bluuebunny/crossref_metadata_2025 huggingface dataset:
In-Depth Investigation of the Soybean Seed-Filling Proteome and Comparison with a Parallel Study of Rapeseed
Authors: Agrawal Ganesh Kumar , Hajduch Martin , Graham Katherine , Thelen Jay J.
Published: July 2008

To better understand the metabolic processes of seed filling in soybean (Glycine max), two complementary proteomic approaches, two-dimensional gel electrophoresis (2-DGE) and semicontinuous multidimensional protein identification technology (Sec-MudPIT) coupled with liquid chromatography-mass spectrometry, were employed to analyze whole seed proteins at five developmental stages. 2-DGE and Sec-MudPIT analyses collectively identified 478 nonredundant proteins with only 70 proteins common to both datasets. 2-DGE data revealed that 38% of identified proteins were represented by multiple 2-DGE species. Identified proteins belonged to 13 (2-DGE) and 15 (Sec-MudPIT) functional classes. Proteins involved in metabolism, protein destination and storage, and energy were highly represented, collectively accounting for 61.1% (2-DGE) and 42.2% (Sec-MudPIT) of total identified proteins. Membrane proteins, based upon transmembrane predictions, were 3-fold more prominent in Sec-MudPIT than 2-DGE. Data were integrated into an existing soybean proteome database (www.oilseedproteomics.missouri.edu). The integrated quantitative soybean database was compared to a parallel study of rapeseed (Brassica napus) to further understand the regulation of intermediary metabolism in protein-rich versus oil-rich seeds. Comparative analyses revealed (1) up to 3-fold higher expression of fatty acid biosynthetic proteins during seed filling in rapeseed compared to soybean; and (2) approximately a 48% higher number of protein species and a net 80% higher protein abundance for carbon assimilatory and glycolytic pathways leading to fatty acid synthesis in rapeseed versus soybean. Increased expression of glycolytic and fatty acid biosynthetic proteins in rapeseed compared to soybean suggests that a possible mechanistic basis for higher oil in rapeseed involves the concerted commitment of hexoses to glycolysis and eventual de novo fatty acid synthesis pathways.
AGL61 Interacts with AGL80 and Is Required for Central Cell Development in Arabidopsis
Authors: Steffen Joshua G. , Kang Il-Ho , Portereiko Michael F. , Lloyd Alan , Drews Gary N.
Published: July 2008

The central cell of the female gametophyte plays a role in pollen tube guidance and in regulating the initiation of endosperm development. Following fertilization, the central cell gives rise to the seed's endosperm, which nourishes the developing embryo within the seed. The molecular mechanisms controlling specification and differentiation of the central cell are poorly understood. We identified AGL61 in a screen for transcription factor genes expressed in the female gametophyte. AGL61 encodes a Type I MADS domain protein, which likely functions as a transcription factor. Consistent with this, an AGL61-green fluorescent protein fusion protein is localized to the nucleus. In the context of the ovule and seed, AGL61 is expressed exclusively in the central cell and early endosperm. agl61 female gametophytes are affected in the central cell specifically. The morphological defects include an overall reduction in size of the central cell and a reduced or absent central cell vacuole. When fertilized with wild-type pollen, agl61 central cells fail to give rise to endosperm. In addition, synergid- and antipodal-expressed genes are ectopically expressed in agl61 central cells. The expression pattern and mutant phenotype of AGL61 are similar to those of AGL80, suggesting that AGL61 may function as a heterodimer with AGL80 within the central cell; consistent with this, AGL61 and AGL80 interact in yeast two-hybrid assays. Together, these data suggest that AGL61 functions as a transcription factor and controls the expression of downstream genes during central cell development.
A Role for a Menthone Reductase in Resistance against Microbial Pathogens in Plants
Authors: Choi Hyong Woo , Lee Byung Gil , Kim Nak Hyun , Park Yong , Lim Chae Woo , Song Hyun Kyu , Hwang Byung Kook
Published: July 2008

Plants elaborate a vast array of enzymes that synthesize defensive secondary metabolites in response to pathogen attack. Here, we isolated the pathogen-responsive CaMNR1 [menthone: (+)-(3S)-neomenthol reductase] gene, a member of the short-chain dehydrogenase/reductase (SDR) superfamily, from pepper (Capsicum annuum) plants. Gas chromatography-mass spectrometry analysis revealed that purified CaMNR1 and its ortholog AtSDR1 from Arabidopsis (Arabidopsis thaliana) catalyze a menthone reduction with reduced nicotinamide adenine dinucleotide phosphate as a cofactor to produce neomenthol with antimicrobial activity. CaMNR1 and AtSDR1 also possess a significant catalytic activity for neomenthol oxidation. We examined the cellular function of the CaMNR1 gene by virus-induced gene silencing and ectopic overexpression in pepper and Arabidopsis plants, respectively. CaMNR1-silenced pepper plants were significantly more susceptible to Xanthomonas campestris pv vesicatoria and Colletotrichum coccodes infection and expressed lower levels of salicylic acid-responsive CaBPR1 and CaPR10 and jasmonic acid-responsive CaDEF1. CaMNR1-overexpressing Arabidopsis plants exhibited enhanced resistance to the hemibiotrophic pathogen Pseudomonas syringae pv tomato DC3000 and the biotrophic pathogen Hyaloperonospora parasitica isolate Noco2, accompanied by the induction of AtPR1 and AtPDF1.2. In contrast, mutation in the CaMNR1 ortholog AtSDR1 significantly enhanced susceptibility to both pathogens. Together, these results indicate that the novel menthone reductase gene CaMNR1 and its ortholog AtSDR1 positively regulate plant defenses against a broad spectrum of pathogens.
Arabidopsis Mitogen-Activated Protein Kinase Kinases MKK1 and MKK2 Have Overlapping Functions in Defense Signaling Mediated by MEKK1, MPK4, and MKS1
Authors: Qiu Jin-Long , Zhou Lu , Yun Byung-Wook , Nielsen Henrik Bjørn , Fiil Berthe Katrine , Petersen Klaus , MacKinlay Jim , Loake Gary J. , Mundy John , Morris Peter C.
Published: July 2008

