bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe muscle disease-causing desmin mutations interfere with
in vitro
filament assembly at distinct stages
Authors: Bär Harald , Mücke Norbert , Kostareva Anna , Sjöberg Gunnar , Aebi Ueli , Herrmann Harald
Published: October 2005

Desmin is the major intermediate filament (IF) protein of muscle. Recently, mutations of the desmin gene have been reported to cause familial or sporadic forms of human skeletal, as well as cardiac, myopathy, termed desmin-related myopathy (DRM). The impact of any of these mutations on filament assembly and integration into the cytoskeletal network of myocytes is currently not understood, despite the fact that all cause the same histopathological defect, i.e., desmin aggregation. To gain more insight into the molecular basis of this process, we investigated how mutations within the α-helical rod domain of desmin affect both the assembly of the recombinant protein
in vitro
as well as the filament-forming capacity in cDNA-transfected cells. Whereas 6 of 14 mutants assemble into seemingly normal IFs in the test tube, the other mutants interfere with the assembly process at distinct stages, i.e., tetramer formation, unit-length filament (ULF) formation, filament elongation, and IF maturation. Correspondingly, the mutants with
in vitro
assembly defects yield dot-like aggregates in transfected cells, whereas the mutants that form IFs constitute a seemingly normal IF cytoskeleton in the cellular context. At present, it is entirely unclear why the latter mutant proteins also lead to aggregate formation in myocytes. Hence, these findings may be a starting point to dissect the contribution of the individual subdomains for desmin pathology and, eventually, the development of therapeutic interventions.
Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease
Authors: Yazawa Norihito , Hamaguchi Yasuhito , Poe Jonathan C. , Tedder Thomas F.
Published: October 2005

Immunotherapy with unconjugated CD20 monoclonal antibodies has proven effective for treating non-Hodgkin's lymphoma and autoimmune disease. CD20 immunotherapy depletes mature B cells but does not effectively deplete pre-B or immature B cells, some B cell subpopulations, antibody-producing cells, or their malignant counterparts. Because CD19 is expressed earlier during B cell development, a therapeutic strategy for the treatment of early lymphoblastic leukemias/lymphomas was developed by using CD19-specific monoclonal antibodies in a transgenic mouse expressing human CD19. Pre-B cells and their malignant counterparts were depleted as well as antibody- and autoantibodyproducing cells. These results demonstrate clinical utility for the treatment of diverse B cell malignancies, autoimmune disease, and humoral transplant rejection.
Regional vegetation die-off in response to global-change-type drought
Authors: Breshears David D. , Cobb Neil S. , Rich Paul M. , Price Kevin P. , Allen Craig D. , Balice Randy G. , Romme William H. , Kastens Jude H. , Floyd M. Lisa , Belnap Jayne , Anderson Jesse J. , Myers Orrin B. , Meyer Clifton W.
Published: October 2005

Future drought is projected to occur under warmer temperature conditions as climate change progresses, referred to here as global-change-type drought, yet quantitative assessments of the triggers and potential extent of drought-induced vegetation die-off remain pivotal uncertainties in assessing climate-change impacts. Of particular concern is regional-scale mortality of overstory trees, which rapidly alters ecosystem type, associated ecosystem properties, and land surface conditions for decades. Here, we quantify regional-scale vegetation die-off across southwestern North American woodlands in 2002-2003 in response to drought and associated bark beetle infestations. At an intensively studied site within the region, we quantified that after 15 months of depleted soil water content, >90% of the dominant, overstory tree species (
Pinus edulis
, a piñon) died. The die-off was reflected in changes in a remotely sensed index of vegetation greenness (Normalized Difference Vegetation Index), not only at the intensively studied site but also across the region, extending over 12,000 km
2
or more; aerial and field surveys confirmed the general extent of the die-off. Notably, the recent drought was warmer than the previous subcontinental drought of the 1950s. The limited, available observations suggest that die-off from the recent drought was more extensive than that from the previous drought, extending into wetter sites within the tree species' distribution. Our results quantify a trigger leading to rapid, drought-induced die-off of overstory woody plants at subcontinental scale and highlight the potential for such die-off to be more severe and extensive for future global-change-type drought under warmer conditions.
Visible and UV coherent Raman spectroscopy of dipicolinic acid
Authors: Pestov Dmitry , Zhi Miaochan , Sariyanni Zoe-Elizabeth , Kalugin Nikolai G. , Kolomenskii Alexandre A. , Murawski Robert , Paulus Gerhard G. , Sautenkov Vladimir A. , Schuessler Hans , Sokolov Alexei V. , Welch George R. , Rostovtsev Yuri V. , Siebert Torsten , Akimov Denis A. , Graefe Stefanie , Kiefer Wolfgang , Scully Marlan O.
Published: October 2005

