bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival Motor Neuron Function in Motor Axons Is Independent of Functions Required for Small Nuclear Ribonucleoprotein Biogenesis
Authors: Carrel Tessa L. , McWhorter Michelle L. , Workman Eileen , Zhang Honglai , Wolstencroft Elizabeth C. , Lorson Christian , Bassell Gary J. , Burghes Arthur H. M. , Beattie Christine E.
Published: October 2006

Spinal muscular atrophy (SMA) is a motor neuron degenerative disease caused by low levels of the survival motor neuron (SMN) protein and is linked to mutations or loss ofSMN1and retention ofSMN2. How low levels of SMN cause SMA is unclear. SMN functions in small nuclear ribonucleoprotein (snRNP) biogenesis, but recent studies indicate that SMN may also function in axons. We showed previously that decreasing Smn levels in zebrafish using morpholinos (MO) results in motor axon defects. To determine how Smn functions in motor axon outgrowth, we coinjectedsmnMO with various humanSMNRNAs and assayed the effect on motor axons. Wild-type SMN rescues motor axon defects caused by Smn reduction in zebrafish. Consistent with these defects playing a role in SMA, SMN lacking exon 7, the predominant form from theSMN2gene, and human SMA mutations do not rescue defective motor axons. Moreover, the severity of the motor axon defects correlates with decreased longevity. We also show that a conserved region in SMN exon 7, QNQKE, is critical for motor axon outgrowth. To address the function of SMN important for motor axon outgrowth, we determined the ability of different SMN forms to oligomerization and bind Sm protein, functions required for snRNP biogenesis. We identified mutations that failed to rescue motor axon defects but retained snRNP function. Thus, we have dissociated the snRNP function of SMN from its function in motor axons. These data indicate that SMN has a novel function in motor axons that is relevant to SMA and is independent of snRNP biosynthesis.
Spine Ca2+Signaling in Spike-Timing-Dependent Plasticity
Authors: Nevian Thomas , Sakmann Bert
Published: October 2006

Calcium is a second messenger, which can trigger the modification of synaptic efficacy. We investigated the question of whether a differential rise in postsynaptic Ca2+([Ca2+]i) alone is sufficient to account for the induction of long-term potentiation (LTP) and long-term depression (LTD) of EPSPs in the basal dendrites of layer 2/3 pyramidal neurons of the somatosensory cortex. Volume-averaged [Ca2+]itransients were measured in spines of the basal dendritic arbor for spike-timing-dependent plasticity induction protocols. The rise in [Ca2+]iwas uncorrelated to the direction of the change in synaptic efficacy, because several pairing protocols evoked similar spine [Ca2+]itransients but resulted in either LTP or LTD. The sequence dependence of near-coincident presynaptic and postsynaptic activity on the direction of changes in synaptic strength suggested that LTP and LTD were induced by two processes, which were controlled separately by postsynaptic [Ca2+]ilevels. Activation of voltage-dependent Ca2+channels before metabotropic glutamate receptors (mGluRs) resulted in the phospholipase C-dependent (PLC-dependent) synthesis of endocannabinoids, which acted as a retrograde messenger to induce LTD. LTP required a large [Ca2+]itransient evoked by NMDA receptor activation. Blocking mGluRs abolished the induction of LTD and uncovered the Ca2+-dependent induction of LTP.

We conclude that the volume-averaged peak elevation of [Ca2+]iin spines of layer 2/3 pyramids determines the magnitude of long-term changes in synaptic efficacy. The direction of the change is controlled, however, via a mGluR-coupled signaling cascade. mGluRs act in conjunction with PLC as sequence-sensitive coincidence detectors when postsynaptic precede presynaptic action potentials to induce LTD. Thus presumably two different Ca2+sensors in spines control the induction of spike-timing-dependent synaptic plasticity.
RET Is Dispensable for Maintenance of Midbrain Dopaminergic Neurons in Adult Mice
Authors: Jain Sanjay , Golden Judith P. , Wozniak David , Pehek Elizabeth , Johnson Eugene M. , Milbrandt Jeffrey
Published: October 2006

Glial cell-line derived neurotrophic factor (GDNF)-mediated RET tyrosine kinase signaling is implicated in the survival of several PNS and CNS neuronal populations that are important in the pathogenesis of several disorders including Parkinson's disease and drug addiction. However, it has been difficult to study these processes and the physiological importance of this pathway in adult mice because of the neonatal lethality ofGdnfandRetnull mice. We report successful creation of RET conditional reporter mice to investigate postnatal physiologic roles of RET and monitor the fate of RET-expressing cell types. To delete RET specifically in dopaminergic neurons and determine the physiologic requirement of RET in the maintenance of substantia nigra compacta (SNC) and ventral tegmental area (VTA), we bred the RET conditional mice with mice that specifically express Cre from the dopamine transporter (Dat) locus. A detailed morphometric and biochemical analysis including dopaminergic neuron number and size in SNC and VTA, and fiber density in the striatum and nucleus accumbens, and dopamine levels indicate that RET is not required for providing global trophic support to midbrain dopaminergic neurons in adult mice. Furthermore, RET deficiency in these neurons does not cause major sensorimotor abnormalities. Hence our results support the idea that RET signaling is not critical for the normal physiology of the SNC and VTA in adult mice.
Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-β Peptide Catabolism
Authors: Yin Ke-Jie , Cirrito John R. , Yan Ping , Hu Xiaoyan , Xiao Qingli , Pan Xiaoou , Bateman Randall , Song Haowei , Hsu Fong-Fu , Turk John , Xu Jan , Hsu Chung Y , Mills Jason C. , Holtzman David M. , Lee Jin-Moo
Published: October 2006

