bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional and post-transcriptional regulation of retrotransposons IAP and MuERV-L affect pluripotency of mice ES cells
Authors: Ramírez Miguel A , Pericuesta Eva , Fernandez-Gonzalez Raul , Moreira Pedro , Pintado Belen , Gutierrez-Adan Alfonso
Published: November 2006

Background

In the mouse, culture of embryonic stem (ES) cells may decrease their pluripotency and give rise to foetal abnormalities in recipient embryos. These abnormalities are frequently associated with both, chromosome abnormalities or epigenetic alteration of imprinting genes; however, little is known about the epigenetic stability of endogenous retrotransposable elements (REs). In our laboratory, we came across a R1 ES cell line, which at passage 27, lost the ability of germline transmission and started inducing the kinky tail phenotype in all chimeric animals produced with it.

Methods

In order to investigate whether this phenotype was associated with chromosome alteration, inadvertent differentiation, or epigenetic modification, we characterized and compared this R1 ES cell line at passage 27 with an early passage and with a second ES cell line C57/CBAF1 generated in our laboratory. We assessed: i) karyotype; ii) expression of pluripotent and differentiation markers, iii) mRNA transcription by qRT-PCR of two REs, intracisternal-A particle (IAP) and murine endogenous-retrovirus-L (MuERV-L), and iv) methylation of IAP and MuERV-L.

Results

The R1 ES cell at passage 27, presented normal morphology, karyotype, and expression of genetic markers characteristic of pluripotent; however, it was detected an altered mRNA transcription of sense and antisense RNA strands of both REs, concomitantly with an altered methylation pattern for the IAP element but not for MuERV-L. These results indicate that besides methylation, other post-transcriptional processes are involved in gene silencing of some REs; and that culture of ES cells may decrease their pluripotency by producing inadvertent alterations in the expression of REs without significantly affecting the morphology, chromosome structure, and expression of pluripotent or differentiation markers.

Conclusion

Inadvertent REs instability may have important consequences for the use of ES cells in transgenesis (chimera formation) or in cell therapy.
Persistent resistance to HIV-1 infection in CD4 T cells from exposed uninfected Vietnamese individuals is mediated by entry and post-entry blocks
Authors: Sáez-Cirión Asier , Versmisse Pierre , Truong Lien X , Chakrabarti Lisa A , Carpentier Wassila , Barré-Sinoussi Françoise , Scott-Algara Daniel , Pancino Gianfranco
Published: November 2006

Background

We have previously reported that CD4 T cells from some exposed uninfected (EU) Vietnamese intravenous drug users are relatively resistant to HIV infection in vitro. Here, we further characterized the restriction of viral replication in CD4 T cells from five EUs and assessed its persistence in serial samples.

Results

CD4 T cells and/or PBMC sampled during a period of between 2 and 6 years were challenged with replication-competent HIV-1 and other retroviral particles pseudotyped with envelope proteins of various tropisms. CCR5 expression and function in resistant CD4 T cells was evaluated. The step at which HIV-1 replication is restricted was investigated by real-time PCR quantification of HIV-1 reverse transcripts.

We identified three patterns of durable HIV-1 restriction in EU CD4 T cells. CD4 T cells from four of the five EU subjects were resistant to HIV-1 R5 infection. In two cases this resistance was associated with low CCR5 surface expression, which was itself associated with heterozygous CCR5 mutations. In the other two cases, CD4 T cells were resistant to HIV-1 R5 infection despite normal CCR5 expression and signaling function, and normal β-chemokine secretion upon CD4 T cell activation. Instead, restriction appeared to be due to enhanced CD4 T cell sensitivity to β-chemokines in these two subjects. In the fifth EU subject the restriction involved post-entry steps of viral replication and affected not only HIV-1 but also other lentiviruses. The restriction was not overcome by a high viral inoculum, suggesting that it was not mediated by a saturable inhibitory factor.

Conclusion

Various constitutive mechanisms of CD4 T cell resistance to HIV-1 infection, affecting entry or post-entry steps of viral replication, are associated with resistance to HIV-1 in subjects who remain uninfected despite long-term high-risk behavior.
Identifying related cancer types based on their incidence among people with multiple cancers
Authors: Bajdik Chris D , Abanto Zenaida U , Spinelli John J , Brooks-Wilson Angela , Gallagher Richard P
Published: November 2006

Background

There are several reasons that someone might be diagnosed with more than one primary cancer. The aim of this analysis was to determine combinations of cancer types that occur more often than expected. The expected values in previous analyses are based on age-and-gender-adjusted risks in the population. However, if cancer in people with multiple primaries is somehow different than cancer in people with a single primary, then the expected numbers should not be based on all diagnoses in the population.

Methods

In people with two or more cancer types, the probability that a specific type is diagnosed was determined as the number of diagnoses for that cancer type divided by the total number of cancer diagnoses. If two types of cancer occur independently of one another, then the probability that someone will develop both cancers by chance is the product of the individual probabilities for each type. The expected number of people with both cancers is the number of people at risk multiplied by the separate probabilities for each cancer. We performed the analysis on records of cancer diagnoses in British Columbia, Canada between 1970 and 2004.

Results

There were 28,159 people with records of multiple primary cancers between 1970 and 2004, including 1,492 people with between three and seven diagnoses. Among both men and women, the combinations of esophageal cancer with melanoma, and kidney cancer with oral cancer, are observed more than twice as often as expected.