We use time-resolved coherent Raman spectroscopy to obtain molecule-specific signals from dipicolinic acid (DPA), which is a marker molecule for bacterial spores. We use femtosecond laser pulses in both visible and UV spectral regions and compare experimental results with theoretical predictions. By exciting vibrational coherence on more than one mode simultaneously, we observe a quantum beat signal that can be used to extract the parameters of molecular motion in DPA. The signal is enhanced when an UV probe pulse is used, because its frequency is near-resonant to the first excited electronic state of the molecule. The capability for unambiguous identification of DPA molecules will lead to a technique for real-time detection of spores.
Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy
Authors: Ragozzino D. , Palma E. , Di Angelantonio S. , Amici M. , Mascia A. , Arcella A. , Giangaspero F. , Cantore G. , Di Gennaro G. , Manfredi M. , Esposito V. , Quarato P. P. , Miledi R. , Eusebi F.
Published: October 2005

Pharmacotherapeutic strategies have been difficult to develop for several forms of temporal lobe epilepsy, which are consequently treated by surgical resection. To examine this problem, we have studied the properties of transmitter receptors of tissues removed during surgical treatment. We find that when cell membranes, isolated from the temporal neocortex of patients afflicted with drug-resistant mesial temporal lobe epilepsy (TLE), are injected into frog oocytes they acquire GABA type A receptors (GABA
A
-receptors) that display a marked rundown during repetitive applications of GABA. In contrast, GABA
A
-receptor function is stable in oocytes injected with cell membranes isolated from the temporal lobe of TLE patients afflicted with neoplastic, dysgenetic, traumatic, or ischemic temporal lesions (lesional TLE, LTLE). Use-dependent GABA
A
-receptor rundown is also found in the pyramidal neurons of TLE neocortical slices and is antagonized by BDNF. Pyramidal neurons in cortical slices of a traumatic LTLE patient did not show GABA
A
-receptor rundown. However, the apparent affinity of GABA
A
-receptor in oocytes microtransplanted with membranes from all of the epileptic patients studied was smaller than the affinity of receptors transplanted from the nonepileptic brain. We conclude that the use-dependent rundown of neocortical GABA
A
-receptor represents a TLE-specific dysfunction, whereas the reduced affinity may be a general feature of brains of both TLE and LTLE patients, and we speculate that our findings may help to develop new treatments for TLE and LTLE.
Tectonic implications of Mars crustal magnetism
Authors: Connerney J. E. P. , Acuña M. H. , Ness N. F. , Kletetschka G. , Mitchell D. L. , Lin R. P. , Reme H.
Published: October 2005

Mars currently has no global magnetic field of internal origin but must have had one in the past, when the crust acquired intense magnetization, presumably by cooling in the presence of an Earth-like magnetic field (thermoremanent magnetization). A new map of the magnetic field of Mars, compiled by using measurements acquired at an ≈400-km mapping altitude by the Mars Global Surveyor spacecraft, is presented here. The increased spatial resolution and sensitivity of this map provide new insight into the origin and evolution of the Mars crust. Variations in the crustal magnetic field appear in association with major faults, some previously identified in imagery and topography (Cerberus Rupes and Valles Marineris). Two parallel great faults are identified in Terra Meridiani by offset magnetic field contours. They appear similar to transform faults that occur in oceanic crust on Earth, and support the notion that the Mars crust formed during an early era of plate tectonics.
Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission
Authors: Thomas Gareth M. , Rumbaugh Gavin R. , Harrar Dana B. , Huganir Richard L.
Published: October 2005

Extracellular signal-regulated kinase (ERK) signaling is important for neuronal synaptic plasticity. We report here that the protein kinase ribosomal S6 kinase (RSK)2, a downstream target of ERK, uses a C-terminal motif to bind several PDZ domain proteins in heterologous systems and
in vivo
. Different RSK isoforms display distinct specificities in their interactions with PDZ domain proteins. Mutation of the RSK2 PDZ ligand does not inhibit RSK2 activation in intact cells or phosphorylation of peptide substrates by RSK2
in vitro
but greatly reduces RSK2 phosphorylation of PDZ domain proteins of the Shank family in heterologous cells. In primary neurons, NMDA receptor (NMDA-R) activation leads to ERK and RSK2 activation and RSK-dependent phosphorylation of transfected Shank3. RSK2–PDZ domain interactions are functionally important for synaptic transmission because neurons expressing kinase-dead RSK2 display a dramatic reduction in frequency of AMPA-type glutamate receptor-mediated miniature excitatory postsynaptic currents, an effect dependent on the PDZ ligand. These results suggest that binding of RSK2 to PDZ domain proteins and phosphorylation of these proteins or their binding partners regulates excitatory synaptic transmission.
The evolutionary origin of a complex scrambled gene
Authors: Chang Wei-Jen , Bryson Paul D. , Liang Han , Shin Mann Kyoon , Landweber Laura F.
Published: October 2005

