bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal regulation of gluconeogenesis in cereal aleurone is strongly cultivar‐dependent and gibberellin action involves SLENDER1 but not GAMYB
Authors: Eastmond Peter J. , Jones Russell L.
Published: October 2005

Storage oil is a major constituent in the cereal aleurone layer. The aim of this study was to investigate how gibberellin (GA) and abscisic acid (ABA) regulate conversion of oil to sugar in barley aleurone. The activity of the glyoxylate cycle enzyme isocitrate lyase (ICL) was surveyed in eight barley cultivars. Surprisingly, some cultivars do not require GA for the induction of ICL (e.g. Himalaya), whereas some do (e.g. Golden Promise). Furthermore, in Golden Promise, GA also stimulates triacylglycerol breakdown and enhances the net flux of carbon from acetate to sugar. In contrast, ABA strongly represses ICL activity and the flux of carbon from oil to sugar in both Golden Promise and Himalaya. Biolistics using a promoter reporter showed that GA and ABA regulate ICL at the level of transcription. Studies using barley and rice mutants and pharmacological agents show that GA‐dependent induction of ICL activity is mediated by SLENDER1 and requires cGMP, but does not involve the transcription factor GAMYB. Gibberellin and ABA therefore act antagonistically to regulate gluconeogenesis in the aleurone layer as well as controlling the production and secretion of hydrolases into the starchy endosperm. We suggest that the variation between different barley cultivars might be a result of selective breeding to alter seed dormancy.
Design of high affinity cyclic pentapeptide ligands for κ‐opioid receptors
Authors: Przydzial M.J. , Pogozheva I.D. , Ho J.C. , Bosse K.E. , Sawyer E. , Traynor J.R. , Mosberg H.I.
Published: October 2005

Abstract:  Using results from our previously reported cyclic opioid peptide series and reliable models for μ‐, δ‐, and κ‐opioid receptors (MOR, DOR, and KOR, respectively) and their complexes with peptide ligands, we have designed and synthesized a series of cyclic pentapeptides of structure Tyr‐c[d‐Cys‐Phe‐Phe‐X]‐NH2, cyclized via disulfide, methylene, or ethylene dithioethers, and where X = d‐ or l‐Cys; or d‐ or l‐penicillamine (Pen; β,β‐dimethylcysteine). Determination of binding affinities to MOR, DOR, and KOR revealed that members of this series with X = d‐ or l‐Cys display KOR affinities in the low nanomolar range, demonstrating that a ‘DPDPE‐like’ tetrapeptide scaffold is suitable not only for DOR and MOR ligands, but also for KOR ligands. The cyclic pentapeptides reported here are not, however, selective for KOR, rather they display significant selectivity and high affinity for MOR. Indeed, peptide 8, Tyr‐c[d‐Cys‐Phe‐Phe‐Cys]‐NH2‐cyclized via a methylene dithioether, shows picomolar binding affinity for MOR ( = 16 pm) with more than 100‐fold selectivity for MOR vs. DOR or KOR, and may be of interest as a high affinity, high selectivity MOR ligand. Nonetheless, the high affinity KOR peptides in this series represent excellent leads for the development of structurally related, selective KOR ligands designed to exploit structurally specific features of KOR, MOR, and DOR.
The role of charged amphipathic helices in the structure and function of surfactant protein B
Authors: Waring A.J. , Walther F.J. , Gordon L.M. , Hernandez‐Juviel J.M. , Hong T. , Sherman M.A. , Alonso C. , Alig T. , Braun A. , Bacon D. , Zasadzinski J.A.
Published: October 2005

Abstract:  Surfactant protein B (SP‐B) is essential for normal lung surfactant function. Theoretical models predict that the disulfide cross‐linked, N‐ and C‐terminal domains of SP‐B fold as charged amphipathic helices, and suggest that these adjacent helices participate in critical surfactant activities. This hypothesis is tested using a disulfide‐linked construct (Mini‐B) based on the primary sequences of the N‐ and C‐terminal domains. Consistent with theoretical predictions of the full‐length protein, both isotope‐enhanced Fourier transform infrared (FTIR) spectroscopy and molecular modeling confirm the presence of charged amphipathic α‐helices in Mini‐B. Similar to that observed with native SP‐B, Mini‐B in model surfactant lipid mixtures exhibits marked in vitro activity, with spread films showing near‐zero minimum surface tensions during cycling using captive bubble surfactometry. In vivo, Mini‐B shows oxygenation and dynamic compliance that compare favorably with that of full‐length SP‐B. Mini‐B variants (i.e. reduced disulfides or cationic residues replaced by uncharged residues) or Mini‐B fragments (i.e. unlinked N‐ and C‐terminal domains) produced greatly attenuated in vivo and in vitro surfactant properties. Hence, the combination of structure and charge for the amphipathic α‐helical N‐ and C‐terminal domains are key to SP‐B function.
The New Public Management and Managerial Roles: the Case of the Police Sergeant
Authors: Butterfield Reginald , Edwards Christine , Woodall Jean
Published: October 2005

