bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors to consider in Micronesian food-based interventions: a case study of preventing vitamin A deficiency
Authors: Englberger L , Marks GC , Fitzgerald MH
Published: May 2004

Background:

Many factors need to be considered in a food-based intervention. Vitamin A deficiency and chronic diseases, such as diabetes, heart disease and cancer, have become serious problems in the Federated States of Micronesia (FSM) following the decreased production and consumption of locally grown foods. However, agricultural and social conditions are still favourable for local food production.

Aim:

To identify key factors to consider in a Micronesian food-based intervention focusing on increased production and consumption of four major Micronesian staple foods: banana, breadfruit, giant swamp taro and pandanus.

Methods:

Ethnographic methods including key informant interviews and a literature review.

Results:

Pacific and Micronesian values, concepts of food and disease, and food classifications differ sharply from Western concepts. There are few FSM professionals with nutrition expertise. Traditional foods and food cultivars vary in nutrient content, consumption level, cost, availability, status, convenience in growing, storing and cooking, and organoleptic factors.

Conclusions:

A systematic consideration of the factors that relate to a food-based intervention is critical to its success. The evaluation of which food and cultivar of that food that might be most effectively promoted is also critical. Regional differences, for example FSM inter-island differences between the staple foods and cultivars, must be considered carefully. The evaluation framework presented here may be relevant to Pacific Island and other countries with similar foods where food-based interventions are being planned. An ethnographic approach was found to be essential in understanding the cultural context and in data collection and analysis.
Why the Bush administration and the global sugar industry are determined to demolish the 2004 WHO global strategy on diet, physical activity and health
Authors: Cannon Geoffrey
Published: May 2004

Objective:

To indicate why the world's most powerful nation state and one powerful sector of the food and drink production and manufacturing industry are determined to demolish the 2004 WHO (World Health Organization) global strategy on diet, physical activity and health, and to disassociate it from the 2003 WHO/FAO (Food and Agriculture Organization) expert report on diet, nutrition and the prevention of chronic diseases, which with its background papers is the immediate scientific basis for the strategy. To encourage representatives of nation states at the 2004 WHO World Health Assembly to support the strategy together with the report, so that the strategy is explicit and quantified, and responds to the need expressed by member states at the 2002 World Health Assembly. This is for an effective global strategy to prevent and control chronic diseases whose prevalence is increased by nutrient-poor food low in vegetables and fruits and high in energy-dense fatty, sugary and/or salty foods and drinks and also by physical inactivity. Of these diseases, obesity, diabetes, cardiovascular diseases and cancers of several sites are now the chief causes of morbidity and mortality in most countries in the world.

Method:

A summary of the global strategy and its roots in scientific knowledge accumulated over the last half-century. Reasons why the global strategy and the expert report are opposed by the current US government and the world sugar industry, with some reference to modern historical context. A summary of the trajectory of the global strategy since its first draft made in early 2003, and a further summary of its weaknesses, strengths and potential.

Conclusion:

The 2004 WHO global strategy and the 2003 WHO/FAO expert report are perceived by the current US administration as an impediment to US trade and international policy, within a general context of current US government hostility to the UN (United Nations) system as a brake on the exercise of its power as the world's dominant nation. Policy-makers throughout the world should be aware of the contexts of current pressures put on them by powerful nation states and sectors of industry whose ideologies and commercial interests are challenged by international initiatives designed to improve public health and to leave a better legacy for future generations.
Health beliefs, optimism, and health‐related decisions: A study with Hong Kong Chinese
Authors: Lai Julian C. L. , Cheng Sheung‐Tak
Published: May 2004

The Health Belief Model (HBM; Rosenstock, 1966) is the most widely used psychological theory of health‐related behaviours but its applicability to non‐Western, especially Asian, populations has not been systematically studied. The main objective of the current study was to examine the effects of components of the HBM and dispositional optimism on preventive intention in two separate samples of 220 Hong Kong Chinese adults and 340 Hong Kong Chinese adolescents. Two HBM variables, benefits and barriers, were experimentally manipulated for an imaginary flu outbreak and a hypothetical vaccine. Optimism in the two samples was assessed using the Chinese revised Life Orientation Test (Lai et al., 1998). Participants indicated their intention to take the hypothetical vaccine after reading information for each of the treatment combinations defined by the two HBM variables. The order of the presentation of each of the six treatment conditions was counterbalanced. Results of ANOVA showed that the effects of the two HBM variables were similar in the two groups. Higher benefits and lower barriers were associated with stronger behavioural intention to take the vaccine. The two HBM variables interacted significantly in the adolescent but not the adult sample. Among the adolescents, the difference in intention scores between low and high barriers became larger when the benefits of taking the vaccine increased. In addition, optimism had significant effect on preventive intention only among the adolescents. These findings suggest that age may be an important factor moderating the effects of HBM components as well as optimism on preventive intention in Hong Kong Chinese. Implications of these findings to future research among Chinese were discussed.
Optimism and realism: A review of self‐efficacy from a cross‐cultural perspective
Authors: Klassen Robert M.
Published: May 2004