The Arabidopsis (Arabidopsis thaliana) MKK1 and MKK2 mitogen-activated protein kinase kinases have been implicated in biotic and abiotic stress responses as part of a signaling cascade including MEKK1 and MPK4. Here, the double loss-of-function mutant (mkk1/2) of MKK1 and MKK2 is shown to have marked phenotypes in development and disease resistance similar to those of the single mekk1 and mpk4 mutants. Because mkk1 or mkk2 single mutants appear wild type, basal levels of MPK4 activity are not impaired in them, and MKK1 and MKK2 are in part functionally redundant in unchallenged plants. These findings are confirmed and extended by biochemical and molecular analyses implicating the kinases in jasmonate- and salicylate-dependent defense responses, mediated in part via the MPK4 substrate MKS1. In addition, transcriptome analyses delineate overlapping and specific effects of the kinases on global gene expression patterns demonstrating both redundant and unique functions for MKK1 and MKK2.
Comparative Proteomics of Chloroplast Envelopes from C3 and C4 Plants Reveals Specific Adaptations of the Plastid Envelope to C4 Photosynthesis and Candidate Proteins Required for Maintaining C4 Metabolite Fluxes
Authors: Bräutigam Andrea , Hoffmann-Benning Susanne , Weber Andreas P.M.
Published: July 2008

C4 plants have up to 10-fold higher apparent CO2 assimilation rates than the most productive C3 plants. This requires higher fluxes of metabolic intermediates across the chloroplast envelope membranes of C4 plants in comparison with those of C3 plants. In particular, the fluxes of metabolites involved in the biochemical inorganic carbon pump of C4 plants, such as malate, pyruvate, oxaloacetate, and phosphoenolpyruvate, must be considerably higher in C4 plants because they exceed the apparent rate of photosynthetic CO2 assimilation, whereas they represent relatively minor fluxes in C3 plants. While the enzymatic steps involved in the C4 biochemical inorganic carbon pump have been studied in much detail, little is known about the metabolite transporters in the envelope membranes of C4 chloroplasts. In this study, we used comparative proteomics of chloroplast envelope membranes from the C3 plant pea (Pisum sativum) and mesophyll cell chloroplast envelopes from the C4 plant maize (Zea mays) to analyze the adaptation of the mesophyll cell chloroplast envelope proteome to the requirements of C4 photosynthesis. We show that C3- and C4-type chloroplasts have qualitatively similar but quantitatively very different chloroplast envelope membrane proteomes. In particular, translocators involved in the transport of triosephosphate and phosphoenolpyruvate as well as two outer envelope porins are much more abundant in C4 plants. Several putative transport proteins have been identified that are highly abundant in C4 plants but relatively minor in C3 envelopes. These represent prime candidates for the transport of C4 photosynthetic intermediates, such as pyruvate, oxaloacetate, and malate.
Before Your Very Eyes: Illness, Agency, and the Management of Tourette Syndrome
Authors: Buckser Andrew
Published: July 2008

In this article, I examine the ways that people with Tourette Syndrome (TS) manage the motor and vocal tics characteristic of this neurological disorder. To mitigate the powerful stigmas associated with TS, individuals must either remove tics from public view or strive to recast the way that they are perceived. Drawing on ethnographic research with TS sufferers in Indiana, I elaborate three strategies by which this is done, strategies referred to here as displacement, misattribution, and contextualization. These processes strongly affect both the symptoms themselves and the subjective experience of the illness. They also affect the perception of TS in the larger culture, associating the disease with florid symptoms like cursing—symptoms that, although not at all typical of TS, are the ones most resistant to these kinds of management. These patterns highlight how individual agency may actively shape the cultural construction of illness.
Pontine respiratory‐modulated activity before and after vagotomy in decerebrate cats
Authors: Dick Thomas E. , Shannon Roger , Lindsey Bruce G. , Nuding Sarah C. , Segers Lauren S. , Baekey David M. , Morris Kendall F.
Published: July 2008

The dorsolateral (DL) pons modulates the respiratory pattern. With the prevention of lung inflation during central inspiratory phase (no‐inflation (no‐I or delayed‐I) tests), DL pontine neuronal activity increased the strength and consistency of its respiratory modulation, properties measured statistically by the η2 value. This increase could result from enhanced respiratory‐modulated drive arising from the medulla normally gated by vagal activity. We hypothesized that DL pontine activity during delayed‐I tests would be comparable to that following vagotomy. Ensemble recordings of neuronal activity were obtained before and after vagotomy and during delayed‐I tests in decerebrate, paralysed and ventilated cats. In general, changes in activity pattern during the delayed‐I tests were similar to those after vagotomy, with the exception of firing‐rate differences at the inspiratory–expiratory phase transition. Even activity that was respiratory‐modulated with the vagi intact became more modulated while withholding lung inflation and following vagotomy. Furthermore, we recorded activity that was excited by lung inflation as well as changes that persisted past the stimulus cycle. Computer simulations of a recurrent inhibitory neural network model account not only for enhanced respiratory modulation with vagotomy but also the varied activities observed with the vagi intact. We conclude that (a) DL pontine neurones receive both vagal‐dependent excitatory inputs and central respiratory drive; (b) even though changes in pontine activity are transient, they can persist after no‐I tests whether or not changes in the respiratory pattern occur in the subsequent cycles; and (c) models of respiratory control should depict a recurrent inhibitory circuitry, which can act to maintain the stability and provide plasticity to the respiratory pattern.
Bidirectional long‐term motor cortical plasticity and metaplasticity induced by quadripulse transcranial magnetic stimulation
Authors: Hamada Masashi , Terao Yasuo , Hanajima Ritsuko , Shirota Yuichiro , Nakatani‐Enomoto Setsu , Furubayashi Toshiaki , Matsumoto Hideyuki , Ugawa Yoshikazu
Published: July 2008