Conclusion

Our analysis suggests there are several pairs of primary cancers that might be related by a shared etiological factor. We think that our method is more appropriate than others when multiple diagnoses of primary cancer are unlikely to be the result of therapeutic or diagnostic procedures.
Quality and safety of genetic testing in Australia and New Zealand: a review of the current regulatory framework
Authors: Goold Imogen L , Pearn Amy , Bettiol Silvana , Ballantyne Angela
Published: November 2006

This paper provides an overview of the regulation of quality assurance for genetic testing in Australia and New Zealand and outlines the steps currently being taken to critically appraise and improve the regulatory framework in each country. It aims to contextualize this framework within the broader context of quality and patient safety concerns; and to draw together the concerns and recommendations of the various organizations that have been working to improve quality assurance in this area.
Hot Receptors in the Brain
Authors: Steenland Hendrik W , Ko Shanelle W , Wu Long-Jun , Zhuo Min
Published: November 2006

Two major approaches have been employed for the development of novel drugs to treat chronic pain. The most traditional approach identifies molecules involved in pain as potential therapeutic targets and has focused mainly on the periphery and spinal cord. A more recent approach identifies molecules that are involved in long-term plasticity. Drugs developed through the latter approach are predicted to treat chronic, but not physiological or acute, pain. The TRPV1 (transient receptor potential vanilloid-1) receptor is involved in nociceptive processing, and is a candidate therapeutic target for pain. While most research on TRPV1 receptors has been conducted at the level of the spinal cord and peripheral structures, considerably less research has focused on supraspinal structures. This short paper summarizes progress made on TRPV1 receptors, and reviews research on the expression and function of TRPV1 receptors in supraspinal structures. We suggest that the TRPV1 receptor may be involved in pain processing in higher brain structures, such as the anterior cingulate cortex. In addition, some regions of the brain utilize the TRPV1 receptor for functions apparently unrelated to pain.
Medical and Nursing Education and Training Opportunities to Improve Survivorship Care
Authors: Ferrell Betty R. , Winn Rodger
Published: November 2006

Improving the quality of care for cancer survivors is contingent on having physicians, nurses, and other professionals with adequate training in survivorship care. Previous literature has documented the deficiencies in existing formal education programs regarding the complex needs of this growing population. Continuing education programs and basic curricula need to incorporate the expanding body of knowledge regarding the physiologic and psychosocial sequlae of survivorship. This article reviews the current status of survivorship education and provides direction for essential content in future education. Topics such as prevention of secondary cancers, long-term complications, rehabilitation services, quality-of-life issues, pain and symptom management, and treatment of recurrent cancer are critical competencies of education that should then become routine care for cancer survivors.
Diverse physiological functions for dual-specificity MAP kinase phosphatases
Authors: Dickinson Robin J. , Keyse Stephen M.
Published: November 2006

A structurally distinct subfamily of ten dual-specificity (Thr/Tyr) protein phosphatases is responsible for the regulated dephosphorylation and inactivation of mitogen-activated protein kinase (MAPK) family members in mammals. These MAPK phosphatases (MKPs) interact specifically with their substrates through a modular kinase-interaction motif (KIM) located within the N-terminal non-catalytic domain of the protein. In addition, MAPK binding is often accompanied by enzymatic activation of the C-terminal catalytic domain, thus ensuring specificity of action. Despite our knowledge of the biochemical and structural basis for the catalytic mechanism of the MKPs, we know much less about their regulation and physiological functions in mammalian cells and tissues. However, recent studies employing a range of model systems have begun to reveal essential non-redundant roles for the MKPs in determining the outcome of MAPK signalling in a variety of physiological contexts. These include development, immune system function, metabolic homeostasis and the regulation of cellular stress responses. Interestingly, these functions may reflect both restricted subcellular MKP activity and changes in the levels of signalling through multiple MAPK pathways.
A systematic RNA interference screen reveals a cell migration gene network inC. elegans
Authors: Cram Erin J. , Shang Hongyu , Schwarzbauer Jean E.
Published: November 2006

Cell migration is essential during embryonic development and tissue morphogenesis. During gonadogenesis in the nematode Caenorhabditis elegans, migration of the distal tip cells forms two U-shaped gonad arms. Malformation results if the distal tip cells stop prematurely or follow an aberrant path, and abnormalities are easily visualized in living nematodes. Here we describe the first comprehensive in vivo RNA interference screen for genes required for cell migration. In this non-biased screen, we systematically analyzed 16,758 RNA-interference depletion experiments by light microscopy and identified 99 genes required for distal tip cell migration. Genetic and physical interaction data connect 59 of these genes to form a cell migration gene network that defines distal tip cell migration in vivo.
Adult Atomoxetine Ingestions Reported to Texas Poison Control Centers, 2003–2005
Authors: Forrester Mathias B
Published: November 2006

Background:

Limited information exists on outcomes from adult ingestions of atomoxetine reported to poison control centers.

Objective:

To identify factors that might affect the outcome of adult atomoxetine ingestions reported to poison control centers.

Methods:

Using adult ingestions of atomoxetine alone reported to Texas poison control centers during 2003–2005, the proportion of cases involving serious outcomes was determined for selected variables and evaluated for statistical significance by calculating the rate ratio (RR) and 95% confidence interval (CI).

