bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Control of Messenger RNA Stability. Association with a Sequence-Specific Messenger RNA Decay Pathway
Authors: Lidder Preetmoninder , Gutiérrez Rodrigo A. , Salomé Patrice A. , McClung C. Robertson , Green Pamela J.
Published: July 2005

Transcriptional and posttranscriptional regulation are well-established mechanisms for circadian gene expression. Among the latter, differential messenger RNA (mRNA) stability has been hypothesized to control gene expression in response to the clock. However, direct proof that the rate of mRNA turnover can be regulated by the clock is lacking. Previous microarray expression data for unstable mRNAs in Arabidopsis (Arabidopsis thaliana) revealed that mRNA instability is associated with a group of genes controlled by the circadian clock. Here, we show that CCR-LIKE (CCL) and SENESCENCE ASSOCIATED GENE 1 transcripts are differentially regulated at the level of mRNA stability at different times of day. In addition, the changes in CCL mRNA stability continue under free-running conditions, indicating that it is controlled by the Arabidopsis circadian clock. Furthermore, we show that these mRNAs are targets of the mRNA degradation pathway mediated by the downstream (DST) instability determinant. Disruption of the DST-mediated decay pathway in the dst1 mutant leads to aberrant circadian mRNA oscillations that correlate with alterations of the half-life of CCL mRNA relative to parental plants in the morning and afternoon. That this is due to an effect on the circadian control is evidenced by mRNA decay experiments carried out in continuous light. Finally, we show that the defects exhibited by dst mutants are reflected by an impact on circadian regulation at the whole plant level. Together, these results demonstrate that regulation of mRNA stability is important for clock-controlled expression of specific genes in Arabidopsis. Moreover, these data uncover a connection between circadian rhythms and a sequence-specific mRNA decay pathway.
Cyclin-Dependent Kinase Inhibitors in Maize Endosperm and Their Potential Role in Endoreduplication
Authors: Coelho Cintia M. , Dante Ricardo A. , Sabelli Paolo A. , Sun Yuejin , Dilkes Brian P. , Gordon-Kamm William J. , Larkins Brian A.
Published: July 2005

Two maize (Zea mays) cyclin-dependent kinase (CDK) inhibitors, Zeama;KRP;1 and Zeama;KRP;2, were characterized and shown to be expressed in developing endosperm. Similar to the CDK inhibitors in Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum), the maize proteins contain a carboxy-terminal region related to the inhibitory domain of the mammalian Cip/Kip inhibitors. Zeama;KRP;1 is present in the endosperm between 7 and 21 d after pollination, a period that encompasses the onset of endoreduplication, while the Zeama;KRP;2 protein declines during this time. Nevertheless, Zeama;KRP;1 accounts for only part of the CDK inhibitory activity that peaks coincident with the endoreduplication phase of endosperm development. In vitro assays showed that Zeama;KRP;1 and Zeama;KRP;2 are able to inhibit endosperm Cdc2-related CKD activity that associates with p13Suc1. They were also shown to specifically inhibit cyclin A1;3- and cyclin D5;1-associated CDK activities, but not cyclin B1;3/CDK. Overexpression of Zeama;KRP;1 in maize embryonic calli that ectopically expressed the wheat dwarf virus RepA protein, which counteracts retinoblastoma-related protein function, led to an additional round of DNA replication without nuclear division.
The Potato Virus X TGBp2 Movement Protein Associates with Endoplasmic Reticulum-Derived Vesicles during Virus Infection
Authors: Ju Ho-Jong , Samuels Timmy D. , Wang Yuh-Shuh , Blancaflor Elison , Payton Mark , Mitra Ruchira , Krishnamurthy Konduru , Nelson Richard S. , Verchot-Lubicz Jeanmarie
Published: July 2005

The green fluorescent protein (GFP) gene was fused to the potato virus X (PVX) TGBp2 gene, inserted into either the PVX infectious clone or pRTL2 plasmids, and used to study protein subcellular targeting. In protoplasts and plants inoculated with PVX-GFP:TGBp2 or transfected with pRTL2-GFP:TGBp2, fluorescence was mainly in vesicles and the endoplasmic reticulum (ER). During late stages of virus infection, fluorescence became increasingly cytosolic and nuclear. Protoplasts transfected with PVX-GFP:TGBp2 or pRTL2-GFP:TGBp2 were treated with cycloheximide and the decline of GFP fluorescence was greater in virus-infected protoplasts than in pRTL2-GFP:TGBp2-transfected protoplasts. Thus, protein instability is enhanced in virus-infected protoplasts, which may account for the cytosolic and nuclear fluorescence during late stages of infection. Immunogold labeling and electron microscopy were used to further characterize the GFP:TGBp2-induced vesicles. Label was associated with the ER and vesicles, but not the Golgi apparatus. The TGBp2-induced vesicles appeared to be ER derived. For comparison, plasmids expressing GFP fused to TGBp3 were transfected to protoplasts, bombarded to tobacco leaves, and studied in transgenic leaves. The GFP:TGBp3 proteins were associated mainly with the ER and did not cause obvious changes in the endomembrane architecture, suggesting that the vesicles reported in GFP:TGBp2 studies were induced by the PVX TGBp2 protein. In double-labeling studies using confocal microscopy, fluorescence was associated with actin filaments, but not with Golgi vesicles. We propose a model in which reorganization of the ER and increased protein degradation is linked to plasmodesmata gating.
Peroxisomal Monodehydroascorbate Reductase. Genomic Clone Characterization and Functional Analysis under Environmental Stress Conditions
Authors: Leterrier Marina , Corpas Francisco J. , Barroso Juan B. , Sandalio Luisa M. , del Río Luis A.
Published: July 2005

