bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of systemic progesterone concentration on the expression of progesterone-responsive genes in the bovine endometrium during the early luteal phase
Authors: McNeill R. E. , Sreenan J. M. , Diskin M. G. , Cairns M. T. , Fitzpatrick R. , Smith T. J. , Morris D. G.
Published: May 2006

Increasing evidence indicates an association between the concentration of systemic progesterone during the early luteal phase of the oestrous cycle and embryo survival rate in cattle. We examined the relationship between the concentration of systemic progesterone on Days 4 to 8 post-ovulation and expression of progesterone receptor (PGR), oestrogen receptor α (ESR1) and retinol-binding protein (RBP) mRNA in the bovine endometrium. Heifers were blood sampled from the day of ovulation (Day 0) to Day 8 post-ovulation. On Day 4, animals were divided into low progesterone control (LC) and high progesterone control (HC) groups based on their plasma progesterone concentrations. Half of each group was supplemented with exogenous progesterone resulting in two further groups, low progesterone supplemented (LS) and high progesterone supplemented (HS). Endometrial tissues were recovered from all groups on Day 6 or Day 8 and gene expression was analysed following Northern blotting. Increasing progesterone concentrations were associated with decreased PGR and ESR1 expression. Duration-dependent effects of progesterone supplementation on ESR1 were evident and there was an effect of systemic progesterone concentrations between Day 0 and Day 4 on the expression of RBP at Days 6 and 8. Such progesterone-responsive changes in uterine gene expression are likely to affect embryo development.
In vivo
incorporation of multiple unnatural amino acids through nonsense and frameshift suppression
Authors: Rodriguez Erik A. , Lester Henry A. , Dougherty Dennis A.
Published: May 2006

Site-specific incorporation of unnatural amino acids (UAAs) into proteins is a valuable tool for studying structure–function relationships, incorporating biophysical probes, and elucidating protein–protein interactions. In higher eukaryotic cells, the methodology is currently limited to incorporation of a single UAA in response to a stop codon, which is known as nonsense suppression. Frameshift suppression is a unique methodology for incorporating UAAs in response to quadruplet codons, but currently, it is mostly limited to
in vitro
protein translation systems. Here, we evaluate the viability of frameshift suppression in
Xenopus
oocytes. We demonstrate UAA incorporation by using yeast phenylalanine frameshift suppressor (YFFS) tRNAs that recognize two different quadruplet codons (CGGG and GGGU)
in vivo
. Suppression efficiency of the YFFS tRNAs increases nonlinearly with the amount of injected tRNA, suggesting a significant competition with endogenous, triplet-recognizing tRNA. Both frameshift suppressor tRNAs are less efficient than the amber suppressor tRNA THG73 (
Tetrahymena thermophila
G73), which has been used extensively for UAA incorporation in
Xenopus
oocytes. However, the two YFFS tRNAs are more “orthogonal” to the
Xenopus
system than THG73, and they offer a viable replacement when suppressing at promiscuous sites. To illustrate the potential of combining nonsense and frameshift suppression, we have site-specifically incorporated two and three UAAs simultaneously into a neuroreceptor expressed
in vivo
.
Structural insights into stereochemical inversion by diaminopimelate epimerase: An antibacterial drug target
Authors: Pillai Bindu , Cherney Maia M. , Diaper Christopher M. , Sutherland Andrew , Blanchard John S. , Vederas John C. , James Michael N. G.
Published: May 2006

d
-amino acids are much less common than their
l
-isomers but are widely distributed in most organisms. Many
d
-amino acids, including those necessary for bacterial cell wall formation, are synthesized from the corresponding
l
-isomers by α-amino acid racemases. The important class of pyridoxal phosphate-independent racemases function by an unusual mechanism whose details have been poorly understood. It has been proposed that the stereoinversion involves two active-site cysteine residues acting in concert as a base (thiolate) and an acid (thiol). Although crystallographic structures of several such enzymes are available, with the exception of the recent structures of glutamate racemase from
Bacillus subtilis
and of proline racemase from
Trypanosoma cruzi
, the structures either are of inactive forms (e.g., disulfide) or do not allow unambiguous modeling of the substrates in the active sites. Here, we present the crystal structures of diaminopimelate (DAP) epimerase from
Haemophilus influenzae
with two different isomers of the irreversible inhibitor and substrate mimic aziridino-DAP at 1.35- and 1.70-Å resolution. These structures permit a detailed description of this pyridoxal 5′-phosphate-independent amino acid racemase active site and delineate the electrostatic interactions that control the exquisite substrate selectivity of DAP epimerase. Moreover, the active site shows how deprotonation of the substrates’ nonacidic hydrogen at the α-carbon (pK
a
≈ 29) by a seemingly weakly basic cysteine residue (pK
a
≈ 8–10) is facilitated by interactions with two buried α-helices. Bacterial racemases, including glutamate racemase and DAP epimerase, are potential targets for the development of new agents effective against organisms resistant to conventional antibiotics.
Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by
Staphylococcus aureus
product in mice
Authors: Terada Makoto , Tsutsui Hiroko , Imai Yasutomo , Yasuda Koubun , Mizutani Hitoshi , Yamanishi Kiyofumi , Kubo Masato , Matsui Kiyoshi , Sano Hajime , Nakanishi Kenji
Published: May 2006

