bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical study of structure of catalytic copper site in nitrite reductase
Authors: Källrot Niklas , Nilsson Kristina , Rasmussen Torben , Ryde Ulf 
Published: November 2004

AbstractThe catalytic copper site in nitrite reductase contains a Cu2+ ion bound to three histidine (His) ligands and a solvent molecule. Sites from various sources show a conspicuous variation in the structure. In some proteins, it is close to tetrahedral (even more so than are blue copper proteins), whereas in other proteins, it has a structure more similar to that expected for a type 2 copper site. We have studied this site with a number of theoretical methods, ranging from vacuum optimizations, combined quantum and molecular mechanics (QM/MM) optimization, quantum refinement (X‐ray crystallography supplemented by quantum chemical calculations), and accurate energy calculations. We show that the difference in the structure arises from a movement of the solvent molecule and that this movement is determined by a compromise between its hydrogen bond interactions and the intrinsic preferences of the copper site. If the solvent molecule is deprotonated, the two structures have a similar energy, whereas if it is protonated, the more tetrahedral structure is energetically favorable. Neither of the structures involves a π interaction as in the blue copper proteins; instead, both are strongly distorted tetragonal structures with σ bonds to all four ligands. We have also examined the position of hydrogen atoms shared between second‐sphere carboxylate groups and the first‐sphere solvent molecule and one of the His ligands. In the oxidized state, the structure with the solvent deprotonated but the His residue protonated seems to be most stable. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Identifying subtle interrelated changes in functional gene categories using continuous measures of gene expression
Authors: Ben-Shaul Yoram , Bergman Hagai , Soreq Hermona 
Published: November 2004

AbstractMotivation: Analysis of large-scale expression data is greatly facilitated by the availability of gene ontologies (GOs). Many current methods test whether sets of transcripts annotated with specific ontology terms contain an excess of ‘changed’ transcripts. This approach suffers from two main limitations. First, since gene expression is continuous rather than discrete, designating a gene as changed or unchanged is arbitrary and oblivious to the actual magnitude of the change. Second, by considering only the number of changed genes, finer changes in expression patterns associated with the category may be ignored. Since genes generally participate in multiple networks, widespread and subtle modifications in expression patterns are at least as important as extreme increases/decreases of a few genes.Results: Numerical simulations confirm that incorporating continuous measures of gene expression for all measured transcripts yields detection of considerably more subtle changes. Applying continuous measures to microarray data from brains of mice injected with the Parkinsonian neurotoxin, MPTP, enables detection of changes in various biologically relevant GO terms, many of which are overlooked by discrete approaches.Availability: Software (MATLAB) is available upon request from the authors.Contact: soreq@cc.huji.ac.ilSupplementary information: www.icnc.huji.ac.il/?GOdisv_supp_info
Do EMU Members Share the Same Business Cycle?*
Authors: ALTAVILLA CARLO 
Published: November 2004

AbstractThe article analyses alternative approaches for dating the business cycles of a set of European monetary union (EMU) member states. First, the framework for analysing cyclical behaviour in economic activity is presented. Second, the dating algorithm is applied to both the classical cycle and the growth cycle in order to recover stylized facts of the business cycle in Europe. Third, the article utilizes different econometric techniques to evaluate the synchronicity of national cycles and the euro area aggregate cycle, and compare the results with that of the USA. A convergence analysis is also employed. Finally, a multivariate extension of the Hamilton‐Markov switching model is constructed to analyse the euro area business cycle. The results suggest that, although during the main recessionary periods the euro area economies shared a similar output dynamic, some differences still remain in the size and timing of the business cycle features. The results also suggest that adhesion to the new currency area is likely to lead to stronger synchronization of EMU members’ business cycles.
European Integration as Organizing: The Case of Armaments
Authors: MÖRTH ULRIKA , BRITZ MALENA 
Published: November 2004

AbstractIn this article we argue that organizations and organizing activities lie at the very heart of the European integration process. Cross‐pillar issues require an analytical framework that allows one to study the interplay between the market and security spheres of European integration, including how supranational and intergovernmental actors, private and public, interact with each other. By using sociological institutionalism and its notion of how organizations are institutionalized, we analyse the organizational complexity in the multifaceted policy area of armaments, without losing theoretical clarity.
The European Union: Democratic Legitimacy in a Regional State?*
Authors: SCHMIDT VIVIEN A. 
Published: November 2004