This paper explores the introduction of New Public Management (NPM) techniques within the UK police service since the late 1990s, and in particular, the impact upon the role of the first line manager: the police sergeant. It draws upon qualitative data collected within ‘City Police Service’ by means of in‐depth interviews with role sets of police sergeants, constables, inspectors and members of the senior management team in two police divisions. After evaluating a number of NPM precepts in the light of the findings, the paper makes a number of conclusions relating to the role of police sergeants. These echo the findings of other research on changes in managerial roles, including a shift towards more strategic responsibilities, but with a significant intensification of work, tighter control and scrutiny through organizational performance management systems, and less daily contact with their police constables. As elsewhere in the public sector, a shift towards becoming a ‘practitioner manager’ was apparent, but with respect to police sergeants the effect was to limit their ability to provide leadership and support for their constables, and to encourage a greater reliance upon peer group networks and on the constables they supervised.
Movie Making at Pixar: A Collaboration of Art and Technology
Authors: Cook Rob
Published: October 2005

This talk takes you behind the scenes at Pixar Animation Studios for an in‐depth look at how its 3d computer graphics films are made. Making a computer animated film involves people with artistic talent and people with technical skills working together in close collaboration. The process starts with the development of the story and continues with modeling the geometry, adding articulation controls, using those controls to animate the characters, simulating things like water and cloth and hair, defining the look of the surfaces, putting lights in the scene, adding special effects, rendering, and post‐production. Special emphasis is given to the roles of technology and computer graphics research in supporting the filmmaker.
Kinematics, Dynamics, Biomechanics: Evolution of Autonomy in Game Animation
Authors: Collins Steve
Published: October 2005

The believeable portrayal of character performances is critical in engaging the immersed player in interactive entertainment. The story, the emotion and the relationship between the player and the world they are interacting within are hugely dependent on how appropriately the world's characters look, move and behave. We’re concerned here with the character's motion; with next generation game consoles like Xbox360

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and Playstation®3 the graphical representation of characters will take a major step forward which places even more emphasis on the motion of the character. The behavior of the character is driven by story and design which are adapted to game context by the game's AI system. The motion of the characters populating the game's world, however, is evolving to an interesting blend of kinematics, dynamics, biomechanics and AI drivenmotion planning.

Our goal here is to present the technologies involved in creating what are essentially character automata, emotionless and largely brainless character shells that nevertheless exhibit enough "behavior" to move as directed while adapting to the environment through sensing and actuating responses. This abstracts the complexities of low level motion control, dynamics, collision detection etc. and allows the game's artificial intelligence system to direct these characters at a higher level.

While much research has already been conducted in this area and some great results have been published, we will present the particular issues that face game developers working on current and next generation consoles, and how these technologies may be integrated into game production pipelines so to facilitate the creation of character performances in games. The challenges posed by the limited memory and CPU bandwidth (though this is changing somewhat with next generation) and the challenges of integrating these solutions with current game design approaches leads to some interesting problems, some of which the industry has solutions for and some others which still remain largely unsolved.
Post‐focus prosodic phrase boundaries in Tokyo Japanese: asymmetric behavior of an f0 cue and domain‐final lengthening*
Authors: Sugahara Mariko
Published: October 2005

Abstract. The present study shows an asymmetric behaviour between an F0 cue and a durational cue in a post‐FOCUS part of an utterance in Tokyo Japanese. Though F0 resetting which marks the left edge of a Major Phonological Phrase is missing at the left edge of a post‐FOCUS clause boundary, word‐final lengthening which marks the right edge of an Intonational Phrase is retained there. Based on this observation, Headless Post‐FOCUS IP Structure is proposed, and such prosodic structure is argued to be compatible with not only the facts obtained in this study but also the theory of FOCUS and prosodic prominence.
Syntactic and eurhythmic constraints on phrasing decisions in Catalan*
Authors: Prieto Pilar
Published: October 2005

Abstract.  This article investigates the role of syntactic and prosodic markedness constraints on the construction of phonological phrases (φ‐ or p‐phrases) in Catalan. It is shown that the construction of prosodic structure in this language cannot solely rely on syntactic information but rather also has to refer to prosodic markedness constraints which regulate the size and eurhythmicity of phrase constituents. Specifically, phonological phrasing in Catalan is determined, among other things, by the interaction of right‐alignment of syntactic and phonological phrases (Align‐XP,R; Selkirk 1986) and the requirement that each XP is contained in a p‐phrase (Wrap‐XP; Truckenbrodt 1995) together with the following set of prosodic factors: 1) a maximal requirement on the length of p‐phrases at the end of utterances, Max‐Bin‐End, which requires that each p‐phrase containing a nuclear stress should contain at most two prosodic words; 2) a minimality constraint on the prosodic parsing of utterances, Min‐Utt, which requires that each utterance contains a minimally binary p‐phrase; 3) a eurhythmic condition, No‐Clash, which does not allow the presence of two immediately adjacent stressed syllables, partly affects phrasing decisions in this language. Size and eurhythmic effects of this type are also active, though in a weaker fashion, in other Romance languages such as Italian (Ghini 1993a, 1993b), in Brazilian Portuguese (Sandalo & Truckenbrodt 2002), and in European Portuguese and Spanish (Elordieta et al. 2003, Prieto (forthcoming)).
Separating similar effects of conjunction and intonation in the resolution of lexical ambiguity*
Authors: Jackson Scott , Townsend David , Bever Thomas
Published: October 2005

