bluuebunny/crossref_metadata_2025 huggingface dataset:
Posterior Quadrantic Epilepsy Surgery: Technical Variants, Surgical Anatomy, and Case Series
Authors: Daniel Roy Thomas , Meagher‐Villemure Kathleen , Farmer Jean‐Pierre , Andermann Frederick , Villemure Jean‐Guy
Published: April 2007

Summary:  Objective: Patients with intractable epilepsy due to extensive lesions involving the posterior quadrant (temporal, parietal, and occipital lobes) form a small subset of epilepsy surgery. This study was done with a view to analyze our experience with this group of patients and to define the changes in the surgical technique over the last 15 years. We also describe the microsurgical technique of the different surgical variants used, along with their functional neuroanatomy.

Methods: In this series there were 13 patients with a median age of 17 years. All patients had extensive presurgical evaluation that provided concordant evidence localizing the lesion and seizure focus to the posterior quadrant. The objective of the surgery was to eliminate the effect of the epileptogenic tissue and preserve motor and sensory functions.

Results: During the course of this study period of 15 years, the surgical procedure performed evolved toward incorporating more techniques of disconnection and minimizing resection. Three technical variants were thus utilized in this series, namely, (i) anatomical posterior quadrantectomy (APQ), (ii) functional posterior quadrantectomy (FPQ), and (iii) periinsular posterior quadrantectomy (PIPQ). After a median follow‐up period of 6 years, 12/13 patients had Engel's Class I seizure outcome.

Conclusion: The results of surgery for posterior quadrantic epilepsy have yielded excellent seizure outcomes in 92% of the patients in the series with no mortality or major morbidity. The incorporation of disconnective techniques in multilobar surgery has maintained the excellent results obtained earlier with resective surgery.
Multivariate Neuropsychological Prediction of Seizure Lateralization in Temporal Epilepsy Surgical Cases
Authors: Keary Therese A. , Frazier Thomas W , Busch Robyn M. , Kubu Cynthia S. , Iampietro Mary
Published: April 2007

Summary:  Purpose: Neuropsychological assessment can be of assistance in determining seizure lateralization in cases where EEG and MRI findings do not provide clear lateralizing data. While several studies have examined the lateralizing value of individual neuropsychological measures, clinicians are still in need of a statistically sound method that permits the incorporation of multiple neuropsychological variables to predict seizure lateralization in the individual patient.

Method: The present study investigated the lateralizing value of several commonly used neuropsychological measures in a large sample of patients (n = 217) who eventually underwent surgical resection to treat their epilepsy. Side of surgery was used to operationally define seizure lateralization. A comparison of the relative utility of a multivariate versus univariate approach to predict seizure lateralization was conducted in temporal epilepsy cases.

Results: The results provide evidence for the incremental validity of neuropsychological measures, other than memory and IQ tests, in the prediction of seizure lateralization in patients with medically intractable epilepsy. These data indicate that a multivariate approach increases the accuracy of prediction of seizure lateralization for temporal lobe epilepsy cases.

Conclusion: This study supports the use of a multivariate approach using neuropsychological measures to predict seizure lateralization in temporal epilepsy surgical candidates. Regression formulas are provided to enhance the clinical utility of these findings.
Evaluation of Subcortical White Matter and Deep White Matter Tracts in Malformations of Cortical Development
Authors: Widjaja Elysa , Blaser Susan , Miller Elka , Kassner Andrea , Shannon Patrick , Chuang Sylvester H. , Snead O. Carter , Raybaud Charles R.
Published: April 2007

Summary:  Aims: Abnormal cortical development will lead to abnormal axons in white matter. The purpose was to investigate (1) the microstructural changes in subcortical white matter adjacent to malformations of cortical development (MCD) and (2) the deep white matter tracts using diffusion tensor imaging (DTI).

Methods: Thirteen children with a variety of MCD were recruited. The fractional anisotropy (FA), trace, and eigenvalues (λmajor, λmedium, λminor) of subcortical white matter of MCD were compared with contralateral normal side. The deep white matter tracts were graded based on the size, color hues and displacement of the tracts as visualized on color vector maps and tractography; grade 1 was normal tract size and color hue, grade 2 was reduced tract size but preserved color hue and grade 3 was loss of color hue or failure of tracking on tractography.

Results: The subcortical white matter adjacent to abnormal cortex demonstrated reduced FA (p < 0.05) and tendency to increase trace (p = 0.06). There was a significant elevation in λmedium and λminor (p < 0.05), but no significant change in λmajor (p > 0.05). Twelve cases demonstrated alteration in white matter tracts. Seven cases of focal cortical dysplasia and two cases of transmantle MCD demonstrated grade 3 pattern of white matter tract.