Results:

Of 64 cases identified, 9 (14%) involved serious outcomes. No serious outcomes were reported with a maximum dose of 100 mg or less. Serious outcomes were significantly more likely to occur with a maximum dose of more than 2 capsules (RR 8.25; 95% CI 1.48 to 83.58), where the circumstances of the exposures involved self-harm or malicious intent (RR 6.02; 95% CI 1.30 to 30.35) or when the patient was already at or en route to a healthcare facility when the poison control center was contacted (RR 18.75; 95% CI 2.10 to 886.83) or was referred to a healthcare facility by the poison control center (RR 22.50; 95% CI 1.81 to 1181.19).

Conclusions:

The severity of the outcomes associated with adult atomoxetine ingestions depended on the dose taken and the circumstances of the ingestion. The management of patients with serious outcomes was more likely to involve healthcare facilities. Such information is useful in creating triage guidelines for the management of adult atomoxetine ingestions.
An Isometric Predictor for Maximum Acceptable Weight of Lift for Chinese Men
Authors: Lee Yung-Hui , Chen Yi-Lang
Published: November 2006

The aim of this study was to examine the practicality of the modified isometric strength tests to predict the maximum acceptable weight of lift (MAWL) of Chinese men. The modified strength tests allow the participant to pull on the load cell in front of the body and to apply force in a functional free posture. Both the modified and the standard strength data of each participant were used as predictors for the MAWLs. The prediction models were constructed and evaluated under task conditions of two lifting ranges, two box sizes, and three lifting frequencies. To realize the effect of modifications, testing posture was recorded and the joint angles were calculated. A stepwise multiple regression analysis indicated that modified composite strength (MCS), chest circumference, and acromial height accounted for 86% to 91% of the variance. Because the strength of the upper extremity body was also recruited in the test, the weak upper extremity strength of the Chinese participants would therefore be better reflected. Evidence for the existence of a close match between MAWL and MCS values, as well as the task conditions for its existence, suggest that a simple isometric strength measure is a good predictor for the MAWL.
SPECIAL SECTION: Users as Designers: How People Cope with Poor HCI Design in Computer-Based Medical Devices
Authors: Obradovich Jodi Heintz , Woods David D.
Published: November 2006

In this paper we examine how users interact with a computer-based infusion device adapted for terbutaline infusion to treat preterm labor in women experiencing high-risk pregnancies. This study examines (a) the human-computer interaction (HCI) deficiencies in the device as related to this context of use, (b) how the device characteristics increase the potential for error, and (c) the tailoring strategies developed by users to insulate themselves from failure. Interviews with nurses and tests of the behavior of the infusion device in different conditions identified several classic HCI deficiencies: complex and arbitrary sequences of operation, mode errors caused by poor differentiation of multiple operating modes intended for different contexts, ambiguous alarms, getting lost in multiple displays, and poor feedback on device state and behavior.
Effects of Adaptive Task Allocation on Monitoring of Automated Systems
Authors: Parasuraman Raja , Mouloua Mustapha , Molloy Robert
Published: November 2006

The effects of adaptive task allocation on monitoring for automation failure during multi task flight simulation were examined. Participants monitored an automated engine status task while simultaneously performing tracking and fuel management tasks over three 3D-min sessions. Two methods of adaptive task allocation, both involving temporary return of the automated engine status task to the human operator (“human control”), were examined as a possible countermeasure to monitoring inefficiency. For the model-based adaptive group, the engine status task was allocated to all participants in the middle of the second session for 10 min, following which it was again returned to automation control. The same occurred for the performance-based adaptive group, but only if an individual participant's monitoring performance up to that point did not meet a specified criterion. For the nonadaptive control groups, the engine status task remained automated throughout the experiment. All groups had low probabilities of detection of automation failures for the first 40 min spent with automation. However, following the lO-min intervening period of human control, both adaptive groups detected significantly more automation failures during the subsequent blocks under automation control. The results show that adaptive task allocation can enhance monitoring of automated systems. Both model-based and performance-based allocation improved monitoring of automation. Implications for the design of automated systems are discussed.
SPECIAL SECTION: Medication Instruction Design: Younger and Older Adult Schemas for Taking Medication
Authors: Morrow Daniel G. , Leirer Von O. , Andrassy Jill M. , Tanke Elizabeth Decker , Stine-Morrow Elizabeth A. L.
Published: November 2006

We examined whether older and younger adults share a schema for taking medication and whether instructions are better recalled when they are organized to match this schema. Experiment 1 examined age differences in schema organization. Participants sorted medication items (e.g., purpose, dose, possible side effects) according to similarity and then ordered the items to create a preferred instruction set. Cluster analysis of the sort and order data showed that younger and older adults share a schema for taking medication. Secondary regression analyses found that verbal ability (i.e., vocabulary scores) predicted individual differences in schema organization. In Experiment 2 participants recalled instructions that were either compatible with this schema in terms of grouping and order of items or were presented in nonpreferred orders. Younger participants remembered more information than did older participants, but both age groups better remembered and preferred the more schema-compatible instructions. Secondary analyses showed that recall was also positively related to verbal ability. Along with our earlier research, this study suggests that older and younger adults possess a schema for taking medication and that instructions that are compatible with this schema provide an environmental support that improves memory for medication information.
A New Look at an Old Study on Information Display: Washburne (1927) Reconsidered
Authors: Meyer Joachim
Published: November 2006

