bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Secondary to Acquired Disease to the Pancreas
Authors: Prato Stefano Del , Coppelli Alberto , Tiengo Antonio
Published: March 2004

Secondary diabetes is a condition of hyperglycemia which develops after the destruction of the pancreatic tissue by an acquired disease with subsequent impairment of exocrine and endocrine pancreatic functions. In general, any pathologic process of the pancreatic acinar tissue may results in an insult to its endocrine component, leading to some degree of hormone insufficiency. This condition was first described in 1788 by Sir Thomas Cawley, but it was soon appreciated that hyperglycemia can ensues acute and chronic pancreatitis, partial and total pancreatectomy, neoplasia as well as systemic processes involving the pancreas, such as hemochromatosis and cystic fibrosis. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association has identified these forms of diabetes as “diabetes secondary to diseases of the exocrine pancreas.” The new diagnostic criteria for diabetes introduced by the ADA and WHO Expert Committees are likely to influence the prevalence of diabetes in patients with diseases of the exocrine pancreas, but direct assessment using the new criteria is still too scanty. When the 1979 NDDG and 1985 WHO criteria are used, it can be calculated that diabetes secondary to disease of the exocrine pancreas represents, approximately, 0.5% of all cases of diabetes mellitus. Its frequency is likely to be twice as high in populations with heavy alcohol consumption. In the tropics, the prevalence of diabetes secondary to fibrocalculous pancreatitis can be as high as 10–20%. At variance with the selective B‐cell destruction occurring in type 1 diabetes, pancreatic diabetes is characterized by concomitant destruction of all endocrine cells of the islet of Langherans. The dual insulin–glucagon deficit is responsible for many of the metabolic and clinical manifestation of this form of diabetes, including lower risk for ketoacidosis and more frequent and severe hypoglycemic episodes. Since the late 1950s, the general idea has been that secondary diabetes was not associated with vascular complications. However, with the improved life expectancy of these patients during the past few years, a similar prevalence of retinopathy and microalbuminuria has been described in pancreatic and type 1 diabetes mellitus. The knowledge of the hormonal, metabolic, and clinical features of these forms of diabetes is essential in defining the most appropriate therapeutic strategies.
Dietary Management of Diabetes Mellitus in Europe and North America
Authors: Mann J.I. , Lewis-Barned N.J.
Published: March 2004

The Japanese diet is widely known to be a healthy one, with a low risk for causing cardiovascular disease. Historically rooted, Japanese gastronomic culture is unique, and includes a wide variety of foodstuffs, original flavoring recipes, and fermentation methods. A distinctive Food Guide Pyramid for Japanese people and a meal log chart, evaluating eight major treatment assessments, have been created to aid dietary guidance. The results are represented diagrammatically in this chapter, with each of the treatment assessments being scored. Straightforward to understand, this guidance is stress‐free for the patient and helps ensure that the patient follows the appropriate dietary regimen.

Since diabetes treatment not only involves blood glucose level monitoring, but also the evaluation of the disease's complications course, the treatment assessments are made on a 3–6‐months timeframe. The case study results indicate that the dietary guidance based on the Food Guide Pyramid is useful and beneficial for treatment of the disease.
Dietary Management of Diabetes Mellitus in Sub‐Saharan Africa
Authors: Steyn Nelia P. , Levitt Naomi S.
Published: March 2004

This chapter provides information about prevailing dietary practices in sub‐Saharan Africa as a background to published data on the dietary management of diabetes in the region. It highlights the finding that there is a paucity of practical and culturally relevant guidelines for people with diabetes. Recommendations in this regard are usually based on those emanating from Europe and the USA that are reliant upon interpretation by a dietitian; however, there are few dietitians in the region. Furthermore, other health workers who have not received nutrition training give the majority of dietary information. The chapter describes the available published data on dietary knowledge and practices for people with diabetes in the region and provides some examples of relevant and affordable meal plans as well as practical advice for health professionals. Suggestions are also given for overcoming some of the health systems barriers currently preventing dietary management from achieving its potential.
Sulfonylureas: Basic Aspects and Clinical Uses
Authors: Lebovitz H.E. , Melander A.
Published: March 2004

This chapter describes the chemistry, mechanism of action, pharmacodynamics, pharmacokinetics, kinetics–effect relations, clinically beneficial and adverse effects of sulfonylurea drugs, as well as the efficacy of these agents in randomized‐controlled clinical trials and other studies. It also compares the different sulfonylurea compounds, especially in terms of differences in potency, rate of onset, and duration of action, and how such differences may contribute to different clinical profiles of the various compounds. In addition, some important interactions with other drugs are listed. Their appropriate place in the therapeutic armamentarium concerning type 2 diabetes is thoroughly discussed.
Metformin and Other Biguanides: Pharmacology and Therapeutic Usage
Authors: Garber Alan J.
Published: March 2004