Some species of ciliates undergo massive DNA elimination and genome rearrangement to construct gene-sized “chromosomes” in their somatic nucleus. An example is the extensively scrambled DNA polymerase α gene that is broken into 48 pieces and distributed over two unlinked loci in
Stylonychia
. To understand the emergence of this complex phenomenon during evolution, we examined DNA polymerase α genes in several earlier diverging species, representing evolutionary intermediates. Mapping these data onto an evolutionary tree suggests that this gene became extensively fragmented and scrambled over evolutionary time through a series of steps, each leading to greater complexity. Our results also suggest a possible mechanism for intron loss by deletion of intron sequences as DNA during development of the somatic nucleus.
DNA damage-induced phosphorylation of the human telomere-associated protein TRF2
Authors: Tanaka Hiromi , Mendonca Marc S. , Bradshaw Paul S. , Hoelz Derek J. , Malkas Linda H. , Meyn M. Stephen , Gilley David
Published: October 2005

Several protein kinases from diverse eukaryotes known to perform important roles in DNA repair have also been shown to play critical roles in telomere maintenance. Here, we report that the human telomere-associated protein TRF2 is rapidly phosphorylated in response to DNA damage. We find that the phosphorylated form of TRF2 is not bound to telomeric DNA, as is the ground form of TRF2, and is rapidly localized to damage sites. Our results suggest that the ataxia-telangiectasia-mutated (ATM) protein kinase signal-transduction pathway is primarily responsible for the DNA damage-induced phosphorylation of TRF2. Unlike DNA damage-induced phosphorylation of other ATM targets, the phosphorylated form of TRF2 is transient, being detected rapidly at DNA damage sites postirradiation, but largely dissipated by 2 hours. In addition, we report that the phosphorylated form of TRF2 is present at telomeres in cell types undergoing telomere-based crisis and a recombination-driven, telomerase-independent, alternative lengthening of telomeres (ALT) pathway, likely as a consequence of a telomere-based DNA damage response. Our results link the induction of TRF2 phosphorylation to the DNA damage-response system, providing an example of direct cross-talk via a signaling pathway between these two major cellular processes essential for genomic stability, telomere maintenance, and DNA repair.
Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E
2
Authors: Leppilampi Mari , Parkkila Seppo , Karttunen Tuomo , Gut Marta Ortova , Gros Gerolf , Sjöblom Markus
Published: October 2005

Duodenal bicarbonate secretion (DBS) is accepted as the primary mucosal defense against acid discharged from the stomach and is impaired in patients with duodenal ulcer disease. The secretory response to luminal acid is the main physiological stimulus for DBS and involves mediation by PGE
2
produced by mucosal cells. The aim of this investigation is to elucidate the role of carbonic anhydrases (CAs) II and IX in PGE
2
-mediated bicarbonate secretion in the murine duodenum. CA II- and IX-deficient mice and different combinations of their heterozygous and WT counterparts were studied. A 10-mm segment of the proximal duodenum with intact blood supply was isolated, and DBS was titrated by pH-stat (TitroLine-easy, Schott, Mainz, Germany). Mean arterial blood pressure (MAP) was continuously recorded, and blood acid/base balance and gastrointestinal morphology were analyzed. The duodenal segment spontaneously secreted HCO
3
-
at a steady basal rate of 5.3 ± 0.6 μmol·cm
-1
·h
-1
. Perfusing the duodenal lumen for 20 min with 47 μM PGE
2
caused a significant increase in DBS to 13.0 ± 2.9 μmol·cm
-1
·h
-1
,
P
< 0.0001. The DBS response to PGE
2
was completely absent in
Car2
-/-
mice, whereas basal DBS was normal. The CA IX-deficient mice with normal
Car2
alleles showed a slight increase in DBS. Histological abnormalities were observed in the gastroduodenal epithelium in both CA II- and IX-deficient mice. Our data demonstrate a gastrointestinal phenotypic abnormality associated with CA II deficiency. The results show that the stimulatory effect of the duodenal secretagogue PGE
2
completely depends on CA II.
The rise and fall of dietetics and of nutrition science, 4000 BCE–2000 CE
Authors: Cannon Geoffrey
Published: October 2005

Objective

To outline the history of dietetics since its beginnings in recorded history, and of nutrition science in its first phase beginning in the mid-nineteenth century and then its second phase in the second half of the twentieth century.

Method

Three narrative overviews: of dietetics from its beginnings until after the end of the mediaeval and then Renaissance periods in Europe; of nutrition science in its first phase from its beginnings in the mid-nineteenth century until the middle of the twentieth century, with reasons for its rise; and of nutrition science in its second phase in the second half of the twentieth century, with reasons for its decline.