Conclusion: Reduced FA is a sensitive but nonspecific marker of alteration in microstructure of white matter. The elevated λmedium and λminor may reflect a dominant effect of abnormal myelin. Alteration in white matter tracts was observed in most cases of MCD.
Effect of protein‐energy malnutrition on erythropoietin requirement in maintenance hemodialysis patients
Authors: AKGUL Arzu , BILGIC Ayse , SEZER Siren , OZDEMİR Fatma Nurhan , OLCAY Irem , ARAT Zubeyde , HABERAL Mehmet
Published: April 2007

Possible interactions between inflammatory and nutritional markers and their impact on recombinant human erythropoietin (rHuEPO) hyporesponsiveness are not well understood. We investigated the role of nutritional status in rHuEPO requirement in maintenance hemodialysis (MHD) patients without evidence of inflammation. This cross‐sectional study included 88 MHD patients. The associations between required rHuEPO dose and malnutrition‐inflammation score (MIS) and several laboratory values known to be related to nutrition and/or inflammation were analyzed. Anthropometric measures including body mass index, triceps skinfold thickness, and midarm circumferences were also measured. Twenty‐three patients with serum C‐reactive protein levels >10 mg/L were excluded from the analysis. The remaining 65 patients (male/female, 41/24; age 49.1±11.4 years; dialysis duration 99.7±63.0 months) were studied. These patients had moderate malnutrition and the average MIS was 7.4 (range 3–17). The average weekly dose of administered rHuEPO was 69.1±63.1 U/kg. Malnutrition‐inflammation score had a positive correlation with the serum concentration of tumor necrosis factor‐α, whereas it had a negative correlation with anthropometric measures, total iron‐binding capacity, prealbumin, phosphorus, creatinine, and triglyceride. According to Pearson's correlation analysis, significant relationships of increased MIS with increased required rHuEPO dose and rHuEPO responsiveness index (EPO divided by hematocrit) were observed (p=0.008, r=−0.326; p=0.017, r=−0.306, respectively). Recombinant human erythropoietin dose requirement is correlated with MIS and adverse nutritional status in MHD patients without evidence of inflammation. Further research should focus on reversing the undergoing microinflammation for a better outcome in dialysis patients.
Regeneration of Seasonal Deciduous Forest Tree Species in Long‐Used Pastures in Central Brazil
Authors: Sampaio Alexandre B. , Holl Karen D. , Scariot Aldicir
Published: April 2007

We tested the relationship between the length of pasture use and the density, richness, and composition of naturally regenerating tropical seasonal deciduous forest in pastures. We sampled regenerating trees in 25 pastures distributed in four age classes ranging from < 6 to 40 yr of use. Density and composition of regenerating trees did not change with pasture age, but richness was lower in 25‐ and 40‐yr‐old pastures. Nonetheless, a number of species seem to be able to resprout even after 40 yr of ranching.
Determinants of Lichen Diversity in a Rain Forest Understory
Authors: Dyer L. A. , Letourneau D. K.
Published: April 2007

Change in lichen diversity is often used as a bioindicator to estimate effects of atmospheric pollution, but natural variation in lichen cover and species richness can be very high. We examined the top‐down effects of spore‐consuming ants and the bottom‐up effects of nutrient and light availability on lichen diversity associated with the leaf surface of the rain forest understory plant, Piper cenocladum. Plots containing P. cenocladum were randomly assigned to treatments in factorial experiments that included high and low light levels, nutrient enrichment, and presence and absence of the ant mutualist, Pheidole bicornis. At the conclusion of the experiments, plants were harvested and size of leaves, secondary metabolite content (amides), epiphyll cover, and the species richness of the lichens (which comprised 85% of the epiphyll community) were quantified. Epiphyll cover (mosses, liverworts, and lichens) was greater on plants that had ant‐mutualists and balanced resources. Lichen species richness was greater for plants with balanced resources, particularly for those with high light availability. Relationships between toxins and lichen cover and richness were weak and unclear. In this system, natural sources of variation were reliable determinants of lichen diversity and both biotic and abiotic influences were important.
The relationships between plasma potassium, muscle excitability and fatigue during voluntary exercise in humans
Authors: Shushakov Vladimir , Stubbe Christian , Peuckert Antje , Endeward Volker , Maassen Norbert
Published: April 2007

The relationships between extracellular potassium elevation and EMG variables in relation to muscle fatigue were investigated during handgrip exercise in humans. Acid–base state, lactate, potassium ([K+]v) and sodium in venous plasma, as well as variables of surface voluntary and evoked (M‐wave) EMG were determined during repeated dynamic (DE) and static (SE) exercise (1 min exercise, 4 min rest). The different rises of [K+]vwere induced by randomly varied workloads. After 15 min of warming up, the M‐wave area increased to 124.9 ± 19.6% (P< 0.001) in comparison with the control value. Simultaneously, the [K+]vdecreased from 4.1 ± 0.3 to 3.6 ± 0.3 mmol l−1(P< 0.01). During both SE and DE, there were marked intensity‐dependent signs of fatigue. The [K+]vcorrelated with changes of the integrated EMG (r= 0.87,P< 0.001 for both DE and SE). Changes in the M‐wave area during the exercise bouts correlated inversely with the [K+]v(r=−0.73,P< 0.001). The M‐wave area did not decrease below the control value at any intensity. The median frequency of the EMG decreased during exercise, depending on the exercise intensity (r=−0.73 for SE,r=−0.47 for DE,P< 0.001) with a maximal decrease to about 80% after SE with the maximal workload. The muscle action potential propagation velocity changed in the range of about ±2%. For the first time, a negative relationship between venous potassium and M‐wave area was shown during voluntary exercise. However, there was no evidence that the decrease in muscle performance was mainly caused by a decrease in sarcolemmal excitability resulting from a high extracellular [K+].
Cross‐sample entropy statistic as a measure of complexity and regularity of renal sympathetic nerve activity in the rat
Authors: Zhang Tao , Yang Zhuo , Coote John H.
Published: April 2007

