bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Novel Mutations of the LHX3 Gene Cause Combined Pituitary Hormone Deficiencies with or without Limited Neck Rotation
Authors: Pfaeffle Roland W. , Savage Jesse J. , Hunter Chad S. , Palme Christina , Ahlmann Martina , Kumar Prasanna , Bellone Jaele , Schoenau Eckhard , Korsch Eckhard , Brämswig Jürgen H. , Stobbe Heike M. , Blum Werner F. , Rhodes Simon J.
Published: February 2007

Context: The Lhx3 LIM-homeodomain transcription factor gene is required for development of the pituitary and motoneurons in mice. Human LHX3 gene mutations have been reported in five subjects with a phenotype consisting of GH, prolactin, TSH, LH, and FSH deficiency; abnormal pituitary morphology; and limited neck rotation.

Objective: The objective of the study was to determine the frequency and nature of LHX3 mutations in patients with isolated GH deficiency or combined pituitary hormone deficiency (CPHD) and characterize the molecular consequences of mutations.

Design: The LHX3 sequence was determined. The biochemical properties of aberrant LHX3 proteins resulting from observed mutations were characterized using reporter gene and DNA binding experiments.

Patients: The study included 366 patients with isolated GH deficiency or CPHD.

Results: In seven patients with CPHD from four consanguineous pedigrees, four novel, recessive mutations were identified: a deletion of the entire gene (del/del), mutations causing truncated proteins (E173ter, W224ter), and a mutation causing a substitution in the homeodomain (A210V). The mutations were associated with diminished DNA binding and pituitary gene activation, consistent with observed hormone deficiencies. Whereas subjects with del/del, E173ter, and A210V mutations had limited neck rotation, patients with the W224ter mutation did not.

Conclusions: LHX3 mutations are a rare cause of CPHD involving deficiencies for GH, prolactin, TSH, and LH/FSH in all patients. Whereas most patients have a severe hormone deficiency manifesting after birth, milder forms can be observed, and limited neck rotation is not a universal feature of patients with LHX3 mutations. This study extends the known molecular defects and range of phenotypes found in LHX3-associated diseases.
Effects of Peroxisome Proliferator-Activated Receptor-α and -γ Agonists on 11β-Hydroxysteroid Dehydrogenase Type 1 in Subcutaneous Adipose Tissue in Men
Authors: Wake Deborah J. , Stimson Roland H. , Tan Garry D. , Homer Natalie Z. M. , Andrew Ruth , Karpe Fredrik , Walker Brian R.
Published: February 2007

Context: In animals, peroxisome proliferator-activated receptor-α (PPARα) and PPARγ agonists down-regulate 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mRNA and activity in liver and adipose tissue, respectively, and PPARγ agonists reduce ACTH secretion from corticotrope cells.

Objective: Our objective was to test whether PPAR agonists alter cortisol secretion and peripheral regeneration by 11β-HSD1 in humans and whether reduced cortisol action contributes to metabolic effects of PPARγ agonists.

Design and Setting: Three randomized placebo-controlled crossover studies were conducted at a clinical research facility.

Patients and Participants: Healthy men and patients with type 2 diabetes participated.

Interventions, Outcome Measures, and Results: In nine healthy men, 7 d of PPARα agonist (fenofibrate) or PPARγ agonist (rosiglitazone) had no effect on cortisol secretion, hepatic cortisol generation after oral cortisone administration, or tracer kinetics during 9,11,12,12-[2H]4-cortisol infusion, although rosiglitazone marginally reduced cortisol generation in sc adipose tissue measured by in vivo microdialysis. In 12 healthy men, 4–5 wk of rosiglitazone increased insulin sensitivity during insulin infusion but did not change 11β-HSD1 mRNA or activity in sc adipose tissue, and insulin sensitization was unaffected by glucocorticoid blockade with a combination of metyrapone and RU38486. In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose tissue and reduced 11β-HSD1 mRNA in sc adipose tissue but increased plasma cortisol concentrations.

Conclusions: Neither PPARα nor PPARγ agonists down-regulate 11β-HSD1 or cortisol secretion acutely in humans. The early insulin-sensitizing effect of rosiglitazone is not dependent on reducing intracellular glucocorticoid concentrations. Reduced adipose 11β-HSD1 expression and increased plasma cortisol during longer therapy with rosiglitazone probably reflect indirect effects, e.g. mediated by changes in body fat.
Origin of de Novo KCNJ11 Mutations and Risk of Neonatal Diabetes for Subsequent Siblings
Authors: Edghill Emma L. , Gloyn Anna L. , Goriely Anne , Harries Lorna W. , Flanagan Sarah E. , Rankin Julia , Hattersley Andrew T. , Ellard Sian
Published: February 2007

Context: Activating mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic β-cell KATP channel, result in permanent and transient neonatal diabetes. The majority of KCNJ11 mutations are spontaneous, but the parental origin of these mutations is not known.

Objective: Our objective was to determine the parental origin of de novo KCNJ11 mutations and investigate the possibility of mosaicism in transmitting parents.

Design: We identified 68 index cases with a KCNJ11 mutation where neither parent was known to be affected. DNA was available from both parents of 41 probands. The parental origin of the mutation was determined in 18 families by examination of pedigrees, microsatellite analysis, or allele-specific PCR.

