bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification of Endocrine Disrupter‐Polluted Water Using High Temperature Superconducting HGMS
Authors: Mitsuhashi K. , Yoshizaki R. , Okada H. , Ohara T. , Wada H.
Published: May 2004

We have developed a superconducting High Gradient Magnetic Separation (HGMS) system to remove endocrine disrupters from water. The system was able to purify 70 L of endocrine disrupter‐polluted water within about 10 min without generating any secondary waste. The system consists of pretreatment processes to form magnetized compounds with endocrine disrupters, and an HGMS device to extract them from water by using a strong magnetic force. We produced novel adsorbent made of micron‐sized ferric oxide particles that are not only magnetic but also hydrophobic. Because some endocrine disrupters are hydrophobic as well, the ferric oxide particles adsorb endocrine disrupters eluted in water according to hydrophobic interaction. We succeeded in decreasing bisphenol A concentrations in the fortified water from 69 to 16 ng/L and nonylphenol from 7.0 to 0.9 mg/L. Furthermore, we have successfully demonstrated that we could regenerate the ferric oxide particles, so that they can be re‐used for adsorption of endocrine disrupters in water.
Electromagnetic De‐Shaling of Coal
Authors: de Jong T. P. R. , Mesina M. B. , Kuilman W.
Published: May 2004

The efficiency with which an electromagnetic sensor array is able to distinguish density and ash content of coal and shale mixtures was determined experimentally. The investigated sensor was originally designed for automatic metal detection and sorting in industrial glass recycle processing, where it is widely applied. In coal preparation, the results indicate good possibilities to remove automatically the remaining shale from the coal product, or to recover the remaining coal from the waste rock. Compared to alternative methods, the system has advantages of simple construction, insensitivity to fluctuating dust or moisture levels and a proven industrial reference. Applications can be either sorting of lump‐sized coal or coal separation in the 10–50mm size range in a dry preparation process.
Development of a Magnetic Hydrocyclone Separation for the Recovery of Titanium From Beach Sands
Authors: Premaratne W. A. P. J. , Rowson N. A.
Published: May 2004

The recovery of titanium from very fine particles of beach sand of Sri Lanka has been investigated using conventional hydrocyclone and novel magnetic hydrocyclone separation methods. A new design for a magnetic hydrocyclone has been developed using a permanent rare earth neodymium–iron–boron (Nd–Fe–B) magnet. Compared to the conventional hydrocyclone, this magnetic hydrocyclone was 5% more efficient in the recovery of titanium from the beach sand deposit with a commercial standard concentrate. It was also found that, for very fine particles, the titanium grade increased significantly (up to 56% TiO2) when titanium‐bearing minerals were separated using the novel magnetic hydrocyclone separation technique. Therefore, this type of magnetic hydrocyclone has potential to produce significant reduction in the processing time, thus saving energy and the running cost in an appropriate industrial application economically and efficiently.
Macrophage Migration Inhibitory Factor is a Constitutively Expressed Cytokine in the Human Adrenal Gland
Authors: Jian Ming , Parker Richard
Published: May 2004

Macrophage migration inhibitory factor (MIF) has been found to be widely expressed in many cell types throughout the body and appears to play several physiologic roles. We sought to determine the expression and cellular distribution of MIF in human fetal (HFA) and adult (HAA) adrenals. A single band of approximately 0.8 kb was revealed by northern blot hybridization using cDNA probes for MIF in total RNA extracts of both HFA and HAA tissues. Immunohistochemical analysis showed strong immunostaining for MIF in the broad fetal zone of the HFA and in both the zona glomerulosa and zona reticularis of HAA. The cells of the zona fasciculata of the HAA and of the neocortex of the HFA were only minimally, if at all, immunopositive for MIF and medullary elements were consistently negative for MIF. These results are indicative of local production of MIF in adrenocortical cells during intrauterine development and also in adulthood. The role of MIF in cortical cells of the human adrenal gland remains to be determined. IUBMB Life, 55: 155‐158, 2003
Dual Regulation of Proton‐ and Sodium‐Coupled Phosphate Transport Systems in the Yarrowia lipolytica Yeast by Extracellular Phosphate and pH
Authors: Zvyagilskaya R. , Persson BL
Published: May 2004

In this study we used a newly isolated osmo‐, salt‐, and alkali‐tolerant Yarrowia lipolytica yeast strain, with a unique capacity to grow over a wide pH range (3.5‐10.5). A procedure was elaborated to follow phosphate accumulation by Y. lipolytica cells grown at different pH values. In this paper we demonstrate that Pi‐starved Y. lipolytica cells are endowed by derepressible high‐affinity, high‐capacity H+‐ and Na+‐driven Pi uptake systems and that activities of these transport systems are under the dual control by the prevailing extracellular Pi concentrations and pH values. IUBMB Life, 55: 151‐154, 2003
Synergism between Genomic and Non Genomic Estrogen Action Mechanisms
Authors: Acconcia Filippo , Marino Maria
Published: May 2004

