bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of the Pupillary Light Reflex in the Alert Rhesus Monkey
Authors: Clarke Robert J. , Zhang Hongyu , Gamlin Paul D. R.
Published: May 2006

This study investigated the static and dynamic characteristics of the pupillary light reflex (PLR) in the alert rhesus monkey. Temporal characteristics of the PLR were investigated with Maxwellian viewing during sinusoidal changes in illumination of a 36° stimulus in both monkeys and humans. Bode plots of the PLR response were fitted by a linear model composed of a delay combined with a cascaded first- and second-order filter. The Bode magnitude plots conformed to this model with a sharp roll-off above 1.3 Hz for the human PLR and 1.9 Hz for the monkey PLR. Bode phase angle plots were fitted by this model with a delay of 280 ms for humans and 160 ms for monkeys. To investigate the influence of the sympathetic innervation of the iris on steady-state pupil diameter, dynamics of pupillary responses, and the latency of the PLR, we blocked this innervation pharmacologically with a selective alpha-1 adrenoreceptor antagonist. Although there was a resultant miosis (decrease in pupil diameter) from the relaxation of the pupil dilator muscle, no other measures of the PLR, including the dynamics and latency, were significantly affected by this treatment. We examined the pupillary responses evoked by visual stimuli presented either binocularly or monocularly at various locations on a 80 × 60° tangent screen. These pupillomotor fields revealed that, as has been reported for humans, stimuli at the fovea and surrounding macular region of monkeys produce substantially larger pupillary responses than more peripheral stimuli and that binocular responses are substantially greater than can be accounted for by the linear summation of binocular retinal illuminance. In conclusion, we found that the spatial characteristics of the PLR of the rhesus monkey are very similar, in all important aspects, to those reported for humans and that the temporal responses of the PLR are comparable between the two species. The rhesus monkey thus provides an excellent model for experimental studies of the neural control of the pupil.
Integration of Motor and Visual Information in the Parietal Area 5 During Locomotion
Authors: Beloozerova Irina N. , Sirota Mikhail G.
Published: May 2006

The parietal cortex receives both visual- and motor-related information and is believed to be one of the sites of visuo-motor coordination. This study for the first time characterizes integration of visual and motor information in activity of neurons of parietal area 5 during locomotion under conditions that require visuo-motor coordination. The activity of neurons was recorded in cats during walking on a flat surface—a task with no visuo-motor coordination required (flat locomotion), walking along a horizontal ladder or a series of barriers—a task requiring visuo-motor coordination for an accurate foot placement on surface that is heterogeneous along the direction of progression (ladder and barriers locomotion), and walking along a narrow pathway—a task requiring visuo-motor coordination on surface homogeneous along the direction of progression (narrow locomotion). During flat locomotion, activity of 66% of the neurons was modulated in rhythm of stepping, usually with one peak per cycle. During ladder and barrier locomotion, the proportion of rhythmically active neurons significantly increased, their modulation became stronger, and the majority of neurons had two peaks of activity per cycle. During narrow locomotion, however, the activity of neurons was similar to that during flat locomotion. We concluded that, during locomotion, parietal area 5 integrates two types of information: signals about the activity of basic locomotion mechanisms and signals about heterogeneity of the surface along the direction of progression. We describe here the modes of integration of these two types of information during locomotion.
Possible Roles of Kainate Receptors on GABAergic Nerve Terminals Projecting to Rat Substantia Nigra Dopaminergic Neurons
Authors: Nakamura Michiko , Jang Il-Sung , Ishibashi Hitoshi , Watanabe Shigenori , Akaike Norio
Published: May 2006

GABAergic afferent inputs are thought to play an important role in the control of the firing pattern of substantia nigra pars compacta (SNc) dopaminergic neurons. We report here the actions of presynaptic kainite (KA) receptors in GABAergic transmission of rat SNc dopaminergic neurons. In mechanically dissociated rat SNc dopaminergic neurons attached with native presynaptic nerve terminals, GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded by use of conventional whole cell patch recording mode. In the voltage-clamp condition, KA (3 μM) significantly increased GABAergic mIPSC frequency without affecting the current amplitude. This facilitatory effect of KA was not affected in the presence of 20 μM GYKI52466, a selective AMPA receptor antagonist, but was completely inhibited in the presence of 20 μM CNQX, an AMPA/KA receptor antagonist. Presynaptic KA receptors on GABAergic terminals were mainly permeable to Na+ but impermeable to Ca2+ because KA-induced facilitation of mIPSC frequency was completely suppressed in either Na+-free or Ca2+-free external solutions, and in the presence of 200 μM Cd2+, a general voltage-dependent Ca2+ channel blocker. In the slice preparation, KA increased GABAergic spontaneous mIPSC frequency, but significantly suppressed evoked IPSC (eIPSC) amplitude. However, this inhibitory action on eIPSCs was reversed by 10 μM CGP55845 , a selective GABAB receptor antagonist, implicating the possible involvement of GABAB autoreceptors in KA-induced modulation of GABAergic transmission. Thus presynaptic KA receptors on GABAergic nerve terminals synapsing onto SNc neurons may play functional roles contributing the fine control of neuronal excitability and firing pattern of SNc.
Neuromotor Noise Limits Motor Performance, But Not Motor Adaptation, in Children
Authors: Takahashi Craig D. , Nemet Dan , Rose-Gottron Christie M. , Larson Jennifer K. , Cooper Dan M. , Reinkensmeyer David J.
Published: May 2006