Conclusions

In its third phase in the twenty-first century, the new nutrition science should regain much of the vision and scope of its preceding disciplines.
Integrating nutrition with ecology: balancing the health of humans and biosphere
Authors: McMichael Anthony J
Published: October 2005

Objective

To show that current rates of global population growth, production and consumption of food, and use of living and physical resources, are evidently not sustainable. To consider ways in which nutrition and allied sciences can respond to this great challenge of the twenty-first century.

Method

Past, current and future projected trends in production and consumption patterns are examined. These show that overall present and projected patterns cannot be sustained; and also show increasing unacceptable inequity between and within rich and poor regions and countries.

Discussion

Nutrition science classically focuses on nutrients in relation to human physiology, metabolism, growth, health and disease. The social and environmental conditions of the modern, interconnected, market-oriented world, and the consequences for food production and consumption, are extending the research and policy agenda with which nutrition science must now urgently engage. Historically, much attention has been paid to eliminating nutritional deficiency states, and this remains an important task. In modern urban populations ‘malnutrition’ encompasses new forms of dietary imbalance, especially excesses of certain nutrients. These contribute to various non-communicable diseases and, particularly, to overweight/obesity and its attendant metabolic derangements and disease risks. As a mass phenomenon the current surge in obesity has no historical precedent. The escalating impact of humankind on the natural environment, with its ramifications for present and future food production, is also unprecedented.

Conclusion

The essential challenge for nutrition science is to develop new understanding and strategies to enable a balance between promoting, equitably, the health of humans while sustaining the long-term health of the biosphere. Extension of nutrition science and food policy to meet those goals will be aided by understanding better how dietary conditions shaped the biological evolution of humankind. The fundamental long-term task is to integrate human health with the health of the biosphere.
Feeding people is easy: but we have to re-think the world from first principles
Authors: Tudge Colin
Published: October 2005

Objective

Agriculture designed to make best use of landscape and to be maximally sustainable would also provide food of the highest nutritional and gastronomic standards, and would inevitably employ a great many people. Thus it would solve the world's food problems, and its principal social problem, at a stroke. But agriculture in practice is designed for a quite different purpose – to generate wealth, in the cause of ‘economic growth’. The pressing need is not for more science and technology, but to recognise the true cause of the problems and to re-think priorities.

Conclusion

We could all be well fed. Indeed, everyone in the world who is ever likely to be born could be fed to the highest standards of gastronomy as well as of nutrition until humanity itself comes to an end. We already have most of the necessary technique – perhaps all that is needed. We could always do with more excellent science but we need not depend, as we are often told from on high, on the next technological fix. The methods that can provide excellent food would also create a beautiful environment, with plenty of scope for other creatures, and agreeable and stable agrarian economies with satisfying jobs for all.

In reality, in absolute contrast, we have created a world in which almost a billion are chronically undernourished; another billion are horribly overnourished, so that obesity and diabetes are epidemic, and rising; a billion live on less than two dollars a day; and a billion live in urban slums – a figure set to increase and probably at least to double over the next half century; while other species are disappearing so fast that biologists speak of mass extinction.
Defining and addressing the nutritional needs of populations
Authors: Uauy Ricardo
Published: October 2005

Objective

To examine the present methods used to define nutritional needs, and to analyse the intrinsic limitations of the reductionist chemical, biological and medical approaches to assess requirements. To establish the necessity to incorporate the complexities emerging from a broader understanding of the biological sciences as well as to include environmental and social dimensions in addressing nutritional needs.

Method

Examples of the limitations of current approaches and the implications of these in defining potential solutions and policy options to address present nutritional problems are presented and discussed.

Conclusion

The chemical and biological sciences have provided a strong base for nutrition and have been essential in establishing nutrition as a science with public health relevance. However, these approaches are clearly insufficient to address the main challenges that confront nutrition science now in the twenty-first century. There is a pressing need to include the social, economic and human rights aspects in order to define future policies that will secure the right to safe and nutritious food for all.
Using research on the obesity pandemic as a guide to a unified vision of nutrition
Authors: Popkin Barry M
Published: October 2005

Objective

To focus on factors that play a major role in our rapid, global nutritional changes.

Design

A range of studies are summarised: these show how an understanding of social, economic and technological change at the global, national and community levels affects diet, activity, and body composition patterns and trends. These studies are used to demonstrate the value of the key global, national, community, household and individual factors that should define the field of nutrition.

Setting

The focus is global.

Result

Large shifts have occurred in diet and in physical activity patterns – particularly in the last one or two decades of the twentieth century. These changes are reflected in nutritional outcomes such as changes in average stature, body composition and morbidity. Understanding the rapidity of these changes and the underlying factors at the global, national and community levels is critical for creating a science of nutrition that can prevent disease and sustain the health and integrity of humans.