This review critically examines much of the research investigating self‐efficacy beliefs through cross‐cultural comparisons. Two sets of cross‐cultural comparison groups are examined: Asian (or immigrant Asian) versus Western, and Eastern European versus Western European and American groups. After an introduction to self‐efficacy theory, some cross‐cultural aspects of self and self‐beliefs are discussed, and the cultural dimensions of individualism and collectivism are introduced. Analysis of the articles focuses on differences in levels of efficacy beliefs, calibration of beliefs with performance, methodological problems, and implications for practice. Almost all of the 20 studies reviewed found efficacy beliefs to be lower for non‐Western cultural groups, but in some cases these lower beliefs were more predictive of subsequent functioning. There is some evidence that the mean efficacy beliefs of a cultural group are modified through immigration or political changes. For some non‐Western groups, collective efficacy appears to operate in much the same way as self‐efficacy operates for Western groups. Realistic—as opposed to optimistic—efficacy beliefs do not necessarily predict poor performance for all cultural groups, as has been suggested by self‐efficacy theory. Only a minority of the studies included measurement of cultural dimensions such as individualism and collectivism, although most of the studies based conclusions on assumed cultural differences. In some cases, self‐efficacy was poorly defined and bore little resemblance to theoretically derived definitions. Conclusions from this research have implications especially for applied settings in education and business: Efficacy beliefs and performance appear to be enhanced when training approaches are congruent with the individual's sense of self. Lower levels of self‐efficacy beliefs found in some collectivist groups do not always signify lower subsequent performance, but are instead reflective of differing construals of self.
Structure and function of the perceived acculturation context of young Moroccans in the Netherlands
Authors: Ait Ouarasse Otmane , van de Vijver Fons J. R.
Published: May 2004

The goals of this research were twofold: (1) to explore the structure of the perceived acculturation context in a group of 155 Moroccan adolescents and young adults living in the Netherlands, and (2) to examine to what extent this structure can predict quality of relationships, success, and mental health. The perceived acculturation context turned out to be multidimensional and its dimensions independent. The perceived mainstream context consisted of a tolerance factor and an integration factor while the perceived minority context consisted of a permissiveness to adjust factor and an ethnic vitality factor. A path model in which both the perceived mainstream and minority contexts predicted acculturation outcomes showed a good fit. The effects flowed from context to relationships to success to acculturative stress, were both direct and indirect, and showed the expected signs. Both perceived mainstream context and perceived minority context were more or less equally, though distinctly, important. While the mainstream context was crucial for work success, the minority context remained especially important in leading to school success and good mental health. A good fit was found for a model in which sociocultural adaptation preceded psychological adaptation and within the sociocultural component of adaptation, quality of relationships preceded school success, which, in turn, preceded work success.
Social competence in Zimbabwean multicultural schools: Effects of ethnic and gender differences
Authors: Mpofu Elias , Thomas Kenneth R. , Chan Fong
Published: May 2004

Students' social competence was investigated in relation to race/ethnicity and gender for a sample of 371 Zimbabwean students attending racially/ethnically integrated schools. About 42% of the students were black, and 58% white (mean age 12 years; SD=9 months). Peer and teacher sociometric ratings of children's social behaviour, social responsibility, and friendliness comprised the social competence measures. Tests of empirical independence among these social competence measures supported their uniqueness in reliably assessing components of the general construct of social competence among Zimbabwean students. Multiple analysis of variance procedures were used to examine the relationship between social competence statuses and group membership (i.e., race/ethnicity, gender) while controlling for aggregate scores and classroom racial proportions. Superior academic achievement and racial/ehnic propinquity are social status levelling factors in multiracial school settings. Teachers rated white students higher on social responsibility and social behaviour. Students rated white students higher on social responsibility only. Comparisons of social competence by ethnicity and gender revealed that white and female students were rated significantly higher on social behaviour and social responsibility than their black and male classmates. Female students were perceived as more socially competent or better adjusted to school than males. Reliable differences in social competence in race/ethnicity and gender groups were concentrated in peer ratings of social responsibility and in teacher ratings of social behaviour and social responsibility. In postcolonial settings or settings with a history of race/ethnicity and gender‐based privilege, minorities from a dominant culture may have higher social status than peers from a majority culture. Superior social competence in females is a resource for school adaptation and social climate. Students have perceptions of social competence in peers that only partially overlap with those of teachers and contribute uniquely to their experience of school. Social competence in students is multifaceted, gendered, and differently perceived by teachers and peers.
Activities of Antioxidant Scavenger Enzymes (Superoxide Dismutase and Glutathione Peroxidase) in Erythrocytes in Adult Women With and Without Type II Diabetes
Authors: Carmeli Eli , Coleman Raymond , Berner Yitshal N.
Published: May 2004