Atopic dermatitis (AD) is a common inflammatory skin disease of unknown etiology. Cutaneous infection with microbes such as
Staphylococcus aureus
and/or skin cleansing with detergent exacerbates clinical AD. Here, we generated an AD animal model by destroying skin barrier function with detergent and subsequent topical application of protein A from
S. aureus
(SpA). NC/Nga mice, which genetically have reduced skin barrier function, and BALB/c mice having intact skin barrier function, were susceptible to this combination and developed severe and moderate AD, respectively, associated with dermal accumulation of eosinophils and mast cells. Both types of mice showed an increase in serum levels of IL-18, but not IgE. The epidermis of the NC/Nga mice rapidly expressed T helper type 1 (Th1)-associated chemokines, including ligands for CXCR3 and CCR5, after application of both SpA and detergent, but not after application of detergent alone. Although treatment with detergent induced moderate Th1 cell response, additional SpA treatment was a prerequisite for induction of the differentiation of naive T cells toward unique Th1 cells, termed “super Th1 cells,” capable of producing both Th1 (IFN-γ) and T helper type 2 cytokine (IL-13), as well as IL-3, and expressing CXCR3 and CCR5. Induction of super Th1 cells required IL-18 stimulation. Blockade of IL-18 prevented AD development, whereas blockade of IL-3 partially prevented AD development, suggesting a contribution of IL-18-dependent IL-3 production to AD with cutaneous mastocytosis.
il18
−/−
BALB/c mice similarly evaded SDS/SpA-induced AD. Thus, IL-18 might be important for the development of infection-associated AD by induction of IL-3 from super Th1 cells.
How azide inhibits ATP hydrolysis by the F-ATPases
Authors: Bowler Matthew W. , Montgomery Martin G. , Leslie Andrew G. W. , Walker John E.
Published: May 2006

In the structure of bovine F
1
-ATPase determined at 1.95-Å resolution with crystals grown in the presence of ADP, 5′-adenylyl-imidodiphosphate, and azide, the azide anion interacts with the β-phosphate of ADP and with residues in the ADP-binding catalytic subunit, β
DP
. It occupies a position between the catalytically essential amino acids, β-Lys-162 in the P loop and the “arginine finger” residue, α-Arg-373, similar to the site occupied by the γ-phosphate in the ATP-binding subunit, β
TP
. Its presence in the β
DP
-subunit tightens the binding of the side chains to the nucleotide, enhancing its affinity and thereby stabilizing the state with bound ADP. This mechanism of inhibition appears to be common to many other ATPases, including ABC transporters, SecA, and DNA topoisomerase IIα. It also explains the stimulatory effect of azide on ATP-sensitive potassium channels by enhancing the binding of ADP.
Anthracothere dental anatomy reveals a late Miocene Chado-Libyan bioprovince
Authors: Lihoreau Fabrice , Boisserie Jean-Renaud , Viriot Laurent , Coppens Yves , Likius Andossa , Mackaye Hassane Taisso , Tafforeau Paul , Vignaud Patrick , Brunet Michel
Published: May 2006

Recent discovery of an abundant and diverse late Miocene fauna at Toros-Ménalla (Chad, central Africa) by the Mission Paléoanthropologique Franco-Tchadienne provides a unique opportunity to examine African faunal and hominid evolution relative to the early phases of the Saharan arid belt. This study presents evidence from an African Miocene anthracotheriid
Libycosaurus
, particularly well documented at Toros-Ménalla. Its remains reveal a large semiaquatic mammal that evolved an autapomorphic upper fifth premolar (extremely rare in Cenozoic mammals). The extra tooth appeared ≈12 million years ago, probably in a small northern African population isolated by climate-driven fragmentation and alteration of the environments inhabited by these anthracotheriids [Flower, B. P. & Kennett, J. P. (1994)
Palaeogeogr. Palaeoclimatol. Palaeoecol.
108, 537–555 and Zachos, J., Pagani, M., Sloan, L., Thomas, E. & Billups, K. (2001)
Science
292, 686–693]. The semiaquatic niche of
Libycosaurus
, combined with the distribution and relationships of its late Miocene species, indicates that by the end of the Miocene, wet environments connected the Lake Chad Basin to the Libyan Sirt Basin, across what is now the Sahara desert.
Cellular inhibitors of long interspersed element 1 and Alu retrotransposition
Authors: Bogerd Hal P. , Wiegand Heather L. , Hulme Amy E. , Garcia-Perez José L. , O’Shea K. Sue , Moran John V. , Cullen Bryan R.
Published: May 2006

Long interspersed element (LINE) 1 retrotransposons are major genomic parasites that represent ≈17% of the human genome. The LINE-1 ORF2 protein is also responsible for the mobility of Alu elements, which constitute a further ≈11% of genomic DNA. Representative members of each element class remain mobile, and deleterious retrotransposition events can induce spontaneous genetic diseases. Here, we demonstrate that APOBEC3A and APOBEC3B, two members of the APOBEC3 family of human innate antiretroviral resistance factors, can enter the nucleus, where LINE-1 and Alu reverse transcription occurs, and specifically inhibit both LINE-1 and Alu retrotransposition. These data suggest that the APOBEC3 protein family may have evolved, at least in part, to defend the integrity of the human genome against endogenous retrotransposons.
Woodford's Interest and Prices from the Perspective of the History and Methodology of Economic Thought: A Mini-Symposium
Authors: Boianovsky Mauro
Published: May 2006