Children do not typically appear to move with the same skill and dexterity as adults, although they can still improve their motor performance in specific tasks with practice. One possible explanation is that their motor performance is limited by an inherently higher level of movement variability, but that their motor adaptive ability is robust to this variability. To test this hypothesis, we examined motor adaptation of 43 children (ages 6–17) and 12 adults as they reached while holding the tip of a lightweight robot. The robot applied either a predictable, velocity-dependent field (the “mean field”) or a similar field that incorporated stochastic variation (the “noise field”), thereby further enhancing the variability of the subjects' movements. We found that children exhibited greater initial trial-to-trial variability in their unperturbed movements but were still able to adapt comparably to adults in both the mean and noise fields. Furthermore, the youngest children (ages 6–8) were able to reduce their variability with practice to levels comparable to the remaining children groups although not as low as adults. These results indicate that children as young as age 6 possess adult-like neural systems for motor adaptation and internal model formation that allow them to adapt to novel dynamic environments as well as adults on average despite increased neuromotor or environmental noise. Performance after adaptation is still more variable than adults, however, indicating that movement inconsistency, not motor adaptation inability, ultimately limits motor performance by children and may thus account for their appearance of incoordination and more frequent motor accidents (e.g., spilling, tripping). The results of this study also suggest that movement variability in young children may arise from two sources—a relatively constant, intrinsic source related to fundamental physiological constraints of the developing motor system and a more rapidly modifiable source that is modulated depending on the current motor context.
Watermaze Learning Enhances Excitability of CA1 Pyramidal Neurons
Authors: Oh M. Matthew , Kuo Amy G. , Wu Wendy W. , Sametsky Evgeny A. , Disterhoft John F.
Published: May 2006

The dorsal hippocampus is crucial for learning the hidden-platform location in the hippocampus-dependent, spatial watermaze task. We have previously demonstrated that the postburst afterhyperpolarization (AHP) of hippocampal pyramidal neurons is reduced after acquisition of the hippocampus-dependent, temporal trace eyeblink conditioning task. We report here that the AHP and one or more of its associated currents ( IAHPand/or s IAHP) are reduced in dorsal hippocampal CA1 pyramidal neurons from rats that learned the watermaze task as compared with neurons from control rats. This reduction was a learning-induced phenomenon as the AHP of CA1 neurons from rats that failed to learn the hidden-platform location was similar to that of neurons from control rats. We propose that reduction of the AHP in pyramidal neurons in regions crucial for learning is a cellular mechanism of learning that is conserved across species and tasks.
Urinary Metabolites of Oxidative Stress and Nitric Oxide in Preterm and Term Infants
Authors: Farkouh Christiana R. , Merrill Jeffrey D. , Ballard Phillip L. , Ballard Roberta A. , Ischiropoulos Harry , Lorch Scott A.
Published: May 2006

Background: Many neonatal diseases have been associated with oxidative stress and altered nitric oxide status. Objective: To determine the effects of clinical interventions on the levels of urinary peroxides, a marker of oxidative stress, and urinary nitrate/nitrites, indices of nitric oxide production and metabolism, in the first 72 h of life in premature infants. Methods: A single, spot urine sample was collected from 82 premature and 20 healthy term infants within the first 72 h of life. The peroxide levels were quantified using a fluorometric method, and nitrate/nitrite levels were quantified by chemiluminescence. Results: Premature infants had a median peroxide level of 10.0 µmol/mmol creatinine (Cr) (interquartile range 4.8–20.0 µmol/mmol Cr). These values were significantly higher than term infants (median 5.0 µmol/mmol Cr, interquartile range 2.7–10.0 µmol/mmol Cr). Urinary nitrate/nitrite levels were not significantly different between preterm (220.5 µmol/mmol Cr, interquartile range 161–287 µmol/mmol Cr) and healthy term infants (244 µmol/mmol Cr, interquartile range 194–316 µmol/mmol Cr). For urinary peroxides, infants on TPN had significantly higher urinary peroxide levels than infants who were not on TPN at the time of urine collection (p = 0.006). Administration of indomethacin was associated with lower levels of urinary nitrate/nitrites (p = 0.0003). Both effects remained significant after controlling for gestational age, degree of respiratory distress and day of urine collection. Conclusion: Monitoring the level of both peroxides and nitrate/nitrite may offer added information about the degree of oxidative stress experienced by a newborn but needs to account for clinical and therapeutic interventions.
Growth Hormone and Prolactin Receptors in Adipogenesis: STAT-5 Activation, Suppressors of Cytokine Signaling, and Regulation of Insulin-Like Growth Factor I
Authors: Fleenor Don , Arumugam Ramamani , Freemark Michael
Published: May 2006

