bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon alpha regulates MAPK and STAT1 pathways in human hepatoma cells
Authors: Zhao Lan-Juan , Hua Xian , He Sheng-Fei , Ren Hao , Qi Zhong-Tian
Published: April 2011

Background

Signaling events triggered by interferon (IFN) account for the molecular mechanisms of antiviral effect. JAK-STAT pathway plays a critical role in IFN signaling, and other pathways are also implicated in IFN-mediated antiviral effect. Changes in mitogen-activated protein kinase (MAPK) and STAT1 pathways were evaluated in human hepatoma cells Huh7 and HepG2 upon IFN alpha treatment.

Results

Phosphorylation of ERK was significantly and specifically up-regulated, whereas enhanced phosphorylation of upstream kinase MEK was unobservable upon IFN alpha treatment. A mild increase in p38 MAPK, SAPK/JNK and downstream target ATF-2 phosphorylation was detectable after exposure to IFN alpha, indicating differential up-regulation of the MAPK signaling cascades. Moreover, STAT1 phosphorylation was strongly enhanced by IFN alpha.

Conclusion

IFN alpha up-regulates MAPK and STAT1 pathways in human hepatoma cells, and may provide useful information for understanding the IFN signaling.
Medical Research Council dyspnea scale does not relate to fibroblast foci profusion in IPF
Authors: Triantafillidou Christina , Manali Effrosyni D , Magkou Christina , Sotiropoulou Christina , Kolilekas Likurgos F , Kagouridis Konstantinos , Rontogianni Dimitra , Papiris Spyros A
Published: April 2011

Background

In Idiopathic pulmonary fibrosis (IPF) irreversibly progressive fibrosing parenchymal damage, leads to defects in mechanics and gas exchange, manifesting with disabling exertional dyspnea. Previous studies have shown a relationship between fibroblast foci (FF) profusion and severity and survival and a relationship between dyspnea grade and severity and outcome. We hypothesized a relationship between Medical Research Council (MRC) dyspnea scale with FF, and a relationship between FF and functional parameters and survival.

Methods

We retrospectively reviewed 24 histologically documented IPF patients. Profusion of FF was semiquantitatively evaluated by two scores, Brompton and Michigan. Survival analysis was performed by fitting Cox regression models to examine the relationship of the two scores with survival and the non-parametric Spearman correlation coefficient was calculated to describe the relationships of FF scores with dyspnea scores and functional parameters.

Results

No statistically significant correlation between FF scores and the MRC scores was observed (p = 0.96 and p = 0.508 respectively). No significant correlation between FF scores and survival (p = 0.438 and p = 0.861 respectively) or any functional parameter was observed.

Conclusions

The lack of relationship between the MRC dyspnea scale and the FF might relate to the fact that dyspnea in IPF better reflects the overall of lung damage and its related consequences on mechanics and gas exchange whereas FF, one of its histological hallmarks, may not reflect its entire histology derangement also constrained by the geographically limited sampled tissue. This might be also valid for the observed lack of association between FF and survival or functional parameters.
Microalbuminuria in relation to the metabolic syndrome and its components in a Chinese population
Authors: Sheng Chang-Sheng , Hu Bang-Chuan , Fan Wang-Xiang , Zou Jun , Li Yan , Wang Ji-Guang
Published: April 2011

Background

We investigated the prevalence of microalbuminuria and its association with the metabolic syndrome and its components in a Chinese population.

Methods

The study subjects were recruited from a newly established residential area in the suburb of Shanghai. We measured anthropometry, blood pressure (BP), fasting plasma glucose, and serum lipids, and collected spot urine samples for the determination of albumin-creatinine ratio. We defined microalbuminuria as a urinary albumin-to-creatinine ratio of 30 to 299 mg/g. The metabolic syndrome was defined according to the International Diabetes Federation criteria.

Results

The 1079 participants included 410 (38.0%) hypertensive patients, and 66 (6.1%) diabetic patients. The prevalence of microalbuminuria (4.3%) was 3.2 times higher in 167 patients with the metabolic syndrome than 912 subjects without the metabolic syndrome (12.0% vs. 2.9%, P < 0.0001). In multiple regression adjusted for sex, age, body mass index, current smoking, alcohol intake and the use of antihypertensive drugs, and mutually adjusted for the components, microalbuminuria was significantly associated with diastolic BP (odds ratio 1.74 for +10 mmHg; 95% confidence interval [CI] 1.10-2.76; P = 0.02) and fasting plasma glucose (1.18; 95% CI 1.01-1.41; P = 0.04), but not with waist circumference, systolic BP, or serum HDL cholesterol and triglycerides (P > 0.10).

