bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality Associated with Neurofibromatosis 1: A Cohort Study of 1895 Patients in 1980-2006 in France
Authors: Duong Tu Anh , Sbidian Emilie , Valeyrie-Allanore Laurence , Vialette Cédric , Ferkal Salah , Hadj-Rabia Smaïl , Glorion Christophe , Lyonnet Stanislas , Zerah Michel , Kemlin Isabelle , Rodriguez Diana , Bastuji-Garin Sylvie , Wolkenstein Pierre
Published: May 2011

Background

Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.

Methods

Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.

Results

Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6;P< 10-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3;P< 10-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8;P< 10-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).

Conclusions

We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.
Tailoring inputs to achieve maximal neuronal firing
Authors: Wang Jiaoyan , Costello Willie , Rubin Jonathan E
Published: May 2011

We consider the constrained optimization of excitatory synaptic input patterns to maximize spike generation in leaky integrate-and-fire (LIF) and theta model neurons. In the case of discrete input kicks with a fixed total magnitude, optimal input timings and strengths are identified for each model using phase plane arguments. In both cases, optimal features relate to finding an input level at which the drop in input between successive spikes is minimized. A bounded minimizing level always exists in the theta model and may or may not exist in the LIF model, depending on parameter tuning. We also provide analytical formulas to estimate the number of spikes resulting from a given input train. In a second case of continuous inputs of fixed total magnitude, we analyze the tuning of an input shape parameter to maximize the number of spikes occurring in a fixed time interval. Results are obtained using numerical solution of a variational boundary value problem that we derive, as well as analysis, for the theta model and using a combination of simulation and analysis for the LIF model. In particular, consistent with the discrete case, the number of spikes in the theta model rises and then falls again as the input becomes more tightly peaked. Under a similar variation in the LIF case, we numerically show that the number of spikes increases monotonically up to some bound and we analytically constrain the times at which spikes can occur and estimate the bound on the number of spikes fired.
Evaluation of 3C microelectromechanical system data on a 2D line: Direct comparison with conventional vertical-component geophone arrays and PS-wave analysis
Authors: Stotter Christian , Angerer Erika
Published: May 2011

A 2D vibroseis line was acquired in the Vienna Basin (Austria) for the purpose of comparing the data of digital multicomponent single sensors based on microelectromechanical system (MEMS) sensors alongside conventional vertical-component geophone arrays. For efficient removal of coherent noise during processing, all source points were recorded in single-sweep mode, i.e., no vertical stacking was performed in the field. On this densely sampled data set, several noise-reduction techniques, such as digital array forming, frequency-wavenumber (f-k) filtering in shot and receiver domains, and polarization filters, proved to be valuable in reducing source-generated noise. The results showed that, with the use of single-sweep recording and polarization filter techniques, it is possible to produce seismic sections for a single-receiver three-component (3C) MEMS line that are comparable to a conventional geophone array line in signal-to-noise ratio. However, the higher number of single geophones and hence the stronger attenuation of random noise in the conventional array resulted in an advantage for the analog geophone data set. The second goal for this survey was to evaluate additional information contained in the horizontal components of the MEMS data. The multicomponent data allowed for the processing of mode-converted shear-wave data, performed for the first time in the Vienna Basin. Azimuthal anisotropy related to horizontal stresses was observed in the Neogene section of the shear-wave data set. A PP-PS event correlation allowed the identification of major shallow horizons. Interpretation of the final sections confirmed that the PS data are useful to distinguish between gas reservoirs and high-porosity water sands, which can cause similar P-wave amplitude variation with offset (AVO) effects.
GH Receptor Plays a Major Role in Liver Regeneration through the Control of EGFR and ERK1/2 Activation
Authors: Zerrad-Saadi Amal , Lambert-Blot Martine , Mitchell Claudia , Bretes Hugo , Collin de l'Hortet Alexandra , Baud Véronique , Chereau Fanny , Sotiropoulos Athanassia , Kopchick John J. , Liao Lan , Xu Jianming , Gilgenkrantz Hélène , Guidotti Jacques-Emmanuel
Published: May 2011

GH is a pleiotropic hormone that plays a major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested that GH signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was to identify the mechanisms by which GH controls liver regeneration. We performed two thirds partial hepatectomies in GH receptor (GHR)-deficient mice and wild-type littermates and showed a blunted progression in the G1/S transition phase of the mutant hepatocytes. This impaired liver regeneration was not corrected by reestablishing IGF-1 expression. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between mutant and wild-type mice, cell cycle progression was significantly blunted in mutant mice. The main defect in GHR-deficient mice was the deficiency of the epidermal growth factor receptor activation during the process of liver regeneration. Finally, among the pathways activated downstream of GHR during G1 phase progression, namely Erk1/2, Akt, and signal transducer and activator of transcription 3, we only found a reduced Erk1/2 phosphorylation in mutant mice. In conclusion, our results demonstrate that GH signaling plays a major role in liver regeneration and strongly suggest that it acts through the activation of both epidermal growth factor receptor and Erk1/2 pathways.
Individual Polychlorinated Biphenyl (PCB) Congeners Produce Tissue- and Gene-Specific Effects on Thyroid Hormone Signaling during Development
Authors: Giera Stefanie , Bansal Ruby , Ortiz-Toro Theresa M. , Taub Daniel G. , Zoeller R. Thomas
Published: May 2011