Michael Woodford's 2003 Interest and Prices has been regarded as the most important contribution to monetary economics since the publication of Don Patinkin's Money, Interest and Prices fifty years ago. Like Patinkin, Woodford sought inspiration in Knut Wicksell's 1898 Interest and Prices. But, while Patinkin built on Wicksell's incipient formulation of the real balance effect and stability analysis of the price level (see Boianovsky 1998), Woodford has elaborated on Wicksell's concept of a pure credit economy (called “cashless economy” in the 2003 version), a theme largely disregarded by Patinkin. This difference in perspective is in part related to the fact that Patinkin's concern was mainly monetary theory, whereas Woodford has focused on monetary policy instead. In early 2004 I invited a group of scholars to discuss Wood-ford's book from the point of view of the history of thought and methodology in a session at the History of Economics Society meetings, held in June of that year at Victoria University, Toronto. Michael Woodford was also invited to participate in the session and reply to the comments. The revised papers are published here as a mini-symposium.
The Microcirculation of Skeletal Muscle in Aging
Authors: PAYNE GEOFFREY W. , BEARDEN SHAWN E.
Published: May 2006

Microvascular structure and function are key aspects of tissue and organ health. At approximately 40% of total body mass, skeletal muscle contains more microvessels than any other organ system in the body. Moreover, skeletal muscle is the most dynamic tissue in the body with the capacity to increase blood flow and metabolic rate 30‐ to 50‐ fold. Aging is associated with decrements in microvascular function and exercise tolerance that are poorly understood. Here, experts in their respective fields of microvascular structure and function are brought together to review the current state of knowledge regarding microvascular adaptations to aging. Reviews are drawn from human and animal studies and focus on age‐related changes in sympathetic nervous system control of microvessels, capillary hemodynamics and oxygen pressure, microvascular network structure and functional integration, microvascular reactivity, whole muscle perfusion, and cellular contacts and inflammation.
Effect of Inflammation on the Aging Microcirculation: Impact on Skeletal Muscle Blood Flow Control
Authors: PAYNE GEOFFREY W.
Published: May 2006

To meet the metabolic demands of skeletal muscle, the vasculature supplying these vascular beds has to be connected to respond in a coordinated uniform manner, thus providing the necessary oxygen and nutrients during increased activity. The skeletal muscle microcirculation is the major resistance network controlling vascular blood supply and it is the integrity of the endothelium lining the blood vessels that is paramount in facilitating this action. Aging is a major risk factor for cardiovascular disease and is associated with significant increases in inflammatory agents that negatively impact the vasculature. Several inflammatory agents such as cytokines (tumor necrosis factor‐α), advanced glycation products (AGEs), and matrix metalloproteinases (MMPs) along with storage cells for inflammatory mediators (mast cells) are associated with a chronic “low‐grade inflammation” state that has been observed over the course of the aging process. Current research suggests that these age‐related increases in inflammatory agents can disrupt the microvascular endothelium and thus impair blood flow. This impairment could exacerbate the common age‐related disease states such as hypertension, diabetes, congestive heart failure, and sarcopenia, leading to increased mortality and morbidity.
What do universities want from publishing?
Authors: Pinfield Stephen
Published: May 2006

At a simple level, universities want publishing to support and further their mission to carry out research and teaching. However, at a detailed level there are major differences within and between universities, which mean there will be different wants and expectations of publishing. Bearing in mind these complexities, this paper examines universities' various requirements as producers, purchasers and consumers of publications. Some of the key wants of universities include impact, affordability, quality and access. The merits of the established system of subscription‐based journal publishing and the emerging system of open‐access publishing and dissemination are discussed in relation to universities' wants.
Scholarly communication in the digital environment: what do authors want?
Authors: Rowlands Ian , Nicholas Dave , Huntington Paul
Published: May 2006

This article reports on a large‐scale international survey of authors' perception and experience of the journals system conducted by ciber in association with National Opinion Polls (NOP). It explores the factors that inform authors' decisions where to publish and, in particular, which groups of readers they perceive to be most important. It probes readership behaviour and the values that underlie authors' attitudes towards copyright and emerging business models, notably open access. It is concluded that many aspects of author behaviour are highly conservative and that a significant shift towards open access is, in the short to medium term, highly unlikely.
Cingulin Regulates Claudin-2 Expression and Cell Proliferation through the Small GTPase RhoA
Authors: Guillemot Laurent , Citi Sandra
Published: May 2006

In mouse embryoid bodies, mutation of the tight junction protein cingulin results in changes in gene expression. Here, we studied the function of cingulin using a gene silencing approach in Madin-Darby canine kidney (MDCK) cells. Cingulin-depleted cells show higher protein and mRNA levels of claudin-2 and ZO-3, increased RhoA activity, activation of G1/S phase transition, and increased cell density. The effects of cingulin depletion on claudin-2 expression, cell proliferation, and density are reversed by coexpression of either a dominant-negative form of RhoA (RhoAN19) or the Rho-inhibiting enzyme C3 transferase. However, the increase in ZO-3 protein and mRNA levels is not reversed by inhibition of either RhoA, p38, extracellular signal-regulated kinase (ERK), or c-Jun NH2-terminal kinase (JNK), suggesting that cingulin modulates ZO-3 expression by a different mechanism. JNK is implicated in the regulation of claudin-2 levels independently of cingulin depletion and RhoA activity, indicating distinct roles of RhoA- and JNK-dependent pathways in the control of claudin-2 expression. Finally, cingulin depletion does not significantly alter the barrier function of monolayers and the overall molecular organization of tight junctions. These results provide novel insights about the mechanisms of cingulin function and the signaling pathways controlling claudin-2 expression in MDCK cells.
Evolutionary transitions and mechanisms of matte and iridescent plumage coloration in grackles and allies (Icteridae)
Authors: Shawkey Matthew D , Hauber Mark E , Estep Laura K , Hill Geoffrey E
Published: May 2006