In this study, we employed both power spectral analysis and cross‐sample entropy measurement to assess the relationship between two time series, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA), during a mild haemorrhage in anaesthetized Wistar rats. Removal of 1 ml of venous blood decreased BP (by 7.1 ± 0.7 mmHg) and increased RSNA (by 25.9 ± 2.4%). During these changes, the power in the RSNA signal at heart rate frequency was reduced but coherence between the spectra at heart rate frequency in RSNA and ABP remained unchanged. Cross‐sample entropy was significantly increased (by 10%) by haemorrhage, revealing that there was greater asynchrony between ABP and the RSNA time series. Intrathecal administration of the glutamate receptor antagonist kynurenic acid (2 mm) almost halved (P < 0.01) the reflex increase in RSNA. Also during kynurenic acid block, haemorrhage failed to change total power, power at heart rate frequency, coherence at heart rate frequency, or the cross‐sample entropy measurements. We conclude that the increase in asynchrony between ABP and RSNA during the reflex increase in RSNA was a consequence of an increase in synaptic input to the spinal renal neurones. The data show that the cross‐sample entropy calculations can characterize the non‐linearities of neural mechanisms underlying cardiovascular control and have a potential to reveal how some aspects of homeostatic regulation of kidney function is achieved by the autonomic nervous system.
The Interaction of Turbine Inter-Platform Leakage Flow With the Mainstream Flow
Authors: Reid Kevin , Denton John , Pullan Graham , Curtis Eric , Longley John
Published: April 2007

Individual nozzle guide vanes (NGV’s) in modern aeroengines are often cast as a single piece with integral hub and casing endwalls. When in operation, there is a leakage flow through the chord-wise interplatform gaps. An investigation into the effect of this leakage flow on turbine performance is presented. Efficiency measurements and NGV exit area traverse data from a low-speed research turbine are reported. Tests show that this leakage flow can have a significant impact on turbine performance, but that below a threshold leakage fraction this penalty does not rise with increasing leakage flow rate. The effect of various seal clearances are also investigated. Results from steady-state simulations using a three-dimensional multiblock Reynolds-averaged Navier-Stokes solver are presented with particular emphasis paid to the physics of the mainstream/leakage interaction and the loss generation.
Effect of Jet Pulsing on Film Cooling—Part I: Effectiveness and Flow-Field Temperature Results
Authors: Coulthard Sarah M. , Volino Ralph J. , Flack Karen A.
Published: April 2007

Pulsed film cooling was studied experimentally to determine its effect on film-cooling effectiveness. The film-cooling jets were pulsed using solenoid valves in the supply air line. Cases with a single row of cylindrical film-cooling holes inclined at 35 deg to the surface of a flat plate were considered at blowing ratios of 0.25, 0.5, 1.0, and 1.5 for a variety of pulsing frequencies and duty cycles. Temperature measurements were made using an infrared camera, thermocouples, and cold-wire anemometry. Hot-wire anemometry was used for velocity measurements. The local film-cooling effectiveness was calculated based on the measured temperatures, and the results were compared to baseline cases with continuous blowing. Phase-locked flow temperature fields were determined from cold-wire surveys. Pulsing at high frequencies helped to improve film-cooling effectiveness in some cases by reducing overall jet liftoff. At lower frequencies, pulsing tended to have the opposite effect. With the present geometry and a steady mainflow, pulsing did not provide an overall benefit. The highest overall effectiveness was achieved with continuous jets and a blowing ratio of 0.5. The present results may prove useful for understanding film-cooling behavior in engines, where mainflow unsteadiness causes film-cooling jet pulsation.
Separate Effects of Mach Number and Reynolds Number on Jet Array Impingement Heat Transfer
Authors: Park Jongmyung , Goodro Matt , Ligrani Phil , Fox Mike , Moon Hee-Koo
Published: April 2007

Limited available data suggest a substantial impact of Mach number on the heat transfer from an array of jets impinging on a surface at fixed Reynolds number. Many jet array heat transfer correlations currently in use are based on tests in which the jet Reynolds number was varied by varying the jet Mach number. Hence, this data may be inaccurate for high Mach numbers. Results from the present study are new and innovative because they separate the effects of jet Reynolds number and jet Mach number for the purposes of validating and improving correlations that are currently in use. The present study provides new data on the separate effects of Reynolds number and Mach number for an array of impinging jets in the form of discharge coefficients, local and spatially averaged Nusselt numbers, and local and spatially averaged recovery factors. The data are unique because data are given for impingement jet Mach numbers as high as 0.60 and impingement jet Reynolds numbers as high as 60,000, and because the effects of Reynolds number and Mach number are separated by providing data at constant Reynolds number because the Mach number is varied, and data at constant Mach number because the Reynolds number is varied. As such, the present data are given for experimental conditions not previously examined, which are outside the range of applicability of current correlations.
Movement of Deposited Water on Turbomachinery Rotor Blade Surfaces
Authors: Williams John , Young John B.
Published: April 2007