AbstractDemocratic legitimacy for the EU is problematic if it is seen as a future nation‐state. If instead the EU were seen as a regional state – with shared sovereignty, variable boundaries, composite identity, compound governance, and a fragmented democracy in which the EU level assures governance for and with the people through effective governing and interest consultation, leaving to the national‐level government by and of the people through political participation and citizen representation – the problems of the democratic deficit diminish at the EU level. But they become even greater at the national level, where the changes to national democratic practices demand better ideas and discourses of legitimization. A further complicating factor results from problems of ‘institutional fit’, because the EU has had a more disruptive impact on ‘simple’polities, where governing activity has traditionally been channelled through a single authority, than on more‘compound’polities, where it has been more dispersed through multiple authorities.
Bleeding and bruising in patients with Ehlers–Danlos syndrome and other collagen vascular disorders
Authors: Paepe Anne De , Malfait Fransiska 
Published: November 2004

SummaryEasy bruising and bleeding are not only characteristic manifestations of clotting and platelet disorders, they are also prominent features in some heritable collagen disorders, such as the Ehlers–Danlos syndromes (EDS). The EDS comprise a heterogeneous group of connective tissue diseases sharing clinical manifestations in skin, ligaments and joints, blood vessels and internal organs. Most EDS subtypes are caused by mutations in genes encoding the fibrillar collagens type I, III and V, or in genes coding for enzymes involved in the post‐translational modification of these collagens. Easy bruising is, to a variable degree, present in all subtypes of EDS, and is because of fragility of the capillaries and the perivascular connective tissues. Vascular fragility affecting medium‐sized and large arteries and veins is typically observed in the vascular subtype of EDS, caused by a molecular defect in collagen type III, an important constituent of blood vessel walls and hollow organs. Extensive bruising, spontaneous arterial rupture, leading to severe internal bleeding or premature death, and rupture of hollow organs, such as the intestine or the gravid uterus are predominant features of this subtype. Haematological studies including evaluation of clotting factors, platelet aggregation and bleeding time are usually normal in patients with EDS, except for the Hess test (Rumple–Leede test), which may be abnormal, indicating capillary fragility. In some forms of EDS confirmation of the clinical diagnosis and subtype is possible with biochemical and molecular studies.
A novel method for simultaneous analysis of specific platelet antibodies: SASPA
Authors: Nguyen Xuan Duc , Dugrillon Alex , Beck Christian , Kerowgan Mohammad , Klüter Harald 
Published: November 2004

SummaryGlycoprotein (GP)‐specific platelet antibodies can cause allo‐immune and auto‐immune thrombocytopenia. The specific detection of relevant antibodies is a prerequisite for diagnosis and treatment. Here, we describe an improved method based on simultaneous detection of various platelet‐specific immunoglobulin G (IgG) and IgM antibodies. Bead populations with distinct fluorescence intensities, coated with monoclonal antibodies specific for mouse heavy chain isotypes, were used for the simultaneous immobilization of platelet‐GP [IIb/IIIa, Ib/IX, human leucocyte antigen (HLA) class I, or Ia/IIa, CD32, GPIV or CD109, Ib/IX, HLA class I]. In order to detect human IgG and IgM antibodies simultaneously, phycoerythrin‐ and fluorescein isotiocyanate‐conjugated goat anti‐human IgG and IgM were added. On this basis, the abundance of six distinct antibodies (three anti‐GP, each with subclasses IgG and IgM) were simultaneously analysed without cross‐reaction by flow cytometry. For evaluation, sera and platelets from 169 patients with platelet‐binding and/or platelet‐associated antibodies were investigated. The monoclonal antibody‐specific immobilization of platelet antigen (MAIPA) assay was performed in parallel as reference test. The simultaneous analysis of platelet‐specific antibodies (SASPA) assay was able to detect all platelet‐specific IgG and IgM that were also recognized by MAIPA with a comparable sensitivity. SASPA proved to be a rapid and reliable assay that required less platelets than other methods. This method has the potential to pave the way for new investigations of platelet‐specific antibodies.
Effect of IL‐2Rβ‐binding cytokines on costimulatory properties of chronic lymphocytic leukaemia cells: implications for immunotherapy
Authors: Spaner David E. , Hammond Caitlin , Mena Jenny , Shi Yonghong 
Published: November 2004

