bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Spinal Injuries in the Invasive Cardiologist II: Prevention and Treatment
Authors: FADL YAZID Y. , ELLENBOGEN KENNETH A. , GRUBB ROBERT L. , KHOO‐SUMMERS LYNNETTE , LINDSAY BRUCE D.
Published: August 2007

This review provides a perspective of spinal injuries related to invasive cardiology, an understanding of the anatomy and physiology of the spine, the etiology and pathophysiology of spinal injuries, and options for prevention and treatment. In this part of our review, conventional surgical and minimally invasive options are discussed as well as emerging techniques for the treatment of back pain. We also discuss methods of preventing back injuries by modifications to the work environment as well as preventive measures that may be practiced by the invasive cardiologist. Our final objective is to describe and illustrate proven techniques for strengthening the supportive musculature to avoid spinal injury as well as to reduce painful exacerbations.
Dexmedetomidine Related Cardiac Arrest in a Patient with Permanent Pacemaker; a Cautionary Tale
Authors: SHAH ARTI N. , KONERU JAYANTHI , NICOARA ALINA , GOLDFEDER LARA B. , THOMAS KURIAN , EHLERT FREDERICK A.
Published: August 2007

Dexmedetomidine (Precedex®), an α‐2 adrenergic receptor agonist is frequently and safely used as sedative agent during surgical procedures. We report a case of a 76‐year‐old woman who developed cardiac arrest from the use of dexmedetomidine during pacemaker lead extraction procedure.
Challenges of Diagnosis of Long‐QT Syndrome in Children
Authors: MORIC‐JANISZEWSKA EWA , MARKIEWICZ‐ŁOSKOT GRAŻYNA , ŁOSKOT MARIA , WĘGLARZ LUDMIŁA , HOLLEK ANDRZEJ , SZYDŁOWSKI LESŁAW
Published: August 2007

We describe the clinical and genetic characteristics of the family, in which the diagnosis of LQT1 had been made. The electrocardiogram (ECG) characteristics of this patient indicated the likelihood of LQTS1. Polymorphic ventricular extrasystolies and episodes of polymorphic non‐sustained ventricular tachycardia were confirmed by Holter ECG monitoring. On the exertional electrocardiogram polymorphic ventricular tachycardia (torsade de pointes) was recorded. Direct sequencing of both DNA strands revealed the absence of mutations or polymorphisms in the KCNQ1, HERG, and SCN5A genes.
Cycle Length Dependent Block in the “Mitral–Pulmonary Vein” Isthmus
Authors: LIM KANG‐TENG , JAÏS PIERRE , O'NEILL MARK D. , KNECHT SEBASTIAN , MATSUO SEIICHIRO , ARANTES LEONARDO , KODALI SATHISH , HOCINI MÉLÈZE , KLEIN GEORGE , CLÉMENTY JACQUES , HAÏSSAGUERRE MICHEL
Published: August 2007

We report a case of cycle length dependent activation sequence in the coronary sinus catheter during assessment of mitral‐pulmonary vein isthmus block. A 61‐year‐old patient presented with atrial tachycardia following a recent pulmonary vein isolation for paroxysmal atrial fibrillation. A perimitral macroreentrant atrial tachycardia was demonstrated during mapping. The isthmus block observed following initial ablation of the mitral‐pulmonary vein appeared to be pacing cycle dependent and to our knowledge has not been previously described.
Predatory hoverflies select their oviposition site according to aphid host plant and aphid species
Authors: Almohamad Raki , Verheggen François J. , Francis Frédéric , Haubruge Eric
Published: August 2007

The hoverfly Episyrphus balteatus De Geer (Diptera: Syrphidae) is an abundant and efficient aphid‐specific predator. Several aphidophagous parasitoids and predators are known to respond positively to aphid‐infested plants. Semiochemicals from the latter association usually mediate predator/parasitoid foraging behavior toward sites appropriate for offspring fitness. In this study, we investigated the effect of aphid host plant and aphid species on foraging and oviposition behavior of E. balteatus. Behavioral observations were conducted using the Noldus Observer v. 5.0, which allows observed insect behavior to be subdivided into different stages. Additionally, the influence of aphid species and aphid host plant on offspring fitness was tested in a second set of experiments. Acyrthosiphon pisum Harris and Megoura viciae Buckton were equally attractive for E. balteatus whereas Aphis fabae Scopoli (all Homoptera: Aphididae) were less attractive. These results were correlated with (i) the number of eggs laid, which was significantly higher for the two first aphid species, and (ii) the fitness of hoverfly larvae, pupae, and adults. Two solanaceous plant species, Solanum nigrum L. and Solanum tuberosum L. (Solanaceae), which were infested with Myzus persicae Sulzer (Homoptera: Aphididae), were also compared using the same approach. Discrimination between these two M. persicae host plants was observed, with S. tuberosum being preferred as an oviposition site by the predatory hoverfly. Larval and adult fitness was correlated with the behavioral observations. Our results demonstrated the importance of the prey–host plant association on the choice of the oviposition site by an aphid predator, which is here shown to be related to offspring fitness.
Typing of the immunological system in human embryos by coelocentesis
Authors: Renda Maria Concetta , Makrydimas George , Nicolaides Kipros H. , Fecarotta Emanuela , Damiani Gianfranca , Picciotto Francesco , Jakil Maria Cristina , Maggio Aurelio
Published: August 2007