Abstract.  Recent work has shown that prosodic information has a number of important effects on human sentence processing, including effects on the semantic integration of clauses (Schafer 1997). In an effort to learn more about the nature of these prosodic effects, we ran an experiment that manipulated not only prosody, but also the type of initial subordinating conjunction, which we predicted might have a similar effect on processing. Our results confirmed previous work on the effects of conjunction type (Townsend & Bever 1978; Townsend 1983), and they replicated the basic pattern of the prosodic effect from Schafer (1997). However, a more in‐depth analysis suggests (i) that prosody and conjunction type are playing different, interacting roles in this ‘‘makes sense’’ decision task, and (ii) that the prosodic effect may be more directly dependent on the gradient phonetic feature of phrase‐final lengthening, rather than on an abstract phonological prosodic category.
Consistent estimation of the memory parameter for nonlinear time series
Authors: Dalla Violetta , Giraitis Liudas , Hidalgo Javier
Published: October 2005

Abstract.  For linear processes, semiparametric estimation of the memory parameter, based on the log‐periodogram and local Whittle estimators, has been exhaustively examined and their properties well established. However, except for some specific cases, little is known about the estimation of the memory parameter for nonlinear processes. The purpose of this paper is to provide the general conditions under which the local Whittle estimator of the memory parameter of a stationary process is consistent and to examine its rate of convergence. We show that these conditions are satisfied for linear processes and a wide class of nonlinear models, among others, signal plus noise processes, nonlinear transforms of a Gaussian process ξt and exponential generalized autoregressive, conditionally heteroscedastic (EGARCH) models. Special cases where the estimator satisfies the central limit theorem are discussed. The finite‐sample performance of the estimator is investigated in a small Monte Carlo study.
Welfare to What? After Workfare in Toronto
Authors: Lightman Ernie , Mitchell Andrew , Herd Dean
Published: October 2005

An employment survey among people in Toronto who left Ontario Works — a classic “work‐first” regime — shows clear secondary labour market status. Most interventions typical of work‐first programmes did not have a positive effect on job quality: contrary to the “stepping stones” theory that poor initial jobs lead to better jobs, those who changed jobs after leaving assistance experienced poorer job quality. A shift in orientation to “sustainable employment” is required to address the employment needs of those on social assistance. Policy must also address the fact that the social assistance caseload includes a size able group that face significant barriers to employment other than education or skills.
The Rise and Fall of Unemployment Insurance in Israel
Authors: Gal John
Published: October 2005

The Israeli unemployment insurance (UI) programme was adopted in 1972 but, in the three decades since, it has undergone major changes. As a result of these changes, the programme is currently far less accessible and less generous than it was in its original form. This article documents the policy process that led to retrenchment of UI in Israel. This process was justified by a professed desire on the part of decision‐makers to deal with the problem of the unemployment trap caused by UI and was facilitated by a legislative manoeuvre that enabled the State to overcome institutional obstacles to change within the Parliament.
Characterization of glycoconjugate antigens in mouse embryonic neural precursor cells
Authors: Yanagisawa Makoto , Taga Tetsuya , Nakamura Kazuo , Ariga Toshio , Yu Robert K.
Published: October 2005

Neuronal and glial cells organizing the central nervous system (CNS) are generated from common neural precursor cells (NPCs) during neural development. However, the expression of cell‐surface glycoconjugates that are crucial for determining the properties and biological function of these cells at different stages of development has not been clearly defined. In this study, we investigated the expression of several stage‐specific glycoconjugate antigens, including several b‐series gangliosides GD3, 9‐O‐acetyl GD3, GT1b and GQ1b, stage‐specific embryonic antigen‐1 (SSEA‐1) and HNK‐1, in mouse embryonic NPCs employing immunocytochemistry and flow cytometry. In addition, several of these antigens were positively identified by chemical means for the first time. We further showed that the SSEA‐1 immunoreactivity was contributed by both glycoprotein and glycolipid antigens, and that of HNK‐1 was contributed only by glycoproteins. Functionally, SSEA‐1 may participate in migration of the cells from neurospheres in an NPC cell culture system, and the effect could be repressed by anti‐SSEA‐1 antibody. Based on this observation, we identified β1 integrin as one of the SSEA‐1 carrier glycoproteins. Our data thus provide insights into the functional role of certain glycoconjugate antigens in NPCs during neural development.
Apparent presence of Ser133‐phosphorylated cyclic AMP response element binding protein (pCREB) in brain mitochondria is due to cross‐reactivity of pCREB antibodies with pyruvate dehydrogenase
Authors: Pláteník Jan , Balcar Vladimír J. , Yoneda Yukio , Mioduszewska Barbara , Buchal Richard , Hynek Radovan , Kilianek Lukasz , Kuramoto Nobuyuki , Wilczynski Grzegorz , Ogita Kiyokazu , Nakamura Yoichi , Kaczmarek Leszek
Published: October 2005