Growth hormone (GH) stimulates lipolysis in mature adipocytes and primary preadipocytes but promotes adipogenesis in preadipocyte cell lines. The lactogenic hormones (prolactin [PRL] and placental lactogen) also stimulate adipogenesis in preadipocyte cell lines but have variable lipolytic and lipogenic effects in mature adipose tissue. We hypothesized that differences in expression of GH receptors (GHR) and PRL receptors (PRLR) during adipocyte development might explain some of the differential effects of the somatogens and lactogens on fat metabolism. To that end, we compared: (a) the expression of GHR and PRLR mRNAs in 3T3-L1 preadipocytes during the course of adipocyte differentiation; (b) the induction of STAT-5 activity by GH and PRL during adipogenesis; and (c) the acute effects of GH and PRL on the suppressors of cytokine signaling (SOCS-1–3 and cytokine-inducible SH2-domain-containing protein [CIS]) and IGF-I. In confluent, undifferentiated 3T3-L1 cells, the levels of GHR mRNA were ∼250-fold higher than the levels of PRLR mRNA. Following induction of adipocyte differentiation the levels of PRLR mRNA rose 90-fold but GHR mRNA increased only 0.8-fold. Expression of both full-length (long) and truncated (short) isoforms of the PRLR increased during differentiation but the long isoform predominated at all time points. Mouse GH (mGH) stimulated increases in STAT-5a and 5b activity in undifferentiated as well as differentiating 3T3-L1 cells; mouse PRL (mPRL) had little or no effect on STAT-5 activity in undifferentiated cells but stimulated increases in STAT-5a and 5b activity in differentiating cells. mGH stimulated increases in SOCS-2 and SOCS-3 mRNAs in undifferentiated cells and SOCS-1–3 and CIS mRNAs in differentiating cells; mPRL induced CIS in differentiating cells but had no effect on SOCS-1–3. mPRL and mGH stimulated increases in IGF-I mRNA in differentiating cells but not in undifferentiated cells; the potency of mGH (3–6-fold increase, p < 0.01) exceeded that of mPRL (40–90% increase, p < 0.05). Our findings reveal disparities in the expression of PRLR and GHR during adipocyte development and differential effects of the hormones on STAT-5, the SOCS proteins, CIS, and IGF-I. These observations suggest that somatogens and lactogens regulate adipocyte development and fat metabolism through distinct but overlapping cellular mechanisms.
Portal Vein Thrombosis and High Factor VIII in Turner Syndrome
Authors: Kopacek Zilz Cristiane , Keller Brenner Juliana , Elnecave Regina Helena
Published: May 2006

Backgrounds/Aims: Turner syndrome is not usually associated with thrombotic events. The aim of this study is to report 3 Turner syndrome patients with portal vein thrombosis and, in 2 of them, high factor VIII. These findings are compared to values in Turner syndrome patients without thrombosis and controls. Methods: In different years, 3 patients with Turner syndrome were initially seen at the Gastroenterology Clinic of Hospital de Clínicas de Porto Alegre, Brazil, for portal vein thrombosis. After the most common causes of portal vein thrombosis and thrombophilias had been excluded, the 2 surviving patients were studied for clotting factors VIII, IX and von Willebrand factor. The same factors were also assessed in 25 Turner syndrome patients without thrombosis and 25 normal girls. Results: One of the patients with portal vein thrombosis died before the study. In the 2 surviving patients, factors VIII and von Willebrand levels were >150 IU/dl, which is considered to be high. In Turner syndrome patients without thrombosis, the mean factor VIII level was 127.2 ± 41.1 IU/dl and for von Willebrand factor 101.2 ± 26.9 IU/dl, while in control girls these were 116.0 ± 27.6 and 94.28 ± 27.5 IU/dl, respectively. Factor VIII and von Willebrand factor were not different between these 2 groups. When non-O blood group Turner syndrome patients and normal girls were compared, the former had significantly higher levels of factor VIII. Conclusions: This is the first report on the unusual finding of portal thrombosis in patients with Turner syndrome in whom high levels of factor VIII and von Willebrand factor were found. Factor VIII is higher in the non-O blood group Turner syndrome patients without thrombosis when compared to normal girls.
Stress and Coping in African American Grandparents Who Are Raising Their Grandchildren
Authors: Ross Mary Ellen Trail , Aday Lu Ann
Published: May 2006

This study investigated the degree of stress in 50 African American grandparents ( M = 63.12 years) who are raising their grandchildren and identified the importance of caregiver characteristics, the caregiving situation, and specific coping strategies that influence stress. Data were collected via interview at senior centers and churches in Harris County, Texas. The instruments used to measure stress and coping were the Parenting Stress Index and the Ways of Coping Questionnaire. Of grandparents, 94% reported a clinically significant level of stress. Use of professional counseling, special school programs, and length of caregiving longer than 5 years were associated with less stress. Coping strategies significantly correlated with less stress included accepting responsibility, confrontive coping, self-control, positive reappraisal, planful problem solving, and distancing. This study adds to the limited information about custodial grandparents and suggests counseling, support groups, and education to help them manage stress associated with their caregiving situation more effectively.
Fetal hemoglobin silencing in humans
Authors: Oneal Patricia A. , Gantt Nicole M. , Schwartz Joseph D. , Bhanu Natarajan V. , Lee Y. Terry , Moroney John W. , Reed Christopher H. , Schechter Alan N. , Luban Naomi L. C. , Miller Jeffery L.
Published: May 2006

Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and beta-thalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from 5 umbilical cords, 99 infants, and 5 adult donors. Unexpectedly, an average of 95% of the cord blood erythrocytes and reticulocytes expressed HbA and the adult beta-globin gene, as well as HbF and the gamma-globin genes. The distribution of hemoglobin and globin gene expression then changed abruptly due to the expansion of cells lacking HbF or gamma-globin mRNA (silenced cells). In adult reticulocytes, less than 5% expressed gamma-globin mRNA. These data are consistent with a “switching” model in humans that initially results largely from gamma- and beta-globin gene coexpression and competition during fetal development. In contrast, early postnatal life is marked by the rapid accumulation of cells that possess undetectable gamma-globin mRNA and HbF. The silencing phenomenon is mediated by a mechanism of cellular replacement. This novel silencing pattern may be important for the development of HbF-enhancing therapies.
FLOWERING LOCUS C-dependent and -independent regulation of the circadian clock by the autonomous and vernalization pathways
Authors: Salathia Neeraj , Davis Seth J , Lynn James R , Michaels Scott D , Amasino Richard M , Millar Andrew J
Published: May 2006

Background

The circadian system drives pervasive biological rhythms in plants. Circadian clocks integrate endogenous timing information with environmental signals, in order to match rhythmic outputs to the local day/night cycle. Multiple signaling pathways affect the circadian system, in ways that are likely to be adaptively significant. Our previous studies of natural genetic variation inArabidopsis thalianaaccessions implicatedFLOWERING LOCUS C(FLC) as a circadian-clock regulator. The MADS-box transcription factorFLCis best known as a regulator of flowering time. Its activity is regulated by many regulatory genes in the "autonomous" and vernalization-dependent flowering pathways. We tested whether these same pathways affect the circadian system.

Results

Genes in the autonomous flowering pathway, includingFLC, were found to regulate circadian period in Arabidopsis. The mechanisms involved are similar, but not identical, to the control of flowering time. By mutant analyses, we demonstrate a graded effect ofFLCexpression upon circadian period. Related MADS-box genes had less effect on clock function. We also reveal an unexpected vernalization-dependent alteration of periodicity.

Conclusion

This study has aided in the understanding ofFLC's role in the clock, as it reveals that the network affecting circadian timing is partially overlapping with the floral-regulatory network. We also show a link between vernalization and circadian period. This finding may be of ecological relevance for developmental programing in other plant species.
Can a GP be a generalist and a specialist? Stakeholders views on a respiratory General Practitioner with a special interest service in the UK
Authors: Moffat Mandy A , Sheikh Aziz , Price David , Peel Annie , Williams Siân , Cleland Jen , Pinnock Hilary
Published: May 2006

Background

Primary care practitioners have a potentially important role in the delivery of specialist care for people with long-term respiratory diseases. Within the UK the development of a General Practitioner with Special Interests (GPwSI) service delivered within Primary Care Trusts (PCTs) involves a process of 'transitional change' which impacts on the professional roles of clinicians who may embrace or resist change. In addition, the perspective of patients on the new roles is important. The objective of the current study is to explore the attitudes and views of stakeholders to the provision of a respiratory GPwSI service within the six PCTs in Leicester, UK.

Methods

Using a qualitative design, GPs, nurses, secondary care doctors, nurse specialists, physiotherapists, a healthcare manager and patients with respiratory disease took part in focus groups and in-depth interviews.

Results

The 25 participants expressed diverse opinions about the challenge of integrating specialist services with generalist care and the specific contribution that GPs might make to the care of people with chronic respiratory disease. A range of potential roles for a respiratory GPwSI, working as part of a multi-disciplinary team, were suggested, and a number of practical issues were highlighted. Success of the GPwSI role is deemed to be dependant on having the trust of their primary and secondary care colleagues as well as patients, credibility as a practitioner, and being politically astute thereby enabling them to act as a champion supporting the transition process within the local health service.

Conclusion

The introduction of a respiratory GPwSI service represents a challenge to traditional roles which, whilst broadly acceptable, raised a number of important issues for the stakeholders in our study. These perspectives need to be taken into account if workforce change is to be successfully negotiated and implemented.
Hypothesis: the antitumor activities of statins may be mediated by IL-18
Authors: Takahashi Hideo Kohka , Weitz-Schmidt Gabriele , Iwagaki Hiromi , Yoshino Tadashi , Tanaka Noriaki , Nishibori Masahiro
Published: May 2006

Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, are thought to reduce the risk of cancer through the inhibition of Ras farnesylation and serum lipid level. A pleiotropic proinflammatory cytokine, interleukin-18 (IL-18), is reported to exhibit significant antitumor activities through the activation of cytotoxic T lymphocytes and natural killer cells and the inhibition of angiogenesis. Previously, we found that pravastatin, fluvastatin, and simvastatin induced the production of IL-18 in human monocytes. The addition of mevalonate abolished the IL-18 production induced by pravastatin, fluvastatin, and simvastatin, indicating that the IL-18 production might be a result of the inhibition of HMG-CoA reductase. We present a new hypothesis that the production of IL-18 might play roles in the action of statins on cancer.
Differential Zonal Expression and Adrenocorticotropin Regulation of Secreted Protein Acidic and Rich in Cysteine (SPARC), a Matricellular Protein, in the Midgestation Human Fetal Adrenal Gland: Implications for Adrenal Development
Authors: Ishimoto Hitoshi , Ginzinger David G. , Matsumoto Tadashi , Hattori Yoshihisa , Furuya Masataka , Minegishi Kazuhiro , Tanaka Mamoru , Yoshimura Yasunori , Jaffe Robert B.
Published: May 2006

Context: Matricellular proteins are a group of secreted, multifunctional extracellular matrix glycoproteins that includes thrombospondins (TSPs), tenascin-C, and secreted protein acidic and rich in cysteine (SPARC). They may be implicated in the dynamic developmental processes of the human fetal adrenal (HFA) in which the outer, definitive zone (DZ) cells are postulated to proliferate, migrate centripetally, differentiate, and populate the inner, steroidogenic fetal zone (FZ).