Coelocentesis offers a new opportunity for gaining access to the human embryos from 28 d postfertilization. However, while some studies about its biochemical composition have been reported, our knowledge about immunological pattern of this compartment is still limited. For this reason, we studied the human coelomic fluids sampled from 6.6 to 10 wk of gestation. The majority of cellular population consisted in mesenchymal/epithelial cells. In fluids sampled before 10 wk we found only a preT Cell Receptor expression and an absence or a very low frequency of B lymphocytes, T lymphocytes and NK (natural killer) antigens. These preliminary data suggest that the immunological system in human embryos could be in the ideal conditions to start a process of tolerance induction.
Maine de Biran et Jens Baggesen Une correspondance inédite
Authors: Aarnes Asbjørn
Published: August 2007

Dans le Journal de Maine de Biran le nom du poète‐philosophe danois Jens Baggesen revient à plusieurs reprises à partir de 1821. Ils se rencontrent à Paris la même année chez le diplomate suisse M. Stapfer, et il en résulte de longues conversations et discussions qui sont cornmentées dans le Journal.

La base de cette étude est une série de quatre lettres échangées entre Biran et Baggesen au cours de quelques mois après leur rencontre. Ces lettres se suivent chronologiquement, sans interruption apparente, et constituent ainsi un dialogue philosophique où une pensée imprégnée de romantisme nordique se heurte à une philosophie soucieuse de clarté et de distinction.

Cette correspondance fournit des traits nouveaux au portrait d'un auteur classique dans les lettres scandinaves, et elle nous renseigne en effet sur certains aspects de la philosophie de Maine de Biran, notamrnent sur la genèse de sa pensée, comme sur l'orientation religieuse dans la dernière partie de sa vie, en apportant des précisions sur ce que Biran, dans les Nouveaux essais d'anthropologie, appelera “la troisième vie, c'est‐à‐dire, la simplicité reconquise sous l'influence de la grâce, après le dédoublement pénible de la réflexion.

La première partie de I'étude donne une brève esquisse de la vie et de l'ouevre de Jens Baggesen, tout en soulignant les circonstances qui le mettaient en rapport avec Maine de Biran. La deuxième partie est consacrée à une analyse des lettres en vue de faire ressortir affinités et divergences entre les deux penseurs.

Finalement, une question se pose: Est‐il légitime de voir dans la derniére philosophie de Biran une sorte de réponse à l'appel de son ami qui soutient avec enthousiasme la thèse de la continuitit de l'être créé?
Zum Mittelaltereinfluss in der modernen Dichtung: Ezra Pounds Chaucerbild
Authors: Gugelberger Georg M.
Published: August 2007

Verschiedene Wege bieten sich an, das komplexe Gesamtwerk von Ezra Pound, vor allem aber dessen “Cantos” dem Verständnis näher zu bringen. Einer der vielleicht aufschlussreichsten Interpretationswege scheint mir eine Analyse der Poundschen Mittelalterschulung zu sein. Sicherlich sind Autoren wie Dante, Cavalcanti, die provenzalischen Dichter, der Autor des altenglischen Seefahrergedichtes für eine derartige Analyse von grösster Bedeutung. Vergessen wird aber oft, dass Pound sich Zeit seines Lebens ausführlich mit Chaucer beschäftigte, der ihn in seiner eigenen Auffassung von Dichtkunst und Ubersetzungskunst bestarkte. Der Sprachduktus vieler Cantos ist von Chaucers Sprache beeinflusst. Dabei stutzt sich Pound weniger auf die Chaucerischen Hauptwerke, sondern hauptsächlich auf dessen kürzere Dichtungen. Ein wesentlicher Canto, Canto 81, vor allem ist völlig von Chaucer geprägt. Eine Analyse des Chaucereinflusses auf Pound bestärkt, vor allem wenn die Analyse in Hinblick auf andere mittelalterliche Dichter wie Dante und Cavalcanti betrieben wird, den Eindruck, dass Pounds Dichtung formell und sprachlich, vor allem aber in ihrem Kompendiencharakter, mittelalterlich bestimmt ist.
Kafka's “Elf Söhne“: A Further Dimension
Authors: Lewis Hanna B.
Published: August 2007

Kafka's “Elf Söhne” has often been considered a listing of eleven stories he was working on in 1917. However, the eleven sons may also be seen as the eleven surviving sons of Jacob (before the arrival of Benjamin or after the loss of Joseph). Another listing in Kafka's Judaic background is that of the four sons in the Haggadah (the Passover narrative) and similarities are evident here. This amplifies the possibilities of interpretation for this simple story without precluding Kafka's own explanation.
Antibodies to periodontal pathogens and coronary artery calcification in type 1 diabetic and nondiabetic subjects
Authors: Colhoun H. M. , Slaney J. M. , Rubens M. B. , Fuller J. H. , Sheiham A. , Curtis M. A.
Published: August 2007

Background and Objective:  The aim of this study was to examine whether serum immunoglobulin G (IgG) levels to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans are higher in type 1 diabetic patients than in controls and are associated with coronary artery calcification, a measure of atherosclerosis.

Material and Methods:  One‐hundred and ninety nine type 1 diabetic patients (mean age 38 ± 4 years) and 201 age‐ and gender‐matched nondiabetic subjects had coronary artery calcification, as measured by electron beam computed tomography. Serum IgG levels to P. gingivalis W50 and to A. actinomycetemcomitans HK1651 whole cells were measured by enzyme‐linked immunosorbent assay.