The role of biguanides in the treatment of type 2 diabetes has evolved along with the understanding of the disease pathogenesis and its associated complications. Metformin is a valuable agent for the treatment of type 2 diabetes, and its ability to improve insulin sensitivity allows for broader use (i.e. insulin‐resistant prediabetic states). The efficacy of metformin in improving glycemic control is similar to that of sulfonylureas or insulin. Additionally, metformin has been shown to reduce macrovascular complications of type 2 diabetes in overweight patients; and it improves serum lipoprotein parameters, reduces body weight, and stimulates fibrinolysis. Metformin can be administered with insulin and other oral antihyperglycemic agents. Reformulation of the drug in an extended‐release form and in combination tablets (glyburide/metformin, glipizide/metformin, or rosiglitazone/metformin) allows for simplified dosage regimens, which may enhance patient adherence.
Thiazolidinediones as PPAR Agonists
Authors: Mudaliar Sunder , Henry Robert R.
Published: March 2004

Type 2 diabetes has now reached epidemic proportions across the world and is the cause of substantial morbidity and mortality. It is now well established that intensive control of blood glucose can significantly reduce and ameliorate the microvascular complications of retinopathy, nephropathy, and neuropathy. Unfortunately however, nearly 80% of type 2 diabetic patients die from macrovascular cardiovascular disease. This increased incidence of atherosclerotic disease is intricately associated with insulin resistance, which is a major pathophysiologic abnormality in type 2 diabetes. There is strong evidence that insulin resistance is intricately involved in the development of not only hyperglycemia, but also dyslipidemia, hypertension, hypercoagulation, vasculopathy, and ultimately atherosclerotic cardiovascular disease. This cluster of metabolic abnormalities has been termed the “insulin resistance or metabolic syndrome.” The thiazolidinediones (rosiglitazone and pioglitazone) constitute a new class of oral antidiabetic agents which are “insulin sensitizers” and exert direct effects on the mechanisms of insulin resistance. Through their PPAR‐γ agonist effects, the thiazolidinediones not only improve insulin sensitivity and glycemic control with reduced insulin requirements, but also have potentially favorable effects on other components of the metabolic syndrome. These beneficial effects on lipid metabolism, vascular tone, and endothelial function might directly and indirectly influence cardiovascular risk by favorably altering several proatherogenic metabolic processes. Long‐term studies are needed to determine whether the insulin‐sensitizing effects of the thiazolidinediones have the potential to prevent or delay the development of type 2 diabetes as well as premature atherosclerotic cardiovascular disease, morbidity, and death.
Difficult Diabetes
Authors: Saunders Simon A. , Williams Gareth
Published: March 2004

Diabetes can be a very difficult disease to manage. This is particularly true when confronted with a patient who attends with recurrent episodes of hypoglycemia, diabetic ketoacidosis, or mixed glycemic instability. This chapter aims to explain the common causes of such presentations, and the suitable investigations to identify a treatable cause. Further to this, if a diagnosis cannot be reached and the problems still persist, the chapter then discusses the diagnosis and management of “brittle diabetes.” This complex and often misunderstood disease affects only a very small minority of patients with type 1 diabetes but requires a considered and careful approach to its diagnosis and treatment. Such issues are discussed within this chapter.
The Care of the Diabetic Patient During Surgery
Authors: Gill G.V. , Alberti K.G.M.M.
Published: March 2004

Most diabetic patients will require surgery at some time in their lives, and this presents problems for glycemic control. Surgery involves a period of starvation, and also the metabolic response to trauma includes counterregulatory hormone hypersecretion (e.g., adrenaline, cortisol, etc.), which opposes insulin action. The major factor influencing the management of diabetes during surgery is assessment of the patient's insulin reserves. Thus, those on insulin treatment (whether they are true type 1, or insulin‐treated type 2 patients) should be assumed to have little or no endogenous insulin reserves, and a system of continuous insulin and glucose delivery is necessary. Those not on insulin, however, clearly have their own insulin reserves and, provided they have reasonable preoperative glycemic control, for all but major surgery simple glycemic observation is usually all that is needed. Delivery of insulin and glucose may be by “separate lines” (intravenous (IV) glucose infusion with a separate IV insulin pump), or by a combined glucose–potassium–insulin infusion. The latter is easier to manage on lower‐staffed general wards, and the former is particularly flexible and suitable for critical care situations with more metabolically unstable patients and higher levels of staffing. Whichever system is used, patients must have regular blood glucose and plasma electrolyte monitoring, with appropriate insulin adjustments to maintain good glycemic control. With good preoperative control and assessment, and well organized and appropriate perioperative management, the risks of surgery in diabetic patients should in most cases be similar to nondiabetic rates.
Dinosaurier‐Skelette als Kriegsziel: Kulturgutraubplanungen, Besatzungspolitik und die deutsche Paläontologie in Belgien im Ersten Weltkrieg
Authors: Roolf Christoph
Published: March 2004