Washburne (1927) conducted the largest study to date on the display of quantitative information with tables and graphs. Measuring the accuracy of information recall, he concluded that bar graphs are particularly suited for complex comparisons between values, pictographs are best for simple comparisons, line graphs are best for identifying and comparing trends, and tables are best for specific values. These conclusions have intuitive appeal and were quoted in the literature on comparative displays. A reanalysis of the results indicates that only the claim that tables are best for recalling specific values is clearly supported by Washburne's data. The other conclusions were probably accepted without questioning because they appeal to intuition. Additional findings of the study, such as the importance of the logical ordering of items in a display, were not acknowledged in subsequent studies. In human factors, as in other fields, naive preconceptions exist which can impede the acquisition of new knowledge.
A Methodology for Optimally Designing Console Panels for Use by a Single Operator
Authors: Sargent Tiffany A. , Kay Michael G. , Sargent Robert G.
Published: November 2006

A seven-step methodology is presented to determine a dimensionally correct optimal layout of a console panel for a single operator. This methodology integrates the steps in the layout design process and uses a mathematical optimization model from facility design to obtain the optimal panel layout. A major difference in this methodology from previous work is that the mathematical optimization model incorporates factors that are only partially included in previous mathematical models. In addition, it includes the areas of the panel components as a new factor. This methodology is illustrated by the design of a nuclear power plant console panel.
The Effects of Response Format and Other Variables on Comparisons of Digital and Dial Displays
Authors: Miller R. J. , Penningroth Scott
Published: November 2006

We compared dial and digital clock displays to determine which could be read faster by 25 young adults. The influence of several variables on differences in response speed between the 2 display types was examined. These variables included response format (times expressed as minutes before the hour, minutes after the hour, or simple reading of hour and minute values), interval difficulty (times displayed in 5-min intervals or in intervals not divisible by 5), and the quadrant from which displayed times were selected. In general, digital displays led to faster responses than did dial displays. However, several combinations of the other variables, particularly those using the before-the-hour response format, effectively eliminated the superiority of digital displays. We suggest that in designing displays requiring such a response format, designers should not assume that a digital display is necessarily the best choice, especially if other factors encourage the selection of a dial display.
Evaluation of the Probability of Spinal Damage Caused by Sustained Cyclic Compression Loading
Authors: van Dieen Jaap H. , Toussaint Huub M.
Published: November 2006

A sensitivity analysis of two alternative models predicting damage to vertebral motion segments (VMS) in cyclic compression was performed to evaluate the relative probability of damage occurring when peak compression force, loading frequency, or duration in a lifting task is changed. The first model is based on the assumption that fatigue failure is the mechanism underlying damage to the VMS in cyclic compression. The second model is based on the assumption that the VMS damage in cyclic compression is determined by the viscoelastic deformation of the segment and that the instant of failure can be predicted on the basis of the energy stored in this process. With both models, we estimated the percentage of the population likely to incur a VMS injury when performing a repetitive lifting task with peak compression forces ranging from 1500 to 4100 N, frequencies from 2 to 12 min-1, and durations between 30 and 120 min. The results indicate a dominant influence of the peak compression force on this outcome over the domain studied. This conclusion holds qualitatively for both models, suggesting that for a comparative analysis they can be considered interchangeable. However, a considerable quantitative difference in the absolute outcomes of the two models was found, which stresses the importance of further study on the validity of these models.
The Effects of Spatial Frequency on Binocular Fusion: From Elementary to Complex Images
Authors: Roumes Corinne , Plantier Justin , Menu Jean-Pierre , Thorpe Simon
Published: November 2006

Factors limiting binocular fusion were studied using 2-dimensional difference of Gaussian (2D-DOG) stimuli. The proportion of fused stimuli and observer's response time were determined for stimuli that varied in spatial frequency composition between 0.22 and 4.8 cycles per degree. At small disparities, mean fusion response times were short and relatively stable but increased rapidly once the disparity reached a certain critical value. This 2-phase function implies the existence of 2 separate fusional mechanism: a rapid neurally based fusional process, which operates at small disparities, and a second mechanism involving reflexive vergence movements operating at disparities 2 to 3 times larger. Both mechanisms are highly influenced by spatial frequency, being 4 to 5 times more effective at low spatial frequencies. Additional experiments demonstrated that with compound stimuli, the fusion limit is not determined by the highest spatial frequency components (as had been reported previously) but, rather, can take advantage of the additional fusional range associated with low spatial frequencies. Such cooperation may be obvious only in the case of 2-dimensional stimuli.
Framing of Task Performance Strategies: Effects on Performance in a Multiattribute Dynamic Decision Making Environment
Authors: Nygren Thomas E.
Published: November 2006

It is well documented that the way a static choice task is "framed" can dramatically alter choice behavior, often leading to observable preference reversals. This framing effect appears to result from perceived changes in the nature or location of a person's initial reference point, but it is not clear how framing effects might generalize to performance on dynamic decision making tasks that are characterized by high workload, time constraints, risk, or stress. A study was conducted to examine the hypothesis that framing can introduce affective components to the decision making process and can influence, either favorably (positive frame) or adversely (negative frame), the implementation and use of decision making strategies in dynamic high-workload environments. Results indicated that negative frame participants were significantly impaired in developing and employing a simple optimal decision strategy relative to a positive frame group. Discussion focuses on implications of these results for models of dynamic decision making.
Stability Limits In Extreme Postures: Effects Of Load Positioning, Foot Placement, and Strength
Authors: Holbein Mary Ann , Chaffin Don B.
Published: November 2006