It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) may result from an imbalance between the generation and clearance of the amyloid-β peptide (Aβ). Although familial AD appears to be caused by Aβ overproduction, sporadic AD (the most prevalent form) may result from impairment in clearance. Recent evidence suggests that several proteases may contribute to the degradation of Aβ. Furthermore, astrocytes have recently been implicated as a potential cellular mediator of Aβ degradation. In this study, we examined the possibility that matrix metalloproteinases (MMPs), proteases known to be expressed and secreted by astrocytes, could play a role in extracellular Aβ degradation. We found that astrocytes surrounding amyloid plaques showed enhanced expression of MMP-2 and MMP-9 in aged amyloid precursor protein (APP)/presenilin 1 mice. Moreover, astrocyte-conditioned medium (ACM) degraded Aβ, lowering levels and producing several fragments after incubation with synthetic human Aβ1–40and Aβ1–42. This activity was attenuated with specific inhibitors of MMP-2 and -9, as well as in ACM derived frommmp-2or-9knock-out (KO) mice.In vivo, significant increases in the steady-state levels of Aβ were found in the brains ofmmp-2and-9KO mice compared with wild-type controls. Furthermore, pharmacological inhibition of the MMPs withN-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-l-tryptophan methylamide (GM 6001) increased brain interstitial fluid Aβ levels and elimination of half-life in APPsw mice. These results suggest that MMP-2 and -9 may contribute to extracellular brain Aβ clearance by promoting Aβ catabolism.
Brain Regions Mediating Flexible Rule Use during Development
Authors: Crone Eveline A. , Donohue Sarah E. , Honomichl Ryan , Wendelken Carter , Bunge Silvia A.
Published: October 2006

During development, children improve at retrieving and using rules to guide their behavior and at flexibly switching between these rules. In this study, we used functional magnetic resonance imaging to examine the changes in brain function associated with developmental changes in flexible rule use. Three age groups (8–12, 13–17, and 18–25 years) performed a task in which they were cued to respond to target stimuli on the basis of simple task rules. Bivalent target stimuli were associated with different responses, depending on the rule, whereas univalent target stimuli were associated with fixed responses. The comparison of bivalent and univalent trials enabled the identification of regions modulated by demands on rule representation. The comparison of rule-switch and rule-repetition trials enabled the identification of regions involved in rule switching. We have used this task previously in adults and have shown that ventrolateral prefrontal cortex (VLPFC) and the (pre)-supplementary motor area (pre-SMA/SMA) have dissociable roles in task-switching, such that VLPFC is associated most closely with rule representation, and pre-SMA/SMA is associated with suppression of the previous task set (Crone et al., 2006a). Based on behavioral data in children (Crone et al., 2004), we had predicted that regions associated with task-set suppression would show mature patterns of activation earlier in development than regions associated with rule representation. Indeed, we found an adult-like pattern of activation in pre-SMA/SMA by adolescence, whereas the pattern of VLPFC activation differed among children, adolescents, and adults. These findings suggest that two components of task-switching—rule retrieval and task-set suppression—follow distinct neurodevelopmental trajectories.
A Large-Conductance Calcium-Selective Mechanotransducer Channel in Mammalian Cochlear Hair Cells
Authors: Beurg Maryline , Evans Michael G. , Hackney Carole M. , Fettiplace Robert
Published: October 2006

Sound stimuli are detected in the cochlea by opening of hair cell mechanotransducer (MT) channels, one of the few ion channels not yet conclusively identified at a molecular level. To define their performancein situ, we measured MT channel properties in inner hair cells (IHCs) and outer hair cells (OHCs) at two locations in the rat cochlea tuned to different characteristic frequencies (CFs). The conductance (in 0.02 mmcalcium) of MT channels from IHCs was estimated as 260 pS at both low-frequency and mid-frequency positions, whereas that from OHCs increased with CFs from 145 to 210 pS. The combination of MT channel conductance and tip link number, assayed from scanning electron micrographs, accounts for variation in whole-cell current amplitude for OHCs and its invariance for IHCs. Channels from apical IHCs and OHCs having a twofold difference in unitary conductance were both highly calcium selective but were distinguishable by a small but significant difference in calcium permeability and in their response to lowering ionic strength. The results imply that the MT channel has properties possessed by few known candidates, and its diversity suggests expression of multiple isoforms.
Mitochondrial-Dependent Ca2+Handling in Huntington's Disease Striatal Cells: Effect of Histone Deacetylase Inhibitors
Authors: Oliveira Jorge M. A. , Chen Sylvia , Almeida Sandra , Riley Rebeccah , Gonçalves Jorge , Oliveira Catarina R. , Hayden Michael R. , Nicholls David G. , Ellerby Lisa M. , Rego A. Cristina
Published: October 2006

