bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the proton ring current energy distribution during 21–25 April 2001 storm
Authors: Ganushkina N. Y. , Pulkkinen T. I. , Milillo A. , Liemohn M.
Published: October 2006

Three ring current models are used to follow the evolution of the proton ring current during the 2001‐04‐21–25 storm: The ring current model combined with tracing particles numerically in the drift approximation by Ganushkina et al. (2005), the empirical model of proton fluxes in the inner magnetosphere developed by Milillo et al. (2003), and the kinetic ring current‐atmosphere interaction model (RAM) by Liemohn et al. (2001). The paper focuses on the effects of the electric and magnetic field models and initial particle distributions on the final energy distribution. We examine a variety of large‐scale magnetic field and convection electric field models as well as substorm‐associated, smaller‐scale, and time‐varying electric fields. We find that (1) using more realistic magnetic field models leads to reduction of the ring current energy content by ∼30%; (2) details of the global convection field have little influence on the overall ring current evolution; (3) smaller‐scale impulsive electric field have profound effects on the ring current evolution, particularly with regard to the acceleration of the higher‐energy particles; and (4) in the ring current models, the choice of the initial and boundary conditions have significant effects on the modeled ring current intensity and energy spectrum.
Correlation of speed and temperature in the solar wind
Authors: Matthaeus W. H. , Elliott H. A. , McComas D. J.
Published: October 2006

We show that the well‐known correlation between solar wind speed and temperature can be understood as a consequence of an elementary symmetry of the solar wind transport equations. Under a reasonably wide range of circumstances, even when including nonadiabatic turbulence effects, the solutions of the transport equations may depend only upon the ratio r/U of distance to solar wind speed. Applied to the temperature equation, the familiar correlation emerges immediately. For a turbulence model of heating, this property is obtained in regions where the Alfvén speed is much smaller than the flow speed, where pickup ions are negligible, and where the flow is locally a spherical, constant‐speed expansion. These fundamental properties, illustrated here using analysis of ACE data, clarify why the correlation is reduced in ensembles that include highly nonspherical effects such as CMEs.
On the association of early/fast very low frequency perturbations with sprites and rare examples of VLF backscatter
Authors: Marshall R. A. , Inan U. S. , Lyons W. A.
Published: October 2006

Very low frequency (VLF) data recorded in the midwestern United States are compared with sprite observations on three different dates of high sprite activity between 1995 and 2000. Sprites are frequently seen to be correlated with “early/fast” events: perturbations of the amplitude and/or phase of a VLF transmitter signal propagating through the storm region. Unlike recent observations of Haldoupis et al. (2004), where a one‐to‐one relationship between forward scatter events and sprites was reported, only ∼48% of sprites in our cases are accompanied by VLF perturbations, or, viewed conversely, ∼61% of VLF perturbations are accompanied by sprites. The difference between the two data sets might be due to the relative location of the causative lightning along the VLF signal path (i.e., near transmitter or near receiver) in that mode coupling of the propagating VLF signal causes some perturbations to be undetectable at long distances from the disturbed region. In addition, there are quite a few cases of early/fast perturbations not accompanied by sprites, although not nearly the preponderance previously expected. In rare cases, observed VLF signal perturbations can only be explained by VLF backscatter from the sprite body because of the geometrical constraints that preclude other mechanisms, including forward scattering from elves or halos. However, such backscatter events are extremely rare and are found to occur only for the largest sprites in terms of their horizontal extent.
Quantifying groundwater discharge to Cockburn River, southeastern Australia, using dissolved gas tracers 222Rn and SF6
Authors: Cook P. G. , Lamontagne S. , Berhane D. , Clark J. F.
Published: October 2006

Groundwater discharge to the Cockburn River, southeast Australia, has been estimated from comparison of natural 222Rn activities in groundwater and river water, interpreted using a numerical flow model that simulates longitudinal radon activities as a function of groundwater inflow, hyporheic exchange, evaporation, gas exchange with the atmosphere, and radioactive decay. An injection of SF6 into the river to estimate the gas transfer velocity assisted in constraining the model. Previous estimates of groundwater inflow using 222Rn activities have not considered possible input of radon due to exchange between river water and water in the hyporheic zone beneath the streambed. In this paper, radon input due to hyporheic exchange is estimated from measurements of radon production by hyporheic zone sediments and rates of water exchange between the river and the hyporheic zone. Total groundwater inflow to the Cockburn River is estimated to be 18500 m3/d, although failure to consider hyporheic exchange would cause overestimation of the volume of groundwater inflow by approximately 70%.
Rho-Kinase Inhibition Acutely Augments Blood Flow in Focal Cerebral Ischemia via Endothelial Mechanisms
Authors: Shin Hwa Kyoung , Salomone Salvatore , Potts E Michelle , Lee Sae-Won , Millican Eric , Noma Kensuke , Huang Paul L , Boas David A , Liao James K , Moskowitz Michael A , Ayata Cenk
Published: October 2006

Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient (eNOS−/–) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS−/– mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS−/– mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke.
Vascular Response to Hypoxic Preconditioning in the Immature Brain
Authors: Gustavsson Malin , Mallard Carina , Vannucci Susan J , Wilson Mary Ann , Johnston Michael V , Hagberg Henrik
Published: October 2006