In plant cells, ascorbate is a major antioxidant that is involved in the ascorbate-glutathione cycle. Monodehydroascorbate reductase (MDAR) is the enzymatic component of this cycle involved in the regeneration of reduced ascorbate. The identification of the intron-exon organization and the promoter region of the pea (Pisum sativum) MDAR 1 gene was achieved in pea leaves using the method of walking polymerase chain reaction on genomic DNA. The nuclear gene of MDAR 1 comprises nine exons and eight introns, giving a total length of 3,770 bp. The sequence of 544 bp upstream of the initiation codon, which contains the promoter and 5′ untranslated region, and 190 bp downstream of the stop codon were also determined. The presence of different regulatory motifs in the promoter region of the gene might indicate distinct responses to various conditions. The expression analysis in different plant organs by northern blots showed that fruits had the highest level of MDAR. Confocal laser scanning microscopy analysis of pea leaves transformed with Agrobacterium tumefaciens having the binary vectors pGD, which contain the autofluorescent proteins enhanced green fluorescent protein and enhanced yellow fluorescent protein with the full-length cDNA for MDAR 1 and catalase, indicated that the MDAR 1 encoded the peroxisomal isoform. The functional analysis of MDAR by activity and protein expression was studied in pea plants grown under eight stress conditions, including continuous light, high light intensity, continuous dark, mechanical wounding, low and high temperature, cadmium, and the herbicide 2,4-dichlorophenoxyacetic acid. This functional analysis is representative of all the MDAR isoforms present in the different cell compartments. Results obtained showed a significant induction by high light intensity and cadmium. On the other hand, expression studies, performed by semiquantitative reverse transcription-polymerase chain reaction demonstrated differential expression patterns of peroxisomal MDAR 1 transcripts in pea plants grown under the mentioned stress conditions. These findings show that the peroxisomal MDAR 1 has a differential regulation that could be indicative of its specific function in peroxisomes. All these biochemical and molecular data represent a significant step to understand the specific physiological role of each MDAR isoenzyme and its participation in the antioxidant mechanisms of plant cells.
SWI3 Subunits of Putative SWI/SNF Chromatin-Remodeling Complexes Play Distinct Roles during Arabidopsis Development
Authors: Sarnowski Tomasz J. , Ríos Gabino , Jásik Jan , Świeżewski Szymon , Kaczanowski Szymon , Li Yong , Kwiatkowska Aleksandra , Pawlikowska Katarzyna , Koźbiał Marta , Koźbiał Piotr , Koncz Csaba , Jerzmanowski Andrzej
Published: July 2005

SWITCH/SUCROSE NONFERMENTING (SWI/SNF) chromatin-remodeling complexes mediate ATP-dependent alterations of DNA–histone contacts. The minimal functional core of conserved SWI/SNF complexes consists of a SWI2/SNF2 ATPase, SNF5, SWP73, and a pair of SWI3 subunits. Because of early duplication of the SWI3 gene family in plants, Arabidopsis thaliana encodes four SWI3-like proteins that show remarkable functional diversification. Whereas ATSWI3A and ATSWI3B form homodimers and heterodimers and interact with BSH/SNF5, ATSWI3C, and the flowering regulator FCA, ATSWI3D can only bind ATSWI3B in yeast two-hybrid assays. Mutations of ATSWI3A and ATSWI3B arrest embryo development at the globular stage. By a possible imprinting effect, the atswi3b mutations result in death for approximately half of both macrospores and microspores. Mutations in ATSWI3C cause semidwarf stature, inhibition of root elongation, leaf curling, aberrant stamen development, and reduced fertility. Plants carrying atswi3d mutations display severe dwarfism, alterations in the number and development of flower organs, and complete male and female sterility. These data indicate that, by possible contribution to the combinatorial assembly of different SWI/SNF complexes, the ATSWI3 proteins perform nonredundant regulatory functions that affect embryogenesis and both the vegetative and reproductive phases of plant development.
The Role of the Arabidopsis E2FB Transcription Factor in Regulating Auxin-Dependent Cell Division
Authors: Magyar Zoltán , De Veylder Lieven , Atanassova Ana , Bakó László , Inzé Dirk , Bögre László
Published: July 2005

The molecular mechanisms by which the phytohormone auxin coordinates cell division with cell growth and differentiation are largely unknown. Here, we show that in Arabidopsis thaliana E2FB, accumulation and stability are positively regulated by auxin. Coexpression of E2FB, but not of E2FA, with its dimerization partner A, stimulated cell proliferation in the absence of auxin in tobacco (Nicotiana tabacum) Bright Yellow-2 cells. E2FB regulated the entry into both S- and M-phases, the latter corresponding to the activation of a plant-specific mitotic regulator, CDKB1;1. Increased E2FB levels led to shortened cell cycle duration, elevated cell numbers, and extremely small cell sizes. In the absence of auxin, cells elongated with concomitant increase in their ploidy level, but both were strongly inhibited by E2FB. We conclude that E2FB is one of the key targets for auxin to determine whether cells proliferate or whether they exit the cell cycle, enlarge, and endoreduplicate their DNA.
Maintenance of Embryonic Auxin Distribution for Apical-Basal Patterning by PIN-FORMED–Dependent Auxin Transport inArabidopsis
Authors: Weijers Dolf , Sauer Michael , Meurette Olivier , Friml Jiří , Ljung Karin , Sandberg Göran , Hooykaas Paul , Offringa Remko
Published: July 2005