SummaryWeak immunogenicity of chronic lymphocytic leukaemia (CLL) cells may contribute to disease progression and inhibit the effectiveness of immunotherapies, such as vaccines. Agents that can enhance the antigen presenting capabilities of CLL cells might then help to improve the clinical results of immunotherapies. This study investigated the effects of the common gamma chain‐binding cytokines, interleukin (IL)‐2 and IL‐15, on costimulatory properties of primary CLL cells from 51 patients. IL‐2 improved the ability of CLL cells to stimulate T cell proliferation and increased the expression of costimulatory molecules (particularly CD80) in a dose‐dependent fashion, especially in CLL cells with weak expression of CD38. CD80 and CD86 induction by IL‐2 were positively regulated through the mitogen‐activated protein kinase pathway, while CD86 expression was negatively regulated through Janus kinase pathways. However, further activation with protein kinase C agonists was required for IL‐2 activated CLL cells to stimulate autologous T cells sufficiently to clear bystander CLL cells from mixed lymphocyte responses. IL‐15 had similar effects on the costimulatory properties of CLL cells. These results suggest a role for IL‐2, or IL‐15, in immunotherapeutic strategies for CLL.
Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L−1): a disorder linked to female gender and psychiatric disorders
Authors: Ofran Y. , Lavi D. , Opher D. , Weiss T. A. , Elinav E. 
Published: November 2004

Abstract.  Ofran Y, Lavi D, Opher D, Weiss TA, Elinav E (Hadassah University Hospital, Jerusalem, Israel). Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L−1): a disorder linked to female gender and psychiatric disorders (Case Report). J Intern Med 2004; 256: 525–528.Excessive ingestion of salt is a well‐recognized cause of hypernatraemia in children, is uncommonly recognized in debilitated elderly persons, but is rarely diagnosed in healthy, independent adults. We report a case of fatal salt poisoning in a 20‐year‐old lady who suffered of post‐natal depression and ingested large quantities of salt as part of exorcism ritual. She presented with the highest ever documented serum sodium level of 255 mmol L−1, associated with severe neurological impairment that was unresponsive to aggressive hypotonic fluid replacement. Post‐mortem examination ruled out any other possible probable cause of death. The medical literature was reviewed, and 16 previous cases of severe hypernatraemia in adults secondary to excessive salt ingestion were retrieved. Common features of all reported cases included female gender (95% of cases) and evidence of underlying cognitive or psychiatric disorders (all reported cases). We conclude that women with documented cognitive or psychiatric disorders, in particular depression, are susceptible for psychogenic salt poisoning. Awareness should be raised to the potentially life‐risking use of salty beverages as emetics or as part of ‘exorcism’ rituals.
Sindbis viruses and other alphaviruses as cause of human arthritic disease
Authors: Laine M. , Luukkainen R. , Toivanen A. 
Published: November 2004

Abstract.Amongst the arthritis‐causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. These viruses occasionally cause vast outbreaks, such as O'nyong‐nyong in Africa in 1959. In Fennoscandia, Sindbis‐related Ockelbo, Pogosta, or Karelian fever viruses have been found to cause significant morbidity. The major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. The joint symptoms may persist for weeks, even months. The diagnosis is based on the clinical picture and serology. The causative viruses are closely related but not identical. It appears that at least in Finland the Pogosta disease is more common than thought, and the symptoms may often be overlooked. Several factors related to the viruses, their hosts, and global environmental changes may affect the spread of these viruses. All over the world arbovirus‐caused diseases have increased, because of global changes.
Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy
Authors: Christensson A. G. , Grubb A. O. , Nilsson J.‐Å. , Norrgren K. , Sterner G. , Sundkvist G. 
Published: November 2004

Abstract.Objective.  To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age.Methods.  Forty‐one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and 51Cr‐EDTA clearance (reference method). Cystatin C was measured by a particle‐enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z‐scores for 51Cr‐EDTA clearance, creatinine, and cystatin C. The cut‐off levels for glomerular filtration rate (GFR) (51Cr‐EDTA clearance) were 60 and 80 mL min−1 1.73 m−2, respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age‐adjusted values (z‐scores).Results.  Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus 51Cr‐EDTA clearance as compared with creatinine (r = 0.678). However, when using age‐adjusted values, the correlation for cystatin C and creatinine, respectively, versus 51Cr‐EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min−1 1.73 m−2 or z‐scores <−1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min−1 1.73 m−2 or z‐score −0.84 SD), serum cystatin C is significantly more useful.Conclusions.  Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.
Elevated plasma homocysteine: cause or consequence of myocardial infarction?
Authors: Hultdin J. , Thøgersen A. M. , Jansson J.‐H. , Nilsson T. K. , Weinehall L. , Hallmans G. 
Published: November 2004