Cyclic AMP response element binding protein (CREB) is a constitutive transcription factor that activates transcription following stimulus‐dependent phosphorylation at Ser133, implicated in synaptic plasticity and neuronal survival pathways. The prevailing view that CREB is exclusively nuclear has been questioned by several studies, and, for example, mitochondrial localization has been reported. Using subcellular fractionation of rat brain cortex coupled with western immunoblotting with Ser133‐phospho‐CREB (pCREB) antibodies, we found a robust pCREB immunoreactivity (IR) in mitochondria‐enriched fractions. The pCREB antibodies also stained the mitochondria, in addition to nuclei, of glial cells in primary cortical cultures. However, two CREB antibodies against different epitopes and gel shift assay detected the CREB protein mainly in the nuclear fraction. The two‐dimensional electrophoretic mobility of mitochondrial pCREB IR differed markedly from the nuclear CREB/pCREB IR, indicating that the pCREB antibody cross‐reacts with another mitochondrial protein. Immunoprecipitation of the mitochondrial pCREB IR produced three bands on sodium dodecyl sulfate–polyacrylamide gel electrophoresis, which were identified by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry as E2, E1 α‐subunit, and E1 β‐subunit of pyruvate dehydrogenase complex. The cross‐reacting epitope was identified as phospho‐Ser300 of the α‐subunit. In conclusion, this study confirms the presence of pCREB‐like IR in brain mitochondria that, after careful scrutiny, turned out to be pyruvate dehydrogenase rather than authentic CREB.
Human spastin has multiple microtubule‐related functions
Authors: Salinas Sara , Carazo‐Salas Rafael E. , Proukakis Christos , Cooper J. Mark , Weston Anne E. , Schiavo Giampietro , Warner Thomas T.
Published: October 2005

Hereditary spastic paraplegias (HSPs) are neurodegenerative diseases caused by mutations in more than 20 genes, which lead to progressive spasticity and weakness of the lower limbs. The most frequently mutated gene causing autosomal dominant HSP is SPG4, which encodes spastin, a protein that belongs to the family of ATPases associated with various cellular activities (AAAs). A number of studies have suggested that spastin regulates microtubule dynamics. We have studied the ATPase activity of recombinant human spastin and examined the effect of taxol‐stabilized microtubules on this activity. We used spastin translated from the second ATG and provide evidence that this is the physiologically relevant form. We showed that microtubules enhance the ATPase activity of the protein, a property also described for katanin, an AAA of the same spastin subgroup. Furthermore, we demonstrated that human spastin has a microtubule‐destabilizing activity and can bundle microtubules in vitro, providing new insights into the molecular pathogenesis of HSP.
Progression of age‐associated cognitive impairment correlates with quantitative and qualitative loss of TrkA receptor protein in nucleus basalis and cortex
Authors: Saragovi H. Uri
Published: October 2005

A direct correlation between disease progression and reduced expression of TrkA receptor in cholinergic neurons has been documented in neurocognitive pathologies including Alzheimer's disease. We investigated whether reduced expression of TrkA protein might also correlate with the level of cognitive impairment in age‐associated cognitive impairment. Quantitative and qualitative measurements of TrkA protein levels in the cortex and nucleus basalis of aged rats that had been well‐characterized behaviorally as ‘unimpaired’, ‘mildly impaired’ or ‘fully impaired’ demonstrated significant changes in TrkA expression. In the mildly impaired cognitive state phenotypic silencing of TrkA was detected in neurons expressing TrkA at high density but before cholinergic atrophy or loss of TrkA+ neurons was detected. In the fully impaired cognitive state a significant loss in TrkA+ cholinergic neurons together with a more significant phenotypic silencing of TrkA expression then took place. These data suggest that TrkA+ cholinergic cells are associated with cognition, TrkA could be a biomarker of the cognitive state and phenotypic loss of TrkA precedes neuronal loss and probably sensitizes cells to death. We speculate that neurotrophic deficits may be a shared mechanism for cognitive decline in aging and Alzheimer's disease.
Inhibition of thrombin‐induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo
Authors: Choi Sang H. , Lee Da Y. , Chung Eun S. , Hong Young B. , Kim Seung U. , Jin Byung K.
Published: October 2005

The present study shows that activation of microglial NADPH oxidase and production of reactive oxygen species (ROS) is associated with thrombin‐induced degeneration of nigral dopaminergic neurons in vivo. Seven days after thrombin injection in the rat substantia nigra (SN), tyrosine hydroxylase immunocytochemistry showed a significant loss of nigral dopaminergic neurons. This cell death was accompanied by localization of terminal deoxynucleotidyl transferase‐mediated fluorecein UTP nick‐end labelling (TUNEL) staining within dopaminergic neurons. This neurotoxicity was antagonized by the semisynthetic tetracycline derivative, minocycline, and the observed neuroprotective effects were associated with the ability of minocycline to suppress NADPH oxidase‐derived ROS production and pro‐inflammatory cytokine expression, including interleukin‐1β and inducible nitric oxide synthase, from activated microglia. These results suggest that microglial NADPH oxidase may be a viable target for neuroprotection against oxidative damage.
Unmet Care Needs and Key Outcomes in Dementia
Authors: Gaugler Joseph E. , Kane Robert L. , Kane Rosalie A. , Newcomer Robert
Published: October 2005

Objectives: To determine how unmet needs for activity of daily living tasks influenced nursing home placement, death, or loss to follow‐up in dementia.