Iridescent structural colour is found in a wide variety of organisms. In birds, the mechanisms that create these colours are diverse, but all are based on ordered arrays of melanin granules within a keratin substrate in barbules. The feathers of the grackles and allies in the family Icteridae range in appearance from matte black to iridescent. In a phylogenetic analysis of this clade, we identified several evolutionary transitions between these colour states. To describe a possible mechanistic explanation for the lability of plumage coloration, we used spectrometry, transmission electron microscopy and thin-film optical modelling of the feathers of 10 icterid species from five genera, including taxa with matte black or iridescent feathers. In matte black species, melanin was densely packed in barbules, while in iridescent species, melanin granules were arranged in ordered layers around the edges of barbules. The structured arrangement of melanin granules in iridescent species created optical interfaces, which are shown by our optical models to be critical for iridescent colour production by coherent scattering. These data imply that rearrangement of melanin granules in barbules is a mechanism for shifts between black and iridescent colours, and that the relative simplicity of this mechanism may explain the lability of plumage colour state within this group.
On the one-dimensional recovery and microstructural evaluation of shocked alumina
Authors: Bourne N.K , Green W.H , Dandekar D.P
Published: May 2006

A technique has been developed in the previous work for determining dislocation interaction mechanisms in metals by shocking, unloading, then decelerating and catching part of the target for subsequent examination. This proceeds by using a system of partial momentum traps around the sample. This technique is further refined here, and is then applied to recover brittle targets that, in three-dimensional loading, would fail into a series of fragments. A number of hydrocode design simulations are presented to illustrate the technique, and the results of the experiments are presented. Sectioned targets indicate fracture, and X-ray tomography gives an overview of the volumetric damage. The response of the alumina above and below the elastic limit is highlighted.
Evolutionary games on cycles
Authors: Ohtsuki Hisashi , Nowak Martin A
Published: May 2006

Traditional evolutionary game theory explores frequency-dependent selection in well-mixed populations without spatial or stochastic effects. But recently there has been much interest in studying the evolutionary game dynamics in spatial settings, on lattices and other graphs. Here, we present an analytic approach for the stochastic evolutionary game dynamics on the simplest possible graph, the cycle. For three different update rules, called ‘birth–death’ (BD), ‘death–birth’ (DB) and ‘imitation’ (IM), we derive exact conditions for natural selection to favour one strategy over another. As specific examples, we consider a coordination game and Prisoner's Dilemma. In the latter case, selection can favour cooperators over defectors for DB and IM updating. We also study the case where the replacement graph of evolutionary updating remains a cycle, but the interaction graph for playing the game is a complete graph. In this setting, all three update rules lead to identical conditions in the limit of weak selection, where we find the ‘1/3-law’ of well-mixed populations.
Subglacial floods beneath ice sheets
Authors: Evatt G.W , Fowler A.C , Clark C.D , Hulton N.R.J
Published: May 2006

Subglacial floods (jökulhlaups) are well documented as occurring beneath present day glaciers and ice caps. In addition, it is known that massive floods have occurred from ice-dammed lakes proximal to the Laurentide ice sheet during the last ice age, and it has been suggested that at least one such flood below the waning ice sheet was responsible for a dramatic cooling event some 8000 years ago. We propose that drainage of lakes from beneath ice sheets will generally occur in a time-periodic fashion, and that such floods can be of severe magnitude. Such hydraulic eruptions are likely to have caused severe climatic disturbances in the past, and may well do so in the future.
Age Bias in the Workplace: The Impact of Ageism and Causal Attributions1
Authors: Rupp Deborah E. , Vodanovich Stephen J. , Credé Marcus
Published: May 2006

This study considers the roles of managerial ageism and causal attributions in the age bias process. Specifically, we predicted that employee age and manager ageism would interact in predicting the severity of recommendations made about an employee's performance errors, such that ageist managers would be more likely to engage in age bias. Second, we proposed that age bias is caused partially by differential attributions made about the performance errors of older vs. younger workers. Results indicated that older employees received more severe recommendations for poor performance than did their younger counterparts. Also, some ageist attitudes moderated the relationship between age and performance recommendations. Stability attributions mediated the relationship of employee age on endorsement of the more punitive recommendations.
Racist Events and Ethnic Identity in Low Income, African Americans
Authors: Sherry Alissa , Wood Keith , Jackson Emily B. , Kaslow Nadine
Published: May 2006

This study was designed to determine the relation between racist events and ethnic identity in a group of 100 low‐income African Americans. Findings indicated that the more racist events one experienced, the more ethnic behaviors they endorsed and the more they had explored the meaning of their ethnic background. In addition, racist events were also indicative of feeling less close to individuals of other ethnic groups. Results suggest that experiencing racist events may contribute to an increased identification with one's own ethnic background and less affiliation with those of other ethnic backgrounds, with the cumulative effect of racist events over one's lifetime contributing the most to this finding.
Biased Lineup Instructions: Examining the Effect of Pressure on Children's and Adults' Eyewitness Identification Accuracy1
Authors: Pozzulo Joanna D. , Dempsey Julie
Published: May 2006