Evidence suggests that neuronal dysfunction in Huntington's disease (HD) striatum involves deficits in mitochondrial function and in Ca2+handling. However, the relationship between mitochondria and Ca2+handling has been incompletely studied in intact HD striatal cells. Treatment with histone deacetylase (HDAC) inhibitors reduces cell death in HD models, but the effects of this promising therapy on cellular function are mostly unknown. Here, we use real-time functional imaging of intracellular Ca2+and mitochondrial membrane potential to explore the role ofin situHD mitochondria in Ca2+handling. Immortalized striatal (STHdh) cells and striatal neurons from transgenic mice, expressing full-length mutant huntingtin (Htt), were used to model HD. We show that (1) active glycolysis in STHdhcells occludes the mitochondrial role in Ca2+handling as well as the effects of mitochondrial inhibitors, (2) STHdhcells and striatal neurons in the absence of glycolysis are critically dependent on oxidative phosphorylation for energy-dependent Ca2+handling, (3) expression of full-length mutant Htt is associated with deficits in mitochondrial-dependent Ca2+handling that can be ameliorated by treatment with HDAC inhibitors (treatment with trichostatin A or sodium butyrate decreases the proportion of STHdhcells losing Ca2+homeostasis after Ca2+-ionophore challenging, and accelerates the restoration of intracellular Ca2+in striatal neurons challenged with NMDA), and (4) neurons with different response patterns to NMDA receptor activation exhibit different average somatic areas and are differentially affected by treatment with HDAC inhibitors, suggesting subpopulation or functional state specificity. These findings indicate that neuroprotection induced by HDAC inhibitors involves more efficient Ca2+handling, thus improving the neuronal ability to cope with excitotoxic stimuli.
Tomographische Laser-Doppler-Anemometrie (TLDA) – ein neues Verfahren zur Steigerung der Ortsauflösung (Tomographic Laser Doppler Anemometry (TLDA) – a New Method to increase Spatial Resolution)
Authors: Fast Gerald , Kuhn Dietmar , Class Andreas G.
Published: October 2006

Bei der Geschwindigkeitsmessung mittels Laser-Doppler-Anemometrie (LDA) kann das Messvolumen meist als punktförmig betrachtet werden. Einige Anwendungen erfordern eine noch höhere örtliche Auflösung, die mit konventionellen Methoden nicht verbessert werden kann. In dieser Arbeit wird ein Algorithmus vorgestellt, mit dem die örtliche Auflösung des Messvolumens durch ein tomographisches Verfahren deutlich gesteigert werden kann. Anhand künstlich generierter Geschwindigkeitsfelder und Partikelverteilungen werden Messwerte für die Verifikation generiert. Das Verfahren eignet sich für optische Messtechniken, bei denen die Messgröße diskret verteilt vorliegt.
Digitale Holografie an Oberflächengittern zur Zustandsbestimmung von Mikrosystemen (Digital Holography applied to Surface Gratings to determine the Condition of Microsystems)
Authors: Falldorf Claas , Wochnowski Carsten , von Kopylow Christoph , Metev Simeon , Jüptner Werner
Published: October 2006

In diesem Beitrag wird ein neuartiges Messverfahren auf interferometrischer Basis vorgestellt, um den Zustand eines in die Oberfläche des zu untersuchenden Objektes eingebrachten optischen Gitters mithilfe der Digitalen Holografie auszuwerten. Die neue Messtechnik erlaubt die Bestimmung von Verschiebungskomponenten senkrecht bzw. parallel zur untersuchten Oberfläche und bietet gleichzeitig interferometrische Genauigkeit. Da das eingeschriebene optische Gitter wie ein passiver Sensor wirkt, eignet sich das Verfahren besonders zur Langzeitüberwachung von polymeren Mikrokomponenten.
Aufbau und Charakterisierung eines kalorimetrischen Strömungssensors in Dickschichttechnik (Development and Characterization of a Calorimetric Flow Sensor Realized in Thick-Film Technology)
Authors: Smetana Walter , Unger Michael , Gschohsmann Walter
Published: October 2006

Gestützt auf eine Finite-Elemente-Analyse wurde ein kalorimetrischer Strömungssensor in Dickschichttechnik auf einem Stahlrohr aufgebaut. Die Sensorkennlinie wurde sowohl experimentell als auch aufgrund der numerischen Simulation ermittelt. Die erforderlichen Maßnahmen zur Erweiterung des linearen Kennlinienbereichs und zur Erhöhung des Signalpegels werden aufgezeigt.
Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy
Authors: Martos-Moreno Gabriel Á , Barrios Vicente , Soriano-Guillén Leandro , Argente Jesús
Published: October 2006

Objective: To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM).

Study design: Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children.

Results: BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-α and IL-6 were increased at diagnosis and normalized at 1 month.

Conclusions: These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.
Expression of cyclooxygenase-2 in orbital fibroadipose connective tissues of Graves’ ophthalmopathy patients
Authors: Konuk E Berrin Yuksel , Konuk Onur , Misirlioglu Muge , Menevse Adnan , Unal Mehmet
Published: October 2006

Objective: The aim of this study is to evaluate the expression of cycloocygenase-2 (COX-2) in orbital fibroadipose connective tissue in Graves’ ophthalmopathy (GO) patients, and investigate the associations between COX-2 expression and GO characteristics.

Methods: The orbital fibroadipose connective tissues of 23 cases demonstrating moderate or severe GO, and eight control subjects without any history of thyroid or autoimmune disease were analyzed for COX-2 mRNA expression. Real-time relative quantitative PCR was performed to assess transcripts of COX-2 using the LightCycler. The disease activity was evaluated by the clinical activity score (CAS). The clinical features of GO were evaluated by total eye score (TES) and the cases were divided into two groups; type 1 cases included higher degrees of proptosis with orbital fat volume increase, and type 2 cases included cases with compressive neuropathy and limited extraocular muscle functions.

Results: The mean ± s.d. disease duration was 5.7 ± 7.1 years. The mean ± s.d. CAS and TES of cases were 1.60 ± 1.04 and 7.5 ± 1.8 respectively. The mean ± s.d. expression of COX-2 was 0.023 ± 0.013 and 0.010 ± 0.002 in GO cases and controls (P = 0.008), and 0.015 ± 0.073 and 0.029 ± 0.135 in type 1 and type 2 cases respectively (P = 0.007). COX-2 expression showed a statistically significant positive correlation with TES (r = 0.634, P = 0.001), and a negative correlation with the disease duration (r = −0.621, P = 0.002).