We hypothesized that hypoxic preconditioning (PC) modifies the microvasculature in the immature brain and thereby affects the cerebral blood flow (CBF) during a subsequent hypoxic—ischemic (HI) insult. On postnatal day 6 rats were exposed to hypoxia (36°C, 8.0% O2) or normoxia for 3 h. Unilateral HI (unilateral carotid ligation and 8% hypoxia) was induced 24 h later. Cortical CBF was measured with the 14C-iodoantipyrine technique (at the end of HI) or with laser Doppler flowmetry (Perimed PF5001) before and during HI. At 0, 2, 8, and 24 h cerebral cortex was sampled and analyzed with gene arrays (Affymetrix 230 2.0). l-nitroarginine or vehicle was administrated before hypoxic PC or 30 mins before HI followed by CBF measurement (laser Doppler) during subsequent HI. Twenty-four hours after PC animals were perfusion-fixed and brains immunolabeled for von Willebrand factor and vascular density was determined by stereological quantification. The decrease in CBF during HI was attenuated significantly in PC versus control animals ( P < 0.01), as detected by both techniques. Several vascular genes (Angpt2, Adm, Apln, Vegf, Flt1, Kdr, Pdgfra, Agtrap, Adora2a, Ednra, serpine1, caveolin, Id1, Prrx1, Ero1l, Acvrl1, Egfl7, Nudt6, Angptl4, Anxa2, and NOS3) were upregulated and a few (Csrp2, Adora2b) were downregulated after PC. A significant increase in vascular density ( P < 0.05) was seen after PC. Nitric oxide synthase inhibition did not affect CBF during HI after PC. In conclusion, hypoxic PC upregulates vascular genes, increases vascular density and attenuates the decrease of CBF during a subsequent HI, which could contribute to tolerance.
Positron Emission Tomography Quantification of [11C]-(+)-PHNO Binding in the Human Brain
Authors: Ginovart Nathalie , Willeit Matthaeus , Rusjan Pablo , Graff Ariel , Bloomfield Peter M , Houle Sylvain , Kapur Shitij , Wilson Alan A
Published: October 2006

The kinetic modeling of [11C]-(+)-PHNO binding to the dopamine D2/3 receptors in six human volunteers using positron emission tomography (PET) is described. [11C]-(+)-PHNO is the first agonist radioligand for the D2/3 in humans and as expected showed high uptake in caudate, putamen, globus pallidus (GP) and ventral striatum, and low uptake in cerebellum. A two-tissue compartment model (2CM) with four parameters was necessary to adequately fit time—activity data in all regions. Although a 2CM provided an excellent estimation of total distribution volumes, which were highly correlated with those obtained with the invasive Logan approach, it provided a poor identification of the k3/ k4 ratios. Coupling K1/ k2 between brain regions (Method C) or fixing K1/ k2 to the value obtained in cerebellum (Method D) enabled more stable estimates of k3/ k4 as compared with an unconstrained 2CM. The k3/ k4 obtained with Method D ranged from 0.12 ± 0.03 in cerebellum to 3.93 ± 0.77 in GP and were similar to those obtained when coupling K1/ k2. Binding potentials (BPs) obtained using the simplified reference tissue model ( BPSRTM) ranged from 2.08 ± 0.34 in caudate to 3.55 ± 0.78 in GP and were highly correlated with k3/ k4 estimates obtained with Method D ( r = 0.98). However, BPSRTM were 11% ± 5% lower than values obtained with Method D. BPs derived using the noninvasive Logan approach were slightly lower but not significantly different than BPSRTM. This study demonstrates that [11C]-(+)-PHNO can be used for the quantitative measurement of D2/3 densities and should enable further studies of potential D2/3 dysregulation in several important psychiatric and neurologic illnesses.
Standard Right Atrial Ablation is Effective for Atrioventricular Nodal Reentry with Earliest Activation in the Coronary Sinus
Authors: CHEN JANE , ANSELME FRÉDÉRIC , SMITH TIMOTHY W. , ZIMETBAUM PETER , EPSTEIN LAURENCE M. , PAPAGEORGIOU PANOS , JOSEPHSON MARK E.
Published: October 2006

Introduction: Reports suggest that coronary sinus (CS) or left atrial ablations may be necessary for treatment of AV nodal reentrant tachycardia (AVNRT) with earliest retrograde atrial activation in the CS. We assessed the efficacy of standard right atrial catheter ablation approaches in these tachycardias and determined the incidence of earliest activation in the CS in AVNRT.

Methods and Results: We retrospectively evaluated intracardiac recordings from 225 consecutive patients who underwent electrophysiologic studies and radiofrequency (RF) ablation for AVNRT in two institutions. Atrial activation during AVNRT was evaluated using multiple catheters according to standard protocol used in our laboratories. RF ablations in the triangle of Koch were performed in all patients. Eighteen of 225 patients (8%) had earliest activation in one of the CS poles. The demographics and AVNRT characteristics of these 18 patients were similar to those of the other 207 patients who did not have CS as earliest activation site and included both typical and atypical AVNRT. Following RF ablation, none of the 18 patients had inducible AVNRT.