Conclusions

Microalbuminuria is common in the Chinese population, and much more prevalent in the presence of the metabolic syndrome, mainly attributable to elevated diastolic BP and plasma glucose.
Kisspeptin Resets the Hypothalamic GnRH Clock in Men
Authors: Chan Yee-Ming , Butler James P. , Pinnell Nancy E. , Pralong François P. , Crowley William F. , Ren Chen , Chan Kenneth K. , Seminara Stephanie B.
Published: April 2011

Context:

Reproduction in all mammals is controlled by a hypothalamic clock that produces periodic secretory pulses of GnRH, but how the timing of these pulses is determined is poorly understood. The neuropeptide kisspeptin potently and selectively stimulates the secretion of GnRH. Although this property of kisspeptin is well described, the effects of kisspeptin on endogenous GnRH pulse generation remain largely unexplored.

Objective:

The objective of the study was to detail the effects of kisspeptin on GnRH secretion, as reflected by LH secretion, in men.

Participants:

Thirteen healthy adult men participated in the study.

Intervention:

The intervention was the administration of a single iv bolus of the C-terminal decapeptide of kisspeptin (amino acids 112–121 of the parent protein).

Results:

Kisspeptin induced an immediate LH pulse, regardless of the timing of the previous endogenous pulse. The kisspeptin-induced pulses were on average larger than endogenous pulses (amplitude 5.0 ± 1.0 vs. 2.1 ± 0.3 mIU/ml, P = 0.02). Comparison of the morphology of kisspeptin-induced LH pulses in healthy men with that of GnRH-induced LH pulses in men with isolated GnRH deficiency suggests that a single iv bolus of kisspeptin triggered sustained GnRH release lasting approximately 17 min. Furthermore, kisspeptin reset the GnRH pulse generator, as it not only induced an immediate LH pulse but also delayed the next endogenous pulse by an interval approximating the normal interpulse interval.

Conclusions:

As the first known agent capable of resetting the hypothalamic GnRH pulse generator, kisspeptin can be used as a physiological tool for studying GnRH pulse generation and opens a door to understanding the mechanisms of biological clocks in general.
SHH propagates distal limb bud development by enhancing CYP26B1-mediated retinoic acid clearance via AER-FGF signalling
Authors: Probst Simone , Kraemer Conradin , Demougin Philippe , Sheth Rushikesh , Martin Gail R. , Shiratori Hidetaka , Hamada Hiroshi , Iber Dagmar , Zeller Rolf , Zuniga Aimée
Published: April 2011

The essential roles of SHH in anteroposterior (AP) and AER-FGF signalling in proximodistal (PD) limb bud development are well understood. In addition, these morphoregulatory signals are key components of the self-regulatory SHH/GREM1/AER-FGF feedback signalling system that regulates distal progression of limb bud development. This study uncovers an additional signalling module required for coordinated progression of limb bud axis development. Transcriptome analysis using Shh-deficient mouse limb buds revealed that the expression of proximal genes was distally extended from early stages onwards, which pointed to a more prominent involvement of SHH in PD limb axis development. In particular, retinoic acid (RA) target genes were upregulated proximally, while the expression of the RA-inactivating Cyp26b1 enzyme was downregulated distally, pointing to increased RA activity in Shh-deficient mouse limb buds. Further genetic and molecular analysis established that Cyp26b1 expression is regulated by AER-FGF signalling. During initiation of limb bud outgrowth, the activation of Cyp26b1 expression creates a distal ‘RA-free’ domain, as indicated by complementary downregulation of a transcriptional sensor of RA activity. Subsequently, Cyp26b1 expression increases as a consequence of SHH-dependent upregulation of AER-FGF signalling. To better understand the underlying signalling interactions, computational simulations of the spatiotemporal expression patterns and interactions were generated. These simulations predicted the existence of an antagonistic AER-FGF/CYP26B1/RA signalling module, which was verified experimentally. In summary, SHH promotes distal progression of limb development by enhancing CYP26B1-mediated RA clearance as part of a signalling network linking the SHH/GREM1/AER-FGF feedback loop to the newly identified AER-FGF/CYP26B1/RA module.
Characterization of Glycolipids in Light-Harvesting Chlorosomes from the Green Photosynthetic Bacterium Chlorobium tepidum
Authors: Yoshitomi Taichi , Mizoguchi Tadashi , Kunieda Michio , Tamiaki Hitoshi
Published: April 2011

Glycolipids were isolated from extramembraneous light-harvesting complexes, called “chlorosomes,” in a thermophilic green photosynthetic bacterium Chlorobium tepidum. The lipids were first characterized in terms of their precise structures of both hydrophilic (saccharides) and hydrophobic (fatty acids) moieties by means of 1H and 13C NMR spectroscopy as well as high-performance liquid chromatography coupled with an evaporative light-scattering detector and an electron spray ionization mass spectrometer. The results clearly demonstrated that glycolipids having a disaccharide group, rhamnosylgalactosyldiacylglycerides, were the majority in the total glycolipid component of the chlorosomes, in addition to the second major glycolipids with a monosaccharide group, monogalactosyldiacylglycerides, which had been believed to be predominant before the report by Miller and her co-workers (Photosynth. Res.2008, 95, 191–196). We also found that these glycolipids had methylene-bridged palmitoleyl (=(Z)-9-hexadecenoyl) (17:1) and palmitoyl groups (16:0) as their predominant acyl chains on the glycerol moiety. By using enzymatically site-specific hydrolysis of the acyl chain at the sn-1 position on the glycerol, the modified palmitoleyl group was determined to be esterified at the sn-1 position. These unique glycolipids might play an important role in maintaining fluidization of chlorosomal envelopes and achieving thermal stability of chlorosomes at 45 °C.
Synthesis of Horn-Like BN Derived from Thorn-Like Ca2B2O5·H2O
Authors: Zhao Guowei , Wang Jilin , Zhang Laiping , Gu Yunle , Li Jie , Qian Qiongli , Pan Xinye
Published: April 2011