Objective: The objective of the study was to identify a matricellular molecule that likely plays a major role in HFA development.

Design: Studies involved RNA, cryosections, and cell cultures from 14- to 23-wk HFAs and human adult adrenal RNA.

Main Outcome Measures: Measures included transcripts encoding matricellular proteins, using real-time quantitative RT-PCR; SPARC localization by immunostaining; and ACTH regulation of SPARC expression and secretion by quantitative RT-PCR and Western blot.

Results: SPARC HFA mRNA was 100-, 700-, and 300-fold higher than TSP-1, TSP-2, and tenascin-C mRNA, respectively. HFA SPARC mRNA was 3-fold higher than adult adrenals (P < 0.005), comparable with levels in adult brain (positive control), whereas mRNAs encoding TSP-1 and TSP-2 were lower in fetal than adult adrenals. SPARC immunoreactivity was detected exclusively in the FZ, not DZ. ACTH, a key regulator of HFA growth and function, increased SPARC mRNA (by 1.7-fold at 1 nm, 48 h, P < 0.05) in isolated FZ cells but not DZ cells. ACTH up-regulation of SPARC protein was also detected in FZ cell lysates and culture medium.

Conclusions: Results suggest a possible role for SPARC in development of functional and/or structural zonation of the HFA.
Epithelial stem cells of the lung: privileged few or opportunities for many?
Authors: Rawlins Emma L. , Hogan Brigid L. M.
Published: May 2006

Most reviews of adult stem cells focus on the relatively undifferentiated cells dedicated to the renewal of rapidly proliferating tissues, such as the skin, gut and blood. By contrast, there is mounting evidence that organs and tissues such as the liver and pancreatic islets, which turn over more slowly,use alternative strategies, including the self-renewal of differentiated cells. The response of these organs to injury may also reveal the potential of differentiated cells to act as stem cells. The lung shows both slow turnover and rapid repair. New experimental approaches, including those based on studies of embryonic development, are needed to identify putative lung stem cells and strategies of lung homeostasis and repair.
TheSzAmutations of the B subunit of theDrosophilavacuolar H+ ATPase identify conserved residues essential for function in fly and yeast
Authors: Du J. , Kean L. , Allan A. K. , Southall T. D. , Davies S. A. , McInerny C. J. , Dow J. A. T.
Published: May 2006

V-ATPases play multiple roles in eukaryotes: in Drosophila, null mutations are recessive lethal. Here, mutations underlying five extant lethal alleles of vha55, encoding the B subunit, were identified, including a premature termination codon and two mutations very close to residues thought to participate in the catalytic site of the enzyme. Lethality of these alleles could be reverted by transformation of flies with a wild type vha55::GFP fusion, confirming that the lethal phenotype described for these alleles was due to defects in V-ATPase function. The chimeric protein was correctly localised to the apical domain of the Malpighian (renal) tubule, and restored fluid transport function to wild-type levels. No dominant-negative phenotype was apparent in heterozygotes. When the vha55::GFP fusion was driven ubiquitously, fluorescent protein was only detectable in tissues known to contain high levels of V-ATPase, suggesting that vha55 requires stoichometric co-expression of other subunits to be stable. Yeast (Saccharomyces cerevisiae) deleted for the corresponding gene (Δvma2) demonstrated a pH-sensitive growth phenotype that was rescued by the vha55::GFP construct. Δvma2 yeast could not be rescued with fly cDNAs encoding any of the mutant vha55 alleles, confirming the functional significance of the mutated residues. In yeast, bafilomycin-sensitive ATPase activity and growth rate correlated with the ability of different constructs to rescue the pH-sensitive conditional-lethal phenotype. These classical Drosophila mutants thus identify residues that are essential for function in organisms with wide phylogenetic separation.
A Branch-and-Cut Algorithm for the Dial-a-Ride Problem
Authors: Cordeau Jean-François
Published: May 2006

In the dial-a-ride problem, users formulate requests for transportation from a specific origin to a specific destination. Transportation is carried out by vehicles providing a shared service. The problem consists of designing a set of minimum-cost vehicle routes satisfying capacity, duration, time window, pairing, precedence, and ride-time constraints. This paper introduces a mixed-integer programming formulation of the problem and a branch-and-cut algorithm. The algorithm uses new valid inequalities for the dial-a-ride problem as well as known valid inequalities for the traveling salesman, the vehicle routing, and the pick-up and delivery problems. Computational experiments performed on randomly generated instances show that the proposed approach can be used to solve small to medium-size instances.
Characterization of the Neutron Field in the HSSI Reusable Irradiation Facility at the Ford Nuclear Reactor
Authors: Remec I , Rosseel TM , Blakeman ED , Baldwin CA , Heatherly DW , Thoms KR
Published: May 2006