The paper deals with the unnoticed and sweeping activities of German scientists and university disciplines in the context of German occupation policy and plannings of plundering cultural assets as war pillage during the First World War. It exemplarily shows the case of palaeontologists in occupied Belgium: Their main project was the famous excavation site of skeletons of the dinosaur Iguanodon in the small town Bernissart. After a new excavation between 1915 and 1918 they planned, with the support of occupation authorities, the transportation of dinosaur skeletons into German natural history museums and collections as war pillage.
Disziplinbildung und Vorlesungsalltag, Funktionen von Lehrbüchern der Physik um 1800 mit einem Fokus auf die Universität Jena
Authors: Frercks Jan
Published: March 2004

Physics textbooks from ca 1800 are on the one hand self reflective texts that consider the then emerging discipline ‚physics’︁, and serve on the other hand as the bread and butter for the day to day work of teachers and students of physics. The two parts of this paper explore this twofold nature. First, those textbooks written and used by professors in Jena, Halle and Göttingen are used in order to identify a typical textbook. This relies on a close examination of the respective introductory chapter and the one on electricity. The result is used in the second part to provide the background for the reconstruction of the use of physics textbooks in Jena. It is shown when and, as far as possible, why each particular textbook was chosen, withdrawn, neglected, changed or written in the course of physics teaching from 1780 to 1820. Some conclusions are drawn with regard to Jena's position in physics at that time.
Karl der Große, Alkuin und die Zeitrechnung
Authors: Springsfeld Kerstin
Published: March 2004

In connection with the Carolingian renewal of education Charlemagne also cared for a homogeneous reckoning of time. He organized the Carolingian reform of the calender with the help of Alkuin of York, an Anglo‐Saxon scholar. Having heard of Alkuin's learning and teaching abilities, the Frankish King invited him to lead his Palace school at Aachen. Moving to Francia 782, Alkuin became the key counselour of Charlemagne for science, education and church matters.

Among other subjects Alkuin taught the King especially calendrical reckoning (computus) and astronomy, in which he took a special personal interest. Charlemagne discussed these subjects often with Alkuin, sometimes even in letters, still preserved today. For this correspondence on astronomy and calendrical reckoning it was assumed that Alkuin was the author of four short anonymous writings on computus. Moreover, Charlemagne comissioned Alkuin to write a standard work on computus, which is lost today. But three Carolingian manuals on computus survived.

Which of the four anonymous writings really stem from Alkuin himself? What influence he had upon the manuals? These two questions are investigated here on the basis of the most important matter of computus: the calculation of the age of the moon in the 19‐year lunar cycle, necessary for dating the movable feast of Easter (on the first Sunday after the first full moon in spring). These facts were discussed in detail, even vehemently, in the correspondence between Alkuin and Charlemagne.
Collaborative energy partnerships in relation to development of core business focus and competence – a study of Swedish pulp and paper companies and energy service companies
Authors: Möllersten Kenneth , Sandberg Peter
Published: March 2004

Several aspects of the growing market for energy‐related collaboration between pulp and paper industries (PPIs) and energy service companies (ESCOs) in Sweden were investigated through in‐depth interviews with PPI and ESCO managers. Aspects of concern are the different forms of co‐operation established, the managers' views on the recent changes made regarding competence and business focus, the managers' views on the opportunities and risks with energy related co‐operation and the implications for sustainable industrial energy management. The study shows that there is a mutual belief among PPI and ESCO managers that co‐operation can provide opportunities for improved competitiveness through a more rational distribution of competences between companies. The main two barriers against the utilization of this potential are that ESCOs must prove that they can bring added values other than capital to pulp and paper mills, and the lack of competition between external energy service providers. Furthermore, we argue that adding aspects related to competence and inter‐firm partnering can improve the existing theory surrounding barriers and opportunities for sustainable industrial energy management in manufacturing industries. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Promoting effective working with parents with learning disabilities
Authors: James Helen
Published: March 2004

The children of parents with learning disabilities are increasingly coming to the attention of child protection and children in need services. The current framework within which services are delivered identiﬁes the need to work cooperatively both across agencies and with parents themselves. The decisions taken by practitioners in the course of their assessment and support work should be inﬂuenced by a recognition of where the risks to this group of children lie and which factors are most likely to be associated with positive outcomes. This paper outlines risks to children associated with the parents' difﬁculty in accessing appropriate antenatal care and the risk of developmental delay arising from both genetic and environmental inﬂuences. This group of children are also more likely to experience behaviour problems and language delay. Research has indicated a risk of neglect, but abuse, where it does occur, is more likely to be associated with partners or relatives. It is also clear that some children are more at risk than others, and intellectually able children, as well as those with high levels of dependency, may be the most vulnerable. Risks can be reduced when parents have access to good family and social support networks and professional support which is acceptable to them. Maintaining a small family size can also be helpful. If parents have had positive childhood emotional experiences, their chances of successful parenting are increased. Copyright © 2004 John Wiley & Sons, Ltd.
Parenting capacity
Authors: Donald Terry , Jureidini Jon
Published: March 2004