Polychlorinated biphenyls (PCB) are industrial chemicals linked to developmental deficits that may be caused in part by disrupting thyroid hormone (TH) action by either reducing serum TH or interacting directly with the TH receptor (TR). Individual PCB congeners can activate the TR in vitro when the metabolic enzyme cytochrome P4501A1 (CYP1A1) is induced, suggesting that specific PCB metabolites act as TR agonists. To test this hypothesis in vivo, we compared two combinations of PCB congeners that either activate the TR (PCB 105 and 118) or not (PCB 138 and 153) in the presence or absence of a PCB congener (PCB 126) that induces CYP1A1 in vitro. Aroclor 1254 was used as a positive control, and a group treated with propylthiouracil was included to characterize the effects of low serum TH. We monitored the effects on TH signaling in several peripheral tissues by measuring the mRNA expression of well-known TH-response genes in these tissues. Aroclor 1254 and its component PCB 105/118/126 reduced total T4 to the same extent as that of propylthiouracil but increased the expression of some TH target genes in liver. This effect was strongly correlated with CYP1A1 expression supporting the hypothesis that metabolism is necessary. Effects were gene and tissue specific, indicating that tissue-specific metabolism is an important component of PCB disruption of TH action and that PCB metabolites interact in complex ways with the TR. These are essential mechanisms to consider when evaluating the health risks of contaminant exposures, for both PCB and other polycyclic compounds known to interact with nuclear hormone receptors.
Highly Visible Expression of an Oxytocin-Monomeric Red Fluorescent Protein 1 Fusion Gene in the Hypothalamus and Posterior Pituitary of Transgenic Rats
Authors: Katoh Akiko , Fujihara Hiroaki , Ohbuchi Toyoaki , Onaka Tatsushi , Hashimoto Takashi , Kawata Mitsuhiro , Suzuki Hideaki , Ueta Yoichi
Published: May 2011

We have generated rats bearing an oxytocin (OXT)-monomeric red fluorescent protein 1 (mRFP1) fusion transgene. The mRFP1 fluorescence was highly visible in ventral part of the supraoptic nucleus (SON) and the posterior pituitary in a whole mount. mRFP1 fluorescence in hypothalamic sections was also observed in the SON, the paraventricular nucleus (PVN), and the internal layer of the median eminence. Salt loading for 5 d caused a marked increase in mRFP1 fluorescence in the SON, the PVN, the median eminence, and the posterior pituitary. In situ hybridization histochemistry revealed that the expression of the mRNA encoding the OXT-mRFP1 fusion gene was observed in the SON and the PVN of euhydrated rats and increased dramatically after chronic salt loading. The expression of the endogenous OXT and the arginine vasopressin (AVP) genes were significantly increased in the SON and the PVN after chronic salt loading in both nontransgenic and transgenic rats. These responses were not different between male and female rats. Compared with nontransgenic rats, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration, OXT, and AVP levels. Finally, we succeeded in generating a double-transgenic rat that expresses both the OXT-mRFP1 fusion gene and the AVP-enhanced green fluorescent protein fusion gene. Our new transgenic rats are valuable new tools to study the physiology of the hypothalamo-neurohypophysial system.
Wish Fulfillment, Detection, and the Production of Knowledge in Bleak House
Authors: Ben-Merre David
Published: May 2011

Charles Dickens's Bleak House depicts the changing epistemologies of the nineteenth century, celebrating the emergent figure of the detective and a verifiable inductive method as the dominant mode of knowledge production. At the climax of the novel, however, this epistemology is abandoned in favor of an unreliable and culturally partial system, which promotes ideology masking as truth. Bleak House thus forces its readership either to reject the knowledge-based system the narrative has so painstakingly established or to reject its final discursive production. By tracing the viability of knowledge systems in both serial and omnibus forms, I argue that Inspector Bucket's conclusions regarding the murder of Tulkinghorn do not meet the epistemological standards set by the novel itself. Contrary to D. A. Miller's account of the novel as a closed disciplinary instrument, I argue that this “open” ending allows readers to question discursive productions and the disciplinary structures underlying them.
Strange Connections: Sensation, Morality, and the Law in Margaret Oliphant'sSalem Chapel
Authors: Bruce Leslie
Published: May 2011