Molecular mechanisms of pattern formation in the plant embryo are not well understood. Recent molecular and cellular studies, in conjunction with earlier microsurgical, physiological, and genetic work, are now starting to define the outlines of a model where gradients of the signaling molecule auxin play a central role in embryo patterning. It is relatively clear how these gradients are established and interpreted, but how they are maintained is still unresolved. Here, we have studied the contributions of auxin biosynthesis, conjugation, and transport pathways to the maintenance of embryonic auxin gradients. Auxin homeostasis in the embryo was manipulated by region-specific conditional expression of indoleacetic acid-tryptophan monooxygenase or indoleacetic acid-lysine synthetase, bacterial enzymes for auxin biosynthesis or conjugation. Neither manipulation of auxin biosynthesis nor of auxin conjugation interfered with auxin gradients and patterning in the embryo. This result suggests a compensatory mechanism for buffering auxin gradients in the embryo. Chemical and genetic inhibition revealed that auxin transport activity, in particular that of the PIN-FORMED1 (PIN1) and PIN4 proteins, is a major factor in the maintenance of these gradients.
The Critical Role of Arabidopsis Electron-Transfer Flavoprotein:Ubiquinone Oxidoreductase during Dark-Induced Starvation
Authors: Ishizaki Kimitsune , Larson Tony R. , Schauer Nicolas , Fernie Alisdair R. , Graham Ian A. , Leaver Christopher J.
Published: July 2005

In mammals, electron-transfer flavoprotein:ubiquinone oxidoreductase (ETFQO) and electron-transfer flavoprotein (ETF) are functionally associated, and ETF accepts electrons from at least nine mitochondrial matrix flavoprotein dehydrogenases and transfers them to ubiquinone in the inner mitochondrial membrane. In addition, the mammalian ETF/ETFQO system plays a key role in β-oxidation of fatty acids and catabolism of amino acids and choline. By contrast, nothing is known of the function of ETF and ETFQO in plants. Sequence analysis of the unique Arabidopsis thaliana homologue of ETFQO revealed high similarity to the mammalian ETFQO protein. Moreover, green fluorescent protein cellular localization experiments suggested a mitochondrial location for this protein. RNA gel blot analysis revealed that Arabidopsis ETFQO transcripts accumulated in long-term dark-treated leaves. Analysis of three independent insertional mutants of Arabidopsis ETFQO revealed a dramatic reduction in their ability to withstand extended darkness, resulting in senescence and death within 10 d after transfer, whereas wild-type plants remained viable for at least 15 d. Metabolite profiling of dark-treated leaves of the wild type and mutants revealed a dramatic decline in sugar levels. In contrast with the wild type, the mutants demonstrated a significant accumulation of several amino acids, an intermediate of Leu catabolism, and, strikingly, high-level accumulation of phytanoyl-CoA. These data demonstrate the involvement of a mitochondrial protein, ETFQO, in the catabolism of Leu and potentially of other amino acids in higher plants and also imply a novel role for this protein in the chlorophyll degradation pathway activated during dark-induced senescence and sugar starvation.
Defects in mucosal immunity leading to ulcerative colitis
Authors: Targan Stephan R. , Karp Loren C.
Published: July 2005

Summary:  Evidence accumulated over the last decade demonstrates that what we call ‘ulcerative colitis’ is actually a heterogeneous group of diseases resulting from different pathogenic mechanisms with a common symptomatic expression. Subgroups of patients with ulcerative colitis can be stratified by presence or absence of serum autoantibodies, which are thought not to be pathogenic but to mark for a distinct disease phenotype. In recent years, animal‐based experimental systems have emerged that reflect human ulcerative colitis and have potential to accelerate our understanding of its pathogenesis. Genetic and immunological data from human studies in combination with results from animal model systems are the foundation of a hypothesis, which includes a role for microbial antigen exposure in the initiation, perpetuation, and amplification of the disease. In ulcerative colitis, it appears as though the T‐cell response to the antigens is not T‐helper (Th) 1 dominant as in the case of Crohn's disease but rather is either Th2 [interleukin (IL)‐4, IL‐13] or is mediated by specialized cells such as natural killer (NK) T cells (IL‐13). Lamina propria T cells from ulcerative colitis patients produce significantly greater amounts of IL‐13. Ulcerative colitis is associated with an atypical Th2 response mediated by a distinct subset of NK T cells that produce IL‐13 and are cytotoxic for epithelial cells. The way in which this response affects the ultimate cascade of inflammatory events has yet to be determined.
Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota
Authors: Elson Charles O. , Cong Yingzi , McCracken Vance J. , Dimmitt Reed A. , Lorenz Robin G. , Weaver Casey T.
Published: July 2005