We describe an approach to the assessment of parenting for families in which child abuse has been established to have occurred. Neither the category of abuse nor its physical severity adequately predicts the future wellbeing or safety of an abused child. The critical variable in determining the child's future is the level of disturbance in parenting. We argue against the most common approach to assessments of parenting, which is to generate a non‐hierarchical list of issues with the emphasis on relatively concrete and readily measurable dimensions such as social support, parental knowledge about parenting and the child's developmental status. We enhance the standard approach to assessment by organizing it around parenting capacity. We do not attempt to operationalize parenting capacity, deﬁning it as the parents' ability to empathically understand and give priority to their child's needs. Adequate parenting requires that the parents be able to meet the challenges posed by their particular child's temperament and development (which may be shaped by the abusive experience) and also to accept and be prepared to address their own intrinsic characteristics which impede their parenting capacity. Parenting capacity is more difﬁcult to assess than the more concrete and commonly measured aspects of parenting, but we argue that its assessment should be central to child protection management decisions. Copyright © 2004 John Wiley & Sons, Ltd.
Parental substance misuse and child care social work: research in a city social work department in England
Authors: Hayden Carol
Published: March 2004

This research set out to establish evidence about the scale and impact of and response to parental substance misuse in child care social work teams in a city social services department in England. The article draws on some aspects of the data collected in the research, which includes: a snapshot survey of all child care social work caseloads in the city; group interviews with practitioners and parents in recovery; individual interviews with parents using a pilot project that focused on parental substance misuse. The research provides evidence of parental substance misuse as a key factor that needs greater consideration within child care social work assessments and as an issue to target in developing preventative responses to child welfare concerns. Child care social workers are shown to need specialist support in undertaking this task to best effect. Copyright © 2004 John Wiley & Sons, Ltd.
Cognitive behavioural psychotherapy intervention in childhood sexual abuse: identifying new directions from the literature
Authors: Ross Gill , O'Carroll Pierce
Published: March 2004

The short‐ and long‐term consequences of childhood sexual abuse have been extensively reported. However, for many years there has been an absence of psychological conceptual frameworks for understanding and treating abuse trauma symptoms. This paper reviews a number of outcome studies for the treatment of child sexual abuse where a post‐traumatic stress disorder (PTSD) conceptualization was used to plan treatment interventions. The paper concludes that, contrary to some concerns expressed by clinicians, sexually abused children and their non‐abusing carers can signiﬁcantly beneﬁt from cognitive behavioural interventions which use reliving and confrontation of the abusive experience. Notwithstanding this, there is a need for further controlled outcome research of cognitive behavioural interventions using reliving techniques to explore how and why these interventions help in reducing abuse‐related PTSD symptoms. Copyright © 2004 John Wiley & Sons, Ltd.
The truth and lie story: developing a tool for assessing child witnesses' ability to differentiate between truth and lies
Authors: McCarron Anna Louise , Ridgway Sue , Williams Anne
Published: March 2004

Within the court arena, the credibility and competency of child witnesses often comes under scrutiny and the decision whether a child is considered to be credible or not strongly inﬂuences whether their evidence will be heard by the court. A child's ability to demonstrate that they understand the difference between truth and lies and the importance of telling the truth is synonymous with competency. Research suggests that many professionals undertaking the task of establishing competency ﬁnd it very difﬁcult, especially with younger children (Aldridge and Wood, 1997, cited in Aldridge and Wood, 1998). This paper describes the process involved in developing an innovative tool for helping professionals assess whether a child understands the difference between truth and lies. The development of the tool arose from the concerns of ofﬁcers from Northumbria Police Force (in the UK) relating to interviews following the protocol of the government's Memorandum of Good Practice (Home Ofﬁce and Department of Health, 1992) on interviewing child witnesses, and the need to establish whether child witnesses can differentiate between truth and lies. As an example of good practice, The Truth and Lie Story described here has now been included in the Home Ofﬁce (2002) guidance Achieving Best Evidence in Criminal Proceedings, which is a revision of the 1992 Memorandum of Good Practice. Copyright © 2004 John Wiley & Sons, Ltd.
The PlaNet consortium: a network of European plant databases connecting plant genome data in an integrated biological knowledge resource
Authors: Schoof H. , Ernst R. , Mayer K. F. X.
Published: March 2004