The 17β‐estradiol (E2) action mechanism for inducing target gene expression can be attributed to both the direct binding of its receptor (ER) to specific sequences, the estrogen response element (ERE), and to the interaction between ER and other DNA‐binding transcription factors. At the present meagre information is available for the role played by the rapid hormone action mechanism(s) (i.e., activation of ERK, PI(3)K, PKC‐α) in modulating E2‐induced gene promoter activity. Here the involvement of the rapid non genomic mechanism in triggering the transcriptional activity of two E2‐regulated target genes in human hepatoma HepG2 cells has been studied, taking into consideration the cyclin D1 (ERE‐devoid) and the complement protein 3 (ERE‐containing) promoter‐luciferase report constructs. The results indicate that the activation of the ERK pathway is essential for the E2‐induced activity of both promoters, whereas the other rapid E2‐induced membrane‐starting signal transduction pathways (i.e., PI(3)K and PKC‐α) were differently required. These results permit the amplification of the E2 action mechanism by the addition of synergy between the non genomic and genomic molecular actions of the E2‐induced gene transcription. IUBMB Life, 55: 145‐150, 2003
Detection of Mitochondrial DNA Deletion by a Modified PCR Method in a 60Co Radiation‐exposed Patient
Authors: Zhen‐Cheng Wang , Xue‐Min Wang , Bing‐Hua Jiao , You‐Xin Jin , Ming‐Yong Miao , Ke‐Jun Zhu , Qing‐Gui Ni
Published: May 2004

A new PCR based method was developed to detect deleted mitochondrial DNA (mtDNA). Peripheral blood cell DNA was obtained from a victim who was accidently exposed to a 60Co radiation source in 1990. Using the DNA as template, first PCR was performed to generate multiple products including true deletions and artifacts. The full length product was recovered and used as template of secondary PCR. The suspicious deletion product of mtDNA could be confirmed only if it was yielded by first PCR. Using either original primers or their nested primers, the suspicious deletion product was amplified and authenticated as a true deletion product. The template was recovered and determined to be a deletion by sequencing directly. The results show that a new mtDNA deletion, which spans 889 bp from nt 11688 to nt 12576, was detected in the peripheral blood cells of the victim. It indicates that this new PCR‐based method was more efficient at detecting small populations of mtDNA deletion than other routine methods. MtDNA deletion was found in the victim, suggesting the relationship between the deletion and phenotypes of the disease. IUBMB Life, 55: 133‐137, 2003
Search for Difference in Aminoacylation of Mitochondrial DNA‐encoded Wild‐type and Mutant Human tRNALeu?(UUR)
Authors: Zhen‐Cheng Wang , Xue‐Min Wang , You‐Xin Jin , Bing‐Hua Jiao , Feng Xu , Ming‐Yong Miao , Ke‐Jun Zhu
Published: May 2004

The pathogenetic mechanism of the most extensively investigated A3243G mutated tRNALeu (UUR) gene, which causes the MELAS encephalomyopathy, maternally inherited diabetes, or chronic progressive external ophlthalmoplegia, is still unresolved, despite the numerous investigations on the topic. Previous evidences presented in published work suggested that the mitochondrial DNA harboring A3243G mutation result decreases in the rates of mitochondrial protein synthesis. To search for differences in aminoacylation of mitochondrial DNA‐encoded wild‐type and mutant human tRNALeu (UUR), we have expressed and purified the two kinds of tRNAsLeu (UUR), and have expressed human mitochondrial leucyl‐tRNA synthetase for in vitro assays of aminoacylation of wild‐type and mutant human tRNALeu (UUR). The results indicate human mitochondrial tRNALeu (UUR) gene A3243G point mutant can remarkably reduce its aminoacylation, suggesting it could be one of the mechanisms that the mutation can produce in such clinical phenotypes. IUBMB Life, 55: 139‐144, 2003
The KRAB Domain of Zinc Finger Gene ZNF268: a Potential Transcriptional Repressor
Authors: Sun Yan , Gou De‐ming , Liu Hui , Peng Xiao , Li Wen‐xin
Published: May 2004

Nearly one‐third of Krupple‐type C2H2 zinc finger proteins have a krupple‐associated box (KRAB) domain, which may act as a transcriptional repressor. ZNF268, which was novelty isolated from early human embryo, is a typical krupple‐type C2H2 zinc finger protein with a conserved KRAB domain. In this report, the KRAB domain of ZNF268 is identified to localize in the nucleus and has transcriptional repressor activity. IUBMB Life, 55: 127‐131, 2003
PDK1 and PKB/Akt: Ideal Targets for Development of New Strategies to Structure‐Based Drug Design
Authors: Harris Thomas
Published: May 2004

Growth factor binding events to receptor tyrosine kinases result in activation of phosphatidylinositol 3‐kinase (PI3K), and activated PI3K generates the membrane‐bound second messengers phosphatidylinositol 3,4‐diphosphate [PI(3,4)P2] and PI(3,4,5)P3, which mediate membrane translocation of the phosphoinositide‐dependent kinase‐1 (PDK1) and protein kinase B (PKB, also known as Akt). In addition to the kinase domain, PDK1 and PKB contain a pleckstrin homology (PH) domain that binds to the second messenger, resulting in the phosphorylation and activation of PKB by PDK1. Recent evidence indicates that constitutive activation of PKB contributes to cancer progression by promoting proliferation and increased cell survival. The indicating of PDK1 and PKB as primary targets for discovery of anticancer drugs, together with the observations that both PDK1 and PKB contain small‐molecule regulatory binding sites that may be in proximity to the kinase active site, make PDK1 and PKB ideal targets for the development of new strategies to structure‐based drug design. While X‐ray structures have been reported for the kinase domains of PDK1 and PKB, no suitable crystals have been obtained for either PDK1 or PKB with their PH domains intact. In this regard, a novel structure‐based strategy is proposed, which utilizes segmental isotopic labeling of the PH domain in combination with site‐directed spin labeling of the kinase active site. Then, long‐range distance restraints between the 15N‐labeled backbone amide groups of the PH domain and the unpaired electron of the active site spin label can be determined from magnetic resonance studies of the enhancement effect that the paramagnetic spin label has on the nuclear relaxation rates of the amide protons. The determination of the structure and position of the PH domain with respect to the known X‐ray structure of the kinase active site could be useful in the rational design of potent and selective inhibitors of PDK1 and PKB by 'linking' the free energies of binding of substrate (ATP) analogs with analogs of the inositol polar head group of the phospholipid second messenger. The combined use of X‐ray crystallography, segmental isotopic and spin labeling, and magnetic resonance studies can be further extended to the study of other dynamic multidomain proteins and targets for structure‐based drug design. IUBMB Life, 55: 117‐126, 2003
Involvement of the Tyrosine Phosphorylation on GSH Transport in NIH3T3 Fibroblasts
Authors: Iantomasi Teresa , Favilli Fabio , Catarzi Serena , Giannoni Elisa , Biagioni Chiara , Vincenzini Maria
Published: May 2004