Summary:  There are now many experimental models of inflammatory bowel disease (IBD), most of which are due to induced mutations in mice that result in an impaired homeostasis with the intestinal microbiota. These models can be clustered into several broad categories that, in turn, define the crucial cellular and molecular mechanisms of host microbial interactions in the intestine. The first of these components is innate immunity defined broadly to include both myeloid and epithelial cell mechanisms. A second component is the effector response of the adaptive immune system, which, in most instances, comprises the CD4+ T cell and its relevant cytokines. The third component is regulation, which can involve multiple cell types, but again particularly involves CD4+ T cells. Severe impairment of a single component can result in disease, but many models demonstrate milder defects in more than one component. The same is true for both spontaneous models of IBD, C3H/HeJBir and SAMPI/Yit mice. The thesis is advanced that ‘multiple hits’ or defects in these interacting components is required for IBD to occur in both mouse and human.
Quantitative assessment of the hepatic pharmacokinetics of the antimicrobial sitafloxacin in humans using in vivo19F magnetic resonance spectroscopy
Authors: Payne Geoffrey S. , Collins David J. , Loynds Peter , Mould Graham , Murphy Philip S. , Dzik‐Jurasz Andrzej S. K. , Kessar Preminda , Haque Nazneen , Yamaguchi Masayuki , Atarashi Shogo , Leach Martin O.
Published: July 2005

Aims

To measure hepatic concentrations of the fluorine‐containing antimicrobial, sitafloxacin, using in vivo19F magnetic resonance spectroscopy (MRS).

Methods

Data were acquired from eight healthy subjects at 2, 5, 8 and 24 h following doses of 500 mg day−1 for 5 days using a 1H/19F surface coil in a 1.5T clinical MR system. Tissue water was used as a reference.

Results

Estimated liver concentrations at 2 h were 15.0 ± 4.0 µg ml−1 (mean ± 95% CI), compared with 3.54 ± 0.58 µg ml−1 in plasma (n = 6), and fell below threshold concentrations (2 µg ml−1) by 24 h.

Conclusions

19F MRS is able to detect and quantify sitafloxacin in the liver. There was no evidence for the hepatic retention of the drug.
A multicentre study of coproxamol poisoning suicides based on coroners’ records in England
Authors: Hawton K. , Simkin S. , Gunnell D. , Sutton L. , Bennewith O. , Turnbull P. , Kapur N.
Published: July 2005

Aims

To examine in detail a series of coproxamol overdose deaths in order to provide information that will assist in the development of strategies to prevent such fatalities.

Method

Inquest records in 24 coroners’ jurisdictions in England on deaths between January 2000 and December 2001 which received a verdict of either suicide or undetermined cause (with a high or moderate probability of suicide) were examined.

Results

One hundred and twenty‐three coproxamol poisoning suicides were identified. Alcohol was involved in 58.5% of the overdoses and these individuals generally had lower blood drug levels and consumed fewer tablets. Younger people were more likely to have consumed alcohol and to have lower levels of suicide intent. Nearly half the individuals had a history of self harm, and a third were under psychiatric care. The coproxamol had been prescribed for the individual in 81.5% of cases, although only in 55.0% of those aged 10–34 years. In other cases the source of the coproxamol was nearly always a family member or partner. Some deaths resulted from relatively small overdoses.

Conclusions

Strategies to reduce self poisoning deaths due to coproxamol should take account of the high toxicity of coproxamol in overdose, especially when combined with alcohol, and the fact that risk of death extends beyond the person for whom the drug is prescribed.
Increased C‐reactive protein in ACE‐inhibitor‐induced angioedema
Authors: Bas M. , Hoffmann T. K. , Bier H. , Kojda G.
Published: July 2005

Aims

This study was designed to identify new factors which may contribute to angiotensin‐converting‐enzyme‐inhibitor (ACEI)‐induced angioedema.

Methods

In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI‐therapy without previous angioedema. We measured markers of inflammation such as acute‐phase proteins (C‐reactive protein, fibrinogen), leukocyte count and body temperature.

Results

The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 ± 5.3 months. During symptomatic angioedema, mean plasma levels of C‐reactive protein and fibrinogen were significantly increased by 7.3‐fold and 1.5‐fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema.

Conclusion

Our findings demonstrate for the first time that ACEI‐induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI‐induced angioedema.
Women, men and coronary heart disease: a review of the qualitative literature
Authors: Emslie Carol
Published: July 2005

Aim.  This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes.

Background.  Understanding patients’ experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients’ detailed understandings and perceptions of illness. As much previous research has been ‘gender neutral’, this review pays particular attention to gender.

Methods.  Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease.

Findings.  Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from ‘male’ experience to ‘human’ experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary ‘candidates’ and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work.

Conclusions.  There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease.
The ethics of relation: public health nurses and child protection clients
Authors: Marcellus Lenora
Published: July 2005

Aim. The aim of this paper is to show how a framework of relational ethics may be used in establishing trusting relationships with at‐risk families.

Background. Public health nurses have historically carried out assessment and monitoring of parenting within the family home, particularly with at‐risk families. In this role, they are placed in the position of simultaneously supporting and policing the family. A trusting relationship may be difficult to develop if parents feel threatened by the surveillance aspect of home visiting and the threat of action (such as removal of children) being taken against the family.