Although injuries related to postural stability are prevalent, ergonomic job analyses traditionally have not addressed stability issues. In this research functional stability limits are quantified for persons standing in extreme postures under various external load and foot positioning conditions. Participants were asked to lean and displace their center of gravity (COG) as far as possible in eight directions to the sides and front of the body. Stability measures based on these COG displacements were calculated. All controlled variables significantly affected the stability measures. When standing unladen, participants extended their COG to within 99% of their theoretical maximum. Movement was much more restricted when handling a load (89%), especially when holding it with one hand on the shoulder (84%). On average, increased separation of the feet in a particular direction resulted in larger COG displacements in that direction. The results are discussed relative to their effects on balance and stability modeling.
Tonic and Phasic Nitric Oxide Signals in Hippocampal Long-Term Potentiation
Authors: Hopper Rachel A. , Garthwaite John
Published: November 2006

Nitric oxide (NO) participates in long-term potentiation (LTP) and other forms of synaptic plasticity in many different brain areas but where it comes from and how it acts remain controversial. Using rat and mouse hippocampal slices, we tested the hypothesis that tonic and phasic NO signals are needed and that they derive from different NO synthase isoforms. NMDA increased NO production in a manner that was potently inhibited by three different neuronal NO synthase (nNOS) inhibitors. Tonic NO could be monitored after sensitizing guanylyl cyclase-coupled NO receptors, allowing the very low ambient NO concentrations to be detected by cGMP measurement. The levels were unaffected by inhibition of NMDA receptors, nNOS, or the inducible NO synthase (iNOS). iNOS was also undetectable in protein or activity assays. Tonic NO was susceptible to agents inhibiting endothelial NO synthase (eNOS) and was missing in eNOS knock-out mice. The eNOS knock-outs exhibited a deficiency in LTP resembling that seen in wild-types treated with a NO synthase inhibitor. LTP in the knock-outs could be fully restored by supplying a low level of NO exogenously. Inhibition of nNOS also caused a major loss of LTP, particularly of late-LTP. Again, exogenous NO could compensate, but higher concentrations were needed compared with those restoring LTP in the eNOS knock-outs. It is concluded that tonic and phasic NO signals are both required for hippocampal LTP and the two are generated, respectively, by eNOS and nNOS, the former in blood vessels and the latter in neurons.
Broad-Spectrum Effects of 4-Aminopyridine to Modulate Amyloid β1–42-Induced Cell Signaling and Functional Responses in Human Microglia
Authors: Franciosi Sonia , Ryu Jae K. , Choi Hyun B. , Radov Lesley , Kim Seung U. , McLarnon James G.
Published: November 2006

We investigated the modulating actions of the nonselective K+channel blocker 4-aminopyridine (4-AP) on amyloid β (Aβ1–42)-induced human microglial signaling pathways and functional processes. Whole-cell patch-clamp studies showed acute application of Aβ1–42(5 μm) to human microglia led to rapid expression of a 4-AP-sensitive, non-inactivating outwardly rectifying K+current (IK). Intracellular application of the nonhydrolyzable analog of GTP, GTPγS, induced an outward K+current with similar properties to the Aβ1–42-inducedIKincluding sensitivity to 4-AP (IC50= 5 mm). Reverse transcriptase-PCR showed a rapid expression of a delayed rectifier Kv3.1 channel in Aβ1–42-treated microglia. Aβ1–42peptide also caused a slow, progressive increase in levels of [Ca2+]i(intracellular calcium) that was partially blocked by 4-AP. Chronic exposure of human microglia to Aβ1–42led to enhanced p38 mitogen-activated protein kinase and nuclear factor κB expression with factors inhibited by 4-AP. Aβ1–42also induced the expression and production of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, the chemokine IL-8, and the enzyme cyclooxygenase-2; 4-AP was effective in reducing all of these pro-inflammatory mediators. Additionally, toxicity of supernatant from Aβ1–42-treated microglia on cultured rat hippocampal neurons was reduced if 4-AP was included with peptide.In vivo, injection of Aβ1–42into rat hippocampus induced neuronal damage and increased microglial activation. Daily administration of 1 mg/kg 4-AP was found to suppress microglial activation and exhibited neuroprotection. The overall results suggest that 4-AP modulation of an Aβ1–42-inducedIK(candidate channel Kv3.1) and intracellular signaling pathways in human microglia could serve as a therapeutic strategy for neuroprotection in Alzheimer's disease pathology.
Myosin Light Chain Kinase Is Not a Regulator of Synaptic Vesicle Trafficking during Repetitive Exocytosis in Cultured Hippocampal Neurons
Authors: Tokuoka Hirofumi , Goda Yukiko
Published: November 2006

