bluuebunny/crossref_metadata_2025 huggingface dataset:
Reading Minds or Dealing with Interactional Implications?
Authors: Antaki Charles
Published: October 2004

The psychological model known as Theory of Mind (ToM) claims that people get along by reading others’ minds, and that one can test how good they are at it by asking them to report on what they themselves, and others, believe or think. This article rehearses objections to both of those propositions. The fundamental objection is that ‘mind-reading’, as a criterion of ordinary mundane competence, sets the bar impossibly high. It assumes a referential theory of meaning, where claims about ‘mind’ and mental terms like ‘beliefs’, ‘thoughts’, and so on, can in principle be checked against a known object. A discursive reading would reject this and start from the proposition that people get along by judging what their interlocutor is visibly doing, as meaningful action. On this reading, ToM’s alleged test of competence is impossible. When we see people use mental terms, we ought to see them as doing something, not reporting something. I give examples from ordinary talk and from the talk of people with an alleged Theory of Mind deficit.
The Roots of Mindblindness
Authors: Shanker Stuart
Published: October 2004

This paper challenges the hypothesis that the type of social impairment observed in children with autism is evidence of an underlying malfunction in their ‘Theory of Mind’, resulting in ‘mindblindness’. To establish this point, the paper takes up two interesting ideas in the Theory of Mind literature, purged of their Cartesianism: first, that the study of autism does indeed provide us with critical insights into the development of social understanding and empathy; and, second, that no meaningful distinction can be drawn between a child’s interpersonal and intrapersonal development. The paper seeks to show how the ability to understand someone else’s thoughts and emotions is a product of endless co-regulated interactions in which the child’s own emotions and sense of self develop. The reason why children with autism so frequently exhibit impaired social relatedness is because basic biological challenges—such as sensory over-and under-reactivity—inhibit their ability to engage in these co-regulated interactive experiences.
Who Really Needs a ‘Theory’ of Mind?
Authors: Williams Emma
Published: October 2004

According to the theory-theory account of understanding other minds, children develop a succession of theories of mind that, just like scientific theories, postulate abstract coherent mental entities and laws, and provide predictions, interpretations and explanations. These, in turn, enable them to interact successfully with other people. Individuals with autism or Asperger’s syndrome are said to be unable to theorize about other minds, resulting in difficulties in relating to the people around them. This paper explores the possibility that we can reconceptualize the assumed relationship from the other direction, proposing that it is misleading to construe the task of achieving social understanding as a logical, scientific one. Rather, it will be suggested that typical children do not have to theorize that there are minds as they can immediately experience other people’s intentions and feelings within their affective, co-regulated interactions with them. High-functioning individuals with autism, on the other hand, do need to engage in theorizing about mind if they are to bridge the gap that exists between themselves and other people. In support of this argument, this paper presents findings from an interpretative phenomenological analysis (IPA) of ten published autobiographical accounts written by individuals diagnosed with either high-functioning autism or Asperger’s syndrome.
Theory of Mind and the Practical Management of Autistic Behavior in the Classroom Environment
Authors: Colombino Tommaso
Published: October 2004

Theory of Mind Theory has provided a description of the mind which has been used as the basis for theories on the nature of the cognitive impairment found in individuals with autism, as exemplified in the work of Simon Baron-Cohen. This paper draws on the personal experience of the author observing autistic children in a special needs school, and provides a critical perspective on the conceptual framework that Theory of Mind Theory uses to account for our perception of other people’s mental states. This paper’s argument is that in the case of autism, the Theory of Mind Mechanism (ToMM) fails to provide a disease model that is sustainable in situated interactions with autistic children such as the one observed here, and that ultimately this is due to the theory’s poorly conceptualized account of mentalistic understanding.
On the Inadequacies of Theory of Mind Explanations of Schizophrenia
Authors: McCabe Rosemarie
Published: October 2004

An influential theory of schizophrenia proposes that it can be explained by an inability to understand and reason about the mental states of others. In particular, an inability to correctly infer the mental states of others is believed to give rise to delusions and other psychotic symptoms. Our recent research has shown that patients adequately represent their own and others’ mental states and use this competence to communicate successfully in naturalistic social interaction. In talk with delusional content, patients recognize that others do not agree with their delusional claims and are not persuaded by the justification they provide for these claims. Importantly, they recognize their own and others’ discomfort at the disagreement this causes. However, they do not revise their claims. It is the tenacity with which delusional claims are held that is striking. This is all the more interesting given their ability to appreciate and respond appropriately to others’ mental states and their evident discomfort in the face of others’ disagreement. Questions for further research are whether this incorrigibility is specific to delusions, psychotic symptoms or the condition generally, and why patients are so tenacious in disregarding others’ accounts of their problems.
Procreative Mothers (Sexual Difference) and Child-Free Sisters (Gender)
Authors: Mitchell Juliet C.W.
Published: October 2004