Conclusions: COX-2 is expressed at higher levels in orbital fibroadipose tissues of GO cases. This showed a positive correlation with increasing severity of orbital disease suggesting possible relation with COX-2 expression and orbital inflammation in GO.
Coordinated regulation of the GH/IGF system genes during refeeding in rainbow trout (Oncorhynchus mykiss)
Authors: Gabillard Jean-Charles , Kamangar Barzan Bahrami , Montserrat Nuria
Published: October 2006

The GH/IGF system is a complex regulation network strongly dependent on nutrient availability. While the effect of starvation on the GH/IGF system has been extensively studied, the time course of events leading to the restoration of GH/IGF system activity after starvation is largely unknown. We, therefore, measured the plasma levels of GH, IGF-I and IGF-II and the expression of the GH/IGF system in liver and muscle. Starvation increased the plasma GH level and 1 day of refeeding completely restored it (1.10 ± 0.27 vs 1.12 ± 0.28 ng/ml). Thereafter, plasma GH continued to decrease until day 7 and returned to control values from day 15. Starvation decreased plasma IGF-I and IGF-II and refeeding raised plasma IGF-I only from day 4. In contrast, the plasma IGF-II level doubled after 1 day’s refeeding (26.5 ± 1.9 vs 44.0 ± 3.4 ng/ml; P < 0.01). Starved fish exhibited higher GH receptor (GHR)1 mRNA abundance in liver and muscle than in controls, whereas GHR2 mRNA abundance was increased only in muscle. In liver, 1 day of refeeding, decreased GHR1 (twofold), but increased GHR2 mRNA abundance (twofold). Thereafter, a progressive return to normal values was observed. Liver IGFBP-4 mRNA abundance was lowered in starved fish followed by a progressive restoration during refeeding. Starvation had no effect on liver IGFBP-2 and IGFBP-6 mRNA abundance, whereas refeeding provoked a peak of IGFBP-2 and IGFBP-6 expression at day 7. In muscle, starvation led to a decrease of the IGFBP-2 mRNA level, which was restored only from day 7. IGFBP-4 mRNA abundance in starved fish was lower than in the controls and refeeding led to a transient upregulation (sevenfold) of IGFBP-4 gene at day 1. IGF-I, IGFBP-5, and IGFBP-related protein 1 (rP1) expression profiles were similar, showing a decrease of expression after starvation, a first peak of expression at day 2, a second peak at day 7, and a return to normal value from day 15. Moreover, IGF-I, IGFBP-5, and IGFBP-rP1 mRNA abundance were positively correlated (r = 0.6–0.8; P < 0.0001). In conclusion, plasma IGF-I was restored later than plasma GH level, which suggests that plasma IGF-I levels cannot account for plasma GH changes. The coordinated regulation of IGF-I, IGFBP-5, and IGFBP-rP1 expression would be a signature for the resumption of myogenic activity.
Regulation of corticotropin-releasing factor and its types 1 and 2 receptors by leptin in rats subjected to treadmill running-induced stress
Authors: Huang Qingling , Timofeeva Elena , Richard Denis
Published: October 2006

The present study was conducted to investigate the long-term effects of subchronic elevation of central leptin levels on the expression of corticotropin-releasing factor (CRF) and its types 1 and 2 receptors in the brain of rats subjected to treadmill running-induced stress. PBS or recombinant murine leptin was infused continuously for a period of 5 days into the third ventricle of rats with the aid of osmotic minipumps at a delivery rate of 2 μg/day. On the fifth day of infusion, rats were killed under resting conditions or after a session of treadmill running, which is known to induce a stress response in rats. Leptin treatment significantly decreased food intake, body weight, white adipose tissue weight, glucose and insulin plasma contents, and blunted the treadmill running-induced elevation in plasma levels of corticosterone. Leptin infusion prevented stress-induced de novo synthesis of CRF in the paraventricular hypothalamic nucleus (PVN), which was measured using the intronic probe for CRF heteronuclear RNA. The induction of the type 1 CRF receptor (CRF1R) in the PVN and supraoptic nucleus in running rats was also significantly blunted by leptin. In contrast, leptin treatment strongly increased the expression of type 2 CRF receptor (CRF2R) in the ventromedial hypothalamic nucleus (VMH). The present results suggest that subchronic elevation of central levels of leptin blunts treadmill running-induced activation of the hypothalamic–pituitary–adrenal axis through the inhibition of activation of the CRFergic PVN neurons, and potentially enhances the anorectic CRF effects via the stimulation of expression of CRF2R in the VMH.
Internalization and trafficking of mouse 24p3 protein in L929 cells
Authors: Chou Hsien-Yeh , Elangovan Namasivayam , Lee Ying-Chu , Lin Hsiou Hsia , Chu Sin-Tak
Published: October 2006

It has been shown that mouse 24p3 protein is a dexamethasone-inducible secretory protein which suggests the involvement of an autocrine mechanism in the L929 cell line. The aim of this study was to investigate the possibilityof this mechanism in L929 cells and to also demonstrate further processing of this protein after association with L929 cells. We have characterized the internalization of 24p3 protein in L929 cells with fluorescein isothiocyanate- and Alexa555-labeled protein supplement instead of secreted 24p3 protein. As endocytotic inhibitors could reveal the inhibition of protein internalization, we confirmed the existence of receptor-mediated 24p3 protein internalization in L929 cells by carrying out an inhibition test. Plus-chase experiment of L929 cells with biotinylated 24p3 protein demonstrated a release of internalized 24p3 protein into the extracellular region. The protein recycling inhibitor, bafilomycin A1, arrests the transport of 24p3 protein by accumulating in early endosome, but no effect could be observed in protein release from early to late endosome by nocodazole. Theseresults providethe first evidence on recycling of apo-24p3 protein in L929 cells.
Knowledge of Memory Aging in Adulthood
Authors: Hawley Karri S. , Cherry Katie E. , Su L. Joseph , Chiu Yu-Wen , Jazwinski S. Michal
Published: October 2006