It is widely believed that oxidative stress plays an important
role in the pathogenesis of type II diabetes. The present
study was undertaken to examine the functioning of two antioxidant
scavenger enzymes, superoxide dismutase (SOD)
and glutathione peroxidase (GSH‐Px), in erythrocytes in a
population of healthy aging adult women compared with
a similar population with type II diabetes. Blood samples
were examined from 42 female adult healthy subjects at
different ages and from 59 female patients with type II diabetes.
A significant increase in SOD activities was correlated
with aging in erythrocytes of the healthy control subjects
(r = .550, P = .001); however, this correlation was
not found in subjects with type II diabetes (r = .250, P <
.07). A trend showing a reduction in glutathione peroxidase
activities was demonstrated with aging (r = −.331, P =
.228); however, this trend was not found in diabetic subjects
(r = .031, P < .820). The results indicate a possible
imbalance in the antioxidant system in erythrocytes of aging adult women, which is even more pronounced in cases
of type II diabetes. This study may indicate possible therapeutic
treatment or preventive measures to limit oxidative
damage and reduce complications of diabetes.
Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder
Authors: Rünker Annette E. , Kobsar Igor , Fink Torsten , Loers Gabriele , Tilling Thomas , Putthoff Peggy , Wessig Carsten , Martini Rudolf , Schachner Melitta
Published: May 2004

Mutations in the gene of the peripheral myelin protein zero (P0) give rise to the peripheral neuropathies Charcot-Marie-Tooth type 1B disease (CMT1B), Déjérine-Sottas syndrome, and congenital hypomyelinating neuropathy. To investigate the pathomechanisms of a specific point mutation in the P0 gene, we generated two independent transgenic mouse lines expressing the pathogenic CMT1B missense mutation Ile106Leu (P0sub) under the control of the P0 promoter on a wild-type background. Both P0sub-transgenic mouse lines showed shivering and ultrastructural abnormalities including retarded myelination, onion bulb formation, and dysmyelination seen as aberrantly folded myelin sheaths and tomacula in all nerve fibers. Functionally, the mutation leads to dispersed compound muscle action potentials and severely reduced conduction velocities. Our observations support the view that the Ile106Leu mutation acts by a dominant-negative gain of function and that the P0sub-transgenic mouse represents an animal model for a severe, tomaculous form of CMT1B.
Calcineurin initiates smooth muscle differentiation in neural crest stem cells
Authors: Mann Kris M. , Ray Jenna Lynn , Moon Edward S. , Sass Kristin M. , Benson Mark R.
Published: May 2004

The process of vascular smooth muscle cell (vSMC) differentiation is critical to embryonic angiogenesis. However, despite its importance, the vSMC differentiation program remains largely undefined. Murine gene disruption studies have identified several gene products that are necessary for vSMC differentiation, but these methodologies cannot establish whether or not a factor is sufficient to initiate the differentiation program. A gain-of-function system consisting of normal vSMC progenitor cells would serve as a useful complement to whole animal loss-of-function studies. We use such a system here, namely freshly isolated rat neural crest stem cells (NCSCs), to show that activation of the calcineurin signaling pathway is sufficient to drive these cells toward a smooth muscle fate. In addition, we present data suggesting that transforming growth factor (TGF)-β1, which also causes NCSCs to differentiate into smooth muscle, activates calcineurin signaling in NCSCs, leading to a model in which activation of calcineurin signaling is the mechanism by which TGF-β1 causes SMC differentiation in these cells.
Inflammation-associated Cell Cycle–independent Block of Apoptosis by Survivin in Terminally Differentiated Neutrophils
Authors: Altznauer Frank , Martinelli Sibylla , Yousefi Shida , Thürig Christine , Schmid Inès , Conway Edward M. , Schöni Martin H. , Vogt Peter , Mueller Christoph , Fey Martin F. , Zangemeister-Wittke Uwe , Simon Hans-Uwe
Published: May 2004

Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle–dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle–independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer.
T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis
Authors: Hao Zhenyue , Hampel Brigitte , Yagita Hideo , Rajewsky Klaus
Published: May 2004

