bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental-stage-specific regulation of the polyubiquitin receptors inDrosophila melanogaster
Authors: Lipinszki Zoltán , Kiss Petra , Pál Margit , Deák Péter , Szabó Áron , Hunyadi-Gulyas Eva , Klement Eva , Medzihradszky Katalin F. , Udvardy Andor
Published: August 2009

Recognition of polyubiquitylated substrates by the proteasome is a highly regulated process that requires polyubiquitin receptors. We show here that the concentrations of the proteasomal and extraproteasomal polyubiquitin receptors change in a developmentally regulated fashion. The stoichiometry of the proteasomal p54/Rpn10 polyubiquitin receptor subunit, relative to that of other regulatory particle (RP) subunits falls suddenly at the end of embryogenesis, remains low throughout the larval stages, starts to increase again in the late third instar larvae and remains high in the pupae, adults and embryos. A similar developmentally regulated fluctuation was observed in the concentrations of the Rad23 and Dsk2 extraproteasomal polyubiquitin receptors. Depletion of the polyubiquitin receptors at the end of embryogenesis is due to the emergence of a developmentally regulated selective proteolytic activity. To follow the fate of subunit p54/Rpn10 in vivo, transgenic Drosophila melanogaster lines encoding the N-terminal half (NTH), the C-terminal half (CTH) or the full-length p54/Rpn10 subunit were established in the inducible Gal4-UAS system. The daughterless-Gal4-driven whole-body expression of the full-length subunit or its NTH did not produce any detectable phenotypic changes, and the transgenic products were incorporated into the 26S proteasome. The transgene-encoded CTH was not incorporated into the 26S proteasome, caused third instar larval lethality and was found to be multi-ubiquitylated. This modification, however, did not appear to be a degradation signal because the half-life of the CTH was over 48 hours. Accumulation of the CTH disturbed the developmentally regulated changes in subunit composition of the RP and the emergence of the selective proteolytic activity responsible for the depletion of the polyubiquitin receptors. Build-up of subunit p54/Rpn10 in the RP had already started in 84-hour-old larvae and reached the full complement characteristic of the non-larval developmental stages at the middle of the third instar larval stage, just before these larvae perished. Similar shifts were observed in the concentrations of the Rad23 and Dsk2 polyubiquitin receptors. The postsynthetic modification of CTH might be essential for this developmental regulation, or it might regulate an essential extraproteasomal function(s) of subunit p54/Rpn10 that is disturbed by the expression of an excess of CTH.
Coronin 2A regulates a subset of focal-adhesion-turnover events through the cofilin pathway
Authors: Marshall Thomas W. , Aloor Heather L. , Bear James E.
Published: August 2009

Coronins are conserved F-actin-binding proteins that are important for motility and actin dynamics. Unlike type I coronins, coronin 2A localizes to stress fibers and some focal adhesions, and is excluded from the leading edge. Depletion of coronin 2A in MTLn3 cells decreases cell motility and turnover of focal adhesions. Surprisingly, none of the pathways known to regulate focal-adhesion turnover are affected by depletion of coronin 2A. Depletion of coronin 2A does, however, increase phospho-cofilin, suggesting that misregulation of cofilin might affect adhesion dynamics. Slingshot-1L, a cofilin-activating phosphatase, localizes to focal adhesions and interacts with coronin 2A. Depletion of coronin 2A reduces cofilin activity at focal adhesions, as measured by barbed-end density and actin FRAP. In both fixed cells and live cells, cofilin localizes to the proximal end of some focal adhesions. Although expression of wild-type cofilin in coronin-2A-depleted cells has no major effect on focal-adhesion dynamics, expression of an active mutant of cofilin bypasses the defects in cell motility and focal-adhesion disassembly. These results implicate both coronin 2A and cofilin as factors that can regulate a subset of focal-adhesion-turnover events.
Wear mechanisms of coated mixed-ceramic tools during finish hard turning of hot tool die steel
Authors: Dureja J S , Gupta V K , Sharma V S , Dogra M
Published: August 2009

The present study aims to investigate the wear mechanisms of a TiN-coated mixed ceramic tool prevalent under different machining conditions during hard turning of hot tool die steel. The different wear mechanisms observed are abrasion wear at low cutting speed, low feed rate, and highest work piece hardness; formation of protective layer and built-up edge (BUE) resulting from tribochemical reactions between constituents of tool and work piece material at moderate speed. High temperature accompanied by high cutting speed resulted in the removal of the protective layer and suppressed the BUE formation. Hard carbide particles of work material at a higher feed rate severely gouged the tool flank land. Chipping and brittle fractures were observed at very low and high depth of cut. Adhesion of work piece material followed by plastic deformation and notching was clearly visible at low work piece hardness.