Two experiments were conducted to examine the effects of pressure on lineup decisions across child and adult eyewitnesses. In both experiments, participants were exposed to a target via videotape and then presented with a 6‐person, target‐absent lineup. Pressure was manipulated via lineup instructions (neutral vs. biased instructions). With neutral lineup instructions, children had a higher false‐positive rate than did adults. With biased lineup instructions, children's patterns of false‐positive responding paralleled that of adults; that is, an increase in false positives occurred. These results suggest that social pressure may not be the only factor driving children's higher false‐positive responding, compared to adults. Potential factors that may be affecting children's lineup decision processes are discussed.
Personality Factors, Money Attitudes, Financial Knowledge, and Credit‐Card Debt in College Students1
Authors: Norvilitis Jill M. , Merwin Michelle M. , Osberg Timothy M. , Roehling Patricia V. , Young Paul , Kamas Michele M.
Published: May 2006

The issue of credit‐card debt among college students has received increasing attention. This study explored factors hypothesized to be causes and effects of credit‐card debt in 448 students on five college campuses. Students reported an average of $1,035 (SD=$1,849) in debt, including students without credit cards or credit‐card debt. Lack of financial knowledge, age, number of credit cards, delay of gratification, and attitudes toward credit‐card use were related to debt. Sensation seeking, materialism, the Student Attitude Toward Debt scale, gender, and grade point average were not unique predictors of debt. Students reporting greater debt reported greater stress and decreased financial well being. Results highlight the need for comprehensive financial literacy education among college students.
A Dual Route in Explaining Health Outcomes in Natural Disaster1
Authors: Tremblay Maxime A. , Blanchard Céline M. , Pelletier Luc G. , Vallerand Robert J.
Published: May 2006

Human beings seem to be resilient and have a great capacity to overcome adverse circumstances. One apparent variable that may predict people's emotional and physical health after a trauma is their general level of psychological well‐being (McMillen, Smith, & Fisher, 1997). The current study explores the role of subjective vitality and the perception of stress as mediators between general life satisfaction and post‐trauma physiological and psychological health related to the Canadian 1998 Ice Storm. Results of this dual route indicate that satisfaction with life positively predicted subjective vitality and negatively predicted perceived stress. In turn, subjective vitality lead to lower levels of ill‐health, whereas perception of stress lead to higher levels of physical symptoms and depression.
High expression of ubiquitin carboxy‐terminal hydrolase‐L1 and ‐L3 mRNA predicts early recurrence in patients with invasive breast cancer
Authors: Miyoshi Yasuo , Nakayama Satoshi , Torikoshi Yasuhiro , Tanaka Satoshi , Ishihara Hideki , Taguchi Tetsuya , Tamaki Yasuhiro , Noguchi Shinzaburo
Published: May 2006

The present study investigated the mRNA expression level of ubiquitin c‐terminal hydrolase (UCH)‐L1 and ‐L3 in breast cancer tissue and aimed to elucidate its association with tumor characteristics and patient prognosis. UCH‐L1 and UCH‐L3 mRNA levels in invasive breast cancer (n = 100) were determined by a real‐time polymerase chain reaction (PCR) assay and their relationship with various clinicopathological characteristics of breast tumors as well as patient prognosis were studied. UCH‐L3 mRNA level was significantly upregulated in breast cancer tissue compared to adjacent normal breast tissue (P < 0.005), and UHC‐L1 mRNA level also showed a non‐significant increase in tumor tissue compared to adjacent normal breast tissue. Both UCH‐L1 and UCH‐L3 mRNA levels were significantly higher in high histological grade tumors than in low histological grade tumors (P < 0.001 and P < 0.005, respectively). High UCH‐L1 mRNA level was significantly associated with negative estrogen receptor status (P < 0.05) and negative progesterone receptor status (P < 0.05). Patients with both UCH‐L1 and UCH‐L3 mRNA high tumors showed a significantly poorer prognosis than those in the UCH‐L1 or UCH‐L3 mRNA low group (P < 0.005). These observations that UCH‐L3 mRNA level is upregulated in breast cancer tissue, and breast tumors with both UCH‐L1 and UCH‐L3 mRNA high expression are associated with a poor prognosis, suggest the possible involvement of UCH‐L1 and UCH‐L3 in the pathogenesis and progression of breast cancer. (Cancer Sci 2006; 97: 523– 529)
Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer
Authors: Matsukawa Yasuko , Semba Shuho , Kato Hirotaka , Ito Akihiko , Yanagihara Kazuyoshi , Yokozaki Hiroshi
Published: May 2006