In their debates preceding the 1857 Divorce Act, legislators unwittingly aligned abused wives and priests in ways that brought into focus both groups' economic dependence upon their superiors. I contend that Margaret Oliphant's Salem Chapel (1863) employs the very alignment Parliament had overlooked to condemn the law's insufficient protection of mistreated wives. Salem Chapel censures the Divorce Act by provocatively juxtaposing the sensational and realistic plots of two characters—an emotionally abused mother and a vocationally dissatisfied minister—and thereby opposes moral and legal authority within a domestic framework. However, Oliphant's ambivalence regarding both the sensation novel and the writing woman impels her to create a “sanitized” sensational plot capable of accommodating her sense of propriety as well as her understanding of women's legal and social limitations. As the novel delineates its characters' attempts to dissolve their clerical and marital contracts, Salem Chapel transforms a dissenting minister straining against his lack of autonomy into an acceptable novelistic surrogate for abused wives mired in marital conflict. In doing so, Salem Chapel's generic combination highlights a conflict between domestic and religious ideologies, which expected women and ministers to cultivate the morality of others, and English law, which denied them the legal authority and autonomy necessary to fulfill this obligation. Oliphant's novel thus demonstrates that women writers could protest legal inequities indirectly by judiciously exploiting the flexibility of disparaged genres within the confines of the respected mode of realism.
On the Rationality of Belief-Invariance in Light of Peer Disagreement
Authors: Lam Barry
Published: May 2011

If you are currently a reliable epistemic agent in some domain, you would not want to adopt a rule of belief-revision in that domain that rendered you less reliable. However, you probably would want to adopt a rule that rendered you more reliable in that domain. In the epistemology of disagreement, there are two main competing rules offered for belief-revision in the face of peer disagreement: maintaining your existing opinion, or meeting halfway. This article investigates the comparative reliability of these two rules using two measures of reliability for degrees of belief, calibration and Brier scoring. Using one measure of reliability, it can be shown that necessarily, meeting halfway is the more reliable rule. Using another measure of reliability, it can be shown that generally, belief-invariance is the more reliable rule. This article argues from these formal results that belief-invariance in light of peer disagreement is sometimes rationally permissible and that, even when it is not, being required to revise your opinions in light of peer disagreement does not lead to any kind of problematic skepticism.
Bare Quantifiers
Authors: Szabó Zoltán Gendler
Published: May 2011

Consider the hypothesis that every quantified sentence in every natural language contains some expression or other whose extension constrains the domain of quantification. If the hypothesis is correct, quantificational domains are fixed in fundamentally different ways in natural languages and in standard artificial languages. For those of us who think sentences with different logical forms express different propositions, it would mean that no proposition expressed in a typical formal language is expressible in any natural language. The article begins by clarifying the hypothesis and by arguing that there is no easy way to defeat it—prima facie counterexamples are many, but none of them withstand serious scrutiny. Then the article presents a real counterexample—a hitherto largely neglected reading of quantified attitude-reports where the attitude verb splits the quantifier from its restrictor. The article shows that split readings can occur not only with attitude verbs but with modals, tense, and aspectual markers as well. The upshot of the article is that although there is a real threat to our comfortable assumption that the sort of bare quantification we routinely employ in logic, mathematics, and the sciences can be fully captured in English, there is also reason to think that the threat can be averted.
Breaking Gridlock: The Determinants of Health Policy Change in Congress
Authors: Volden Craig , Wiseman Alan E.
Published: May 2011

Prior to the 2010 health care reforms, scholars often commented that health policy making in Congress was mired in political gridlock, that reforms were far more likely to fail than to succeed, and that the path forward was unclear. In light of recent events, new narratives are being advanced. In formulating these assessments, scholars of health politics tend to analyze individual major reform proposals to determine why they succeeded or failed and what lessons could be drawn for the future. Taking a different approach, we examine all health policies proposed in the U.S. House of Representatives between 1973 and 2002. We analyze these bills' fates and the effectiveness of their sponsors in guiding these proposals through Congress. Setting these proposed policies against a baseline of policy advancements in other areas, we demonstrate that health policy making has indeed been far more gridlocked than policy making in most other areas. We then isolate some of the causes of this gridlock, as well as some of the conditions that have helped to bring about health policy change.
Commercial Importation of Prescription Drugs in the United States: Short-Run Implications
Authors: Danzon Patricia M. , Johnson Scott J. , Long Genia , Furukawa Michael F.
Published: May 2011

The option of legalizing the commercial importation of prescription drugs is of continued policy interest as a way to reduce U.S. drug spending. Using IMS data, we estimate potential savings from commercial drug importation under assumptions about percentage of drugs likely to attract imports; potential supply from foreign countries; and share of savings passed on to payers. Our base case estimate is that $1.7 billion per year, or 0.6 percent of total drug spending, would be saved by payers; sensitivity analyses range from 0.2 to 2.5 percent under plausible assumptions and up to 17.4 percent under unrealistic assumptions about unlimited foreign supply, costless trade, and zero profits for intermediaries. Estimated savings to payers are less than the average price differentials between the United States and foreign countries because proposed legislation exempts certain drugs from importation; foreign markets are small relative to the United States; regulatory and other constraints may limit the volume of exports; trade is costly; and intermediaries will retain some savings. Although savings to U.S. payers/consumers would likely be small and have minimal impact on total U.S. health care spending, costs to other countries could be significant, due to reduced access and possibly higher prices. In the long run, reduced investment in R&D could adversely affect consumers globally.
How Brazil Outpaced the United States When It Came to Aids: The Politics of Civic Infiltration, Reputation, and Strategic Internationalization
Authors: Gómez Eduardo J.
Published: May 2011