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising tool to induce plastic changes that are thought in some cases to reflect N‐methyl‐d‐aspartate‐sensitive changes in synaptic efficacy. As in animal experiments, there is some evidence that the sign of rTMS‐induced plasticity depends on the prior history of cortical activity, conforming to the Bienenstock–Cooper–Munro (BCM) theory. However, experiments exploring these plastic changes have only examined priming‐induced effects on a limited number of rTMS protocols, often using designs in which the priming alone had a larger effect than the principle conditioning protocol. The aim of this study was to introduce a new rTMS protocol that gives a broad range of after‐effects from suppression to facilitation and then test how each of these is affected by a priming protocol that on its own has no effect on motor cortical excitability, as indexed by motor‐evoked potential (MEP). Repeated trains of four monophasic TMS pulses (quadripulse stimulation: QPS) separated by interstimulus intervals of 1.5–1250 ms produced a range of after‐effects that were compatible with changes in synaptic plasticity. Thus, QPS at short intervals facilitated MEPs for more than 75 min, whereas QPS at long intervals suppressed MEPs for more than 75 min. Paired‐pulse TMS experiments exploring intracortical inhibition and facilitation after QPS revealed effects on excitatory but not inhibitory circuits of the primary motor cortex. Finally, the effect of priming protocols on QPS‐induced plasticity was consistent with a BCM‐like model of priming that shifts the crossover point at which synaptic plasticity reverses from depression to potentiation. The broad range of after‐effects produced by the new rTMS protocol opens up new possibilities for detailed examination of theories of metaplasticity in humans.
c‐Src tyrosine kinase, a critical component for 5‐HT2Areceptor‐mediated contraction in rat aorta
Authors: Lu Rong , Alioua Abderrahmane , Kumar Yogesh , Kundu Pallob , Eghbali Mansoureh , Weisstaub Noelia V. , Gingrich Jay A. , Stefani Enrico , Toro Ligia
Published: July 2008

Serotonin (5‐hydroxytryptamine, 5‐HT) receptors (5‐HTRs) play critical roles in brain and cardiovascular functions. In the vasculature, 5‐HT induces potent vasoconstrictions, which in aorta are mainly mediated by activation of the 5‐HT2AR subtype. We previously proposed that one signalling mechanism of 5‐HT‐induced vasoconstriction could be c‐Src, a member of the Src tyrosine kinase family. We now provide evidence for a central role of c‐Src in 5‐HT2AR‐mediated contraction. Inhibition of Src kinase activity with 10 μm4‐amino‐5‐(4‐chlorophenyl)‐7‐(t‐butyl)pyrazolo[3,4‐d]pyrimidine (PP2) prior to contraction resulted in ∼90–99% inhibition of contractions induced by 5‐HT or by α‐methyl‐5‐HT (5‐HT2R agonist). In contrast, PP2 pretreatment only partly inhibited contractions induced by angiotensin II and the thromboxane A2mimetic, U46619, and had no significant action on phenylephrine‐induced contractions. 5‐Hydroxytryptamine increased Src kinase activity and PP2‐sensitive tyrosine‐phosphorylated proteins. As expected for c‐Src identity, PP2 pretreatment inhibited 5‐HT‐induced contraction with an IC50of ∼1 μm. Ketanserin (10 nm), a 5‐HT2Aantagonist, but not antagonists of 5‐HT2BR (100 nmSB204741) or 5‐HT2CR (20 nmRS102221), prevented 5‐HT‐induced contractions, mimicking PP2 and implicating 5‐HT2AR as the major receptor subtype coupled to c‐Src. In HEK 293T cells, c‐Src and 5‐HT2AR were reciprocally co‐immunoprecipitated and co‐localized at the cell periphery. Finally, 5‐HT‐induced Src activity was unaffected by inhibition of Rho kinase, supporting a role of c‐Src upstream of Rho kinase. Together, the results highlight c‐Src activation as one of the early and pivotal mechanisms in 5‐HT2AR contractile signalling in aorta.
Peripheral sensory activation of cortical circuits in the leg motor cortex of man
Authors: Roy François D. , Gorassini Monica A.
Published: July 2008