A theoretical approach for calculating the movement of liquid water following deposition onto a turbomachine rotor blade is described. Such a situation can occur during operation of an aero-engine in rain. The equation of motion of the deposited water is developed on an arbitrarily oriented plane triangular surface facet. By dividing the blade surface into a large number of facets and calculating the water trajectory over each one crossed in turn, the overall trajectory can be constructed. Apart from the centrifugal and Coriolis inertia effects, the forces acting on the water arise from the blade surface friction, and the aerodynamic shear and pressure gradient. Nondimensionalization of the equations of motion provides considerable insight and a detailed study of water flow on a flat rotating plate set at different stagger angles demonstrates the paramount importance of blade surface friction. The extreme cases of low and high blade friction are examined and it is concluded that the latter (which allows considerable mathematical generalization) is the most likely in practice. It is also shown that the aerodynamic shear force, but not the pressure force, may influence the water motion. Calculations of water movement on a low-speed compressor blade and the fan blade of a high bypass ratio aero-engine suggest that in low rotational speed situations most of the deposited water is centrifuged rapidly to the blade tip region.
Numerical Investigation of the Effect of Different Back Sweep Angle and Exducer Width on the Impeller Outlet Flow Pattern of a Centrifugal Compressor With Vaneless Diffuser
Authors: Hildebrandt A. , Genrup M.
Published: April 2007

This paper presents a numerical investigation of the effect of different back sweep angles and exducer widths on the steady-state impeller outlet flow pattern of a centrifugal compressor with a vaneless diffuser. The investigations have been performed with commercial computational fluid dynamics (CFD) and in-house programmed one-dimensional (1D) codes. CFD calculations aim to investigate how flow pattern from the impeller is quantitatively influenced by compressor geometry parameters; thereby, the location of wake and its magnitude (flow angle and relative velocity magnitude) are analyzed. Results show that the increased back sweep impeller provides a more uniform flow pattern in terms of velocity and flow deviation angle distribution, and offers better potential for the diffusion process inside a vaneless (or vaned) diffuser. Secondary flux fraction and flow deviation angle from CFD simulation are implemented into the 1D two-zone program to improve 1D prediction results.
High-Resolution Film Cooling Effectiveness Measurements of Axial Holes Embedded in a Transverse Trench With Various Trench Configurations
Authors: Waye Scot K. , Bogard David G.
Published: April 2007

Adiabatic film cooling effectiveness of axial holes embedded within a transverse trench on the suction side of a turbine vane was investigated. High-resolution two-dimensional data obtained from infrared thermography and corrected for local conduction provided spatial adiabatic effectiveness data. Flow parameters of blowing ratio, density ratio, and turbulence intensity were independently varied. In addition to a baseline geometry, nine trench configurations were tested, all with a depth of 1∕2 hole diameter, with varying widths, and with perpendicular and inclined trench walls. A perpendicular trench wall at the very downstream edge of the coolant hole was found to be the key trench characteristic that yielded much improved adiabatic effectiveness performance. This configuration increased adiabatic effectiveness up to 100% near the hole and 40% downstream. All other trench configurations had little effect on the adiabatic effectiveness. Thermal field measurements confirmed that the improved adiabatic effectiveness that occurred for a narrow trench with perpendicular walls was due to a lateral spreading of the coolant and reduced coolant jet separation. The cooling levels exhibited by these particular geometries are comparable to shaped holes, but much easier and cheaper to manufacture.
Gas Turbine Heat Transfer: Ten Remaining Hot Gas Path Challenges
Authors: Bunker Ronald S.
Published: April 2007

The advancement of turbine cooling has allowed engine design to exceed normal material temperature limits, but it has introduced complexities that have accentuated the thermal issues greatly. Cooled component design has consistently trended in the direction of higher heat loads, higher through-wall thermal gradients, and higher in-plane thermal gradients. The present discussion seeks to identify ten major thermal issues, or opportunities, that remain for the turbine hot gas path (HGP) today. These thermal challenges are commonly known in their broadest forms, but some tend to be little discussed in a direct manner relevant to gas turbines. These include uniformity of internal cooling, ultimate film cooling, microcooling, reduced incident heat flux, secondary flows as prime cooling, contoured gas paths, thermal stress reduction, controlled cooling, low emission combustor-turbine systems, and regenerative cooling. Evolutionary or revolutionary advancements concerning these issues will ultimately be required in realizable engineering forms for gas turbines to breakthrough to new levels of performance. Herein lies the challenge to researchers and designers. It is the intention of this summary to provide a concise review of these issues, and some of the recent solution directions, as an initial guide and stimulation to further research.
UV Light Inactivation of
Mycobacterium avium
subsp.
paratuberculosis
in Milk as Assessed by
FASTPlaque
TB Phage Assay and Culture
Authors: Altic Leslie C. , Rowe Michael T. , Grant Irene R.
Published: April 2007