This study demonstrates the involvement of phosphotyrosine phosphatases on the activity and regulation of GSH ATP‐dependent transport system that we have previously identified in NIH3T3 fibroblasts. This is shown by the fact that increases of the initial rate of GSH uptake were measured in NIH3T3 overexpressing a synthetic gene coding for a low‐Mr‐phosphotyrosine protein phosphatase (LMW‐PTP), while decreases were obtained in NIH3T3 overexpressing the phosphatase inactive mutant (LMW‐C12SPTP), with respect to NIH3T3neo. Moreover, these results have been confirmed by experiments performed in the same cells by vanadate, and H2O2 treatment on both GSH transport and mediated passive transport of glucose. A possible regulation of this transport system by platelet‐derived growth factor receptor (PDGFr) with tyrosine kinase activity is also demonstrated. Moreover, these data show a relationship among GSH, PDGFr and phosphotyrosine phosphatase activity, and suggest a role of GSH transport systems on the cell proliferation process. IUBMB Life, 55: 159‐165, 2003
The Differential Susceptibility of Specific Neuronal Populations: Insights from Huntington's Disease
Authors: Mitchell Ian , Griffiths Mark
Published: May 2004

Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to show how the mutant protein could interact with associated proteins to form an aggregation product. This could lead to neuronal death by direct actions on caspases, or by raising the levels of intracellular calcium ions and reactive oxygen species above a threshold that cannot be resisted by the protection normally conferred by endogenous factors such as calcium binding proteins, free radical scavengers and trophic factors. The local distributions of vulnerability and protective factors could ultimately dictate the pattern of damage induced by the mutant gene. IUBMB Life, 55: 293‐298, 2003
Trophic Factors in Neurodegenerative Disorders
Authors: Weis Joachim , Saxena Smita , Evangelopoulos Maria , Kruttgen Alex
Published: May 2004

Neuronal survival is dependent on continuous trophic stimulation by neurotrophic factors. Anterograde and retrograde transport of neurotrophic factors and their receptors within neurites is essential for the communication of these survival signals. Lack of neurotrophic input has been proposed as a pathomechanism leading to neurodegenerative disease. The present short review provides a summary of some of the recent data on neurotrophic factors in neurodegenerative disorders and describes how disturbances of axonal trafficking might deprive neurons from trophic input. IUBMB Life, 55: 00‐00, 2003
Molecular Mechanisms of Neurodegeneration in Parkinson's Disease: Clues from Mendelian Syndromes
Authors: Lim Kah Leong , Lim Tit Meng
Published: May 2004

The recent identification and characterization of gene products responsible for familial forms of Parkinson disease (PD) have provided significant insights into the pathogenesis of PD. Collectively, these studies point towards ubiquitin‐proteasome system (UPS) dysfunction as an underlying mechanism responsible for dopaminergic cell death in PD. Emerging evidence further indicates a complex interplay between UPS derangements and other PD pathogenetic factors, all interwoven in an integrated network leading to dopaminergic cell death in PD. Taken together, these findings suggest that neuronal degeneration in PD is a result of a cascade of events, rather than a primary pathogenic event. Here, we review the clues uncovered from various Mendelian‐inherited forms of PD that have helped shaped our understanding of the molecular mechanisms underlying PD pathogenesis. IUBMB Life, 55: 315‐322, 2003
A Role for NOX NADPH Oxidases in Alzheimer's Disease and Other Types of Dementia?
Authors: Zekry Dina , Epperson Terry Kay , Krause Karl‐Heinz
Published: May 2004

Because of population ageing, dementias are likely to become a major scourge of the 21st century. Causes of dementia include Alzheimer's disease, cerebrovascular disease, and lesser known entities such as frontotemporal dementia or dementia with Lewy bodies. Neuroinflammation is likely to play an important role in the pathogenesis of dementia by the killing of neurons through inflammatory mechanisms. Such a role of neuroinflammation is well documented for Alzheimer's disease, and it is likely to play a role in other types of dementia as well. Reactive oxygen species (ROS) play a key role in inflammatory tissue destruction. The phagocyte NADPH oxidase NOX2 is the best studied ROS‐generating system. In the central nervous system, it is expressed in microglia and‐‐to a lesser extent‐‐in neurons. Indeed, there is emerging experimental evidence for a role of NOX2 in Alzheimer's and cerebrovascular disease. Recently, six novel ROS‐generating NADPH oxidases with homology to NOX2 have been discovered. Several of them are also expressed in the central nervous system. In this article, we hypothesize a role of NOX‐type NADPH oxidases in inflammatory neuronal loss. We review presently available evidence and suggest that NOX‐type NADPH oxidases may become promising pharmacological targets for the treatment and prevention of dementia. IUBMB Life, 55: 307‐313, 2003
Interactions Between Environmental and Genetic Factors in the Pathophysiology of Parkinson's Disease
Authors: Tsang Fai. , Soong Tuck Wah
Published: May 2004