Conclusion

The vision of the nutrition field is one where scholars who work on many levels will intersect; equal weight in the nutrition profession will be provided to all dimensions as they are welcomed into the field of nutrition – particularly those that will directly or indirectly affect dietary patterns, physical activity patterns, and energetics. This vision of the nutrition field is one where scholars from a range of disciplines and perspectives meet to work together with the goal being a focus on improving nutritional status and the human condition.
Wholesome nutrition: a suitable dietfor the new nutrition science project
Authors: Leitzmann Claus
Published: October 2005

Objective

To show that the practice of wholesome nutrition meets the demands of the concept of the new nutrition science, at present and in the future.

Method

To define ‘wholesome nutrition’, to describe its origin and to discuss its recommendations; and to cite practical examples showing that wholesome nutrition includes the dimensions and domains that are the basis of the concept of the new nutrition science.

Conclusion

The recommendations of wholesome nutrition are an effective implementation of the concept of the new nutrition science.
Human health in nature – towards a holistic philosophy of nutrition
Authors: Meyer-Abich Klaus Michael
Published: October 2005

Objective

To explain how the philosophy of nutrition is part of the philosophy of health. To show that this link allows practical solutions for equity and sustainability.

Method

An analysis of the historical philosophies concerned with nutrition and health. A comparison of the definitions in the history of mind from antiquity to the beginning of the twenty-first century.

Conclusion

We are not individually healthy, but we are so in togetherness, even with animals and plants. Comprehensive nutrition science has physical, social and environmental attributes. It follows that nutrition is good for the enhancement of good company with human beings as well as with the connatural world. We recognise that we owe to others what we are and this constitutes the equity of being.
Essential role for CD103 in the T cell–mediated regulation of experimental colitis
Authors: Annacker Oliver , Coombes Janine L. , Malmstrom Vivianne , Uhlig Holm H. , Bourne Tim , Johansson-Lindbom Bengt , Agace William W. , Parker Christina M. , Powrie Fiona
Published: October 2005

The integrin CD103 is highly expressed at mucosal sites, but its role in mucosal immune regulation remains poorly understood. We have analyzed the functional role of CD103 in intestinal immune regulation using the T cell transfer model of colitis. Our results show no mandatory role for CD103 expression on T cells for either the development or CD4+CD25+ regulatory T (T reg) cell–mediated control of colitis. However, wild-type CD4+CD25+ T cells were unable to prevent colitis in immune-deficient recipients lacking CD103, demonstrating a nonredundant functional role for CD103 on host cells in T reg cell–mediated intestinal immune regulation. Non–T cell expression of CD103 is restricted primarily to CD11chighMHC class IIhigh dendritic cells (DCs). This DC population is present at a high frequency in the gut-associated lymphoid tissue and appears to mediate a distinct functional role. Thus, CD103+ DCs, but not their CD103− counterparts, promoted expression of the gut-homing receptor CCR9 on T cells. Conversely, CD103− DCs promoted the differentiation of IFN-γ–producing T cells. Collectively, these data suggest that CD103+ and CD103− DCs represent functionally distinct subsets and that CD103 expression on DCs influences the balance between effector and regulatory T cell activity in the intestine.
Actin and agonist MHC–peptide complex–dependent T cell receptor microclusters as scaffolds for signaling
Authors: Campi Gabriele , Varma Rajat , Dustin Michael L.
Published: October 2005

T cell receptor (TCR) microclusters form within seconds of T cell contact with supported planar bilayers containing intercellular adhesion molecule-1 and agonist major histocompatibility complex (MHC)–peptide complexes, and elevation of cytoplasmic Ca2+ is observed within seconds of the first detectable microclusters. At 0–30 s after contact, TCR microclusters are colocalized with activated forms of Lck, ZAP-70, and the linker for activation of T cells. By 2 min, activated kinases are reduced in the older central microclusters, but are abundant in younger peripheral microclusters. By 5 min, TCR in the central supramolecular activation cluster have reduced activated kinases, whereas faint peripheral TCR microclusters efficiently generated activated Lck and ZAP-70. TCR microcluster formation is resistant to inhibition by Src family kinase inhibitor PP2, but is abrogated by actin polymerization inhibitor latrunculin A. We propose that Src kinase–independent formation of TCR microclusters in response to agonist MHC–peptide provides an actin-dependent scaffold for signal amplification.
ATID: a web-oriented database for collection of publicly available alternative translational initiation events
Authors: Cai Jun , Zhang Jing , Huang Ying , Li Yanda
Published: October 2005

Summary: Alternative translational initiation is an important cellular mechanism contributing to the diversity of protein products and functions. We develop a database that provides a comprehensive collection of alternative translational initiation events. The purpose of this alternative translational initiation database (ATID) is to facilitate the systematic study of alternative translational initiation of genes. The current version of database contains 300 genes from Homo sapiens, Mus musculus and other species. Each of the genes has two or more isoforms due to alternative translational initiation. Resources in ATID, including gene information, alternative products of genes and domain structures of isoforms, are provided through a user-friendly web interface.