Boron nitride (BN) with horn-like morphology was synthesized by the reaction of thorn-like Ca2B2O5·H2O and ammonia at 950 °C for 10 h. XRD, SEM, TEM, and HRTEM were used for characterization. Possible reaction and growth mechanisms were also discussed.
The role of circumflex femoral veins in the saphenofemoral junction incompetence: a case report
Authors: Passariello F
Published: April 2011

A 31 year-old female patient, an opera singer, came for a consultation, mainly for aesthetic problems of the lower limbs. An asymptomatic bilateral P-point pelvic shunt was demonstrated by the EchoDoppler, while no nutcracker syndrome was detected. The examination demonstrated a medial circumflex femoral vein (MCFV), going into the common femoral vein and then into the great saphenous vein (GSV). The Valsalva manoeuvre showed the GSV terminal valve incompetence. A dilated MCFV vein at the level of the saphenofemoral junction was the source of the reflux through the GSV, while the external iliac vein was competent. GSV reflux with Valsalva was present only in the lying position. Flow in the MCFV was directed toward the CFV during and after the Valsalva. The examination shows clearly that a GSV reflux can sometimes occur in absence of iliac reflux. Circumflex femoral veins (medial and lateral) are anatomical variations, but common findings during ordinary EchoColourDoppler investigations of the venous system of the lower limbs.
Thermodynamics of impurities in hydrometallurgical processes
Authors: Königsberger Erich , Bochmann Sebastian , May Peter M. , Hefter Glenn
Published: April 2011

Impurities in hydrometallurgical process liquors frequently impact on product quality and yield, change physicochemical properties of the liquor, and form hard scale on heat exchangers and condensers. Organic compounds are of particular concern especially in the Bayer process, where impurities build up in the recycled liquor if not controlled. Depending on the redox state of the liquor, such compounds can undergo a variety of complex chemical reactions, including the formation of volatiles that can potentially cause environmental, health, and safety concerns. To aid in the development of appropriate control strategies, robust thermodynamic models for multicomponent aqueous systems containing large numbers of electrolytes and nonelectrolytes are required. Applications of thermodynamic models are discussed that range from the partitioning of volatile compounds in flash trains to the prediction of mixing properties of organic impurities with major Bayer liquor components.
Cystic Fibrosis Carrier Testing in an Ethnically Diverse US Population
Authors: Rohlfs Elizabeth M , Zhou Zhaoqing , Heim Ruth A , Nagan Narasimhan , Rosenblum Lynne S , Flynn Kerry , Scholl Thomas , Akmaev Viatcheslav R , Sirko-Osadsa D Alexa , Allitto Bernice A , Sugarman Elaine A
Published: April 2011

BACKGROUND

The incidence of cystic fibrosis (CF) and the frequency of specific disease-causing mutations vary among populations. Affected individuals experience a range of serious clinical consequences, notably lung and pancreatic disease, which are only partially dependent on genotype.

METHODS

An allele-specific primer-extension reaction, liquid-phase hybridization to a bead array, and subsequent fluorescence detection were used in testing for carriers of 98 CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations among 364 890 referred individuals with no family history of CF.

RESULTS

One in 38 individuals carried one of the 98 CFTR mutations included in this panel. Of the 87 different mutations detected, 18 were limited to a single ethnic group. African American, Hispanic, and Asian individuals accounted for 33% of the individuals tested. The mutation frequency distribution of Caucasians was significantly different from that of each of these ethnic groups (P < 1 × 10−10).

CONCLUSIONS

Carrier testing using a broad mutation panel detects differences in the distribution of mutations among ethnic groups in the US.
Übersetzung von Metasprache: Bericht einer Untersuchung am Beispiel der französischen Version von T. W. Adornos Jargon der Eigentlichkeit
Authors: Linares Pablo
Published: April 2011

Metalanguage is the expression of language's self-referentiality. It is most evident in cases of autonymy, i. e. when a word is used to signify itself, which provide for downright untranslability on a semantical level. However, a language-critical text like Adorno's
Textanalyse und Übersetzungskommentar des Backrezeptes „KEY LIME PIE“ aus dem Backbuch „United Cakes of America“ von Warren Brown
Authors: Haberland Jana
Published: April 2011