Conclusion: Successful RF ablation can be performed at standard sites in the triangle of Koch regardless of earliest site of atrial activation. The incidence of CS as earliest retrograde atrial activation site in AVNRT is 8%. (J Cardiovasc Electrophysiol, Vol. 15, pp. 2‐7, January 2004)
Technique and Results of Pulmonary Vein Angiography in Patients Undergoing Catheter Ablation of Atrial Fibrillation
Authors: VASAMREDDY CHANDRASEKHAR R. , JAYAM VINOD , LICKFETT LARS , NASIR KHURRAM , BRADLEY DAVID J. , ELDADAH ZAYD , DICKFELD TIMM , DONAHUE KEVIN , HALPERIN HENRY R. , BERGER RONALD , CALKINS HUGH
Published: October 2006

Introduction: Delineation of pulmonary vein (PV) anatomy is an integral part of the PV isolation procedure. The aims of the present study were to (1) describe the technique of selective PV angiography, (2) show the typical fluoroscopic locations and appearance of the PVs, and (3) compare the ostial diameters of PVs measured by angiography and magnetic resonance imaging (MRI).

Methods and Results: Twenty consecutive patients undergoing a PV isolation procedure underwent selective PV angiography using a deflectable 8‐French lumened catheter (Naviport, Cardima). The left superior PV (LSPV) runs upward and away from the spine in the right anterior oblique (RAO) projection and upward and toward the spine in the left anterior oblique (LAO) projection. The opposite is true for the right superior PV (RSPV). The left inferior PV (LIPV) has a bull's‐eye appearance in the RAO projection, and the right inferior PV (RIPV) has a bull's‐eye appearance in the LAO projection due to their end‐on trajectories. The LIPV in the LAO projection and the RIPV in the RAO projection run horizontally toward the spine. An excellent correlation was noted in PV ostial size as assessed by angiography and MRI (r2 < 0.90, P < 0.0001).

Conclusion: This study describes the technique and results of PV angiography and fluoroscopy. The study also demonstrates good correlation of PV ostial diameters by contrast venography and MRI. PV angiography can be used as an alternate to MRI or computed tomographic imaging, particularly when these tests are unavailable or are contraindicated in the patient. (J Cardiovasc Electrophysiol, Vol. 15, pp. 21‐26, January 2004)
Acute Coronary Artery Stenosis During Slow Pathway Ablation for Atrioventricular Nodal Reentrant Tachycardia in a Child
Authors: BLAUFOX ANDREW D. , SAUL J. PHILIP
Published: October 2006

Coronary injury during radiofrequency ablation is a rare but potentially life‐threatening complication that has been reported for attempted elimination of accessory pathways. This is the first report of coronary artery injury during slow pathway ablation for AV nodal reentrant tachycardia. Manifest signs of injury may be transient or nonexistent and easily missed. Controlled studies are needed to determine the true risk of coronary artery injury during radiofrequency ablation for supraventricular tachycardia, particularly in small children. (J Cardiovasc Electrophysiol, Vol. 15, pp. 97‐100, January 2004)
Implications of Implantable Cardioverter Defibrillator Therapy in Congenital Heart Disease and Pediatrics
Authors: ALEXANDER MARK E. , CECCHIN FRANK , WALSH EDWARD P. , TRIEDMAN JOHN K. , BEVILACQUA LAURA M. , BERUL CHARLES I.
Published: October 2006

Introduction: The incidence of appropriate and inappropriate discharges, indicators of system failure, and clinical implications of implantable cardioverter defibrillator (ICD) therapy in children and young adults with heart disease is poorly defined.

Methods and Results: In a retrospective study at a single medical center, a total of 90 ICD procedures were performed in 76 patients younger than age 30 years (median 16 years, range 1–30): 42% with congenital heart disease, 33% with primary electrical disease, 17% with hypertrophic cardiomyopathy, and 8% with idiopathic dilated cardiomyopathy. Indications for ICD included arrest or sustained ventricular tachycardia (n = 27), and combinations of syncope (n = 32), palpitations (n = 17), spontaneous ventricular arrhythmia (n = 40), inducible ventricular tachycardia (n = 36), or severe hypertrophic cardiomyopathy. Transvenous dual‐chamber ICDs were implanted in 29 patients. Subcutaneous arrays or epicardial patches were used in 9 patients. Over a median 2‐year follow‐up, 28% of patients received appropriate shocks for ventricular tachycardia (median 13 months to first shock) and 25% experienced inappropriate shocks for multiple causes (median 16 months). With multivariate analysis, growth strongly correlated with lead failure (odds ratio 73, 3.5–1530, P = 0.006). Complications occurred in 29 patients, including lead failure in 16 (21%), ICD “storm” with sequential shocks in 5, and infection in 2 patients. No deaths were attributable to ICD placement or subsequent device failure.

