides as Gramicidin S Precursors with a Benzyloxycarbonyl Group on the Side Chain of Orn Residue
Authors: Tamaki Makoto , Akabori Sadatoshi , Muramatsu Ichiro
Published: August 2006

Five pentapeptides related to gramicidin S, H–Val–Orn(Z)–Leu–d-Phe–Pro–OH, H–Orn(Z)–Leu–d-Phe–Pro–Val–OH, H–Leu–d-Phe–Pro–Val–Orn(Z)–OH, H–d-Phe–Pro–Val–Orn(Z)–Leu–OH, and H–Pro–Val–Orn(Z)–Leu–d-Phe–OH, were cyclized with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1-hydroxybenzotriazole. The pentapeptide with a Pro residue at the C-terminal formed predominantly the cyclic dimer (diZ-gramicidin S), while the pentapeptide with an Orn(Z) residue at the C-terminal produced exclusively the cyclic monomer (Z-semigramicidin S). The reaction mode of those pentapeptides was correlated with their CD spectra.
Isolation of (η5-Cyclopentadienyl)(1,2,3,4,5-η6-exo-methoxy-7-oxo-2,4-cycloheptadienyl)ruthenium(II) as a Key Intermediate for the Selective H/D Exchange on Its Coordinated Tropone Moiety by KOH/CD3OD
Authors: Kimura Masaru , Morita Mitsunobu
Published: August 2006

(η5-Cyclopentadienyl)(η5-ligand)ruthenium(II) (ligand = 1,2,3,4,5-η6-exo-methoxy-d3-7-oxo-2,4-cycloheptadienyl-2d  3a, 1,2,3,4,5-η6-exo-methoxy-7-oxo-2,4-cycloheptadienyl-2d, 1,2,3,4,5-η6-exo-methoxy-7-oxo-2,4-cycloheptadienyl, and 1,2,3,4,5-η6-exo-ethoxy-7-oxo-2,4-cycloheptadienyl) was isolated in fairly good yields by treatment of (η5-C5H5)(η6-tropone)ruthenium(II)BF4 with KOH in CD3OD, CH3OD, CH3OH, and ethanol, respectively. The selectively deuterated tropone-2d was readily removed by photolysis of 3a accompanied by demethoxylation with visible light in the presence of large excess of P(OCH3)3.
Emulsion Copolymerization of Styrene with Amphiphilic Poly(2-oxazoline) Macromonomer Bearing Ammonio Group at the Chain End
Authors: Uyama Hiroshi , Sato Masahiro , Matsumoto Yasuhiro , Kobayashi Shiro
Published: August 2006

Emulsion copolymerization of styrene with a block-type amphiphilic poly(2-oxazoline) macromonomer having a quaternary ammonio group at the chain end was performed to produce monodisperse polymer particles in the submicron range. Poly(2-oxazoline) chains and the ammonio group were localized on the particle surface.
The Lowest Lying Singlet and Triplet States of the Halonitrenium Ions NX2+ and NHX+ and a Comparison with the Carbon Analogues CX2 and CHX (X = F, Cl, Br, I). A Theoretical Study
Authors: Gobbi Alberto , Frenking Gernot
Published: August 2006

The equilibrium geometries, energy differences, and vibrational frequencies for the energetically lowest lying 1A1 and 3B1 states of NH2+, NHX+, and NX2+ (X = F, Cl, Br, I) are theoretically predicted using ab initio quantum mechanical methods at the MP4/6-311G(2df)//MP2/6-31G(d) level of theory. Effective core potentials are employed for bromine and iodine. The isoelectronic carbenes CH2, CHX, and CX2 are also calculated. The electronic structure of the molecules is investigated using the topological analysis of the electronic wave function.
Energy Levels and Line Intensities of Diatomic Molecules. Application to Alkali Metal Molecules
Authors: Katô Hajime
Published: August 2006

Calculation of rotational level energies and line intensities of diatomic molecules and its application to alkali metal diatomic molecules are reported. The effects of spin–orbit interaction, rotational interaction, spin–rotation interaction, spin–spin interaction, hyperfine interaction, and Zeeman interaction are considered.
Theoretical Studies of the Aluminum–Water Clusters Al(H2O)n and Their Ions [Al(H2O)n]+
Authors: Watanabe Hidekazu , Aoki Masaharu , Iwata Suehiro
Published: August 2006