UV light inactivation of
Mycobacterium avium
subsp.
paratuberculosis
in Middlebrook 7H9 broth and whole and semiskim milk was investigated using a laboratory-scale UV machine that incorporated static mixers within UV-penetrable pipes. UV treatment proved to be less effective in killing
M. avium
subsp.
paratuberculosis
suspended in milk (0.5- to 1.0-log
10
reduction per 1,000 mJ/ml) than that suspended in Middlebrook 7H9 broth (2.5- to 3.3-log
10
reduction per 1,000 mJ/ml). The
FASTPlaque
TB phage assay provided more rapid enumeration of surviving
M. avium
subsp.
paratuberculosis
(within 24 h) than culture on Herrold's egg yolk medium (6 to 8 weeks). Despite the fact that plaque counts were consistently 1 to 2 log
10
lower than colony counts throughout the study, UV inactivation rates for
M. avium
subsp.
paratuberculosis
derived using the phage assay and culture results were not significantly different (
P
= 0.077).
New Insights into the
Enterococcus faecalis
CroRS Two-Component System Obtained Using a Differential-Display Random Arbitrarily Primed PCR Approach
Authors: Le Breton Yoann , Muller Cécile , Auffray Yanick , Rincé Alain
Published: April 2007

Using a modified random arbitrarily primed PCR approach, the operon encoding the
Enterococcus faecalis
JH2-2 CroRS two-component regulatory system was shown to be repressed during stationary phase, and a CroRS-regulated operon (
glnQHMP
) was identified. Gel retardation assays showed that the CroR regulator binds specifically to the
glnQHMP
promoter.
Phylogenetic Analysis of Deformed Wing Virus Genotypes from Diverse Geographic Origins Indicates Recent Global Distribution of the Virus
Authors: Berényi Olga , Bakonyi Tamás , Derakhshifar Irmgard , Köglberger Hemma , Topolska Gražyna , Ritter Wolfgang , Pechhacker Hermann , Nowotny Norbert
Published: April 2007

Honeybees originating from 10 different countries (Austria, Poland, Germany, Hungary, Slovenia, Nepal, Sri Lanka, the United Arab Emirates, Canada, and New Zealand) located on four continents were analyzed for the presence of deformed wing virus (DWV) nucleic acid by reverse transcription-PCR. Two target regions within the DWV genome were selected for PCR amplification and subsequent sequencing, i.e., a region within the putative VP2 and VP4 structural-protein genes and a region within the RNA helicase enzyme gene. DWV nucleic acid was amplified from 34 honeybee samples representing all the above-mentioned countries with the notable exception of New Zealand. The amplification products were sequenced, and phylogenetic analyses of both genomic regions were performed independently. The phylogenetic analyses included all sequences determined in this study as well as previously published DWV sequences and the sequences of two closely related viruses, Kakugo virus (KGV) and
Varroa destructor
virus 1 (VDV-1). In the sequenced regions, the DWV genome turned out to be highly conserved, independent of the geographic origins of the honeybee samples: the partial sequences exhibited 98 to 99% nucleotide sequence identity. Substitutions were most frequently observed at the same positions in the various DWV sequences. Due to the high level of sequence conservation, no significant clustering of the samples in the phylogenetic trees could be identified. On the other hand, the phylogenetic analyses support a genetic segregation of KGV and VDV-1 from DWV.
FlavobacteriaBlooms in Four Eutrophic Lakes: Linking Population Dynamics of Freshwater Bacterioplankton to Resource Availability
Authors: Eiler Alexander , Bertilsson Stefan
Published: April 2007

Heterotrophic bacteria are major contributors to biogeochemical cycles and influence water quality. Still, the lack of representative isolates and the few quantitative surveys leave the ecological role and significance of single bacterial populations to be revealed. Here we analyzed the diversity and dynamics of freshwaterFlavobacteriapopulations in four eutrophic temperate lakes. From each lake, clone libraries were constructed using primers specific for either the classFlavobacteriaorBacteria. Sequencing of 194Flavobacteriaclones from 8 libraries revealed a diverse freshwaterFlavobacteriacommunity and distinct differences among lakes. Abundance and seasonal dynamics ofFlavobacteriawere assessed by quantitative PCR with class-specific primers. In parallel, the dynamics of individual populations within theFlavobacteriacommunity were assessed with terminal restriction fragment length polymorphism analysis using identical primers. The contribution ofFlavobacteriato the total bacterioplankton community ranged from 0.4 to almost 100% (average, 24%). Blooms whereFlavobacteriarepresented more than 30% of the bacterioplankton were observed at different times in the four lakes. In general, high proportions ofFlavobacteriaappeared during episodes of high bacterial production. Phylogenetic analyses combined withFlavobacteriacommunity fingerprints suggested dominance of twoFlavobacterialineages. Both drastic alterations in totalFlavobacteriaand in community composition of this class significantly correlated with bacterial production, emphasizing that resource availability is an important driver of heterotrophic bacterial succession in eutrophic lakes.
Mcp4, a Meiotic Coiled-Coil Protein, Plays a Role in F-Actin Positioning during
Schizosaccharomyces pombe
Meiosis
Authors: Ohtaka Ayami , Okuzaki Daisuke , Saito Takamune T. , Nojima Hiroshi
Published: April 2007