One of the most important fields in translator's work is the translation of instruction texts – a text type that clearly ref lects the functional concept of intercultural text transfer. Its text type norms are highly conventionalised and vary from one culture to another. But instruction texts may also contain several other cultural and language specifics that need to be adapted to the target culture. Using the example of a recipe, the author points out the importance of a thorough text analysis to sustain functional adequacy, which is the priority objective for that kind of text. The analysis is followed by a commentary on the translational decisions, stating the strategies and methods used to achieve the priority objective.
Cannabinoid Receptor Blockade Reduces the Opportunity Cost at Which Rats Maintain Operant Performance for Rewarding Brain Stimulation
Authors: Trujillo-Pisanty Ivan , Hernandez Giovanni , Moreau-Debord Ian , Cossette Marie-Pierre , Conover Kent , Cheer Joseph F. , Shizgal Peter
Published: April 2011

There is ample evidence that blockade of CB1receptors reduces reward seeking. However, the reported effects of CB1blockade on performance for rewarding electrical brain stimulation stand out as an exception. By applying a novel method for conceptualizing and measuring reward seeking, we show that AM-251, a CB1receptor antagonist, does indeed decrease performance for rewarding electrical stimulation of the medial forebrain bundle in rats. Reward seeking depends on multiple sets of variables, including the intensity of the reward, its cost, and the value of competing rewards. In turn, reward intensity depends both on the sensitivity and gain of brain reward circuitry. We show that drug-induced changes in sensitivity cannot account for the suppressive effect of AM-251 on reward seeking. Therefore, the role of CB1receptors must be sought among the remaining determinants of performance. Our analysis provides an explanation of the inconsistencies between prior reports, which likely arose from the following: (1) the averaging of data across subjects showing heterogeneous effects and (2) the use of methods that cannot distinguish between the different determinants of reward pursuit. By means of microdialysis, we demonstrate that blockade of CB1receptors attenuates nucleus accumbens dopamine release in response to rewarding medial forebrain bundle stimulation, and we propose that this action is responsible for the ability of the drug to decrease performance for the electrical reward.
Rapid Synaptic Remodeling in the Adult Somatosensory Cortex following Peripheral Nerve Injury and Its Association with Neuropathic Pain
Authors: Kim Sun Kwang , Nabekura Junichi
Published: April 2011

Structural and functional plastic changes in the primary somatosensory cortex (S1) have been observed following peripheral nerve injury that often leads to neuropathic pain, which is characterized by tactile allodynia. However, remodeling of cortical connections following injury has been believed to take months or years; this is not temporally correlated with the rapid development of allodynia and S1 hyperexcitability. Here we first report, by using long-term two-photon imaging of postsynaptic dendritic spines in living adult mice, that synaptic connections in the S1 are rewired within days following sciatic nerve ligation through phase-specific and size-dependent spine survival/growth. Spine turnover in the S1 area corresponding to the injured paw markedly increased during an early phase of neuropathic pain and was restored in a late phase of neuropathic pain, which was prevented by immediate local blockade of the injured nerve throughout the early phase. New spines that generated before nerve injury showed volume decrease after injury, whereas more new spines that formed in the early phase of neuropathic pain became persistent and substantially increased their volume during the late phase. Further, preexisting stable spines survived less following injury than controls, and such lost persistent spines were smaller in size than the surviving ones, which displayed long-term potentiation-like enlargement over weeks. These results suggest that peripheral nerve injury induces rapid and selective remodeling of cortical synapses, which is associated with neuropathic pain development, probably underlying, at least partially, long-lasting sensory changes in neuropathic subjects.
A Requirement for Nuclear Factor-κB in Developmental and Plasticity-Associated Synaptogenesis
Authors: Boersma Matthew C. H. , Dresselhaus Erica C. , De Biase Lindsay M. , Mihalas Anca B. , Bergles Dwight E. , Meffert Mollie K.
Published: April 2011

Structural plasticity of dendritic spines and synapses is a fundamental mechanism governing neuronal circuits and may form an enduring basis for information storage in the brain. We find that the p65 subunit of the nuclear factor-κB (NF-κB) transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-κB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. Duringin vitrosynaptogenesis, NF-κB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-κB within the postsynaptic neuron is sufficient to regulate the formation of both presynaptic and postsynaptic elements. During synapse developmentin vivo, loss of NF-κB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-κB activity is low and p65 deficiency no longer attenuates basal spine density. Instead, NF-κB in mature neurons is activated by stimuli that induce demand for new synapses, including estrogen and short-term bicuculline, and is essential for upregulating spine density in response to these stimuli. p65 is enriched in dendritic spines making local protein–protein interactions possible; however, the effects of NF-κB on spine density require transcription and the NF-κB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-κB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density.
Signaling of the Strongest Stimulus in the Owl Optic Tectum
Authors: Mysore Shreesh P. , Asadollahi Ali , Knudsen Eric I.
Published: April 2011