Parkinson's disease (PD) is a progressive neurodegenerative disease with no known cure and affects approximately 1% of the elderly population. The major question in PD relates to the selective loss of dopaminergic neurons in patients. The underlying mechanism of genetic dysfunction and environmental toxins in contributing to the pathogenesis of PD may be oxidative stress. The interactions of genetic and environmental factors in PD may provide some answers to the longstanding question. In particular, the possibility that iron may provide selectivity to genetic susceptibility or dopamine reactivity in dopaminergic neuronal death is enhanced by the neuroprotection demonstrated in transgenic mice overexpressing ferritin or the use of iron chelators in MPTP‐induced PD mouse. It will be important to dissect and understand the contributions of genes, environment and intrinsic cellular states in the generation and progression of the pathophysiology of PD. IUBMB Life, 55: 323‐327, 2003
Hereditary Spastic Paraplegia: Clues from a Rare Disorder for a Common Problem?
Authors: Burgunder Jean‐Marc , Hunziker Walter
Published: May 2004

Hereditary spastic paraplegia is a rare disorder with gait disturbance due to a degeneration of the corticospinal tract, sometimes accompanied by involvement of other systems. Out of the 20 loci known so far, eight genes have now been identified, allowing the first molecular and cell studies in the pathophysiology of the disorder. These should also help to understand the function of the corticospinal tract at the molecular level and design strategies to prevent and treat spasticity due to more common causes. The proteins encoded by these genes play a role in development, in signal transduction between axons and myelinating cells, in cellular, particularly axonal trafficking or in energy metabolism. Some of them have actions in several areas of cellular function. Here we review the present knowledge about the genes involved in hereditary spastic paraplegia, a field presently undergoing rapid change. IUBMB Life, 55: 347‐352, 2003
Nitric Oxide and Reactive Oxygen Species in Parkinson's Disease
Authors: Tieu Kim , Ischiropoulos Harry , Przedborski Serge
Published: May 2004

Parkinson's disease is a neurodegenerative disorder of unknown pathogenesis. Oxidative stress has been proposed as one of several pathogenic hypotheses. Evidence for the participation of oxidative processes in the pathogenesis of Parkinson's disease have been obtained in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) model by the use of genetically altered mice. MPTP administration has been shown to increase levels of superoxide both intracellularly, via the inhibition of mitochondrial respiration and other mechanisms and extracellularly, via the activation of NADPH‐oxidase in microglia. In addition to superoxide, nitric oxide production by nNOS or by microglial iNOS also contributes to the MPTP neurotoxocity. Mice with endowed defences against superoxide or with deficiency in the nNOS and iNOS are protected from MPTP toxicity suggesting that formation of reactive oxygen and nitrogen intermediates both intracellularly and extracellularly contributes to the demise of dopaminergic neurons. Similar contribution of reactive nitrogen and oxygen species may well underlie the neurodegenerative processes in Parkinson's disease. IUBMB Life, 55: 329‐335, 2003
Polyglutamine Diseases and Molecular Chaperones
Authors: Kimura Yoko , Kakizuka Akira
Published: May 2004

The polyglutamine diseases, a group of diseases currently thought to consist of nine inherited neurodegenerative diseases, are caused by the expansion of unstable CAG trinucleotide repeats that code for polyglutamine tracts in the responsible genes. These diseases are now recognized as being of a type with conformationally abnormal or amyloid‐related proteins, and thus are called 'conformational diseases'. Recently, many studies using cell cultures and model organisms have suggested that the two major machineries for protein quality control (the molecular chaperone and the protein degradation machineries) play important roles in the pathogenesis of the polyglutamine diseases. Interestingly, molecular chaperones have been shown to behave in totally different ways in these studies, namely in suppressing as well as enhancing neurodegeneration or cell death. These apparently opposite actions of molecular chaperones suggest that a certain balance between the activities of molecular chaperones and the expression level of polyglutamine is an important determinant of the pathogenesis. In this review, we summarize recent findings on such ambiguous effects of molecular chaperones on polyglutamine diseases, and discuss possible mechanisms by which molecular chaperones, especially VCP, are involved in the pathogenesis. IUBMB Life, 55: 337‐345, 2003
The Neuropathological Spectrum of Neurodegenerative Tauopathies
Authors: Tolnay Markus , Probst Alphonse
Published: May 2004

Abundant neurofibrillary lesions made of abnormal and hyperphosphorylated microtubule‐associated protein tau constitute one of the defining neuropathological features of Alzheimer's disease. However, tau containing filamentous deposits in neurons and/or glial cells also define a heterogeneous group of neurodegenerative disorders clinically characterized by dementia and/or motor syndromes. Thus, all these disorders are collectively grouped under the generic term of tauopathies. In the present review we outline the morphological and biochemical characteristics of some major tauopathies, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease. The second part will deal with the recent discovery of tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 which demonstrates that tau dysfunction can lead to neurodegeneration. Finally, we will discuss the very recent finding of 'tau‐deficient' tauopathy in a subset of frontotemporal dementia cases. IUBMB Life, 55: 299‐305, 2003
Coordination of technological knowledge flows in firms
Authors: Malik Khaleel
Published: May 2004