Results: A nonsignificant excess of paternally derived mutations was found with 13 of 18 (72%) shown to have arisen on the paternal allele. There was no evidence to suggest an association with increased age at conception. In two families, there were half-siblings with permanent neonatal diabetes born to an unaffected father, suggesting germline mosaicism that was confirmed by the presence of the R201C mutation in one father’s semen. Somatic mosaicism was detected in one unaffected mother, and this mutation will also be present in her germ cells.

Conclusion: De novo KCNJ11 mutations can arise either during gametogenesis or embryogenesis. The possibility of germline mosaicism means that future siblings are at increased risk of neonatal diabetes, and we recommend that molecular genetic testing is routinely offered at birth for subsequent siblings of children with de novo KCNJ11 mutations.
Metalloproteinase axes increase β-catenin signaling in primary mouse mammary epithelial cells lacking TIMP3
Authors: Hojilla Carlo V. , Kim Ira , Kassiri Zamaneh , Fata Jimmie E. , Fang Hui , Khokha Rama
Published: February 2007

Multiple cancers exhibit mutations in β-catenin that lead to increased stability, altered localization or amplified activity. β-catenin is situated at the junction between the cadherin-mediated cell adhesion and Wnt signaling pathways, and TIMP3 functions to alter β-catenin signaling. Here we demonstrate that primary mouse embryonic fibroblasts (MEFs) and mammary epithelial cells (MECs) deficient in Timp3 have increased β-catenin signaling. Functionally, the loss of TIMP3 exerted cell-type-specific effects, with Timp3–/– MEFs being more sensitive and Timp3–/– MECs more resistant to EGTA-induced cell detachment than the wild type. Timp3–/– MECs had higher dephosphorylated β-catenin levels and increased β-catenin transcriptional activity as measured by TCF/LEF-responsive reporter assays. Real-time PCR analysis of β-catenin target genes in MEFs and MECs showed no alteration in Myc, decreased Ccnd1 (cyclin D1) and increased Mmp7 mRNA levels upon loss of TIMP3, with the latter occurring only in epithelial cells. Recombinant TIMP3 and synthetic metalloproteinase inhibitors reverted the increase in dephosphorylated β-catenin, decrease in Ccnd1 gene expression and increase in Mmp7 gene expression. Physiologically, Timp3–/– mammary glands displayed accelerated mammary ductal elongation during pubertal morphogenesis. Gain-of-function studies using slow-release TIMP-containing pellets revealed distinct effects of individual TIMPs on ductal morphogenesis. Recombinant TIMP1, TIMP3 and TIMP4 inhibited ductal elongation whereas TIMP2 promoted this process.
Kinetic-structural analysis of neuronal growth cone veil motility
Authors: Mongiu Anne K. , Weitzke Elizabeth L. , Chaga Oleg Y. , Borisy Gary G.
Published: February 2007

Neuronal growth cone advance was investigated by correlative light and electron microscopy carried out on chick dorsal root ganglion cells. Advance was analyzed in terms of the two principal organelles responsible for protrusive motility in the growth cone – namely, veils and filopodia. Veils alternated between rapid phases of protrusion and retraction. Electron microscopy revealed characteristic structural differences between the phases. Our results provide a significant advance in three respects: first, protruding veils are comprised of a densely branched network of actin filaments that is lamellipodial in appearance and includes the Arp2/3 complex. On the basis of this structural and biomarker evidence, we infer that the dendritic nucleation and/or array-treadmilling mechanism of protrusive motility is conserved in veil protrusion of growth cones as in the motility of fibroblasts; second, retracting veils lack dendritic organization but contain a sparse network of long filaments; and third, growth cone filopodia have the capacity to nucleate dendritic networks along their length, a property consistent with veil formation seen at the light microscopic level but not previously understood in supramolecular terms. These elements of veil and filopodial organization, when taken together, provide a conceptual framework for understanding the structural basis of growth cone advance.
Perturbed gap-filling synthesis in nucleotide excision repair causes histone H2AX phosphorylation in human quiescent cells
Authors: Matsumoto Megumi , Yaginuma Kie , Igarashi Ai , Imura Mayumi , Hasegawa Mizuho , Iwabuchi Kuniyoshi , Date Takayasu , Mori Toshio , Ishizaki Kanji , Yamashita Katsumi , Inobe Manabu , Matsunaga Tsukasa
Published: February 2007

Human histone H2AX is rapidly phosphorylated on serine 139 in response to DNA double-strand breaks and plays a crucial role in tethering the factors involved in DNA repair and damage signaling. Replication stress caused by hydroxyurea or UV also initiates H2AX phosphorylation in S-phase cells, although UV-induced H2AX phosphorylation in non-cycling cells has recently been observed. Here we study the UV-induced H2AX phosphorylation in human primary fibroblasts under growth-arrested conditions. This reaction absolutely depends on nucleotide excision repair (NER) and is mechanistically distinct from the replication stress-induced phosphorylation. The treatment of cytosine-β-D-arabinofuranoside strikingly enhances the NER-dependent H2AX phosphorylation and induces the accumulation of replication protein A (RPA) and ATR-interacting protein (ATRIP) at locally UV-damaged subnuclear regions. Consistently, the phosphorylation appears to be mainly mediated by ataxia-telangiectasia mutated and Rad3-related (ATR), although Chk1 (Ser345) is not phosphorylated by the activated ATR. The cellular levels of DNA polymerases δ and ϵ and proliferating cell nuclear antigen are markedly reduced in quiescent cells. We propose a model that perturbed gap-filling synthesis following dual incision in NER generates single-strand DNA gaps and hence initiates H2AX phosphorylation by ATR with the aid of RPA and ATRIP.
Integrin-ECM interactions regulate the changes in cell shape driving the morphogenesis of theDrosophilawing epithelium
Authors: Domínguez-Giménez Paloma , Brown Nicholas H. , Martín-Bermudo María D.
Published: February 2007