Design: An 18‐month longitudinal design, with interviews administered every 6 months.

Setting: Eight catchment areas in the United States.

Participants: Five thousand eight hundred thirty‐one dementia patients and their caregivers were included at baseline.

Measurements: Measures of sociodemographic context of care; functional, cognitive, and behavioral status of care recipients; caregiver stress and well‐being; and formal and informal resources served as covariates. The independent variables of interest were unweighted unmet care need scores and unmet need scores weighted by importance and severity in a prior sample of older consumers of long‐term care. Outcomes included nursing home placement, death, and loss to follow‐up.

Results: Cox regression models suggested that greater unmet need was predictive of nursing home placement, death, and loss to follow‐up. These results were apparent when the unweighted and the weighted scores for unmet need with activity of daily living dependencies were used.

Conclusion: Unmet need may be useful in identifying dementia care recipients at risk for nursing home placement and death. Further study of unmet need is needed to effectively assess and target intervention protocols during the course of dementia.
Setting Eligibility Criteria for a Care‐Coordination Benefit
Authors: Cigolle Christine T. , Langa Kenneth M. , Kabeto Mohammed U. , Blaum Caroline S.
Published: October 2005

Objectives: To examine different clinically relevant eligibility criteria sets to determine how they differ in numbers and characteristics of individuals served.

Design: Cross‐sectional analysis of the 2000 wave of the Health and Retirement Study (HRS), a nationally representative longitudinal health interview survey of adults aged 50 and older.

Setting: Population‐based cohort of community‐dwelling older adults, subset of an ongoing longitudinal health interview survey.

Participants: Adults aged 65 and older who were respondents in the 2000 wave of the HRS (n=10,640, representing approximately 33.6 million Medicare beneficiaries).

Measurements: Three clinical criteria sets were examined that included different combinations of medical conditions, cognitive impairment, and activity of daily living/instrumental activity of daily living (ADL/IADL) dependency.

Results: A small portion of Medicare beneficiaries (1.3–5.8%) would be eligible for care coordination, depending on the criteria set chosen. A criteria set recently proposed by Congress (at least four severe complex medical conditions and one ADL or IADL dependency) would apply to 427,000 adults aged 65 and older in the United States. Criteria emphasizing cognitive impairment would serve an older population.

Conclusion: Several criteria sets for a Medicare care‐coordination benefit are clinically reasonable, but different definitions of eligibility would serve different numbers and population groups of older adults.
Baseline Laboratory Monitoring of Cardiovascular Medications in Elderly Health Maintenance Organization Enrollees
Authors: Simon Steven R. , Andrade Susan E. , Ellis Jennifer L. , Nelson Winnie W. , Gurwitz Jerry H. , Lafata Jennifer Elston , Davis Robert L. , Feldstein Adrianne , Raebel Marsha A.
Published: October 2005

Objectives: To identify correlates of laboratory monitoring errors in elderly health maintenance organization (HMO) members at the initiation of therapy with cardiovascular medications.

Design: Cross‐sectional study in 10 HMOs.

Setting: United States.

Participants: From a 2 million‐member sample, individuals aged 65 and older who received one of seven cardiovascular medications (angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), amiodarone, digoxin, diuretics, potassium supplements, and statins) and did not have recommended baseline monitoring performed during the 180 days before or 14 days after the index dispensing.

Measurements: The proportion of members receiving each drug for whom recommended laboratory monitoring was not performed. Laboratory monitoring error rates stratified by sex, age group, chronic disease score, and HMO site were examined, and logistic regression was used to identify predictors of laboratory monitoring errors.

Results: Error rates varied by medication class, ranging from 23% of patients receiving potassium supplementation without serum potassium and serum creatinine monitoring to 58% of patients receiving amiodarone who did not have recommended monitoring for thyroid and liver function. Highest error rates occurred in the youngest elderly for ACE inhibitors, ARBs, digoxin, diuretics, and potassium supplements, although in patients receiving amiodarone and statins, errors were most frequent in the oldest elderly. Errors occurred more frequently in patients with less comorbidity.

Conclusion: Laboratory monitoring errors occurred frequently in elderly HMO members at the initiation of therapy with cardiovascular medications. Further study must examine the association between these errors and adverse outcomes.
Do‐Not‐Resuscitate Policy on Acute Geriatric Wards in Flanders, Belgium
Authors: De Gendt Cindy , Bilsen Johan , Stichele Robert Vander , Lambert Margareta , Noortgate NeleVan Den , Deliens Luc
Published: October 2005

Objectives: To describe the historical development and status of a do‐not‐resuscitate (DNR) policy on acute geriatric wards in Flanders, Belgium, and to compare it with the international situation.

Design: Structured mail questionnaires.

Setting: All 94 acute geriatric wards in hospitals in Flanders in 2002 (the year Belgium voted a law on euthanasia).

Participants: Head geriatricians.

Measurements: A questionnaire was mailed about the existence, development, and implementation of the DNR policy (guidelines and order forms), with a request to return copies of existing DNR guidelines and DNR order forms.