One of the major challenges inside firms is how to effectively manage their knowledge assets in the context of managing the transfer of technological knowledge across the firm’s organizational boundaries. This paper explores technological knowledge flows and the coordination of knowledge activity through use of geographically dispersed cross‐functional teams, as a way of integrating diverse knowledge via technology transfer projects. As multinational companies (MNCs) have increased the volume of technological knowledge that flows between their corporate headquarters and subsidiary operations, with rapid speed in many cases, many large firms are having to face increasing challenges of now transferring more ‘softer’ forms of technological knowledge, since this is recognized as an enabler of competitive advantage for firms. Developing this theme, the paper provides a theoretical review of some helpful contributions in this area and provides some empirical research knowledge management insights, gained from conducting research interviews with different functional managers from four UK‐based multinational firms.
Hemochromatosis mutations are not linked to dilated cardiomyopathy in Israeli patients
Authors: Goland Sorel , Beilinson Nick , Kaftouri Avinoam , Shimoni Sara , Caspi Abraham , Malnick Stephen D.H.
Published: May 2004

Aims.

Hemochromatosis is a condition in which iron loading impairs the function of many organs, including the heart. Congestive heart failure with left ventricular dilatation is commonly found in patients with hemochromatosis. Two missense mutations (C282Y and H63D) have been shown to be responsible for the majority of cases of hemochromatosis.

Methods and results.

We examined 156 patients with congestive heart failure due to dilated cardiomyopathy. Details were recorded of clinical and echocardiographic parameters. DNA was extracted from peripheral blood and checked for the presence of the C282Y and H63D mutations by a commercially available single nucleotide primer extension assay. A control group of 98 healthy blood donors was also checked for the presence of these mutations. Of the 157 patients, 42 (26.75%) had at least one mutation. Five (3.65%) were homozygotic for the H63D mutation and 37 (23.6%) were heterozygotic for the H63D mutation. The C282Y mutation was not present. In a control population of 98 healthy blood donors, 27 (27.6%) were heterozygous for the H63D population and none had the C282Y mutation (no significant difference between the patients with cardiomyopathy and the healthy blood donors, χ2 test 0.754). There was a non‐significant trend to a difference in the prevalence of homozygotic H63D between the cardiomyopathy patients and the healthy blood donors (3.18% vs. 0%, P=0.076, χ2 test). There was no statistically significant difference between the cardiomyopathy patients with and without the mutations in terms of age, gender, hemoglobin, iron, transferrin, ferritin, presence of diabetes mellitus, hypertension and previous coronary artery bypass grafting.

Conclusion.

In our population of patients with dilated cardiomyopathy, there was no evidence for hemochromatosis being an important etiology.
Impact of atrial fibrillation on mortality and readmission in older adults hospitalized with heart failure
Authors: Ahmed Ali , Thornton Phillip , Perry Gilbert J. , Allman Richard M. , DeLong James F.
Published: May 2004

Background:

Atrial fibrillation is common in older adults with heart failure. It is known to adversely affect outcomes.

Aim:

To examine the associations of atrial fibrillation with 4‐year mortality and 30‐day readmission in older adults hospitalized with heart failure.

Methods:

Patients were Medicare beneficiaries 65 years of age and older discharged with a primary diagnosis of heart failure. Baseline data were obtained by retrospective chart reviews and data on mortality and readmission were obtained from Medicare administrative files. Presence of atrial fibrillation was confirmed using electrocardiogram during hospital admission. Using Cox proportional hazards models we estimated bivariate and multivariable (adjusted for various patient and care covariates) hazards ratios (HR) and 95% confidence intervals (CI) for 4‐year mortality and 30‐day readmission of patients with atrial fibrillation compared with those without.

Results:

Patients (n=944) had a mean age (±S.D.) of 79 (±7) years, 61% were women, 18% African–Americans, 25% had atrial fibrillation by admission electrocardiogram, 64% died within 4 years, and 8% were readmitted. Patients with atrial fibrillation had a 52% increased risk of 4‐year mortality (adjusted HR=1.52; 95%CI=1.11–2.07). Atrial fibrillation was also associated with higher risk of readmission (unadjusted HR=1.64; 95%CI=1.01–2.68). However, the association lost its statistical significance after adjustment for various patient and care variables (adjusted HR=2.09; 95%CI=0.94–4.65).

Conclusion:

Presence of atrial fibrillation was associated with significant increased risk of long‐term mortality in older adults hospitalized with heart failure and was associated with a non‐significant higher risk of hospital readmission.
Living with advanced heart failure: a prospective, community based study of patients and their carers
Authors: Boyd Kirsty J. , Murray Scott A. , Kendall Marilyn , Worth Allison , Benton T. Frederick , Clausen Hans
Published: May 2004

Background:

Services for people with heart failure are under‐developed. The perspectives of patients, their informal and professional carers should inform development of service models.

Aim:

To describes how patients and carers view health and social care in the last year of life.

Methods:

Qualitative, serial interviews at three monthly intervals with 20 patients (New York Heart Association Grade IV heart failure), their main informal carer, general practitioner and other key professionals in an urban, community setting in SE Scotland. These were tape‐recorded, and analysed with the aid of the qualitative data analysis package NVivo and techniques of narrative analysis.