Availability: The ATID database is available for public use at

Contact:  caijun99@mails.tsinghua.edu.cn

Supplementary information: Supplementary instructions about this database and further statistical analyses can be found on the web page ()
The influence of missing value imputation on detection of differentially expressed genes from microarray data
Authors: Scheel Ida , Aldrin Magne , Glad Ingrid K. , Sørum Ragnhild , Lyng Heidi , Frigessi Arnoldo
Published: October 2005

Motivation: Missing values are problematic for the analysis of microarray data. Imputation methods have been compared in terms of the similarity between imputed and true values in simulation experiments and not of their influence on the final analysis. The focus has been on missing at random, while entries are missing also not at random.

Results: We investigate the influence of imputation on the detection of differentially expressed genes from cDNA microarray data. We apply ANOVA for microarrays and SAM and look to the differentially expressed genes that are lost because of imputation. We show that this new measure provides useful information that the traditional root mean squared error cannot capture. We also show that the type of missingness matters: imputing 5% missing not at random has the same effect as imputing 10–30% missing at random. We propose a new method for imputation (LinImp), fitting a simple linear model for each channel separately, and compare it with the widely used KNNimpute method. For 10% missing at random, KNNimpute leads to twice as many lost differentially expressed genes as LinImp.

Availability: The R package for LinImp is available at

Contact:  idasch@math.uio.no

Supplementary information:
Complementary and Alternative Medicine for Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Authors: Capodice Jillian L. , Bemis Debra L. , Buttyan Ralph , Kaplan Steven A. , Katz Aaron E.
Published: October 2005

To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross‐searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPP Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder.
The negative regulator of Borna disease virus polymerase is a non-structural protein
Authors: Schwardt Malte , Mayer Daniel , Frank Ronald , Schneider Urs , Eickmann Markus , Planz Oliver , Wolff Thorsten , Schwemmle Martin
Published: October 2005

The X protein of Borna disease virus (BDV) negatively regulates viral polymerase activity. With a BDV mini-replicon system, 30 % inhibition of polymerase activity was observed at an X to phosphoprotein (P) plasmid ratio of 1 : 6 and 100 % inhibition at a ratio of 1 : 1. It was therefore hypothesized that (i) the X : P ratio in infected cells is not significantly higher than 1 : 6 to prevent complete inhibition of polymerase activity and (ii) X is not efficiently incorporated into viral particles, allowing efficient replication early in infection. To test these assumptions, a monoclonal antibody directed against BDV X was generated. Immunofluorescence analysis revealed co-localization of X with the nucleoprotein (N) and P in the nucleus, as well as in the cytoplasm of BDV-infected cells. Quantification of viral protein levels by Western blot analysis, using purifiedEscherichia coli-derived X, P and N as protein standards, revealed an X : P : N ratio in BDV-infected cells of approximately 1 : 6 : 40. However, only traces of X could be detected in purified BDV stock, suggesting that X is excluded from virus particles. These results indicate that X is a non-structural protein. The lack of X in virus particles may facilitate polymerase activity early in infection; however, the presence of X in persistently infected cells may result in partial inhibition of the polymerase and thus contribute to viral persistence.
Heterotopic Ossification of Brachialis Muscle
Authors: George Jacob
Published: October 2005

A 13-year-old girl with seizure disorder presented with 90º fixed flexion deformity of right elbow. She had history of encephalitis, 2 years ago, from which she recovered completely except for the deformity of the elbow. Plain X-ray revealed extensive ossification of the brachialis muscle from its origin at the lower anterior aspect of the humerus to its insertion at the coronoid process of the ulna. The alkaline phosphatase value was 500 IU. The middle segment of the ossified mass was surgically excised. The mobility of the elbow was restored and she achieved a range of movement between 45–120º.
Clinical Holistic Medicine: The Patient with Multiple Diseases
Authors: Ventegodt Søren , Merrick Joav
Published: October 2005