Discussion. Development of optimal trust relationships may be a challenge when families are experiencing powerlessness and oppression. The four themes of relational ethics – mutual respect, engaged interaction, embodiment and creating environment – provide a framework for developing trusting relationships with families.

Conclusion. It is possible to have a moral and trusting relationship with at‐risk families, but this needs to based on critical self‐reflection by nurses and mutually respectful nurse–family relations.
Elective single embryo transfer: Comparison of blastocyst and cleavage‐stage embryo transfer
Authors: KAWAMURA TOSHIHIRO , MORI MICHIKO , ARICHI AKANE , TAJIMA YUKO , KARASAWA YASUHIRO , SUGA KAHORI , IKUMI SACHIKO , ISHIKAWA SEIKA , KAWAMURA MAKIKO
Published: July 2005

Objective:   Blastocysts are reportedly suitable for preventing multiple pregnancies as a result of the high implantation rate per embryo. The present study compared clinical results for elective single embryo transfer (ET) between blastocysts and cleavage‐stage embryos in order to ascertain the usefulness of blastocyst culturing in single ET.

Methods:   Between January 2002 and December 2004, conventional in vitro fertilization ET and/or intracytoplasmic sperm injection was carried out for single ET in 86 cycles, to prevent multiple pregnancies (for medical reasons or because of patient wishes).

Results:   Among the 80 cycles in which a fresh embryo was transferred, pregnancy/implantation rates per ET were 35.3% for day 2/3 ET and 50.0% for day 5 ET, and pregnancy/implantation rates per oocyte retrieval were 35.3% for day 2/3 ET and 44.2% for day 5 ET. Ongoing pregnancy/delivery rates per oocyte retrieval were 32.4% for day 2/3 ET and 38.5% for day 5 ET. Monozygotic twinning occurred in one case of day 5 ET.

Conclusions:   Pregnancy rates per single ET tended to be higher for day 5 ET than for day 2/3 ET. However, no marked differences were identified in ongoing pregnancy/delivery rates per oocyte retrieval between groups. (Reprod Med Biol 2005; 4: 197–201)
Topiramate ameliorates hyperglycaemia and improves glucose‐stimulated insulin release in ZDF rats and db/db mice
Authors: Liang Y. , Chen X. , Osborne M. , DeCarlo S. O. , Jetton T. L. , Demarest K.
Published: July 2005

Topiramate (TPM) is a novel neurotherapeutic agent. Clinical studies reported that TPM treatment reduced body weight and decreased fasting blood glucose levels in obese patients with or without type 2 diabetes. It is unclear whether the blood glucose‐normalizing phenomenon observed during TPM treatment is a primary effect or the consequence of reduced food intake and weight loss. In the present studies, we chronically treated female Zucker diabetic fatty (ZDF) rats (fed with a diabetogenic diet) and db/db mice with TPM (30–300 mg/kg/day) to examine the effect of TPM on hyperglycaemia and its relationship with food intake and body weight gain. Our data showed that TPM treatment markedly reduced blood glucose levels in both ZDF rats and db/db mice without a significant reduction in body weight gain. Pair‐fed db/db mice treated with the vehicle alone did not exhibit a significant decrease in blood glucose levels compared with mice fed ad libitum. TPM treatment increased glucose‐stimulated insulin release by 2–3‐fold during an oral glucose tolerance test in both ZDF rats and db/db mice. We also observed a 1.4‐fold increase of pancreatic insulin content and heightened insulin immunostaining in pancreatic β cells in db/db mice treated with TPM. Our data suggest that the antidiabetic effect of TPM is independent of the changes in body weight gain and food intake. Improved glucose‐induced insulin release may, in part, underlie the mechanisms by which TPM ameliorates the hyperglycaemia.
Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia
Authors: Farvid M. S. , Ng T. W. K. , Chan D. C. , Barrett P. H. R. , Watts G. F.
Published: July 2005

Aim:  In this study, we investigated the association of plasma adiponectin and resistin concentrations with adipose tissue compartments in 41 free‐living men with a wide range of body mass index (22–35 kg/m2).

Methods:  Using enzyme immunoassays, plasma adiponectin and resistin were measured. Intraperitoneal, retroperitoneal, subcutaneous abdominal and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, SAATM and PSAATM, respectively) were determined using magnetic resonance imaging. Total adipose tissue mass (TATM) was measured using bioelectrical impedance. Insulin resistance was estimated with the help of homeostasis model assessment (HOMA) score.

Results:  In univariate regression, plasma adiponectin levels were inversely related to IPATM (r = −0.389, p < 0.05), SAATM (r = −0.500, p < 0.001), PSAATM (r = −0.502, p < 0.001), anterior SAATM (r = −0.422, p < 0.01) and TATM (r = −0.421, p < 0.01). In multiple regression models, adiponectin was chiefly correlated with PSAATM. Plasma adiponectin concentrations were also inversely correlated with HOMA score (r = −0.540, p < 0.001) and triglyceride (r = −0.632, p < 0.001), and positively correlated with high‐density lipoprotein cholesterol (r = 0.508, p < 0.001). There were no significant correlations between resistin levels and adipose tissue masses, insulin resistance or dyslipidaemia.