Results:

112 interviews comprised; patients (50), informal carers (27), professionals (30), bereavement interviews (5). Patients with heart failure and their carers felt unsupported by services, and had little understanding of their condition, treatment aims or prognosis. Quality of life was severely compromised by physical limitations and psychological morbidity. Psychosocial care, patient and carer education, co‐ordination of care between primary and secondary sectors and with social services was generally poor. Many patients had no access to a heart failure nurse specialist. A palliative care approach was rarely apparent.

Conclusions:

Patients with advanced heart failure may benefit from specific models of care with strategic planning across primary and secondary care, and involvement of health and social care services and specialist palliative care providers. Models of care, which focus on quality of life, symptom control, and psychosocial support for patients and their families while continuing active treatment, should be developed.
Heart failure—the importance of ethnicity
Authors: Sosin Michael D. , Bhatia Gurbir S. , Davis Russell C. , Lip Gregory Y.H.
Published: May 2004

Heart failure is a major public health problem in the Western world. Aetiological factors involved in its development include hypertension, diabetes, and ischaemic heart disease—all of which differ in prevalence, and possibly mechanism, between patients of differing ethnicity. Unfortunately, epidemiological and therapeutic trials have involved almost exclusively white populations, and evidence from these trials cannot necessarily be assumed to be generalisable to populations that include high proportions of patients from other ethnic origins. This review will discuss the mechanistic and therapeutic differences that exist in heart failure between those of European origin, and patients from the major ethnic minority groups of the UK.
The effect of dietary sodium restriction on neurohumoral activity and renal dopaminergic response in patients with heart failure
Authors: Alvelos Margarida , Ferreira António , Bettencourt Paulo , Serrão Paula , Pestana Manuel , Cerqueira‐Gomes Mário , Soares‐da‐Silva Patrício
Published: May 2004

Background:

This work evaluates the effect of a low‐sodium diet on clinical and neurohumoral parameters and on renal dopaminergic system activity in heart failure (HF) patients.

Methods:

We included 24 patients with mild‐to‐moderate stable HF with left ventricle ejection fraction <40%. Twelve patients were studied before and after a 15‐day low‐sodium diet; 12 maintained their usual diet. Serum sodium and creatinine, plasma l‐DOPA, dopamine, its metabolites, BNP and aldosterone, and 24‐h urinary sodium, creatinine, l‐DOPA, dopamine and metabolites were measured.

Results:

The two groups were matched respecting to demographic and clinical parameters. Low‐sodium diet caused significant reductions in weight, 24‐h urinary volume and sodium and sodium fractional excretion. Renal delivery of l‐DOPA and urinary excretion of l‐DOPA significantly decreased while dopamine and metabolites were not affected. Urinary dopamine/l‐DOPA and urinary dopamine/renal delivery of l‐DOPA ratios increased, plasma l‐DOPA decreased and plasma dopamine increased. Plasma aldosterone slightly rose, BNP decreased and noradrenaline and adrenaline increased. NYHA functional class was not affected by sodium restriction. Controls showed no differences.

Conclusions:

These results suggest that sodium restriction leads to activation of antinatriuretic antidiuretic systems in HF patients. However, renal ability to synthesize dopamine is increased in this condition, probably as a counter‐regulatory mechanism.
Comparison of treatment initiation with bisoprolol vs. enalapril in chronic heart failure patients: rationale and design of CIBIS‐III
Authors: Willenheimer Ronnie , Erdmann Erland , Follath Ferenc , Krum Henry , Ponikowski Piotr , Silke Bernard , van Veldhuisen Dirk J. , van de Ven Louis , Verkenne Patricia , Lechat Philippe ,   on behalf of the CIBIS‐III investigators
Published: May 2004

Background:

Angiotensin‐converting‐enzyme (ACE) inhibitors and β‐blockers are standard therapy for chronic heart failure (CHF). β‐blockers are recommended to be initiated after ACE‐inhibitors, but this order is not evidence based. The initiation order may be important since many, especially elderly CHF patients cannot tolerate target doses of both. Data suggest that β‐blockers may be more important to CHF patients than ACE‐inhibitors, especially in early stages of CHF.

Aims:

To compare the effect on combined death or hospitalisation of initial monotherapy with either bisoprolol or enalapril, followed by combination therapy.

Methods:

One‐thousand CHF patients without ACE‐inhibitor, β‐blocker or angiotensin‐receptor‐blocker therapy will be randomised 1:1 to monotherapy with either enalapril or bisoprolol for 6 months, followed by combined therapy for 6–18 months. The primary objective is to show non‐inferiority for bisoprolol‐first vs. enalapril‐first regarding combined death or hospitalisation. If that is shown, superiority for bisoprolol‐first will be tested.

Conclusions:

If the trial shows non‐inferiority for bisoprolol‐first vs. enalapril‐first, the first CHF therapy may be chosen based on individual judgement in each patient. If bisoprolol‐first is superior to enalapril‐first, a β‐blocker should be given prior to an ACE‐inhibitor in CHF, and the paradigm of testing CHF compounds against a background of ACE‐inhibitor therapy will be challenged.
Cardiac rotation and relaxation in patients with chronic heart failure
Authors: Fuchs Esther , Müller Markus F. , Oswald Helmut , Thöny Harriet , Mohacsi Paul , Hess Otto M.
Published: May 2004

Background:

The normal left ventricle shows a systolic wringing motion with clockwise rotation at the base and counterclockwise rotation at the apex.