Using a temporal approach dividing the reform process into two periods, this article explains how both Brazil and the United States were slow to respond to AIDS. However, Brazil eventually outpaced the United States in its response due to international rather than democratic pressures. Since the early 1990s, Brazil's success has been attributed to “strategic internationalization”: the concomitant acceptance and rejection of global pressure for institutional change and antiretroviral treatment, respectively. The formation of tripartite partnerships among donors, AIDS officials, and nongovernmental organizations has allowed Brazil to avoid foreign aid dependency, while generating ongoing incentives for influential AIDS officials to incessantly pressure Congress for additional funding. Given the heightened international media attention, concern about Brazil's reputation has contributed to a high level of political commitment. By contrast, the United States' more isolationist relationship with the international community, its focus on leading the global financing of AIDS efforts, and the absence of tripartite partnerships have prevented political leaders from adequately responding to the ongoing urban AIDS crisis. Thus, Brazil shows that strategically working with the international health community for domestic rather than international influence is vital for a sustained and effective response to AIDS.
A comprehensive assessment of the SOD1G93A low-copy transgenic mouse, which models human amyotrophic lateral sclerosis
Authors: Acevedo-Arozena Abraham , Kalmar Bernadett , Essa Shafa , Ricketts Thomas , Joyce Peter , Kent Rosie , Rowe Claire , Parker Andy , Gray Anna , Hafezparast Majid , Thorpe Julian R. , Greensmith Linda , Fisher Elizabeth M. C.
Published: May 2011

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that results in the death of motor neurons in the brain and spinal cord. The disorder generally strikes in mid-life, relentlessly leading to paralysis and death, typically 3–5 years after diagnosis. No effective treatments are available. Up to 10% of ALS is familial, usually autosomal dominant. Several causative genes are known and, of these, mutant superoxide dismutase 1 (SOD1) is by far the most frequently found, accounting for up to 20% of familial ALS. A range of human mutant SOD1 transgenic mouse strains has been produced, and these largely successfully model the human disease. Of these, the most widely used is the SOD1 mouse, which expresses a human SOD1 transgene with a causative G93A mutation. This mouse model is excellent for many purposes but carries up to 25 copies of the transgene and produces a great excess of SOD1 protein, which might affect our interpretation of disease processes. A variant of this strain carries a deletion of the transgene array such that the copy number is dropped to eight to ten mutant SOD1 genes. This ‘deleted’ ‘low-copy’ mouse undergoes a slower course of disease, over many months. Here we have carried out a comprehensive analysis of phenotype, including nerve and muscle physiology and histology, to add to our knowledge of this ‘deleted’ strain and give baseline data for future studies. We find differences in phenotype that arise from genetic background and sex, and we quantify the loss of nerve and muscle function over time. The slowly progressive pathology observed in this mouse strain could provide us with a more appropriate model for studying early-stage pathological processes in ALS and aid the development of therapies for early-stage treatments.
Condensin phosphorylated by the Aurora-B-like kinase Ark1 is continuously required until telophase in a mode distinct from Top2
Authors: Nakazawa Norihiko , Mehrotra Rajesh , Ebe Masahiro , Yanagida Mitsuhiro
Published: May 2011

Condensin is a conserved protein complex that functions in chromosome condensation and segregation. It has not been previously unequivocally determined whether condensin is required throughout mitosis. Here, we examined whether Schizosaccharomyces pombe condensin continuously acts on chromosomes during mitosis and compared its role with that of DNA topoisomerase II (Top2). Using double mutants containing a temperature-sensitive allele of the condensin SMC2 subunit cut14 (cut14-208) or of top2, together with the cold-sensitive nda3-KM311 mutation (in β-tubulin), temperature-shift experiments were performed. These experiments allowed inactivation of condensin or Top2 at various stages throughout mitosis, even after late anaphase. The results established that mitotic chromosomes require condensin and Top2 throughout mitosis, even in telophase. We then showed that the Cnd2 subunit of condensin (also known as Barren) is the target subunit of Aurora-B-like kinase Ark1 and that Ark1-mediated phosphorylation of Cnd2 occurred throughout mitosis. The phosphorylation sites in Cnd2 were determined by mass spectrometry, and alanine and glutamate residue replacement mutant constructs for these sites were constructed. Alanine substitution mutants of Cnd2, which mimic the unphosphorylated protein, exhibited broad mitotic defects, including at telophase, and overexpression of these constructs caused a severe dominant-negative effect. By contrast, glutamate substitution mutants, which mimic the phosphorylated protein, alleviated the segregation defect in Ark1-inhibited cells. In telophase, the condensin subunits in cut14-208 mutant accumulated in lumps that contained telomeric DNA and proteins that failed to segregate. Condensin might thus serve to keep the segregated chromosomes apart during telophase.
Medusa structure of the gene regulatory network: dominance of transcription factors in cancer subtype classification
Authors: Guo Yuchun , Feng Ying , Trivedi Niraj S , Huang Sui
Published: May 2011