During development, morphogenesis involves migration and changes in the shape of epithelial sheets, both of which require coordination of cell adhesion. Thus, while modulation of integrin-mediated adhesion to the ECM regulates epithelial motility, cell-cell adhesion via cadherins controls the remodelling of epithelial sheets. We have used the Drosophila wing epithelium to demonstrate that cell-ECM interactions mediated by integrins also regulate the changes in cell shape that underly epithelial morphogenesis. We show that integrins control the transitions from columnar to cuboidal cell shape underlying wing formation, and we demonstrate that eliminating the ECM has the same effect on cell shape as inhibiting integrin function. Furthermore, lack of integrin activity also induces detachment of the basal lamina and failure to assemble the basal matrix. Hence, we propose that integrins control epithelial cell shape by mediating adherence of these cells to the ECM. Finally, we show that the ECM has an instructive rather than a structural role, because inhibition of Raf reverses the cell shape changes caused by perturbing integrins.
An essential role forDrosophila hus1in somatic and meiotic DNA damage responses
Authors: Abdu Uri , Klovstad Martha , Butin-Israeli Veronika , Bakhrat Anna , Schüpbach Trudi
Published: February 2007

The checkpoint proteins Rad9, Rad1 and Hus1 form a clamp-like complex which plays a central role in the DNA-damage-induced checkpoint response. Here we address the function of the 9-1-1 complex in Drosophila. We decided to focus our analysis on the meiotic and somatic requirements of hus1. For that purpose, we created a null allele of hus1 by imprecise excision of a P element found 2 kb from the 3′ of the hus1 gene. We found that hus1 mutant flies are viable, but the females are sterile. We determined that hus1 mutant flies are sensitive to hydroxyurea and methyl methanesulfonate but not to X-rays, suggesting that hus1 is required for the activation of an S-phase checkpoint. We also found that hus1 is not required for the G2-M checkpoint and for post-irradiation induction of apoptosis. We subsequently studied the role of hus1 in activation of the meiotic checkpoint and found that the hus1 mutation suppresses the dorsal-ventral pattering defects caused by mutants in DNA repair enzymes. Interestingly, we found that the hus1 mutant exhibits similar oocyte nuclear defects as those produced by mutations in DNA repair enzymes. These results demonstrate that hus1 is essential for the activation of the meiotic checkpoint and that hus1 is also required for the organization of the oocyte DNA, a function that might be independent of the meiotic checkpoint.
Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1α
Authors: Rey Mercedes , Valenzuela-Fernández Agustín , Urzainqui Ana , Yáñez-Mó María , Pérez-Martínez Manuel , Penela Petronila , Mayor Federico , Sánchez-Madrid Francisco
Published: February 2007

Endocytosis of chemokine receptors regulates signal transduction initiated by chemokines, but the molecular mechanisms underlying this process are not fully defined. In this work, we assessed the involvement of the motor protein nonmuscle myosin heavy chain IIA (MIIA) in the endocytosis of CXCR4 induced by SDF-1α (also known as CXCL12) in T lymphocytes. Overexpression of the C-terminal half of MIIA inhibited the ligand-induced endocytosis of CXCR4, but not that of transferrin receptor. Targeting MIIA either by silencing its expression with small interfering RNA (siRNA) or by blebbistatin treatment also inhibited endocytosis of CXCR4. Inhibition of endocytosis of CXCR4 by targeting endogenous MIIA resulted in an increased migration of T cells induced by SDF-1α, and in the inhibition of the HIV-1-Env antifusogenic activity of this chemokine. Coimmunoprecipitation and protein-protein binding studies demonstrated that MIIA interacts with both the cytoplasmic tail of CXCR4 and β-arrestin. Moreover, SDF-1α promotes a rapid MIIA-β-arrestin dissociation. Our data reveal a novel role for MIIA in CXCR4 endocytosis, which involves its dynamic association with β-arrestin and highlights the role of endogenous MIIA as a regulator of CXCR4 internalization and, therefore, the onset of SDF-1α signaling.
Crack simulation in pneumatic tyres using the finite element method
Authors: Ök A , Özüpek S , Becker E B
Published: February 2007

The study is concerned with the durability problem of pneumatic tyres, in particular the simulation of belt edge separation. The finite element method and fracture mechanics concepts are combined to study the initiation and growth of a rectangular crack at the belt edge. Implicit steady state formulation of rolling and the global-local modelling technique are used in the analysis. J-integral is calculated as part of the fatigue crack growth in the circumferential and meridional directions. The reliability and accuracy of J-integral calculations for crack models with sharp corners is studied by comparing the results with smoother crack models as well as more robust methods of calculating energy release rate.
A comparison of component zooming simulation strategies using streamline curvature
Authors: Pachidis V , Pilidis P , Texeira J , Templalexis I
Published: February 2007