Purpose:

The aim of the present study was (1) to assess left ventricular (LV) contraction and relaxation in patients with chronic heart failure (CHF), and (2) to evaluate the effect of medical therapy on LV contraction–relaxation behavior.

Methods:

Magnetic resonance was used to examine LV motion by labeling specific LV regions in three planes (myocardial tagging). Twenty‐three subjects were included, nine healthy controls and 14 CHF patients. Cardiac motion was determined from the deformation of a rectangular grid in a basal and apical plane. CHF patients were put on triple therapy with ACE‐inhibitors, β‐blockers and spironolactone. Follow‐up examination (n=9) was performed after 6 months.

Results:

In controls, systolic rotation was −9.5±2° at the base and +3.3±1° at the apex. In CHF patients, rotation was reduced both at the base (−3.4±2°, P<0.01) and the apex (+0.9±3°, P<0.05). Similarly, regional ejection fraction (REF) was reduced in CHF patients both at the base and the apex. Medical therapy was associated with an improvement in REF, but systolic rotation improved only at the base (−4.6±2°, P<0.05).

Conclusions:

Systolic wringing motion with clockwise rotation at the base and counterclockwise rotation at the apex is maintained in CHF although reduced. Heart failure treatment is associated with an improvement in REF, whereas rotation improved only at the base, but not at the apex. Thus, there is an uncoupling between regional shortening and rotation in CHF patients.
Diastolic heart failure. Paroxysmal or chronic?
Authors: Banerjee Prithwish , Clark Andrew L. , Nikitin Nikolay , Cleland John G.F.
Published: May 2004

Heart failure with preserved systolic function is considered by some to be synonymous with diastolic heart failure (DHF). Although recent epidemiological studies have suggested that DHF constitutes 30–50% of all patients with heart failure, many cardiologists dealing with ambulant heart failure patients on a daily basis find that the vast majority of heart failure patients have systolic dysfunction. What could be the reasons for this? Referral bias and varying diagnostic thresholds and interpretation of results could be one important reason. Heart failure with preserved systolic function comprises a heterogeneous group of conditions: whilst some patients may truly have DHF, others may have heart failure due to subtle systolic dysfunction (noted on tissue Doppler imaging of the left ventricular long axis). Other patients actually have pulmonary disease, obesity or ischaemic heart disease, and have their symptoms attributed to ‘diastolic heart failure’ on the basis of ‘abnormal’ mitral diastolic flow indices that may, in fact, simply reflect aging. True DHF may be much less prevalent than suggested. A further possibility is that heart failure in patients with diastolic dysfunction might be paroxysmal rather than chronic. This group of patients may present predominantly to acute units like accident and emergency, coronary care units and intensive care units and are, therefore unlikely to figure prominently in the usual outpatient population of chronic systolic left ventricular dysfunction.
Reconstructing habitats in central Amazonia using megafauna, sedimentology, radiocarbon, and isotope analyses
Authors: de Fátima Rossetti Dilce , de Toledo Peter Mann , Moraes-Santos Heloı́sa Maria , de Araújo Santos Antônio Emı́dio
Published: May 2004

A paleomegafauna site from central Amazonia with exceptional preservation of mastodons and ground sloths allows for the first time a precise age control based on14C analysis, which, together with sedimentological and δ13C isotope data, provided the basis to discuss habitat evolution within the context of climate change during the past 15,000 yr. The fossil-bearing deposits, trapped within a depression in the Paleozoic basement, record three episodes of sedimentation formed on floodplains, with an intermediate unit recording a catastrophic deposition through debris flows, probably favored during fast floodings. The integrated approach presented herein supports a change in humidity in central Amazonia through the past 15,000 yr, with a shift from drier to arboreal savanna at 11,340 (±50)14C yr B.P. and then to a dense forest like we see today at 4620 (±60)14C yr B.P.
Imprinting of the human
L3MBTL
gene, a polycomb family member located in a region of chromosome 20 deleted in human myeloid malignancies
Authors: Li Juan , Bench Anthony J. , Vassiliou George S. , Fourouclas Nasios , Ferguson-Smith Anne C. , Green Anthony R.
Published: May 2004

L3MBTL
encodes a member of the Polycomb family of proteins, which, together with Trithorax group proteins, is responsible for the coordinated regulation of patterns of gene activity. Members of the Polycomb family also regulate self renewal of normal and malignant hematopoietic stem cells.
L3MBTL
lies in a region of chromosome 20, deletion of which is associated with myeloid malignancies and represents a good candidate for a 20q target gene. However, mutations of
L3MBTL
have not been identified in patients with 20q deletions or in cytogenetically normal patients. Here we demonstrate that monoallelic methylation of two CpG islands correlates with transcriptional silencing of
L3MBTL
, and that
L3MBTL
transcription occurs from the paternally derived allele in five individuals from two families. Expression of the paternally derived allele was observed in multiple hematopoietic cell types as well as in bone marrow derived mesenchymal cells. Deletions of 20q associated with myeloid malignancies resulted in loss of either the unmethylated or methylated allele. Our results demonstrate that
L3MBTL
represents a previously undescribed imprinted locus, a vertebrate Polycomb group gene shown to be regulated by this mechanism, and has implications for the pathogenesis of myeloid malignancies associated with 20q deletions.
Application of evolutionary algorithm methods to polypeptide folding: Comparison with experimental results for unsolvated Ac-(Ala-Gly-Gly)
5
-LysH
+
Authors: Damsbo Martin , Kinnear Brian S. , Hartings Matthew R. , Ruhoff Peder T. , Jarrold Martin F. , Ratner Mark A.
Published: May 2004