The article considers the changing position of women and the family from the Second World War until today using the UK as its example. It offers a theoretical perspective by setting out to examine the possibility that the rise of second-wave feminism both reflected and spearheaded an aspect of demographic transition to non-replacement populations. It considers the tension between the formation of ‘sexual difference’ to enable reproduction and what it calls the ‘engendering of gender’ in lateral relations which are indifferent to procreation. With the achievements of feminism as a political vanguard and the demographic transition as its socioeconomic base, women were no longer defined by the family; their definition ceased to depend on procreation. The article proposes that the new use of the term ‘gender’ entered the political arena to become a key concept of feminism to indicate non-procreative sexuality and sexual relations that need not be heterosexual or biologically procreative. Judith Butler’s well-known suggestion that ‘gender’ troubles the status quo in a revolutionary manner cannot be sustained. Rather than disturbing the universe, the advent of ‘gender’ reflects the transition to a new demographic order.
Passing on Feminism
Authors: Adkins Lisa
Published: October 2004

As has been widely observed, histories of feminism have often been conceived via notions of generation where feminism is positioned as a kind of familial property, a form of inheritance and legacy which is transmitted through generations. Thus feminism and its history have been imagined as following a familial mode of social reproduction. Despite the dominance of this model, it has nonetheless been subject to critique, not least because of its reliance on teleological and progressive notions of history. Judith Roof, for example, has called for new conceptualizations of temporality in an attempt to decouple histories of feminism from a generational model. This need to move away from a generational model is also underscored by what commentators such as Angela McRobbie have identified as a dispersal of feminism – a broad-scale circulation of feminist values in popular culture – as well as by the emergence of a certain kind of reflexivity whereby past and current feminist practices are increasingly subject to critique. For McRobbie such developments are understood as part of the articulation of a post-feminism in which feminism can no longer be passed on as it is positioned as having already passed away. However, in this article via an exploration of recent accounts of the passing of feminism it is suggested that what allows for a declaration of this passing is an attachment to feminism as a particular way of knowing as well as to a particular arrangement of the social. Indeed, it will be suggested that recent histories of feminism and commentaries on the state of contemporary feminism are driven not only by generational logics but also by these attachments – attachments which lose and fix both feminism and women in time.
Voiceless Woman
Authors: Giannessi Belinda
Published: October 2004

This article argues that present (Italian) feminism has been translating its practical principles into a cultural and theoretical phenomenon. Drawing on her own genealogical achievement of freedom, the author discusses the main issues concerning present feminism – ranging from the intergenerational shift, feminist production and the control of its texts and practices – in order to construct her own understanding and doing feminism. Against a feminine feminist revival of traditional culture, the article focuses on creative and humanitarian agency. After having discussed the relationships between second-wave and present feminism, the contradictions and misunderstanding of feminist ideas, the relevance of a rhizomatic assimilation of feminism by both feminists and not feminists, the article examines the dynamics that have led to a present static separatism, and proposes, as a line of flight, international feminist humanitarianism. It also suggests a way of rethinking a possible materialization of feminism into (feminist) women activists and lay missionaries.
Feminist Cross-Mainstreaming within ‘East–West’ Mapping
Authors: Kašić Biljana
Published: October 2004

The article addresses the tempting questions around feminist cross-mainstreaming, keeping in mind that the feminist movement and feminist critical studies are deeply challenged by globalized marketing, boundary changes and displacements, and ‘over-genderization’. Taking feminist cross-mainstreaming into consideration not only as a concept and/or ‘act of normality’ at the threshold of the 21st century but also as a provocative stand for claiming authority across diverse worlds and boundaries, the author explores this through the problem of the globality of feminism in its contextualization and complexity; the status of feminism from a postsocialist perspective; and implications and potential obstacles of gender mainstreaming.
Still Crazy after All Those Years...
Authors: Wekker Gloria
Published: October 2004