Conclusion: ICD therapy can effectively manage malignant arrhythmias in selected pediatric and congenital heart patients. Spurious shocks or ICD storm may increase morbidity and emphasize the need for concomitant medical and ablative therapy. ICD lead failure was relatively frequent in this population. (J Cardiovasc Electrophysiol, Vol. 15, pp. 72‐76, January 2004)
Surface science of single-site heterogeneous olefin polymerization catalysts
Authors: Kim Seong H. , Somorjai Gabor A.
Published: October 2006

This article reviews the surface science of the heterogeneous olefin polymerization catalysts. The specific focus is on how to prepare and characterize stereochemically specific heterogeneous model catalysts for the Ziegler–Natta polymerization. Under clean, ultra-high vacuum conditions, low-energy electron irradiation during the chemical vapor deposition of model Ziegler–Natta catalysts can be used to create a “single-site” catalyst film with a surface structure that produces only isotactic polypropylene. The polymerization activities of the ultra-high vacuum-prepared model heterogeneous catalysts compare well with those of conventional Ziegler–Natta catalysts. X-ray photoelectron spectroscopic analyses identify the oxidation states of the Ti ions at the active sites. Temperature-programmed desorption distinguishes the binding strength of a probe molecule to the active sites that produce polypropylenes having different tacticities. These findings demonstrate that a surface science approach to the preparation and characterization of model heterogeneous catalysts can improve the catalyst design and provide fundamental understanding of the single-site olefin polymerization process.
Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia
Authors: Ridler Khanum , Veijola Juha M. , Tanskanen Päivikki , Miettunen Jouko , Chitnis Xavier , Suckling John , Murray Graham K. , Haapea Marianne , Jones Peter B. , Isohanni Matti K. , Bullmore Edward T.
Published: October 2006

Delineating longitudinal relationships between early developmental markers, adult cognitive function, and adult brain structure could clarify the pathogenesis of neurodevelopmental disorders such as schizophrenia. We aimed to identify brain structural correlates of infant motor development (IMD) and adult executive function in nonpsychotic adults and to test for abnormal associations between these measures in people with schizophrenia. Representative samples of nonpsychotic adults (
n
= 93) and people with schizophrenia (
n
= 49) were drawn from the Northern Finland 1966 general population birth cohort. IMD was prospectively assessed at age 1 year; executive function testing and MRI were completed at age 33–35 years. We found that earlier motor development in infancy was correlated with superior executive function in nonpsychotic subjects. Earlier motor development was also normally associated with increased gray matter density in adult premotor cortex, striatum, and cerebellum and increased white matter density in frontal and parietal lobes. Adult executive function was normally associated with increased gray matter density in a fronto-cerebellar system that partially overlapped, but was not identical to, the gray matter regions normally associated with IMD. People with schizophrenia had relatively delayed IMD and impaired adult executive function in adulthood. Furthermore, they demonstrated no normative associations between fronto-cerebellar structure, IMD, or executive function. We conclude that frontal cortico-cerebellar systems correlated with adult executive function are anatomically related to systems associated with normal infant motor development. Disruption of this anatomical system may underlie both the early developmental and adult cognitive abnormalities in schizophrenia.
Diminishing catalyst concentration in atom transfer radical polymerization with reducing agents
Authors: Matyjaszewski Krzysztof , Jakubowski Wojciech , Min Ke , Tang Wei , Huang Jinyu , Braunecker Wade A. , Tsarevsky Nicolay V.
Published: October 2006

The concept of initiators for continuous activator regeneration (ICAR) in atom transfer radical polymerization (ATRP) is introduced, whereby a constant source of organic free radicals works to regenerate the Cu
I
activator, which is otherwise consumed in termination reactions when used at very low concentrations. With this technique, controlled synthesis of polystyrene and poly(methyl methacrylate) (
M
w
/
M
n
< 1.2) can be implemented with catalyst concentrations between 10 and 50 ppm, where its removal or recycling would be unwarranted for many applications. Additionally, various organic reducing agents (derivatives of hydrazine and phenol) are used to continuously regenerate the Cu
I
activator in activators regenerated by electron transfer (ARGET) ATRP. Controlled polymer synthesis of acrylates (
M
w
/
M
n
< 1.2) is realized with catalyst concentrations as low as 50 ppm. The rational selection of suitable Cu complexing ligands {tris[2-(dimethylamino)ethyl]amine (Me
6
TREN) and tris[(2-pyridyl)methyl]amine (TPMA)} is discussed in regards to specific side reactions in each technique (i.e., complex dissociation, acid evolution, and reducing agent complexation). Additionally, mechanistic studies and kinetic modeling are used to optimize each system. The performance of the selected catalysts/reducing agents in homo and block (co)polymerizations is evaluated.
Metallocene-catalyzed alkene polymerization and the observation of Zr-allyls
Authors: Landis Clark R. , Christianson Matthew D.
Published: October 2006