The Knowledge of Memory Aging Questionnaire (KMAQ) measures laypersons' knowledge of memory changes in adulthood for research or educational purposes. Half of the questions pertain to normal memory aging and the other half cover pathological memory deficits due to non-normative factors, such as adult dementia. In this study, we compared memory knowledge in middle age adults (40–59 years), young-old adults (60–79 years) and very old adults (80 years and over). These data were collected as a part of the Louisiana Healthy Aging Study, a multidisciplinary population-based study that examines the determinants of healthy aging in adulthood. Results indicated that very old adults performed more poorly overall. Follow-up analyses revealed that they endorsed stereotyped views of normal memory aging more often than did the other age groups. Analyses of response accuracy by gender yielded comparable performance for men and women. Implications for research and the design of educational programs are considered.
Managing the Secrets of Dying Backstage: The Voices of Nursing Home Staff
Authors: Oliver Debra Parker , Porock Davina , Oliver David B.
Published: October 2006

The project analyzed staff descriptions of undocumented care given to dying nursing home residents. Registered nurses, licensed practical nurses, certified nurse aids, and social service designees were interviewed using an unstructured interview guide. Transcripts were coded by two members of the team and a thematic analysis was guided with the theoretical framework of Erving Goffman's dramaturgical model of social interaction. Analysis of interview transcripts revealed practices related to end of life care that went undocumented. Viewed through the lens of Goffman's theoretical model, this undocumented care revealed “secrets” related to socialization processes, communication, tension, superstitions, and interactions between staff and dying residents. Findings show that while dying is not formally acknowledged in the nursing home setting, staff experiences the reality of death and informally responds to the special needs of residents.
Nicknames Increase Longevity
Authors: Abel Ernest L. , Kruger Michael L.
Published: October 2006

We investigated the effect of having a nickname on the longevity of major league baseball players. Ages of death, birth year, and career lengths of major league baseball players who debuted prior to 1950 were obtained and we compared longevities of players with nicknames with those who did not have a nickname. After controlling for these factors in analysis of covariance, there was a statistically significant increase in longevity of 2.5 years associated with having a nickname. Players with nicknames ( N = 2,666; 38.1%) lived an average of 68.6 (±15.1 S.D.) years compared to players without nicknames ( N = 4,329; 61.9%) who lived an average of 66.1 (±16.1) years. We attributed this nickname-related effect on longevity to enhanced self-esteem.
Construction of a Death Anxiety Scale–Extended
Authors: Templer Donald I. , Awadalla Abdelwahid , Al-Fayez Ghenaim , Frazee James , Bassman Lynette , Connelly Heather Joy , Arikawa Hiroko , Abdel-Khalek Ahmed M.
Published: October 2006

A 51-item Death Anxiety Scale—Extended was constructed. This scale consists of the 15 Death Anxiety Scale items plus 36 new items which were generated on a rational basis that both survived content validity ratings and correlated at the .001 level with three out of four groups (one Kuwaiti, one Sudanese, and two American) participants. The Death Anxiety Scale—Extended correlated .81 with the Death Anxiety Scale. The 36 new items (Death Anxiety Scale—New) correlated .64 with the Death Anxiety Scale and .97 with the Death Anxiety Scale—Extended. The Kuder-Richardson formula 20 coefficients of internal consistency were .73 for the Death Anxiety Scale, .91 for the Death Anxiety Scale—New, and .92 for the Death Anxiety Scale—Extended.
The Portrayal of Older People in Television Advertisements: A Cross-Cultural Content Analysis of the United States and South Korea
Authors: Lee Byoungkwan , Kim Bong-Chul , Han Sangpil
Published: October 2006

A cross-cultural content analysis of 2,295 prime-time television ads-859 ads from the United States and 1,436 ads from South Korea–was conducted to examine the differences in the portrayal of older people between U.S. and Korean ads. In two countries, the underrepresentation of older people in ads was found in terms of proportions of the actual population. The findings also showed that older people are more likely to play major roles in Korean television ads than in U.S. ads. In terms of the attributes of older people depicted in ads, differences between U.S. and Korean ads were also found. The results showed that Korean television ads are likely to more positively depict older people than American television ads are. These findings supported the basic assumption of cross-cultural advertising, in which the differences in cultural values between the two cultures are related to the differences in the contents of their advertisements. However, the problems of underrepresentation and stereotypes in the portrayal of older people were still identified both in Korean and U.S. prime-time television ads.
A Continued Look at Doka's Grieving Rules: Deviance and Anomie as Clinical Tools
Authors: Kalich DeAnn , Brabant Sarah
Published: October 2006

Rather than focusing on a psychological perspective that emphasizes individual deficiencies in dealing with loss, we use a sociological perspective to guide both an understanding of and clinical work with grieving people. The use of deviance and anomie as theoretical and clinical tools is a natural progression of the work begun with Doka's (1989) introduction of the concepts disenfranchised grief and grieving rules. Our approach encourages both theorists and clinicians to rethink the use of terms such as “complicated,” “abnormal,” and “pathological” grief.
Neuropeptide Y Deficiency Attenuates Responses to Fasting and High-Fat Diet in Obesity-Prone Mice
Authors: Patel Hiralben R. , Qi Yong , Hawkins Evan J. , Hileman Stanley M. , Elmquist Joel K. , Imai Yumi , Ahima Rexford S.
Published: October 2006