Essential to the selection of the next target for gaze or attention is the ability to compare the strengths of multiple competing stimuli (bottom-up information) and to signal the strongest one. Although the optic tectum (OT) has been causally implicated in stimulus selection, how it computes the strongest stimulus is unknown. Here, we demonstrate that OT neurons in the barn owl systematically encode the relative strengths of simultaneously occurring stimuli independently of sensory modality. Moreover, special “switch-like” responses of a subset of neurons abruptly increase when the stimulus inside their receptive field becomes the strongest one. Such responses are not predicted by responses to single stimuli and, indeed, are eliminated in the absence of competitive interactions. We demonstrate that this sensory transformation substantially boosts the representation of the strongest stimulus by creating a binary discrimination signal, thereby setting the stage for potential winner-take-all target selection for gaze and attention.
Neural Correlates of Forward Planning in a Spatial Decision Task in Humans
Authors: Simon Dylan Alexander , Daw Nathaniel D.
Published: April 2011

Although reinforcement learning (RL) theories have been influential in characterizing the mechanisms for reward-guided choice in the brain, the predominant temporal difference (TD) algorithm cannot explain many flexible or goal-directed actions that have been demonstrated behaviorally. We investigate such actions by contrasting an RL algorithm that is model based, in that it relies on learning a map or model of the task and planning within it, to traditional model-free TD learning. To distinguish these approaches in humans, we used functional magnetic resonance imaging in a continuous spatial navigation task, in which frequent changes to the layout of the maze forced subjects continually to relearn their favored routes, thereby exposing the RL mechanisms used. We sought evidence for the neural substrates of such mechanisms by comparing choice behavior and blood oxygen level-dependent (BOLD) signals to decision variables extracted from simulations of either algorithm. Both choices and value-related BOLD signals in striatum, although most often associated with TD learning, were better explained by the model-based theory. Furthermore, predecessor quantities for the model-based value computation were correlated with BOLD signals in the medial temporal lobe and frontal cortex. These results point to a significant extension of both the computational and anatomical substrates for RL in the brain.
Cannabinoid Transmission in the Basolateral Amygdala Modulates Fear Memory Formation via Functional Inputs to the Prelimbic Cortex
Authors: Tan Huibing , Lauzon Nicole M. , Bishop Stephanie F. , Chi Ning , Bechard Melanie , Laviolette Steven R.
Published: April 2011

The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala–prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic division (PLC) of the medial prefrontal cortex (mPFC). However, the precise role of CB1 receptor transmission within the BLA during the processing of fear memory is not fully understood. We examined the potential role of BLA CB1 receptor transmission during an olfactory fear-conditioning procedure in rats by pharmacologically modulating CB1 cannabinoid transmission directly within the BLA. We report that blockade of BLA CB1 receptor transmission prevents the acquisition of associative fear memory, while having no effect on the recall or consolidation of these memories. In contrast, intra-BLA activation of CB1 receptor transmission or blockade of endocannabinoid reuptake strongly potentiated the emotional salience of normally subthreshold fear-conditioning stimuli. In addition, pharmacological inactivation of the mPFC before intra-BLA CB1 activation blocked CB1-receptor-mediated potentiation of fear memory formation.In vivosingle-unit electrophysiological recordings within the PLC revealed that modulation of BLA CB1 receptor transmission strongly influences neuronal activity within subpopulations of PLC neurons, with blockade of intra-BLA CB1 receptor transmission inhibiting spontaneous PLC neuronal activity and activation of CB1 receptors producing robust activation, in terms of neuronal firing frequency and bursting activity. Thus, cannabinoid transmission within the BLA strongly modulates the processing of associative fear memory via functional interactions with PLC neuronal populations.
Top-Down Controlled Alpha Band Activity in Somatosensory Areas Determines Behavioral Performance in a Discrimination Task
Authors: Haegens Saskia , Händel Barbara F. , Jensen Ole
Published: April 2011

The brain receives a rich flow of information which must be processed according to behavioral relevance. How is the state of the sensory system adjusted to up- or downregulate processing according to anticipation? We used magnetoencephalography to investigate whether prestimulus alpha band activity (8–14 Hz) reflects allocation of attentional resources in the human somatosensory system. Subjects performed a tactile discrimination task where a visual cue directed attention to their right or left hand. The strength of attentional modulation was controlled by varying the reliability of the cue in three experimental blocks (100%, 75%, or 50% valid cueing). While somatosensory prestimulus alpha power lateralized strongly with a fully predictive cue (100%), lateralization was decreased with lower cue reliability (75%) and virtually absent if the cue had no predictive value at all (50%). Importantly, alpha lateralization influenced the subjects' behavioral performance positively: both accuracy and speed of response improved with the degree of alpha lateralization. This study demonstrates that prestimulus alpha lateralization in the somatosensory system behaves similarly to posterior alpha activity observed in visual attention tasks. Our findings extend the notion that alpha band activity is involved in shaping the functional architecture of the working brain by determining both the engagement and disengagement of specific regions: the degree of anticipation modulates the alpha activity in sensory regions in a graded manner. Thus, the alpha activity is under top-down control and seems to play an important role for setting the state of sensory regions to optimize processing.
Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse
Authors: Banks Gareth T. , Haas Matilda A. , Line Samantha , Shepherd Hazel L. , AlQatari Mona , Stewart Sammy , Rishal Ida , Philpott Amelia , Kalmar Bernadett , Kuta Anna , Groves Michael , Parkinson Nicholas , Acevedo-Arozena Abraham , Brandner Sebastian , Bannerman David , Greensmith Linda , Hafezparast Majid , Koltzenburg Martin , Deacon Robert , Fainzilber Mike , Fisher Elizabeth M. C.
Published: April 2011