The influence of cutting speed, feed rate, depth of cut, and work piece hardness on the progressive tool flank wear, and flank wear rate (VBr-μm/km) in the steady wear region was also analysed.
A direct route to the reciprocal Bennett linkage
Authors: Baker J E
Published: August 2009

The notion of reciprocity between screws is extended by Baker (2000) to put forward the concept of ‘reciprocal linkages’, those governed by screw systems that are mutually reciprocal. In that article, the 13 four-bars of Delassus, including the Bennett ‘isogram’, are so categorized. Presented here is an alternative means of defining the Bennett loop's reciprocal system and linkage, one based upon the chain's own geometrical properties rather than its principal screw system.
A comparative evaluation of compression ignition engine performance using preheated jatropha, karanja, and neem oils
Authors: Yadav A , Singh O
Published: August 2009

A steep rise worldwide in petroleum products and increased consumption have made the search for renewable sources, such as vegetable oils, biodiesels, alcohols from molasses/sugarcane, and so on, inevitable. In an agricultural economy-based country, there are lots of possibilities in the rural sector for improving the proper and efficient use of energy. Vegetable oils, being renewable, are widely available from a variety of sources and have low sulphur contents, being close to zero, and hence cause less environmental damage (lower greenhouse effect) than diesel. This article presents the results of tests using three non-edible oils, namely jatropha, karanja, and neem, at three different fuel injection temperatures in an unmodified small size compression ignition engine employing exhaust gas recirculation. Results show that oils at preheated temperatures can be a good substitute for conventional diesel fuel with a much smaller decrement in power and thermal efficiency in the case of engines without turbo charging.
Underwater sound radiation control by active vibration isolation: An experiment
Authors: Zhang Z , Huang X , Chen Y , Hua H
Published: August 2009

An experimental system, mainly including a rotary machine, four active vibration isolators and a water container, was established to investigate the role of active vibration isolation in suppressing vibration transmission as well as underwater sound radiation. Finite element analysis and experimental modal testing were employed to exhibit and validate vibration modes of the fluid-coupled structure and the radiated sound field in water. Sound field given by this validated finite element model is taken as the substitution for a real measurement. In the experiment, the fundamental frequency of the rotary machine was chosen to be nearly equal to a natural frequency of the coupled system in order to create a sound field in the water container by resonant structural vibration. The rotary machine is supported by the four electromagnetic vibration isolators, which suppress the quasi-periodical local vibration independently according to an adaptive control method. The measured results have demonstrated that low-frequency sound radiation can be reduced by local active vibration isolation.
Book Reviews
Authors: Lev Benjamin
Published: August 2009

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. However, we do not review software. To submit a book for review, please send it to me at the above address. Although we cannot review all books because of space limitations, we do list all books that we receive. We commission all book reviews and do not accept unsolicited reviews. To become a reviewer, please send me your name, address, and specific areas of expertise. We encourage readers to suggest books for review or to ask publishers to send copies of such books.

The authors or editors of books we review in this issue are Asvin Goel, David L. Olson, Dursun Delen, William B. Rouse, and Kenneth R. Boff.
People Skills: Implementing Strategic Goals—A Change Management Perspective
Authors: Levasseur Robert E.
Published: August 2009

This is another in a series of articles about some of the most effective models, methods, and processes of organization development (OD), also known as change management, a discipline that offers much to the OR/MS practitioner who is determined to help clients solve real-world problems. Because it is based on a systemic view of organizations, OD includes the whole universe of fuzzy people issues that increasingly determine the success or failure of efforts to implement otherwise flawless technical solutions. This article examines several options that the Institute for Operations Research and the Management Sciences (INFORMS) has for engaging the OR/MS community in the accomplishment of the organization's strategic objectives, called big audacious goals, as set forth by the INFORMS Strategic Planning Committee.
Optimization Helps Shermag Gain Competitive Edge
Authors: Ouhimmou Mustapha , D'Amours Sophie , Beauregard Robert , Ait-Kadi Daoud , Chauhan Satyaveer Singh
Published: August 2009

Shermag Inc. is a vertically integrated furniture company with business units across the supply chain from the forest to the final customer. During the last decade, Shermag has been losing market share to low-cost Asian manufacturers. To reduce the procurement and other significant costs of Shermag's raw material (wood), which constitute a major component of its total furniture cost, we developed a tool to optimize the tactical planning of the company's wood supply chain. We propose an optimization-based approach for coordinating operations at each echelon of the wood supply chain. However, the problem size caused computer-related issues, such as long processing times and computer crashes. In our proposed solution approach, we use decomposition to overcome these issues. Our implementation uses C++, CPLEX (optimization software), and Microsoft Access. In this paper, we present a comparative study of traditional decision making versus optimal decision making. Using Shermag data for 2004 and 2005, we show that our solution reduces total operations costs by more than 22 percent. For any set of parameters, the tool can generate a good, feasible solution. These results convinced Shermag to use our tool for future configurations of its supply chain network.
Sapropterin: A New Therapeutic Agent for Phenylketonuria
Authors: Hegge Karly A , Horning Kristin K , Peitz Gregory J , Hegge Kassy
Published: August 2009

Objective:

To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile of sapropterin for this indication.

Data Sources:

A literature search was conducted using MEDLINE (1966–May 2009), International Pharmaceutical Abstracts (1970–May 2009), and Cochrane database (2008) for the following key words: sapropterin, tetrahydrobiopterin, phenylketonurias, and phenylalanine.