Peripheral sensory afferents in the hand activate both excitatory and inhibitory intracortical circuits to potentially facilitate and prune descending motor commands. In this study, we characterized how afferent inputs modulate the excitability of cortical circuits in the leg area of the primary motor cortex by examining how stimulation of the tibial nerve (TN) at the ankle alters motor evoked potentials (MEPs) activated by transcranial magnetic stimulation (TMS). Resting MEPs in the tibialis anterior (TA) muscle were facilitated in response to heteronymous activation of the TN 45–50 ms earlier, whereas MEPs were inhibited at interstimulus intervals of 32.5–37.5 ms. Similar time‐dependent modulation occurred in the soleus (SOL) muscle with stimulation of the homonymous posterior tibial nerve (PTN) at the knee. To determine the site of this afferent‐evoked facilitation and inhibition (spinal or cortical), we compared the effects of afferent stimulation to responses evoked at subcortical sites. At interstimulus intervals where MEP facilitation was observed (near 50 ms), spinal H‐reflexes and responses evoked from corticospinal tract stimulation at the brainstem were predominantly depressed by the sensory stimulus suggesting that the observed MEP facilitation was cortical in origin. At interstimulus intervals where MEP depression was observed (near 35 ms), brainstem evoked responses were depressed to a similar degree and, in contrast to the hand, this suggests that spinal rather than cortical circuits mediate short‐latency afferent inhibition (SAI) of leg MEPs. When the MEP was facilitated by afferent inputs, short‐interval intracortical inhibition (SICI) was reduced and intracortical facilitation (ICF) was increased, but long‐interval intracortical inhibition (LICI) at a 100 ms interval was unchanged. In addition, sensory excitation increased the recruitment of early, middle and late descending corticospinal volleys as evidenced from increases in MEP facilitation at the corresponding I‐wave periodicity. We propose that sensory activation from the leg has a diffuse and predominantly facilitatory effect on the leg primary motor cortex.
Human solute carrier SLC6A14 is the β‐alanine carrier
Authors: Anderson Catriona M. H. , Ganapathy Vadivel , Thwaites David T.
Published: July 2008

The β‐alanine carrier was characterized functionally in the 1960s to 1980s at the luminal surface of the ileal mucosal wall and is a Na+‐ and Cl−‐dependent transporter of a number of essential and non‐essential cationic and dipolar amino acids including lysine, arginine and leucine. β‐Alanine carrier‐like function has not been demonstrated by any solute carrier transport system identified at the molecular level. A series of experiments were designed to determine whether solute carrier SLC6A14 is the molecular correlate of the intestinal β‐alanine carrier, perhaps the last of the classical intestinal amino acid transport systems to be identified at the molecular level. Following expression of the human SLC6A14 transporter in Xenopus laevis oocytes, the key functional characteristics of the β‐alanine carrier, identified previously in situ in ileum, were demonstrated for the first time. The transport system is both Na+ and Cl− dependent, can transport non‐α‐amino acids such as β‐alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine. N‐methylation of its substrates reduces the affinity for transport. These observations confirm the hypothesis that the SLC6A14 gene encodes the transport protein known as the β‐alanine carrier which, due to its broad substrate specificity, is likely to play an important role in absorption of essential nutrients and drugs in the distal regions of the human gastrointestinal tract.
Paroxysmal extreme pain disorder mutations within the D3/S4–S5 linker of Nav1.7 cause moderate destabilization of fast inactivation
Authors: Jarecki Brian W. , Sheets Patrick L. , Jackson James O. , Cummins Theodore R.
Published: July 2008

Single‐point missense mutations in the peripheral neuronal voltage‐gated sodium channel Nav1.7 are implicated in the painful inherited neuropathy paroxysmal extreme pain disorder (PEPD). The Nav1.7 PEPD mutations are located in regions of the channel suggested to play important roles in fast inactivation. PEPD mutations in the putative inactivation gate have been reported to significantly impair fast inactivation, resulting in pronounced persistent currents. However, PEPD mutations in the S4–S5 linker of domain 3 (D3/S4–S5) had not been characterized and the roles of specific residues in this linker in channel gating are unclear. We functionally characterized two of the D3/S4–S5 PEPD mutations (V1298F and V1299F) and compared their effects on gating to an adjacent non‐PEPD mutation (V1300F) and the I1461T PEPD mutation, located in the putative inactivation gate. The primary effect of the V1298F and V1299F mutations is to shift the voltage dependence of fast inactivation by ∼20 mV in the depolarizing direction. We observed a similar effect with the PEPD mutation I1461T. Interestingly, while all three PEPD mutations increased persistent currents, the relative amplitudes (∼6% of peak) were much smaller than previously reported for the I1461T mutation. In contrast, the main effect of the V1300F mutation was a depolarizing shift in the voltage dependence of activation. These data demonstrate that (1) mutations within D3/S4–S5 affect inactivation of Nav1.7 in a residue‐specific manner and (2) disruption of the fast‐inactivated state by PEPD mutations can be more moderate than previously indicated, which has important implications for the pathophysiology of PEPD.
Dynamic contrast change produces rapid gain control in visual cortex
Authors: Crowder N. A. , Hietanen M. A. , Price N. S. C. , Clifford C. W. G. , Ibbotson M. R.
Published: July 2008

During normal vision, objects moving in the environment, our own body movements and our eye movements ensure that the receptive fields of visual neurons are being presented with continually changing contrasts. Thus, the visual input during normal behaviour differs from the type of stimuli traditionally used to study contrast coding, which are presented in a step‐like manner with abrupt changes in contrast followed by prolonged exposure to a constant stimulus. The abrupt changes in contrast typically elicit brief periods of intense firing with low variability called onset transients. Onset transients provide the visual system with a powerful and reliable cue that the visual input has changed. In this paper we investigate visual processing in the primary visual cortex of cats in response to stimuli that change contrast dynamically. We show that 1–4 s presentations of dynamic increases and decreases in contrast can generate stronger contrast gain control than several minutes exposure to a stimulus of constant contrast. Thus, transient mechanisms of contrast coding are not only less variable than sustained responses but are also more rapid and flexible. Finally, we propose a quantitative model of contrast coding which accounts for changes in spike rate over time in response to dynamically changing image contrast.
Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans
Authors: Lundbye‐Jensen Jesper , Nielsen Jens Bo
Published: July 2008

