bluuebunny/crossref_metadata_2025 huggingface dataset:
Attachment of Histidine Tags to Recombinant Tumor Necrosis Factor-Alpha Drastically Changes Its Properties
Authors: Fonda Irena , Kenig Maja , Gaberc-Porekar Vladka , Pristovaek Primo , Menart Viktor
Published: March 2005

When studying two different histidine tags attached to the N-termini of the trimeric cytokine tumor necrosis factor alpha (TNF), the biological activity — measured as cytotoxicity on the L-929 cell line — of both tagged proteins was drastically reduced. The longer His10 tag reduced cytotoxicity to approximately 16% and the shorter His7 tag to 6% of the activity of their nontagged counterparts. After removal of the tags, biological activities reverted to the expected normal values, which clearly shows the key role of the attached histidine tags in diminishing biological activity. Studies on the mechanism of these effects revealed no specific interactions and showed that even the natural flexible N-terminus of TNF presents a steric hindrance for receptor binding, while any extension of the N-terminus increases this hindrance and consequently reduces biological activity. Also, in other proteins, the ligand or substrate binding sites may be hindered by histidine tags, leading to wrong conclusions about biological activity or other properties of the proteins. Thus caution is advised when using His-tagged proteins directly in screening procedures or in research.
Fractionation of Golgi, Endoplasmic Reticulum, and Plasma Membrane from Cultured Cells in a Preformed Continuous Iodixanol Gradient
Authors: Graham John
Published: March 2005

A continuous iodixanol gradient within the range 0-30% (w/v) iodixanol can resolve the major membrane compartments of the endoplasmic reticulum, Golgi membranes, and plasma membrane from a postnuclear supernatant prepared from a cultured cell homogenate. The precise density range of the gradient and the centrifugation conditions (100,000-200,000gfor 2-16 h) vary with the type of cell and the requirements of the separation. The strategy is widely used to study the processing of proteins within cells.
Periphyton Function in Lake Ecosystems
Authors: Vadeboncoeur Yvonne , Steinman Alan D.
Published: March 2005

Periphyton communities have received relatively little attention in lake ecosystems. However, evidence is increasing that they play a key role in primary productivity, nutrient cycling, and food web interactions. This review summarizes those findings and places them in a conceptual framework to evaluate the functional importance of periphyton in lakes. The role of periphyton is conceptualized based on a spatial hierarchy. At the coarsest scale, landscape properties such as lake morphometry, influence the amount of available habitat for periphyton growth. Watershed-related properties, such as loading of dissolved organic matter, nutrients, and sediments influence light availability and hence periphyton productivity. At the finer scale of within the lake, both habitat availability and habitat type affect periphyton growth and abundance. In addition, periphyton and phytoplankton compete for available resources at the within-lake scale. Our review indicates that periphyton plays an important functional role in lake nutrient cycles and food webs, especially under such conditions as relatively shallow depths, nutrient-poor conditions, or high water-column transparency. We recommend more studies assessing periphyton function across a spectrum of lake morphometry and trophic conditions.
Mitochondria: Regulators of Cell Death and Survival
Authors: Granville David J. , Gottlieb Roberta A.
Published: March 2005

The past 5 years has seen an intense surge in research devoted toward understanding the critical role of mitochondria in the regulation of cell death. Apoptosis can be initiated by a wide array of stimuli, inducing multiple signaling pathways that, for the most part, converge at the mitochondrion. Although classically considered the powerhouses of the cell, it is now understood that mitochondria are also “gatekeepers” that ultimately determine the fate of the cell. The mitochondrial decision as to whether a cell lives or dies is complex, involving protein-protein interactions, ionic changes, reactive oxygen species, and other mechanisms that require further elucidation. Once the death process is initiated, mitochondria undergo conformational changes, resulting in the release of cytochrome c (cyt c), caspases, endonucleases, and other factors leading to the onset and execution of apoptosis. The present review attempts to outline the complex milieu of events regulating the mitochondrial commitment to and processes involved in the implementation of the executioner phase of apoptotic cell death.
Functional Properties and Molecular Architecture of Leukotriene A4 Hydrolase, a Pivotal Catalyst of Chemotactic Leukotriene Formation
Authors: Haeggström Jesper Z. , Nordlund Pär , Thunnissen Marjolein M.G.M.
Published: March 2005

The leukotrienes are a family of lipid mediators involved in inflammation and allergy. Leukotriene B4is a classical chemoattractant, which triggers adherence and aggregation of leukocytes to the endothelium at only nM concentrations. In addition, leukotriene B4modulates immune responses, participates in the host defense against infections, and is a key mediator of PAF-induced lethal shock. Because of these powerful biological effects, leukotriene B4 is implicated in a variety of acute and chronic inflammatory diseases, e.g., nephritis, arthritis, dermatitis, and chronic obstructive pulmonary disease. The final step in the biosynthesis of leukotriene B4is catalyzed by leukotriene A4hydrolase, a unique bifunctional zinc metalloenzyme with an anion-dependent aminopeptidase activity. Here we describe the most recent developments regarding our understanding of the function and molecular architecture of leukotriene A4hydrolase.
Low-Avidity Antibodies to Carbonic Anhydrase-I and -II in Autoimmune Chronic Pancreatitise
Authors: Bartolomé Maria J. , de las Heras Gonzalo , López-Hoyos Marcos
Published: March 2005