Study Selection and Data Extraction:

English-language studies involving humans examining the role of tetrahydrobiopterin (BH4) in the management of PKU were reviewed to evaluate the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile for sapropterin. All Phase 2 and 3 randomized controlled trials assessing the safety and efficacy of sapropterin were included in this literature evaluation.

Data Synthesis:

Sapropterin represents the only Food and Drug Administration–approved medication for BH4-responsive PKU, marking an important advance in the treatment of this condition. Among individuals with hyperphenylalaninemia and some residual phenylalanine hydroxylase function, sapropterin can enhance activity of this enzyme to decrease serum phenylalanine concentrations. Sapropterin has been compared with placebo in one Phase 2 and one Phase 3 clinical trial, demonstrating significantly better response rates. Based on available studies, this agent appears to be safe and well tolerated, with adverse event rates similar to those of placebo. However, additional studies are warranted to assess the long-term safety and efficacy of sapropterin therapy.

Conclusions:

Sapropterin offers a promising therapeutic option for select individuals with BH4-responsive PKU, although long-term data are limited evaluating its safety and efficacy in traditional clinical practice settings. When considering sapropterin therapy, clinicians must consider factors such as cost and patient adherence to drug therapy and/or diet.
Correlated and Coupled Within-Person Change in Emotional and Behavioral Disturbance in Individuals With Intellectual Disability
Authors: Hofer Scott M. , Gray Kylie M. , Piccinin Andrea M. , Mackinnon Andrew , Bontempo Daniel E. , Einfeld Stewart L. , Hoffman Lesa , Parmenter Trevor , Tonge Bruce J.
Published: August 2009

Individual change and variation in emotional/behavioral disturbance in children and adolescents with intellectual disability has received little empirical investigation. Based on 11 years of longitudinal data from the Australian Child to Adult Development Study, we report associations among individual differences in level, rate of change, and occasion-specific variation across subscales of the Developmental Behavior Checklist (DBC) with 506 participants who had intellectual disability and were ages 5 to 19 years at study entry. Correlations among the five DBC subscales ranged from .43 to .66 for level, .43 to .88 for rate of change, and .31 to .61 for occasion-specific variation, with the highest correlations observed consistently between disruptive, self-absorbed, and communication disturbance behaviors. These interdependencies among dimensions of emotional/behavioral disturbance provide insight into the developmental dynamics of psychopathology from childhood through young adulthood.
Abnormal fMRI Activation Pattern During Story Listening in Individuals With Down Syndrome
Authors: Reynolds Losin Elizabeth A. , Rivera Susan M. , O'Hare Elizabeth D. , Sowell Elizabeth R. , Pinter Joseph D.
Published: August 2009

Down syndrome is characterized by disproportionately severe impairments of speech and language, yet little is known about the neural underpinnings of these deficits. We compared fMRI activation patterns during passive story listening in 9 young adults with Down syndrome and 9 approximately age-matched, typically developing controls. The typically developing group exhibited greater activation than did the Down syndrome group in classical receptive language areas (superior and middle temporal gyri) for forward > backward speech; the Down syndrome group exhibited greater activation in cingulate gyrus, superior and inferior parietal lobules, and precuneus for both forward speech > rest and backward speech > rest. The Down syndrome group showed almost no difference in activation patterns between the language (forward speech) and nonlanguage (backward speech) conditions.
The Effects of Cultural Values in Word-of-Mouth Communication
Authors: Lam Desmond , Lee Alvin , Mizerski Richard
Published: August 2009

When new products and brands are introduced into other cultures, the speed and extent of the product's acceptance are important concerns for marketers. The spread of positive word of mouth (WOM) and the lack of negative WOM about the product or brand by early adopter groups are critical to the product's successful diffusion in a population. This is the first study to investigate the effects of consumers’ cultural values on their WOM behavior. Data analysis from two samples indicates that the pattern, type, and target receivers of consumers’ WOM activity depend on their cultural values. The authors use Hofstede's four cultural dimensions to test the effects of cultural values on WOM behavior to social in- and out-groups. They find that all four dimensions have significant effects on WOM engagement to those groups. Although the authors could not determine the causal nature of the relationships because of the sample design used, they argue that marketers should monitor the cultural values of their market to anticipate in- and out-group discussions and the choice of appropriate brand communication strategies in other countries.
Brand-Specific Leadership: Turning Employees into Brand Champions
Authors: Morhart Felicitas M. , Herzog Walter , Tomczak Torsten
Published: August 2009

This article reports two studies on how managers can elicit brand-building behavior from frontline employees. Study 1 examines the mechanisms by which brand-specific transactional and transformational leadership influence employees’ brand-building behavior. The results from a survey of 269 customer-contact employees show that brand-specific transactional leaders influence followers through a process of compliance, leading to an increase in turnover intentions and a decrease in in-role and extra-role brand-building behaviors. In contrast, brand-specific transformational leaders influence followers through a process of internalization, leading to a decrease in turnover intentions and an increase in in-role and extra-role brand-building behaviors. In turn, both processes are mediated by employees’ perceptions of autonomy, competence, and relatedness with regard to their work roles as brand representatives. Moreover, the results show that brand-specific transactional leadership moderates the influence of brand-specific transformational leadership in a nonlinear, inverse U-shaped way, so that a medium level of transactional leadership maximizes the positive effects of transformational leadership. Study 2 addresses whether managers can learn brand-specific transformational leadership. A field experiment shows that brand-specific transformational leadership can indeed be learned through management training.
Marketing Alliances, Firm Networks, and Firm Value Creation
Authors: Swaminathan Vanitha , Moorman Christine
Published: August 2009