The completion of the Arabidopsis genome and the large collections of other plant sequences generated in recent years have sparked extensive functional genomics efforts. However, the utilization of this data is inefficient, as data sources are distributed and heterogeneous and efforts at data integration are lagging behind. PlaNet aims to overcome the limitations of individual efforts as well as the limitations of heterogeneous, independent data collections. PlaNet is a distributed effort among European bioinformatics groups and plant molecular biologists to establish a comprehensive integrated database in a collaborative network. Objectives are the implementation of infrastructure and data sources to capture plant genomic information into a comprehensive, integrated platform. This will facilitate the systematic exploration of Arabidopsis and other plants. New methods for data exchange, database integration and access are being developed to create a highly integrated, federated data resource for research. The connection between the individual resources is realized with BioMOBY. BioMOBY provides an architecture for the discovery and distribution of biological data through web services. While knowledge is centralized, data is maintained at its primary source without a need for warehousing. To standardize nomenclature and data representation, ontologies and generic data models are defined in interaction with the relevant communities. Minimal data models should make it simple to allow broad integration, while inheritance allows detail and depth to be added to more complex data objects without losing integration. To allow expert annotation and keep databases curated, local and remote annotation interfaces are provided. Easy and direct access to all data is key to the project. Copyright © 2004 John Wiley & Sons, Ltd.
From databases to modelling of functional pathways
Authors: Nasi Sergio
Published: March 2004

This short review comments on current informatics resources and methodologies in the study of functional pathways in cell biology. It highlights recent achievements in unveiling the structural design of protein and gene networks and discusses current approaches to model and simulate the dynamics of regulatory pathways in the cell. Copyright © 2004 John Wiley & Sons, Ltd.
Interoperability of CABRI services and biochemical pathways databases
Authors: Romano Paolo , Aresu Ottavia , Assunta Manniello Maria , Parodi Barbara
Published: March 2004

Common Access to Biological Resources and Information (CABRI) service is a ‘one‐stop‐shop’ for materials that are collected by a number of European culture collections that engage themselves in a quality service for the scientific community by adhering to Quality Guidelines for the management of resources and related information. It includes collections' catalogues that can be searched in an SRS implementation. A simple search facility, including a synonym search and a shopping cart, is also available. Within the European Biological Resource Centres Network (EBRCN) project, an extension and improvement of the catalogues' information is under way. This includes adding links to bibliographic databanks and sequence databases. Revision of ‘in‐house’ controlled vocabularies used by data annotators is under way, in order to improve the setting up of external links, and new links to biochemical pathways databases are being set up for some of the catalogues. Copyright © 2004 John Wiley & Sons, Ltd.
Interactome data and databases: different types of protein interaction
Authors: De Las Rivas Javier , de Luis Alberto
Published: March 2004

In recent years, the biomolecular sciences have been driven forward by overwhelming advances in new biotechnological high‐throughput experimental methods and bioinformatic genome‐wide computational methods. Such breakthroughs are producing huge amounts of new data that need to be carefully analysed to obtain correct and useful scientific knowledge. One of the fields where this advance has become more intense is the study of the network of ‘protein–protein interactions’, i.e. the ‘interactome’. In this short review we comment on the main data and databases produced in this field in last 5 years. We also present a rationalized scheme of biological definitions that will be useful for a better understanding and interpretation of ‘what a protein–protein interaction is’ and ‘which types of protein–protein interactions are found in a living cell’. Finally, we comment on some assignments of interactome data to defined types of protein interaction and we present a new bioinformatic tool called APIN (Agile Protein Interaction Network browser), which is in development and will be applied to browsing protein interaction databases. Copyright © 2004 John Wiley & Sons, Ltd.
Looking for cancer clues in publicly accessible databases
Authors: Medjahed Djamel , Lemkin Peter F. , Smythers Gary W. , Munroe David J.
Published: March 2004

What started out as a mere attempt to tentatively identify proteins in experimental cancer‐related 2D‐PAGE maps developed into VIRTUAL2D, a web‐accessible repository for theoretical pI/MW charts for 92 organisms. Using publicly available expression data, we developed a collection of tissue‐specific plots based on differential gene expression between normal and diseased states. We use this comparative cancer proteomics knowledge base, known as the tissue molecular anatomy project (TMAP), to uncover threads of cancer markers common to several types of cancer and to relate this information to established biological pathways. Copyright © 2004 John Wiley & Sons, Ltd.
Shaping biological knowledge: applications in proteomics
Authors: Lisacek F. , Chichester C. , Gonnet P. , Jaillet O. , Kappus S. , Nikitin F. , Roland P. , Rossier G. , Truong L. , Appel R.
Published: March 2004

The central dogma of molecular biology has provided a meaningful principle for data integration in the field of genomics. In this context, integration reflects the known transitions from a chromosome to a protein sequence: transcription, intron splicing, exon assembly and translation. There is no such clear principle for integrating proteomics data, since the laws governing protein folding and interactivity are not quite understood. In our effort to bring together independent pieces of information relative to proteins in a biologically meaningful way, we assess the bias of bioinformatics resources and consequent approximations in the framework of small‐scale studies. We analyse proteomics data while following both a data‐driven (focus on proteins smaller than 10 kDa) and a hypothesis‐driven (focus on whole bacterial proteomes) approach. These applications are potentially the source of specialized complements to classical biological ontologies. Copyright © 2004 John Wiley & Sons, Ltd.
A fragment of 21 ORFs around the direct repeat (DR) region of Mycobacterium tuberculosis is absent from the other sequenced mycobacterial genomes: implications for the evolution of the DR region
Authors: Caimi Karina , Cataldi Angel
Published: March 2004