Conclusions:  In men, total body fat is significantly correlated with plasma adiponectin, but not with plasma resistin levels. Low plasma adiponectin levels appear to be chiefly determined by the accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra‐abdominal fat, and are strongly predictive of insulin resistance and dyslipidaemia.
Predictors of programme adherence and weight loss in women in an obesity programme using meal replacements
Authors: Packianathan I. , Sheikh M. , Boniface D. , Finer N.
Published: July 2005

Objective:  To explore predictors of programme adherence and weight loss in patients participating in a weight management programme using meal replacements (MR).

Design:  One hundred and fifty healthy obese women, age 48.5 years (s.d. = 8.3); weight, 97.6 kg (13.4); body mass index (BMI) 36.5 (3.7), participated in a longitudinal study with a 16‐week acute weight loss phase (Phase 1) followed by 1 year of a trial of weight‐loss maintenance (Phase 2). Energy intake during Phase 1 totaled 900 kcal (3.7 MJ) a day from a diet including two MR. Energy intake during Phase 2 consisted of either MR or a low‐fat diet with a calculated energy deficit of 600 kcal/day (2.5 MJ).

Methods:  Weight, height and waist circumference were measured and body composition assessed by air plethysmography (Bodpod). Glucose and insulin were measured by standard immunoassays and insulin sensitivity assessed by homeostatic model assessment.

Results:  At the end of 16 weeks, 114 subjects (76%) completed Phase 1 and achieved a mean weight loss of 8.95 kg (3.38). Adherence to Phase 1 was predicted by weight loss over the first 2 weeks (p < 0.001). Weight loss during Phase 1 was predicted by initial weight and initial systolic blood pressure. Adherence to Phase 2 was not predicted by physiological measures. Weight loss maintenance in Phase 2 (not gaining more than 3% of the weight at start of phase 2) was predicted by cholesterol and triglyceride measured at the start of Phase 2 but otherwise was not predicted by the physiological measures. Initial insulin sensitivity did not predict weight loss in either phase.

Conclusion:  Participants whose weight loss over the first 2 weeks falls in the bottom third may need additional intervention if they are to continue in this type of programme. A battery of physiological measures at entry to a MR weight loss and maintenance programme explains only a very small proportion of the variation in weight loss.
Loss of α‐conotoxinMII‐ and A85380‐sensitive nicotinic receptors in Parkinson's disease striatum
Authors: Quik M. , Bordia T. , Forno L. , McIntosh J. M.
Published: July 2005

Multiple nicotinic receptors are present in rodent and monkey striatum, with a selective localization of α‐conotoxinMII‐sensitive sites in the striatum and preferential declines in their numbers after nigrostriatal damage. Here we report the presence of125I‐α‐conotoxinMII and α‐conotoxinMII‐sensitive125I‐epibatidine nicotinic receptors in human control and Parkinson's disease striatum.125I‐α‐ConotoxinMII bound to control striatum with the characteristics of a nicotinic receptor ligand although the number of sites was approximately fivefold lower than in rodent and monkey. Competition analyses of α‐conotoxinMII with125I‐epibatidine showed that toxin‐sensitive sites comprised ≈15% of nicotinic receptors in human striatum. In Parkinson's disease caudate, there was a ≈50% decline in125I‐α‐conotoxinMII sites with a similar decline in the dopamine transporter. In putamen, there were substantially greater losses of the dopamine transporter (80–90%) but only 50–60% decreases in125I‐α‐conotoxinMII sites with corresponding declines in α‐conotoxinMII‐sensitive125I‐epibatidine sites,125I‐epibatidine (multiple) sites and125I‐A85380 (β2‐containing) nicotinic receptors. The greater loss of the transporter compared with nicotinic sites suggests that only a subpopulation of nicotinic receptors is located pre‐synaptically on striatal dopaminergic neurons in man. Correlation analyses between changes in nicotinic receptors and the dopamine transporter in Parkinson's disease striatum suggest that α‐conotoxinMII‐sensitive125I‐epibatidine sites (low‐affinity sites),125I‐A85380 and125I‐epibatidine sites are localized in part to dopaminergic terminals. In summary, these results show that α‐conotoxinMII‐sensitive sites are present in human striatum and that there are high‐ and low‐affinity subtypes which are both decreased in Parkinson's disease.
ESTIMATING THE VALUE OF DELIVERY OPTIONS IN FUTURES CONTRACTS
Authors: Hranaiova Jana , Jarrow Robert A. , Tomek William G.
Published: July 2005

We analyze the effect various delivery options embedded in commodity futures contracts have on the futures price. The two embedded options considered are the timing and location options. We show that early delivery is always optimal when only a timing option is present, but not so when joint options are present. The estimates of the combined options are much smaller than the comparable estimates for the timing option alone. The average value of the joint option is about 5% of the average basis on the first day of the maturity month. This suggests that joint options can increase deliverable supplies while potentially having only a small effect on basis behavior.
MARKET STRUCTURE, CHANGING INCENTIVES, AND UNDERWRITER CERTIFICATION
Authors: Dolvin Steven D.
Published: July 2005

Early studies find that higher quality underwriters are associated with lower underpricing; however, more recent evidence suggests the opposite relation. By controlling for influences associated with the changing market structure of the underwriter industry, I provide a potential explanation for this conflict, that is, that higher quality underwriters do certify initial public offerings, resulting in lower underpricing. However, effects associated with increasing market shares tend to offset certification benefits, particularly for issues underwritten by the largest investment banks.
Effects of Forest Fragmentation on a Dung Beetle Community in French Guiana
Authors: FEER FRANÇOIS , HINGRAT YVES
Published: July 2005