Results: The response was 76.6%, with hospital characteristics not significantly different for responders and nonresponders. Development of DNR policy began in 1985, with a step‐up in 1997 and 2001. In 2002, a DNR policy was available in 86.1% of geriatric wards, predominantly with institutional DNR guidelines and individual, patient‐specific DNR order forms. Geriatric wards in private hospitals implemented their policy later (P=.01) and more often had order forms (P=.04) than those in public hospitals. The policy was initiated and developed predominantly from an institutional perspective by the hospital. The forms were not standardized and generally lacked room to document patient involvement in the decision making process.

Conclusion: Implementation of institutional DNR guidelines and individual DNR order forms on geriatric wards in Flanders lagged behind that of other countries and was still incomplete in 2002. DNR policies varied in content and scope and were predominantly an expression of institutional defensive attitudes rather than a tool to promote patient involvement in DNR and other end‐of‐life decisions.
Uterine Response to Multiple Inoculations with Arcanobacterium pyogenes and Escherichia coli in Nulliparous Ewes
Authors: Wulster‐Radcliffe Meghan C. , Seals Richard C. , Lewis Gregory S.
Published: October 2005

Problem

Uterine infections seem more severe in nulliparous animals. Our objective was to determine whether intrauterine inoculation of nulliparous ewes with Arcanobacterium pyogenes and Escherichia coli would produce an antibody response and reduce the severity of subsequent infections.

Method of study

Nulliparous ewes (n = 9/treatment) received (i) ‘primary intrauterine inoculation’ with phosphate‐buffered saline (PBS) and ‘secondary intrauterine inoculation’ with PBS; (ii) primary PBS‐secondary 75 × 107 cfu of A. pyogenes and 35 × 107 cfu of E. coli (PBS–Bacteria); (iii) primary bacteria‐secondary PBS; or (iv) primary bacteria–secondary bacteria (Bacteria–Bacteria).

Results

Inoculations evoked an antibody response. Postmortem examinations 6 days after the secondary inoculation indicated that PBS‐treated ewes did not develop uterine infections, but all bacteria‐treated ewes did. Infections were either less severe or closer to resolution in Bacteria–Bacteria than they were in PBS–Bacteria ewes.

Conclusions

Intrauterine inoculation of nulliparous ewes with A. pyogenes and E. coli evokes an antibody response that may help the uterus reduce the severity of subsequent infections.
IgG, IgA and IgM Antibodies against FSH: Serological Markers of Pathogenic Autoimmunity or of Normal Immunoregulation?
Authors: Haller Kadri , Mathieu Christine , Rull Kristiina , Matt Kadri , Béné Marie C. , Uibo Raivo
Published: October 2005

Problem

Autoimmune mechanisms are often involved in causing infertility. Among the possible targets of autoantibodies, the follicle‐stimulating hormone (FSH) which regulates the follicular maturation in human ovary is a promising candidate. We aimed to study whether anti‐FSH‐antibodies might be involved in different clinical types of infertility.

Method of study

The study group consisted of 178 patients (75 with polycystic ovary syndrome (PCOS), 103 with endometriosis) and 75 pregnant women. Female blood donors formed the control group (n = 85). Indirect enzyme‐linked immunosorbent assay tests were performed using purified FSH as antigens and a synthetic peptide corresponding to the 78–93 region (V14D) of the human FSH β‐chain.

Conclusion

We showed that anti‐FSH‐antibodies were present in controls and their production decreased during pregnancy. Endometriosis and PCOS were associated with higher values of anti‐FSH‐immunoglobulin (Ig)A, anti‐V14D‐IgA, and endometriosis with anti‐V14D‐IgG. Our data suggest that anti‐FSH‐IgA could be a marker of ovarian disorders that cause infertility.
Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice
Authors: Pennanen L. , Wolfer D. P. , Nitsch R. M. , Götz J.
Published: October 2005

The neuropathological hallmark shared between Alzheimer's disease (AD) and familial frontotemporal dementia (FTDP‐17) are neurofibrillary tangles (NFT) which are composed of filamentous aggregates of the microtubule‐associated protein tau. Their formation has been reproduced in transgenic mice, which express the FTDP‐17‐associated mutation P301L of tau. In these mice, tau aggregates are found in many brain areas including the hippocampus and the amygdala, both of which are characterized by NFT formation in AD. Previous studies using an amygdala‐specific test battery revealed an increase in exploratory behavior and an accelerated extinction of conditioned taste aversion in these mice. Here, we assessed P301L mice in behavioral tests known to depend on an intact hippocampus. Morris water maze and Y‐maze revealed intact spatial working memory but impairment in spatial reference memory at 6 and 11 months of age. In addition, a modest disinhibition of exploratory behavior at 6 months of age was confirmed in the open field and the elevated O‐maze and was more pronounced during aging.
Visual detection, pattern discrimination and visual acuity in 14 strains of mice
Authors: Wong A. A. , Brown R. E.
Published: October 2005