Overexpression of the enhancer of zeste homolog 2 (EZH2) protein, a known repressor of gene transcription, has been reported to be associated with biological malignancy of prostate cancer and several other cancers. The purpose of this study was to examine the expression of EZH2 and analyze its relationship with the clinicopathological features of human gastric cancers. Expression levels of EZH2 mRNA and protein were examined in 13 gastric cancer cell lines and in 83 surgically removed human gastric cancer tissues. Immunohistochemical analysis of the 83 tissue samples and corresponding non‐cancerous gastric mucosa showed that EZH2 was more highly expressed in the cancerous than in the non‐cancerous tissues, and the expression levels of EZH2 were highly correlated with tumor size, depth of invasion, vessel invasion, lymph node metastasis and clinical stages. Univariate analysis of survival rate calculated by the Kaplan‐Meier method revealed that gastric cancer patients with high‐level EZH2 expression had poorer prognosis than those expressing no or low levels of EZH2 (P = 0.0271). These findings suggest that overexpression of EZH2 may contribute to the progression and oncogenesis of human gastric cancers, and thus immunohistochemical study of EZH2 expression may serve as a new biomarker for predicting the prognosis of gastric cancers. (Cancer Sci 2006; 97: 484 – 491)
Characterization of target genes at the 2p15–16 amplicon in diffuse large B‐cell lymphoma
Authors: Fukuhara Noriko , Tagawa Hiroyuki , Kameoka Yoshihiro , Kasugai Yumiko , Karnan Sivasundaram , Kameoka Junichi , Sasaki Takeshi , Morishima Yasuo , Nakamura Shigeo , Seto Masao
Published: May 2006

Amplification of 2p has been observed as a recurrent alteration in diffuse large B‐cell lymphoma (DLBCL). Whereas two candidate oncogenes, REL and BCL11A, have been investigated as targets for 2p amplification, the question remains as to whether the true target gene in the amplicon is REL, BCL11A or both. We previously identified frequent genomic gains of chromosomal 2p in 25 out of 99 DLBCL cases by means of genome‐wide array comparative genomic hybridization (CGH). All of these 25 cases included recurrent copy number gain at 2p15–16. In the study presented here, cases were analyzed in greater detail by means of contig bacterial artificial chromosome (BAC) array CGH for the 4.5‐Mb region at 2p15–16, which contained 33 BAC clones. We confined the minimal common region to 500‐kb in length, where only the candidate oncogene REL, and not BCL11A, is located. Real‐time quantitative PCR was carried out to investigate the correlation between genomic gain and expression. It showed a significant correlation for both genes, indicating that these two genes are common targets for the 2p15–16 amplicon. However, given the fact that REL is more frequently amplified than BCL11A, the REL gene may play a more important role than BCL11A in the pathogenesis of DLBCL. (Cancer Sci 2006; 97: 499 – 504)
DNA damage and altered gene expression of enzymes for metabolism and DNA repair by tamoxifen and toremifene in the female rat liver
Authors: Hashiba Masamichi , Kasahara Toshihiko , Kim Sung Yeon , Shibutani Shinya , Degawa Masakuni
Published: May 2006

Effects of hepatocarcinogenic TAM and non‐hepatocarcinogenic TOR on the formation of hepatic DNA adducts and on the gene expression of hepatic drug‐metabolizing enzymes and DNA repair enzymes/proteins were comparatively examined in female Sprague‐Dawley rats treated with TAM (20 or 40 mg/kg/day, i.g.) or TOR (40 mg/kg/day, i.g.) for 1, 2 or 8 weeks. Hepatic TAM‐DNA adducts were formed even after 1 week of treatment with TAM at either dose, and the adduct levels increased in a dose‐ and treatment period‐dependent manner, whereas no DNA adducts were detected in any of the TOR‐treated rats. Conversely, TAM and TOR showed almost the same capacity for increasing the gene expression of drug‐metabolizing enzymes responsible for metabolic activation and detoxification, at least up to the 2‐week treatment mark. Accordingly, differences in DNA adduct formation between TAM‐ and TOR‐treated rats would not be primarily dependent on the capacity for inducing hepatic drug‐metabolizing enzymes. In addition, a drastic increase in the gene expression of cytochrome P4503A2 (CYP3A2), an activation enzyme of TAM, by the 8‐week treatment with TAM might have contributed to the increased formation of DNA adducts. Gene expressions of DNA repair enzymes/proteins responsible for a nucleotide excision repair system were not significantly changed in any of the rats treated with either drug. The present findings suggest that the difference between TAM and TOR in hepatocarcinogenic potency is dependent on the capacity to form DNA adducts rather than modulating the expression of drug‐metabolizing enzymes and DNA repair enzymes/proteins. (Cancer Sci2006; 97: 468– 477)
Determination of the site of tracheal tube impingement during nasotracheal fibreoptic intubation*
Authors: Marfin A. G. , Iqbal R. , Mihm F. , Popat M. T. , Scott S. H. , Pandit J. J.
Published: May 2006

This study examines the incidence and site of tracheal tube impingement during nasotracheal fibreoptic intubation, and the efficacy of anticlockwise tube rotation to overcome the problem. Forty‐three patients underwent fibreoptic‐assisted nasotracheal intubation using a preformed nasal tube, and a second fibrescope was used to observe any obstruction to passage of the tracheal tube. Impingement occurred in 10 cases, with the most common site being the right arytenoid cartilage. Rotation resulted in successful intubation in all 10 cases, but proximal rotation did not always result in an equal degree of rotation at the tube tip. We conclude that the site of impingement for nasotracheal intubation with preformed nasal tubes is located at the posterior structures of the laryngeal inlet and that anticlockwise rotation is a simple and effective solution.
The effect of the withdrawal of rofecoxib on prescribing patterns of COX‐2 inhibitors in Scotland
Authors: Williams D. , Singh M. , Hind C.
Published: May 2006

Background

Concerns have been raised regarding the cardiovascular safety of the COX‐2 inhibitors. In September 2004, rofecoxib was withdrawn from the market as a result of concerns regarding its cardiovascular safety.