Abstract: Fragmentation is the most common disturbance induced by humans in tropical forests. Some insect groups are particularly suitable for studying the effects of fragmentation on animal communities because they are taxonomically and ecologically homogenous. We investigated the effects of forest fragmentation on a dung beetle species community in the forest archipelago created in 1994–1995 by the dam of Petit Saut, French Guiana. We set and baited an equal number of pitfall traps for dung beetles on three mainland sites and seven island sites. The sites ranged from 1.1 to 38 ha. In 250 trap days, we captured 50 species in 19 genera. Diversity indices were high (2.18–4.06). The lowest diversity was on the small islands and one mainland site. Species richness and abundance were positively related to fragment area but not to distance from mainland or distance to the larger island. The islands had lower species richness and population than mainland forest, but rarefied species richness was relatively invariant across sites. There was a marked change in species composition with decreasing fragment that was not caused by the presence of a common fauna of disturbed‐area species on islands. Small islands differed from larger islands, which did not differ significantly from mainland sites. Partial correlation analyses suggested that species richness and abundance of dung beetle species were positively related to the number of species of nonflying mammals and the density index of howler monkeys (Alouatta seniculus), two parameters positively related to fragment area.
Global Warming, Human Population Pressure, and Viability of the World's Smallest Butterfly
Authors: HOYLE MARTIN , JAMES MIKE
Published: July 2005

Abstract: The effects of climate change and habitat destruction and their interaction are likely to be the greatest challenge to animal and plant conservation in the twenty‐first century. We used the world's smallest butterfly, the Sinai baton blue (Pseudophilotes sinaicus), as an exemplar of how global warming and human population pressures may act together to cause species extinctions. We mapped the entire global range of this butterfly and obtained extensive data on the intensity of livestock grazing. As with an increasing number of species, it is confined to a network of small habitat patches and is threatened both by indirect human‐induced factors (global warming) and by the direct activities of humans (in this case, livestock grazing and collection of medicinal plants). In the absence of global warming, grazing, and plant collection, our model suggested that the butterfly will persist for at least 200 years. Above a threshold intensity of global warming, the chance of extinction accelerated rapidly, implying that there may be an annual average temperature, specific to each endangered species, above which extinction becomes very much more likely. By contrast, there was no such threshold of grazing pressure—the chance of extinction increased steadily with increasing grazing. The impact of grazing, however, decreased with higher levels of year‐to‐year variation in habitat quality. The effect of global warming did not depend on the future level of grazing, suggesting that the impacts of global warming and grazing are additive. If the areas of habitat patches individually fall below certain prescribed levels, the butterfly is likely to go extinct. Two patches were very important for persistence: if either were lost the species would probably go extinct. Our results have implications for the conservation management of all species whose habitats are at risk because of the direct activities of humans and in the longer term because of climate change.
Waiting Lists and Patient Selection
Authors: Barros Pedro Pita , Olivella Pau
Published: July 2005

We develop a positive model of waiting lists for public hospitals when physicians are able to divert patients from the public to the private sector. Public treatment is free but rationed, i.e., only cases meeting some medical criteria are admitted. Private treatment has no waiting time but entails payment of a fee. Physicians and patients take into account that each patient treated in the private practice reduces the waiting list for public treatment. We show that physicians do not necessarily end up treating the mildest cases from the waiting list. Our analysis is valid for a wide class of doctors' utility functions.
Antipsychotic Medications and Drug‐Induced Movement Disorders Other Than Parkinsonism: A Population‐Based Cohort Study in Older Adults
Authors: Lee Philip E. , Sykora Kathy , Gill Sudeep S. , Mamdani Muhammad , Marras C. , Anderson Geoff , Shulman Ken I. , Stukel Thérèse , Normand Sharon‐Lise , Rochon Paula A.
Published: July 2005

Objectives:
To study the relationship between initiating therapy with an antipsychotic medication and a subsequent new diagnosis of a drug‐induced movement disorder other than parkinsonism in older adults with dementia.

Design: Retrospective, population‐based cohort study.

Setting: Ontario, Canada.

Participants: Ontario residents aged 66 and older with a diagnosis of dementia newly started on treatment with typical or atypical antipsychotic therapy.

Measurement: Estimated relative risk of developing a drug‐induced movement other than parkinsonism in the 1‐year follow‐up period after starting therapy with an antipsychotic medication.

Results: From April 1, 1997, to March 31, 2001, 21, 835 older adults with dementia who were newly started on antipsychotic medications were identified. Nine thousand seven hundred ninety subjects were started on atypical antipsychotics and 12,045 subjects started on typical antipsychotics. Demographic characteristics were similar between the groups. There were 5.24 cases of tardive dyskinesia (TD) or other drug‐induced movement disorder per 100 person‐years on therapy with a typical antipsychotic and 5.19 cases per 100 person‐years on therapy with an atypical antipsychotic. The risk of developing drug‐induced movement disorder while being treated with an atypical agent was not statistically different from that with a typical antipsychotic (relative risk=0.99, 95% confidence interval=0.86–1.15; P<.93).