We present an evolutionary method for finding the low-energy conformations of polypeptides. The application, called
foldaway
,is based on a generic framework and uses several evolutionary operators as well as local optimization to navigate the complex energy landscape of polypeptides. It maintains two complementary representations of the structures and uses the
charmm
force field for evaluating the energies. The method is applied to unsolvated Met-enkephalin and Ac-(Ala-Gly-Gly)
5
-Lys
+
H
+
. Unsolvated Ac-(Ala-Gly-Gly)
5
-Lys
+
H
+
has been the object of recent experimental studies using ion mobility measurements. It has a flat energy landscape where helical and globular conformations have similar energies.
foldaway
locates several large groups of structures not found in previous molecular dynamics simulations for this peptide, including compact globular conformations, which are probably present in the experiments. However, the relative energies of the different conformations found by
foldaway
do not accurately match the relative energies expected from the experimental observations.
CRE recombinase-inducible RNA interference mediated by lentiviral vectors
Authors: Tiscornia Gustavo , Tergaonkar Vinay , Galimi Francesco , Verma Inder M.
Published: May 2004

Recently, several systems designed to trigger RNA interference by using small hairpin RNA driven by polymerase III promoters have been described. Here, we report a lentiviral-mediated small interfering RNA delivery system that can be induced by CRE recombinase. The system consists of a lentiviral vector carrying a mouse U6 promoter that is separated from a small hairpin RNA by a random DNA stuffer sequence flanked by modified loxP sites. The silencing cassette is not expressed until activated by addition of CRE recombinase delivered by a lentiviral vector. We have used this system to show specific down-regulation of GFP and two endogenous genes (the tumor suppressor p53 and the NF-κB transcription factor subunit p65)
in vitro
. Furthermore, down-regulation of both p53 and p65 resulted in the expected effect on downstream genes and cellular phenotype. We foresee multiple applications of this system both
in vitro
and
in vivo
to down-regulate specific targets in a tissue-specific and localized manner.
New thioredoxin targets in the unicellular photosynthetic eukaryote
Chlamydomonas reinhardtii
Authors: Lemaire Stéphane D. , Guillon Blanche , Le Maréchal Pierre , Keryer Eliane , Miginiac-Maslow Myroslawa , Decottignies Paulette
Published: May 2004

Proteomics were used to identify the proteins from the eukaryotic unicellular green alga
Chlamydomonas reinhardtii
that can be reduced by thioredoxin. These proteins were retained specifically on a thioredoxin affinity column made of a monocysteinic thioredoxin mutant able to form mixed disulfides with its targets. Of a total of 55 identified targets, 29 had been found previously in higher plants or
Synechocystis
, but 26 were new targets. Biochemical tests were performed on three of them, showing a thioredoxin-dependent activation of isocitrate lyase and isopropylmalate dehydrogenase and a thioredoxin-dependent deactivation of catalase that is redox insensitive in
Arabidopsis
. In addition, we identified a Ran protein, a previously uncharacterized nuclear target in a photosynthetic organism. The metabolic and evolutionary implications of these findings are discussed.
Strength, Sharing and Service: Restorying and the legitimation of research texts
Authors: MULHOLLAND JUDITH , WALLACE JOHN
Published: May 2004

This article uses data from a longitudinal qualitative research project exploring the experiences of elementary teachers as they both learnt and taught science in the transition from a pre‐service to an in‐service situation. Interviews, journal entries and observations were the original data sources from which case studies were derived by narrative analysis. The material used in this article concerns a single participant. The purpose is to examine a narrative device, restorying, and explore its usefulness as a way of enhancing legitimation in narrative inquiry. Three sets of criteria for legitimation of qualitative studies are suggested; a set that requires research to be conducted in ways that provide evidence of thoroughness and fairness; a set that allows the reader to experience vicariously the world of the participants; and a set concerned with the ways in which education is enhanced for researcher, participants and reader. The authors suggest that a single text cannot fully satisfy all of these criteria sets but that by using multiple tellings or restorying, the legitimation of findings in qualitative research can be enhanced.
Social Class, Ability and Choice of Subject in Secondary and Tertiary Education in Britain
Authors: VAN DE WERFHORST HERMAN G. , SULLIVAN ALICE , CHEUNG SIN YI
Published: May 2004

This article examines the impact of family background (social class, cultural and economic capital) and ability on the choice of subjects in secondary and tertiary education in Britain. Using a framework that integrates rational choice perspectives and cultural reproduction theory, we assume that children take their parents' social position as a reference for their own choices, and are guided mainly by the amount of economic and cultural capital that is available within the family. Using longitudinal data from the 1958 British birth cohort (N =13,245), the empirical analysis shows that children from higher social class backgrounds achieved a higher standard in both humanities and scientific subjects in primary and secondary school. Furthermore, children of the professional class were relatively likely to choose the prestigious subjects of medicine and law in university, independent of ability. Both absolute and relative levels of ability were relevant to the choice of subject at degree level, as it was found that people chose subjects that they were relatively good at compared to other subjects. This concept of ‘comparative advantage’ gives additional insight into field‐of‐study choices, but does not explain the gender segregation across disciplines.