The direct repeat (DR) region is a singular locus of the Mycobacterium tuberculosis complex genome. This region consists of 36 bp repetitive sequences separated by non‐repetitive unique spacer sequences. Around this region there are several genes coding for proteins of unknown function. To determine whether the M. smegmatis, M. avium, M. marinum and M. leprae genomes contain sequences and ORFs similar to those of the DR locus of the M. tuberculosis complex, we analysed the corresponding regions in these species. As a first step, some conserved genes that flank the DR genes [Rv2785c (rpsO), Rv2786c (ribF), Rv2790c (ltp1), Rv2793c (truB), Rv2800, Rv2825, Rv2828, Rv2831 (echA16), Rv2838 (rbfA) and Rv2845 (proS)] were used as markers to locate the corresponding orthologues in M. smegmatis, M. avium, M. marinum and M. leprae in silico. Most of these M. tuberculosis marker genes have highly similar orthologues located in the same order and orientation in the other mycobacteria. In contrast, no orthologues were found for ORFs Rv2801–Rv2824, suggesting that these genes are unique to M. tuberculosis within the genus Mycobacterium. We observed that in M. smegmatis and M. avium, Rv2800 and Rv2825 are adjacent. This observation was experimentally confirmed by PCR. In conclusion, as the DR locus and the ORFs around it are absent in M. smegmatis and M. avium and, as it is possible that these species are older than M. tuberculosis, we postulated that the DR locus was acquired by the M. tuberculosis complex species or by an ancestor bacterium. Copyright © 2004 John Wiley & Sons, Ltd.
Phylogenetics in the bioinformatics culture of understanding
Authors: Allaby Robin G. , Woodwark Mathew
Published: March 2004

Bioinformatics, as a relatively young discipline, has grown up in a world of high‐throughput large volume data that requires automatic analysis to enable us to stay on top of it all. As a response, the bioinformatics discipline has developed strategies to find patterns in a ‘low signal : noise ratio’ environment. While the need to process large amounts of information and extract hypotheses is both laudable and inescapable, the pressures that such requirements have introduced can lead to short cuts and misapprehensions. This is particularly the case with reference to assumptions about the underlying evolutionary theories that are implicitly invoked by the algorithms utilised in the analysis pipelines. The classic example is the misuse of the term ‘homologous’ to mean ‘similar’ or even ‘functionally similar’, rather than the correct definition of ‘having the same evolutionary origin’, which may or may not imply similarity of function. In this review, we outline some of the common phylogenetic questions from a bioinformatics perspective that can be better addressed with a deeper understanding of evolutionary principles and show, with examples from the amidohydrolase and Toll families, that quite different conclusions can be drawn if such approaches are taken. This review focuses on the importance of the underlying evolutionary biology, rather than assessing the merits of different phylogenetic techniques. The relative merits of a priori and a posteriori inclusion of biological information are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Three novel pigmentation mutants generated by genome‐wide random ENU mutagenesis in the mouse
Authors: Tsipouri Vicky , Curtin John A. , Nolan Pat M. , Vizor Lucie , Parsons Claire A. , Clapham Colin M. , Latham Ian D. , Rooke Lesley J. , Martin Jo E. , Peters Jo , Hunter A. Jackie , Rogers Derek , Rastan Sohaila , Brown Steve D.M. , Fisher Elizabeth M.C. , Spurr Nigel K. , Gray Ian C.
Published: March 2004

Three mutant mice with pigmentation phenotypes were recovered from a genome‐wide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome‐wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximal Mmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes. Copyright © 2004 John Wiley & Sons, Ltd.
TRANSPATH®—a high quality database focused on signal transduction
Authors: Choi Claudia , Krull Mathias , Kel Alexander , Kel‐Margoulis Olga , Pistor Susanne , Potapov Anatolij , Voss Nico , Wingender Edgar
Published: March 2004