Gene expression profiles consisting of ten thousands of transcripts are used for clustering of tissue, such as tumors, into subtypes, often without considering the underlying reason that the distinct patterns of expression arise because of constraints in the realization of gene expression profiles imposed by the gene regulatory network. The topology of this network has been suggested to consist of a regulatory core of genes represented most prominently by transcription factors (TFs) and microRNAs, that influence the expression of other genes, and of a periphery of ‘enslaved’ effector genes that are regulated but not regulating. This ‘medusa’ architecture implies that the core genes are much stronger determinants of the realized gene expression profiles. To test this hypothesis, we examined the clustering of gene expression profiles into known tumor types to quantitatively demonstrate that TFs, and even more pronounced, microRNAs, are much stronger discriminators of tumor type specific gene expression patterns than a same number of randomly selected or metabolic genes. These findings lend support to the hypothesis of a medusa architecture and of the canalizing nature of regulation by microRNAs. They also reveal the degree of freedom for the expression of peripheral genes that are less stringently associated with a tissue type specific global gene expression profile.
Mevalonate depletion mediates the suppressive impact of geranylgeraniol on murine B16 melanoma cells
Authors: Katuru Rajasekhar , Fernandes Nicolle V , Elfakhani Manal , Dutta Dibyendu , Mills Nathaniel , Hynds DiAnna L , King Clay , Mo Huanbiao
Published: May 2011

The diterpene geranylgeraniol (all trans-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraen-1-ol) suppresses the growth of human liver, lung, ovary, pancreas, colon, stomach and blood tumors with undefined mechanisms. We evaluated the growth-suppressive activity of geranylgeraniol in murine B16 melanoma cells. Geranylgeraniol induced dose-dependent suppression of B16 cell growth (IC50 = 55 ± 13 µmol/L) following a 48-h incubation in 96-well plates. Cell cycle arrest at the G1 phase, manifested by a geranylgeraniol-induced increase in the G1/S ratio and decreased expression of cyclin D1 and cyclin-dependent kinase 4, apoptosis detected by Guava Nexin™ assay and fluorescence microscopy following acridine orange and ethidium bromide dual staining, and cell differentiation shown by increased alkaline phosphatase activity, contributed to the growth suppression. Murine 3T3-L1 fibroblasts were 10-fold more resistant than B16 cells to geranylgeraniol-mediated growth suppression. Geranylgeraniol at near IC50 concentration (60 µmol/L) suppressed the mRNA level of 3-hydroxy-3-methylglutaryl coenzyme A (HMG‐CoA) reductase by 50%. The impact of geranylgeraniol on B16 cell growth, cell cycle arrest and apoptosis were attenuated by supplemental mevalonate, the product of HMG‐CoA reductase that is essential for cell growth. Geranylgeraniol and d- δ-tocotrienol, a down-regulator of HMG‐CoA reductase, additively suppressed the growth of B16 cells. These results support our hypothesis that mevalonate depletion mediates the tumor-specific growth-suppressive impact of geranylgeraniol. Geranylgeraniol may have potential in cancer chemoprevention and/or therapy.
Consumers’ Emotional Bonds with Foreign Countries: Does Consumer Affinity Affect Behavioral Intentions?
Authors: Oberecker Eva M. , Diamantopoulos Adamantios
Published: May 2011

The construct of consumer affinity, which captures country-specific favorable feelings toward particular foreign countries, was recently introduced in the international marketing literature. In this study, the authors conceptually advance the consumer affinity construct and develop a measurement instrument for capturing affinity feelings. They also link consumer affinity, country image, and consumer ethnocentrism to key consumer behavior variables—namely, perceived risk and willingness to buy products from, invest in, and visit the affinity country. The findings indicate that consumer affinity is more powerful than consumers’ ethnocentric tendencies in explaining both perceived risk and willingness to buy. The results also show that consumer affinity is more influential than cognitive evaluations of a country for the majority of the behavioral outcomes considered in the study (perceived risk, visit intentions, and investment intentions). Thus, internationally active companies can benefit from leveraging consumer affinity feelings in addition to positive country images. Overall, the study emphasizes the important role of positive affect in shaping consumer behavior, thus complementing prior research that focuses exclusively on the behavioral implications of negative affect (most notably consumer animosity).
Efficacy of two organic biocides with co-added antioxidants
Authors: Schultz Tor P. , Nicholas Darrel D.
Published: May 2011

No abstract available
Soluble Aβ Oligomers Inhibit Long-Term Potentiation through a Mechanism Involving Excessive Activation of Extrasynaptic NR2B-Containing NMDA Receptors
Authors: Li Shaomin , Jin Ming , Koeglsperger Thomas , Shepardson Nina E. , Shankar Ganesh M. , Selkoe Dennis J.
Published: May 2011