Results:  A similar proportion of diabetic patients (29%) and controls (31%, p = 0.7) had elevated serum IgG to periodontal bacteria, defined as being above the median antibody level for both microorganisms. Elevated antibody levels were associated with higher systolic blood pressure (p = 0.02) and an increased odds of coronary artery calcification in all subjects combined (odds ratio = 1.7, p = 0.047) and in diabetic subjects examined separately (odds ratio = 2.01, p = 0.027). Association of serum IgG levels with coronary artery calcification was independent of social class, lipids and antibody levels to other microorganisms, but not systolic blood pressure (odds ratio = 1.4, p = 0.1 on adjustment for blood pressure). There was no association between serum IgG level and vascular endothelial function.

Conclusion:  Elevated levels of serum IgG to P. gingivalis and A. actinomycetemcomitans are associated with coronary artery atherosclerosis. This may reflect a direct role for periodontal infection or a role for the host response to infection in coronary atherosclerosis, particularly in patients with type 1 diabetes.
rAAV6‐Microdystrophin Rescues Aberrant Golgi Complex Organization in mdx Skeletal Muscles
Authors: Percival Justin M. , Gregorevic Paul , Odom Guy L. , Banks Glen B. , Chamberlain Jeffrey S. , Froehner Stanley C.
Published: August 2007

Muscular dystrophies are a diverse group of severe degenerative muscle diseases. Recent interest in the role of the Golgi complex (GC) in muscle disease has been piqued by findings that several dystrophies result from mutations in putative Golgi‐resident glycosyltransferases. Given this new role of the Golgi in sarcolemmal stability, we hypothesized that abnormal Golgi distribution, regulation and/or function may constitute part of the pathology of other dystrophies, where the primary defect is independent of Golgi function. Thus, we investigated GC organization in the dystrophin‐deficient muscles of mdx mice, a mouse model for Duchenne muscular dystrophy. We report aberrant organization of the synaptic and extrasynaptic GC in skeletal muscles of mdx mice. The GC is mislocalized and improperly concentrated at the surface and core of mdx myofibers. Golgi complex localization is disrupted after the onset of necrosis and normal redistribution is impaired during regeneration of mdx muscle fibers. Disruption of the microtubule cytoskeleton may account in part for aberrant GC localization in mdx myofibers. Golgi complex distribution is restored to wild type and microtubule cytoskeleton organization is significantly improved by recombinant adeno‐associated virus 6‐mediated expression of ΔR4‐R23/ΔCT microdystrophin showing a novel mode of microdystrophin functionality. In summary, GC distribution abnormalities are a novel component of mdx skeletal muscle pathology rescued by microdystrophin expression.
Trafficking of Siderophore Transporters in Saccharomyces cerevisiae and Intracellular Fate of Ferrioxamine B Conjugates
Authors: Froissard Marine , Belgareh‐Touzé Naïma , Dias Marylène , Buisson Nicole , Camadro Jean‐Michel , Haguenauer‐Tsapis Rosine , Lesuisse Emmanuel
Published: August 2007

We have studied the intracellular trafficking of Sit1 [ferrioxamine B (FOB) transporter] and Enb1 (enterobactin transporter) in Saccharomyces cerevisiae using green fluorescent protein (GFP) fusion proteins. Enb1 was constitutively targeted to the plasma membrane. Sit1 was essentially targeted to the vacuolar degradation pathway when synthesized in the absence of substrate. Massive plasma membrane sorting of Sit1 was induced by various siderophore substrates of Sit1, and by coprogen, which is not a substrate of Sit1. Thus, different siderophore transporters use different regulated trafficking processes. We also studied the fate of Sit1‐mediated internalized siderophores. Ferrioxamine B was recovered in isolated vacuolar fractions, where it could be detected spectrophotometrically. Ferrioxamine B coupled to an inhibitor of mitochondrial protoporphyrinogen oxidase (acifluorfen) could not reach its target unless the cells were disrupted, confirming the tight compartmentalization of siderophores within cells. Ferrioxamine B coupled to a fluorescent moiety, FOB‐nitrobenz‐2‐oxa‐1,3‐diazole, used as a Sit1‐dependent iron source, accumulated in the vacuolar lumen even in mutants displaying a steady‐state accumulation of Sit1 at the plasma membrane or in endosomal compartments. Thus, the fates of siderophore transporters and siderophores diverge early in the trafficking process.
In Vitro Fusion Catalyzed by the Sporulation‐Specific t‐SNARE Light‐Chain Spo20p is Stimulated by Phosphatidic Acid
Authors: Liu Song , Wilson Kirilee A. , Rice‐Stitt Travis , Neiman Aaron M , McNew James A.
Published: August 2007