To study the role of Fas–Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through Cre-mediated recombination. Experiments in which Fas was ablated in T cells, B cells, T and B cells, or in a more generalized manner demonstrated that the development of lymphoproliferative disease as seen in Fas-deficient mice requires Fas ablation in lymphoid and nonlymphoid tissues. Selective inactivation of Fas in T cells led to a severe lymphopenia over time, accompanied by up-regulation of FasL on activated T cells and apoptosis of peripheral lymphocytes. In addition, the mutant animals developed a fatal wasting syndrome caused by massive leukocyte infiltration in the lungs together with increased inflammatory cytokine production and pulmonary fibrosis. Inhibition of Fas–FasL interaction in vivo completely prevented the loss of lymphocytes and initial lymphocyte infiltration in the lungs. Thus, FasL-mediated interaction of activated, Fas-deficient T cells with Fas-expressing cells in their environment leads to break down of lymphocyte homeostasis and development of a lung disease strikingly resembling idiopathic pulmonary fibrosis in humans, a common and severe disease for which the mutant mice may serve as a first animal model.
Mannose-binding Lectin-deficient Mice Are Susceptible to Infection with Staphylococcus aureus
Authors: Shi Lei , Takahashi Kazue , Dundee Joseph , Shahroor-Karni Sarit , Thiel Steffen , Jensenius Jens Christian , Gad Faten , Hamblin Michael R. , Sastry Kedarnath N. , Ezekowitz R. Alan B.
Published: May 2004

Gram-positive organisms like Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Humoral response molecules together with phagocytes play a role in host responses to S. aureus. The mannose-binding lectin (MBL, also known as mannose-binding protein) is an oligomeric serum molecule that recognizes carbohydrates decorating a broad range of infectious agents including S. aureus. Circumstantial evidence in vitro and in vivo suggests that MBL plays a key role in first line host defense. We tested this contention directly in vivo by generating mice that were devoid of all MBL activity. We found that 100% of MBL-null mice died 48 h after exposure to an intravenous inoculation of S. aureus compared with 45% mortality in wild-type mice. Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus. Our study provides direct evidence that MBL plays a key role in restricting the complications associated with S. aureus infection in mice and raises the idea that the MBL gene may act as a disease susceptibility gene against staphylococci infections in humans.
A Population-based Study of Morbidity and Mortality in Mannose-binding Lectin Deficiency
Authors: Dahl Morten , Tybjærg-Hansen Anne , Schnohr Peter , Nordestgaard Børge G.
Published: May 2004

Reduced levels of wild-type mannose-binding lectin (MBL) may increase susceptibility for infection, other common diseases, and death. We investigated associations between MBL deficiency and risk of infection, other common diseases, and death during 24, 24, and 8 yr of follow-up, respectively. We genotyped 9,245 individuals from the adult Danish population for three MBL deficiency alleles, B, C, and D, as opposed to the normal noncarrier A allele. Hospitalization incidence per 10,000 person · yr was 644 in noncarriers compared with 631 in heterozygotes (log-rank: P = 0.39) and 658 in deficiency homozygotes (P = 0.53). Death incidence per 10,000 person · yr was 235 in noncarriers compared with 244 in heterozygotes (P = 0.44) and 274 in deficiency homozygotes (P = 0.12). After stratification by specific cause of hospitalization or death, only hospitalization from cardiovascular disorders was increased in deficiency homozygotes versus noncarriers (P = 0.02). When retested in two case control studies, this association could not be confirmed. Incidence of hospitalization or death from infections or other serious common disorders did not differ between deficiency homozygotes and noncarriers. In conclusion, in this large study in an ethnically homogenous Caucasian population, there was no evidence for significant differences in infectious disease or mortality in MBL-deficient individuals versus controls. Our results suggest that MBL deficiency is not a major risk factor for morbidity or death in the adult Caucasian population.
CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1
Authors: Lee Steven P. , Brooks Jill M. , Al-Jarrah Hatim , Thomas Wendy A. , Haigh Tracey A. , Taylor Graham S. , Humme Sibille , Schepers Aloys , Hammerschmidt Wolfgang , Yates John L. , Rickinson Alan B. , Blake Neil W.
Published: May 2004

The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I–restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon γ release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter–dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies.
Telomere Erosion in Memory T Cells Induced by Telomerase Inhibition at the Site of Antigenic Challenge In Vivo
Authors: Reed John R. , Vukmanovic-Stejic Milica , Fletcher Jean M. , Soares Maria Vieira D. , Cook Joanne E. , Orteu Catherine H. , Jackson Sarah E. , Birch Katie E. , Foster Graham R. , Salmon Mike , Beverley Peter C.L. , Rustin Malcolm H.A. , Akbar Arne N.
Published: May 2004