In Alzheimer's disease (AD), dementia severity correlates strongly with decreased synapse density in hippocampus and cortex. Numerous studies report that hippocampal long-term potentiation (LTP) can be inhibited by soluble oligomers of amyloid β-protein (Aβ), but the synaptic elements that mediate this effect remain unclear. We examined field EPSPs and whole-cell recordings in wild-type mouse hippocampal slices. Soluble Aβ oligomers from three distinct sources (cultured cells, AD cortex, or synthetic peptide) inhibited LTP, and this was prevented by the selective NR2B inhibitors ifenprodil and Ro 25-6981. Soluble Aβ enhanced NR2B-mediated NMDA currents and extrasynaptic responses; these effects were mimicked by the glutamate reuptake inhibitordl-threo-β-benzyloxyaspartic acid. Downstream, an Aβ-mediated rise in p38 mitogen-activated protein kinase (MAPK) activation was followed by downregulation of cAMP response element-binding protein, and LTP impairment was prevented by inhibitors of p38 MAPK or calpain. Thus, soluble Aβ oligomers at low nanomolar levels present in AD brain increase activation of extrasynaptic NR2B-containing receptors, thereby impairing synaptic plasticity.
Recalling and Forgetting Dreams: Theta and Alpha Oscillations during Sleep Predict Subsequent Dream Recall
Authors: Marzano Cristina , Ferrara Michele , Mauro Federica , Moroni Fabio , Gorgoni Maurizio , Tempesta Daniela , Cipolli Carlo , De Gennaro Luigi
Published: May 2011

Under the assumption that dream recall is a peculiar form of declarative memory, we have hypothesized that (1) the encoding of dream contents during sleep should share some electrophysiological mechanisms with the encoding of episodic memories of the awake brain and (2) recalling a dream(s) after awakening from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep should be associated with different brain oscillations. Here, we report that cortical brain oscillations of human sleep are predictive of successful dream recall. In particular, after morning awakening from REM sleep, a higher frontal 5–7 Hz (theta) activity was associated with successful dream recall. This finding mirrors the increase in frontal theta activity during successful encoding of episodic memories in wakefulness. Moreover, in keeping with the different EEG background, a different predictive relationship was found after awakening from stage 2 NREM sleep. Specifically, a lower 8–12 Hz (alpha) oscillatory activity of the right temporal area was associated with a successful dream recall. These findings provide the first evidence of univocal cortical electroencephalographic correlates of dream recall, suggesting that the neurophysiological mechanisms underlying the encoding and recall of episodic memories may remain the same across different states of consciousness.
Active and Passive Antennal Movements during Visually Guided Steering in FlyingDrosophila
Authors: Mamiya Akira , Straw Andrew D. , Tómasson Egill , Dickinson Michael H.
Published: May 2011

Insects use feedback from a variety of sensory modalities, including mechanoreceptors on their antennae, to stabilize the direction and speed of flight. Like all arthropod appendages, antennae not only supply sensory information but may also be actively positioned by control muscles. However, how flying insects move their antennae during active turns and how such movements might influence steering responses are currently unknown. Here we examined the antennal movements of flyingDrosophiladuring visually induced turns in a tethered flight arena. In response to both rotational and translational patterns of visual motion,Drosophilaactively moved their antennae in a direction opposite to that of the visual motion. We also observed two types of passive antennal movements: small tonic deflections of the antenna and rapid oscillations at wing beat frequency. These passive movements are likely the result of wing-induced airflow and increased in magnitude when the angular distance between the wing and the antenna decreased. In response to rotational visual motion, increases in passive antennal movements appear to trigger a reflex that reduces the stroke amplitude of the contralateral wing, thereby enhancing the visually induced turn. Although the active antennal movements significantly increased antennal oscillation by bringing the arista closer to the wings, it did not significantly affect the turning response in our head-fixed, tethered flies. These results are consistent with the hypothesis that flyingDrosophilause mechanosensory feedback to detect changes in the wing induced airflow during visually induced turns and that this feedback plays a role in regulating the magnitude of steering responses.
The Calyx of Held Develops Adult-Like Dynamics and Reliability by Hearing Onset in the MouseIn Vivo
Authors: Sonntag Mandy , Englitz Bernhard , Typlt Marei , Rübsamen Rudolf
Published: May 2011

The development of the auditory system has received increasing attention since the mechanisms of patterned, spontaneous activity in prehearing mammals were discovered. This early activity originates in the cochlea and is assumed to be of importance for the establishment and refinement of synaptic connections in the auditory system. In the present study we investigate synaptic transmission and its interplay with spontaneous discharges in the developing auditory system. We used the calyx of Held as a model system, where this question can be investigatedin vivoover a broad range of ages [postnatal day 8 (P8)–P28]. To precisely quantify the timing and reliability of synaptic transmission, we developed a novel fitting approach which decomposes the extracellularly recorded signal into its presynaptic and postsynaptic components. In prehearing mice, we found signal transmission to be unreliable, with high variability in the transmission delay and in the amplitude of postsynaptic components. These timing and amplitude changes were strongly correlated with the preceding activity. Around hearing onset (P12–P14), the properties of signal transmission converged to the adult-like state which was characterized by high transmission reliability as well as high consistency in timing and amplitude. Although activity-dependent depression was still found in action potentials, EPSP depression no longer played a prominent role. In conclusion, the maturation of synaptic transmission at the calyx of Held seems to be precisely timed to achieve its adult potential by the time acoustically evoked signal processing commences.
Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a Biological Intersection between Cancer and Neurodegeneration
Authors: Sleiman Sama F. , Langley Brett C. , Basso Manuela , Berlin Jill , Xia Li , Payappilly Jimmy B. , Kharel Madan K. , Guo Hengchang , Marsh J. Lawrence , Thompson Leslie Michels , Mahishi Lata , Ahuja Preeti , MacLellan W. Robb , Geschwind Daniel H. , Coppola Giovanni , Rohr Jürgen , Ratan Rajiv R.
Published: May 2011