Neural plasticity occurs throughout adult life in response to maturation, use and disuse. Recent studies have documented that H‐reflex amplitudes increase following a period of immobilization. To elucidate the mechanisms contributing to the increase in H‐reflex size following immobilization we immobilized the left foot and ankle joint for 2 weeks in 12 able‐bodied subjects. Disynaptic reciprocal inhibition of soleus (SOL) motoneurons and presynaptic control of SOL group Ia afferents was measured before and after the immobilization as well as following 2 weeks of recovery. Following immobilization, maximal voluntary plantar‐ and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H‐reflex amplitude increased with no changes in the maximal compound motor response (Mmax). Decreased presynaptic inhibition of the Ia afferents probably contributed to the increase of the H‐reflex size, since we observed a significant decrease in the long‐latency depression of the SOL H‐reflex evoked by peroneal nerve stimulation (D2 inhibition) and an increase in the size of the monosynaptic Ia facilitation of the SOL H‐reflex evoked by femoral nerve stimulation. These two measures provide independent evidence of changes in presynaptic inhibition of SOL Ia afferents and taken together suggest that GABAergic presynaptic inhibition of the SOL Ia afferents is decreased following 2 weeks of immobilization. The depression of the SOL H‐reflex when evoked at intervals shorter than 10 s (homosynaptic post‐activation depression) also decreased following immobilization, suggesting that the activity‐dependent regulation of transmitter release from the afferents was also affected by immobilization. We observed no significant changes in disynaptic reciprocal Ia inhibition. Two weeks after cast removal measurements returned to pre‐immobilization levels. Together, these observations suggest that disuse causes plastic changes in spinal interneuronal circuitries responsible for presynaptic control of sensory input to the spinal cord. This may be of significance for the motor disabilities seen following immobilization as well as the development of spasticity following central motor lesions.
Mechanisms by which atrial fibrillation‐associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels
Authors: Restier Lioara , Cheng Lan , Sanguinetti Michael C.
Published: July 2008

The slow delayed rectifier K+ current (IKs) is a major determinant of action potential repolarization in the heart. IKs channels are formed by coassembly of pore‐forming KCNQ1 α‐subunits and ancillary KCNE1 β‐subunits. Two gain of function mutations in KCNQ1 subunits (S140G and V141M) have been associated with atrial fibrillation (AF). Previous heterologous expression studies found that both mutations caused IKs to be instantaneously activated, presumably by preventing channel closure. The purpose of this study was to refine our understanding of the channel gating defects caused by these two mutations located in the S1 domain of KCNQ1. Site‐directed mutagenesis was used to replace S140 or V141 with several other natural amino acids. Wild‐type and mutant channels were heterologously expressed in Xenopus oocytes and channel function was assessed with the two‐microelectrode voltage clamp technique. Long intervals between voltage clamp pulses revealed that S140G and V141M KCNQ1‐KCNE1 channels are not constitutively active as previously reported, but instead exhibit extremely slow deactivation. The slow component of IKs deactivation was decreased 62‐fold by S140G and 140‐fold by the V141M mutation. In addition, the half‐point for activation of these mutant IKs channels was ∼50 mV more negative than wild‐type channels. Other substitutions of S140 or V141 in KCNQ1 caused variable shifts in the voltage dependence of activation, but slowed IKs deactivation to a much lesser extent than the AF‐associated mutations. Based on a published structural model of KCNQ1, S140 and V141 are located near E160 in S2 and R237 in S4, two charged residues that could form a salt bridge when the channel is in the open state. In support of this model, mutational exchange of E160 and R237 residues produced a constitutively open channel. Together our findings suggest that altered charge‐pair interactions within the voltage sensor module of KCNQ1 subunits may account for slowed IKs deactivation induced by S140 or V141.
Interdependent roles for hypoxia inducible factor and nuclear factor‐κB in hypoxic inflammation
Authors: Taylor Cormac T.
Published: July 2008

Decreased oxygen availability (hypoxia) is a hallmark feature of the microenvironment in a number of chronic inflammatory conditions including arthritis and inflammatory bowel disease (IBD). Recent advances in our understanding of oxygen‐dependent cell signalling have uncovered several mechanisms by which hypoxia impacts upon the development of inflammation through the coordinated expression of adaptive, inflammatory and apoptotic genes. Two central transcription factors involved in the regulation of this response are hypoxia inducible factor (HIF) and nuclear factor‐κB (NF‐κB) which display different degrees of sensitivity to activation during hypoxia. Furthermore, HIF and NF‐κB demonstrate an intimate interdependence at several mechanistic levels. Recent studies indicate that these pathways may represent important new therapeutic targets in diseases characterized by hypoxic inflammation.
ON THE POWER EFFICIENCY OF CASCODE COMPENSATION OVER MILLER COMPENSATION IN TWO-STAGE OPERATIONAL AMPLIFIERS
Authors: AMINZADEH HAMED , LOTFI REZA
Published: July 2008