Sec9p and Spo20p are two SNAP25 family SNARE proteins specialized for different developmental stages in yeast. Sec9p interacts with Sso1/2p and Snc1/2p to mediate intracellular trafficking between post‐Golgi vesicles and the plasma membrane during vegetative growth. Spo20p replaces Sec9p in the generation of prospore membranes during sporulation. The function of Spo20p requires enzymatically active Spo14p, which is a phosphatidylcholine (PC)‐specific phospholipase D that hydrolyzes PC to generate phosphatidic acid (PA). Phosphatidic acid is required to localize Spo20p properly during sporulation; however, it seems to have additional roles that are not fully understood. Here we compared the fusion mediated by all combinations of the Sec9p or Spo20p C‐terminal domains with Sso1p/Sso2p and Snc1p/Snc2p. Our results show that Spo20p forms a less efficient SNARE complex than Sec9p. The combination of Sso2p/Spo20c is the least fusogenic t‐SNARE complex. Incorporation of PA in the lipid bilayer stimulates SNARE‐mediated membrane fusion by all t‐SNARE complexes, likely by decreasing the energetic barrier during membrane merger. This effect may allow the weak SNARE complex containing Spo20p to function during sporulation. In addition, PA can directly interact with the juxtamembrane region of Sso1p, which contributes to the stimulatory effects of PA on membrane fusion. Our results suggest that the fusion strength of SNAREs, the composition of organelle lipids and lipid–SNARE interactions may be coordinately regulated to control the rate and specificity of membrane fusion.
Homodimerization Antagonizes Nuclear Export of Survivin
Authors: Engelsma Dieuwke , Rodriguez Jose A. , Fish Alexander , Giaccone Giuseppe , Fornerod Maarten
Published: August 2007

Survivin plays separate roles during different phases of the cell cycle. In mitosis, Survivin is a key regulator of cell division, while in interphase, Survivin is able to protect cells from apoptosis. Survivin shuttles between nucleus and cytoplasm under the influence of one or more nuclear export signals (NESs). Paradoxically, our data show that Survivin poorly binds CRM1 in vitrobecause hydrophobic residues of the NES are occupied in homodimer contacts. We show that NES‐preserving dimerization mutants behave as monomers in solution, show dramatically increased CRM1 binding and are more efficiently exported in vivothan wild‐type Survivin. These data indicate that Survivin contains a monomer‐specific NES and that dimerization modulates cytoplasmic access of the protein. Our findings have implications for both the mitotic and interphase roles of survivin.
Vps22/EAP30 in ESCRT‐II Mediates Endosomal Sorting of Growth Factor and Chemokine Receptors Destined for Lysosomal Degradation
Authors: Malerød Lene , Stuffers Susanne , Brech Andreas , Stenmark Harald
Published: August 2007

The ubiquitin‐binding protein Hrs and endosomal sorting complex required for transport (ESCRT)‐I and ESCRT‐III are involved in sorting endocytosed and ubiquitinated receptors to lysosomes for degradation and efficient termination of signaling. In this study, we have investigated the role of the ESCRT‐II subunit Vps22/EAP30 in degradative protein sorting of ubiquitinated receptors. Vps22 transiently expressed in HeLa cells was detected in endosomes containing endocytosed epidermal growth factor receptors (EGFRs) as well as Hrs and ESCRT‐I and ESCRT‐III. Depletion of Vps22 by small interfering RNA, which was accompanied by decreased levels of other ESCRT‐II subunits, greatly reduced degradation of EGFR and its ligand EGF as well as the chemokine receptor CXCR4. EGFR accumulated on the limiting membranes of early endosomes and aberrantly small multivesicular bodies in Vps22‐depleted cells. Phosphorylation and nuclear translocation of extracellular‐signal‐regulated kinase1/2 downstream of the EGF‐activated receptor were sustained by depletion of Hrs or the ESCRT‐I subunit Tsg101. In contrast, this was not the case when Vps22 was depleted. These results indicate an important role for Vps22 in ligand‐induced EGFR and CXCR4 turnover and suggest that termination of EGF signaling occurs prior to ESCRT‐II engagement.
Detection of Childhood Visual Impairment in At‐Risk Groups
Authors: Evenhuis Heleen , Van Der Graaf Gabrielle , Walinga Margreet , Bindels‐de Heus Karen , Van Genderen Maria , Verhoeff Marleen , Lantau Kathleen , Van Der Meulen‐Ennema Helen , Meester Nelleke , Wienen Lien , Schalij‐Delfos Nicoline
Published: August 2007

Abstract Children with intellectual disabilities have an increased risk of visual impairment, caused by both ocular and cerebral abnormalities, but this risk has not been quantified. The same applies to preterm children and children with cerebral palsy with a normal intelligence. Many cases probably go unidentified, because participation of these children in preschool vision screening programs is not guaranteed, or because no screening program is available. Although there may be a case for specific screening, there is insufficient scientific evidence supporting such a claim. A “safety net” construction for vision screening is proposed by a Dutch expert working party, based on scientific information and joint professional expertise, to improve identification of both ocular and cerebral visual impairment in at‐risk groups. Costs and gains of the model should be scientifically evaluated in a test region.
Who Cares About Disabled Victims of Crime? Barriers and Facilitators for Redress
Authors: Lewin Barbro
Published: August 2007

Abstract  The author identified and discusses barriers and facilitators for public action after the occurrence of abuse against an adult with an intellectual disability (ID). Data were collected via a postal survey sent to guardians in one Swedish region with questions about suspected abuse against their wards (n = 978), of whom 392 had an ID (the remaining were affected by dementia or had another physical or mental disability). The rate of abuse was 4.8% (n = 19) among those wards with an ID. A range of abuses were reported, but there were no significant statistical differences attributed by sex of the wards. Facilitating examples for redress in the statutory framework were identified, but it was observed that implementation of redress was often flawed. Three alternative public actions were discussed: (1) victims' refusal to contact the public sector; (2) internal handling by the social services; and (3) reporting to police (but case closed). Findings showed that there were difficulties in understanding that passive respect for integrity and autonomy is not in line with the public ethos that demands actively caring for dependent wards, that offences in residential settings were sometimes handled internally and not reported in accord with the statutory framework, and that the ability of the criminal justice system to compensate for communicative disabilities seemed deficient.
The Male Workforce in Intellectual Disability Services
Authors: McConkey Roy , McAuley Patricia , Simpson Leanne , Collins Suzanne
Published: August 2007