The mechanism by which synaptic vesicles (SVs) are recruited to the release site is poorly understood. One candidate mechanism for trafficking of SVs is the myosin–actin motor system. Myosin activity is modulated by myosin light chain kinase (MLCK), which in turn is activated by calmodulin. Ca2+signaling in presynaptic terminals, therefore, may serve to regulate SV mobility along actin filaments via MLCK. Previous studies in different types of synapses have supported such a hypothesis. Here, we further investigated the role of MLCK in neurotransmitter release at glutamatergic synapses in cultured hippocampal neurons by examining the effects of two MLCK inhibitors, 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine·HCl (ML-7) and wortmannin. Bath application of ML-7 enhanced short-term depression of EPSCs to repetitive stimulation, whereas it reduced presynaptic release probability. However, ML-7 also inhibited action potential amplitude and voltage-gated Ca2+channel currents. These effects were not mimicked by wortmannin, suggesting that ML-7 was not specific to MLCK in hippocampal neurons. When SV exocytosis was directly triggered by a Ca2+ionophore, calcimycin, to bypass voltage-gated Ca2+channels, ML-7 had no effect on neurotransmitter release. Furthermore, when SV exocytosis elicited by electrical field stimulation was monitored by styryl dye, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide], the unloading kinetics of the dye was not altered in the presence of wortmannin. These data indicate that MLCK is not a major regulator of presynaptic SV trafficking during repetitive exocytosis at hippocampal synapses.
Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects
Authors: Du Congwu , Yu Mei , Volkow Nora D. , Koretsky Alan P. , Fowler Joanna S. , Benveniste Helene
Published: November 2006

Cocaine abuse increases the risk of life-threatening neurological complications such as strokes and seizures. Although the vasoconstricting properties of cocaine underlie its cerebrovascular effects, the mechanisms underlying its neurotoxicity remain incompletely understood. Here, we use optical techniques to measure cerebral blood volume, hemoglobin oxygenation (StO2), and intracellular calcium ([Ca2+]i) to test the hypothesis that cocaine increases [Ca2+]iin the brain. The effects of cocaine were compared with those of methylphenidate, which has similar catecholaminergic effects as cocaine (except for serotonin increases) but no local anesthetic properties, and of lidocaine, which has similar local anesthetic effects as cocaine but is devoid of catecholaminergic actions. To control for the hemodynamic effects of cocaine, we assessed the effects of cocaine in animals in which normal blood pressure was maintained by infusion of phenylephrine, and we also measured the effects of transient hypotension (mimicking that induced by cocaine). We show that cocaine induced significant increases (∼10–15%) in [Ca2+]ithat were independent of its hemodynamic effects and of the anesthetic used (isofluorance or α-chloralose). Lidocaine but not methylphenidate also induced significant [Ca2+]iincreases (∼10–13%). This indicates that cocaine at a dose within the range used by drug users significantly increases the [Ca2+]iin the brain and its local anesthetic, but neither its catecholaminergic nor its hemodynamic actions, underlies this effect. Cocaine-induced [Ca2+]iincreases are likely to accentuate the neurotoxic effects from cocaine-induced vasoconstriction and to facilitate the occurrence of seizures from the catecholaminergic effects of cocaine. These findings support the use of calcium channel blockers as a strategy to minimize the neurotoxic effects of cocaine.
Adaptabilidade e estabilidade de linhagens experimentais de soja selecionadas para caracteres agronômicos através de método uni-multivariado
Authors: Maia Maria Clideana Cabral , Vello Natal Antonio , Rocha Maurisrael de Moura , Pinheiro José Baldin , Silva Júnior Nelson Fonseca da
Published: November 2006

Esta pesquisa visou estudar a interação entre genótipos e ambientes (G x E), a adaptabilidade e estabilidade fenotípica, com o uso do modelo biométrico AMMI (Additive Main Effects and Multiplicative Interaction Analysis), para avaliação da produtividade de grãos de linhagens experimentais (F10 e F11) de soja. O material envolveu três populações obtidas a partir de um dialelo parcial 4 x 4 com quatro genitores resistentes a insetos (IAC-100, Crokett, Lamar e D72-9601-1) e quatro cultivares adaptadas (BR-6, IAS-5, Davis, OCEPAR-4). Em F2 foram empregados três procedimentos distintos de seleção de plantas individuais: PCI, população formada a partir de plantas F2 obtidas com controle total de insetos; PRIM e PRIS formadas a partir de plantas F2 selecionadas para resistência a insetos mastigadores e sugadores respectivamente. De F3 a F11 foi praticada seleção entre progênies para produtividade de grãos e tolerância ao fotoperíodo. Foram desenvolvidos 24 experimentos delineados em blocos ao acaso com duas repetições subdivididas em conjuntos experimentais com testemunhas comuns, combinando as três populações e oito ambientes. Os ambientes (E1 a E8) combinaram dois locais (Anhembi, Areão), dois anos agrícolas (1999/2000, 2000/2001) e dois sistemas de manejo (controle intensivo de insetos ou CII e controle ecológico de insetos ou CEI). Os experimentos de 1999/2000 e 2000/2001 incluíram, respectivamente, 40 e 20 linhagens de uma população. Com base na produtividade de grãos, concluiu-se: o método AMMI evidenciou como linhagens F11 estáveis e produtivas, 70% da PCI, 65% da PRIS e 55% da PRIM; o local Anhembi destacou-se como de alta produtividade em todas as situações (três populações, dois anos e dois manejos; para as três populações, dentre os ambientes mais produtivos, o método AMMI destacou E1 (Anhembi, 1999/2000, CII) como de máxima estabilidade e E6 (Anhembi, 2000/2001, CEI) como de máxima instabilidade; para a capacidade de gerar linhagens superiores em adaptabilidade e estabilidade, sobressaíram-se os genitores IAC-100, D72-9601-1, BR-6, Davis e IAS-5; destaques especiais envolveram os cruzamentos do genitor IAC-100 com IAS-5, Davis, OCEPAR-4 e BR-6.
Influência da salinidade sobre o crescimento, absorção e distribuição de sódio, cloro e macronutrientes em plântulas de maracujazeiro-amarelo
Authors: Cruz Jailson Lopes , Pelacani Claudinéia Regina , Coelho Eugênio Ferreira , Caldas Ranulfo Correa , Almeida Adriana Queiroz de , Queiroz Jurema Rosa de
Published: November 2006