The author argues for passing on a particular brand of feminism to next generations. The cultural archive (after Said) to be passed on should be transnational, intersectional, interdisciplinary, relational and reflexive. In particular, the author focuses on processes and practices of racialization as they impact on and are practised within the discipline. In the current backlash against feminism and women’s studies in different parts of Europe, frequently divisionary tactics are deployed, by which women are pitted against each other, based on assumed immutable differences which are conceived of as either ‘raciological’ (after Gilroy), ethnicized or as cultural, in such a way that ‘race’ enters again through the back door. The author argues that we need a European brand of feminism that is not complicit with the legacies of modernity, which continue to construct ‘race’. That is, we should be deeply concerned with thinking through the parameters of a viable anti-racist European women’s studies. By analysing various case studies, taken from the everyday Dutch reality at the beginning of this new millennium, the author shows the necessity and inescapability of the feminism she advocates.
Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis, and perivascular cell recruitment in vivo
Authors: Skovseth Dag K. , Veuger Marjan J. T. , Sorensen Dag R. , De Angelis Paula M. , Haraldsen Guttorm
Published: October 2004

Endostatin is a proteolytic fragment of collagen XVIII that inhibits endothelial cell migration in vitro and experimental tumor growth in vivo. To determine how endostatin affects the in vivo behavior of endothelial cells, we took advantage of a surrogate model of human angiogenesis, in which human endothelial cells are transferred to immunodeficient mice and develop into complex vessels in the course of 30 days. Systemic delivery of human yeast-derived endostatin (serum levels of 30-35 ng/mL) inhibited the number of human vessels dramatically (95% at day 20), as most endothelial cells remained suspended as single cells. The fraction of cells with a migratory phenotype (F-actin–positive, extending pseudopods) was strongly reduced (from 50% to 13% at day 10), while the number of apoptotic and mitotic cells remained unchanged. Endostatin also hampered the recruitment of α-smooth muscle actin–expressing perivascular cells and thus reduced the number of mature vessels (from 64.3% to 28.6% at day 30). Moreover, transcripts of pericyte-recruiting platelet-derived growth factor-B (PDGFB) were strongly reduced in endothelial cells of endostatin-treated mice. Our results are strong evidence that endostatin inhibits angiogenesis at several levels in vivo, including perivascular cell recruitment.
Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing
Authors: Solomon Lawrence R.
Published: October 2004

Early recognition of cobalamin (Cbl)–responsive disorders in the ambulatory care setting is essential to prevent irreversible neurologic deficits. However, diagnostic algorithms using Cbl, methylmalonic acid (MMA), and homocysteine (HCys) measurements reflect studies in academic centers, and their negative predictive values have not been established. Thus, records of 456 ambulatory patients evaluated for Cbl deficiency at a staff model HMO were reviewed. Pretherapy Cbl, MMA, and HCys values in individual patients varied by 23%, 23%, and 17%, respectively, over 2 to 6 weeks. Hematologic or neurologic responses to pharmacologic doses of Cbl occurred in 37 of the 95 evaluable patients. In these patients, pretherapy Cbl, MMA, and HCys values were normal in 54%, 23%, and 50%, respectively. If therapy had been restricted to symptomatic patients with both low or intermediate Cbl levels and increased metabolite values, 63% of responders would not have been treated. Twenty-five patients did not respond to treatment, including 5 of 11 patients (45%) with low Cbl, 22 of 49 patients (45%) with high MMA, and 13 of 30 patients (43%) with high HCys values. It is concluded that Cbl, MMA, and HCys levels fluctuate with time and neither predict nor preclude the presence of Cbl-responsive hematologic or neurologic disorders.
Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells
Authors: Boasso Adriano , Herbeuval Jean-Philippe , Hardy Andrew W. , Winkler Christiana , Shearer Gene M.
Published: October 2004

Indoleamine-2,3-dioxygenase (IDO) and tryptophanyl-tRNA-synthetase (TTS) are interferon-γ (IFN-γ)–inducible enzymes that are responsible for tryptophan degradation and for its use in protein synthesis, respectively. IFN-γ–induced IDO has immunomodulatory properties in murine and human models. A concomitant increase of TTS has been postulated to protect the IDO-expressing cells from tryptophan catabolism. IDO can be induced in dendritic cells (DCs) by recombinant soluble cytotoxic T lymphocyte antigen-4 (CTLA-4-Fc). We investigated the effects of CTLA-4-Fc on IDO and TTS mRNA expression in human peripheral blood mononuclear cells (PBMCs) and isolated leukocyte subsets. CTLA-4-Fc exposure induced increased IDO and TTS expression in unseparated PBMCs, as well as in monocyte-derived mature DCs. CD4+ T cells isolated from CTLA-4-Fc–treated PBMCs showed increased IDO and TTS compared with untreated cells. CD8+ T cells from CTLA-4-Fc–treated PBMCs expressed increased levels of TTS but not IDO. Pretreatment of PBMCs with CTLA-4-Fc inhibited the activation of CD4+ T cells induced by influenza A virus (Flu) or phytohemagglutinin A (PHA), but had no effect on CD8+ T cells. This is the first report of IDO and TTS regulation by the CTLA-4-B7 system in human CD4+ and CD8+ T cells, and raises the possibility that these 2 tryptophan-modulating enzymes provide an important mechanism for regulating immune responses.
Profiled support vector machines for antisense oligonucleotide efficacy prediction
Authors: Camps-Valls Gustavo , Chalk Alistair M , Serrano-López Antonio J , Martín-Guerrero José D , Sonnhammer Erik LL
Published: October 2004