Single-site polymerization catalysts enable exquisite control over alkene polymerization reactions to produce new materials with unique properties. Knowledge of catalyst speciation and fundamental kinetics are essential for full mechanistic understanding of zirconocene-catalyzed alkene polymerization. Currently the effect of activators on fundamental polymerization steps is not understood. Progress in understanding activator effects requires determination of fundamental kinetics for zirconocene catalysts with noncoordinating anions such as [B(C
6
F
5
)
4
]
−
. Kinetic NMR studies at low temperature demonstrate a very fast propagation rate for 1-hexene polymerization catalyzed by [(SBI)Zr(CH
2
SiMe
3
)][B(C
6
F
5
)
4
] [where SBI is
rac
-Me
2
Si(indenyl)
2
] with complete consumption of 1-hexene before the first NMR spectrum. Surprisingly, the first NMR spectrum reveals, aside from uninitiated catalyst, Zr-allyls as the sole catalyst-containing species. These Zr-allyls, which exist in two diastereomeric forms, have been characterized by physical and chemical methods. The mechanism of Zr-allyl formation was probed with a trapping experiment, leading us to favor a mechanism in which Zr-polymeryl undergoes β-H transfer to metal without dissociation of coordinated alkene followed by σ-bond metathesis to form H
2
and Zr-allyl. Zr-allyl species undergo slow reactions with alkene but react rapidly with H
2
to form hydrogenation products.
Folliculin encoded by the
BHD
gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling
Authors: Baba Masaya , Hong Seung-Beom , Sharma Nirmala , Warren Michelle B. , Nickerson Michael L. , Iwamatsu Akihiro , Esposito Dominic , Gillette William K. , Hopkins Ralph F. , Hartley James L. , Furihata Mutsuo , Oishi Shinya , Zhen Wei , Burke Terrence R. , Linehan W. Marston , Schmidt Laura S. , Zbar Berton
Published: October 2006

Birt–Hogg–Dubé syndrome, a hamartoma disorder characterized by benign tumors of the hair follicle, lung cysts, and renal neoplasia, is caused by germ-line mutations in the
BHD(FLCN)
gene, which encodes a tumor-suppressor protein, folliculin (FLCN), with unknown function. The tumor-suppressor proteins encoded by genes responsible for several other hamartoma syndromes, LKB1, TSC1/2, and PTEN, have been shown to be involved in the mammalian target of rapamycin (mTOR) signaling pathway. Here, we report the identification of the FLCN-interacting protein, FNIP1, and demonstrate its interaction with 5′ AMP-activated protein kinase (AMPK), a key molecule for energy sensing that negatively regulates mTOR activity. FNIP1 was phosphorylated by AMPK, and its phosphorylation was reduced by AMPK inhibitors, which resulted in reduced FNIP1 expression. AMPK inhibitors also reduced FLCN phosphorylation. Moreover, FLCN phosphorylation was diminished by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression, suggesting that FLCN may be regulated by mTOR and AMPK signaling. Our data suggest that FLCN, mutated in Birt–Hogg–Dubé syndrome, and its interacting partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways.
Switching off calcium-dependent inactivation in
l
-type calcium channels by an autoinhibitory domain
Authors: Wahl-Schott Christian , Baumann Ludwig , Cuny Hartmut , Eckert Christian , Griessmeier Kristina , Biel Martin
Published: October 2006

The retinal
l
-type Ca
2+
channel Cav1.4 is distinguished from all other members of the high voltage-activated (HVA) Ca
2+
channel family by lacking Ca
2+
-calmodulin-dependent inactivation. In synaptic terminals of photoreceptors and bipolar cells, this feature is essential to translate graded membrane depolarizations into sustained Ca
2+
influx and tonic glutamate release. The sequences conferring Ca
2+
-dependent inactivation (CDI) are conserved throughout the HVA calcium channel family, raising the question of how Cav1.4 manages to switch off CDI. Here, we identify an autoinhibitory domain in the distal C terminus of Cav1.4 that serves to abolish CDI. We show that this domain (ICDI, inhibitor of CDI) uncouples the molecular machinery conferring CDI from the inactivation gate by binding to the EF hand motif in the proximal C terminus. Deletion of ICDI completely restores Ca
2+
-calmodulin-mediated CDI in Cav1.4. CDI can be switched off again in the truncated Cav1.4 channel by coexpression of ICDI, indicating that ICDI works as an autonomous unit. Furthermore, we show that in the Cav1.2
l
-type Ca
2+
-channel replacement of the distal C terminus by the corresponding sequence of Cav1.4 is sufficient to block CDI. This finding suggests that autoinhibition of CDI can be introduced principally into other Ca
2+
channel types. Our data provide a previously undescribed perspective on the regulation of HVA calcium channels by Ca
2+
.
Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase
Authors: Wang Lin , Goodey Nina M. , Benkovic Stephen J. , Kohen Amnon
Published: October 2006

One of the most intriguing questions in modern enzymology is whether enzyme dynamics evolved to enhance the catalyzed chemical transformation. In this study, dihydrofolate reductase, a small monomeric protein that catalyzes a single C-H–C transfer, is used as a model system to address this question. Experimental and computational studies have proposed a dynamic network that includes two residues remote from the active site (G121 and M42). The current study compares the nature of the H-transfer step of the WT enzyme, two single mutants, and their double mutant. The contribution of quantum mechanical tunneling and enzyme dynamics to the H-transfer step was examined by determining intrinsic kinetic isotope effects, their temperature dependence, and activation parameters. Different patterns of environmentally coupled tunneling were found for these four enzymes. The findings indicate that the naturally evolved WT dihydrofolate reductase requires no donor–acceptor distance fluctuations (no gating). Both single mutations affect the rearrangement of the system before tunneling, so some gating is required, but the overall nature of the environmentally coupled tunneling appears similar to that of the WT enzyme. The double mutation, on the other hand, seems to cause a major change in the nature of H transfer, leading to poor reorganization and substantial gating. These findings support the suggestion that these distal residues synergistically affect the H transfer at the active site of the enzyme. This observation is in accordance with the notion that these remote residues are part of a dynamic network that is coupled to the catalyzed chemistry.
A missense mutation in
Caenorhabditis elegans
prohibitin 2 confers an atypical multidrug resistance
Authors: Zubovych Iryna , Doundoulakis Thomas , Harran Patrick G. , Roth Michael G.
Published: October 2006