Conclusion: Older adults with dementia who are treated with typical or atypical antipsychotic therapy are at risk for developing TD and other drug‐induced movement disorders.
Decisions to Hospitalize Nursing Home Residents Dying with Advanced Dementia
Authors: Lamberg Jennifer L. , Person Carmel J. , Kiely Dan K. , Mitchell Susan L.
Published: July 2005

Objectives: To describe the prevalence of, timing of, and factors associated with decisions not to hospitalize nursing home residents with advanced dementia who were dying.

Design: Retrospective cohort study.

Setting: Six hundred seventy five–bed nursing facility in Boston.

Participants: Two hundred forty residents in a teaching nursing home who died between January 2001 and December 2003 with advanced dementia.

Measurements: The prevalence and timing of do‐not‐hospitalize (DNH) orders were determined from the medical record. Data describing demographic characteristics, health conditions, advance care planning, sentinel events, and health services usage during the last 6 months of life were examined. Factors associated with having a DNH order were identified.

Results: At the time of death, 83.8% of subjects had a DNH order. The prevalence of DNH orders was 50.0% and 34.4%, 30 and 180 days before death, respectively. Hospital transfers were common during the last 6 months of life (24.6%). Factors independently associated with having a DNH order before death included surrogate decision‐maker was not the subject's child (adjusted odds ratio (AOR)=4.39, 95% confidence interval (CI)=1.52–12.66), eating problems (AOR=4.17, 95% CI=1.52–11.47), aged 92 and older (AOR=2.78, 95% CI=1.29–5.96), and length of stay 2 years or longer (AOR=2.34, 95% CI=1.11–4.93).

Conclusion: For most institutionalized persons with advanced dementia, a decision to forgo hospitalization is not made until death is imminent. Thus, hospital transfers are common near the end of life. The finding that DNH orders are associated with patient and surrogate factors can help clinicians identify cases in which decisions to forgo hospitalizations may be facilitated.
A PANEL PERFORMANCE PROCEDURE IMPLEMENTED IN R
Authors: DERNDORFER EVA , BAIERL ANDREAS , NIMMERVOLL ELISABETH , SINKOVITS ELVIRA
Published: July 2005

Monitoring performance is essential for the efficient use of a sensory panel both during training and while carrying out product assessments. We present a concise procedure to monitor panel performance based on classical statistical methods. The program includes tests for the ability to discriminate between products, repeatability of assessments, scale use, agreement between panelists and a principal component analysis map of panelist means across attributes. The algorithm is implemented in R – a state‐of‐the‐art, freely available statistical software package. The program output is summarized in graphs and tables. This easily applicable panel performance procedure is aimed at improving sensory practice, especially in areas where the use of highly complex systems is not feasible.
N‐Benzyl‐p‐toluene sulphonamide allows the recording of trains of intracellular action potentials from nervestimulated intact fast‐twitch skeletal muscle of the rat
Authors: Macdonald W. A. , Pedersen T. H. , Clausen T. , Nielsen O. B.
Published: July 2005

In skeletal muscle, the intracellular recording of trains of action potentials is difficult owing to the movement of the muscle upon stimulation. A potential tool for the removal of muscle movement is the cross‐bridge cycle blocker, N‐benzyl‐p‐toluene sulphonamide (BTS), although the effects of BTS on the passive and active membrane properties of intact muscle fibres are not known. Rat extensor digitorum longus (EDL) muscle was used to show that 50 μm BTS reduced tetanic force to ∼10% of control force, without markedly altering muscle excitability. Incubation with BTS did not alter intracellular K+ content or Na+–K+ pump activity, but produced minor decreases in intracellular Na+ content (7%), resting 22Na+ influx (14%) and excitation‐induced 22Na+ influx (29%). Despite these alterations to Na+ fluxes, BTS did not impair muscle excitability, since membrane conductance, resting membrane potential (RMP), rheobase current and the amplitude, overshoot and maximum rate of depolarization of the action potential were all unaltered. However, BTS did induce a small (8%) decrease in the maximum rate of repolarization of the action potential and an increase in the refractory period. The minor effects of BTS on muscle membrane properties did not compromise the ability of the muscle to propagate action potentials, even during tetanic stimulation. In conclusion, BTS can be used successfully to reduce contractility, allowing the intracellular recording of action potentials during both twitch and tetanic contraction of nerve‐stimulated muscle, thus making it an excellent tool for the study of electrophysiology in fast‐twitch skeletal muscle.
Implementation of a Level Set Interface Tracking Method in the FIDAP and CFX-4 Codes
Authors: Shepel Sergey V. , Smith Brian L. , Paolucci Samuel
Published: July 2005

We present a streamline-upwind–Petrov-Galerkin (SUPG) finite element level set method that may be implemented into commercial computational fluid dynamics (CFD) software, both finite element (FE) and finite volume (FV) based, to solve problems involving incompressible, two-phase flows with moving interfaces. The method can be used on both structured and unstructured grids. Two formulations are given. The first considers the coupled motion of the two phases and is implemented within the framework of the commercial CFD code CFX-4. The second can be applied for those gas-liquid flows for which effects of the gaseous phase on the motion of the liquid phase are negligible; consequently, the gaseous phase is removed from consideration. This level set formulation is implemented in the commercial CFD code FIDAP. The resulting level set formulations are tested and validated on sample problems involving two-phase flows with density ratios of the order of 103 and viscosity ratios as high as 1.6×105.