TRANSPATH® can either be used as an encyclopedia, for both specific and general information on signal transduction, or can serve as a network analyser. Therefore, three modules have been created: the first one is the data, which have been manually extracted, mostly from the primary literature; the second is PathwayBuilder™, which provides several different types of network visualization and hence faciliates understanding; the third is ArrayAnalyzer™, which is particularly suited to gene expression array interpretation, and is able to identify key molecules within signalling networks (potential drug targets). These key molecules could be responsible for the coordinated regulation of downstream events. Manual data extraction focuses on direct reactions between signalling molecules and the experimental evidence for them, including species of genes/proteins used in individual experiments, experimental systems, materials and methods. This combination of materials and methods is used in TRANSPATH® to assign a quality value to each experimentally proven reaction, which reflects the probability that this reaction would happen under physiological conditions. Another important feature in TRANSPATH® is the inclusion of transcription factor–gene relations, which are transferred from TRANSFAC®, a database focused on transcription regulation and transcription factors. Since interactions between molecules are mainly direct, this allows a complete and stepwise pathway reconstruction from ligands to regulated genes. More information is available at www.biobase.de/pages/products/databases.html. Copyright © 2004 John Wiley & Sons, Ltd.
Classification of chemical compounds to support complex queries in a pathway database
Authors: Wittig Ulrike , Weidemann Andreas , Kania Renate , Peiss Christian , Rojas Isabel
Published: March 2004

Data quality in biological databases has become a topic of great discussion. To provide high quality data and to deal with the vast amount of biochemical data, annotators and curators need to be supported by software that carries out part of their work in an (semi‐) automatic manner. The detection of errors and inconsistencies is a part that requires the knowledge of domain experts, thus in most cases it is done manually, making it very expensive and time‐consuming. This paper presents two tools to partially support the curation of data on biochemical pathways. The tool enables the automatic classification of chemical compounds based on their respective SMILES strings. Such classification allows the querying and visualization of biochemical reactions at different levels of abstraction, according to the level of detail at which the reaction participants are described. Chemical compounds can be classified in a flexible manner based on different criteria. The support of the process of data curation is provided by facilitating the detection of compounds that are identified as different but that are actually the same. This is also used to identify similar reactions and, in turn, pathways. Copyright © 2004 John Wiley & Sons, Ltd.
The ESF Programme on Functional Genomics workshop on ‘Data Integration in Functional Genomics: Application to Biological Pathways’
Authors: Binz Pierre‐Alain , Hermjakob Henning , van der Vet Paul
Published: March 2004

We report from the second ESF Programme on Functional Genomics workshop on Data Integration, which covered topics including the status of biological pathways databases in existing consortia; pathways as part of bioinformatics infrastructures; design, creation and formalization of biological pathways databases; generating and supporting pathway data and interoperability of databases with other external databases and standards. Key issues emerging from the discussions were the need for continued funding to cover maintenance and curation of databases, the importance of quality control of the data in these resources, and efforts to facilitate the exchange of data and to ensure the interoperability of databases. Copyright © 2004 John Wiley & Sons, Ltd.
Differential mRNA expression and protein localization of the SAP90/PSD‐95–associated proteins (SAPAPs) in the nervous system of the mouse
Authors: Welch Jeffrey M. , Wang Dongqing , Feng Guoping
Published: March 2004

The supramolecular anchoring/signaling complex at the postsynaptic density of glutamatergic synapses has been proposed to play a key role in regulating synaptic function and plasticity. One class of proteins present in the complex is the SAP90/PSD‐95‐associated protein family (SAPAPs). The SAPAPs, identified by their direct interaction with PSD‐95 family proteins, were initially proposed to function in the anchoring/signaling complex as linker proteins between glutamate receptor binding proteins and the cytoskeleton. However, recent studies have indicated that the SAPAPs also bind to signaling molecules and may thus have multiple roles at synapses. Four homologous genes encoding SAPAP proteins have been previously identified. As a first step toward understanding the physiological function of the SAPAPs, we have investigated in detail, at both the mRNA and protein levels, the localization of the individual SAPAP genes in the adult murine nervous system. We find that the SAPAP mRNAs are highly, yet differentially, expressed in many regions of the brain, including the hippocampus and cerebellum. Furthermore, SAPAP3 mRNA is targeted to dendrites, whereas SAPAP1, ‐2, and ‐4 mRNAs are detected mainly in cell bodies. The SAPAP proteins are localized at synapses in a manner consistent with mRNA expression. Surprisingly, in addition to glutamatergic synapse localization, antibody staining also reveals that the SAPAP proteins are localized at cholinergic synapses, including neuronal cholinergic synapses and the neuromuscular junction. Together, these results indicate that the SAPAPs are general components of excitatory synapses and that each of these proteins may perform a distinct function. J. Comp. Neurol. 472:24–39, 2004. © 2004 Wiley‐Liss, Inc.
The population of bipolar cells in the rabbit retina
Authors: MacNeil Margaret A. , Heussy John K. , Dacheux Ramon F. , Raviola Elio , Masland Richard H.
Published: March 2004