Aims & Methods

We set out to examine the effect of the withdrawal of rofecoxib on the prescription of other COX‐2 inhibitors and nonselective nonsteroidal anti‐inflammatory drugs (nsNSAIDs) in Scotland, using a national prescription database.

Results

The withdrawal of rofecoxib led to an initial increase in the prescription of celecoxib as prescribers presumably switched to this alternative agent. However, this rise was short‐lived, presumably as a result of concerns that the safety concerning rofecoxib may be a class effect. A parallel increase in the prescription of diclofenac and ibuprofen was also noted, suggesting that prescribers were prescribing these medications as alternatives to COX‐2 inhibitors.

Conclusions

While prescribers and their patients may have initially interpreted safety concerns regarding rofecoxib to be drug specific, prescribers appear to have interpreted this effect to be class specific.
Recent developments in the clinical pharmacology of classical cytotoxic chemotherapy
Authors: Boddy Alan V.
Published: May 2006

Advances in analytical methods, imaging techniques and an increased understanding of the influence of pharmacogenetic factors have added to our knowledge of the pharmacology of many chemotherapeutic agents. Extending the use of these approaches to pharmacodynamic end‐points, together with the application of population‐based modelling techniques, offers the potential to develop truly individualized therapy in the future.
Degradation and humification of maize straw in soil microcosms inoculated with simple and complex microbial communities
Authors: Liebich J. , Schloter M. , Schäffer A. , Vereecken H. , Burauel P.
Published: May 2006

Microbial communities are responsible for soil organic matter cycling and thus for maintaining soil fertility. A typical Orthic Luvisol was freed from organic carbon by thermal destruction at 600°C. Then the degradation and humification of 14C‐labelled maize straw by defined microbial communities was analysed. To study the role of microbial diversity on the humification of plant material, microcosms containing sterilized soil were inoculated with a natural microbial community or with microbial consortia consisting of bacterial and fungal soil isolates. Within 6 weeks, 41 ± 4% of applied 14C‐labelled maize straw was mineralized in the soil microcosms containing complex communities derived from a soil suspension, whilst the most efficient communities composed of soil isolates mineralized less than 35%. The humification products were analysed by solution state 13C‐NMR‐spectroscopy and gel permeation chromatography (GPC). The analyses of humic acids extracts by solution state 13C‐NMR‐spectroscopy revealed no difference in the development of typical chemical functional groups for humic substances during incubation. However, the increase in specific molecular size fractions of the extracted humic acids occurred only after inoculation with complex communities, but not with defined isolates. While it seems to be true that redundancy in soil microbial communities contributes to the resilience of soils, specific soil functions may no longer be performed if a microbial community is harshly affected in its diversity or growth conditions.
Impact of crop residue location on carbon and nitrogen distribution in soil and in water‐stable aggregates
Authors: Coppens F. , Merckx R. , Recous S.
Published: May 2006

One of the main effects of soil tillage is that it determines the distribution of crop residues in the soil profile. Little information is available on how this affects the distribution of carbon (C) and nitrogen (N) in the soil and more specifically in soil aggregates, as in general the contribution of other effects of tillage (i.e. mechanical disturbance) cannot be distinguished. A laboratory experiment was conducted with repacked soil columns to improve our understanding of the mechanisms of soil aggregate stabilization and storage of organic C in relation to residue location. Double‐labelled oilseed rape residues (13C and 15N) were incorporated in the 0–10 cm soil layer or left on the soil surface. The soil columns were incubated for 33 weeks at 20°C. Artificial rain events followed by evaporation imposed several dry‐wet cycles on the soil‐residue system. Spatial separation of surface‐placed residues from the soil slowed down the decomposition rate compared with incorporated residues. This resulted, in the short term, in a large fraction of residue fragments at the soil surface (equivalent to 52% of carbon applied). In contrast, initial crop residue location did not significantly affect incorporation of residue‐C in soil aggregates (only 10–12% of carbon applied), as new C entered the aggregate fractions mainly as soluble C. However, concentrations of residue‐derived C and N were greater and aggregation increased near the soil surface with mulch, which in the longer term can modify physical and biological properties of the upper cm of the soil.
ATM activation by a sulfhydryl‐reactive inflammatory cyclopentenone prostaglandin
Authors: Kobayashi Masahiko , Ono Hirohito , Mihara Keiko , Tauchi Hiroshi , Komatsu Kenshi , Shibata Takashi , Shimizu Hiroko , Uchida Koji , Yamamoto Ken‐ichi
Published: May 2006

ATM (ataxia‐telangiectasia mutated) is activated by a variety of noxious agent, including oxidative stress, and ATM deficiency results in an anomalous cellular response to oxidative stress. However, the mechanisms for ATM activation by oxidative stress remain to be established. Furthermore, it is not clear whether ATM responds to oxidative DNA damage or to a change in the intracellular redox state, independent of DNA damage. We found that ATM is activated by N‐methyl‐N′‐nitro‐nitrosoguanidine (MNNG) and 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2), in NBS1‐ or MSH6‐deficient cells. We further found that ATM is activated by treating chromatin‐free immunoprecipitated ATM with MNNG or 15d‐PGJ2, which modifies free sulfhydryl (SH) groups, and that 15d‐PGJ2 binds covalently to ATM. Interestingly, 15d‐PGJ2‐induced ATM activation leads to p53 activation and apoptosis, but not to Chk2 or H2AX phosphorylation. These results indicate that ATM is activated through the direct modification of its SH groups, independent of DNA damage, and this activation leads, downstream, to apoptosis.
Different roles for the TOS and RAIP motifs of the translational regulator protein 4E‐BP1 in the association with raptor and phosphorylation by mTOR in the regulation of cell size
Authors: Eguchi Satoshi , Tokunaga Chiharu , Hidayat Sujuti , Oshiro Noriko , Yoshino Ken‐ichi , Kikkawa Ushio , Yonezawa Kazuyoshi
Published: May 2006