A presença de sódio (Na) e de cloro (Cl) no substrato tem ocasionado redução no crescimento dos vegetais, em virtude desses íons causarem, entre outros efeitos negativos, mudanças na capacidade das plantas em absorver, transportar e utilizar alguns dos nutrientes. Assim, o objetivo do presente trabalho foi o de avaliar a influência da salinidade sobre o crescimento e a absorção e distribuição do Na e Cl e dos macronutrientes em plântulas de Maracujazeiro-amarelo, durante 50 dias de crescimento sob condições salinas, em vasos com capacidade para 2,2 dm³. Foram utilizados três níveis de NaCl (0, 50 e 100 m mol L-1). Observou-se que a altura, o número de folhas, a área foliar e a massa seca de todas as partes da planta foram significativamente reduzidas pela salinidade. A concentração dos íons Na e Cl aumentaram com o acréscimo da salinidade no meio de cultivo, porém, foram parcialmente retidos na raiz, no caso do Cl, e nas folhas mais velhas, no caso do Na. As concentrações de nitrogênio (N), fósforo (P) e cálcio (Ca) não foram afetadas pela salinidade. As concentrações de potássio (K), ao contrário, decresceram em todas as partes da planta, enquanto as do enxofre (S) foi reduzida apenas nas raízes. Dada a pequena redução nas características de crescimento conclui-se que o Maracujazeiro-amarelo é uma espécie moderadamente tolerante ao estresse salino.
Adequação de uma dieta artificial para os biótipos "milho" e "arroz" de Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Busato Gustavo Rossato , Garcia Mauro Silveira , Loeck Alci Enimar , Zart Marcelo , Nunes Adrise Medeiros , Bernardi Oderlei , Andersson Fabiana da Silva
Published: November 2006

Spodoptera frugiperda é considerada uma das principais pragas da cultura do milho (lagarta-do-cartucho) e do arroz irrigado (lagarta-da-folha), ocasionando altos índices de desfolhamento. O objetivo do estudo foi obter uma dieta artificial adequada para criar os biótipos "milho" e "arroz" de S. frugiperda (J.E. Smith), em laboratório. Os insetos foram coletados em áreas cultivadas com milho e arroz irrigado no ecossistema de várzea e a identificação foi realizada pela análise do DNA genômico. O desenvolvimento dos dois biótipos foi acompanhado sobre a dieta de Greene e a mesma dieta modificada a 25 ± 1ºC, UR de 70 ± 10% e fotofase de 14 horas. O estudo foi realizado com 150 lagartas por dieta, individualizadas em tubos de vidro e contendo dieta artificial. Por ocasião da emergência, 20 casais foram individualizados e alimentados com solução aquosa de mel a 10%. A dieta Greene possibilitou melhor desenvolvimento dos dois biótipos, proporcionando maior velocidade de desenvolvimento, maior massa de lagartas no máximo desenvolvimento, massa de pupas e fecundidade total, além de valores mais elevados da taxa líquida de reprodução, taxa intrínseca de crescimento e taxa finita de aumento.
Análise de crescimento em Heteranthera reniformis, sob diferentes teores de Ca, Mg e S
Authors: Domingos Vanessa David , Martins Dagoberto , Fernandes Dirceu Maximino , Costa Neumarcio Vilanova da , Paschoa Paulo Lovo de
Published: November 2006

O objetivo deste trabalho foi estudar o crescimento, alocação de biomassa e teores de nutrientes em Heteranthera reniformis Ruiz & Pav., sob o efeito de diferentes concentrações de Ca, Mg e S. As plantas foram cultivadas em vasos plásticos preenchidos com pedra rolada, em soluções nutritivas a 80% da concentração original de Sarruge, correspondente à solução-base. O experimento foi desenvolvido em delineamento experimental inteiramente casualizado, com quatro teores (0%, 25%, 50% e 75% da solução base de 80%) avaliados em Ca, Mg e S, além da testemunha (solução-base), com quatro repetições no período de 35 dias em casa de vegetação. O aumento dos teores de Ca na solução propiciou uma redução significativa na área foliar. As maiores áreas foliares ocorreram em soluções a 25% de Ca e 50% de Mg e S. A maior proporção de biomassa seca está no caule, exceto a 25% de Ca (40 mg L-1) que propiciou maior área foliar e área foliar específica. Entre os teores de Mg na solução, as maiores biomassas foram observadas a 50% de Mg (19,2 mg.L-1) e, para o S, não houve diferenças significativas, exceto a 0%. A solução com 160 mg L-1 de Ca propiciou maior concentração de Ca na folha (56,6 g kg-1). Os teores de Ca, Mg e S em solução corresponderam a um aumento proporcional na planta. Os teores de enxofre nas folhas e nos caules aumentaram com a concentração de S na solução, enquanto o teor nas raízes reduziu nas concentrações entre 12,8 e 38,4 mg.L-1.
Hidropsia endolinfática experimental sob ação de inibidor da óxido nítrico sintase tipo II: avaliação com emissões otoacústicas e eletrococleografia
Authors: Ikino Claudio Marcio Yudi , Bittar Roseli Saraiva Moreira , Sato Karina Midori , Capella Newton Macuco
Published: November 2006