Optimization of power consumption is one of the main design challenges in today's low-power high-speed analog integrated circuits. In this paper, two popular techniques to stabilize two-stage operational amplifiers, namely, Miller and cascode compensations are compared from power efficiency point of view. To accomplish this, cascode-compensated topologies are basically analyzed to derive the required equations for the comparison. In the analysis, a new method to take into account the effect of transfer function zeros is proposed. By assuming that the zeros' magnitudes are fairly nondominant, the method increases the accuracy of the analyses. The relationships show that for the same specifications, cascode compensation is more power-efficient than Miller compensation, especially for heavy capacitive loads. This has been confirmed by SPICE simulations.
A COMBINED SIMPLEX–TRUST-REGION METHOD FOR ANALOG CIRCUIT OPTIMIZATION
Authors: BŰRMEN ÁRPÁD , TUMA TADEJ , FAJFAR IZTOK
Published: July 2008

The analog-integrated circuits industry is exerting increasing pressure to shorten the analog circuit design time. This pressure is put primarily on the analog circuit designers that in turn demand automated circuit design tools evermore vigorously. Such tools already exist in the form of circuit optimization software packages but they all suffer a common ailment — slow convergence. Even taking into account the increasing computational power of modern computers the convergence times of such optimization tools can range from a few days to even weeks. Different authors have tried diverse approaches for speeding up the convergence with varying success. In this paper authors propose a combined optimization algorithm that attempts to improve the speed of convergence by exploiting the positive properties of the underlying optimization methods. The proposed algorithm is tested on a number of test cases and the convergence results are discussed.
ON CONTROL OF INTERMEDIATE CAPACITOR VOLTAGE IN SINGLE-STAGE AC/DC PFC CONVERTER
Authors: LU DYLAN DAH-CHUAN
Published: July 2008

To reduce the intermediate storage capacitor voltage stress in single-stage power-factor-corrected (S2PFC) converters due to the change of load, some effective approaches such as variable frequency control and negative bus voltage feedback have been proposed. However, this intermediate capacitor voltage still varies largely against the change of line voltage. This paper proposes a S2PFC converter which is constructed in a way such that the amount of energy to and from the intermediate storage capacitor can be varied when the line voltage is changed, hence narrowed the range of intermediate capacitor voltage fluctuation. This is achieved by an auxiliary bidirectional switch, which operates at zero-voltage-switching (ZVS) condition. A dual-loop voltage mode control is proposed for the converter to achieve power factor correction, output voltage regulation, and intermediate capacitor voltage control simultaneously. Simulation and experimental results show that the proposed approach is effective.
ACCURATE ANALYTICAL MODELING OF FREQUENCY DEPENDENT LOOP SELF-INDUCTANCE
Authors: MONDAL MOSIN , MASSOUD YEHIA
Published: July 2008

Parasitic inductance of global interconnects has gained much attention in the recent past since the inductance can no longer be neglected due to different design and fabrication issues. This has led to a paradigm shift from RC to RLC modeling of global interconnects in modern integrated circuits. However, the extraction of inductance is often expensive and presents a bottleneck in performing RLC analysis of interconnects. Unlike capacitance, the frequency dependence of current distribution through return paths present a major challenge in inductance extraction. In this paper, an efficient analytical model of frequency dependent self-inductance that can be applied to model a wide range of real design scenarios was presented. The model is based on the determination of the inductances at low and very high frequencies, an intermediate frequency point and the corresponding slope of the inductance frequency response. It is demonstrate that the approach is computationally efficient and it produces accurate values of frequency dependent inductance. It is also investigate how the frequency dependence of loop self-inductance affects the RLC delay and show that the pessimism in RLC propagation delay estimation could be as high as 49% if the frequency dependence of inductance is not considered properly. Thus, realistic (less pessimistic) delay values can be obtained using our model, leading to improved system performance.
FIRST-ORDER FILTERS GENERALIZED TO THE FRACTIONAL DOMAIN
Authors: RADWAN A. G. , SOLIMAN A. M. , ELWAKIL A. S.
Published: July 2008

Traditional continuous-time filters are of integer order. However, using fractional calculus, filters may also be represented by the more general fractional-order differential equations in which case integer-order filters are only a tight subset of fractional-order filters. In this work, we show that low-pass, high-pass, band-pass, and all-pass filters can be realized with circuits incorporating a single fractance device. We derive expressions for the pole frequencies, the quality factor, the right-phase frequencies, and the half-power frequencies. Examples of fractional passive filters supported by numerical and PSpice simulations are given.
STUDY OF THE QUASI-ISOTROPIC SOLUTION NEAR THE COSMOLOGICAL SINGULARITY IN THE PRESENCE OF BULK VISCOSITY
Authors: CARLEVARO NAKIA , MONTANI GIOVANNI
Published: July 2008

We analyze the dynamical behavior of a quasi-isotropic universe in the presence of a cosmological fluid endowed with bulk viscosity. We express the viscosity coefficient as a power law of the fluid energy density: ζ = ζ0∊s. Then we fix s = 1/2 as the only case in which viscosity plays a significant role in the singularity physics but does not dominate the universe dynamics (as required by its microscopic perturbative origin). The parameter ζ0is left free to define the intensity of the viscous effects.