Prior research has found that the announcement of marketing alliances tends to produce no effect on firm value creation in a high-tech context. This article reexamines this issue and investigates whether the characteristics of a firm's network of alliances affect the firm value created from the announcement of a new marketing alliance. The authors investigate whether network centrality, network density, network efficiency, network reputation, and marketing alliance capability influence firm value creation. They examine this question using an event study of 230 announcements for marketing alliances in the software industry. The results indicate that, in general, marketing alliance announcements create value (i.e., abnormal stock returns) for the firm in the announcement period event window. Furthermore, network efficiency and network density have the strongest positive impact when they are moderate; network reputation and network centrality have no effect. These results point to the greater role of relational network characteristics than size-/status-based benefits. Finally, marketing alliance capability, which reflects a firm's ability to manage a network of previous marketing alliances, has a positive impact on value creation.
Effects of Word-of-Mouth versus Traditional Marketing: Findings from an Internet Social Networking Site
Authors: Trusov Michael , Bucklin Randolph E. , Pauwels Koen
Published: August 2009

The authors study the effect of word-of-mouth (WOM) marketing on member growth at an Internet social networking site and compare it with traditional marketing vehicles. Because social network sites record the electronic invitations from existing members, outbound WOM can be precisely tracked. Along with traditional marketing, WOM can then be linked to the number of new members subsequently joining the site (sign-ups). Because of the endogeneity among WOM, new sign-ups, and traditional marketing activity, the authors employ a vector autoregressive (VAR) modeling approach. Estimates from the VAR model show that WOM referrals have substantially longer carryover effects than traditional marketing actions and produce substantially higher response elasticities. Based on revenue from advertising impressions served to a new member, the monetary value of a WOM referral can be calculated; this yields an upper-bound estimate for the financial incentives the firm might offer to stimulate WOM.
Identification and Mode of Formation and Re-Solution of Sigma Phase in Austenitic Chromium-Nickel Steels
Authors: Dulis E. J. , Smith G. V.
Published: August 2009

A comprehensive investigation of the etching characteristics of the several phases occurring in austenitic stainless steels, supplemented by X-ray diffraction and magnetic permeability studies, has suggested procedures by which the sigma, carbide, and ferrite phases can be differentiated, with certain exceptions, under the microscope. The mode of formation and re-solution of sigma was observed, and transient formation of ferrite was detected during re-solution of sigma at a temperature above its stable range.
Sigma Phase in Several Cast Austenitic Steels
Authors: Malcolm V. T. , Low S.
Published: August 2009

Since there are many applications of modern piping systems that involve metal that will withstand temperatures up to 1750 F., producers of cast austenitic steel valves and fittings have been faced with the problem of structural stability of these castings when operated long periods of time at temperatures ranging from 1000 F. to 1750 F. Six materials commonly used for cast valves and fittings were investigated, three cast 18-8 alloys and three cast 16–35 alloys, with respect to the embrittling effect of the sigma phase after exposure to temperatures of 1000 F. to 1500 F. The chemical compositions of the materials tested are given in Table I. The embrittling effect was determined by means of keyhole notch Charpy impact testing at both room and elevated temperatures. Identification of the sigma phase was made by means of metallographic and X-ray diffraction techniques. The C9 and C9 + Mo material was annealed by water-quenching from 2100 F. The C9 + Cb material was annealed by air cooling from 1850 F. All the 16–35 type material was annealed by water quenching from 1950 F.
The Tetragonality of the Sigma Phase in the Iron-Chromium System
Authors: Menezes L. , Roros J. K. , Read T. A.
Published: August 2009

Single crystal specimens of the 50 per cent iron-50 per cent chromium sigma phase were prepared by isothermal transformation of coarse-grained ferrite of this composition at 775 C. In some cases, single grains of ferrite transformed to single crystals of sigma phase, which could then be isolated by careful fragmentation of the brittle sample. Back-reflection Laue diffraction patterns were prepared, and the specimen fragments selected which yielded the best patterns. These patterns revealed a four-fold symmetry axis and two two-fold axes orthogonal to it and to each other, characteristic of tetragonal crystals with the Laue symmetry 4/mmm. Even in the best samples, crystal imperfections existed which led to diffuseness and multiplicity of the Laue pattern spots.
Functional Coupling between mGluR1 and Cav3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines
Authors: Hildebrand Michael E. , Isope Philippe , Miyazaki Taisuke , Nakaya Toshitaka , Garcia Esperanza , Feltz Anne , Schneider Toni , Hescheler Jürgen , Kano Masanobu , Sakimura Kenji , Watanabe Masahiko , Dieudonné Stéphane , Snutch Terrance P.
Published: August 2009