With the ab initio molecular orbital calculations, the structures of the neutral clusters Al(H2O)n were optimized, and the vertical ionization energy was evaluated. Two types of the stable clusters are found; the one has a structure [Al(H2O)](H2O)n−1 and the other has [Al(H2O)2](H2O)n−2. The former type of the clusters, in which only one water molecule is directly bonded, is more stable than the latter. The calculated ionization energy with the multi-reference configuration interaction is in very good agreement with the experimental energy determined recently by Fuke’s group, only for the series of the former type of clusters. The structures of the [Al(H2O)n]+ were determined, and the incremental stability energy was evaluated. A very stable ring structure is found in [Al(H2O)4]+. The ring structure persists in [Al(H2O)5]+, but only substantial deformation. The extremely stable structure of [Al(H2O)4]+ explains the observed product distribution of the photo-dissociation recently reported by Fuke’s group.
Structure and Vibrational Analysis of Protonated Ethane C2H7+
Authors: Obata Shigeki , Hirao Kimihiko
Published: August 2006

The stability and vibrational frequencies of protonated ethane, C2H7+, have been studied by ab initio molecular orbital theory. The IR spectra for C2H7+ recorded by Y. T. Lee’s group were interpreted from a theoretical point of view. Ab initio computations predict the existence of two isomers, a bridged structure, and a tight and loose open form. The loose open form is represented as an H2 molecule attached loosely to a classical open C2H5+ ion. The different behavior observed in the IR spectra can be attributed to the changing ratio of the bridged C2H7+ to the open C2H5+ isomers. The final interpretation of these data is that the spectrum at 150 Torr (1 Torr = 133.322 Pa) arises from the bridged structure which is the most stable form of C2H7+. The additional band in the spectrum observed at 60 Torr originates form the weakly bound complex which dissociates upon absorbing a single IR photon.
Formation of the Oxanickelacyclopentene Complex from Nickel(0), Carbon Dioxide, and Alkyne. An ab initio MO/SD-CI Study
Authors: Sakaki Shigeyoshi , Mine Kazuya , Taguchi Daisaku , Arai Toru
Published: August 2006

An ab initio MO/SD-CI study was carried out on the formation reaction of oxanickelacyclopentene,  1, from Ni(PH3), CO2, C2H2. Because C2H2 coordinates to Ni(PH3) more strongly than does CO2 by ca. 11 kcal mol−1 at the SD-CI level, coordination of C2H2 to Ni(PH3) takes place first. The resultant Ni(PH3)(C2H2) reacts with CO2 to yield 1 with no activation barrier and a significant exo-thermicity of 68 kcal mol−1 at the HF level, but a moderate barrier of 30 kcal mol −1 and exo-thermicity of 17 kcal mol−1 at the SD-CI level. 1 takes a three-coordinate T-shaped structure, due to the low-spin d8 electron configuration of Ni(II). Ni(PH3) stabilizes the transition state through a charge-transfer interaction from the occupied d orbital of Ni to the unoccupied π* orbitals of CO2 and C2H2. The electron re-distribution during the reaction is discussed, based on orbital mixing among the d orbital of Ni and the π and π* orbitals of C2H2 and CO2.
An Ab Initio Molecular Orbital Approach to Electronic Structures of the F Center in NaCl. Effects of Basis Set and Cluster Size
Authors: Adachi Jun-ichi , Kosugi Nobuhiro
Published: August 2006

NaCl clusters with a Cl− ion vacancy, Na66+, Na6Cl126−, Na14Cl122+, and Na14Cl184−, are calculated by ab initio molecular orbital calculations to investigate electronic states of F centers in alkali halides. The model clusters are embedded in a point charge field. Description of “1s” ground and “2s” and “2p” excited states of an electron trapped by the vacancy is discussed concerning to basis set and cluster size. The 1s and 2p wave functions of the F-center electron are efficiently described by one s Gaussian-type function placed on the vacancy center and one p Gaussian-type functions placed on the nearest neighbor Na ions when Na 3s is of double ζ quality. The 1s–2p excitation energy is in good agreement with the experimental data. As regards the electron binding energies and the orbital size the 1s wave function almost converges in the cluster Na6Cl126− but the 2p wave function does not converge even in the largest cluster Na14Cl184−.
Synthesis and Structures of Infinite Sheet Copper(I) Complex Polymers with 2,6-Dimethylpyrazine, {[Cu2(C6H8N2)3](ClO4)2(C3H6O)2}∞, and with 2-Chloropyrazine, {[Cu2(C4H3N2Cl)4.5](ClO4)2}∞
Authors: Kitagawa Susumu , Kawata Satoshi , Kondo Mitsuru , Nozaka Youichi , Munakata Megumu
Published: August 2006