Typically gas turbine engine component characteristics are represented via non-dimensional maps of experimental or default data. In those cases where actual component characteristics are not available and default characteristics are used instead, conventional engine cycle simulation tools can deviate substantially at off-design and transient conditions. Similarly, when real component characteristics are available, conventional tools cannot predict the performance of the engine at other than nominal conditions satisfactorily, or account for the impact of changes in component geometry. Component zooming simulation strategies allow the performance characteristics of an isolated gas turbine engine component, resolved from a detailed, high-fidelity analysis, to be transferred to an engine system analysis carried out at a lower level of resolution. This study looked into the direct comparison of three, well-established zooming strategies utilizing a two-dimensional streamline curvature component model and a low fidelity cycle program. The validated performance of a two-dimensional, low-pressure, compressor model was integrated with a notional, two-spool, low-bypass ratio, military engine model, according to the ‘de-coupled’, ‘iterative’, and ‘fully integrated’ approaches to high-fidelity analysis. The two-dimensional model was used in the engine cycle analysis to provide a more accurate, physics- and geometry-based estimate of fan performance. Although large differences in the simulated engine performance were not observed as expected, this analysis provided a very valuable insight as to the actual speed of execution, practicality, applicability, and potential of the zooming strategies mentioned above. More importantly, this research effort established the necessary methodology and technology required towards a full, two-dimensional engine cycle analysis at an affordable computational resource in the very short term.
Design and analysis of a double superimposed chamber valveless MEMS micropump
Authors: Zordan E , Amirouche F
Published: February 2007

The newly designed micropump model proposed consists of a valveless double chamber pump completely simulated and optimized for drug delivery conditions. First, the inertia force and viscous loss in relation to actuation, pressure, and frequency is considered, and then a model of the nozzle/diffuser elements is introduced. The value of the flowrate obtained from the first model is then used to determine the loss coefficients starting from geometrical properties and flow velocity. From the developed model IT analysis is performed to predict the micropump performance based on the actuation parameters and no energy loss. A single-chamber pump with geometrical dimensions equal to each of the chambers of the double-chamber pump was also developed, and the results from both models are then compared for equally applied actuation pressure and frequency. Results show that the proposed design gives a maximum flow working frequency that is about 30 per cent lower than the single chamber design, with a maximum flowrate that is 140 per cent greater than that of the single chamber. Finally, the influences of geometrical properties on flowrate, maximum flow frequency, loss coefficients, and membrane strain are examined. The results show that the nozzle/diffuser initial width and chamber side length are the most critical dimensions of the design.
Effects of localized roughness over reaction and impulse blades on loss coefficient
Authors: Samsher
Published: February 2007

With use, new turbine blades experience a change in profile and surface roughness. An experimental study has been carried out in rectilinear cascades of reaction and impulse blades with smooth and rough surfaces. The roughnesses of 220, 100, and 50 grades emery paper, one at a time, is applied over suction and pressure surfaces at one-third of surface at leading edge, mid-chord and trailing edge regions. Measurement of pressure, exit angle, and velocity at exit of the cascade has been taken with a three-hole probe. It has been observed that the same roughness at mid-chord of suction surface is most detrimental and least detrimental when applied at mid-chord of pressure surface. It has also been seen that the same roughness over impulse blade is more detrimental than that over reaction blade.
Prediction of the long-term electric power demand under the influence of A/C systems
Authors: Alsayegh O , Almatar O , Fairouz F , Ali A. Al-Mulla.
Published: February 2007

This paper examines the long-term power demand behaviour under the influence of air-conditioning (A/C) systems in Kuwait. An artificial neural network- (ANN-) based simulation model has been developed to forecast the long-term power demand considering different A/C-system quantity import scenarios. Beside the A/C factor, four socio-economic factors are utilized as inputs for the simulation model, including gross national product, population, number of buildings, and historic peak power demand. The baseline scenario shows that the peak power demand will reach 27 440 MW by the year 2025, with an average annual power growth rate of 5.9 per cent. The A/C import quantity scenario shows that an average A/C import quantity change of 1 per cent is proportionate to an ∼1.1 per cent change in power demand.
Modelling and simulation of friction for toroidal drive
Authors: Xu L , Huang Z
Published: February 2007

In this paper, the relative motions for the toroidal drive are analysed. The sliding factors between the planet and the stator or the worm are given. The friction coefficients between the planet and the stator or the worm under asperity contact or hydrodynamic lubrication are presented. The friction coefficients between the planet and the stator or the worm under partial hydrodynamic lubrication are also given. Changes of the sliding factors between the planet and the stator or the worm along with drive parameters are presented. The friction coefficients between the planet and the stator or the worm under hydrodynamic lubrication are compared, and the changes of them along with drive parameters are discussed. Under asperity contact, the changes of the friction coefficient between the planet and the stator along with the drive parameters are given as well. Under partial hydrodynamic lubrication, the changes of the friction coefficient between the planet and the stator along with the ratio of the film thickness to mean standard deviations of the height distributions for two teeth are also discussed. These results can be used for friction design of the toroidal drive.
Real-time monitoring of wear debris using electrostatic sensing techniques
Authors: Harvey T. J. , Morris S , Wang L , Wood R. J. K. , Powrie H. E. G.
Published: February 2007