Background

This paper presents the use of Support Vector Machines (SVMs) for prediction and analysis of antisense oligonucleotide (AO) efficacy. The collected database comprises 315 AO molecules including 68 features each, inducing a problem well-suited to SVMs. The task of feature selection is crucial given the presence of noisy or redundant features, and the well-known problem of the curse of dimensionality. We propose a two-stage strategy to develop an optimal model: (1) feature selection using correlation analysis, mutual information, and SVM-based recursive feature elimination (SVM-RFE), and (2) AO prediction using standard and profiled SVM formulations. A profiled SVM gives different weights to different parts of the training data to focus the training on the most important regions.

Results

In the first stage, the SVM-RFE technique was most efficient and robust in the presence of low number of samples and high input space dimension. This method yielded an optimal subset of 14 representative features, which were all related to energy and sequence motifs. The second stage evaluated the performance of the predictors (overall correlation coefficient between observed and predicted efficacy, r; mean error, ME; and root-mean-square-error, RMSE) using 8-fold and minus-one-RNA cross-validation methods. The profiled SVM produced the best results (r = 0.44, ME = 0.022, and RMSE= 0.278) and predicted high (>75% inhibition of gene expression) and low efficacy (<25%) AOs with a success rate of 83.3% and 82.9%, respectively, which is better than by previous approaches. A web server for AO prediction is available online at http://aosvm.cgb.ki.se/.

Conclusions

The SVM approach is well suited to the AO prediction problem, and yields a prediction accuracy superior to previous methods. The profiled SVM was found to perform better than the standard SVM, suggesting that it could lead to improvements in other prediction problems as well.
Few amino acid positions in rpoB are associated with most of the rifampin resistance in Mycobacterium tuberculosis
Authors: Cummings Michael P , Segal Mark R
Published: October 2004

Background

Mutations in rpoB, the gene encoding the β subunit of DNA-dependent RNA polymerase, are associated with rifampin resistance in Mycobacterium tuberculosis. Several studies have been conducted where minimum inhibitory concentration (MIC, which is defined as the minimum concentration of the antibiotic in a given culture medium below which bacterial growth is not inhibited) of rifampin has been measured and partial DNA sequences have been determined for rpoB in different isolates of M. tuberculosis. However, no model has been constructed to predict rifampin resistance based on sequence information alone. Such a model might provide the basis for quantifying rifampin resistance status based exclusively on DNA sequence data and thus eliminate the requirements for time consuming culturing and antibiotic testing of clinical isolates.

Results

Sequence data for amino acid positions 511–533 of rpoB and associated MIC of rifampin for different isolates of M. tuberculosis were taken from studies examining rifampin resistance in clinical samples from New York City and throughout Japan. We used tree-based statistical methods and random forests to generate models of the relationships between rpoB amino acid sequence and rifampin resistance. The proportion of variance explained by a relatively simple tree-based cross-validated regression model involving two amino acid positions (526 and 531) is 0.679. The first partition in the data, based on position 531, results in groups that differ one hundredfold in mean MIC (1.596 μg/ml and 159.676 μg/ml). The subsequent partition based on position 526, the most variable in this region, results in a > 354-fold difference in MIC. When considered as a classification problem (susceptible or resistant), a cross-validated tree-based model correctly classified most (0.884) of the observations and was very similar to the regression model. Random forest analysis of the MIC data as a continuous variable, a regression problem, produced a model that explained 0.861 of the variance. The random forest analysis of the MIC data as discrete classes produced a model that correctly classified 0.942 of the observations with sensitivity of 0.958 and specificity of 0.885.

Conclusions

Highly accurate regression and classification models of rifampin resistance can be made based on this short sequence region. Models may be better with improved (and consistent) measurements of MIC and more sequence data.
A population-based statistical approach identifies parameters characteristic of human microRNA-mRNA interactions
Authors: Smalheiser Neil R , Torvik Vetle I
Published: October 2004

Background

MicroRNAs are ~17–24 nt. noncoding RNAs found in all eukaryotes that degrade messenger RNAs via RNA interference (if they bind in a perfect or near-perfect complementarity to the target mRNA), or arrest translation (if the binding is imperfect). Several microRNA targets have been identified in lower organisms, but only one mammalian microRNA target has yet been validated experimentally.