Based on the procedure of Prusky et al. (2000, Vision Research, 40, 2201–2209), we used a computer‐based, two‐alternative swim task to evaluate visual detection, pattern discrimination and visual acuity in 14 strains of mice from priority groups A and B of the JAX phenome project (129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/Ei, DBA/2J, FVB/NJ, MOLF/Ei, SJL/J, SM/J and SPRET/Ei). Each mouse was tested for eight trials/day for 8 days on each of the three tests. There was a significant strain difference in visual ability in all three tests. Mice with reported normal vision (129S1/SvImJ, C57BL/6J and DBA/2J) and one albino strain (AKR/J) performed very well in these tasks. The other albino strains (A/J, BALB/cByJ and BALB/cJ) took longer to learn the tasks than mice with normal vision and did not reach the criterion of 70% correct. Mice with retinal degeneration (C3H/HeJ, FVB/NJ, MOLF/Ei and SJL/J) performed only at chance levels as did the three strains with unknown visual abilities (CAST/Ei, SM/J and SPRET/Ei). Because many behavioral tasks for rodents rely on visual cues, we suggest that the visual abilities of mice should be evaluated before they are tested in commonly used visuo‐spatial learning and memory tasks.
Auditory and visual prepulse inhibition in mice: parametric analysis and strain comparisons
Authors: Aubert L. , Reiss D. , Ouagazzal A.‐M.
Published: October 2005

Prepulse inhibition (PPI) is a multimodal phenomenon where the prepulse and the startling stimulus can be presented in either the same or the different sensory modalities. The aim of the present study was to characterize intramodal and cross‐modal PPI in mice. We first examined the effects of varying prepulse intensity and prepulse duration on auditory and visual PPI in three inbred mouse strains C57BL/6J, 129S2 and BALB/cByJ mice. Increasing the intensity (5–15 dB above the background) and the duration (1–25 milliseconds) of the acoustic prepulse increased auditory PPI, and maximum level of inhibition was reached with each prepulse intensity at specific prepulse duration (between 5 and 15 milliseconds). Varying the intensity (30–300 lux) and the duration (1–25 milliseconds) of the light flashes had similar impact on visual PPI level (optimal durations between 1 and 10 milliseconds). There were also marked strain differences in PPI performances, with 129S2 and BALB/cByJ mice displaying the highest and the lowest scores of auditory PPI, respectively. In contrast, opposite strain ranking was obtained for visual PPI. The temporal expression of PPI was then studied in the same mouse strains using a wide range of interstimulus intervals (2–2000 milliseconds between the prepulse offset and the pulse onset). The time–course of the auditory and the visual PPI were relatively comparable (bell‐shaped curve) with optimal lead‐times between 10 and 100 milliseconds, but the shape of the temporal function varied between the mouse strains depending on the prepulse modality. These findings demonstrate that PPI has many physiological and genetic determinants that vary greatly across temporal and intensity domain, as well as stimulus modality.
Type I antifreeze proteins expressed in snailfish skin are identical to their plasma counterparts
Authors: Evans Robert P. , Fletcher Garth L.
Published: October 2005

Type I antifreeze proteins (AFPs) are usually small, Ala‐rich α‐helical polypeptides found in right‐eyed flounders and certain species of sculpin. These proteins are divided into two distinct subclasses, liver type and skin type, which are encoded by separate gene families. Blood plasma from Atlantic (Liparis atlanticus) and dusky (Liparis gibbus) snailfish contain type I AFPs that are significantly larger than all previously described type I AFPs. In this study, full‐length cDNA clones that encode snailfish type I AFPs expressed in skin tissues were generated using a combination of library screening and PCR‐based methods. The skin clones, which lack both signal and pro‐sequences, produce proteins that are identical to circulating plasma AFPs. Although all fish examined consistently express antifreeze mRNA in skin tissue, there is extreme individual variation in liver expression – an unusual phenomenon that has never been reported previously. Furthermore, genomic Southern blot analysis revealed that snailfish AFPs are products of multigene families that consist of up to 10 gene copies per genome. The 113‐residue snailfish AFPs do not contain any obvious amino acid repeats or continuous hydrophobic face which typify the structure of most other type I AFPs. These structural differences might have implications for their ice‐crystal binding properties. These results are the first to demonstrate a dual liver/skin role of identical type I AFP expression which may represent an evolutionary intermediate prior to divergence into distinct gene families.
A possible role of mitochondria in the apoptotic‐like programmed nuclear death of Tetrahymena thermophila
Authors: Kobayashi Takashi , Endoh Hiroshi
Published: October 2005

The ciliated protozoan Tetrahymena has a unique apoptosis‐like process, which is called programmed nuclear death (PND). During conjugation, the new germinal micro‐ and somatic macro‐nuclei differentiate from a zygotic fertilized nucleus, whereas the old parental macronucleus degenerates, ensuring that only the new macronucleus is responsible for expression of the progeny genotype. As is the case with apoptosis, this process encompasses chromatin cleavage into high‐molecular mass DNA, oligonucleosomal DNA laddering, and complete degradation of the nuclear DNA, with the ultimate outcome of nuclear resorption. Caspase‐8‐ and caspase‐9‐like activities are involved in the final resorption process of PND. In this report, we show evidence for mitochondrial association with PND. Mitochondria and the degenerating macronucleus were colocalized in autophagosome using two dyes for the detection of mitochondria. In addition, an endonuclease with similarities to mammalian endonuclease G was detected in the isolated mitochondria. When the macronuclei were incubated with isolated mitochondria in a cell‐free system, DNA fragments of 150–400 bp were generated, but no DNA ladder appeared. Taking account of the present observations and the timing of autophagosome formation, we conclude that mitochondria might be involved in Tetrahymena PND, probably with the process of oligonucleosomal laddering.
Flexible nets
Authors: Dunker A. Keith , Cortese Marc S. , Romero Pedro , Iakoucheva Lilia M. , Uversky Vladimir N.
Published: October 2005