Antibodies (Abs) to carbonic anhydrase (isoforms CA-I and CA-II) have been considered pathogenic factors in the development of autoimmune pancreatitis. Besides, such autoAbs might accelerate the pancreatic damage in alcoholic chronic pancreatitis (CP). The aim of the present study was to evaluate the presence of serum Abs to CA-I and CA-II in CP and the relative affinity of these Abs.

Serum anti-CA-I and -CA-II Abs were measured in 89 patients with CP (48 alcoholic and 41 nonalcoholic) by an ELISA technique. The prevalence of those autoAbs in CP was compared with other autoimmune diseases where they have also been found. The presence of other serological manifestations of autoimmunity, such as hypergammaglobulinemia or antinuclear Abs, was determined in CP patients as well.

Elevated serum levels of both anti-CA-I (24%) and -CA-II (18%) Abs were observed in CP, although their prevalence was lower than in autoimmune diseases like rheumatoid arthritis (44 and 25%, respectively) or systemic lupus erythematosus (39% for anti-CA-I Abs). Furthermore, these Abs were of low average avidity. On the other hand, a significantly higher proportion of nonalcoholic CP had anti-CA-II Abs with respect to alcoholic CP (15.2 vs. 2.4%,p< 0.05

Anti-CA-I and -CA-II Abs might be helpful in the diagnosis of autoimmune CP, and the detection of the latter Abs seems to discard alcoholic etiology. Although it does not discard any pathogenic role in autoimmune CP, the low-avidity of anti-CA Abs argues against such idea.
Rapid Purification of Nuclei from Animal and Plant Tissues and Cultured Cells
Authors: Graham John
Published: March 2005

Nuclei are isolated by buoyant density banding in a discontinuous iodixanol gradient, under isoosmotic conditions. The low viscosity of the gradient allows the purification to be carried out at 10,000g in only 20 min. The method avoids possible damage to nucleoprotein complexes caused by hyperosmotic sucrose gradients. Although developed for mammalian liver the method can be applied (with or without minor modifications) to any tissue or cell type.
Separation of Membrane Vesicles and Cytosol from Cultured Cells and Bacteria in a Preformed Discontinuous Gradient
Authors: Graham John
Published: March 2005

There are many situations when it is necessary to separate rapidly and efficiently a cytosolic and a membrane vesicle fraction from either cultured cells or from bacteria. Flotation of the vesicles through a low-density barrier from a dense sample zone using the low viscosity medium iodixanol allows complete separation of these compartments. As the sample is exposed to the gmax the tendency of the proteins to sediment overcomes any diffusion in the opposite direction.
Purification of Peroxisomes in a Self-Generated Gradient
Authors: Graham John
Published: March 2005

In iodixanol, peroxisomes are the densest organelle in the light mitochondrial fraction and are therefore easily separated from the other components (lysosomes, mitochondria, etc.) in a self-generated gradient. Self-generated gradients make sample handling very easy and are highly reproducible but need to be formed in either a vertical, near-vertical, or small volume high-performance fixed-angle rotor. The resolution of the peroxisomes is far superior than that in sucrose and, unlike in PercollⓇ there is no contamination from endoplasmic reticulum.
OptiPrepTMDensity Gradient Solutions for Nonmammalian Organelles
Authors: Graham John M.
Published: March 2005

Any density gradient for the isolation of nonmammalian organelles should ideally only expose the sedimenting biological particles to an increasing concentration of the gradient solute. Thus they will experience only an increasing density and viscosity, other parameters such as osmolality, pH, ionic strength and the concentration of important additives (such as EDTA and DTT) should remain as close to constant as possible. This Protocol Article describes the strategies for the dilution of OptiPrep™ in order to prepare such solutions for organelles and membranes from nonmammalian sources such as yeast.
OptiPrep™ Density Gradient Solutions for Mammalian Organelles
Authors: Graham John
Published: March 2005

Any density gradient for the isolation of mammalian organelles should ideally only expose the sedimenting biological particles to an increasing concentration of the gradient solute. Thus they will experience only an increasing density and viscosity, other parameters such as osmolality, pH, ionic strength and the concentration of important additives (such as EDTA and DTT) should remain as close to constant as possible. This Protocol Article describes the strategies for the dilution of OptiPrep™ in order to prepare such solutions for mammalian organelles and membranes.
Isolation of Peripheral Blood Mononuclear Cells from Macaques on a Density Barrier
Authors: Graham John
Published: March 2005