In clinical practice, patients can present with many different diseases, often both somatic and mental. Holistic medicine will try to see the diseases as a whole, as symptoms of a more fundamental imbalance in the state of being. The holistic physician must help the patient to recover existence and a good relationship with self. According to the life mission theory, theory of character, and holistic process theory of healing, recovering the purpose of life (the life mission) is essential for the patient to regain life, love, and trust in order to find happiness and realize the true purpose of life. We illustrate the power of the holistic medical approach with a case study of an invalidated female artist, aged 42 years, who suffered from multiple severe health problems, many of which had been chronic for years. She had a combination of neurological disturbances (tinnitus, migraine, minor hallucinations), immunological disturbances (recurrent herpes simplex, phlegm in the throat, fungal infection in the crotch), hormonal disturbances (14 days of menstruation in each cycle), muscle disturbances (neck tensions), mental disturbances (tendency to cry, inferiority feeling, mild depression, desolation, anxiety), abdominal complaints, hemorrhoids, and more. The treatment was a combined strategy of improving the general quality of life, recovering her human character and purpose of life (“renewing the patients life energy”, “balancing her global information system”), and processing the local blockages, thus healing most of her many different diseases in a treatment using 30 h of intense holistic therapy over a period of 18 months.
Childhood Injury Prevention: Intervention in the Bedouin City of Rahat
Authors: Hemmo-Lotem Michal , Merrick Efrat , Endy-Findling Liri , Abu Freh Aziza , Jinich-Aronowitz Claudia , Korn Liat , Merrick Joav
Published: October 2005

For several years, the National Center for Children's Health and Safety (Beterem) has worked on many levels to promote safety and prevent injury of the children in Israel. As part of intervention programs in 20 communities around Israel, this paper describes a 1-year, multidisciplinary, multistrategic childhood safety promotion and injury prevention project. The project took place in the Bedouin city of Rahat in the Southern part of Israel, the Negev, conducted by a local safety coordinator. This specific intervention study took place from March 2003 to March 2004. The main goal was to identify hazards and dangerous obstacles in public places in Rahat, then remove or repair the obstacles found, in order to secure a safe public environment for children. “Obstacle” was defined as any barrier that could endanger the safety of a child. Ten examples are used to illustrate this applied research project, and 80% of the problems were solved within the project period (time to solve between 1 week to 3 months, depending on various factors). We recommend the involvement of a safety coordinator from the community to focus on safety hazards for children, the use of a documentation diary to log the time frame, and also the use of pictures to illustrate the hazards and the changes, or to use as arguments in the lobbying process.
Trends in Adolescent Suicide in Hong Kong for the Period 1980 to 2003
Authors: Shek Daniel T.L. , Lee Britta M. , Chow Joyce
Published: October 2005

This paper utilizes existing statistics on adolescent suicide to examine adolescent suicide trends and patterns in Hong Kong for the period 1980 to 2003. Several trends and patterns could be revealed from the analyses. First, there was a gradual rising trend where adolescent suicide rates in the 1990's and the early 2000's were higher than those in the 1980's. Second, suicide rates for adolescents aged 10-24 years were lower than those of other adult age groups. Third, although adolescent suicide rates in Hong Kong were lower than those reported in some English-speaking countries and Mainland China, the figures were higher than those reported in Taiwan. Fourth, suicide rates among teenagers in early adolescence were lower than those among adolescents in late adolescence. Fifth, although male adolescent suicide rates were in general higher than female adolescent suicide rates (10-24 age group), gender differences in suicide rates appeared to be moderated by age. Sixth, there was a gradual rising trend in adolescent proportional mortality rates for suicide since the 1990's. Seventh, proportional mortality rates for suicide among teenagers in early adolescence were lower than those among adolescents in late adolescence. Finally, although jumping from a height was a common method of adolescent suicide, there was a rising trend of using other methods, such as taking drugs, hanging and charcoal burning. The observed adolescent suicide phenomena are discussed in this study with reference to the socio-cultural context of Hong Kong.
A review of Suicide Behavior Among Arab Adolescents
Authors: Morad Mohammed , Merrick Efrat , Schwarz Amir , Merrick Joav
Published: October 2005

Islam prohibits the taking of one's life, because this way you will interfere with the work of G-d (Allah), which is clear from several places in the Quran. Concerning individual suicide or suicide attempts in various Arab countries the literature is sparse and the incidence low. In this paper we present a review of research from Israel showing that suicide epidemiology among the Arab population of children and adolescents display a low incidence, but an increase has been observed over the past decade, but still much lower than the Jewish population. We believe that there is a need for the development of prevention and intervention strategies in order to keep this incidence low.
The International Rice Information System. A Platform for Meta-Analysis of Rice Crop Data
Authors: McLaren Christopher Graham , Bruskiewich Richard M. , Portugal Arllet M. , Cosico Alexander B.
Published: October 2005

Ambiguous germplasm identification; difficulty in tracing pedigree information; and lack of integration between genetic resources, characterization, breeding, evaluation, and utilization data are constraints in developing knowledge-intensive crop improvement programs. To address these constraints, the International Crop Information System (www.icis.cgiar.org), a database system for the management and integration of global information on genetic resources and crop improvement for any crop, was developed by genetic resource specialists, crop scientists, and information technicians associated with the Consultative Group for International Agricultural Research and collaborative partners. The International Rice Information System (www.iris.irri.org) is the rice (Oryza species) implementation of the International Crop Information System. New components are now being added to the International Rice Information System to handle the diversity of rice functional genomics data including genomic sequence data, molecular genetic data, expression data, and proteomic information. Users access information in the database through stand-alone programs and Web interfaces, which offer specialized applications and customized views to researchers with different interests.
GrainGenes 2.0. An Improved Resource for the Small-Grains Community
Authors: Carollo Victoria , Matthews David E. , Lazo Gerard R. , Blake Thomas K. , Hummel David D. , Lui Nancy , Hane David L. , Anderson Olin D.
Published: October 2005