In this article, electrostatic charge sensing technology has been used to monitor adhesive wear in oil-lubricated contacts. Previous work in this area using FZG gear wear rig and pin-on-disc tribometers demonstrated that ‘precursor’ charge events may be detected prior to the onset of scuffing. Possible charging mechanisms associated with the precursor events were identified as tribocharging, surface charge variation, exo-emissions, and debris generation. This article details tests carried out to investigate the contribution of wear debris. Tests were carried out on a modified pin-on-disc rig using a sliding point contact and fitted with electrostatic sensors, one of which monitored the disc wear track and the other the disc surface just outside the wear track. Baseline tests used mild wear conditions with no seeded particles added to the entrained lubricant, whereas the high wear tests entrained seeded steel particles into the contact to promote wear. The wear debris produced dynamic charge features and the overall charging activities are directly related to the wear rate (i.e. charging levels increase with increasing wear rate). There appears to be a link between the net volume loss and the charge levels, relating charge directly to the increasing rate of debris production. Wear debris due to natural wear produced positive dynamic charge features, whereas debris from the seeded tests produced negative dynamic charge features. The polarity of the charge on debris is thought to depend on which charging and wear mechanism is predominant.
Anandamide Regulates Postnatal Development of Long-Term Synaptic Plasticity in the Rat Dorsolateral Striatum
Authors: Ade Kristen K. , Lovinger David M.
Published: February 2007

Long-term changes in synaptic efficacy produced by high-frequency stimulation (HFS) of glutamatergic afferents to the rat dorsolateral striatum exhibit heterogeneity during early stages of postnatal development. Whereas HFS most often induces striatal long-term potentiation (LTP) in rats postnatal day 12 (P12)–P14, the same stimulation tends to induce long-term depression (LTD) at ages P16–P34. Previous studies have shown that striatal LTD induction depends on retrograde endocannabinoid signaling and activation of the CB1 cannabinoid receptor. It is also known that levels of one of the primary endogenous CB1 receptor agonists, anandamide (AEA), increases during development in whole-brain samples. In the present study, we sought to determine whether this developmental increase in AEA also takes place in striatal tissue and whether increased AEA levels contribute to the postnatal switch in the response to HFS. We observed a pronounced increase in striatal levels of AEA, but not the other major endogenous cannabinoid 2-arachidonoylglycerol (2-AG), during the postnatal period characterized by the switch from LTP to LTD. Furthermore, application of synthetic AEA during HFS in field recordings of slices from P12–P14 rats allowed for induction of LTD whereas blocking the CB1 receptor during HFS in animals P16–P34 resulted in expression of LTP. However, blocking 2-AG synthesis with the DAG-lipase inhibitor tetrahydrolipstatin did not alter HFS-induced striatal LTD. In addition, synaptic depression produced by a synthetic CB1 agonist was similar across development. Together, these findings suggest that the robust developmental increase in striatal AEA may be the key factor in the emergence of HFS-induced striatal LTD.
Organization and Regulation of Small Conductance Ca2+-activated K+Channel Multiprotein Complexes
Authors: Allen Duane , Fakler Bernd , Maylie James , Adelman John P.
Published: February 2007

Small conductance Ca2+-activated K+channels (SK channels) are complexes of four α pore-forming subunits each bound by calmodulin (CaM) that mediate Ca2+gating. Proteomic analysis indicated that SK2 channels also bind protein kinase CK2 (CK2) and protein phosphatase 2A (PP2A). Coexpression of SK2 with the CaM phosphorylation surrogate CaM(T80D) suggested that the apparent Ca2+sensitivity of SK2 channels is reduced by CK2 phosphorylation of SK2-bound CaM. By using 4,5,6,7-tetrabromo-2-azabenzimidazole, a CK2-specific inhibitor, we confirmed that SK2 channels coassemble with CK2. PP2A also binds to SK2 channels and counterbalances the effects of CK2, as shown by coexpression of a dominant-negative mutant PP2A as well as a mutant SK2 channel no longer able to bind PP2A.In vitrobinding studies have revealed interactions between the N and C termini of the channel subunits as well as interactions among CK2 α and β subunits, PP2A, and distinct domains of the channel. In the channel complex, lysine residue 121 within the N-terminal domain of the channel activates SK2-bound CK2, and phosphorylation of CaM is state dependent, occurring only when the channels are closed. The effects of CK2 and PP2A indicate that native SK2 channels are multiprotein complexes that contain constitutively associated CaM, both subunits of CK2, and at least two different subunits of PP2A. The results also show that the Ca2+sensitivity of SK2 channels is regulated in a dynamic manner, directly through CK2 and PP2A, and indirectly by Ca2+itself via the state dependence of CaM phosphorylation by CK2.
Inhibition of Kainate Receptors Reduces the Frequency of Hippocampal Theta Oscillations
Authors: Huxter John R. , Zinyuk Larissa E. , Roloff Eva v. L. , Clarke Vernon R. J. , Dolman Nigel P. , More Julia C. A. , Jane David E. , Collingridge Graham L. , Muller Robert U.
Published: February 2007