The standard techniques for the isolation of human peripheral blood mononuclear cells (PBMCs) using commercial “lymphocyte isolation media” cannot be satisfactorily extended to experimental animals without manipulating either the density or the osmolality of the medium. PBMCs from Macaques can also be isolated from whole blood by sedimentation on to a density barrier containing approx. 10% iodixanol, polysucrose (Ficoll) with a density of approx 1.074 g/ml.
Purification of Islets of Langerhans from Porcine Pancreas
Authors: Graham John
Published: March 2005

Flotation through a slightly hyperosmotic discontinuous gradient iodixanol achieves a much higher recovery of islets of an improved viability than the customary method using sedimentation on to a diatrizoate/polysaccharide barrier. Flotation techniques achieve an enhanced separation of the islets from any residual digestive enzymes and from acinar cells. The method has been extended to human pancreas.
Preparation of Crude Subcellular Fractions by Differential Centrifugation
Authors: Graham John
Published: March 2005

The employment of differential centrifugation to prepare crude fractions of subcellular particles from homogenates is often a necessary first step to a subsequent purification of one or more particles on a density gradient. Buoyant density gradient purification of peroxisomes or lysosomes for example is almost invariably carried out on a light mitochondrial fraction so as to eliminate smaller particles that may have similar densities. Unless they are first removed, large rapidly sedimenting particles in homogenates may also disturb shallow gradients designed to fractionate small low-density microsomes.
Membrane Pathology in Schizophrenia: Implication for Arachidonic Acid Signaling
Authors: Yao Jeffrey K. , Reddy Ravinder K.
Published: March 2005

Schizophrenia is a major mental disorder with no clearly identified pathophysiology. A variety of theories has been proposed to explain the pathophysiology of schizophrenia. One approach that is finding empirical support is the investigation of membrane composition and function. Evidence to date suggests that there are defects in phospholipid metabolism and cell signaling in schizophrenia. Specifically, low levels of arachidonic acid (AA)–enriched phospholipids have been observed in both central and peripheral tissues. It is well known that changes in membrane composition are associated with a variety of functional consequences. Since AA has many key roles in neural functioning, understanding its significance for the pathophysiology of schizophrenia may lead to novel approaches to improving treatment of schizophrenia. The purpose of this review is thus to explore some of the roles of AA signaling in biological, physiological, and clinical phenomena observed in schizophrenia.
Proteins Involved in the Trafficking and Functional Synaptic Expression of AMPA and KA Receptors
Authors: De La Rue Sarah A. , Henley Jeremy M.
Published: March 2005

α-Amino-3-hydroxy-5-methylisoxazolepropionate receptors (AMPARs) mediate the majority of fast synaptic transmission in the mammalian central nervous system, play a central role in synapse stabilisation and plasticity, and their prolonged activation is potently neurotoxic. The functional roles of kainate receptors (KARs) are less well defined but they play a role in some forms of synaptic plasticity. Both receptor types have been shown to be highly developmentally and activity-dependently regulated and their functional synaptic expression is under tight cellular regulation. The molecular and cellular mechanisms that regulate the synaptic localisation and functional expression of AMPARs and KARs are objects of concerted research. There has been significant progress towards elucidating some of the processes involved with the discovery of an array of proteins that selectively interact with individual AMPAR and KAR subunits. These proteins have been implicated in, among other things, the regulation of post-translational modification, targeting and trafficking, surface expression, and anchoring. The aim of this review is to present an overview of the major interacting proteins and suggest how they may fit into the hierarchical series of events controlling the trafficking of AMPARs and KARs.
Protein Repair and Degradation during Aging
Authors: Friguet Bertrand
Published: March 2005

Cellular aging is characterized by a build-up of oxidatively modified proteins. The steady-state level of oxidized proteins depends on the balance between the rate of protein oxidative damage and the rates of protein degradation and repair. Therefore, the accumulation of oxidized protein with age can be due to increased protein damage, decreased oxidized protein degradation and repair, or the combination of both mechanisms. The proteasomal system is the major intracellular proteolytic pathway implicated in the degradation of oxidized protein, and the peptide methionine sulfoxide reductase catalyzes the reduction of methionine sulfoxide (i.e., oxidized methionine) to methionine within proteins. A short summary on protein oxidative damage and oxidized protein degradation is given, and evidence for a decline of proteasome function with age is presented. Arguments for the implication of peptide methionine sulfoxide reductase in the age-related accumulation of oxidized protein are also discussed.
DNA Polymerase e - More Than a Polymerase
Authors: Pospiech Helmut , Syväoja Juhani E.
Published: March 2005