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown fromin vivostudies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system.
Calcium Microdomains Near R-Type Calcium Channels Control the Induction of Presynaptic Long-Term Potentiation at Parallel Fiber to Purkinje Cell Synapses
Authors: Myoga Michael H. , Regehr Wade G.
Published: April 2011

R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium/calmodulin-sensitive potassium channel that in turn regulates postsynaptic hippocampal long-term potentiation (LTP). Here, we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Although most presynaptic calcium influx is through N-type and P/Q-type calcium channels, blocking these channels does not disrupt PF-LTP, but blocking R-type calcium channels does. Moreover, global calcium signaling cannot account for the calcium dependence of PF-LTP because R-type channels contribute modestly to overall calcium entry. These findings indicate that, within presynaptic terminals, R-type calcium channels produce calcium microdomains that evoke presynaptic LTP at moderate frequencies that do not greatly increase global calcium levels.
Functional Elimination of Excitatory Feedforward Inputs Underlies Developmental Refinement of Visual Receptive Fields in Zebrafish
Authors: Zhang Min , Liu Yan , Wang Sheng-zhi , Zhong Wen , Liu Bao-hua , Tao Huizhong Whit
Published: April 2011

In many sensory systems, receptive fields (RFs) measured by spike responses undergo progressive refinement during development. It has been proposed that elimination of excitatory synaptic inputs underlies such functional refinement. However, despite many extracellular recording and anatomical studies, directin vivointracellular evidence has remained limited. In this study, by cell-attached recordings in the developing optic tectum of zebrafish, we found that during a short period after the initial formation of retinotectal synapses, spike visual RFs of tectal neurons underwent a two-stage developmental modulation: from an initial expansion to a later refinement. Whole-cell voltage-clamp recordings revealed that the underlying excitatory synaptic RF exhibited a similar developmental progression, with its spatial extent first increased and then reduced, and its spatial tuning profile gradually sharpened. The inhibitory RF was initially larger than the excitatory RF but became matched with the excitatory RF at later stages. Simulation with the integrate-and-fire neuron model suggested that the developmental changes of excitatory RFs primarily accounted for the initial enlargement and later refinement of spike RFs, whereas inhibitory inputs generally reduced the size of the spike RF without affecting its developmental progression. In addition, spike RF of individual retinal ganglion cells did not significantly change in size during the same period, and the spatial extent and tuning profile of the tectal excitatory RF barely changed after intratectal excitatory connections were silenced. Together, our results demonstrate that the functional refinement of tectal visual RFs results primarily from a selective elimination of feedforward retinotectal inputs.
Neural Mechanisms of Surround Attenuation and Distractor Competition in Visual Search
Authors: Boehler Carsten N. , Tsotsos John K. , Schoenfeld Mircea A. , Heinze Hans-Jochen , Hopf Jens-Max
Published: April 2011

Visual attention biases relevant processing in the visual system by amplifying relevant or attenuating irrelevant sensory input. A potential signature of the latter operation, referred to as surround attenuation, has recently been identified in the electromagnetic brain response of human observers performing visual search. It was found that a zone of attenuated cortical excitability surrounds the target when the search required increased spatial resolution for item discrimination. Here we address the obvious hypothesis that surround attenuation serves distractor suppression in the vicinity of the target where interference from irrelevant search items is maximal. To test this hypothesis, surround attenuation was assessed under conditions when the target was presented in isolation versus when it was surrounded by distractors. Surprisingly, substantial and indistinguishable surround attenuation was seen under both conditions, indicating that it reflects an attentional operation independent of the presence of distractors. Adding distractors in the target's surround, however, increased the amplitude of the N2pc—an evoked response known to index distractor competition in visual search. Moreover, adding distractors led to a topographical change of source activity underlying the N2pc toward earlier extrastriate areas. In contrast, the topography of reduced source activity due to surround attenuation remained unaltered with and without distractors in the target's surround. We conclude that surround attenuation is not a direct consequence of the attenuation of distractors in visual search and that it dissociates from attentional operations reflected by the N2pc. A theoretical framework is proposed that links both operations in a common model of top-down attentional selection in visual cortex.
Neonatal Novelty-Induced Persistent Enhancement in Offspring Spatial Memory and the Modulatory Role of Maternal Self-Stress Regulation
Authors: Tang Akaysha C. , Reeb-Sutherland Bethany C. , Yang Zhen , Romeo Russell D. , McEwen Bruce S.
Published: April 2011