The population of bipolar cells in the rabbit retina was studied using Golgi impregnation and photocatalyzed filling of single cells with dihydrorhodamine, a quantitative sampling technique. The Golgi method revealed the morphology and stratification of cells in detail. The photofilling method allowed us to estimate the frequency of the cell types. From a sample of 243 Golgi‐impregnated bipolar cells and 107 photofilled cells, we identified 1 type of rod bipolar cell and 12 types of cone bipolar cells. An analysis based on retinal coverage indicates that this number of types could be contained within the number of bipolar cells known to exist. The dendrites of most cone bipolars contacted all the cones within the individual cone bipolar cell's dendritic field. Types of bipolar cell were encountered at roughly similar frequency, without any one type predominating. The rabbit retina thus contains about a dozen parallel and roughly equipotent through‐pathways. J. Comp. Neurol. 472:73–86, 2004. © 2004 Wiley‐Liss, Inc.
Cuii in Liquid Ammonia: An Approach by Hybrid Quantum‐Mechanical/Molecular‐Mechanical Molecular Dynamics Simulation
Authors: Schwenk Christian F. , Rode Bernd M.
Published: March 2004

To investigate the solvation structure of the Cuii ion in liquid ammonia, ab initio quantum‐mechanical/molecular‐mechanical (QM/MM) molecular dynamics (MD) simulations were carried out at Hartree Fock (HF) and hybrid density functional theory (B3 LYP) levels. A sixfold‐coordinated species was found to be predominant in the HF case whereas five‐ and sixfold‐coordinated complexes were obtained in a ratio 2:1 from the B3 LYP simulation. In contrast to hydrated Cuii, which exhibits a typical Jahn–Teller distortion, the geometrical arrangement of ligand molecules in the case of ammonia can be described as a [2+4] ([2+3]) configuration with 4 (3) elongated copper–nitrogen bonds. First shell solvent exchange reactions at picosecond rate took place in both HF and B3 LYP simulations, again in contrast to the more stable sixfold‐coordinated hydrate. NH3 ligands apparently lead to strongly accelerated dynamics of the Cuii solvate due to the “inverse” [2+4] structure with its larger number of elongated copper–ligand bonds. Several dynamical properties, such as mean ligand residence times or ion–ligand stretching frequencies, prove the high lability of the solvated complex.
Cover Picture: Activation of Integrin Function by Nanopatterned Adhesive Interfaces (ChemPhysChem 3/2004)
Authors: Arnold Marco , Cavalcanti‐Adam Elisabetta Ada , Glass Roman , Blümmel Jacques , Eck Wolfgang , Kantlehner Martin , Kessler Horst , Spatz Joachim P.
Published: March 2004

The cover picture shows the first demonstration of cell adhesion activation through a nanoadhesive pattern with single integrin resolution. Scanning electron microscopy images nanoscopic 6‐nm large Au particles as white dots, which are functionalized with cell ligands and organized in a square pattern. The free glass substrate area between the Au is covered with a biologically inert polymer, thereby avoiding protein or cell interactions with the glass. A few cell lamellipodia experience this environment and adhere entirely to the Au–nanoparticle pattern squares. The substrate forms a well‐defined, rigid adhesion pattern where Au particles control integrin–integrin interactions in focal adhesions by their separation distance. A separation between single intergrins of ≥73 nm results in limited cell attachment and spreading, and dramatically reduces the formation of focal adhesion and actin stress fibers. The range of 58–73 nm is found to be a universal length scale for integrin clustering and activation, since these properties are shared by a variety of cultured cells. Find out more in the Communication by Spatz et al. on page 383.
Preparation and investigation of (CuInSe2)x(2ZnSe)1‐x and (CuInTe2)x(2ZnTe)1‐x solid solution crystals
Authors: Bodnar I. V. , Gremenok V. F. , Schmitz W. , Bente K. , Doering Th.
Published: March 2004

The (CuInSe2)x(2ZnSe)1‐x and (CuInTe2)x(2ZnTe)1‐x solid solution crystals prepared by Bridgman method and chemical vapor transport have been studied. The nature of the crystalline phases, the local structure homogeneity and composition of these materials have been investigated by X‐ray diffraction (XRD) and Electron Probe Microanalysis (EPMA) methods. The analysis revealed the presence of chalcopyrite‐sphalerite phase transition between 0.6 ≤ X ≤ 0.7. Lattice constants, value of σ position parameter and bond length between atoms were also calculated. It was found that the lattice parameters exhibit a linear dependence versus composition. The transmission spectra of solid solution crystals in the region of the main absorption edge were studied. It was established that the optical band gap of these materials changes non‐linearly with the X composition. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal growth of some urinary stone constituents: III. In‐vitro crystallization of L‐cystine and its characterization
Authors: Ramachandran E. , Natarajan S.
Published: March 2004

L‐Cystine (‐SCH2· CHNH2· COOH), having the morphology of hexagonal plates, an amino acid constituent of urinary stone, is crystallized in silica gel under suitable pH conditions by double diffusion method. The grown crystals were characterized by density measurement, Fourier transform infra‐red spectroscopy, X‐ray powder diffraction and thermogravimetric analysis. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)