T-type voltage-gated calcium channels are expressed in the dendrites of many neurons, although their functional interactions with postsynaptic receptors and contributions to synaptic signaling are not well understood. We combine electrophysiological and ultrafast two-photon calcium imaging to demonstrate that mGluR1 activation potentiates cerebellar Purkinje cell Cav3.1 T-type currents via a G-protein- and tyrosine-phosphatase-dependent pathway. Immunohistochemical and electron microscopic investigations on wild-type and Cav3.1 gene knock-out animals show that Cav3.1 T-type channels are preferentially expressed in Purkinje cell dendritic spines and colocalize with mGluR1s. We further demonstrate that parallel fiber stimulation induces fast subthreshold calcium signaling in dendritic spines and that the synaptic Cav3.1-mediated calcium transients are potentiated by mGluR1 selectively during bursts of excitatory parallel fiber inputs. Our data identify a new fast calcium signaling pathway in Purkinje cell dendritic spines triggered by short burst of parallel fiber inputs and mediated by T-type calcium channels and mGluR1s.
Robust Conjunctive Item–Place Coding by Hippocampal Neurons Parallels Learning What Happens Where
Authors: Komorowski Robert W. , Manns Joseph R. , Eichenbaum Howard
Published: August 2009

Previous research indicates a critical role of the hippocampus in memory for events in the context in which they occur. However, studies to date have not provided compelling evidence that hippocampal neurons encode event–context conjunctions directly associated with this kind of learning. Here we report that, as animals learn different meanings for items in distinct contexts, individual hippocampal neurons develop responses to specific stimuli in the places where they have differential significance. Furthermore, this conjunctive coding evolves in the form of enhanced item-specific responses within a subset of the preexisting spatial representation. These findings support the view that conjunctive representations in the hippocampus underlie the acquisition of context-specific memories.
Transient Receptor Potential Canonical 5 Channels Activate Ca2+/Calmodulin Kinase Iγ to Promote Axon Formation in Hippocampal Neurons
Authors: Davare Monika A. , Fortin Dale A. , Saneyoshi Takeo , Nygaard Sean , Kaech Stefanie , Banker Gary , Soderling Thomas R. , Wayman Gary A.
Published: August 2009

Functionality of neurons is dependent on their compartmentalized polarization of dendrites and an axon. The rapid and selective outgrowth of one neurite, relative to the others, to form the axon is critical in initiating neuronal polarity. Axonogenesis is regulated in part by an optimal intracellular calcium concentration. Our investigation of Ca2+-signaling pathways involved in axon formation using cultured hippocampal neurons demonstrates a role for Ca2+/calmodulin kinase kinase (CaMKK) and its downstream target Ca2+/calmodulin kinase I (CaMKI). Expression of constitutively active CaMKI induced formation of multiple axons, whereas blocking CaMKK or CaMKI activity with pharmacological, dominant-negative, or short hairpin RNA (shRNA) methods significantly inhibited axon formation. CaMKK signals via the γ-isoform of CaMKI as shRNA to CaMKIγ, but not the other CaMKI isoforms, inhibited axon formation. Furthermore, overexpression of wild-type CaMKIγ, but not a mutant incapable of membrane association, accelerated the rate of axon formation. Pharmacological or small interfering RNA inhibition of transient receptor potential canonical 5 (TRPC5) channels, which are present in developing axonal growth cones, suppressed CaMKK-mediated activation of CaMKIγ as well as axon formation. We demonstrate using biochemical fractionation and immunocytochemistry that CaMKIγ and TRPC5 colocalize to lipid rafts. These results are consistent with a model in which highly localized calcium influx through the TRPC5 channels activates CaMKK and CaMKIγ, which subsequently promote axon formation.
Ca Currents Activated by Spontaneous Firing and Synaptic Disinhibition in Neurons of the Cerebellar Nuclei
Authors: Zheng Nan , Raman Indira M.
Published: August 2009

In neurons of the cerebellar nuclei, long-term potentiation of EPSCs is induced by high-frequency synaptic excitation by mossy fibers followed by synaptic inhibition by Purkinje cells. Induction requires activation of synaptic receptors as well as voltage-gated Ca channels. To examine how Purkinje-mediated inhibition of nuclear neurons affects Ca levels during plasticity-inducing stimuli, we have combined electrophysiology, Ca imaging, and pharmacology of cerebellar nuclear neurons in mouse cerebellar slices. We find that spontaneous firing generates tonic Ca signals in both somata and dendrites, which drop during 500 ms, 100 Hz trains of Purkinje IPSPs or hyperpolarizing steps. Although the presence of low-voltage-activated (T-type) Ca channels in nuclear neurons has fostered the inference that disinhibition activates these channels, synaptic inhibition with a physiological chloride equilibrium potential (ECl) (−75 mV) fails to hyperpolarize neurons sufficiently for T-type channels to recover substantially. Consequently, after IPSPs, Ca signals return to baseline, although firing is accelerated by ∼20 Hz for ∼300 ms. Only after hyperpolarizations beyondECldoes Ca rise gradually beyond baseline, as firing further exceeds spontaneous rates. Cd2+(100 μm), which nearly eliminates L-type, N-type, P/Q-type, and R-type Ca currents while sparing approximately one-half the T-type current, prevents Ca changes during and after hyperpolarizations toECl. Thus, high-frequency IPSPs in cerebellar nuclear neurons evoke little postinhibitory current through T-type channels. Instead, inhibition regulates Ca levels simply by preventing action potentials, which usually permit Ca influx through high-voltage-activated channels. The decreases and restoration of Ca levels associated with Purkinje-mediated inhibition are likely to contribute to synaptic plasticity.
Krüppel-Like Factor 9 Is Necessary for Late-Phase Neuronal Maturation in the Developing Dentate Gyrus and during Adult Hippocampal Neurogenesis
Authors: Scobie Kimberly N. , Hall Benjamin J. , Wilke Scott A. , Klemenhagen Kristen C. , Fujii-Kuriyama Yoshiaki , Ghosh Anirvan , Hen René , Sahay Amar
Published: August 2009