Hemiasterlin is a potent antimitotic peptide that interferes with microtubule dynamics at picomolar concentrations in cell culture. The molecule largely eludes P glycoprotein-mediated drug efflux, and an analog is currently being evaluated in clinical trials as cancer chemotherapy. From a nonclonal genetic screen in
Caenorhabditis elegans
we isolated eight independent mutants resistant to a synthetic hemiasterlin analog. In one recessive mutant,
phb-2(ad2154)
, a point mutation in prohibitin 2 (E130K) protects worms from drug-induced injury. Data indicate that direct binding of hemiasterlin to prohibitin 2 is unlikely. In fact,
C. elegans
phb-2(ad2154)
was also found to be resistant to numerous other drugs that bind tubulin and to camptothecin, yet this mutant was sensitive to nocodazole and phalloidin. Thus, prohibitin 2 is implicated in a previously uncharacterized pathway of multidrug resistance.
GATA factors participate in tissue-specific immune responses in
Drosophila
larvae
Authors: Senger Kate , Harris Kristina , Levine Mike
Published: October 2006

Drosophila
responds to infection by producing a broad range of antimicrobial agents in the fat body and more restricted responses in tissues such as the gut, trachea, and malpighian tubules. The regulation of antimicrobial genes in larval fat depends on linked Rel/NF-κB and GATA binding sites. Serpent functions as the major GATA transcription factor in the larval fat body. However, the transcriptional regulation of other tissue-specific responses is less well understood. Here, we present evidence that dGATAe regulates antimicrobial gene expression in the midgut. Regulatory regions for antimicrobial genes
Diptericin
and
Metchnikowin
require GATA sites for activation in the midgut, where Grain (dGATAc), dGATAd, and dGATAe are expressed in overlapping domains. Ectopic expression of dGATAe in the larval fat body, where it is normally absent, causes dramatic up-regulation of numerous innate immunity and gut genes, as judged by microarray analysis and
in situ
hybridization. Ectopic dGATAe also causes a host of symptoms reminiscent of hyperactive Toll (Toll
10b
) mutants, but without apparent activation of Toll signaling. Based on this evidence we propose that dGATAe mediates a Toll-independent immune response in the midgut, providing a window into the first and perhaps most ancient line of animal defense.
Survival analysis of longitudinal microarrays
Authors: Rajicic Natasa , Finkelstein Dianne M. , Schoenfeld David A. ,   the Inflammation Host Response to Injury Research Program Investigators
Published: October 2006

Motivation: The development of methods for linking gene expressions to various clinical and phenotypic characteristics is an active area of genomic research. Scientists hope that such analysis may, for example, describe relationships between gene function and clinical events such as death or recovery. Methods are available for relating gene expression to measurements that are categorized or continuous, but there is less work in relating expressions to an observed event time such as time to death, response or relapse. When gene expressions are measured over time, there are methods for differentiating temporal patterns. However, methods have not yet been proposed for the survival analysis of longitudinally collected microarrays.

Results: We describe an approach for the survival analysis of longitudinal gene expression data. We construct a measure of association between the time to an event and gene expressions collected over time. Statistical significance is addressed using permutations and control of the false discovery rate. Our proposed method is illustrated on a dataset from a multi-center research study of inflammation and response to injury that aims to uncover the biological reasons why patients can have dramatically different outcomes after suffering a traumatic injury ().

Contact:  dfinkelstein@partners.org
Integration of gel-based proteome data with pProRep
Authors: Laukens Kris , Matthiesen Rune , Lemière Filip , Esmans Eddy , Onckelen Harry Van , Jensen Ole Nørregaard , Witters Erwin
Published: October 2006

Summary: pProRep is a web application integrating electrophoretic and mass spectral data from proteome analyses into a relational database. The graphical web-interface allows users to upload, analyse and share experimental proteome data. It offers researchers the possibility to query all previously analysed datasets and can visualize selected features, such as the presence of a certain set of ions in a peptide mass spectrum, on the level of the two-dimensional gel.

Availability: The pProRep package and instructions for its use can be downloaded from . The application requires a web server that runs PHP 5 () and MySQL. Some (non-essential) extensions need additional freely available libraries: details are described in the installation instructions.

Contact:  kris.laukens@ua.ac.be
Evaluating the performance of microarray segmentation algorithms
Authors: Lehmussola Antti , Ruusuvuori Pekka , Yli-Harja Olli
Published: October 2006

Motivation: Although numerous algorithms have been developed for microarray segmentation, extensive comparisons between the algorithms have acquired far less attention. In this study, we evaluate the performance of nine microarray segmentation algorithms. Using both simulated and real microarray experiments, we overcome the challenges in performance evaluation, arising from the lack of ground-truth information. The usage of simulated experiments allows us to analyze the segmentation accuracy on a single pixel level as is commonly done in traditional image processing studies. With real experiments, we indirectly measure the segmentation performance, identify significant differences between the algorithms, and study the characteristics of the resulting gene expression data.