The translational regulator protein 4E‐BP1, that binds to eukaryotic initiation factor‐4E (eIF4E) to prevent the formation of the active translation complex, dissociates from eIF4E by phosphorylation through the mammalian target of rapamycin (mTOR) in the cells stimulated by amino acids. 4E‐BP1 has been shown to associate with the scaffold protein raptor through its TOS and RAIP motifs to be recognized by mTOR. We revealed that the TOS motif mutant was phosphorylated by mTOR only at the priming sites of Thr37/46 but the RAIP motif mutant was phosphorylated not only at the priming sites but also at the subsequent site of Thr70 in vitro and in response to amino acid treatment in HEK293 cells. Analysis using the phosphorylation site mutants indicated that phosphorylation of the priming and subsequent sites of 4E‐BP1 was required for dissociation from raptor as well as for the release of eIF4E. The expression of the 4E‐BP1 mutants replacing the TOS motif and phosphorylation sites, that are poor substrates for mTOR and have no or little dissociation ability from raptor and eIF4E, respectively, significantly reduced the size of K562 cells. These results indicate that the the TOS motif has an essential function whereas the RAIP motif has an accessory role in the association with raptor and mTOR‐mediated phosphorylation of 4E‐BP1 to dissociate it from raptor and release eIF4E in response to amino acid stimulation leading to the control of cell size.
The complement regulatory proteins CD55 (decay accelerating factor) and CD59 are expressed on the inner acrosomal membrane of human spermatozoa as well as CD46 (membrane cofactor protein)
Authors: Cummerson J. A. , Flanagan B. F. , Spiller D. G. , Johnson P. M.
Published: May 2006

The complement regulatory proteins CD55 and CD59 are expressed on the plasma membrane of human spermatozoa, whereas CD46 is only on the inner acrosomal membrane (IAM) which becomes surfaced exposed after the acrosome reaction when sperm assume fertilisation‐competence. CD55 & CD59, two glycosylphosphatidylinositol (GPI)‐anchored proteins, have been detected previously in some studies also in the acrosomal region of chemically fixed spermatozoa but never demonstrated at this site on unfixed spermatozoa. Dual labelling immunofluorescence and confocal microscopy on fresh unfixed spermatozoa, with minimal subsequent time to fixation, has shown CD55 to be markedly expressed on the IAM, more than on the plasma membrane. However, unlike for CD46, CD55 displayed patchy staining over the acrosome, with some variation between individual spermatozoa. All IAM‐associated CD55 was localised within GM1‐containing lipid rafts. CD59 was expressed also on the IAM, but in a pronounced granular pattern with more variation observed from one spermatozoa to another. Both CD55 & CD59 were released from the IAM by PI‐PLC, demonstrating them to be GPI‐anchored. Analysis of acrosome‐reacted spermatozoal CD55 by Western blotting revealed a novel single 55 kDa protein lacking significant oligosaccharides susceptible to glycosidases. Antibody‐induced membrane rafting and release of CD55 & CD59 in vitro may have influenced previous results. Significant coexpression of CD55 & CD46 on the IAM suggests some functional cooperation at this site.
T‐bet is essential for the progression of experimental autoimmune encephalomyelitis
Authors: Nath Narender , Prasad Ratna , Giri Shailendra , Singh Avtar K. , Singh Inderjit
Published: May 2006

Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin‐specific CD4+ T helper 1 (Th1) cells, while recovery from the disease is associated with the presence of Th2 cells. Here we used animals with targeted deletion of the T‐bet gene to determine its role in the progression of EAE. T‐bet regulates the production of interferon‐γ (IFN‐γ) in CD4+ and natural killer cells, and CD4+ T cells from T‐bet‐deficient mice were unable to differentiate into a Th1 phenotype. Moreover BALB/c mice deficient in T‐bet were resistant to the induction of EAE disease, with minimal inflammatory infiltrates in the central nervous system. These mice were resistant to EAE induction even when PLP(180−199) peptide specific effector T cells from BALB/c wild type were transferred to BALB/c T‐bet‐deficient mice. This resistance to EAE is may be caused by the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) from the spleen cells upon ex vivo stimulation with PLP(180−199) peptide and in vivo presence in the central nervous system. There was no difference in the recall responses in spleen cells from T‐bet‐deficient and wild type mice; however, less secretion of IFN‐γ was observed from primed splenocytes. The expression of IFN‐γ was less in the central nervous system of T‐bet‐deficient mice whereas IL‐10 was significantly higher in T‐bet‐deficient as compared to wild type mice. These data indicate that T‐bet genes play a critical role in maintaining the encephalitogenic nature of CD4+ T cells in autoimmune responses during EAE disease progression.