We investigated the role of kainate receptors in the generation of theta oscillations using (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-yl-methyl)pyrimidine-2,4-dione (UBP304), a novel, potent and highly selective antagonist of GLUK5-containing kainate receptors. EEG and single-unit recordings were made from the dorsal hippocampus of awake, freely moving rats trained to forage for food. Bilateral intracerebroventricular injections of UBP304 (2.0 μl, two times; 2.08 mm) caused a clear (∼25%) reduction in theta frequency that was dissociable from behavioral effects of the drug. The locations of firing fields of principal cells in the hippocampal formation were generally preserved, but both field firing rates and the precision of field organization decreased. UBP304 lowered the frequency of the theta modulation of hippocampal interneuron discharge, accurately matching the reduced frequency of the theta field oscillation. UBP308 [(R)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-yl-methyl)pyrimidine-2,4-dione], the inactive enantiomer of UBP304, caused none of these effects. Our results suggest that GLUK5receptors have an important role in modulating theta activity. In addition, the effects on cellular responses provide both insight into the mechanisms of theta pacing, and useful information for models of temporal coding.
Two Streams of Attention-Dependent β Activity in the Striate Recipient Zone of Cat's Lateral Posterior–Pulvinar Complex
Authors: Wróbel Andrzej , Ghazaryan Anaida , Bekisz Marek , Bogdan Wojciech , Kamiński Jan
Published: February 2007

Local field potentials from different visual cortical areas and subdivisions of the cat's lateral posterior–pulvinar complex of the thalamus (LP-P) were recorded during a behavioral task based on delayed spatial discrimination of visual or auditory stimuli. During visual but not auditory attentive tasks, we observed an increase of β activity (12–25 Hz) as calculated from signals recorded from the caudal part of the lateral zone of the LP-P (LPl-c) as well as from cortical areas 17 and 18 and the complex located at the middle suprasylvian sulcus (MSS). This β activity appeared only in the trials that ended with a successful response, proving its relationship to the mechanism of visual attention. In contrast, no enhanced β activity was observed in the rostral part of the lateral zone of the LP-P and in the pulvinar proper. Two subregions of LPl-c (ventromedial and dorsolateral) were distinguished by visually related, attentional β activity of low (12–18 Hz) and high (18–25 Hz) frequencies, respectively. At the same time, area 17 exhibited attentional activation in the whole β range, and an increase of power in low-frequency β was observed in the medial bank of MSS, whereas cortical area 18 and the lateral bank of the MSS were activated in the high β range. Phase-correlation analysis revealed that two distinct corticothalamic systems were synchronized by the β activity of different frequencies. One comprised of cortical area 17, ventromedial region of LPl-c, and medial MSS, the second involved area 18 and the dorsolateral LPl-c. Our observations suggest that LPl-c belongs to the wide corticothalamic attentional system, which is functionally segregated by distinct streams of β activity.
Functional Axonal Regeneration through Astrocytic Scar Genetically Modified to Digest Chondroitin Sulfate Proteoglycans
Authors: Cafferty William B. J. , Yang Shih-Hung , Duffy Philip J. , Li Shuxin , Strittmatter Stephen M.
Published: February 2007

Axotomized neurons within the damaged CNS are thought to be prevented from functional regeneration by inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors. Here, we provide a transgenic test of the role of CSPGs in limiting regeneration, using thegfappromotor to express a CSPG-degrading enzyme chondroitinase ABC (ChABC) in astrocytes. Corticospinal axons extend within the lesion site, but not caudal to it, after dorsal hemisection in the transgenic mice. The presence of thegfap–ChABC transgene yields no significant improvement in motor function recovery in this model. In contrast, functionally significant sensory axon regeneration is observed after dorsal rhizotomy in transgenic mice. These transgenic studies confirm a local efficacy for reduced CSPG to enhance CNS axon growth after traumatic injury. CSPGs appear to function in a spatially distinct role from myelin inhibitors, implying that combination-based therapy will be especially advantageous for CNS injuries.
Transcription Factor Expression in the Hypothalamo-Neurohypophyseal System of the Dehydrated Rat: Upregulation of Gonadotrophin Inducible Transcription Factor 1 mRNA Is Mediated by cAMP-Dependent Protein Kinase A
Authors: Qiu Jing , Yao Song , Hindmarch Charles , Antunes Vagner , Paton Julian , Murphy David
Published: February 2007

The supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamo-neurohypophyseal system (HNS) undergo a dramatic function-related plasticity during dehydration. We hypothesize that alterations in steady-state transcript levels might be partially responsible for this remodeling. In turn, regulation of transcript abundance might be mediated by transcription factors. We used microarrays to identify changes in the expression of mRNAs encoding transcription factors in response to water deprivation in the SON. We observed downregulation of 10 and upregulation of 28 transcription factor transcripts. For five of the upregulated mRNAs, namely gonadotropin inducible ovarian transcription factor 1 (Giot1), Giot2, cAMP-responsive element binding protein 3-like 1, CCAAT/enhancer binding protein β, and activating transcription factor 4,in situhybridization was used to confirm the array results, demonstrating a significant increase in expression in SON and PVN magnocellular neurons (MCNs) after 3 d of water deprivation and, in some cases, upregulation in parvocellular PVN neurons. Using a viral vector expressing a potent inhibitor of cAMP-dependent protein kinase A (PKA), we show that the osmotically induced increase in the abundance of transcripts encoding Giot1 is mediatedin vivoby the PKA pathway. We thus suggest that signaling pathways activated by dehydration in MCNs mediate transcription factor gene activation, which, in turn, regulate target genes that mediate HNS remodeling.
Using Electronic Portfolios to Make Learning Public
Authors: Fahey Kevin , Lawrence Joshua , Paratore Jeanne
Published: February 2007