No modelo experimental de hidropsia endolinfática há redução na amplitude das emissões otoacústicas produtos de distorção (EOAPD) e elevação nos limiares eletrofisiológicos na eletrococleografia. Estudos mostraram que há expressão da óxido nítrico sintase tipo II (ONS II) na cóclea com hidropsia, sugerindo a participação do óxido nítrico (ON) na patogênese desta doença. O objetivo deste trabalho foi avaliar a ação de um inibidor da ONS II nas EOAPD e eletrococleografia em cobaias com hidropisia endolinfática experimental. MATERIAL E MÉTODOS: Foram estudadas 16 cobaias nas quais se induziu hidropsia endolinfática experimental por obliteração do ducto e saco endolinfático na orelha direita durante 16 semanas, divididas em dois grupos: oito cobaias recebendo um inibidor da ONS II, a aminoguanidina, por via oral e um grupo de oito cobaias como controle. Comparamos as amplitudes das EOAPD nas médias geométricas de freqüências de 1062, 2187, 4375 e 7000Hz, os limiares eletrofisiológicos nas freqüências de 1000, 2000, 4000 e 6000Hz e a relação entre os potenciais de somação e de ação (PS/PA) entre os grupos. RESULTADOS: Não houve diferença significante nas EOAPD e na relação PS/PA entre os grupos. O grupo que recebeu a aminoguanidina apresentou menor elevação nos limiares eletrofisiológicos nas freqüências de 2000 (p<0,05) e 6000 Hz (p<0,05) na 12ª semana e nas freqüências de 1000 (p<0,05), 2000 (p<0,001), 4000 (p<0,001) e 6000Hz (p<0,001) na 16ª semana. CONCLUSÕES: O inibidor da ONS II reduziu a elevação dos limiares eletrofisiológicos na eletrococleografia na hidropsia endolinfática experimental.
Comparação entre os bioenxertos de hidroxiapatita de cálcio e submucosa de intestino delgado porcino no preenchimento de defeitos ósseos criados em mandíbula de ratos
Authors: Soccol Andréa Thomaz , Bettega Silvio , Noronha Lúcia , Sass Sheila , Soccol Vanete T. , Scholz Marcos Renato , Mocellin Marcos
Published: November 2006

OBJETIVO: O objetivo do presente estudo consiste em avaliar a regeneração óssea em defeito criado na mandíbula de ratos utilizando dois bioenxertos: hidroxiapatita de cálcio sintética e submucosa de intestino delgado porcina. FORMA DE ESTUDO: Experimental randomizado. MATERIAL E MÉTODO: Foram utilizados 24 ratos da linhagem Wisthar-Furth. Um defeito ósseo de 0,75cm x 1,5cm no corpo de cada hemimandíbula foi realizado em todos os animais com broca esférica de baixa rotação. Padronizou-se à esquerda o preenchimento do defeito ósseo, no grupo I com 15 microgramas de hidroxiapatita e no grupo II com preenchimento de submucosa de intestino delgado porcina (SID), e à direita o não-preenchimento serviu como controle. A eutanásia foi realizada no 40° dia de pós-operatório, após a qual se procederam as análises macroscópicas e histológicas das peças. RESULTADOS: O comprimento médio em milímetros das hemimandíbulas do grupo hidroxiapatita foi de 3,75, e o do grupo SID 3,03 e o do grupo controle foi de 2,63 (p: 0,0022). No grupo hidroxiapatita a neoformação óssea perfez uma área correspondente à 76,64% do total já no grupo SID 63,64% do total. CONCLUSÃO: Os resultados macroscópios e microscópicos foram superiores com a utilização do enxerto de hidroxiapatita quando comparado ao grupo submucosa de intestino delgado porcino. Entretanto os dois bioenxertos mostraram-se osteoindutores quando comparados ao controle.
Supressão contralateral das emissões otoacústicas nos indivíduos com zumbido
Authors: Fávero Mariana Lopes , Sanchez Tanit Ganz , Bento Ricardo Ferreira , Nascimento Andreia Ferreira
Published: November 2006

INTRODUÇÃO: A função do trato olivococlear medial é estudada pela supressão das emissões otoacústicas com o uso de uma estimulação contralateral e sofre influência da lateralidade do sistema nervoso central, não apresentando respostas iguais entre as orelhas. Uma disfunção neste trato pode implicar na geração do zumbido, porém isto ainda não foi confirmado. OBJETIVO: Estudar a supressão das emissões otoacústicas por produto de distorção em indivíduos com zumbido. MATERIAL E MÉTODO: Estudo caso-controle com 44 pessoas com zumbido, matriculadas no Ambulatório de Zumbido da Divisão de Clínica Otorrinolaringológica do Hospital das Clínicas da Universidade de São Paulo e 44 voluntários submetidos à emissão otoacústica por produto de distorção com e sem estimulação contralateral. Comparou-se os resultados das orelhas direita dos dois grupos. RESULTADOS: Houve associação entre zumbido e ausência de supressão em todas as freqüências estudadas (OR>2,1). CONCLUSÕES: Houve uma correlação entre menor efetividade do trato olivococlear medial e a presença de zumbido.