Oncogenic transformation of postmitotic neurons triggers cell death, but the identity of genes critical for degeneration remain unclear. The antitumor antibiotic mithramycin prolongs survival of mouse models of Huntington's diseasein vivoand inhibits oxidative stress-induced death in cortical neuronsin vitro. We had correlated protection by mithramycin with its ability to bind to GC-rich DNA and globally displace Sp1 family transcription factors. To understand how antitumor drugs prevent neurodegeneration, here we use structure–activity relationships of mithramycin analogs to discover that selective DNA-binding inhibition of the drug is necessary for its neuroprotective effect. We identify several genes (Myc, c-Src, Hif1α, and p21waf1/cip1) involved in neoplastic transformation, whose altered expression correlates with protective doses of mithramycin or its analogs. Most interestingly, inhibition of one these genes, Myc, is neuroprotective, whereas forced expression of Myc inducesRattus norvegicusneuronal cell death. These results support a model in which cancer cell transformation shares key genetic components with neurodegeneration.
Distribution of Phosphorylated TrkB Receptor in the Mouse Hippocampal Formation Depends on Sex and Estrous Cycle Stage
Authors: Spencer-Segal Joanna L. , Waters Elizabeth M. , Bath Kevin G. , Chao Moses V. , McEwen Bruce S. , Milner Teresa A.
Published: May 2011

Tropomyosin-related kinase B receptor (TrkB) is a neurotrophin receptor important for the synaptic plasticity underlying hippocampal-dependent learning and memory. Because this receptor is widely expressed in hippocampal neurons, the precise location of TrkB activation is likely important for its specific actions. The goal of this study was to identify the precise sites of TrkB activation in the mouse hippocampal formation and to determine any changes in the distribution of activated TrkB under conditions of enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal excitability. Using electron microscopy, we localized TrkB phosphorylated at tyrosine 816 (pTrkB) in the hippocampal formation of male and female mice under conditions of naturally low circulating estradiol and naturally high circulating estradiol, when BDNF expression, TrkB signaling, and synaptic plasticity are enhanced. To compare relative amounts of pTrkB in each group, we counted profiles containing pTrkB-immunoreactivity (pTrkB-ir) in all hippocampal subregions. pTrkB-ir was in axons, axon terminals, dendrites, and dendritic spines of neurons in the hippocampal formation, but the majority of pTrkB-ir localized to presynaptic profiles. pTrkB-ir also was abundant in glial profiles, which were further identified as microglia using immunofluorescence and confocal microscopy. Axonal and glial pTrkB-ir and pTrkB-ir in the CA1 stratum radiatum were more abundant in high-estradiol states (proestrus females) than low-estradiol states (estrus and diestrus females and males). These findings suggest that presynaptic TrkB is positioned to modulate estradiol-mediated and BDNF-dependent synaptic plasticity. Furthermore, they suggest a novel role for TrkB in microglial function in the neuroimmune system.
Effective Connectivity Reveals Important Roles for Both the Hyperdirect (Fronto-Subthalamic) and the Indirect (Fronto-Striatal-Pallidal) Fronto-Basal Ganglia Pathways during Response Inhibition
Authors: Jahfari Sara , Waldorp Lourens , van den Wildenberg Wery P. M. , Scholte H. Steven , Ridderinkhof K. Richard , Forstmann Birte U.
Published: May 2011

Fronto-basal ganglia pathways play a crucial role in voluntary action control, including the ability to inhibit motor responses. Response inhibition might be mediated via a fast hyperdirect pathway connecting the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA) with the subthalamic nucleus or, alternatively, via the indirect pathway between the cortex and caudate. To test the relative contribution of these two pathways to inhibitory action control, we applied an innovative quantification method for effective brain connectivity. Functional magnetic resonance imaging data were collected from 20 human participants performing a Simon interference task with an occasional stop signal. A single right-lateralized model involving both the hyperdirect and indirect pathways best explained the pattern of brain activation on stop trials. Notably, the overall connection strength of this combined model was highest on successfully inhibited trials. Inspection of the relationship between behavior and connection values revealed that fast inhibitors showed increased connectivity between rIFG and right caudate (rCaudate), whereas slow inhibitors were associated with increased connectivity between preSMA and rCaudate. In compliance, connection strengths from the rIFG and preSMA into the rCaudate were correlated negatively. If participants failed to stop, the magnitude of experienced interference (Simon effect), but not stopping latency, was predictive for the hyperdirect–indirect model connections. Together, the present results suggest that both the hyperdirect and indirect pathways act together to implement response inhibition, whereas the relationship between performance control and the fronto-basal ganglia connections points toward a top-down mechanism that underlies voluntary action control.
Dendrite-Derived Supernumerary Axons on Adult Axotomized Motor Neurons Possess Proteins That Are Essential for the Initiation and Propagation of Action Potentials and Synaptic Vesicle Release
Authors: Meehan Claire F. , MacDermid Victoria E. , Montague Steven J. , Neuber-Hess Monica , Rose P. Ken
Published: May 2011