Electronic portfolio technology can be used in different contexts to create classroom communities in which everyone, not just the teacher, cares about each student's learning. The authors describe how students in an urban middle school, undergraduate teacher preparation program, and graduate leadership program used an electronic bulletin board and portfolio process to make all of their work public. In these classrooms, student work was not simply handed in to the teacher, graded, and quickly forgotten.

The article also reports three preliminary findings:

First, students at every level were able to share their work.

Second, students who had little experience in giving one another feedback learned to reflect on one another's work, share ideas, build on those ideas, and use the feedback to leverage further learning.

Third, the electronic portfolio process encouraged students to generate and focus on ideas that were personally compelling. The middle school students became deeply interested in exploring and reading and writing about community issues, and both the undergraduate and graduate students used the feedback to learn about and change important aspects of their own practice.
10 Rules for Reading
Authors: Litt Deborah G.
Published: February 2007

In the author's experience, a significant source of reading difficulty for many beginning and struggling readers are misconceptions about print concepts so basic teachers assume their students are aware of them. Many children fail to grasp implicit principles of print such as the following: the reader cannot make up the words, the order of letters within a word makes a difference, and each letter in a word must be considered.

Using brief vignettes from her work with beginning and struggling readers, the author draws attention to these often‐overlooked misconceptions. The author explains how she helped students overcome their faulty understandings by providing “rules” about reading, which enabled them to regulate their own reading.
ACCase-Inhibitor Herbicide Resistance in Downy Brome (Bromus tectorum) in Oregon
Authors: Ball Daniel A. , Frost Sandra M. , Bennett Larry H.
Published: February 2007

In spring 2005, a downy brome population with possible resistance to fluazifop-P, an acetyl-CoA carboxylase (ACCase) inhibitor (group 1) herbicide was found in a commercial creeping red fescue seed production field, near La Grande, OR, where fluazifop-P had been used to control downy brome repeatedly over 7 yr. Greenhouse experiments were conducted to confirm resistance to a number of group 1 herbicides. The suspected resistant downy brome accession was tested for resistance to fluazifop-P and tested for cross-resistance to other aryloxyphenoxy propionate (APP) and cyclohexanedione (CHD) herbicides, including quizalofop-P, sethoxydim, and clethodim. Data recorded included plant-mortality counts and biomass. Tests revealed that the La Grande downy brome accession was highly resistant to fluazifop-P and sethoxydim at all tested rates. The La Grande accession suffered no mortality from fluazifop-P or sethoxydim treatments up to the maximum tested rate of eight times (8×) the labeled recommendation. The La Grande accession was resistant to quizalofop-P and clethodim at the labeled rate or less but was susceptible to application rates higher than the labeled rate. The control downy brome accession was completely susceptible to fluazifop-P, quizalofop-P, and clethodim at all rates and exhibited increasing susceptibility with increasing sethoxydim rate. This pattern of cross-resistance differs from that of a previously reported case of ACCase resistance in downy brome.
Effect of Egyptian Broomrape (Orobanche aegyptiaca) Seed-Burial Depth on Parasitism Dynamics and Chemical Control in Tomato
Authors: Eizenberg Hanan , Lande Tal , Achdari Gay , Roichman Asia , Hershenhorn Joseph
Published: February 2007

Broomrapes (Orobanche spp.) are chlorophyll-lacking root parasites of many dicotyledonous species that cause severe damage to vegetables and field crops worldwide. Egyptian broomrape is common throughout Israel, where it parasitizes a wide range of crops. The main damage caused by this parasite is to processing tomatoes. The objectives of this study were to determine (1) the relationship between the parasitism process on tomato roots and Egyptian broomrape seed depth, and (2) the effect of herbicide application on Egyptian broomrape control at depths of 0 to 30 cm. The study was conducted in controlled conditions in 25-L pots containing soil that was artificially infested with Egyptian broomrape seeds. Seeds (1-cm layer) were infested at soil surface and at depths of 6, 12, 18, 24, and 30 cm. Sulfosulfuron was applied PRE to Egyptian broomrape shoots, 14 and 42 d after tomato planting. Egyptian broomrape emergence was highly correlated to the depth of the seed infestation: the deeper the seeds were buried, the more pronounced the delay in Egyptian broomrape emergence. A four-parameter sigmoid equation was found that describes the relationship between Egyptian broomrape parasitism and seed depth. No Egyptian broomrape shoots were observed aboveground when sulfosulfuron was applied on tomato foliage. However, live and dead attachments were observed at different levels in all seed-depth treatments. No significant difference in the efficacies of sulfosulfuron at rates of 37.5 and 75 ai ha−1 was observed at depths of 6, 12, and 18 cm. The best control was obtained at a depth of 6 cm at both sulfosulfuron rates. At depths of 24 and 30 cm, no broomrape control was achieved at 37.5 ai g ha−1 sulfosulfuron, and only low control efficacy was obtained at 75 ai g ha−1.
Southern Root-Knot Nematode (Meloidogyne incognita) Affects Common Cocklebur (Xanthium strumarium) Interference with Cotton
Authors: Webster Theodore M. , Davis Richard F.
Published: February 2007