This paper presents a comprehensive review of the structure and function of DNA polymerase e. Together with DNA polymerases a and d, this enzyme replicates the nuclear DNA in the eukaryotic cell. During this process, DNA polymerase a lays down RNA-DNA primers that are utilized by DNA polymerases d and e for the bulk DNA synthesis. Attempts have been made to assign these two enzymes specifically to the synthesis of the leading and the lagging strand. Alternatively, the two DNA polymerases may be needed to replicate distinct regions depending on chromatin structure. Surprisingly, the essential function of DNA polymerase e does not depend on its catalytic activity, but resides in the nonenzymatic carboxy-terminal domain. This domain not only mediates the interaction of the catalytic subunit with the three smaller regulatory subunits, but also links the replication machinery to the S phase checkpoint. In addition to its role in DNA replication, DNA polymerase e fulfils roles in the DNA synthesis step of nucleotide excision and base excision repair, and has been implicated in recombinational processes in the cell.
Quality of Life Philosophy I. Quality of Life, Happiness, and Meaning in Life
Authors: Ventegodt Søren , Andersen Niels Jørgen , Merrick Joav
Published: March 2005

In the Danish Quality of Life Survey, we asked 10,000 people about their quality of life with the validated SEQOL questionnaire with more than 300 questions on their quality of life. How did they feel? How content were they with their lives? How happy were they? Did they feel their needs were fulfilled? And many more questions. We asked the questions we believed to be important for their quality of life (QOL). The results were quite surprising and forced us to recontemplate the following philosophical questions: What is quality of life, happiness, and meaning in life? What is a human being? Do we need a new biology? Is the brain the seat of consciousness? How do we seize the meaning of life and by doing so, will we become well again? What are the key concepts of quality of life? The meaning of life is connectedness and development. It is about realizing every opportunity and potential in one’s existence. The opportunities must be found and acknowledged. What do you find when you find yourself deep down? You find your real self and your purpose in life. You realize that you are already a part of a larger totality. Antonovsky called it “coherence”. Maslow called it “transcendence”. Frankl called it “meaning of life”. We call it simply “being”.To test if these philosophical questions are actually relevant for medicine, we looked at the consequences for patients being taught the quality of life philosophy. Quite surprisingly we learned from our pilot studies with “quality of life as medicine” that just by assimilating the basic concepts of the quality of life philosophy presented in this series of papers, patients felt better and saw their lives as more meaningful. The improvement of the patient’s personal philosophy of life seems to be the essence of holistic medicine, helping the patient to assume more responsibility for his or her own existence.
Quality of Life Philosophy III. Towards a New Biology: Understanding the Biological Connection between Quality of Life, Disease, and Healing
Authors: Ventegodt Soren , Andersen Niels Jørgen , Merrick Joav
Published: March 2005

This paper addresses (in a philosophical way) the complex and enigmatic interface between matter, life, and consciousness in modern medical science. The problem today in understanding living matter is not at the molecular level, but at the macro level where all molecular activities in the individual cell are coordinated, and especially at a higher level, where the activities of all the organism’s cells are coordinated. Although we understand very much of the body’s chemistry, we have only just started to get the gist of the tremendous organization of living matter. We are just beginning to acknowledge the enormous flow of information that is needed to make everything function in a healthy organism, including consciousness, where every cell does exactly what it has to do to make the organs function.A concept that seems to be able to bridge the scientifically very different domains of matter, life, and consciousness seems to be “biological information”. If a cell is seen as a liquid crystal in which the cell’s molecules constantly connect in firm mutual relationships only to dissolve again and become fluid and free, whenever the cell needs it, the backbone of the cell seems to be the information that organizes the cell. For example, in cell motion a cell is able to crawl with the help of a skeleton of fibers that can be created guided by biological information, whenever the cell needs the solidity provided by the fibers. The moment it has finished crawling or intends to crawl in another direction, these fibers will dissolve again. The fibers are made of millions of molecules that connect in an arranged pattern, and they dissolve when these molecules again let go of each other. How the cell precisely regulates such processes is today a complete mystery. How cells cocreate consciousness is also an enigma. All we can do is describe the cell and the organisms arising from its cells as filled with energy and information as well as an unbeatable ability to organize itself way down to the molecular level, where apparently the cell is in control of almost every single molecule.Our understanding today of how the information is stored and how it flows through living matter is still very limited. The source of the qualities (the qualia) characterizing the human being as a whole — like joy, love, motivation, consciousness, free will, wisdom, intuitive competence — is still practically unknown and scientifically unexplained, more than 50 years after science has turned itself towards these fundamental problems. We believe that we need a radically new biology and medicine to give the scientific explanations of the structure, dynamics, and quality of life, and of its consciousness.
Making Headway: The Roles of Hox Genes and Neural Crest Cells in Craniofacial Development
Authors: Trainor Paul A.
Published: March 2005

Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.
The Life Mission Theory IV. Theory on Child Development
Authors: Ventegodt Soren , Merrick Joav
Published: March 2005