Axotomy can trigger profound alterations in the neuronal polarity of adult neuronsin vivo. This can manifest itself in the development of new axon-like processes emanating from the tips of distal dendrites. Previously, these processes have been defined as axonal based on their axonal morphology. This study extends this definition to determine whether, more importantly, these processes possess the prerequisite molecular machinery to function as axons. Using a combination of intracellular labeling and immunohistochemistry, we demonstrate that the distribution of voltage-gated sodium channels on these processes matches the arrangement of these channels that is necessary for the initiation and conduction of action potentials. At terminal bouton-like structures they possess key proteins necessary for the release of synaptic vesicles (SV2 and synaptophysin). Thus, axon-like processes emanating from the tips of distal dendrites represent a rearrangement of neuronal polarity whereby axotomized neurons can develop additional functional axonsin vivo.
Nicotine Potentiation of Excitatory Inputs to Ventral Tegmental Area Dopamine Neurons
Authors: Mao Danyan , Gallagher Keith , McGehee Daniel S.
Published: May 2011

Drug-induced changes in synaptic strength are hypothesized to contribute to appetitive behavior and addiction. Nicotine, the major addictive substance in tobacco, activates nicotinic receptors (nAChRs) to initiate a series of adaptive changes at the cellular and circuit levels in brain, particularly the ventral tegmental area (VTA). Our laboratory previously reported that nicotine facilitates induction of long-term potentiation (LTP) in VTA dopamine (DA) neurons by increasing glutamate release via activation of α7 nAChRs on the glutamate terminals, suggesting a critical presynaptic contribution of nicotine in LTP induction. In the present study, we used anin vitroexposure paradigm to study the effect of nicotine on excitatory synaptic strength. Brief exposure of nicotine to brain slices from drug-naive adult rats followed by a period of recovery resulted in an NMDA receptor (NMDAR)-dependent increase of AMPA receptor/NMDAR ratio in VTA DA neurons, which is consistent with the induction of LTP. These effects are similar to that induced by a singlein vivonicotine injection intraperitoneally. The induction of synaptic potentiation required excitation of DA neurons mediated by somatodendritic α4β2 nAChRs, as well as enhancement of NMDAR function via D5dopamine receptors, also on DA neurons. Nicotine-induced increase of presynaptic glutamate release also contributed to the induction of synaptic plasticity, likely through increased activation of NMDAR. These results identified important receptor systems involved in nicotine-induced long-term changes in excitatory synaptic input to VTA DA neurons. The data also revealed remarkable similarity in the mechanisms underlying synaptic plasticity induced by nicotine and cocaine in the VTA.
Transcription Factor Short Stature Homeobox 2 Is Required for Proper Development of Tropomyosin-Related Kinase B-Expressing Mechanosensory Neurons
Authors: Scott Alexandra , Hasegawa Hiroshi , Sakurai Katsuyasu , Yaron Avraham , Cobb John , Wang Fan
Published: May 2011

Dorsal root ganglia (DRG) contain somatosensory neurons of diverse sensory modalities. Among these different types of sensory neurons, the molecular mechanisms that regulate the development and specification of touch neurons are the least well understood. We took a candidate approach and searched for transcription factors that are expressed in subsets of DRG neurons, and found that the transcription factor Shox2 (short stature homeobox 2) is expressed in subpopulations of TrkB (tropomyosin-related kinase B)- and Ret-expressing neurons at neonatal stages. Since TrkB is a known marker that is selectively expressed in touch sensory neurons, we decided to examine the function of Shox2 in specifying TrkB-positive DRG neurons. Conditional deletion ofShox2in neural crest cells (which give rise to all DRG neurons) caused a 60 ∼ 65% reduction in the number of TrkB-expressing neurons. It also resulted in an increase in coexpression of TrkC in Ret-positive sensory neurons. Deletion ofShox2in differentiating DRG neurons at later time points caused only a moderate reduction in TrkB expression. Overexpression of Shox2 in all neural crest cells resulted in a small increase in the number of TrkB-expressing neurons. Finally,Shox2deletion also caused reduced touch sensory axonal innervation to layers III/IV of the spinal cord. Together, our findings identify Shox2 as an essential but not sufficient component of the transcription programs required in neural progenitor cells for the proper specification of subsets of TrkB-expressing touch/mechanosensory neurons.