Results: Overall, our results show clear differences between the algorithms. The results demonstrate how the segmentation performance depends on the image quality, which algorithms operate on significantly different performance levels, and how the selection of a segmentation algorithm affects the identification of differentially expressed genes.

Availability: Supplementary results and the microarray images used in this study are available at the companion web site

Contact: antti.lehmussola@tut.fi
Proteomic Analysis of Seed Dormancy in Arabidopsis
Authors: Chibani Kamel , Ali-Rachedi Sonia , Job Claudette , Job Dominique , Jullien Marc , Grappin Philippe
Published: October 2006

The mechanisms controlling seed dormancy in Arabidopsis (Arabidopsis thaliana) have been characterized by proteomics using the dormant (D) accession Cvi originating from the Cape Verde Islands. Comparative studies carried out with freshly harvested dormant and after-ripened non-dormant (ND) seeds revealed a specific differential accumulation of 32 proteins. The data suggested that proteins associated with metabolic functions potentially involved in germination can accumulate during after-ripening in the dry state leading to dormancy release. Exogenous application of abscisic acid (ABA) to ND seeds strongly impeded their germination, which physiologically mimicked the behavior of D imbibed seeds. This application resulted in an alteration of the accumulation pattern of 71 proteins. There was a strong down-accumulation of a major part (90%) of these proteins, which were involved mainly in energetic and protein metabolisms. This feature suggested that exogenous ABA triggers proteolytic mechanisms in imbibed seeds. An analysis of de novo protein synthesis by two-dimensional gel electrophoresis in the presence of [35S]-methionine disclosed that exogenous ABA does not impede protein biosynthesis during imbibition. Furthermore, imbibed D seeds proved competent for de novo protein synthesis, demonstrating that impediment of protein translation was not the cause of the observed block of seed germination. However, the two-dimensional protein profiles were markedly different from those obtained with the ND seeds imbibed in ABA. Altogether, the data showed that the mechanisms blocking germination of the ND seeds by ABA application are different from those preventing germination of the D seeds imbibed in basal medium.
Molecular Interactions between the Specialist Herbivore Manduca sexta (Lepidoptera, Sphingidae) and Its Natural Host Nicotiana attenuata. VII. Changes in the Plant's Proteome
Authors: Giri Ashok P. , Wünsche Hendrik , Mitra Sirsha , Zavala Jorge A. , Muck Alexander , Svatoš Aleš , Baldwin Ian T.
Published: October 2006

When Manduca sexta attacks Nicotiana attenuata, fatty acid-amino acid conjugates (FACs) in the larvae's oral secretions (OS) are introduced into feeding wounds. These FACs trigger a transcriptional response that is similar to the response induced by insect damage. Using two-dimensional gel electrophoresis, matrix-assisted laser desorption ionization-time of flight, and liquid chromatography-tandem mass spectrometry, we characterized the proteins in phenolic extracts and in a nuclear fraction of leaves elicited by larval attack, and/or in leaves wounded and treated with OS, FAC-free OS, and synthetic FACs. Phenolic extracts yielded approximately 600 protein spots, many of which were altered by elicitation, whereas nuclear protein fractions yielded approximately 100 spots, most of which were unchanged by elicitation. Reproducible elicitor-induced changes in 90 spots were characterized. In general, proteins that increased were involved in primary metabolism, defense, and transcriptional and translational regulation; those that decreased were involved in photosynthesis. Like the transcriptional defense responses, proteomic changes were strongly elicited by the FACs in OS. A semiquantitative reverse transcription-PCR approach based on peptide sequences was used to compare transcript and protein accumulation patterns for 17 candidate proteins. In six cases the patterns of elicited transcript accumulation were consistent with those of elicited protein accumulation. Functional analysis of one of the identified proteins involved in photosynthesis, RuBPCase activase, was accomplished by virus-induced gene silencing. Plants with decreased levels of RuBPCase activase protein had reduced photosynthetic rates and RuBPCase activity, and less biomass, responses consistent with those of herbivore-attacked plants. We conclude that the response of the plant's proteome to herbivore elicitation is complex, and integrated transcriptome-proteome-metabolome analysis is required to fully understand this ubiquitous ecological interaction.
A Posttranslationally Regulated Protease, VheA, Is Involved in the Liberation of Juveniles from Parental Spheroids inVolvox carteri
Authors: Fukada Kazutake , Inoue Tan , Shiraishi Hideaki
Published: October 2006

The lineage of volvocine algae includes unicellular Chlamydomonas and multicellular Volvox in addition to their colonial relatives intermediate in size and cell number. In an asexual life cycle, daughter cells of Chlamydomonas hatch from parental cell walls soon after cell division, while Volvox juveniles are released from parental spheroids after the completion of various developmental events required for the survival of multicellular juveniles. Thus, heterochronic change in the timing of hatching is considered to have played an important role in the evolution of multicellularity in volvocine algae. To study the hatching process in Volvox carteri, we purified a 125-kD Volvox hatching enzyme (VheA) from a culture medium with enzymatic activity to degrade the parental spheroids. The coding region of vheA contains a prodomain with a transmembrane segment, a subtilisin-like Ser protease domain, and a functionally unknown domain, although purified 125-kD VheA does not contain a prodomain. While 143-kD VheA with a prodomain is synthesized long before the hatching stage, 125-kD VheA is released into the culture medium during hatching due to cleavage processing at the site between the prodomain and the subtilisin-like Ser protease domain, indicating that posttranslational regulation is involved in the determination of the timing of hatching.
Evaluating the Evaluators: Perceptions of Interviewers by Rejected Job Applicants as a Function of Interviewer and Applicant Sex1
Authors: Holloway Rebecca , Johnston Lucy
Published: October 2006