Neuropeptide Y (NPY) stimulates feeding and weight gain, but deletion of the NPY gene does not affect food intake and body weight in mice bred on a mixed genetic background. We reasoned that the orexigenic action of NPY would be evident in C57Bl/6J mice susceptible to obesity. NPY deficiency has no significant effect in mice fed a normal rodent diet. However, energy expenditure is elevated during fasting, and hyperphagia and weight gain are blunted during refeeding. Expression of agouti-related peptide (AGRP) in the hypothalamus is increased in NPY knockout (NPYko) than wild-type mice, but unlike wild type there is no further increase in AGRP when NPYko mice are fasted. Moreover, NPYko mice have higher oxygen consumption and uncoupling protein-1 expression in brown adipose tissue during fasting. The failure of an increase in orexigenic peptides and higher thermogenesis may contribute to attenuation of weight gain when NPYko mice are refed. C57Bl/6J mice lacking NPY are also less susceptible to diet-induced obesity (DIO) as a result of reduced feeding and increased energy expenditure. The resistance to DIO in NPYko mice is associated with a reduction in nocturnal feeding and increased expression of anorexigenic hypothalamic peptides. Insulin, leptin, and triglyceride levels increase with adiposity in both wild-type and NPYko mice.
Analysis of 14 Candidate Genes for Diabetic Nephropathy on Chromosome 3q in European Populations
Authors: Vionnet Nathalie , Tregouët David , Kazeem Gbenga , Gut Ivo , Groop Per-Henrik , Tarnow Lise , Parving Hans-Henrik , Hadjadj Samy , Forsblom Carol , Farrall Martin , Gauguier Dominique , Cox Roger , Matsuda Fumihiko , Heath Simon , Thévard Alexandre , Rousseau Rachel , Cambien François , Marre Michel , Lathrop Mark
Published: October 2006

Linkage studies have mapped loci for diabetic nephropathy and associated phenotypes on chromosome 3q. We studied 14 plausible candidate genes in the linkage region because of their potential role in vascular complications. In a large-scale study of patients from Denmark, Finland, and France who have type 1 diabetes, 1,057 case and 1,127 control subjects, as well as 532 trios, were investigated for association with diabetic nephropathy. We analyzed 69 haplotype-tagging single nucleotide polymorphisms and nonsynonymous variants that were identified by sequencing. Polymorphisms in three genes, glucose transporter 2 (SLC2A2), kininogen (KNG1), and adiponectin (ADIPOQ), showed nominal association with diabetic nephropathy in single-point analysis. The T-allele of SLC2A2_16459CT was associated with a decreased risk of diabetic nephropathy (odds ratio 0.79 [95% CI 0.66–0.96], P = 0.016), whereas the T-allele of KNG_7965CT and the A-allele of ADIPOQ_prom2GA were associated with increased risk of nephropathy (1.17 [1.03–1.32], P = 0.016; 1.46 [1.11–1.93], P = 0.006, respectively). Analyses of the transmission disequilibrium test showed similar trends only for ADIPOQ_prom2GA with the overtransmission of the A-allele to patients with diabetic nephropathy (1.52 [0.86–2.66], P = NS) and of the G-allele to patients without diabetic nephropathy (0.50 [0.27–0.92], P = 0.026). The overall significance for this variant (nominal P = 0.011) suggests that ADIPOQ might be involved in the development of diabetic nephropathy.
Pancreatic Islet Production of Vascular Endothelial Growth Factor-A Is Essential for Islet Vascularization, Revascularization, and Function
Authors: Brissova Marcela , Shostak Alena , Shiota Masakazu , Wiebe Peter O. , Poffenberger Greg , Kantz Jeannelle , Chen Zhongyi , Carr Chad , Jerome W. Gray , Chen Jin , Baldwin H. Scott , Nicholson Wendell , Bader David M. , Jetton Thomas , Gannon Maureen , Powers Alvin C.
Published: October 2006

To investigate molecular mechanisms controlling islet vascularization and revascularization after transplantation, we examined pancreatic expression of three families of angiogenic factors and their receptors in differentiating endocrine cells and adult islets. Using intravital lectin labeling, we demonstrated that development of islet microvasculature and establishment of islet blood flow occur concomitantly with islet morphogenesis. Our genetic data indicate that vascular endothelial growth factor (VEGF)-A is a major regulator of islet vascularization and revascularization of transplanted islets. In spite of normal pancreatic insulin content and β-cell mass, mice with β-cell–reduced VEGF-A expression had impaired glucose-stimulated insulin secretion. By vascular or diffusion delivery of β-cell secretagogues to islets, we showed that reduced insulin output is not a result of β-cell dysfunction but rather caused by vascular alterations in islets. Taken together, our data indicate that the microvasculature plays an integral role in islet function. Factors modulating VEGF-A expression may influence islet vascularity and, consequently, the amount of insulin delivered into the systemic circulation.
Oral Glucosamine for 6 Weeks at Standard Doses Does Not Cause or Worsen Insulin Resistance or Endothelial Dysfunction in Lean or Obese Subjects
Authors: Muniyappa Ranganath , Karne Rajaram J. , Hall Gail , Crandon Sonja K. , Bronstein Joel A. , Ver Maria R. , Hortin Glen L. , Quon Michael J.
Published: October 2006