The dentate gyrus (DG) is modified throughout life by integration of new adult-born neurons. Similarities in neuronal maturation during DG development and adult hippocampal neurogenesis suggest that genetically encoded intrinsic regulatory mechanisms underlying these temporally distinct processes are conserved and reused. Here, we identify a novel transcriptional regulator of dentate granule neuron maturation, Krüppel-like factor 9 (Klf-9). We show thatKlf-9expression is induced by neuronal activity and as dentate granule neurons functionally integrate in the developing and adult DG. During development, dentate granule neurons lackingKlf-9show delayed maturation as reflected by altered expression of early-phase markers, dendritic spine formation, and electrophysiological properties. AdultKlf-9-null mice exhibit normal stem cell proliferation and cell fate specification in the DG but show impaired differentiation of adult-born neurons and decreased neurogenesis-dependent synaptic plasticity. Behavioral analysis ofKlf-9-null mice revealed a subtle increase in anxiety-like behavior and an impairment in contextual fear discrimination learning. Thus, Klf-9 is necessary for late-phase maturation of dentate granule neurons both in DG development and during adult hippocampal neurogenesis. Klf-9-dependent neuronal maturation may therefore represent a candidate regulatory mechanism underlying these temporally distinct processes.
Motor Representations of Articulators Contribute to Categorical Perception of Speech Sounds
Authors: Möttönen Riikka , Watkins Kate E.
Published: August 2009

Listening to speech modulates activity in human motor cortex. It is unclear, however, whether the motor cortex has an essential role in speech perception. Here, we aimed to determine whether the motor representations of articulators contribute to categorical perception of speech sounds. Categorization of continuously variable acoustic signals into discrete phonemes is a fundamental feature of speech communication. We used repetitive transcranial magnetic stimulation (rTMS) to temporarily disrupt the lip representation in the left primary motor cortex. This disruption impaired categorical perception of artificial acoustic continua ranging between two speech sounds that differed in place of articulation, in that the vocal tract is opened and closed rapidly either with the lips or the tip of the tongue (/ba/–/da/ and /pa/–/ta/). In contrast, it did not impair categorical perception of continua ranging between speech sounds that do not involve the lips in their articulation (/ka/–/ga/ and /da/–/ga/). Furthermore, an rTMS-induced disruption of the hand representation had no effect on categorical perception of either of the tested continua (/ba/–da/ and /ka/–/ga/). These findings indicate that motor circuits controlling production of speech sounds also contribute to their perception. Mapping acoustically highly variable speech sounds onto less variable motor representations may facilitate their phonemic categorization and be important for robust speech perception.
Validation of Decision-Making Models and Analysis of Decision Variables in the Rat Basal Ganglia
Authors: Ito Makoto , Doya Kenji
Published: August 2009

Reinforcement learning theory plays a key role in understanding the behavioral and neural mechanisms of choice behavior in animals and humans. Especially, intermediate variables of learning models estimated from behavioral data, such as the expectation of reward for each candidate choice (action value), have been used in searches for the neural correlates of computational elements in learning and decision making. The aims of the present study are as follows: (1) to test which computational model best captures the choice learning process in animals and (2) to elucidate how action values are represented in different parts of the corticobasal ganglia circuit. We compared different behavioral learning algorithms to predict the choice sequences generated by rats during a free-choice task and analyzed associated neural activity in the nucleus accumbens (NAc) and ventral pallidum (VP). The major findings of this study were as follows: (1) modified versions of an action–value learning model captured a variety of choice strategies of rats, including win-stay–lose-switch and persevering behavior, and predicted rats' choice sequences better than the best multistep Markov model; and (2) information about action values and future actions was coded in both the NAc and VP, but was less dominant than information about trial types, selected actions, and reward outcome. The results of our model-based analysis suggest that the primary role of the NAc and VP is to monitor information important for updating choice behaviors. Information represented in the NAc and VP might contribute to a choice mechanism that is situated elsewhere.
Crystal and molecular structure of the saline complex hexaaquairon(II) hexachloroplatinate, [Fe(H2O)6][PtCl6]
Authors: Capobianchi Aldo , Campi Gaetano , Camalli Mercedes , Veroli Claudio
Published: August 2009