In spirit of the work by Lifshitz and Khalatnikov on the quasi-isotropic solution, we analyze both Einstein and hydrodynamic equations up to first and second order in time. As a result, we get a power law solution existing only in correspondence to a restricted domain of ζ0.
A NEW TWO-SPHERE SINGULARITY IN GENERAL RELATIVITY
Authors: BÖHMER CHRISTIAN G. , LOBO FRANCISCO S. N.
Published: July 2008

The Florides solution, proposed as an alternative to the interior Schwarzschild solution, represents a static and spherically symmetric geometry with vanishing radial stresses. It is regular at the center, and is matched to an exterior Schwarzschild solution. The specific case of a constant energy density has been interpreted as the field inside an Einstein cluster. In this work, we are interested in analyzing the geometry throughout the permitted range of the radial coordinate without matching it to the Schwarzschild exterior space–time at some constant radius hypersurface. We find an interesting picture; namely, the solution represents a three-sphere, whose equatorial two-sphere is singular, in the sense that the curvature invariants and the tangential pressure diverge. As far as we know, such singularities have not been discussed before. In the presence of a large negative cosmological constant (anti-de Sitter) the singularity is removed.
ON BRANE INFLATION POTENTIALS AND BLACK HOLE ATTRACTORS
Authors: BELHAJ ADIL , DIAZ PABLO , SEGUI ANTONIO , NACIRI MOHAMED
Published: July 2008

We propose a new potential in brane inflation theory, which is given by the arctangent of the square of the scalar field. Then we perform an explicit computation for inflationary quantities. This potential has many nice features. In the small field approximation, it reproduces the chaotic and MSSM potentials. It allows one, in the large field approximation, to implement the attractor mechanism for bulk black holes where the geometry on the brane is de Sitter. In particular, we show, up to some assumptions, that the Friedman equation can be reinterpreted as a Schwarzschild black hole attractor equation for its mass parameter.
OPTIMALITY CONDITIONS FOR COOPERATIVE PARABOLIC SYSTEMS GOVERNED BY SCHRÖDINGER OPERATORS WITH CONTROL CONSTRAINTS
Authors: Bahaa G. M.
Published: July 2008

A distributed control problem for cooperative parabolic systems governed by Schrödinger operator is considered. The performance index is more general than the quadratic one and has an integral form. Constraints on controls are imposed. Making use of the Dubovitskii-Milyutin Theorem given by Walczak (1984, On some control problems Acta Univ. Lod. Folia Math., 1, 187-196), the optimality conditions are derived for the Neumann problem. Finally, several mathematical examples for derived optimality conditions are presented.
REES MATRIX THEOREM FOR $\mathcal{D}^{(\ell)}$-SIMPLE STRONGLY RPP SEMIGROUPS
Authors: Guo Xiaojiang , Guo Yuqi , Shum K. P.
Published: July 2008

A semigroup S is called rpp if all right principal ideals of S, regarded as S1-systems, are projective. An rpp semigroup S is said to be strongly rpp if for any a ∈ S, there exists a unique idempotent e such that [Formula: see text] and a = ea. In this paper, we show that a [Formula: see text]-simple strongly rpp semigroup can be expressed by a Rees matrix semigroup over a left cancellative monoid and conversely. Our result generalizes the classical theorem of Rees in 1940 and also amplifies the Rees theorem in semigroup given by Lallement and Petrich in 1969.
Las Transferencias Monetarias Condicionadas Como Política Social en América Latina. Un Balance: Aportes, Límites y Debates
Authors: Valencia Lomelí Enrique
Published: July 2008

Recientemente se han diseminado por AL los programas de transferencias monetarias condicionadas (CCT). Rápidamente se han resaltado sus potencialidades para superar la pobreza y acumular capital humano, y se ha promovido su difusión. Así, se ha formado ya una teoría convencional sobre los programas CCT. Este texto plantea un balance de ellos y discute con esta teoría; concluye que los resultados son limitados: positivos en escolaridad y algunas aspectos de salud y alimentación de hogares pobres, débiles en la disminución (ligera) de la pobreza en el corto plazo e inciertos en los impactos en el aspecto educativo del capital humano y en la reducción de la pobreza en el largo plazo. En una visión amplia e integral de la política social, en contraposición a un enfoque minimalista, el debate es cómo integrar los programas CCT con las instituciones de seguridad social para superar la tradicional segmentación latinoamericana y para construir ciudadanía.
From Mead to a Structural Symbolic Interactionism and Beyond
Authors: Stryker Sheldon
Published: July 2008

This review discusses the continuing value of and problems in G.H. Mead's contributions to sociology from the standpoint of the contemporary discipline. It argues that the value is considerable and the problems largely avoidable with modifications to Mead's framework; it also offers necessary modifications via structural symbolic interactionism. Permitting the development of testable theories such as identity theory is a major criterion in evaluating a frame, and capacity to bridge to other frames and theories inside and outside sociology is another. The review examines bridges from the structural symbolic interactionist frame and identity theory to other symbolic interactionist theories, to other social psychological frames and theories in sociology, to cognitive social psychology, and to structural sociology.
Gender Inequalities in Education
Authors: Buchmann Claudia , DiPrete Thomas A. , McDaniel Anne
Published: July 2008

The terrain of gender inequalities in education has seen much change in recent decades. This article reviews the empirical research and theoretical perspectives on gender inequalities in educational performance and attainment from early childhood to young adulthood. Much of the literature on children and adolescents attends to performance differences between girls and boys. Of course, achievement in elementary and secondary school is linked to the level of education one ultimately attains including high school completion, enrollment in postsecondary education, college completion, and graduate and professional school experiences. We recommend three directions for future research: (a) interdisciplinary efforts to understand gender differences in cognitive development and noncognitive abilities in early childhood, (b) research on the structure and practices of schooling, and (c) analyses of how gender differences might amplify other kinds of inequalities, such as racial, ethnic, class, or nativity inequalities.
Length-tension relationship of the external anal sphincter muscle: implications for the anal canal function
Authors: Rajasekaran Mahadevan Raj , Jiang Yanfen , Bhargava Valmik , Littlefield Ryan , Lee Andrew , Lieber Richard L. , Mittal Ravinder K.
Published: July 2008