Students who had recently had an unsuccessful job interview rated the competence of their interviewer and completed the Women As Managers Scale (WAMS; Terborg, Peters, Ilgen, & Smith, 1977). The results showed an impact of the sex of interviewer on judgments of interviewer competence and WAMS scores, but only for male participants. Male participants gave lower ratings of interviewer competence to female than to male interviewers, and ratings for the female interviewers were also lower than those given by female participants. Scores on the WAMS were lower for male participants who were interviewed by a female interviewer than those interviewed by a male interviewer, and were lower for male than for female participants with a female interviewer.
The Impact of Having Children on the Lives of Women: The Effects of Children Questionnaire
Authors: Johnson Amber B. , Lee Rodgers Joseph
Published: October 2006

The current study uses a newly developed questionnaire, the Effects of Children Questionnaire, to examine the impact of having children on women's lives. Participants were lower‐ and lower‐middle‐class women. The questionnaire assessed women's perceptions of their own change and other women's experiences of change as a result of having children in a number of life domains. Exploratory analyses, repeated‐measures analyses, factor analyses, and regression analyses were used to test hypotheses. Results suggested that women do compare themselves with other women, that there are two primary factors underlying perceptions of change, and that there are significant changes from having children in various life domains. Results are discussed in terms of the costs and benefits of having children.
Predicting Intention to Save Water: Theory of Planned Behavior, Response Efficacy, Vulnerability, and Perceived Efficiency of Alternative Solutions1
Authors: Lam San‐Pui
Published: October 2006

These 2 studies attempted to predict people's intention to save water. Study 1 used a model based on Ajzen's (1991) theory of planned behavior (TPB) and other variables: vulnerability, 2 collective efficacy variables, and subjective effectiveness of alternative solutions (SEAS) to ease drought impact. Study 2 tested a model similar to that of Study 1, but with 2 personal efficacy variables added. Respondents in both studies were residents of Taiwan (Ns= 166 and 210). Analysis indicated that the modified models (R2>.32) were better than the TPB model (R2<.19), and SEAS and response efficacy had crucial effects on people's intentions to retrofit. The studies also found some significant but inconsistent effects of income, dwelling, and education.
Bad nights or bad bars? Multi‐level analysis of environmental predictors of aggression in late‐night large‐capacity bars and clubs
Authors: Graham Kathryn , Bernards Sharon , Osgood D. Wayne , Wells Samantha
Published: October 2006

Aims  To clarify environmental predictors of bar‐room aggression by differentiating relationships due to nightly variations versus across bar variations, frequency versus severity of aggression and patron versus staff aggression.

Design, setting and participants  Male–female pairs of researcher–observers conducted 1334 observations in 118 large capacity (> 300) bars and clubs in Toronto, Canada.

Measurements  Observers independently rated aspects of the environment (e.g. crowding) at every visit and wrote detailed narratives of each incident of aggression that occurred. Measures of severity of aggression for the visit were calculated by aggregating ratings for each person in aggressive incidents.

Findings  Although bivariate analyses confirmed the significance of most environmental predictors of aggression identified in previous research, multivariate analyses identified the following key visit‐level predictors (controlling for bar‐level relationships): rowdiness/permissive environment and people hanging around after closing predicted both frequency and severity of aggression; sexual activity, contact and competition and people with two or more drinks at closing predicted frequency but not severity of aggression; lack of staff monitoring predicted more severe patron aggression, while having more and better coordinated staff predicted more severe staff aggression. Intoxication of patrons was significantly associated with more frequent and severe patron aggression at the bar level (but not at the visit level) in the multivariate analyses and negatively associated with severity of staff aggression at the visit level.

Conclusions  The results demonstrate clearly the importance of the immediate environment (not just the type of bar or characteristics of usual patrons) and the importance of specific environmental factors, including staff behaviour, in predicting both frequency and severity of aggression.
Quantitative trait loci analysis of egg and meat production traits in a red junglefowl × White Leghorn cross
Authors: Wright D. , Kerje S. , Lundström K. , Babol J. , Schütz K. , Jensen P. , Andersson L.
Published: October 2006

Egg and production traits are of considerable economic importance in chickens. Using a White Leghorn × red junglefowl F2 intercross, standard production measures of liver weight and colour, egg size, eggshell thickness, egg taste and meat quality were taken. A total of 160 markers covering 29 autosomes and the Z chromosome were genotyped on 175–243 individuals, depending on the trait under consideration. A total of nine significant quantitative trait loci (QTL) and three suggestive QTL were found on chicken chromosomes 1, 2, 4, 5, 7, 8, 10, 12, E47W24 and E22C19W28.