Development of spatial memory in the rat is influenced by both maternal and nonmaternal aspects of the postnatal environment. Yet it remains poorly understood how these two aspects of the postnatal environment interact to program offspring cognitive development. By considering the joint influence of neonatal environmental novelty and maternal self-stress regulation on the development of spatial memory function in Long–Evans hooded rats, we show a persistent neonatal novelty-induced enhancement in spatial reference and working memory functions among the same individual offspring from juvenility to adulthood and a contrasting transient maternal modulatory influence on this novelty-related enhancement present during only juvenility. Specifically, at and only at juvenility, for mothers with good self-stress regulation as indexed by a low circulating basal corticosterone level, offspring showed a novelty-induced enhancement in spatial memory function, whereas for mothers with poor self-stress regulation, indexed by a high basal corticosterone level, offspring showed little enhancement or even small impairments. These findings indicate that maternal and nonmaternal postnatal environments exert separate but interacting influences on offspring cognitive development and support a maternal modulation model of cognitive development that considers maternal self-stress regulation as an important factor among the multitude of maternal influences.
Reactions in Trifluoropropene and Trifluoropropyne Triggered by Low-Energy (0–12 eV) Electrons: From Single Bond Cleavages to Complex Unimolecular Decompositions
Authors: Kopyra Janina , Dabkowska Iwona , Illenberger Eugen
Published: April 2011

Electron impact to trifluoropropene (CF3CH=CH2) and trifluoropropyne (CF3C≡CH) leads to rich resonant structures observed in the ion yields of various negatively charged fragment ions which are formed via resonant dissociative electron attachment (DEA). In the range between 1.8 and 3 eV the transient negative ions (TNIs) formed by electron attachment are assigned to one particle shape resonances of π
* character, above 5 eV as two particle core excited resonances and in the energy range below 1 eV as diffuse transient negative ion states formed by polarisation and dipole forces. These transient parent anions decompose into various negatively charged fragments by the cleavage of single bonds (formation of F− and CF3
−) but also via surprisingly complex unimolecular processes involving multiple bond cleavages, geometrical and electronic rearrangement in the transient anion and formation of new bonds.
Quantitative Study of 4He Real Gas Effects Using Supersonic Beams
Authors: Christen Wolfgang , Rademann Klaus
Published: April 2011

The experimental realization of accurately defined source conditions, combined with an undisturbed flight path of precisely known length, permits the generation of supersonic molecular beams with an extremely well characterized axial velocity distribution. This achievement can be used for a quantitative assessment of theoretical models of condensation during the jet expansion, based on high accuracy equations of state. For helium-4, which is commonly put on a level with the ideal gas, we contrast two empirical equations of state with respect to enthalpy changes. These can be validated through a comparison with experimentally determined mean terminal flow velocities. At cryogenic temperatures, strong deviations from the ideal gas behavior are observed. Most notably, even the differences between the predictions of the two fundamental equations are large enough to be distinguished by high-resolution time-of-flight measurements.
AME Position Statement on adrenal incidentaloma
Authors: Terzolo M , Stigliano A , Chiodini I , Loli P , Furlani L , Arnaldi G , Reimondo G , Pia A , Toscano V , Zini M , Borretta G , Papini E , Garofalo P , Allolio B , Dupas B , Mantero F , Tabarin A
Published: April 2011

Objective

To assess currently available evidence on adrenal incidentaloma and provide recommendations for clinical practice.

Design

A panel of experts (appointed by the Italian Association of Clinical Endocrinologists (AME)) appraised the methodological quality of the relevant studies, summarized their results, and discussed the evidence reports to find consensus.

Radiological assessment

Unenhanced computed tomography (CT) is recommended as the initial test with the use of an attenuation value of ≤10 Hounsfield units (HU) to differentiate between adenomas and non-adenomas. For tumors with a higher baseline attenuation value, we suggest considering delayed contrast-enhanced CT studies. Positron emission tomography (PET) or PET/CT should be considered when CT is inconclusive, whereas fine needle aspiration biopsy may be used only in selected cases suspicious of metastases (after biochemical exclusion of pheochromocytoma).

Hormonal assessment

Pheochromocytoma and excessive overt cortisol should be ruled out in all patients, whereas primary aldosteronism has to be considered in hypertensive and/or hypokalemic patients. The 1 mg overnight dexamethasone suppression test is the test recommended for screening of subclinical Cushing's syndrome (SCS) with a threshold at 138 nmol/l for considering this condition. A value of 50 nmol/l virtually excludes SCS with an area of uncertainty between 50 and 138 nmol/l.

Management

Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess. Data are insufficient to make firm recommendations for or against surgery in patients with SCS. However, adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.
Clinical and metabolic characteristics of acromegalic patients with high IGF1/normal GH levels during somatostatin analog treatment
Authors: Matta Maria , Bongard Vanina , Grunenwald Solange , Maiza Jean-Christophe , Bennet Antoine , Caron Philippe
Published: April 2011

Context

Divergence between GH and IGF1 values are often reported in treated acromegalic patients, but the mechanisms of this discrepancy have not been completely explored.