Results

We carried out a population-wide statistical analysis of how human microRNAs interact complementarily with human mRNAs, looking for characteristics that differ significantly as compared with scrambled control sequences. These characteristics were used to identify a set of 71 outlier mRNAs unlikely to have been hit by chance.

Unlike the case in C. elegans and Drosophila, many human microRNAs exhibited long exact matches (10 or more bases in a row), up to and including perfect target complementarity. Human microRNAs hit outlier mRNAs within the protein coding region about 2/3 of the time. And, the stretches of perfect complementarity within microRNA hits onto outlier mRNAs were not biased near the 5'-end of the microRNA. In several cases, an individual microRNA hit multiple mRNAs that belonged to the same functional class.

Conclusions

The analysis supports the notion that sequence complementarity is the basis by which microRNAs recognize their biological targets, but raises the possibility that human microRNA-mRNA target interactions follow different rules than have been previously characterized in Drosophila and C. elegans.
Long branch attraction, taxon sampling, and the earliest angiosperms: Amborella or monocots?
Authors: Stefanović Saša , Rice Danny W , Palmer Jeffrey D
Published: October 2004

Background

Numerous studies, using in aggregate some 28 genes, have achieved a consensus in recognizing three groups of plants, including Amborella, as comprising the basal-most grade of all other angiosperms. A major exception is the recent study by Goremykin et al. (2003; Mol. Biol. Evol. 20:1499–1505), whose analyses of 61 genes from 13 sequenced chloroplast genomes of land plants nearly always found 100% support for monocots as the deepest angiosperms relative to Amborella, Calycanthus, and eudicots. We hypothesized that this conflict reflects a misrooting of angiosperms resulting from inadequate taxon sampling, inappropriate phylogenetic methodology, and rapid evolution in the grass lineage used to represent monocots.

Results

We used two main approaches to test this hypothesis. First, we sequenced a large number of chloroplast genes from the monocot Acorus and added these plus previously sequenced Acorus genes to the Goremykin et al. (2003) dataset in order to explore the effects of altered monocot sampling under the same analytical conditions used in their study. With Acorus alone representing monocots, strongly supported Amborella-sister trees were obtained in all maximum likelihood and parsimony analyses, and in some distance-based analyses. Trees with both Acorus and grasses gave either a well-supported Amborella-sister topology or else a highly unlikely topology with 100% support for grasses-sister and paraphyly of monocots (i.e., Acorus sister to "dicots" rather than to grasses). Second, we reanalyzed the Goremykin et al. (2003) dataset focusing on methods designed to account for rate heterogeneity. These analyses supported an Amborella-sister hypothesis, with bootstrap support values often conflicting strongly with cognate analyses performed without allowing for rate heterogeneity. In addition, we carried out a limited set of analyses that included the chloroplast genome of Nymphaea, whose position as a basal angiosperm was also, and very recently, challenged.

Conclusions

These analyses show that Amborella (or Amborella plus Nymphaea), but not monocots, is the sister group of all other angiosperms among this limited set of taxa and that the grasses-sister topology is a long-branch-attraction artifact leading to incorrect rooting of angiosperms. These results highlight the danger of having lots of characters but too few and, especially, molecularly divergent taxa, a situation long recognized as potentially producing strongly misleading molecular trees. They also emphasize the importance in phylogenetic analysis of using appropriate evolutionary models.
Strengths and weaknesses of EST-based prediction of tissue-specific alternative splicing
Authors: Gupta Shobhit , Zink Dorothea , Korn Bernhard , Vingron Martin , Haas Stefan A
Published: October 2004

Background

Alternative splicing contributes significantly to the complexity of the human transcriptome and proteome. Computational prediction of alternative splice isoforms are usually based on EST sequences that also allow to approximate the expression pattern of the related transcripts. However, the limited number of tissues represented in the EST data as well as the different cDNA construction protocols may influence the predictive capacity of ESTs to unravel tissue-specifically expressed transcripts.

Methods

We predict tissue and tumor specific splice isoforms based on the genomic mapping (SpliceNest) of the EST consensus sequences and library annotation provided in the GeneNest database. We further ascertain the potentially rare tissue specific transcripts as the ones represented only by ESTs derived from normalized libraries. A subset of the predicted tissue and tumor specific isoforms are then validated via RT-PCR experiments over a spectrum of 40 tissue types.