The characterization of the neutron environment in a reusable facility for irradiation of metallurgical specimens, located at the Ford Nuclear reactor in Michigan, was performed with a combination of transport calculations, extensive dosimeter measurements, and neutron spectrum adjustment. The average difference between the calculated and “measured” reaction rates was ∼7% (the calculations underpredicted the measurements), and the average absolute difference was ∼10%. Therefore, the calculations and measurements agreed very well. The flexible facility performed excellently during several years of operation but was discontinued when the Ford reactor ceased operation. The heavy-section steel irradiation (HSSI) program is taking the initial steps toward selecting a site for a new irradiation facility, similar to the one described here.
Saccadic Suppression of Retinotopically Localized Blood Oxygen Level-Dependent Responses in Human Primary Visual Area V1
Authors: Vallines Ignacio , Greenlee Mark W.
Published: May 2006

Saccadic eye movements are responsible for bringing relevant parts of the visual field onto the fovea for detailed analysis. Because the retina is physiologically unable to deliver sharp images at very high transsaccadic speeds, the visual system minimizes the repercussion of the blurry images we would otherwise perceive during transsaccadic vision by reducing general visual sensitivity and increasing the detection threshold for visual stimuli. Ruling out a pure retinal origin, the effects of saccadic suppression can be already observed some 75 ms before the onset of a saccadic eye movement and are maximal at the onset of motion. The perception of a briefly presented stimulus immediately before the onset of any retinal motion is thus impaired despite the fact that this stimulus is projected onto the stationary retina and is, therefore, physically identical to that presented when no saccadic programming is in course. In this functional magnetic resonance imaging event-related study, we flashed Gabor patches at different times before the onset of a horizontal saccade and measured blood oxygen level-dependent responses at their encoding regions in primary visual cortex (V1) while subjects judged the relative orientation of the stimuli. Closely matching the significant reduction in behavioral performance, the amplitude of the responses in V1 consistently decreased as the stimuli were presented closer to the saccadic onset. These results demonstrate that the neural processes underlying saccade programming transiently modulate cortical responses to briefly presented visual stimuli in areas as early a V1, providing additional evidence for the existence of an active saccadic suppression mechanism in humans.
Noradrenaline Unmasks Novel Self-Reinforcing Motor Circuits within the Mammalian Spinal Cord
Authors: Machacek David W. , Hochman Shawn
Published: May 2006

Spiking activity in motor axons represents the final central coding for muscle contraction. Recurrent collaterals in spinal cord from these same axons are known to offer a negative feedback control of motor output via a class of interposed inhibitory interneurons. Here we demonstrate that, during noradrenergic drive, a previously unknown recurrent excitatory pathway is unmasked and expressed. These excitatory projections are shown to have broad bilateral actions within and between hindlimb spinal segments and can alter ongoing pattern-generating motor behaviors. Thus, motor output strength is controlled via central positive and negative feedback loops, undoubtedly to provide a greater flexibility and dynamic range of control. That this novel function is regulated by a descending neuromodulatory transmitter indicates a conditional recruitment during certain behavioral states as part of the central noradrenergic arousal apparatus.
Neuromodulation of Spike-Timing Precision in Sensory Neurons
Authors: Billimoria Cyrus P. , DiCaprio Ralph A. , Birmingham John T. , Abbott L. F. , Marder Eve
Published: May 2006

The neuropeptide allatostatin decreases the spike rate in response to time-varying stretches of two different crustacean mechanoreceptors, the gastropyloric receptor 2 in the crabCancer borealisand the coxobasal chordotonal organ (CBCTO) in the crabCarcinus maenas. In each system, the decrease in firing rate is accompanied by an increase in the timing precision of spikes triggered by discrete temporal features in the stimulus. This was quantified by calculating the standard deviation or “jitter” in the times of individual identified spikes elicited in response to repeated presentations of the stimulus. Conversely, serotonin increases the firing rate but decreases the timing precision of the CBCTO response. Intracellular recordings from the afferents of this receptor demonstrate that allatostatin increases the conductance of the neurons, consistent with its inhibitory action on spike rate, whereas serotonin decreases the overall membrane conductance. We conclude that spike-timing precision of mechanoreceptor afferents in response to dynamic stimulation can be altered by neuromodulators acting directly on the afferent neurons.
Ipsilateral Input Modifies the Primary Somatosensory Cortex Response to Contralateral Skin Flutter
Authors: Tommerdahl Mark , Simons Stephen B. , Chiu Joannellyn S. , Favorov Oleg , Whitsel Barry L.
Published: May 2006

We recorded the optical intrinsic signal response of squirrel monkey primary somatosensory cortex (SI) to 25 Hz vibrotactile (“flutter”) stimulation applied independently to the thenar eminence on each hand and also to bilateral (simultaneous) stimulation of both thenars. The following observations were obtained in every subject (n= 5). (1) Ipsilateral stimulation was accompanied by an increase in absorbance within the SI hand region substantially smaller than the absorbance increase evoked by contralateral stimulation. (2) The absorbance increase evoked by simultaneous bilateral stimulation was smaller (by ∼30%) than that evoked by contralateral stimulation. (3) The spatiointensive pattern of the SI response to bilateral flutter was distinctly different than the pattern that accompanied contralateral flutter stimulation: with contralateral flutter, the center of the responding region of SI underwent a large increase in absorbance, whereas absorbance decreased in the surrounding region; in contrast, during bilateral flutter, absorbance decreased (relative to that evoked by contralateral flutter) in the central region of SI but increased in the surround. The results raise the possibility that somatosensory perceptual experiences specific to bimanual tactile object exploration derive, at least in part, from the unique spatiointensive activity pattern evoked in SI when the stimulus makes contact with both hands. It is suggested that modulatory influences evoked by ipsilateral thenar flutter stimulation reach SI via a two-stage pathway involving interhemispheric (callosal) connections between information processing levels higher than SI and subsequently via intrahemispheric (corticocortical) projections to the SI hand region.
Matrix Metalloproteinase 2 (MMP2) and MMP9 Secreted by Erythropoietin-Activated Endothelial Cells Promote Neural Progenitor Cell Migration
Authors: Wang Lei , Zhang Zheng Gang , Zhang Rui Lan , Gregg Sara R. , Hozeska-Solgot Ann , LeTourneau Yvonne , Wang Ying , Chopp Michael
Published: May 2006