The extent of human memory T cell proliferation, differentiation, and telomere erosion that occurs after a single episode of immune challenge in vivo is unclear. To investigate this, we injected tuberculin purified protein derivative (PPD) into the skin of immune individuals and isolated responsive T cells from the site of antigenic challenge at different times. PPD-specific CD4+ T cells proliferated and differentiated extensively in the skin during this secondary response. Furthermore, significant telomere erosion occurred in specific T cells that respond in the skin, but not in those that are found in the blood from the same individuals. Tissue fluid obtained from the site of PPD challenge in the skin inhibited the induction of the enzyme telomerase in T cells in vitro. Antibody inhibition studies indicated that type I interferon (IFN), which was identified at high levels in the tissue fluid and by immunohistology, was responsible in part for the telomerase inhibition. Furthermore, the addition of IFN-α to PPD-stimulated CD4+ T cells directly inhibited telomerase activity in vitro. Therefore, these results suggest that the rate of telomere erosion in proliferating, antigen-specific CD4+ T cells may be accelerated by type I IFN during a secondary response in vivo.
Endogenous Presentation of CD8+ T Cell Epitopes from Epstein-Barr Virus–encoded Nuclear Antigen 1
Authors: Tellam Judy , Connolly Geoff , Green Katherine J. , Miles John J. , Moss Denis J. , Burrows Scott R. , Khanna Rajiv
Published: May 2004

Epstein-Barr virus (EBV)–encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type–dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I–restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8+ T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8+ T cell epitopes from EBNA1.
In Vivo Instruction of Suppressor Commitment in Naive T Cells
Authors: Apostolou Irina , von Boehmer Harald
Published: May 2004

The induction of antigen-specific tolerance in the mature immune system of the intact organism has met with limited success. Therefore, nonspecific immunosuppression has been the treatment of choice to prevent unwanted immunity. Here, it is shown that prolonged subcutaneous infusion of low doses of peptide by means of osmotic pumps transforms mature T cells into CD4+25+ suppressor cells that can persist for long periods of time in the absence of antigen and confer specific immunologic tolerance upon challenge with antigen. The described procedure resembles approaches of tolerance induction used decades ago, induces tolerance in the absence of immunity, and holds the promise to become an effective means of inducing antigen-specific tolerance prospectively, whereas its power to suppress already ongoing immune responses remains to be determined.
Human Mannose-binding Lectin in Immunity
Authors: Casanova Jean-Laurent , Abel Laurent
Published: May 2004

Human mannose-binding lectin (MBL) recognizes a wide range of microorganisms and triggers the most ancient pathway of complement activation. However, ∼5% of individuals lack functional serum MBL and have not been found to be prone to severe infections in prospective studies. These data suggest that human MBL is largely redundant for protective immunity and may even have been subject to counter selection because of a deleterious impact.
Epstein-Barr Virus Nuclear Antigen 1
Authors: Münz Christian
Published: May 2004

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)—the one EBV antigen that is expressed in all EBV-associated malignancies—has long been thought to go undetected by the cell-mediated immune system. However, recent studies show that EBNA1 can be presented to both CD4+ and CD8+ T cells, making it a potential new target for immunotherapy of EBV-related cancers.
Algorithms for sequence analysis via mutagenesis
Authors: Keith Jonathan M. , Adams Peter , Bryant Darryn , Cochran Duncan A. E. , Lala Gita H. , Mitchelson Keith R.
Published: May 2004

Motivation: Despite many successes of conventional DNA sequencing methods, some DNAs remain difficult or impossible to sequence. Unsequenceable regions occur in the genomes of many biologically important organisms, including the human genome. Such regions range in length from tens to millions of bases, and may contain valuable information such as the sequences of important genes. The authors have recently developed a technique that renders a wide range of problematic DNAs amenable to sequencing. The technique is known as sequence analysis via mutagenesis (SAM). This paper presents a number of algorithms for analysing and interpreting data generated by this technique.

Results: The essential idea of SAM is to infer the target sequence using the sequences of mutants derived from the target. We describe three algorithms used in this process. The first algorithm predicts the number of mutants that will be required to infer the target sequence with a desired level of accuracy. The second algorithm infers the target sequence itself, using the mutant sequences. The third algorithm assigns quality values to each inferred base. The algorithms are illustrated using mutant sequences generated in the laboratory.

Availability: Software will be made available upon request.
A mixture model for estimating the local false discovery rate in DNA microarray analysis
Authors: Liao J.G. , Lin Yong , Selvanayagam Zachariah E. , Shih Weichung Joe
Published: May 2004

Motivation: Statistical methods based on controlling the false discovery rate (FDR) or positive false discovery rate (pFDR) are now well established in identifying differentially expressed genes in DNA microarray. Several authors have recently raised the important issue that FDR or pFDR may give misleading inference when specific genes are of interest because they average the genes under consideration with genes that show stronger evidence for differential expression. The paper proposes a flexible and robust mixture model for estimating the local FDR which quantifies how plausible each specific gene expresses differentially.