Results

Our strategy revealed 427 genes with at least one tissue specific transcript as well as 1120 genes showing tumor specific isoforms. While our experimental evaluation of computationally predicted tissue-specific isoforms revealed a high success rate in confirming the expression of these isoforms in the respective tissue, the strategy frequently failed to detect the expected restricted expression pattern. The analysis of putative lowly expressed transcripts using normalized cDNA libraries suggests that our ability to detect tissue-specific isoforms strongly depends on the expression level of the respective transcript as well as on the sensitivity of the experimental methods. Especially splice isoforms predicted to be disease-specific tend to represent transcripts that are expressed in a set of healthy tissues rather than novel isoforms.

Conclusions

We propose to combine the computational prediction of alternative splice isoforms with experimental validation for efficient delineation of an accurate set of tissue-specific transcripts.
Genome wide analysis of common and specific stress responses in adult drosophila melanogaster
Authors: Girardot Fabrice , Monnier Véronique , Tricoire Hervé
Published: October 2004

Background

During their life, multicellular organisms are challenged with oxidative stress. It is generated by several reactive oxygen species (ROS), may limit lifespan and has been related to several human diseases. ROS can generate a wide variety of defects in many cellular components and thus the response of the organism challenged with oxidative stress may share some features with other stress responses. Conversely, in spite of recent progress, a complete functional analysis of the transcriptional responses to different oxidative stresses in model organisms is still missing. In addition, the functional significance of observed transcriptional changes is still elusive.

Results

We used oligonucleotide microarrays to address the specificities of transcriptional responses of adult Drosophila to different stresses induced by paraquat and H2O2, two oxidative stressors, and by tunicamycin which induces an endoplasmic reticulum (ER) stress. Both specific and common responses to the three stressors were observed and whole genome functional analysis identified several important classes of stress responsive genes. Within some functional classes, we observed that isozymes do not all behave similarly, which may reflect unsuspected functional specificities. Moreover, genetic experiments performed on a subset of lines bearing mutations in genes identified in microarray experiments showed that a significant number of these mutations may affect resistance of adult Drosophila to oxidative stress.

Conclusions

A long term common stress response to paraquat- or H2O2-induced oxidative stresses and ER stress is observed for a significant number of genes. Besides this common response, the unexpected complexity of the stress responses to oxidative and ER stresses in Drosophila, suggest significant specificities in protective properties between genes associated to the same functional classes. According to our functional analysis, a large part of the genome may play a role in protective mechanisms against oxidative stress in Drosophila.
Moderate exercise may attenuate some aspects of immunosenescence
Authors: Drela Nadzieja , Kozdron Ewa , Szczypiorski Piotr
Published: October 2004

Background

Immunosenescence is related to the deterioration of many immune functions, which may be manifested in increased susceptibility to infection, cancer, and autoimmunity. Lifestyle factors, such as diet or physical activity, may influence the senescence of the immune system. It is widely accepted that moderate physical activity may cause beneficial effects for physical and psychological health as well as for the immune system activity in aged people.

Methods

Thirty elderly women aged 62 to 86 were subjected to a two-years authorized physical activity program. Peripheral blood lymphocytes distribution and the production of cytokines involved in the immune response development and regulation (IL-2, IL-4 and IFN-γ) were investigated. The same parameters were evaluated in two control groups of women: a sedentary group of 12 elderly women selected for the second round of the physical activity program and in a group of 20 sedentary young women. Flow cytometry methods were used for the examination of surface markers on peripheral blood lymphocytes and intracellular cytokines expression.

Results

The distribution of the main lymphocytes subpopulations in the peripheral blood of elderly women did not show changes after long-term moderate physical training. The percentage of lymphocytes expressing intracellular IL-2 was higher in the group of women attending 2-years physical activity program than in the control group of elderly sedentary women, and it was similar to the value estimated in the group of young sedentary women. There was no difference in the intracellular expression of IL-4 and IFN-γ between the active and elderly sedentary women.

Conclusions

Our results suggest that moderate, long-term physical activity in elderly women may increase the production of IL-2, an important regulator of the immune response. This may help ameliorate immunosenescence in these women.
Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949]
Authors: Besselink Marc GH , Timmerman Harro M , Buskens Erik , Nieuwenhuijs Vincent B , Akkermans Louis MA , Gooszen Hein G ,   the members of the Dutch Acute Pancreatitis Study Group
Published: October 2004

Background

Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth.

Methods/design

PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated.

Conclusion

The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis.
Topically applied vitamin C increases the density of dermal papillae in aged human skin
Authors: Sauermann Kirsten , Jaspers Sören , Koop Urte , Wenck Horst
Published: October 2004

Background

The influence of ageing on the density of the functional entities of the papillae containing nutritive capillaries, here in terms as the papillary index, and the effect of topically applied vitamin C were investigated by confocal laser scanning microscopy (CLSM) in vivo.