We can identify five important needs that children have: the need for acknowledgment, acceptance, awareness or attention, respect, and care. If these needs are not met, children will modify themselves by denying central parts of their nature in order to adjust to their parents and the situation at large. When a child denies his or her talents, powers, and gender or aspects thereof, he or she loses quality of life, the ability to function, and physical or mental health. The loss of ability takes the form of diminished social ability, psychosexual potency, joy, energy, and fantasy while playing, as well as diminished ability to concentrate, focus, and learn. Many modifications result in a child with severely damaged self-confidence, self-worth, and poor performance. A child more or less deprived of self-worth cannot enjoy, give, or receive. A child deprived of emotions turns cold, rational, asocial, socially stiff, uncomfortable, and in the extreme case... intentionally “evil”. When a child denies his or her own sex, it becomes invisible, uninteresting, and vague or becomes like the opposite sex in behavior and appearance. The general holistic solution to the vast diversity of symptoms in children with low quality of life is to improve the situation for the child and give the child the holding and support he or she needs. It is very important to realize that a negative belief often has survival value to the child as it helps the child to avoid taking responsibility for problems, which really belong to the parents or other adults. Children have a fine capability for spontaneous healing, and seem to enter this process more easily than adults, given sufficient holding. The symptoms of children with poor thriving ability are often difficult to understand, as they are caused by a complex combination of self-modification in five existential dimensions. This often leads to complex medical diagnosis, giving the idea that the child is sick and without therapeutic reach, while sufficient holding could solve the problem. If holding and support of the child is not enough, the situation must be carefully analyzed to find other possible causes of poor quality of life, health, and functional ability. Education of the parent in holding is often mandatory. Most children with bad thriving ability can thus be helped by simple means.
AFM Imaging of Lipid Domains in Model Membranes
Authors: Milhiet Pierre Emmanuel , Giocondi Marie-Cecile , Le Grimellec Christian
Published: March 2005

Characterization of the two-dimensional organization of biological membranes is one of the most important issues that remains to be achieved in order to understand their structure-function relationships. According to the current view, biological membranes would be organized in in-plane functional microdomains. At least for one category of them, called rafts, the lateral segregation would be driven by lipid-lipid interactions. Basic questions like the size, the kinetics of formation, or the transbilayer organization of lipid microdomains are still a matter of debate, even in model membranes. Because of its capacity to image structures with a resolution that extends from the molecular to the microscopic level, atomic force microscopy (AFM) is a useful tool for probing the mesoscopic lateral organization of lipid mixtures. This paper reviews AFM studies on lateral lipid domains induced by lipid-lipid interactions in model membranes.
Atmospheric Chemistry and Air Pollution
Authors: Gaffney Jeffrey S. , Marley Nancy A.
Published: March 2005

Atmospheric chemistry is an important discipline for understanding air pollution and its impacts. This mini-review gives a brief history of air pollution and presents an overview of some of the basic photochemistry involved in the production of ozone and other oxidants in the atmosphere. Urban air quality issues are reviewed with a specific focus on ozone and other oxidants, primary and secondary aerosols, alternative fuels, and the potential for chlorine releases to amplify oxidant chemistry in industrial areas. Regional air pollution issues such as acid rain, long-range transport of aerosols and visibility loss, and the connections of aerosols to ozone and peroxyacetyl nitrate chemistry are examined. Finally, the potential impacts of air pollutants on the global-scale radiative balances of gases and aerosols are discussed briefly.
Migration and Enrichment of Arsenic in the Rock-Soil-Crop Plant System in Areas Covered with Black Shale, Korea
Authors: Yi Ji-Min , Chon Hyo-Taek , Park Min
Published: March 2005

The Okchon black shale, which is part of the Guryongsan Formation or the Changri Formation of Cambro-Ordovician age in Korea provides a typical example of natural geological materials enriched with potentially toxic elements such as U, V, Mo, As, Se, Cd, and Zn. In this study, the Dukpyung and the Chubu areas were selected to investigate the migration and enrichment of As and other toxic elements in soils and crop plants in areas covered with black shale. Rock and soil samples digested in 4-acid solution (HCl+HNO3+HF+HClO4) were analyzed for As and other heavy metals by ICP-AES and ICP-MS, and plant samples by INAA. Mean concentration of As in Okchon black shale is higher than those of both world average values of shale and black shale. Especially high concentration of 23.2 mg As kg-1is found in black shale from the Dukpyung area. Mean concentration of As is highly elevated in agricultural soils from the Dukpyung (28.2 mg kg-1) and the Chubu areas (32.6 mg kg-1). As is highly elevated in rice leaves from the Dukpyung (1.14 mg kg-1) and the Chubu areas (1.35 mg kg-1). The biological absorption coefficient (BAC) of As in plant species decreases in the order of rice leaves > corn leaves > red pepper = soybean leaves = sesame leaves > corn stalks > corn grains. This indicates that leafy plants tend to accumulate As from soil to a greater degree than cereal products such as grains.
Creative Problem Solving and Social Cooperation of Effective Physical Therapy Practice: A Pioneer Study and Overview
Authors: Carmeli Eli
Published: March 2005