Some meiosis-specific proteins of
Schizosaccharomyces pombe
harbor coiled-coil motifs and play essential roles in meiotic progression. Here we describe Mcp4, a novel meiosis-specific protein whose expression is abruptly induced at the horsetail phase and which remains expressed until sporulation is finished. Fluorescence microscopic analysis revealed that Mcp4 alters its subcellular localization during meiosis in a manner that partially resembles the movement of F-actin during meiosis. Mcp4 and F-actin never colocalize; rather, they are located in a side-by-side manner. When forespore membrane formation begins at metaphase II, the Mcp4 signals assemble at the lagging face of the dividing nuclei. At this stage, they are sandwiched between F-actin and the nucleus. Mcp4, in turn, appears to sandwich F-actin with Meu14. In
mcp4
Δ cells at anaphase II, the F-actin, which is normally dumbbell-shaped, adopts an abnormal balloon shape. Spores of
mcp4
Δ cells were sensitive to NaCl, although their shape and viability were normal. Taken together, we conclude that Mcp4 plays a role in the accurate positioning of F-actin during
S. pombe
meiosis.
Evidence that Noncoding RNA
dutA
Is a Multicopy Suppressor of
Dictyostelium discoideum
STAT Protein Dd-STATa
Authors: Shimada Nao , Kawata Takefumi
Published: April 2007

Dd-STATa, a
Dictyostelium discoideum
homologue of metazoan STAT transcription factors, is necessary for culmination. We created a mutant strain with partial
Dd-STATa
activity and used it to screen for unlinked suppressor genes. We screened approximately 450,000 clones from a slug-stage cDNA library for their ability to rescue the culmination defect when overexpressed. There were 12 multicopy suppressors of Dd-STATa, of which 4 encoded segments of a known noncoding RNA,
dutA
. Expression of
dutA
is specific to the pstA zone, the region where Dd-STATa is activated. In suppressed strains the expression patterns of several putative Dd-STATa target genes become similar to the wild-type strain. In addition, the amount of the tyrosine-phosphorylated form of Dd-STATa is significantly increased in the suppressed strain. These results indicate that partial copies of
dutA
may act upstream of Dd-STATa to regulate tyrosine phosphorylation by an unknown mechanism.
Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid
Authors: Xu Xuehua , Müller-Taubenberger Annette , Adley Kathryn E. , Pawolleck Nadine , Lee Vivian W. Y. , Wiedemann Claudia , Sihra Talvinder S. , Maniak Markus , Jin Tian , Williams Robin S. B.
Published: April 2007

Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoebaDictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PHCrac-green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP2phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis—processes previously shown to be dependent upon PIP3production. These results suggest that inDictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug.
Acclimation to Singlet Oxygen Stress in
Chlamydomonas reinhardtii
Authors: Ledford Heidi K. , Chin Brian L. , Niyogi Krishna K.
Published: April 2007

In an aerobic environment, responding to oxidative cues is critical for physiological adaptation (acclimation) to changing environmental conditions. The unicellular alga
Chlamydomonas reinhardtii
was tested for the ability to acclimate to specific forms of oxidative stress. Acclimation was defined as the ability of a sublethal pretreatment with a reactive oxygen species to activate defense responses that subsequently enhance survival of that stress.
C. reinhardtii
exhibited a strong acclimation response to rose bengal, a photosensitizing dye that produces singlet oxygen. This acclimation was dependent upon photosensitization and occurred only when pretreatment was administered in the light. Shifting cells from low light to high light also enhanced resistance to singlet oxygen, suggesting an overlap in high-light and singlet oxygen response pathways. Microarray analysis of RNA levels indicated that a relatively small number of genes respond to sublethal levels of singlet oxygen. Constitutive overexpression of either of two such genes, a glutathione peroxidase gene and a glutathione
S
-transferase gene, was sufficient to enhance singlet oxygen resistance.
Escherichia coli
and
Saccharomyces cerevisiae
exhibit well-defined responses to reactive oxygen but did not acclimate to singlet oxygen, possibly reflecting the relative importance of singlet oxygen stress for photosynthetic organisms.
Membrane Association and Multimerization of TcpT, the Cognate ATPase Ortholog of the
Vibrio cholerae
Toxin-Coregulated-Pilus Biogenesis Apparatus
Authors: Tripathi Shital A. , Taylor Ronald K.
Published: April 2007

The toxin-coregulated pilus (TCP) is one of the major virulence factors of
Vibrio cholerae
. Biogenesis of this type 4 pilus (Tfp) requires a number of structural components encoded by the
tcp
operon. TcpT, the cognate putative ATPase, is required for TCP biogenesis and all TCP-mediated functions. We studied the stability and localization of TcpT in cells containing in-frame deletions in each of the
tcp
genes. TcpT was detectable in each of the biogenesis mutants except the Δ
tcpT
strain. TcpT was localized to the inner membrane (IM) in a TcpR-dependent manner. TcpR is a predicted bitopic inner membrane protein of the TCP biogenesis apparatus. Using metal affinity pull-down experiments, we demonstrated interaction between TcpT and TcpR. Using
Escherichia coli
as a heterologous system, we investigated direct interaction between TcpR and TcpT. We report that TcpR is sufficient for TcpT IM localization per se; however, stable IM localization of TcpT requires an additional
V. cholerae
-specific factor(s). A LexA-based two-hybrid system was utilized to define interaction domains of the two proteins. We demonstrate a strong interaction between the cytoplasmic domain of TcpR and the N-terminal 100 amino acid residues of TcpT. We also demonstrated the ability of the C-terminal domain of TcpT to multimerize.
SigM-Responsive Genes of
Bacillus subtilis
and Their Promoters
Authors: Jervis Adrian J. , Thackray Penny D. , Houston Chris W. , Horsburgh Malcolm J. , Moir Anne
Published: April 2007