In this work the structure of a hexachloroplatinate of a bivalent metal as iron with the formula FePtCl6 · 6 H2O is reported. The crystal contains [PtCl6]2– and [Fe(H2O)6]2+ ions adopting a regular octahedral coordination. A 3D hydrogen bond framework takes part in the cohesion of the structure paking anions and cations in like-chain structures along the c-axis. The structure can also be regarded as alternating Fe and Pt atomic planes stacking along the 001 and 011 directions. Taking advantage from this Fe and Pt arrangement, we propose the hydrogen reduction of FePtCl6 · 6 H2O crystallites as a new chemical strategy in the fabrication of FePt nanoparticle-based functional devices for advanced nanomagnetic applications.
Responses to maternal GH or ractopamine during early–mid pregnancy are similar in primiparous and multiparous pregnant pigs
Authors: Gatford Kathryn L , De Blasio Miles J , Roberts Claire T , Nottle Mark B , Kind Karen L , van Wettere William H E J , Smits Robert J , Owens Julie A
Published: August 2009

Fetal growth is restricted in primiparous pigs (gilts) compared with dams who have had previous pregnancies (sows), as in other species. In gilts, daily maternal porcine GH (pGH) injections from day 25 to 50 of pregnancy (term ∼115 day) increase fetal growth and progeny muscularity, and responses in sows are unknown. Whether feeding the β2-adrenergic agonist ractopamine during this period increases progeny growth rates in either parity and fetal responses in gilts, have not been investigated. We hypothesised that fetal and placental growth and fetal muscle development would be increased more by maternal pGH and/or ractopamine during early–mid pregnancy in gilts than sows, since fetal growth is restricted in gilts causing lower birth weights. Large White×Landrace gilts and sows were injected daily with water (controls) or pGH (∼15 μg/kg per day), or were fed 20 ppm ractopamine, between day 25 and 50 of pregnancy. Maternal pGH increased litter average fetal weight (11%, P=0.007) and length (3%, P=0.022), but not placental weight, at day 50 of pregnancy, irrespective of parity, and had the greatest effects in the heaviest fetuses of each litter. Maternal ractopamine increased average fetal weight (9%, P=0.018), but not length. Muscle fiber diameter was increased by pGH in heavy littermates and by ractopamine in median littermates. Similar fetal growth responses to pGH and ractopamine in gilts and sows suggest that these hormones increase fetal nutrient availability similarly in both parities. We therefore predict that sustained pGH treatment will increase progeny birth weight, postnatal growth and survival, in both sows and gilts.
The bovine mammary gland expresses multiple functional isoforms of serotonin receptors
Authors: Hernandez Laura L , Limesand Sean W , Collier Jayne L , Horseman Nelson D , Collier Robert J
Published: August 2009

Recent studies in dairy cows have demonstrated that serotonergic ligands affect milk yield and composition. Correspondingly, serotonin (5-HT) has been demonstrated to be an important local regulator of lactational homeostasis and involution in mouse and human mammary cells. We determined the mRNA expression of bovine 5-HT receptor (HTR) subtypes in bovine mammary tissue (BMT) and used pharmacological agents to evaluate functional activities of 5-HT receptors. The mRNAs for five receptor isoforms (HTR1B, 2A, 2B, 4, and 7) were identified by conventional real-time (RT)-PCR, RT quantitative PCR, and in situ hybridization in BMT. In addition to luminal mammary epithelial cell expression, HTR4 was expressed in myoepithelium, and HTR1B, 2A, and 2B were expressed in small mammary blood vessels. Serotonin suppressed milk protein mRNA expression (α-lactalbumin and β-casein mRNA) in lactogen-treated primary bovine mammary epithelial cell (BMEC) cultures. To probe the functional activities of individual receptors, caspase-3 activity and expression of α-lactalbumin and β-casein were measured. Both SB22489 (1B antagonist) and ritanserin (2A antagonist) increased caspase-3 activity. Expression of α-lactalbumin and β-casein mRNA levels in BMEC were stimulated by low concentrations of SB224289, ritanserin, or pimozide. These results demonstrate that there are multiple 5-HT receptor isoforms in the bovine mammary gland, and point to profound differences between serotonergic systems of the bovine mammary gland and the human and mouse mammary glands. Whereas human and mouse mammary epithelial cells express predominately the protein for the 5-HT7 receptor, cow mammary epithelium expresses multiple receptors that have overlapping, but not identical, functional activities.
Assessment of trace organic chemical removal by a membrane bioreactor using gas chromatography/mass spectrometry and a yeast screen bioassay
Authors: Coleman Heather M. , Troester Martin , Khan Stuart J. , McDonald James A. , Watkins Graeme , Stuetz Richard M.
Published: August 2009