The new copper(I) coordination polymers, {[Cu2(2,6-Me2pz)3](ClO4)2(C3H6O)2}∞ (1) and {[Cu2(2-Clpz)4.5](ClO4)2}∞ (2) (2,6–Me2pz = 2,6-dimethylpyrazine; 2–Clpz = 2-chloropyrazine) have been synthesized and their structures have been X-ray crystallographically characterized. 1 crystallizes in the monoclinic, space group P21/a with a = 15.520(5), b = 19.315(2), c = 12.493(2) Å, β = 110.82(2)°, U = 3322(2) Å3, and Z = 4. 2 is orthorhombic, space group Pbca with a = 28.567(6), b = 17.560(9), c = 11.512(9) Å, U = 5774(8) Å3, and Z = 8. These complexes show an infinite sheet structure of macrocations with uninteracting ClO4− anion. 1 shows planar sheets composed of Cu6 hexagons, in which copper atoms are three-coordinate and linked by 2,6-Me2pz molecules. Acetone molecules sit over the cavities of the Cu6 hexagons, resulting in an intercalated layer between the copper sheets. 2 provides the unique polymers having an unprecedented four coordination geometry in binary copper–pyrazine systems. There are terminal and bridging types of 2-Clpz molecules, which produce Cu6 and Cu4 motifs for infinite pleated sheets. The factors governing the mode of polymerization are found by examination of the crystal structures for a series of copper(I) polymers of pyrazine derivatives.
51V NMR Studies of Crystalline Divalent Metal Vanadates and Divanadates
Authors: Hayakawa Satoshi , Yoko Toshinobu , Sakka Sumio
Published: August 2006

51V static and magic-angle spinning (MAS) NMR spectra of crystalline divalent metal vanadates, M3(VO4)2 (M = Mg, Sr, Ba, Zn, Pb) and Mg2M′(VO4)2 (M′ = Sr, Ba, Pb) and divanadates, M2V2O7 (M = Mg, Ca, Sr, Ba, Zn, Pb) have been measured. In vanadates and dichromate-type divanadates, the 51V isotropic chemical shifts decrease linearly with decreasing electronegativity of divalent metal atom adjacent to the VO4-tetrahedron. This was interpreted by considering that the electron density and the symmetry of VO4-tetrahedron increases with decreasing electronegativity of divalent metal atom. This effect was more significant in vanadates than in divanadates. In divanadates the isotropic chemical shifts of the thortveitite-type configuration appeared at lower frequencies than that of the dichromate-type configuration. This was explained by assuming that the degree of s-hybridization of the oxygen orbitals in the V–O–V bonds is higher in the thortveitite-type than in the dichromate-type.
Pressure Effects on the Complexation of t-Butylammonium Perchlorate by Crown Ether
Authors: Yamada Hiroaki , Kazuoka Mayumi , Moriguchi Naoyuki , Sera Akira
Published: August 2006

The effects of hydrostatic pressure on the complexation of t-butylammonium perchlorate by crown ether in methanol were studied by means of a high-pressure high-resolution NMR method at 33.5 °C. The complexation was shown to be promoted upon pressurization.
Intramolecular Charge-Transfer Interaction in 7,12-Epoxy-7,12-dihydrobenz[a]anthracene-8,11-dione and 5,12-Epoxy-5,12-dihydronaphthacene-1,4-dione
Authors: Yamamura Kimiaki , Miyake Hideyoshi
Published: August 2006

7,12-Epoxy-7,12-dihydrobenz[a]anthracene-8,11-dione and 5,12-epoxy-5,12-dihydronaphthacene-1,4-dione have been synthesized. Both of them had pronounced intramolecular charge-transfer bands, although the donor and the acceptor were in unfavorable spatial position and furthermore in one of them its HOMO–LUMO interaction is forbidden.
Detection of Superoxide Ions from Photoexcited Semiconductors in Non-Aqueous Solvents Using the ESR Spin-Trapping Technique
Authors: Noda Hiroyuki , Oikawa Kazuo , Ohya-Nishiguchi Hiroaki , Kamada Hitoshi
Published: August 2006

The ESR spin-trapping technique using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-t-butylbenzylideneamine N-oxide (PBN) as spin-trap reagents has been applied to detect active oxygen radicals generated by the photoexcitation of powdery semiconductors (TiO2, WO3, CdS, and Fe2O3) in non-aqueous solvents such as dimethylsulfoxide (DMSO), benzene, ethanol, and acetonitrile. Appreciable amounts of superoxide ion (O2−) were detected from TiO2, WO3, Fe2O3, and CdS suspensions under photoexcitation. The hyperfine splitting constants (hfsc) of the superoxide ion and carbon(C)-centered radical spin adducts for DMPO and PBN could be determined in various non-aqueous solvents. Some characteristic features for the production of the superoxide ion and C-centered radicals are discussed in connection with the energy-level diagrams of the semiconductors and the redox potentials of the superoxide ion and non-aqueous solvents.