Southern Root-Knot nematode and common cocklebur interfere with cotton growth and yield. A greater understanding of the interaction of these pests with cotton growth and yield is needed for effective integrated pest management (IPM). An additive design was used in outdoor microplots with five common cocklebur densities (0, 1, 2, 4, and 8 plants per plot) growing in competition with cotton, with and without the presence of southern Root-Knot nematode. Differences in cotton height could not be detected among common cocklebur densities or nematode presence at 3 wk after transplanting (WAT); however, differences in crop height were observed at 5 WAT between nematode treatments. In the absence of nematodes, the relationship between cotton yield loss and common cocklebur density was described by a rectangular hyperbolic regression model (P < 0.0001). Maximum yield loss from common cocklebur in the absence of nematodes exceeded 80%. In the presence of nematodes, there was a linear relationship between cotton yield loss and common cocklebur density (P = 0.0506). The presence of nematodes at each common cocklebur density increased cotton yield loss 15 to 35%. Common cocklebur plant biomass was 25% greater in nematode treatments, likely because of the reduced competitiveness of the cotton plants in these plots. This study demonstrates that multiple pests can interact to cause an additive reduction in crop yield.
Dipole‐Generated Unsaturated Flow in Gardner Soils
Authors: Kacimov Anvar
Published: February 2007

The Bystrov explicit analytical solution for viscous, low‐Reynolds number flow in layers of variable thickness is interpreted as infiltration in a Gardner homogeneous soil obstructed by a subterranean cavity, stone, or other obstacle. Mathematically, the two‐dimensional advection–dispersion equation for the Kirchhoff potential is solved by combination of a term responsible for incident unidirectional infiltration, and a term describing a dipole. Superposition results in a separatrix (a cavity or stone contour), outside of which streamlines are deflected from vertical lines, and constant potential (pressure, moisture content) lines demarcating lobe‐shaped domains. The physical impedance of the obstacle causes a buildup of moisture near the leading edge and a dry zone near the trailing edge of the obstacle. The criticality conditions of the model were also tested (i.e., that the moisture content in the flow domain is less than porosity but greater than zero).
Conceptual Models and Simulations for Biological Clogging in Unsaturated Soils
Authors: Mostafa M. , Van Geel P. J.
Published: February 2007

Biological clogging in unsaturated soils is an important concern in the design of biofilters that are used to treat wastewater in rural areas. Several conceptual models have been developed to simulate biological clogging in saturated flow systems but limited research has been performed to develop similar conceptual models in unsaturated soils. This study developed three conceptual models for biological clogging in unsaturated soils. The model formulations varied from microscale to macroscale and from analytically derived to empirical equations. They were all formulated based on the approaches proposed by Burdine and Mualem to estimate the relative permeability based on the effective water saturation and the soil moisture curve. A one‐dimensional unsaturated flow and transport code was developed, which incorporates Monod kinetics to simulate the biodegradation of an organic substrate. The three conceptual models that were developed relate the relative permeability to the microbial growth term in the unsaturated flow equation. The models were implemented in a numerical model to illustrate the impact of microbial growth on the biological clogging of unsaturated soils. Also the effect of continuous loading versus pulse loading was simulated to illustrate the difference between the loading scenarios on the clogging process within biofilters.
The Central Image (CI) in Recent Dreams, Dreams That Stand out, and Earliest Dreams: Relationship to Boundaries
Authors: Hartmann Ernest , Kunzendorf Robert G.
Published: February 2007

The CI (Central Image or Contextualizing Image) can be considered the emotional center of the dream. The CI can sometimes be seen as picturing the emotion behind the dream—as in the paradigmatic “Tidal Wave Dream.” The CI is the best-remembered part of the dream. CI Intensity, rated on a reliable scale, is higher after trauma, after 9/11/01, and in dreams considered “important” by the dreamer. In this study we examined CI Intensity, as well as “dream-likeness” and “bizarreness,” of recent dreams, dreams that stand out, and earliest dreams in 40 students, 20 who scored very “thick” and 20 who scored very “thin” on the short form of the Boundary Questionnaire. Results showed, first of all, that for the group as a whole, CI Intensity was rated higher in dreams that stand out, and in earliest dreams, than in recent dreams. “Thin” students had higher CI Intensity than “thick” students in recent dreams and dreams that stand out, but not in earliest dreams. In “dreams that stand out,” there was a significant positive correlation between CI Intensity and how long ago the dream had occurred. The same was true for bizarreness but not for dreamlikeness. There was a significant interaction between thick versus thin boundaries and earliest versus recent dreams: in the earliest dreams (generally reported as occurring at age 5–7) thick and thin students had equal CI Intensity, but in recent dreams (experienced usually at age 18–20) there was a great difference between the groups, thin students having a higher CI Intensity. This is consistent with the view that all children may start with fairly thin boundaries, but that some undergo more change (”thickening“) than others between age 6 and 18.