Glucosamine is a popular nutritional supplement used to treat osteoarthritis. Intravenous administration of glucosamine causes insulin resistance and endothelial dysfunction. However, rigorous clinical studies evaluating the safety of oral glucosamine with respect to metabolic and cardiovascular pathophysiology are lacking. Therefore, we conducted a randomized, placebo-controlled, double-blind, crossover trial of oral glucosamine at standard doses (500 mg p.o. t.i.d.) in lean (n = 20) and obese (n = 20) subjects. Glucosamine or placebo treatment for 6 weeks was followed by a 1-week washout and crossover to the other arm. At baseline, and after each treatment period, insulin sensitivity was assessed by hyperinsulinemic-isoglycemic glucose clamp (SIClamp) and endothelial function evaluated by brachial artery blood flow (BAF; Doppler ultrasound) and forearm skeletal muscle microvascular recruitment (ultrasound with microbubble contrast) before and during steady-state hyperinsulinemia. Plasma glucosamine pharmacokinetics after oral dosing were determined in each subject using a high-performance liquid chromatography method. As expected, at baseline, obese subjects had insulin resistance and endothelial dysfunction when compared with lean subjects (SIClamp [median {25th–75th percentile}] = 4.3 [2.9–5.3] vs. 7.3 [5.7–11.3], P < 0.0001; insulin-stimulated changes in BAF [% over basal] = 12 [−6 to 84] vs. 39 [2–108], P < 0.04). When compared with placebo, glucosamine did not cause insulin resistance or endothelial dysfunction in lean subjects or significantly worsen these findings in obese subjects. The half-life of plasma glucosamine after oral dosing was ∼150 min, with no significant changes in steady-state glucosamine levels detectable after 6 weeks of therapy. We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects.
Expression of ATP-Insensitive KATP Channels in Pancreatic β-Cells Underlies a Spectrum of Diabetic Phenotypes
Authors: Koster Joseph C. , Remedi Maria S. , Masia Ricard , Patton Brian , Tong Ailing , Nichols Colin G.
Published: October 2006

Glucose metabolism in pancreatic β-cells elevates cytoplasmic [ATP]/[ADP], causing closure of ATP-sensitive K+ channels (KATP channels), Ca2+ entry through voltage-dependent Ca2+ channels, and insulin release. Decreased responsiveness of KATP channels to the [ATP]/[ADP] ratio should lead to decreased insulin secretion and diabetes. We generated mice expressing KATP channels with reduced ATP sensitivity in their β-cells. Previously, we described a severe diabetes, with nearly complete neonatal lethality, in four lines (A–C and E) of these mice. We have now analyzed an additional three lines (D, F, and G) in which the transgene is expressed at relatively low levels. These animals survive past weaning but are glucose intolerant and can develop severe diabetes. Despite normal islet morphology and insulin content, islets from glucose-intolerant animals exhibit reduced glucose-stimulated insulin secretion. The data demonstrate that a range of phenotypes can be expected for a reduction in ATP sensitivity of β-cell KATP channels and provide models for the corollary neonatal diabetes in humans.
Interactions Between Delivery, Transport, and Phosphorylation of Glucose in Governing Uptake Into Human Skeletal Muscle
Authors: Bertoldo Alessandra , Pencek R. Richard , Azuma Koichiro , Price Julie C. , Kelley Carol , Cobelli Claudio , Kelley David E.
Published: October 2006

Skeletal muscle accounts for a large proportion of insulin-stimulated glucose utilization. It is generally regarded that much of the control over rates of uptake is posited within the proximal steps of delivery, transport, and phosphorylation of glucose, with glucose transport as the main locus of control. Whether insulin modulates the distribution of control across these steps and in what manner remains uncertain. The current study addressed this in vivo using dynamic positron emission tomography (PET) imaging of human muscle with sequential injections of three tracers ([15O]H2O, [11C]3-O-methyl glucose [3-OMG], and [18F]fluoro-deoxy glucose [FDG]) that enabled quantitative determinations of glucose delivery, transport, and its phosphorylation, respectively. Lean, healthy, research volunteers were studied during fasting conditions (n = 8) or during a euglycemic insulin infusion at 30 mU/min per m2 (n = 8). PET images were coregistered with magnetic resonance imaging to contrast glucose kinetics in soleus, a highly oxidative muscle, with tibialis anterior, a less oxidative muscle. During fasting conditions, uptake of [11C]3-OMG was similar in soleus and tibialis anterior muscles, despite higher delivery to soleus (by 35%; P < 0.01). Uptake of [18F]FDG was also similar between muscle during fasting, and glucose transport was found to be the dominant locus of control (90%) for glucose uptake under this condition. Insulin increased uptake of [11C]3-OMG substantially and strongly stimulated the kinetics of bidirectional glucose transport. Uptake of [11C]3-OMG was higher in soleus than tibialis anterior muscle (by 22%; P < 0.01), a difference partially due to higher delivery, which was again found to be 35% higher to soleus (P < 0.01). The uptake of [18F]FDG was 65% greater in soleus compared with tibialis anterior muscle, a larger difference than for [11C]3-OMG (P < 0.01), indicating an added importance of glucose phosphorylation in defining insulin sensitivity. Analysis of the distribution of control during insulin-stimulated conditions revealed that most of the control was posited at delivery and transport and was equally divided between these steps. Thus, insulin evokes a broader distribution of control than during fasting conditions in governing glucose uptake into skeletal muscle. This redistribution of control is triggered by the robust stimulation of glucose transport, which in turn unmasks a greater dependence upon delivery and glucose phosphorylation.
Islet Autoimmunity in Children With Down’s Syndrome
Authors: Gillespie Kathleen M. , Dix Rachel J. , Williams Alistair J.K. , Newton Richard , Robinson Zoey F. , Bingley Polly J. , Gale Edwin A.M. , Shield Julian P.H.
Published: October 2006