Action research (AR) has an important role to play in educating physical therapists. Increasing efforts should be encouraged to instigate AR programs in physical therapy practice and clinical education. Such programs commonly require considerable effort and understanding by clinical instructors, and require adoption of new educational methods. AR programs can lead physical therapists and clinicians to be more questioning and reflective in evaluating practical questions regarding patient therapy and education. The purpose of this article is to educate the readers on the importance of AR and to provide a few relevant references on that topic. A specific study is described in this paper in which physical therapy clinical instructors participated in a structured workshop designed to demonstrate the values of AR and how such values can be incorporated in teaching their students. AR can lead to improved therapist-patient interaction and help solve specific practical problems arising during therapy sessions.
Validation of Two Global and Generic Quality of Life Questionnaires for Population Screening: SCREENQOL and SEQOL
Authors: Ventegodt Soren , Henneberg Eskild W. , Merrick Joav , Lindholt Jes S.
Published: March 2005

Population screening may harm quality of life (QoL), and traditional health-related QoL tools could be inadequate to evaluate this risk. Two global and generic QoL instruments were developed for studying the QoL consequences of screening (SCREENQOL), and QoL variation in a normal population (SEQOL). SCREENQOL and SEQOL (Self-Evaluation of Quality of Life Questionnaire) are self-administered questionnaires with items rated on 5-point Likert scales. SCREENQOL consists of 21 items measuring QoL across 6 different dimensions based upon validated QoL questionnaires. SEQOL consists of 317 items measuring QoL across 8 different dimensions, based on an integrative theory of QoL, a theoretical framework from a Danish QoL survey involving 7,222 persons 31 to 33 years old. For further validation, SEQOL and SCREENQOL were sent to 2,460 persons 18 to 88 years old randomly selected from the Danish Central Person Register together with Nottingham Health Profile (NHP) and Sickness Impact Profile (SIP). For SCREENQOL and SEQOL, test-retest reliability correlation was both >0.8, Cronbach�s alpha was 0.65 and 0.75, correlation (r) to NHP was 0.67 and 0.49, to SIP 0.46 and 0.27, respectively (p
Are There Mutator Polymerases?
Authors: Garcia-Diaz Miguel , Ruiz Jose F. , Juarez Raquel , Terrados Gloria , Blanco Luis
Published: March 2005

DNA polymerases are involved in different cellular events, including genome replication and DNA repair. In the last few years, a large number of novel DNA polymerases have been discovered, and the biochemical analysis of their properties has revealed a long list of intriguing features. Some of these polymerases have a very low fidelity and have been suggested to play mutator roles in different processes, like translesion synthesis or somatic hypermutation. The current view of these processes is reviewed, and the current understanding of DNA polymerases and their role as mutator enzymes is discussed.
Treatment of Bulbar Urethral Strictures. A Review, with Personal Critical Remarks
Authors: Oosterlinck Willem
Published: March 2005

This is a review article on treatment of bulbar urethral strictures with personal critical remarks on newer developments. As a treatment of first intention there exists 4 options : dilatation, urethrotomy, end to end anastomosis and free graft, open urethroplasty. Success rate of dilatation and visual urethrotomy after 4 years is only 20 en 40 % respectively. Laser urethrotomy could not fulfill expectations. End to end anastomosis obtains a very high success rate but is only applicable for short strictures. Free graft urethroplasty obtains success rates of ± 80 %. There is considerable debate on the best material for grafting. Buccal mucosa graft is the new wave, but this is not based on scientific data. Whether this graft should be used dorsally or ventrally is also a point of discussion. In view of the good results published with both techniques it is probably of no importance. Intraluminal stents are not indicated for complicated cases and give only good results in those cases which can easily be treated with other techniques. Metal self-retaining urethral stent , resorbable stents and endoscopic urethroplasty is briefly discussed. Redo’s and complicated urethral strictures need often other solutions. Here skin flap from the penile skin and scrotal flap can be used. Advantages and drawbracks of both are discussed. There is still a place for two-stage procedures in complicated redo�s. The two-stage mesh-graft urethroplasty offers advantage over the use of scrotal skin. Some other rare techniques like substitution with bowel and pudendal thigh flap, to cover deep defects, are also discussed.
Combining the Performance Strengths of the Logistic Regression and Neural Network Models: A Medical Outcomes Approach
Authors: Wong Wun , Fos Peter J. , Petry Frederick E.
Published: March 2005

The assessment of medical outcomes is important in the effort to contain costs, streamline patient management, and codify medical practices. As such, it is necessary to develop predictive models that will make accurate predictions of these outcomes. The neural network methodology has often been shown to perform as well, if not better, than the logistic regression methodology in terms of sample predictive performance. However, the logistic regression method is capable of providing an explanation regarding the relationship(s) between variables. This explanation is often crucial to understanding the clinical underpinnings of the disease process. Given the respective strengths of the methodologies in question, the combined use of a statistical (i.e., logistic regression) and machine learning (i.e., neural network) technology in the classification of medical outcomes is warranted under appropriate conditions. The study discusses these conditions and describes an approach for combining the strengths of the models.
A Retrospective Review of Thiazolidinediones with Development of a Troglitazone Conversion Protocol
Authors: Lindsey Cameron , Graham Maqual , McMurphy Julie
Published: March 2005