Results: We develop a special mixture model tailored to multiple testing by requiring the P-value distribution for the differentially expressed genes to be stochastically smaller than the P-value distribution for the non-differentially expressed genes. A smoothing mechanism is built in. The proposed model gives robust estimation of local FDR for any reasonable underlying P-value distributions. It also provides a single framework for estimating the proportion of differentially expressed genes, pFDR, negative predictive values, sensitivity and specificity. A cervical cancer study shows that the local FDR gives more specific and relevant quantification of the evidence for differential expression that can be substantially different from pFDR.

Availability: An R function implementing the proposed model is available at http://www.geocities.com/jg_liao/software
Rainbow: a toolbox for phylogenetic supertree construction and analysis
Authors: Chen D. , Eulenstein O. , Fernández-Baca D.
Published: May 2004

Summary: Rainbow is a program that provides a graphic user interface to construct supertrees using different methods. It also provides tools to analyze the quality of the supertrees produced. Rainbow is available for Mac OS X, Windows and Linux.

Availability: Rainbow is a free open-source software. Its binary files, source code, and manual can be downloaded from the Rainbow web page: http://genome.cs.iastate.edu/Rainbow/
Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae
Authors: Kadaba Sujatha , Krueger Anna , Trice Tamyra , Krecic Annette M. , Hinnebusch Alan G. , Anderson James
Published: May 2004

The tRNA m1A58 methyltransferase is composed of two subunits encoded by the essential genes TRM6 and TRM61 (formerly GCD10 and GCD14). The trm6-504 mutation results in a defective m1A methyltransferase (Mtase) and a temperature-sensitive growth phenotype that is attributable to the absence of m1A58 and consequential tRNAiMet instability. We used a genetic approach to identify the genes responsible for tRNAiMet degradation in trm6 cells. Three recessive extragenic mutations that suppress trm6-504 mutant phenotypes and restore hypomodified tRNAiMet to near normal levels were identified. The wild-type allele of one suppressor, DIS3/RRP44, encodes a 3′-5′ exoribonuclease and a member of the multisubunit exosome complex. We provide evidence that a functional nuclear exosome is required for the degradation of tRNAiMet lacking m1A58. A second suppressor gene encodes Trf4p, a DNA polymerase (pol σ) with poly(A) polymerase activity. Whereas deletion of TRF4 leads to stabilization of tRNAiMet, overexpression of Trf4p destabilizes the hypomodified tRNAiMet in trm6 cells. The hypomodified, but not wild-type, pre-tRNAiMet accumulates as a polyadenylated species, whose abundance and length distribution both increase upon Trf4p overexpression. These data indicate that a tRNA surveillance pathway exists in yeast that requires Trf4p and the exosome for polyadenylation and degradation of hypomodified pre-tRNAiMet.
Putative Ancestral Origins of Chromosomal Segments in Individual African Americans: Implications for Admixture Mapping
Authors: Seldin Michael F. , Morii Takanobu , Collins-Schramm Heather E. , Chima Bill , Kittles Rick , Criswell Lindsey A. , Li Hongzhe
Published: May 2004

Theoretically, markers that distinguish European from West African ancestry can be used to examine the origin of chromosomal segments in individual African Americans. In this study, putative ancestral origin was examined by using haplotypes estimated from genotyping 268 African Americans for 29 ancestry informative markers spaced over a 60-cM segment of chromosome 5. Analyses using a Bayesian algorithm (STRUCTURE) provided evidence that blocks of individual chromosomes derive from one or the other parental population. In addition, modeling studies were performed by using hidden real marker data to simulate patient and control populations under different genotypic risk ratios. Ancestry analysis showed significant results for a genotypic risk ratio of 2.5 in the African American population for modeled susceptibility genes derived from either putative parental population. These studies suggest that admixture mapping in the African American population can provide a powerful approach to defining genetic factors for some disease phenotypes.
New view of the high-pressure behaviour of GdFeO3-type perovskites
Authors: Zhao J. , Ross N. L. , Angel R. J.
Published: May 2004

Recent determinations of the structures of several GdFeO3-type orthorhombic perovskites (ABO3) show that the octahedra in some become more tilted with increasing pressure. In others the octahedra become less tilted and the structure evolves towards a higher-symmetry configuration. This variety of behaviour can be explained in terms of the relative compressibilities of the octahedral and dodecahedral cation sites in the perovskite structure. If the BO6 octahedra are less compressible than the AO12 sites then the perovskite will become more distorted with pressure, but the perovskite will become less distorted if the BO6 site is more compressible than the AO12 site. In this contribution we use the bond-valence concept to develop a model that predicts the relative compressibilities of the cation sites in oxide perovskites. We introduce the site parameter M