Objective

To evaluate the frequency of divergence between GH and IGF1 values and identify the role of clinical and metabolic factors in treated patients with acromegaly, according to the latest criteria of Cure published in July 2010.

Design

Retrospective study of patients' records between October 2002 and March 2008. Patients were grouped according to their mean GH and IGF1 values as ‘controlled’ (normal GH and IGF1), ‘divergent’ (high IGF1 and normal GH) and ‘uncontrolled’ (high GH and IGF1), and compared with respect to their clinical characteristics and metabolic markers.

Results

Patients (n=104) were grouped as ‘controlled’ (n=20), ‘divergent’ (n=43) and ‘uncontrolled’ (n=41). More patients in the divergent group (93%) and uncontrolled group (98%) were treated with somatostatin analogs than in the controlled group (65%; P=0.001 for the comparison of the three groups). Patients in the divergent group had higher fasting blood glucose (0.94 g/l (interquartile range: 0.83–1.17)) and systolic blood pressure (130 mmHg (120–140) compared with the controlled group (0.84 g/l (0.80–0.92); P=0.017) and 120 mmHg (interquartile range: 110–130; P=0.029). In patients with divergent IGF1/GH levels, fasting glucose and GH were both strongly associated with IGF1.

Conclusion

Totally 41% of treated acromegalic patients had a high IGF1 and normal GH level. In these divergent patients treated with somatostatin analogs, these clinical and metabolic parameters might either play a causal role or be a marker for disease activity.
Postablation 131I scintigraphy with neck and thorax SPECT–CT and stimulated serum thyroglobulin level predict the outcome of patients with differentiated thyroid cancer
Authors: Ciappuccini Renaud , Heutte Natacha , Trzepla Géraldine , Rame Jean-Pierre , Vaur Dominique , Aide Nicolas , Bardet Stéphane
Published: April 2011

Objective

Neck and thorax single photon emission computed tomography with computed tomography (SPECT–CT) improves the reliability of postablation 131I whole-body scan (WBS) for differentiated thyroid cancer (DTC). The aim of this study was to assess the prognostic value for persistent or recurrent disease of postablation 131I scintigraphy combining WBS and neck and thorax SPECT–CT with that of the previously known predictive factors.

Methods

This is a single referral center prospective study with a median follow-up of 29 months. Postablation 131I WBS and neck and thorax SPECT–CT were performed in 170 consecutive patients treated between 2006 and 2008. Stimulated serum thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb) levels were measured. The impact on disease-free survival of age; gender; postablation 131I scintigraphy; stimulated serum Tg level; T, N, and M status; and macroscopic lymph node involvement was assessed by univariate and multivariate analyses.

Results

Persistent or recurrent disease was observed in 32 (19%) patients. In the whole group of patients, only positive WBS with SPECT–CT was related to an increased risk of persistent or recurrent disease (hazards ratio (HR)=65.21, 95% confidence interval (CI)=26.03–163.39, P<0.0001). In patients without TgAb (n=146), both positive WBS with SPECT–CT (HR=18.86, 95% CI=5.02–70.85, P<0.0001) and serum Tg level ≥58 ng/ml (HR=4.42, 95% CI=1.18–16.53, P=0.0271) were associated with an increased risk.

Conclusion

In patients with DTC, the cross analysis of postablation 131I scintigraphy with neck and thorax SPECT–CT and stimulated serum Tg level enables early assessment of the risk of persistent or recurrent disease.
Visfatin inhibits apoptosis of pancreatic β-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway
Authors: Cheng Qun , Dong Weipin , Qian Lei , Wu Jingcheng , Peng Yongde
Published: April 2011

Visfatin is an adipocytokine that plays an important role in attenuating insulin resistance by binding to insulin receptor. It has been suggested that visfatin plays a role in the regulation of cell apoptosis and inflammation by an as yet unidentified mechanism. This study investigated the protective effects of visfatin on palmitate-induced islet β-cell apoptosis in the clonal mouse pancreatic β-cell line MIN6. The cells were treated with palmitate and/or recombinant visfatin. An 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay was used to detect cell proliferation, V-FITC/propidium iodide staining was used to measure cell apoptosis and necrosis, and western blot analysis was used to detect the expression of proapoptotic proteins. The incubation of the cells with visfatin led to a concentration-dependent increase of cell proliferation (1.55-fold at 10−7 M and 24 h compared with control,P<0.05). Visfatin significantly reduced the cell apoptosis induced by palmitate and caused a significant change in the expression of several proapoptotic proteins, including upregulation of Bcl-2 and a marked downregulation of cytochromecand caspase 3. Visfatin also activated the ERK1/2 and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathways in a time- and concentration-dependent manner, and the effect of visfatin on apoptosis was blocked by the specific ERK1/2 and PI3K/AKT inhibitors, PD098059 and LY294002. We conclude that visfatin can increase β-cell proliferation and prevent apoptosis, activate intracellular signaling, and regulate the expression of proapoptotic proteins. The antiapoptotic action of visfatin is mediated by activation of mitogen-activated protein kinase-dependent and PI3K-dependent signaling pathways.