The objective of this paper was (1) to assess compliance with the National Veterans Affairs Guidelines for the use of troglitazone and rosiglitazone and (2) to develop and implement a conversion protocol that allows effective management of patients receiving troglitazone. A retrospective chart review was conducted to assess adherence to guidelines for all patients receiving troglitazone and rosiglitazone at the medical center. Appropriateness of therapy through indication evaluation, safety through alanine aminotransferase (ALT) monitoring compliance, and efficacy through hemoglobin A1c(HbA1c) changes were used to assess adherence. According to National Veterans Affairs (VA) Guidelines, 68% of troglitazone and 63% of rosiglitazone patients had an appropriate indication for the use of these agents. Baseline ALT levels were obtained in 40% of troglitazone and 71% of rosiglitazone patients. Full compliance with continual ALT monitoring was seen in 6 and 54% of patients, respectively. Goal HbA1cwas achieved in 57 and 29% of patients, respectively. Of the 33 patients receiving troglitazone, 19 were converted to rosiglitazone therapy; 11 were maintained on current regimens without troglitazone, and 3 were lost to follow up. Adherence to guidelines needs to be reinforced, in particular, compliance with ALT monitoring. However, there were no reported cases of hepatotoxicity in the patients reviewed. Many patients did not achieve a HbA1c
Genetics of Early-Onset Alzheimer Dementia
Authors: Rademakers Rosa , Cruts Marc , Van Broeckhoven Christine
Published: March 2005

Alzheimer�s dementia (AD) is the most common degenerative disorder of the central nervous system. Although the onset of dementia is above 65 years of age in the majority of the patients (late-onset AD, LOAD), a small subgroup of patients develops AD before 65 years of age (early-onset AD, EOAD). To date 3 genes responsible for EOAD have been identified: the amyloid precursor protein gene (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). PSEN1 is the most frequently mutated EOAD gene with a mutation frequency of 18 to 50% in autosomal dominant EOAD. In addition, the e4 allele of the gene encoding apolipoprotein E (APOE) was identified as a risk factor for both LOAD and EOAD. Many studies reported other susceptibility genes, but the APOE?4 alelle has been the only risk factor that was consistently replicated in all AD populations. Extensive cell biology research in the past ten years led to the hypothesis that the 4 EOAD genes lead to AD through a common biological pathway resulting in abnormal APP processing by subtle different mechanisms. Now, transgenic mice are produced to study the influence of EOAD mutations in vivo, eventually leading to the development of novel therapeutic strategies.
Planning and Representing Intentional Action
Authors: Hommel Bernhard
Published: March 2005

This paper reviews recent approaches to human action planning and the cognitive representation of intentional actions. Evidence suggests that action planning takes place in terms of anticipated features of the intended goal, that is, in terms of action effects. These effects are acquired from early infancy on by registering contingencies between movements and perceptual movement outcomes. Co-occurrence of movements and effects leads to the creation of bidirectional associations between the underlying internal codes, thus establishing distributed perception-action networks subserving both perceiving external events and intentionally producing them. Action plans determine only the general, goal-relevant features of intended actions, while the fine-tuning is left to on-line sensory-motor processing. Action plans emerge from competition for action control between several factors: overlearned habits, perceptual events, and emotional influences, among others. Accordingly, action control represents a balance between personal intentions and wishes on the one hand and environmental affordances and demands on the other.
Molecular Mechanics Study of the Cyclic and Unsymmetric Diborane(4) Compounds
Authors: Rendtorff N. , Castro E. A.
Published: March 2005

The results of a theoretical study on the structure of some diborane(4) compounds are presented in order to analyze the issue related to the relative stabilities of the 1,1- vs. 1,2-isomers. Through the employment of the molecular mechanics method, characteristic distances and angles are given and they are compared with available experimental data. In order to rationalize the results, the different energy components are discussed in a comparative fashion. We find a rather satisfactory agreement between theoretical and experimental data. Some possible future extensions are pointed out to complement this sort of analysis.
Homicides and Suicides by Mentally Ill People
Authors: Shahtahmasebi Said
Published: March 2005

In 1992, following consultations with the Royal College of Psychiatrists, the confidential inquiry into homicides and suicides by mentally ill people was set up by the United Kingdom Department of Health. The inquiry collects detailed information on contact with secondary mental health services by means of a questionnaire from clinical audit or information departments from these organisations. In Leeds, however, a wider range of available records including Coroner Reports, police, social, educational, and all health records were consulted. This resulted in a series of health/life event histories of suicide cases that had been in contact with psychiatric services. This paper presents an exploratory analysis of these data. The Leeds suicide cases formed less than one-third of all suicide cases in Leeds; the remainder had not come into contact with psychiatric services. This proportion is consistent with the U.K. national figures. Records show that 46% of the sample's first contact with the psychiatric services was through a first failed attempted suicide. Other results include the role of prescribed drugs in repeat suicide attempts, education levels, and employment stability. It is concluded that the link between mental illness and suicide is questionable. Life event history type data on all suicide cases is desperately required to study suicide as a social process.
Interactions of LC8 with N-Terminal Segments of the Intermediate Chain of Cytoplasmic Dynein
Authors: Nyarko Afua , Hare Michael , Makokha Moses , Barbar Elisar
Published: March 2005