Methods

The age dependency of the papillary index was determined by CLSM on 3 different age groups. Additionally, we determined the effect of a topical cream containing 3% vitamin C against the vehicle alone using daily applications for four months on the volar forearm of 33 women.

Results

There were significant decreases in the papillary index showing a clear dependency on age. Topical vitamin C resulted in a significant increase of the density of dermal papillae from 4 weeks onward compared to its vehicle. Reproducibility was determined in repeated studies.

Conclusions

Vitamin C has the potential to enhance the density of dermal papillae, perhaps through the mechanism of angiogenesis. Topical vitamin C may have therapeutical effects for partial corrections of the regressive structural changes associated with the aging process.
Dietary analysis and patterns of nutritional supplement use in normal and age-related macular disease affected subjects: a prospective cross-sectional study
Authors: Bartlett Hannah , Eperjesi Frank
Published: October 2004

Background

Poor diet is thought to be a risk factor for many diseases, including age-related macular disease (ARMD), which is the leading cause of blind registration in those aged over 60 years in the developed world. The aims of this study were 1) to evaluate the dietary food intake of three subject groups: participants under the age of 50 years without ARMD (U50), participants over the age of 50 years without ARMD (O50), and participants with ARMD (AMD), and 2) to obtain information on nutritional supplement usage.

Methods

A prospective cross-sectional study designed in a clinical practice setting. Seventy-four participants were divided into three groups: U50; 20 participants aged < 50 years, from 21 to 40 (mean ± SD, 37.7 ± 10.1 years), O50; 27 participants aged > 50 years, from 52 to 77 (62.7 ± 6.8 years), and ARMD; 27 participants aged > 50 years with ARMD, from 55 to 79 (66.0 ± 5.8 years). Participants were issued with a three-day food diary, and were also asked to provide details of any daily nutritional supplements. The diaries were analysed using FoodBase 2000 software. Data were input by one investigator and statistically analysed using Microsoft Excel for Microsoft Windows XP software, employing unpaired t-tests.

Results

Group O50 consumed significantly more vitamin C (t = 3.049, p = 0.005) and significantly more fibre (t = 2.107, p = 0.041) than group U50. Group ARMD consumed significantly more protein (t = 3.487, p = 0.001) and zinc (t = 2.252, p = 0.029) than group O50. The ARMD group consumed the highest percentage of specific ocular health supplements and the U50 group consumed the most multivitamins.

Conclusions

We did not detect a deficiency of any specific nutrient in the diets of those with ARMD compared with age- and gender-matched controls. ARMD patients may be aware of research into use of nutritional supplementation to prevent progression of their condition.
Effect of time of administration on cholesterol-lowering by psyllium: a randomized cross-over study in normocholesterolemic or slightly hypercholesterolemic subjects
Authors: Van Rosendaal Guido MA , Shaffer Eldon A , Edwards Alun L , Brant Rollin
Published: October 2004

Background

Reports of the use of psyllium, largely in hypercholesterolemic men, have suggested that it lowers serum cholesterol as a result of the binding of bile acids in the intestinal lumen. Widespread advertisements have claimed an association between the use of soluble fibre from psyllium seed husk and a reduced risk of coronary heart disease. Given the purported mechanism of cholesterol-lowering by psyllium, we hypothesized that there would be a greater effect when psyllium is taken with breakfast than when taken at bedtime. Secondarily, we expected to confirm a cholesterol-lowering effect of psyllium in subjects with "average" cholesterol levels.

Methods

Sixteen men and 47 women ranging in age from 18 to 77 years [mean 53 +/- 13] with LDL cholesterol levels that were normal or slightly elevated but acceptable for subjects at low risk of coronary artery disease were recruited from general gastroenterology and low risk lipid clinics. Following a one month dietary stabilization period, they received an average daily dose of 12.7 g of psyllium hydrophilic mucilloid, in randomized order, for 8 weeks in the morning and 8 weeks in the evening. Change from baseline was determined for serum total cholesterol, LDL, HDL and triglycerides.

Results

Total cholesterol for the "AM first" group at baseline, 8 and 16 weeks was 5.76, 5.77 and 5.80 mmol/L and for the "PM first" group the corresponding values were 5.47, 5.61 and 5.57 mmol/L. No effect on any lipid parameter was demonstrated for the group as a whole or in any sub-group analysis.