The length at which a muscle operates in vivo (operational length) and the length at which it generates maximal force (optimal length) may be quite different. We studied active and passive length-tension characteristics of external anal sphincter (EAS) in vivo and in vitro to determine the optimal and operational length of rabbit EAS. For the in vitro studies, rings of EAS ( n = 4) were prepared and studied in a muscle bath under isometric conditions. For in vivo studies, female rabbits ( n = 19) were anesthetized and anal canal pressure was recorded by use of a sleeve sensor placed in the custom-designed catheter holders of 4.5-, 6-, and 9-mm diameters. Measurements were obtained at rest and during EAS electrical stimulation. Sarcomere length of EAS muscle was measured by laser diffraction technique with no probe and three probes in the anal canal. In vitro studies revealed 2,054 mN/cm2active tension at optimal length. In vivo studies revealed a probe size-dependent increase in anal canal pressure and tension. Maximal increase in anal canal tension with stimulation was recorded with the 9-mm probe. Increases in anal canal tension with increase in probe size were completely abolished by pancuronium bromide. EAS muscle sarcomere length without and with 9-mm probe in the anal canal were 2.11 ± 0.08 and 2.99 ± 0.07 μm, respectively. Optimal sarcomere length, based on the thin filament length measured by thin filament analysis, is 2.44 ± 0.10 μm. These data show that the operational length of EAS is significantly shorter than its optimal length. Our findings provide insight into EAS function and we propose the possibility of increasing anal canal pressure by surgical manipulation of the EAS sarcomere length.
Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells
Authors: Kenny Susan , Duval Cedric , Sammut Stephen J. , Steele Islay , Pritchard D. Mark , Atherton John C. , Argent Richard H. , Dimaline Rod , Dockray Graham J. , Varro Andrea
Published: July 2008

The gastric pathogen Helicobacter pylori ( H. pylori) is linked to peptic ulcer and gastric cancer, but the relevant pathophysiological mechanisms are unclear. We now report that H. pylori stimulates the expression of plasminogen activator inhibitor (PAI)-1, urokinase plasminogen activator (uPA), and its receptor (uPAR) in gastric epithelial cells and the consequences for epithelial cell proliferation. Real-time PCR of biopsies from gastric corpus, but not antrum, showed significantly increased PAI-1, uPA, and uPAR in H. pylori-positive patients. Transfection of primary human gastric epithelial cells with uPA, PAI-1, or uPAR promoters in luciferase reporter constructs revealed expression of all three in H+/K+ATPase- and vesicular monoamine transporter 2-expressing cells; uPA was also expressed in pepsinogen- and uPAR-containing trefoil peptide-1-expressing cells. In each case expression was increased in response to H. pylori and for uPA, but not PAI-1 or uPAR, required the virulence factor CagE. H. pylori also stimulated soluble and cell surface-bound uPA activity, and both were further increased by PAI-1 knockdown, consistent with PAI-1 inhibition of endogenous uPA. H. pylori stimulated epithelial cell proliferation, which was inhibited by uPA immunoneutralization and uPAR knockdown; exogenous uPA also stimulated proliferation that was further increased after PAI-1 knockdown. The proliferative effects of uPA were inhibited by immunoneutralization of the EGF receptor and of heparin-binding EGF (HB-EGF) by the mutant diphtheria toxin CRM197 and an EGF receptor tyrosine kinase inhibitor. H. pylori induction of uPA therefore leads to epithelial proliferation through activation of HB-EGF and is normally inhibited by concomitant induction of PAI-1; treatments directed at inhibition of uPA may slow the progression to gastric cancer.
Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo
Authors: Véliz Loreto P. , González Francisco G. , Duling Brian R. , Sáez Juan C. , Boric Mauricio P.
Published: July 2008

To assess the hypothesis that gap junctions (GJs) participate on leukocyte-endothelium interactions in the inflammatory response, we compared leukocyte adhesion and transmigration elicited by cytokine stimulation in the presence or absence of GJ blockers in the hamster cheek pouch and also in the cremaster muscle of wild-type (WT) and endothelium-specific connexin 43 (Cx43) null mice (Cx43e−/−). In the cheek pouch, topical tumor necrosis factor-α (TNF-α; 150 ng/ml, 15 min) caused a sustained increment in the number of leukocytes adhered to venular endothelium (LAV) and located at perivenular regions (LPV). Superfusion with the GJ blockers 18-α-glycyrrhetinic acid (AGA; 75 μM) or 18-β-glycyrrhetinic acid (50 μM) abolished the TNF-α-induced increase in LAV and LPV; carbenoxolone (75 μM) or oleamide (100 μM) reduced LAV by 50 and 75%, respectively, and LPV to a lesser extent. None of these GJ blockers modified venular diameter, blood flow, or leukocyte rolling. In contrast, glycyrrhizin (75 μM), a non-GJ blocker analog of AGA, was devoid of effect. Interestingly, when AGA was removed 90 min after TNF-α stimulation, LAV started to rise at a similar rate as in control. Conversely, application of AGA 90 min after TNF-α reduced the number of previously adhered cells. In WT mice, intrascrotal injection of TNF-α (0.5 μg/0.3 ml) increased LAV (fourfold) and LPV (threefold) compared with saline-injected controls. In contrast to the observations in WT animals, TNF-α stimulation did not increase LAV or LPV in Cx43e−/−mice. These results demonstrate an important role for GJ communication in leukocyte adhesion and transmigration during acute inflammation in vivo and further suggest that endothelial Cx43 is key in these processes.