LC8, a highly conserved 10-kDa light chain, and IC74, a 74-kDa intermediate chain, are presumed to promote the assembly of the cytoplasmic dynein motor protein complex and to be engaged in the controlled binding and release of cargo. The interactions of LC8 from Drosophila melanogaster with constructs of IC74 were characterized in vitro by affinity methods, limited proteolysis, and circular dichroism spectroscopy. Previously, we have performed limited proteolysis on the N-terminal domain of IC74, IC(1-289), when free and when bound to dynein light chains LC8 and Tctex-1[1]. We have also shown that upon addition of LC8, IC(1-289) undergoes a significant conformational change from a largely unfolded to a more ordered structure. The purpose of the work presented here is to determine whether residues 1-30 in IC74, predicted to be in a coiled coil, are involved in the stabilization of the protein upon binding to LC8. Constructs of IC74, IC(1-143), and IC(30-143) that include the LC8 binding site but with and without the first 30 residues were prepared, and their binding and protection patterns were compared to our previous results for IC(1-289). The results suggest that coiled coil residues 1-30 are not responsible for the increase in structure we observe when IC(1-289) binds to LC8.
Adenosine, Energy Metabolism, and Sleep
Authors: Porkka-Heiskanen Tarja , Kalinchuk Anna , Alanko Lauri , Urrila Anna , Stenberg Dag
Published: March 2005

While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness. The key molecule in the induction of sleep appears to be adenosine, which induces sleep locally in the basal forebrain.
Measurement of Quality of Life I. A Methodological Framework
Authors: Ventegodt Soren , Hilden Jorgen , Merrick Joav
Published: March 2005

Despite the widespread acceptance of quality of life (QOL) as the ideal guideline in healthcare and clinical research, serious conceptual and methodological problems continue to plague this area. In an attempt to remedy this situation, we propose seven criteria that a quality-of-life concept must meet to provide a sound basis for investigation by questionnaire. The seven criteria or desiderata are: (1) an explicit definition of quality of life; (2) a coherent philosophy of human life from which the definition is derived; (3) a theory that operationalizes the philosophy by specifying unambiguous, nonoverlapping, and jointly exhaustive questionnaire items; (4) response alternatives that permit a fraction-scale interpretation; (5) technical checks of reproducibility; (6) meaningfulness to investigators, respondents, and users; and (7) an overall aesthetic appeal of the questionnaire. These criteria have guided the design of a validated 5-item generic, global quality-of-life questionnaire (QOL5), and a validated 317-item generic, global quality-of-life questionnaire (SEQOL), administered to a well-documented birth cohort of 7,400 Danes born in 1959�1961, as well as to a reference sample of 2,500 Danes. Presented in outline, the underlying integrative quality-of-life (IQOL) theory is a meta-theory. To illustrate the seven criteria at work, we show the extent to which they are satisfied by one of the eight component theories. Next, two sample results of our investigation are presented: satisfaction with one's sex life has the expected covariation with one's quality of life, and so does mother's smoking during pregnancy, albeit to a much smaller extent. It is concluded that the methodological framework presented has proved helpful in designing a questionnaire that is capable of yielding acceptably valid and reliable measurements of global and generic quality of life.
Measurement of Quality of Life II. From the Philosophy of Life to Science
Authors: Ventegodt Soren , Merrick Joav , Andersen Niels Jorgen
Published: March 2005

We believe it should be possible to make operational the philosophical ideas of the good life in order to make it the object of scientific research. The Quality of Life Research Center in Copenhagen, Denmark has therefore spent the last several years with these questions and tried to find practical and evidence-based scientific solutions.This paper describes the theoretical road taken in moving from the abstract philosophy of life to the actual questionnaire. It presents an important aspect of our work with the quality-of-life (QOL) concept though the last decade. We have developed the quality-of-life philosophy; the SEQOL, QOL5, and QOL1 questionnaires; the quality-of-life theory; and the quality-of-life research methodology. We carried out quality-of-life population surveys and developed techniques for improving quality of life with the chronically sick patient. This paper presents the struggle to create a rating scale for the generic measurement of the global quality of life, based on quality-of-life theory, derived from quality-of-life philosophy. The developed rating scale is a ratio scale combining a Likert scale, a visual analogue scale, and a numerical scale, to a reduced combination scale. This allows for the extraction of as much information from the respondents as possible without exhausting them unduly or demanding more than can be reasonably expected.