There is an unexplained excess of type 1 diabetes and other organ-specific autoimmune diseases in children with Down’s syndrome, but the immunogenetic characteristics of diabetes in Down’s syndrome have not been investigated. We studied the frequency of islet autoantibodies in 106 children with Down’s syndrome and no history of autoimmunity and analyzed HLA class II genotypes in 222 children with Down’s syndrome, 40 children with Down’s syndrome and type 1 diabetes, 120 age- and sex-matched children with type 1 diabetes, and 621 healthy control subjects. Co-occurrence of at least two islet autoantibody markers was observed in 6 of 106 nondiabetic children with Down’s syndrome compared with 13 of 2,860 healthy age-matched children (P < 0.001). There was an excess of diabetes-associated HLA class II genotypes in children with Down’s syndrome and type 1 diabetes compared with age- and sex-matched healthy control subjects (P < 0.001). Down’s syndrome children with type 1 diabetes were, however, less likely to carry the highest risk genotype DR4-DQ8/DR3-DQ2 than children with type 1 diabetes from the general population (P = 0.01) but more likely to carry low-risk genotypes (P < 0.0001). The frequency of subclinical islet autoimmunity is increased in Down’s syndrome, and susceptibility to type 1 diabetes in Down’s syndrome is partially HLA mediated. Other factors, possibly including genes on chromosome 21, may increase the penetrance of type 1 diabetes in Down’s syndrome.
Reduction of Diabetes-Induced Oxidative Stress, Fibrotic Cytokine Expression, and Renal Dysfunction in Protein Kinase Cβ–Null Mice
Authors: Ohshiro Yuzuru , Ma Ronald C. , Yasuda Yutaka , Hiraoka-Yamamoto Junko , Clermont Allen C. , Isshiki Keiji , Yagi Kunimasa , Arikawa Emi , Kern Timothy S. , King George L.
Published: October 2006

Diabetes induces the activation of several protein kinase C (PKC) isoforms in the renal glomeruli. We used PKC-β−/− mice to examine the action of PKC-β isoforms in diabetes-induced oxidative stress and renal injury at 8 and 24 weeks of disease. Diabetes increased PKC activity in renal cortex of wild-type mice and was significantly reduced (<50% of wild-type) in diabetic PKC-β−/− mice. In wild-type mice, diabetes increased the translocation of PKC-α and -β1 to the membrane, whereas only PKC-α was elevated in PKC-β−/− mice. Increases in urinary isoprostane and 8-hydroxydeoxyguanosine, parameters of oxidative stress, in diabetic PKC-β−/− mice were significantly reduced compared with diabetic wild-type mice. Diabetes increased NADPH oxidase activity and the expressions of p47phox, Nox2, and Nox4 mRNA levels in the renal cortex and were unchanged in diabetic PKC-β−/− mice. Increased expression of endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β, connective tissue growth factor (CTGF), and collagens IV and VI found in diabetic wild-type mice was attenuated in diabetic PKC-β−/− mice. Diabetic PKC-β−/− mice were protected from renal hypertrophy, glomerular enlargement, and hyperfiltration observed in diabetic wild-type mice and had less proteinuria. Lack of PKC-β can protect against diabetes-induced renal dysfunction, fibrosis, and increased expressions of Nox2 and -4, ET-1, VEGF, TGF-β, CTGF, and oxidant production.
Development of a Non-Pneumatic Wheel
Authors: Rhyne T. B. , Cron S. M.
Published: October 2006

The pneumatic tire has proven to be the dominant design for rolling transport since shortly after its invention by John Boyd Dunlop in 1888. This paper identifies four critical characteristics that led to the success of the pneumatic tire: low energy loss on rough surfaces, low vertical stiffness, low contact pressure, and low mass. A non-pneumatic structure is proposed that exhibits these four critical characteristics while breaking some of the most restrictive design constraints imposed by pneumatic mechanics. This structure consists of a circular beam composed of two inextensible membranes separated by a relatively low modulus elastic material. The beam is connected to a hub by thin elastic spokes. This structure forming an integrated tire∕wheel is called a Tweel™.
A Finite Element Algorithm for the Prediction of Steady-State Temperatures of Rolling Tires
Authors: Narasimha Rao K. V. , Kumar R. Krishna , Bohara P. C. , Mukhopadhyay R.
Published: October 2006

A review of the literature on the numerical techniques used for the determination of tire temperatures shows that many attempts have been made to simulate tire temperatures with axisymmetric geometry through a simple decoupled representation of the total thermomechanical behavior. The deformation models used in these studies are primarily statically loaded tires with centrifugal forces to simulate tire-rolling behavior at different speeds. These techniques are usually limited to axisymmetric tires, which make the models applicable to only smooth or circumferential grooved tires. In this study, a finite element (FE) algorithm is developed using Petrov-Galerkin Eulerian technique in cylindrical coordinates. An objective of this approach is to provide a technique that is more appropriate for extension to nonaxisymmetric tires with tread patterns. The developed algorithm has been implemented for the prediction of three-dimensional operating temperatures for axisymmetric tires through a simple decoupled procedure. An iterative procedure is used to determine that the equilibrium temperatures, as loss modulus properties, are functions of strain and temperature. The experimental techniques required to determine tire operating temperatures are fairly involved and highly sophisticated. Therefore, the computation results of the developed algorithm for a smooth treaded tire are compared with the results obtained from a standard FE solver.