Abstract  Staff shortages are predicted in community social care sector services for people with intellectual disabilities (ID). One option is to attract more men to the workforce, which would also counter the present sex‐ratio (gender) imbalance among workers. Potential strategies for recruitment could be identified by analyzing the characteristics and experiences of the male staff currently employed in such jobs. To do this, the authors undertook three studies: (1) a census of 653 staff in statutory services within one Health and Social Services Board district in Northern Ireland; (2) a survey of 463 staff from both statutory and nonstatutory services; and (3) small sample focus groups with designated male staff. Findings were that fewer than 1 in 5 of the workforce in ID sector services in Northern Ireland were men, with significant variance (0–40%) depending upon the type of services. Men were more likely than women to be in full‐time posts; to be the main wage‐earner in the household, and to have entered ID sector jobs from noncare settings. Male staff reported that their motivation for undertaking work in this sector was often questioned by peers and that they felt exposed to accusations of abuse. Authors conclude that male staff recruitment could be boosted by increased pay and more opportunities for full‐time work and career progression. Career advisers, teachers, and parents need to promote the value and opportunities of work available in ID sector services. The unique contributions of male staff also need to be identified and recognized as a means of retaining existing staff and recruiting others.
“Parenting With Support”: The Views and Experiences of Parents With Intellectual Disabilities
Authors: Tarleton Beth , Ward Linda
Published: August 2007

Abstract  The international literature on parents with intellectual disabilities (ID) has focused on concerns about their ability to parent and strategies to enable them to develop parenting skills. Traditionally, the views and experiences of parents themselves have not been the focus of studies. With this in mind, the authors talked to a cohort of 30 parents as part of a mapping study of issues and positive practice in supporting parents with ID and their children in the UK. They report on the parents' experiences of being provided with ongoing, proactive support, to enable them to parent to the best of their ability and describe the types of practical and emotional support that helped them to develop parenting skills and overcome wider problems, such as falling into debt, that were impacting their families. Enabling adults with ID to “parent with support” appeared to safeguard their children, whose health and safety is a primary object of concern for services. If parents had access to supports, they could keep their children and enjoy an enhanced quality of family life together. The authors conclude that with appropriate help from services parents can be enabled to support each other, to develop confidence, and to engage more positively with the professionals and systems responsible for safeguarding the welfare of their children.
Personal vs. Proxy Focus Groups' Perspectives on Quality of Life
Authors: Holburn Steve , Cea Christine D. , Coull Linda , Goode David
Published: August 2007

Abstract  The authors present a finding from a larger study that investigated variation in perspective among different stakeholder focus groups about enhancing quality of life (QoL) of individuals with intellectual disabilities living in group residences in New York. The report illustrates how self‐advocates' interests in enhancing QoL were distributed approximately evenly across home life, relationships, and community, while other groups (family members, direct support staff, and residence managers) were principally concerned about QoL as it pertained to home life. This finding speaks to the importance of querying people with intellectual disabilities personally when assessing QoL.
Protein kinase CK2 activates the atypical Rio1p kinase and promotes its cell‐cycle phase‐dependent degradation in yeast
Authors: Angermayr Michaela , Hochleitner Elisabeth , Lottspeich Friedrich , Bandlow Wolfhard
Published: August 2007

Using co‐immunoprecipitation combined with MS analysis, we identified the α′ subunit of casein kinase 2 (CK2) as an interaction partner of the atypical Rio1 protein kinase in yeast. Co‐purification of Rio1p with CK2 from Δcka1 or Δcka2 mutant extracts shows that Rio1p preferentially interacts with Cka2p in vitro. The C‐terminal domain of Rio1p is essential and sufficient for this interaction. Six C‐terminally located clustered serines were identified as the only CK2 sites present in Rio1p. Replacement of all six serine residues by aspartate, mimicking constitutive phosphorylation, stimulates Rio1p kinase activity about twofold in vitro compared with wild‐type or the corresponding (S > A)6 mutant proteins. Both mutant alleles (S > A)6 or (S > D)6 complement in vivo, however, growth of the RIO1 (S > A)6 mutant is greatly retarded and shows a cell‐cycle phenotype, whereas the behaviour of the RIO1 (S > D)6 mutant is indistinguishable from wild‐type. This suggests that phosphorylation by protein kinase CK2 leads to moderate activation of Rio1p in vivo and promotes cell proliferation. Physiological studies indicate that phosphorylation by CK2 renders the Rio1 protein kinase susceptible to proteolytic degradation at the G1/S transition in the cell‐division cycle, whereas the non‐phosphorylated version is resistant.
Novel repressor of the humanFMR1gene − identification of p56 human (GCC)n‐binding protein as a Krüppel‐like transcription factor ZF5
Authors: Orlov Sergey V. , Kuteykin‐Teplyakov Konstantin B. , Ignatovich Irina A. , Dizhe Ella B. , Mirgorodskaya Olga A. , Grishin Alexander V. , Guzhova Olga B. , Prokhortchouk Egor B. , Guliy Pavel V. , Perevozchikov Andrej P.
Published: August 2007