Abstract.Objectives.  To determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow‐up compared with baseline.Design.  A population‐based, prospective, nested case‐referent study.Setting.  Screening took place at the nearest health survey centre in northern Sweden.Subjects.  Of more than 36 000 persons screened, 78 developed a first myocardial infarction (average 18 months after sampling). Fifty of these had participated in a follow‐up health survey (average 8½ years between surveys) and were sex‐ and age‐matched with 56 referents.Main outcome measures.  Comparison of plasma homocysteine levels in case and referent subjects before and after development of a first myocardial infarction.Results.  No statistically significant difference was found between cases and referents regarding homocysteine at baseline or follow‐up. Plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow‐up but not baseline was associated with first myocardial infarction (OR 2.49; 95% CI: 1.03–6.02), but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline (OR 2.94; 95% CI: 1.05–8.21) and follow‐up (OR 3.38; 95% CI: 1.21–9.48).Conclusion.  In this study, first myocardial infarction did not cause increased plasma homocysteine concentration.
Two minimal Tat translocases in Bacillus
Authors: Jongbloed Jan D. H. , Grieger Ulrike , Antelmann Haike , Hecker Michael , Nijland Reindert , Bron Sierd , Van Dijl Jan Maarten 
Published: November 2004

SummaryActivity of the Tat machinery for protein transport across the inner membrane of Escherichia coli and the chloroplast thylakoidal membrane requires the presence of three membrane proteins: TatA, TatB and TatC. Here, we show that the Tat machinery of the Gram‐positive bacterium Bacillus subtilis is very different because it contains at least two minimal Tat translocases, each composed of one specific TatA and one specific TatC component. A third, TatB‐like component is apparently not required. This implies that TatA proteins of B. subtilis perform the functions of both TatA and TatB of E. coli and thylakoids. Notably, the two B. subtilis translocases named TatAdCd and TatAyCy both function as individual, substrate‐specific translocases for the twin‐arginine preproteins PhoD and YwbN, respectively. Importantly, these minimal TatAC translocases of B. subtilis are representative for the Tat machinery of the vast majority of Gram‐positive bacteria, Streptomycetes being the only known exception with TatABC translocases.
Positive control of tylosin biosynthesis: pivotal role of TylR
Authors: Stratigopoulos George , Bate Neil , Cundliffe Eric 
Published: November 2004

SummaryControl of tylosin production in Streptomyces fradiae features interplay between a repressor, TylQ, and an activator, TylS, during regulation of tylR. The latter encodes a pathway‐specific activator that controls most of the tylosin‐biosynthetic (tyl) genes that are subject to regulation. This was established by targeted gene disruption applied separately to tylR and tylS together with transcript analysis involving reverse transcription polymerase chain reaction (RT‐PCR). TylR controls multiple genes that encode the synthesis or addition of all three tylosin sugars, plus polyketide  ring  oxidation,  and  at  least  one  of the polyketide synthase (PKS) megagenes, tylGI. (Expression of a few tyl genes, plus the resistance determinants tlrB and tlrD, together with some ancillary or unassigned genes, is not apparently regulated during fermentation, consistent with constitutive expression.) In contrast, the only gene known for sure to be directly controlled by TylS is tylR, and there are very few additional candidates. These include the mycinose‐biosynthetic gene, tylJ, and two previously unassigned genes, ORF12* (tylU) plus ORF11* (tylV). TylS also controls the PKS genes [tylGIII‐tylGIV‐tylGV] although not in obligatory fashion. These genes can be transcribed (i.e. tylosin can be produced) in a tylS‐KO strain by forcing overexpression of tylR using a foreign promoter. We therefore suspect that TylS might control the PKS genes indirectly, although this remains to be established unequivocally. Conceivably, the direct effects of TylS are exerted exclusively on other regulators. Tylosin production levels were elevated when tylS or (especially) tylR was overexpressed in S. fradiae wild‐type and yield increments of industrial significance were generated by similar manipulation of an enhanced production strain.
Physical and functional interactions among RNase E, polynucleotide phosphorylase and the cold‐shock protein, CsdA: evidence for a ‘cold shock degradosome’
Authors: Prud’homme‐Généreux Annie , Beran Rudolf K. , Iost Isabelle , Ramey C. Shane , Mackie George A. , Simons Robert W. 
Published: November 2004

Summary Escherichia coli contains at least five ATP‐dependent DEAD‐box RNA helicases which may play important roles in macromolecular metabolism, especially in translation and mRNA decay. Here we demonstrate that one member of this family, CsdA, whose expression is induced by cold shock, interacts physically and functionally with RNase E. Three independent approaches show that after a shift of cultures to 15°C, CsdA co‐purifies with RNase E and other components of the RNA degradosome. Moreover, functional assays using reconstituted minimal degradosomes prepared from purified components in vitro show that CsdA can fully replace the resident RNA helicase of the RNA degradosome, RhlB. In addition, under these conditions, CsdA displays RNA‐dependent ATPase activity. Taken together, our data are consistent with a model in which CsdA accumulates during the early stages of cold acclimatization and subsequently assembles into degradosomes with RNase E synthesized in cold‐adapted cultures. These findings show that the RNA degradosome is a flexible macromolecular machine capable of adapting to altered environmental conditions.