We investigated the hypothesis that endothelial cells activated by erythropoietin (EPO) promote the migration of neuroblasts. This hypothesis is based on observationsin vivothat treatment of focal cerebral ischemia with EPO enhances the migration of neuroblasts to the ischemic boundary, a site containing activated endothelial cells and angiogenic microvasculature. To model the microenvironment within the ischemic boundary zone, we used a coculture system of mouse brain endothelial cells (MBECs) and neural progenitor cells derived from the subventricular zone of the adult mouse. Treatment of MBECs with recombinant human EPO (rhEPO) significantly increased secretion of matrix metalloproteinase 2 (MMP2) and MMP9. rhEPO-treated MBEC supernatant as conditioned medium significantly increased the migration of neural progenitor cells. Application of an MMP inhibitor abolished the supernatant-enhanced migration. Incubation of neurospheres alone with rhEPO failed to increase progenitor cell migration. rhEPO activated phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase (ERK1/2) in MBECs. Selective inhibition of the PI3K/Akt and ERK1/2 pathways significantly attenuated the rhEPO-induced MMP2 and MMP9, which suppressed neural progenitor cell migration promoted by the rhEPO-activated MBECs. Collectively, our data show that rhEPO-activated endothelial cells enhance neural progenitor cell migration by secreting MMP2 and MMP9 via the PI3K/Akt and ERK1/2 signaling pathways. These data demonstrate that activated endothelial cells can promote neural progenitor cell migration, and provide insight into the molecular mechanisms underlying the attraction of newly generated neurons to injured areas in brain.
Vibrissa-Signaled Eyeblink Conditioning Induces Somatosensory Cortical Plasticity
Authors: Galvez Roberto , Weiss Craig , Weible Aldis P. , Disterhoft John F.
Published: May 2006

Whisker deflection conditioned stimuli (CS) were demonstrated to activate physiologically and anatomically defined barrels in the contralateral somatosensory cortex and to support trace–eyeblink conditioned responses when paired with corneal airpuff unconditioned stimuli in rabbits. Analysis of cytochrome-oxidase-stained somatosensory whisker-associated cortical barrels revealed a row-specific expansion of the conditioned compared with the nontrained hemisphere. This expansion was not evident in pseudo-conditioned rabbits, suggesting that this expansion of conditioned cortical barrels in response to a hippocampal- and forebrain-dependent learning task (trace conditioning) is associative rather than activity dependent. Using whisker stimulation as a CS in the well studied eyeblink conditioning paradigm will facilitate characterizing sensory cortical involvement in controlling and modulating an associatively learned response at the neural systems and cellular level.
Prevalence, Severity, and Risk Variables Associated With Gingival Overgrowth in Renal Transplant Subjects Treated Under Tacrolimus or Cyclosporin Regimens
Authors: de Oliveira Costa Fernando , Diniz Ferreira Sérgio , de Miranda Cota Luís Otávio , da Costa José Eustáquio , Aguiar Marco Antonio
Published: May 2006

Background: Some reports suggest that the prevalence and severity of gingival overgrowth (GO) is lower in patients taking tacrolimus (Tcr) than in those taking cyclosporin A (CsA). The present study was conducted to determine the prevalence and severity of GO in a group of renal transplant recipients treated with Tcr in comparison to those treated with CsA and to evaluate the risk variables associated with the development of GO in these two drug regimens.

Methods: A cross‐sectional study was conducted in a public hospital in Belo Horizonte City, Brazil. Demographic, pharmacological, and periodontal data were recorded for each subject. Variables from 134 subjects taking Tcr were compared to 451 subjects taking CsA using independent sample t, χ2 statistic, or Mann‐Whitney tests. The effects of potential risk factors on GO severity were determined using forward and backward stepwise regression analysis.

Results: Subjects taking CsA showed a higher mean GO score (29.03% ± 22.9%) compared to subjects taking Tcr (16.9% ± 3.4%) (P = 0.0038). In the Tcr group, 17.9% of the subjects had clinically significant GO compared to 38.1% in the CsA group (P = 0.045). In the multivariate final model, papillary bleeding index, azathioprine dosage, and concomitant use of calcium channel blockers (CCB) were significant variables associated with severity of GO in Tcr and CsA groups. In addition, previous CsA use also remained significant for GO in subjects under a Tcr regimen.