A series of relatively short (GCC)ntriplet repeats (n = 3–30) located within regulatory regions of many mammalian genes may be considered as putativecis‐acting transcriptional elements (GCC‐elements). Fragile X‐mental retardation syndrome is caused by an expansion of (GCC)ntriplet repeats within the 5′‐untranslated region of the human fragile X‐mental retardation 1 (FMR1) gene. The present study aimed to characterize a novel human (GCC)n‐binding protein and investigate its possible role in the regulation of theFMR1gene. A novel human (GCC)n‐binding protein, p56, was isolated and identified as a Krüppel‐like transcription factor, ZF5, by MALDI‐TOF analysis. The capacity of ZF5 to specifically interact with (GCC)ntriplet repeats was confirmed by the electrophoretic mobility shift assay with purified recombinant ZF5 protein. In cotransfection experiments, ZF5 overexpression repressed activity of the GCC‐element containing mouse ribosomal protein L32 gene promoter. Moreover, RNA interference assay results showed that endogenous ZF5 acts as a repressor of the humanFMR1gene. Thus, these data identify a new class of ZF5 targets, a subset of genes containing GCC‐elements in their regulatory regions, and raise the question of whether transcription factor ZF5 is implicated in the pathogenesis of fragile X syndrome.
Mapping of the active site of glutamate carboxypeptidase II by site‐directed mutagenesis
Authors: Mlčochová Petra , Plechanovová Anna , Bařinka Cyril , Mahadevan Daruka , Saldanha Jose W. , Rulíšek Lubomír , Konvalinka Jan
Published: August 2007

Human glutamate carboxypeptidase II [GCPII (EC 3.4.17.21)] is recognized as a promising pharmacological target for the treatment and imaging of various pathologies, including neurological disorders and prostate cancer. Recently reported crystal structures of GCPII provide structural insight into the organization of the substrate binding cavity and highlight residues implicated in substrate/inhibitor binding in the S1′ site of the enzyme. To complement and extend the structural studies, we constructed a model of GCPII in complex with its substrate, N‐acetyl‐l‐aspartyl‐l‐glutamate, which enabled us to predict additional amino acid residues interacting with the bound substrate, and used site‐directed mutagenesis to assess the contribution of individual residues for substrate/inhibitor binding and enzymatic activity of GCPII. We prepared and characterized 12 GCPII mutants targeting the amino acids in the vicinity of substrate/inhibitor binding pockets. The experimental results, together with the molecular modeling, suggest that the amino acid residues delineating the S1′ pocket of the enzyme (namely Arg210) contribute primarily to the high affinity binding of GCPII substrates/inhibitors, whereas the residues forming the S1 pocket might be more important for the ‘fine‐tuning’ of GCPII substrate specificity.
Early generation selection for high yielding cowpea genotypes in additive series intercropping systems with sorghum
Authors: Padi F.K.
Published: August 2007

Defining appropriate selection strategies for developing cowpea varieties adapted to additive series intercropping systems is an important requirement for cowpea breeders and producers in sub‐Saharan Africa. One hundred and forty‐three F2:3 cowpea families and their subsequent 99 F3:4 families derived from a cross between a sole bred cultivar, Apagbaala, and a traditional variety, SARC‐L02, were evaluated under additive series intercropping with sorghum. Intercropping imposed a strong selection pressure for days to flowering such that 31% of F2:3 families that flowered after 50 days produced too few grains to permit their subsequent evaluation in the F3:4 generation. Narrow‐sense heritabilities estimated by parent–offspring regression were high for 100 seed weight and days to flowering, moderate for biomass, low for grain yield and insignificant for branches/plant and pods/plant. Retrospective selection at 40% intensity based on F3 grain yield recovered 5 of the 10 top yielding families in the F4. No significant difference was observed between mean grain yield of selected and rejected families (at the 40% selection intensity) as estimated by a t‐test. Sole and intercrop yields produced by six advanced breeding lines included as controls showed poor correlation, and suggests selecting cultivars under the target cropping system will produce better selection response.
Testing Alternative Ground Water Models Using Cross‐Validation and Other Methods
Authors: Foglia L. , Mehl S.W. , Hill M.C. , Perona P. , Burlando P.
Published: August 2007

Many methods can be used to test alternative ground water models. Of concern in this work are methods able to (1) rank alternative models (also called model discrimination) and (2) identify observations important to parameter estimates and predictions (equivalent to the purpose served by some types of sensitivity analysis). Some of the measures investigated are computationally efficient; others are computationally demanding. The latter are generally needed to account for model nonlinearity. The efficient model discrimination methods investigated include the information criteria: the corrected Akaike information criterion, Bayesian information criterion, and generalized cross‐validation. The efficient sensitivity analysis measures used are dimensionless scaled sensitivity (DSS), composite scaled sensitivity, and parameter correlation coefficient (PCC); the other statistics are DFBETAS, Cook’s D, and observation‐prediction statistic. Acronyms are explained in the introduction. Cross‐validation (CV) is a computationally intensive nonlinear method that is used for both model discrimination and sensitivity analysis. The methods are tested using up to five alternative parsimoniously constructed models of the ground water system of the Maggia Valley in southern Switzerland. The alternative models differ in their representation of hydraulic conductivity. A new method for graphically representing CV and sensitivity analysis results for complex models is presented and used to evaluate the utility of the efficient statistics. The results indicate that for model selection, the information criteria produce similar results at much smaller computational cost than CV. For identifying important observations, the only obviously inferior linear measure is DSS; the poor performance was expected because DSS does not include the effects of parameter correlation and PCC reveals large parameter correlations.
Methods for Computer‐aided Chemical Biology. Part 1: Design of a Benchmark System for the Evaluation of Compound Selectivity
Authors: Stumpfe Dagmar , Ahmed Hany E. A. , Vogt Ingo , Bajorath Jürgen
Published: August 2007