Proteins participate in complex sets of interactions that represent the mechanistic foundation for much of the physiology and function of the cell. These protein–protein interactions are organized into exquisitely complex networks. The architecture of protein–protein interaction networks was recently proposed to be scale‐free, with most of the proteins having only one or two connections but with relatively fewer ‘hubs’ possessing tens, hundreds or more links. The high level of hub connectivity must somehow be reflected in protein structure. What structural quality of hub proteins enables them to interact with large numbers of diverse targets? One possibility would be to employ binding regions that have the ability to bind multiple, structurally diverse partners. This trait can be imparted by the incorporation of intrinsic disorder in one or both partners. To illustrate the value of such contributions, this review examines the roles of intrinsic disorder in protein network architecture. We show that there are three general ways that intrinsic disorder can contribute: First, intrinsic disorder can serve as the structural basis for hub protein promiscuity; secondly, intrinsically disordered proteins can bind to structured hub proteins; and thirdly, intrinsic disorder can provide flexible linkers between functional domains with the linkers enabling mechanisms that facilitate binding diversity. An important research direction will be to determine what fraction of protein–protein interaction in regulatory networks relies on intrinsic disorder.
Booster Seat or Seat Belt? Motor Vehicle Injuries and Child Restraint Laws in Preschool and Early School‐Age Children
Authors: Angulo‐Vazquez Vicki , De Santis Joseph P.
Published: October 2005

ISSUES AND PURPOSE.  Despite numerous interventions to reduce motor vehicle injuries and deaths in children living in the United States, unintentional motor vehicle injuries continue to be the leading cause of death of U.S. children.

CONCLUSION.  Even though child restraint laws have been enacted, many children 5 to 9 years of age continue to be injured in motor vehicle crashes. These injuries are related to the improper use of child restraints. Reasons for injuries in this age group were explored by a review of the current literature.

PRACTICE IMPLICATIONS.  Nurses have a unique role in educating families about proper restraint and in contributing to the evidence base for practice.
Organ‐specific ligation‐induced changes in harmonic components of the pulse spectrum and regional vasoconstrictor selectivity in Wistar rats
Authors: Hsu Tse Lin , Chao Pin Tsun , Hsiu Hsin , Wang Wei Kung , Li Sai Ping , Wang Yuh Ying Lin
Published: October 2005

It has been shown previously that the amplitudes of the harmonic components of the pulse spectrum vary in specific patterns when the arteries leading to different organs are ligated, with the variations in the harmonics being linearly additive. Since ligation can be regarded as a vast increase in organ resistance, the present study examined the potential of using these ligation‐induced variations in the pulse spectrum as reference parameters for an increase in vascular resistance and for regional vasoconstrictor selectivity. A vasoconstrictor, either arginine vasopressin (AVP) or angiotensin II (Ang II), was infused into anaesthetized Wistar rats via the femoral vein for 1 h. The distinct harmonic‐specific drug effects on the pulse spectrum were simulated by combining renal artery and superior mesenteric artery ligations in different ratios, the ratio with the lowest mean square difference determining the regional drug selectivity. The ratios indicated that the effect of AVP on the pulse spectrum was attributable to the combined effect of ligating the renal and superior mesenteric arteries, while the effect of Ang II was attributable to ligation of the renal artery. The results are comparable with those of investigations of regional vascular resistance performed using traditional methods. Our findings indicate that the ligation‐induced variations in the pulse spectrum can be used to determine regional increases in vascular resistance. This implies that blood pressure can be used as the sole parameter to determine which arterial bed has been affected by the vasoconstrictor, and how seriously.
Arterial baroreflex resetting during exercise: a current perspective
Authors: Raven Peter B. , Fadel Paul J. , Ogoh Shigehiko
Published: October 2005

Within the past 20 years numerous animal and human experiments have provided supportive evidence of arterial baroreflex resetting during exercise. In addition, it has been demonstrated that both the feedforward mechanism of central command and the feedback mechanism associated with skeletal muscle afferents (the exercise pressor reflex) play both independent and interactive roles in the resetting of the arterial baroreflex with exercise. A fundamental alteration associated with baroreflex resetting during exercise is the movement of the operating point of the reflex away from the centring point and closer to the threshold, thereby increasing the ability of the reflex to buffer hypertensive stimuli. Recent studies suggest that central command and the cardiopulmonary baroreceptors may play a role in this movement of the operating point on the baroreflex–heart rate and baroreflex–blood pressure curve, respectively. Current research is focusing on the investigation of central neural mechanisms involved in cardiovascular control, including use of electrophysiological and molecular biological techniques in rat and mouse models to investigate baroreflex resetting as well as use of state of the art brain imaging techniques in humans. However, the purpose of this review is to describe the role of the arterial baroreflex in the regulation of arterial blood pressure during physical activity from a historical perspective with a particular emphasis on human investigations.