Conclusion

The timing of psyllium administration had no effect on cholesterol-lowering and, in fact, no cholesterol-lowering was observed. Conclusions regarding the effectiveness of psyllium for the prevention of heart disease in the population at large may be premature.
Chromosome loops arising from intrachromosomal tethering of telomeres occur at high frequency in G1 (non-cycling) mitotic cells: Implications for telomere capture
Authors: Daniel Art , St Heaps Luke
Published: October 2004

Background

To investigate potential mechanisms for telomere capture the spatial arrangement of telomeres and chromosomes was examined in G1 (non-cycling) mitotic cells with diploid or triploid genomes. This was examined firstly by directly labelling the respective short arm (p) and long arm subtelomeres (q) with different fluorophores and probing cell preparations using a number of subtelomere probe pairs, those for chromosomes 1, 3, 4, 5, 6, 7, 9, 10, 12, 17, 18, and 20. In addition some interstitial probes (CEN15, PML and SNRPN on chromosome 15) and whole chromosome paint probes (e.g. WCP12) were jointly hybridised to investigate the co-localization of interphase chromosome domains and tethered subtelomeres. Cells were prepared by omitting exposure to colcemid and hypotonic treatments.

Results

In these cells a specific interphase chromosome topology was detected. It was shown that the p and q telomeres of the each chromosome associate frequently (80% pairing) in an intrachromosomal manner, i.e. looped chromosomes with homologues usually widely spaced within the nucleus. This p-q tethering of the telomeres from the one chromosome was observed with large (chromosomes 3, 4, 5), medium sized (6, 7, 9, 10, 12), or small chromosomes (17, 18, 20). When triploid nuclei were probed there were three tetherings of p-q subtelomere signals representing the three widely separated looped chromosome homologues. The separate subtelomere pairings were shown to coincide with separate chromosome domains as defined by the WCP and interstitial probes. The 20% of apparently unpaired subtelomeric signals in diploid nuclei were partially documented to be pairings with the telomeres of other chromosomes.

Conclusions

A topology for telomeres was detected where looped chromosome homologues were present at G1 interphase. These homologues were spatially arranged with respect to one-another independently of other chromosomes, i.e. there was no chromosome order on different sides of the cell nuclei and no segregation into haploid sets was detected. The normal function of this high frequency of intrachromosomal loops is unknown but a potential role is likely in the genesis of telomere captures whether of the intrachromosomal type or between non-homologues. This intrachromosomal tethering of telomeres cannot be related to telomeric or subtelomeric sequences since these are shared in varying degree with other chromosomes. In our view, these intrachromosomal telomeric tetherings with the resulting looped chromosomes arranged in a regular topology must be important to normal cell function since non-cycling cells in G1 are far from quiescent, are in fact metabolically active, and these cells represent the majority status since only a small proportion of cells are normally dividing.
Isolation of suppressor genes that restore retrovirus susceptibility to a virus-resistant cell line
Authors: Gao Guangxia , Goff Stephen P
Published: October 2004

Background

Genetic selections in mammalian cell lines have recently been developed for the isolation of mutant cells that are refractory to infection by retroviruses. These selections have been used to recover lines that block early postentry stages of infection, either before reverse transcription or before nuclear entry. The mechanisms of action of these blocks remain unknown.

Results

We have devised a method for the selection of genes from cDNA libraries that suppress the block to virus infection, and so restore virus susceptibility. The protocol involves the transformation of pools of resistant cells by cDNA expression libraries, followed by the selection for rare virus-sensitive cells, using multiple rounds of selection after infection by marked viral vector genomes. The suppressor genes were then recovered from these virus sensitive cells, and their ability to restore virus susceptibility was confirmed by reintroduction of these cDNAs into the resistant line.

Conclusions

The identities of these genes provide insights into the mechanism of virus resistance and will help to define new pathways used during retrovirus infection. The methods for gene isolation developed here will also permit the identification of similar suppressors that modify or override other recently identified virus resistance genes.
Introducing "Frontiers in Zoology"
Authors: Heinze Jürgen , Tautz Diethard
Published: October 2004

As a biological discipline, zoology has one of the longest histories. Today it occasionally appears as though, due to the rapid expansion of life sciences, zoology has been replaced by more or less independent sub-disciplines amongst which exchange is often sparse. However, the recent advance of molecular methodology into "classical" fields of biology, and the development of theories that can explain phenomena on different levels of organisation, has led to a re-integration of zoological disciplines promoting a broader than usual approach to zoological questions. Zoology has re-emerged as an integrative discipline encompassing the most diverse aspects of animal life, from the level of the gene to the level of the ecosystem.

The new journal Frontiers in Zoology is the first Open Access journal focussing on zoology as a whole. It aims to represent and re-unite the various disciplines that look at animal life from different perspectives and at providing the basis for a comprehensive understanding of zoological phenomena on all levels of analysis. Frontiers in Zoology provides a unique opportunity to publish high quality research and reviews on zoological issues that will be internationally accessible to any reader at no cost.