Computational drug design and discovery methods have traditionally put much emphasis on the identification of novel active compounds and the optimization of their potency. For chemical genetics and genomics applications, an important task is the identification of small molecules that are selective against target families, subfamilies, or individual targets and can be used as molecular probes for specific functions. In order to develop or tune computational methods for such applications, there is a need for molecular benchmark systems that focus on compound selectivity, rather than biological activity (in qualitative terms) or potency. We have constructed a selectivity‐oriented test system that consists of 26 compound selectivity sets against 13 individual targets belonging to three distinct families and contains a total of 558 selective compounds. The targets were chosen because of pharmaceutical relevance and the availability of suitable ligands, privileged structural motifs and/or target structure information. Compound selectivity sets were characterized by structural diversity, chemical scaffold and selectivity range analysis. The test system is made freely available and should be useful for the development of computational approaches in chemical biology.
Methods for Computer‐aided Chemical Biology. Part 2: Evaluation of Compound Selectivity Using 2D Molecular Fingerprints
Authors: Vogt Ingo , Stumpfe Dagmar , Ahmed Hany E. A. , Bajorath Jürgen
Published: August 2007

We analyze 558 compounds with selectivity against members of different protein families using two‐dimensional molecular fingerprint methods. The calculations target compounds selective for 13 targets belonging to three families. These compound sets were especially designed for selectivity studies. The identification of compounds displaying different selectivity patterns against related protein targets is a prerequisite for chemical genetics and genomics applications to specifically interfere with functions of individual members of protein families. Thus far, computational methods have only little impact on the search for selective compounds. This is in part due to the fact that selectivity is more difficult to study computationally than activity because selectivity analysis requires the evaluation of compounds binding to multiple targets. Here, we investigate the ability of state‐of‐the‐art two‐dimensional molecular fingerprints to detect compounds having different selectivity. The results of systematic similarity search calculations reveal that two‐dimensional fingerprints are capable of identifying compounds having different selectivity against closely related target proteins, although fingerprints were originally not developed for such applications. In addition to target‐selective molecules, fingerprints are also found to preferentially recognize compounds that are active at the target family level. Our findings suggest that similarity methods should merit further exploration in the study of compound selectivity across target families.
Crystal Structure of the T315I Mutant of Abl Kinase
Authors: Zhou Tianjun , Parillon Lois , Li Feng , Wang Yihan , Keats Jeff , Lamore Sarah , Xu Qihong , Shakespeare William , Dalgarno David , Zhu Xiaotian
Published: August 2007

Imatinib (Gleevec) is currently the frontline therapy for chronic myeloid leukemia (CML), a disease characterized by the presence of a constitutively activated chimeric tyrosine kinase protein Bcr‐Abl. However, drug resistance often occurs at later stages of the disease, principally because of the occurrence of mutations in the kinase domain. Second generation Bcr‐Abl inhibitors, such as dasatinib and nilotinib are capable of inhibiting many imatinib‐resistant forms of the kinase but not the form in which threonine is mutated to isoleucine at the gatekeeper position (T315I). In this study, we present the crystal structure of the kinase domain of the c‐Abl T315I mutant, as well as the wild‐type form, in complex with a pyrrolopyridine inhibitor, PPY‐A. The side chain of Ile315 is accommodated in the Abl T315I mutant structure without large conformational changes proximal to the site of mutation. In contrast to other inhibitors, such as imatinib and dasatinib, PPY‐A does not occupy the hydrophobic pocket behind the gatekeeper residue. This binding mode, coupled with augmented contacts with the glycine‐rich loop, appears to be critical for its ability to override the T315I mutation. The data presented here may provide structural guidance for the design of clinically useful inhibitors of Bcr‐Abl T315I.
Direct measurements of reaeration rates using noble gas tracers in the River Lagan, Northern Ireland
Authors: Reid Sally E. , Mackinnon Pauline A. , Elliot Trevor
Published: August 2007

Dissolved oxygen (DO) in river systems is often depleted by polluting substances, sometimes rendering the water unfit for habitats and human use. The natural mass transfer of oxygen from the atmosphere can help to alleviate this. The reaeration coefficient, K2, which describes the rate of oxygen absorption, is an important parameter in water‐quality modelling. Owing to difficulties in the direct measurement of K2, values for use in water quality models are typically derived using predictive equations, but these are notoriously inaccurate. This paper presents a field method for the direct measurement of K2 by two alternative analysis methods and includes the results of eight tests conducted on a reach of the River Lagan, in Northern Ireland. The method is based on a long‐established protocol but replaces a now‐unacceptable radioactive tracer (85Kr) with stable noble gases. K2(20) values between 3 and 80/day are reported for the test reach.
The effect of antiepileptic drugs on vitamin B12 metabolism
Authors: ASLAN K. , BOZDEMIR H. , UNSAL C. , GÜVENC B.
Published: August 2007