A membrane bioreactor (MBR) was assessed for the removal of estrogens, androgens, and a selection of pharmaceuticals and personal care products. The biomass and aqueous components of the MBR were investigated to determine whether removal was by biodegradation or by adsorption to the biomass. Removal was monitored using chemical analysis by gas chromatography/mass spectrometry (GC-MS) as well as biological analysis using estrogenic and androgenic yeast assays. Results showed that the MBR was effective in removing the compounds of concern from raw influent with removal rates between 78 and 99%. Removal efficiencies were comparable or better than those reported for conventional activated sludge systems, which was attributed to the relatively high sludge retention time of the MBR. The biomass component showed significant concentrations of salicylic acid, triclosan, and 4-tert-octylphenol. Estrogenic and androgenic activity was also measured in the biomass. Estrone was identified as the main compound responsible for the estrogenic activity. It was concluded that the main removal pathway was biodegradation, but sorption to biomass may also be important, particularly for triclosan and 4-tert-octylphenol.
Sorption of estrone and estrone-3-sulfate from CaCl2 solution and artificial urine in pastoral soils of New Zealand
Authors: Scherr Frank F. , Sarmah Ajit K. , Di Hong J. , Cameron Keith C.
Published: August 2009

Estrone (E1) and its sulfate conjugate estrone-3-sulfate (E1–3S) are released to the environment in animal wastes in significant amounts, and direct exposure occurs in grazed pasture systems. Both compounds have been shown to potentially contribute to endocrine disruption in wildlife, and knowledge about the sorption behavior of these compounds is necessary for a sound risk assessment. For labile compounds such as E1 and E1–3S, however, the standard protocols might overestimate sorption by not considering metabolite formation or allowing for equilibration that exceeds the commonly reported half-lives of these compounds. We therefore conducted modified batch sorption experiments with 0.005 M calcium chloride (CaCl2) and artificial urine solution to determine the influence of the mediator solution on the sorption of E1 and E1–3S in three pasture soils from New Zealand. Sorption isotherms of both compounds were nonlinear, and the Freundlich equation was found adequate to describe the isotherms. The sorption potential of E1–3S was about one order of magnitude lower than for the free counterpart, and the Kf values significantly changed between the two mediator solutions. The calculation of concentration-dependent effective distribution coefficients (Keffd) revealed that for a range of realistic exposure concentrations in a grazed dairy system, the common approach of using CaCl2 would deliver incorrect inferences for a sound risk assessment.
Severe Postpartum Gingival Enlargement
Authors: McLeod Dwight E. , Stoeckel Daniel , Contreras Juan , Reyes Elio
Published: August 2009

Background: Gingival enlargement is a clinical condition that has been widely studied and is directly associated with specific local or systemic conditions. It is very rare that gingival enlargement presents without a clear underlying etiology.

Methods: A 24‐year‐old African American female presented with gingival enlargement that manifested postpartum and was most likely related to changes in estrogen/progesterone. The gingival enlargement was treated with non‐surgical and surgical periodontal therapies.

Results: There was no evidence of recurrence of the gingival enlargement at 9 years post‐treatment.

Conclusions: The etiology in this case remains unclear and could not be strongly supported by any reports in the literature. Future studies on gingival enlargement may explain such an unusual clinical occurrence.
Ceruloplasmin Induces Polymorphonuclear Leukocyte Priming in Localized Aggressive Periodontitis
Authors: Iwata Tomoyuki , Kantarci Alpdogan , Yagi Motohiko , Jackson Tina , Hasturk Hatice , Kurihara Hidemi , Van Dyke Thomas E.
Published: August 2009

Background: Polymorphonuclear leukocytes (PMNs) from subjects with localized aggressive periodontitis (LAgP) present multiple functional abnormalities associated with a phenotypically primed PMN phenotype. Local inflammation is characterized by hypoxia, which leads to increased production of superoxide (O2−) by PMNs. Ceruloplasmin (CP) is also induced by hypoxia and inflammation. The aim of this study was to investigate the role of CP in O2− generation in PMNs from healthy subjects and patients with LAgP.

Methods: PMNs were isolated from healthy subjects and those with LAgP (N = 36). Superoxide was measured by cytochrome‐C reduction at 550 nm. Intracellular CP expression was analyzed by real‐time polymerase chain reaction and Western blotting. Serum levels of CP were measured by enzyme‐linked immunosorbent assay. Intracellular iron ion conversion was spectrophotometrically determined by measuring the absorbance of σ‐phenanthroline at 510 nm.

Results: O2− generation was significantly higher in LAgP PMNs before and after stimulation with formyl‐methionyl‐leucyl‐phenylalanine (100 nM). CP expression in PMNs and CP levels in serum were significantly higher in subjects with LAgP compared to the PMNs and serum samples from matched healthy donors (P <0.05). LAgP PMNs also had significantly higher levels of Fe3+ and lower levels of Fe2+ compared to healthy PMNs (P <0.05), suggesting increased iron conversion. Exogenous CP treatment of healthy PMNs resulted in significant increases in O2− generation and iron ion conversion similar to LAgP PMNs.

Conclusion: LAgP PMNs are primed to express higher levels of CP, leading to hypoxia‐mediated O2− generation in PMNs and increased oxidative stress and neutrophil‐mediated tissue injury in LAgP.