Promoters of nine
Bacillus subtilis
genes (
bcrC
,
yacK
,
ydaH
,
yfnI
,
yjbD
,
ypbG
,
ypuA
,
yraA
, and
ysxA
), all responsive to artificially induced increases in the stress-responsive extracytoplasmic function sigma factor, SigM, were mapped by rapid amplification of cDNA ends-PCR. The resulting promoter consensus suggests that overlapping control by SigX or SigW is common.
Adaptation of coronary microvascular exchange in arterioles and venules to exercise training and a role for sex in determining permeability responses
Authors: Huxley Virginia H. , Wang Jian Jie , Sarelius Ingrid H.
Published: April 2007

Studies of physical performance and energy metabolism during and following exercise have shown significant sex-specific musculoskeletal adaptations; less is known of vascular adaptations, particularly with respect to exchange capacity. In response to adenosine (ADO), a metabolite produced during exercise, permeability ( Ps) of coronary arterioles from female pigs changed acutely; the magnitude and direction of the change (Δ Ps) were determined by training status. In the present study Psto albumin was assessed in arterioles ( n = 138) and venules ( n = 24) isolated from hearts of male ( N = 2 7) and female ( N = 59) pigs in the exercise training group (EX). We evaluated the hypothesis that coronary microvessel exchange adapts to endurance exercise training not by altering basal Ps, per se, but by elevating Pson exposure to ADO. In contrast, training resulted in a reduction of basal Psin all arterioles, and in venules from males, with no change in venules from EX females. Exposure to ADO resulted in the predicted increase in Psexcept for venules from EX males where Pswas reduced. Δ Psresponses of arterioles to mediators of adenylyl cyclase (isoproterenol)- and guanylyl cyclase (atrial natriuretic peptide)-signaling pathways were attenuated in EX pigs relative to pigs in the sedentary group. The adaptation of EX arterioles involves an upregulation of a nitric oxide-dependent pathway since nitric oxide synthase inhibition blocks Δ Psby ADO. Thus adaptation of microvascular exchange capacity to endurance exercise training not only occurs but also involves multiple mechanisms that differ in arterioles and venules with their relative contribution to net flux being a function of sex.
Dissociation between metabolic and vascular insulin resistance in aging
Authors: Schulman Ivonne Hernandez , Zhou Ming-Sheng , Jaimes Edgar A. , Raij Leopoldo
Published: April 2007

Physiological actions of insulin via activation of the phosphatidylinositol 3-kinase/Akt pathway in the endothelium serve to couple regulation of hemodynamic and metabolic homeostasis. Insulin resistance, endothelial dysfunction, and hypertension increase in prevalence with aging. We investigated the metabolic and endothelial actions of insulin in 24- vs. 3-mo Sprague-Dawley rats. With the use of the hyperinsulinemic euglycemic clamp, the rate of glucose infusion necessary to maintain equivalent plasma glucose (5.5 mmol/l) was similar in 24- vs. 3-mo rats, as was fasting glucose (5.2 ± 0.33 vs. 4.4 ± 0.37 mmol/l; mean ± SE) and insulin (0.862 ± 0.193 vs. 1.307 ± 0.230 mg/l). Systolic blood pressure was higher in 24-mo rats (133 ± 5 vs. 110 ± 4 mmHg; P = 0.005). Endothelial nitric oxide (NO)-dependent relaxation to insulin was impaired in aortas of 24- vs. 3-mo rats (maximal response 8.9 ± 4.3 vs. 34.9 ± 3.9%; P = 0.002); NG-nitro-l-arginine methyl ester abolished insulin-mediated relaxation in 3- but not 24-mo rats. Endothelium NO-dependent (acetylcholine) and -independent (sodium nitroprusside) relaxation, as well as NADPH oxidase activity, were similar in 3- and 24-mo rats. Insulin increased aortic serine phosphorylation of Akt in 3-mo rats by 120% over 24-mo rats ( P < 0.05) and serine phosphorylation of endothelial NO synthase (eNOS) in 3-mo rats by 380% over 24-mo rats ( P < 0.05). Aortic expression of phosphorylated c-Jun NH2-terminal kinase-1 and serine phosphorylated insulin receptor substrate-1, known mediators of metabolic insulin resistance, was similar in 3- and 24-mo rats. Expression of caveolin-1, a regulator of eNOS activity and insulin signaling, was 55% lower in 24- than 3-mo rats ( P = 0.002). In summary, impaired vasorelaxation to insulin in aging was independent of metabolic insulin sensitivity and associated with impaired insulin-mediated activation of the Akt/eNOS pathway, but intact activation of the acetylcholine-mediated Ca2+-calmodulin/eNOS pathway. Vascular insulin resistance in aging may add to the increased susceptibility of this population to vascular injury induced by traditional cardiovascular risk factors.
Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase
Authors: Bátkai Sándor , Rajesh Mohanraj , Mukhopadhyay Partha , Haskó György , Liaudet Lucas , Cravatt Benjamin F. , Csiszár Anna , Ungvári Zoltan , Pacher Pál
Published: April 2007