The effects of antiepileptic drugs (AED) on the serum concentration of vitamin B12, folic acid and homocysteine (HMC), and erythrocyte folic acid levels were determined in 45 epileptic patients (30 women, 15 men; mean age 31.7 years) and 23 healthy volunteers (control group; 18 women, five men; mean age 33.4 years). All patients were either on carbamazepine (CMZ), oxcarbazepine (OXZ), or valporate (VP) monotherapy. Serum vitamin B12 levels were low in 17.8% of patients and 8.7% of the controls (P = 0.299). Serum homocysteine levels were high in 17.8% of the patients (P = 0.008). Fifty percent of the patients who had hyperhomocysteinemia, and 75% of the patients who had low serum vitamin B12 level were on CMZ monotherapy. Peripheral blood smears showed hypersegmented neutrophils and macrocytosis in 13.3%, hypochromia and microcytosis in 26.7%, acanthocytes in 2.2%, and thrombocytosis in 2.2% of all patients. The control group had normal peripheral blood smears, except in four cases that showed hypocromia and microcytosis. Long‐term administration of AED may cause elevation of homocysteine and development of subnormal serum vitamin B12 levels. Peripheral blood smear abnormalities were frequently seen in patients receiving antiepileptic treatment (P = 0.022), particularly in patients on CMZ monotherapy (P = 0.281). However, homocysteine, vitamin B12, folic acid levels and peripheral blood smear findings did not correlate with the drugs used (P = 0.665, 0.336, 0.249 for CMZ, OXZ, VP, respectively).
Effect of hydroxyurea on extramedullary haematopoiesis in thalassaemia intermedia: case reports and literature review
Authors: MEO A. , CASSINERIO E. , CASTELLI R. , BIGNAMINI D. , PEREGO L. , CAPPELLINI M. D.
Published: August 2007

Extramedullary haematopoiesis (EH) is the production of blood cell precursors outside the bone marrow that occurs in various disorders, such as thalassaemia, sickle cell anaemia, hereditary spherocytosis, polycythaemia vera, myelofibrosis and other haematological diseases. In chronic anaemia, it is a physiological response to increased erythropoietin. In some other conditions, such as myeloid metaplasia, polycythaemia vera or chronic myeloid leukaemia, EH is due to a clonal disorder of haematopoiesis that enables progenitor cells to escape from the marrow and lodge in other organs. EH usually involves the liver, spleen and lymph nodes or it can be paravertebral, intrathoracic, pelvic. It is often asymptomatic but can sometimes lead to symptomatic tumour‐like masses. Treatment options are still controversial and limited, including hypertransfusion regimen, surgical treatment, radiotherapy and hydroxyurea (HU). We describe intrathoracic and symptomatic pelvic EH masses in a 48‐year‐old woman and intrathoracic bilateral masses causing respiratory insufficiency with pleural effusion in a 42‐year‐old male, both affected by thalassaemia intermedia. Both patients showed a clinical improvement with hydroxyurea therapy and occasional blood transfusions.
Probabilistic Streamflow Generation Model for Data Sparse Arid Watersheds1
Authors: Shamir Eylon , Wang Jianzhong , Georgakakos Konstantine P.
Published: August 2007

Abstract:  The authors present a model that generates streamflow for ephemeral arid streams. The model consists of a stochastic hourly precipitation point process model and a conceptual model that transforms precipitation into flow. It was applied to the Santa Cruz River at the border crossing from Mexico into Southern Arizona. The model was constructed for four different seasons and three categories of inter‐annual variability for the wet seasons of summer and winter. The drainage area is ungauged and precipitation information was inferred from a precipitation gauge downstream. The precipitation gauge record was evaluated against simulated precipitation from a mesoscale numerical weather prediction model, and was found to be the representative of the regional precipitation variability. The flow generation was found to reproduce the variability in the observed record at the daily, seasonal and annual time scales, and it is suitable for use in planning studies for the study site.
Evaluation of Three Watershed‐Scale Pesticide Environmental Transport and Fate Models1
Authors: Parker Ronald , Arnold J.G. , Barrett Michael , Burns Lawrence , Carrubba Lee , Neitsch S.L. , Snyder N.J. , Srinivasan R.
Published: August 2007

Abstract:  The U.S. Environmental Protection Agency (USEPA) Office of Pesticide Programs (OPP) has completed an evaluation of three watershed‐scale simulation models for potential use in Food Quality Protection Act pesticide drinking water exposure assessments. The evaluation may also guide OPP in identifying computer simulation tools that can be used in performing aquatic ecological exposure assessments. Models selected for evaluation were the Soil Water Assessment Tool (SWAT), the Nonpoint Source Model (NPSM), a modified version of the Hydrologic Simulation Program‐Fortran (HSPF), and the Pesticide Root Zone Model‐Riverine Water Quality (PRZM‐RIVWQ) model. Simulated concentrations of the pesticides atrazine, metolachlor, and trifluralin in surface water were compared with field data monitored in the Sugar Creek watershed of Indiana’s White River basin by the National Water Quality Assessment (NAWQA) program. The evaluation not only provided USEPA with experience in using watershed models for estimating pesticide concentration in flowing water but also led to the development of improved statistical techniques for assessing model accuracy. Further, it demonstrated the difficulty of representing spatially and temporally variable soil, weather, and pesticide applications with relatively infrequent, spatially fixed, point estimates. It also demonstrated the value of using monitoring and modeling as mutually supporting tools and pointed to the need to design monitoring programs that support modeling.