i
defined in terms of the coordination number N

i
, average bond length at room pressure R

i
, and the bond-valence parameters R
0 and B,M_i = ({R_i N_i }/ B)\exp [({{R_0 - R_i }) / B}].M

i
represents the variation in the bond-valence sum at the central cation in a polyhedral site because of the change of the average bond distance. Experimental data suggest that the pressure-induced changes in the bond-valence sums at the two cation sites within any given perovskite are equal. With this condition we show that the ratio of cation-site compressibilities is given by \beta _B /\beta _A = M_A /M_B. This model, based only upon room-pressure bond lengths and bond-valence parameters, correctly predicts the structural behaviour and some physical properties of the oxide perovskites that have been measured at high pressure.
First bent form for the hydroxo-bridged cis-diammineplatinum(II) dimer [Pt2(NH3)4(μ-OH)2](ClO4)2
Authors: Sakai Ken , Konno Yosuke , Takayama Noboru , Takahashi Satoru
Published: May 2004

The third crystal structure containing the hydroxo-bridged cis-diammineplatinum(II) dimer has been determined for a perchlorate salt of the complex, [Pt2(NH3)4(μ-OH)2](ClO4)2. However, the dinuclear cations in the nitrate and the carbonate salts, [Pt2(NH3)4(μ-OH)2](NO3)2 [Faggiani, Lippert, Lock & Rosenberg (1977). J. Am. Chem. Soc. 99, 777–781] and [Pt2(NH3)4(μ-OH)2](CO3)·H2O [Lippert, Lock, Rosenberg & Zvagulis (1978). Inorg. Chem.
17, 2971−2975], were reported to possess a nearly planar geometry. The cation in the title perchlorate salt has been found to possess an exceptional bent form in which two Pt coordination planes within the dimer are tilted at an angle of 151.7 (1)° to one another. The diplatinum entity has a syn orientation with regard to the conformation of two hydroxo bridges, in part due to the one-dimensional hydrogen-bonding network achieved in the crystal structure. DFT MO investigations have also been carried out to reveal that the planar-bent selection could be induced by the anti–syn selection at the H(hydroxo) atoms. Comparison has also been made between the geometrical features of the three salts from the viewpoint of the orientation of H(hydroxo) atoms.
Methods of crystallochemical analysis of supramolecular complexes by means of Voronoi–Dirichlet polyhedra: a study of cucurbituril host–guest compounds
Authors: Virovets A. V. , Blatov V. A. , Shevchenko A. P.
Published: May 2004

Crystallochemical analysis methods based on the Voronoi–Dirichlet partition of crystal space are extended to supramolecular complexes of any complexity. The sizes and shapes of receptor cavities and substrate molecules are shown to be successfully estimated as volumes and the second moments of inertia of the corresponding molecular Voronoi–Dirichlet polyhedra. To predict which organic substrates can occupy the receptor cavity a mini-expert system known as MOLVOL was created, comprising a database on completely determined crystal structures of almost 60 000 organic molecular compounds. Using the developed methods, volumes and shapes are assessed for cucurbit[n]uril receptors (n = 5–10) and their cavities. A number of organic and inorganic molecules are found which can optimally fit the cavities inside the cucurbit[5]uril and cucurbit[6]uril molecules.
Non-aromatic endocyclic angle at the ring fusion with the aromatic ring in benzocyclopentene and -hexene, revisited
Authors: De Ridder Dirk J. A. , Bürgi Hans-Beat
Published: May 2004

X-ray geometries of monocycloalkenobenzenes with a fused-ring size of r = 5, 6 were obtained by the use of the Cambridge Structural Database. In contrast to Allen's study [Acta Cryst. (1981), B37, 900–906], the data were not averaged over exact or imposed m
ad symmetry (m
ad is the mirror plane going through the midpoint of the aromatic ring fusion bond and the aromatic bond parallel to it). The distribution of the non-aromatic endocyclic angle ∊ at the ring fusion clearly shows two and three, respectively, distinct curves for r = 5 and r = 6. The respective ranges are 104.3–112.6 and 104.4–123.2°. If one of the C atoms directly attached to the aromatic ring is sp
2 hybridized, the bond length e between the aromatic ring and this atom is shortened by some 0.044 (15) and 0.027 (12) Å for r = 5 and r = 6, respectively. However, for r = 5, e is only shortened by 0.030 (17) Å when both C atoms directly attached to the aromatic ring are sp
2 hybridized. For r = 5, the endocyclic angle ∊ is 1.2 (13)° smaller at the side involving the sp
2 hybridized C atom.
Packing-dependent photochromism: the case of photoinduced intramolecular proton transfer in 6-(2′,4′-dinitrobenzyl)-2,2′-bipyridine
Authors: Naumov Pance , Ohashi Yuji
Published: May 2004