Recent studies have uncovered important cross talk between inflammation, generation of reactive oxygen and nitrogen species, and lipid metabolism in the pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acid amide hydrolase (FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. In this study, we have investigated the age-associated decline of cardiac function and changes in inflammatory gene expression, nitrative stress, and apoptosis in FAAH knockout (FAAH−/−) mice and their wild-type (FAAH+/+) littermates. Additionally, we have explored the effects of anandamide on TNF-α-induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). There was no difference in the cardiac function (measured by the pressure-volume conductance catheter system) between 2- to 3-mo-old (young) FAAH−/− and FAAH+/+ mice. In contrast, the aging-associated decline in cardiac function and increased myocardial gene expression of TNF-α, gp91phox, matrix metalloproteinase (MMP)-2, MMP-9, caspase-3 and caspase-9, myocardial inducible nitric oxide synthase protein expression, nitrotyrosine formation, poly (ADP-ribose)polymerase cleavage and caspase-3/9 activity, observed in 28- to 31-mo-old (aging) FAAH+/+ mice, were largely attenuated in knockouts. There was no difference in the myocardial cannabinoid CB1 and CB2 receptor gene expression between young and aging FAAH−/− and FAAH+/+ mice. Anandamide dose dependently attenuated the TNF-α-induced ICAM-1 and VCAM-1 expression, NF-κB activation in HCAECs, and the adhesion of monocytes to HCAECs in a CB1- and CB2-dependent manner. These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis.
Response of cardiac mast cells to atrial natriuretic peptide
Authors: Murray David B. , Gardner Jason D. , Levick Scott P. , Brower Gregory L. , Morgan Loren G. , Janicki Joseph S.
Published: April 2007

Previously, our laboratory demonstrated that cardiac mast cell degranulation induces adverse ventricular remodeling in response to chronic volume overload. The purpose of this study was to investigate whether atrial natriuretic peptide (ANP), which is known to be elevated in chronic volume overload, causes cardiac mast cell degranulation. Relative to control, ANP induced significant histamine release from peritoneal mast cells, whereas isolated cardiac mast cells were not responsive. Infusion of ANP (225 pg/ml) into blood-perfused isolated rat hearts produced minimal activation of cardiac mast cells, similar to that seen in the control group. ANP also did not increase matrix metalloproteinase-2 activity, reduce collagen volume fraction, or alter diastolic or systolic cardiac function compared with saline-treated controls. In a subsequent study to evaluate the effects of natriuretic peptide receptor antagonism on volume overload-induced ventricular remodeling, anantin was administered to rats with an aortocaval fistula. Comparable increases of myocardial MMP-2 activity in treated and untreated rats with an aortocaval fistula were associated with equivalent decreases in ventricular collagen ( P < 0.05 vs. sham-operated controls). Cardiac functional parameters and left ventricular hypertrophy were unaffected by anantin. We conclude that ANP is not a cardiac mast cell secretagogue and is not responsible for the cardiac mast cell-mediated adverse ventricular remodeling in response to volume overload.
HIV and the Ramifications for Food Security and Child Health in Affected Communities
Authors: Solomons Noel W. , O’Donnell Gwen Ellen
Published: April 2007

The first cases of the acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), were recognized in 1981. Today, an estimated 39 million people worldwide are infected with the virus. Sixty-four percent of these individuals currently live in the poverty of sub-Saharan Africa, but the pandemic is now spreading fastest in the largest nations of Asia. A state of food security is said to exist when all people, at all times, have access to sufficient, safe and nutritious food to meet their dietary needs and food preferences for an active and healthy life. A concern for food insecurity arose in the HIV/AIDS pandemic, based on the well-known principles of the interaction of malnutrition and infection; more poorly nourished individuals are more severely affected by infectious pathogens while the ravages of infection tend to deplete the nutritional reserves. The social and clinical consequences of HIV/AIDS endanger access to food in areas already stressed by poverty and environmental deterioration. Interventions related to agricultural productivity, income generation and food assistance, must each be crafted and adapted within the local, community contexts, and recognized as necessary to mitigate the adverse effect of HIV/AIDS on food security. UNICEF has made caring, defined as the provision in the household and the community of time, attention, and support to meet the physical, mental, and social needs of the growing child and other household members, into one of the components of its efforts to promote child survival. Its domain includes care for women, breastfeeding and child feeding practices, psychosocial care, food preparation, hygiene practices, and household health practices. The positive deviance approach, that of identifying household caring behaviors that have the best growth, health and development outcomes in children, is now being applied in the context of HIV-positive children. Stigma is a pervasive factor, which tends to isolate households affected with HIV-positive members, and complicates the social context in which food security and care-related interventions can be delivered. Outstanding gaps in our knowledge of food security–HIV/AIDS relationships have been identified. The research questions include the true effectiveness of food assistance to mitigate the effects of HIV and the interaction of food security status with the efficacy and safety of antiretroviral therapy. However, investigation is somewhat of a luxury within the allocation of scarce financial resources, placing a premium on gathering and codifying useful pragmatic experience for mitigating interventions from the valuable experience currently being gathered on the ground by field workers and communities themselves.