GrainGenes (http://wheat.pw.usda.gov) is an international database for genetic and genomic information about Triticeae species (wheat [Triticum aestivum], barley [Hordeum vulgare], rye [Secale cereale], and their wild relatives) and oat (Avena sativa) and its wild relatives. A major strength of the GrainGenes project is the interaction of the curators with database users in the research community, placing GrainGenes as both a data repository and information hub. The primary intensively curated data classes are genetic and physical maps, probes used for mapping, classical genes, quantitative trait loci, and contact information for Triticeae and oat scientists. Curation of these classes involves important contributions from the GrainGenes community, both as primary data sources and reviewers of published data. Other partially automated data classes include literature references, sequences, and links to other databases. Beyond the GrainGenes database per se, the Web site incorporates other more specific databases, informational topics, and downloadable files. For example, unique BLAST datasets of sequences applicable to Triticeae research include mapped wheat expressed sequence tags, expressed sequence tag-derived simple sequence repeats, and repetitive sequences. In 2004, the GrainGenes project migrated from the AceDB database and separate Web site to an integrated relational database and Internet resource, a major step forward in database delivery. The process of this migration and its impacts on database curation and maintenance are described, and a perspective on how a genomic database can expedite research and crop improvement is provided.
GERMINATE. A Generic Database for Integrating Genotypic and Phenotypic Information for Plant Genetic Resource Collections
Authors: Lee Jennifer M. , Davenport Guy F. , Marshall David , Ellis T.H. Noel , Ambrose Michael J. , Dicks Jo , van Hintum Theo J.L. , Flavell Andrew J.
Published: October 2005

The extensive germplasm resource collections that are now available for major crop plants and their wild relatives will increasingly provide valuable biological and bioinformatics resources for plant physiologists and geneticists to dissect the molecular basis of key traits and to develop highly adapted plant material to sustain future breeding programs. A key to the efficient deployment of these resources is the development of information systems that will enable the collection and storage of biological information for these plant lines to be integrated with the molecular information that is now becoming available through the use of high-throughput genomics and post-genomics technologies. The GERMINATE database has been designed to hold a diverse variety of data types, ranging from molecular to phenotypic, and to allow querying between such data for any plant species. Data are stored in GERMINATE in a technology-independent manner, such that new technologies can be accommodated in the database as they emerge, without modification of the underlying schema. Users can access data in GERMINATE databases either via a lightweight Perl-CGI Web interface or by the more complex Genomic Diversity and Phenotype Connection software. GERMINATE is released under the GNU General Public License and is available at http://germinate.scri.sari.ac.uk/germinate/.
Combining Experimental and Predicted Datasets for Determination of the Subcellular Location of Proteins in Arabidopsis
Authors: Heazlewood Joshua L. , Tonti-Filippini Julian , Verboom Robert E. , Millar A. Harvey
Published: October 2005

Substantial experimental datasets defining the subcellular location of Arabidopsis (Arabidopsis thaliana) proteins have been reported in the literature in the form of organelle proteomes built from mass spectrometry data (approximately 2,500 proteins). Subcellular location for specific proteins has also been published based on imaging of chimeric fluorescent fusion proteins in intact cells (approximately 900 proteins). Further, the more diverse history of biochemical determination of subcellular location is stored in the entries of the Swiss-Prot database for the products of many Arabidopsis genes (approximately 1,800 proteins). Combined with the range of bioinformatic targeting prediction tools and comparative genomic analysis, these experimental datasets provide a powerful basis for defining the final location of proteins within the wide variety of subcellular structures present inside Arabidopsis cells. We have analyzed these published experimental and prediction data to answer a range of substantial questions facing researchers about the veracity of these approaches to determining protein location and their interrelatedness. We have merged these data to form the subcellular location database for Arabidopsis proteins (SUBA), providing an integrated understanding of protein location, encompassing the plastid, mitochondrion, peroxisome, nucleus, plasma membrane, endoplasmic reticulum, vacuole, Golgi, cytoskeleton structures, and cytosol (www.suba.bcs.uwa.edu.au). This includes data on more than 4,400 nonredundant Arabidopsis protein sequences. We also provide researchers with an online resource that may be used to query protein sets or protein families and determine whether predicted or experimental location data exist; to analyze the nature of contamination between published proteome sets; and/or for building theoretical subcellular proteomes in Arabidopsis using the latest experimental data.