A new photoactive monoclinic polymorph (γ-form) of 6-(2′,4′-dinitrobenzyl)-2,2′-bipyridine was obtained from an acetone–methanol solution. The crystal structure was compared with those of two polymorphs reported previously (photoactive orthorhombic α-form and photoinactive monoclinic β-form) and with structures of related nitrobenzylpyridines to explain the relation between the structure and photochromism. The comparison of the reaction cavities around the reactive pyridyl–benzyl–nitro fragment among the polymorphs and related nitrobenzylpyridines revealed that a crucial factor for photochromic activity is the rotational freedom of the ortho-nitro group in their crystals and its accessibility from the proton–donor and proton–acceptor sites. This is because the ortho-nitro group should rotate around the N—C bond to transfer a proton from the methylene group to the N atom of the pyridine ring.
Packing conflicts in the Z′ = 5 structure of CF3(CF2)3(CH2)10COOH
Authors: Lehmler Hans-Joachim , Parkin Sean , Brock Carolyn Pratt
Published: May 2004

Dimers of the partially fluorinated amphiphile 1-(perfluorobutyl)undecanoic acid, CF3(CF2)3(CH2)10COOH, crystallize in the same basic packing arrangement found for many n-alkyl carboxylic acids. The unit cell of the fluorinated compound, however, contains five independent molecules rather than the one found for most n-alkyl carboxylic acids including CH3(CH2)13COOH. The structures of the two C15 acids are compared. The structural modulations that lead to the large value of Z′ can be understood as resulting from the conflict between the necessity of filling space densely and uniformly and the tendency of unlike groups to be segregated spatially. The few other known structures of compounds with both (CF2)
n
and (CH2)
m
regions show evidence of the same conflict.
Structural phase transitions, and Br...N and Br...Br interactions in 1-phenyl-2-methyl-4-nitro-5-bromoimidazole
Authors: Kubicki Maciej
Published: May 2004

Crystals of C10H8N3O2Br undergo two reversible phase transitions between 295 and 100 K. The first, of an order–disorder nature, is a second-order transition and takes place continuously over a wide temperature range. This transition is connected with the doubling of the length of the c axis of the unit cell and with the change of the space group from P21/m with Z′ = 1/2 (room-temperature α-phase) to P21/c, Z′ = 1 (β-phase, 200–120 K). During this transition the molecule loses the C

s
symmetry of the α-phase. The second transition takes place between 118 and 115 K, and is accompanied by a change of the crystal symmetry to the triclinic space group P\bar 1 (low-temperature γ-phase). This second phase transition is accompanied by the twinning of the crystal. Neither the molecular geometry nor the crystal packing shows any dramatic changes during these phase transitions. Halogen bonds C—Br...N and dihalogen interactions Br...Br play a crucial role in determining the crystal packing and compete successfully with other kinds of weak intermolecular interactions.
30 Space-group corrections: two examples of false polymorphism and one of incorrect interpretation of the fine details of an IR spectrum
Authors: Clemente Dore Augusto , Marzotto Armando
Published: May 2004

Revised structures are reported for 30 crystalline compounds, based on space groups of higher symmetry than originally reported. In 18 cases the Laue class is revised, in seven cases the center of symmetry is added, in two cases the Laue class change is coupled with the addition of the center of symmetry, in two cases the addition of the center of symmetry also requires the addition of systematic absences and, finally, one case of the addition of systematic absences without changing the Laue group is reported. Two examples (CSD refcodes: DAMLIM and ABPZCU01) of false polymorphism and one (PAVJUR) of the erroneous interpretation of the fine details of IR spectra, owing to incorrect space-group determination, have been detected.
Structural study of Cu2−x
Se alloys produced by mechanical alloying
Authors: Machado K. D. , de Lima J. C. , Grandi T. A. , Campos C. E. M. , Maurmann C. E. , Gasperini A. A. M. , Souza S. M. , Pimenta A. F.
Published: May 2004

The crystalline structures of the superionic high-temperature copper selenides Cu2−x
Se (0 < x < 0.25) produced using mechanical alloying were investigated using X-ray diffraction (XRD). The measured XRD patterns showed the presence of peaks corresponding to the crystalline superionic high-temperature α-Cu2Se phase in the as-milled sample, and its structural data were determined by means of a Rietveld refinement procedure. After heat treatment in argon at 473 K for 90 h, this phase transforms to the superionic high-temperature α-Cu1.8Se phase, whose structural data were also determined by Rietveld refinement. In this phase, a very low occupation of the trigonal 32(f) sites (∼ 3%) by Cu ions is found. In order to explain the evolution of the phases in the samples, two possible mechanisms are suggested: (i) the high mobility of Cu ions in superionic phases and (ii) the important diffusive processes in the interfacial component of samples produced by mechanical alloying.