Conclusions: The prevalence and severity of GO is lower in transplant subjects taking Tcr compared to CsA. GO severity in both groups was strongly associated with the papillary bleeding index, highlighting the role of inflammation in this condition. Concomitant CCB use, azathioprine dosage, and previous CsA use in the Tcr group reinforces the possible synergistic effects of these pharmacological variables on GO severity.
Behavior of Transplanted Bone Marrow–Derived Mesenchymal Stem Cells in Periodontal Defects
Authors: Hasegawa Naohiko , Kawaguchi Hiroyuki , Hirachi Akio , Takeda Katsuhiro , Mizuno Noriyoshi , Nishimura Masahiro , Koike Chika , Tsuji Koichiro , Iba Hideo , Kato Yukio , Kurihara Hidemi
Published: May 2006

Background: Recently, there have been an increased number of basic and clinical reports indicating the superior potential of bone marrow–derived mesenchymal stem cells (MSCs) for tissue regeneration. In periodontal treatment, previous animal studies indicated that autotransplantation of bone marrow MSCs into experimental periodontal defects enhanced periodontal tissue regeneration. However, mechanisms for periodontal tissue regeneration with MSCs are still unclear. The purpose of this study was to elucidate the behavior of transplanted MSCs in periodontal defects.

Methods: Bone marrow MSCs were isolated from beagle dogs, labeled with green fluorescent protein (GFP), and expanded in vitro. The expanded MSCs were mixed with atelocollagen (2% type I collagen) at final concentrations of 2 × 107 cells/ml and transplanted into experimental Class III periodontal defects. Localizations of GFP and proliferating cell nuclear antigen (PCNA)‐positive cells were evaluated by immunohistochemical analysis.

Results: Four weeks after transplantation, the periodontal defects were almost regenerated with periodontal tissue. Cementoblasts, osteoblasts, osteocytes, and fibroblasts of the regenerated periodontal tissue were positive with GFP. PCNA‐positive cells were present in regenerating connective tissue.

Conclusion: These findings suggest that transplanted mesenchymal stem cells could survive and differentiate into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration.
Guided Bone Regeneration of a Pronounced Gingivo‐Alveolar Cleft Due to Orthodontic Space Closure
Authors: Pinheiro Maria Letícia B. , Moreira Teresa Cristina , Feres‐Filho Eduardo J.
Published: May 2006

Background: Gingival invagination is a relatively common occurrence following orthodontic closure of extraction sites. The present paper reports a combined periodontal and orthodontic treatment in a patient with a severe gingivo‐alveolar cleft due to orthodontic closure of maxillary central incisor extraction space.

Methods: A definite interdental gingival cleft, extending 8 mm into the alveolar bone, required the correction of the gingival deformity as a first step, followed by guided bone regeneration (GBR). The GBR approach included the emptying of the incisive foramen to ∼5 mm in depth followed by the insertion of bioabsorbable hydroxyapatite and covering with a bioabsorbable barrier membrane. Six months afterward, the orthodontic therapy was resumed.

Results: Radiographs and clinical examination 4 years after the completion of therapy indicates functionally and aesthetically satisfactory and stable results.

Conclusion: The present paper illustrates an additional application for the guided bone regeneration technique.
Access to Care, Health Status, and Health Disparities in the United States and Canada: Results of a Cross-National Population-Based Survey
Authors: Lasser Karen E. , Himmelstein David U. , Woolhandler Steffie
Published: May 2006

Objectives. We compared health status, access to care, and utilization of medical services in the United States and Canada and compared disparities according to race, income, and immigrant status.

Methods. We analyzed population-based data on 3505 Canadian and 5183 US adults from the Joint Canada/US Survey of Health. Controlling for gender, age, income, race, and immigrant status, we used logistic regression to analyze country as a predictor of access to care, quality of care, and satisfaction with care and as a predictor of disparities in these measures.

Results. In multivariate analyses, US respondents (compared with Canadians) were less likely to have a regular doctor, more likely to have unmet health needs, and more likely to forgo needed medicines. Disparities on the basis of race, income, and immigrant status were present in both countries but were more extreme in the United States.

Conclusions. United States residents are less able to access care than are Canadians. Universal coverage appears to reduce most disparities in access to care.
Discrimination, Symptoms of Depression, and Self-Rated Health Among African American Women in Detroit: Results From a Longitudinal Analysis
Authors: Schulz Amy J. , Gravlee Clarence C. , Williams David R. , Israel Barbara A. , Mentz Graciela , Rowe Zachary
Published: May 2006

Objectives. Our understanding of the relationships between perceived discrimination and health was limited by the cross-sectional design of most previous studies. We examined the longitudinal association of self-reported everyday discrimination with depressive symptoms and self-rated general health.

Methods. Data came from 2 waves (1996 and 2001) of the Eastside Village Health Worker Partnership survey, a community-based participatory survey of African American women living on Detroit’s east side (n=343). We use longitudinal models to test the hypothesis that a change in everyday discrimination over time is associated with a change in self-reported symptoms of depression (positive) and on self-reported general health status (negative).

Results. We found that a change over time in discrimination was significantly associated with a change over time in depressive symptoms (positive) (b=0.125; P<.001) and self-rated general health (negative) (b=−0.163; P<.05) independent of age, education, or income.

Conclusions. The results reported here are consistent with the hypothesis that everyday encounters with discrimination are causally associated with poor mental and physical health outcomes. In this sample of African American women, this association holds above and beyond the effects of income and education.