bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective observational study on tracheal tube cuff pressures in emergency patients– is neglecting the problem the problem?
Authors: Harm Falko , Zuercher Mathias , Bassi Marco , Ummenhofer Wolfgang
Published: December 2013

Background

Inappropriately cuffed tracheal tubes can lead to inadequate ventilation or silent aspiration, or to serious tracheal damage. Cuff pressures are of particular importance during aeromedical transport as they increase due to decreased atmospheric pressure at flight level. We hypothesised, that cuff pressures are frequently too high in emergency and critically ill patients but are dependent on providers’ professional background.

Methods

Tracheal cuff pressures in patients intubated before arrival of a helicopter-based rescue team were prospectively recorded during a 12-month period. Information about the method used for initial cuff pressure assessment, profession of provider and time since intubation was collected by interview during patient handover. Indications for helicopter missions were either Intensive Care Unit (ICU) transports or emergency transfers. ICU transports were between ICUs of two hospitals. Emergency transfers were either evacuation from the scene or transfer from an emergency department to a higher facility.

Results

This study included 101 patients scheduled for aeromedical transport. Median cuff pressure measured at handover was 45 (25.0/80.0) cmH2O; range, 8-120 cmH2O. There was no difference between patient characteristics and tracheal tube-size or whether anaesthesia personnel or non-anaesthesia personnel inflated the cuff (30 (24.8/70.0) cmH2O vs. 50 (28.0/90.0) cmH2O); p = 0.113.

With regard to mission type (63 patients underwent an emergency transfer, 38 patients an ICU transport), median cuff pressure was different: 58 (30.0/100.0) cmH2O in emergency transfers vs. 30 (20.0/45.8) cmH2O in inter-ICU transports; p < 0.001. For cuff pressure assessment by the intubating team, a manometer had been applied in 2 of 59 emergency transfers and in 20 of 34 inter-ICU transports (method was unknown for 4 cases each). If a manometer was used, median cuff pressure was 27 (20.0/30.0) cmH2O, if not 70 (47.3/102.8) cmH2O; p < 0.001.

Conclusions

Cuff pressures in the pre-hospital setting and in intensive care units are often too high. Interestingly, there is no significant difference between non-anaesthesia and anaesthesia personnel. Acceptable cuff pressures are best achieved when a cuff pressure manometer has been used. This method seems to be the only feasible one and is recommended for general use.
A Modified ELISA Accurately Measures Secretion of High Molecular Weight Hyaluronan (HA) by Graves' Disease Orbital Cells
Authors: Krieger Christine C. , Gershengorn Marvin C.
Published: December 2013

Excess production of hyaluronan (hyaluronic acid [HA]) in the retro-orbital space is a major component of Graves' ophthalmopathy, and regulation of HA production by orbital cells is a major research area. In most previous studies, HA was measured by ELISAs that used HA-binding proteins for detection and rooster comb HA as standards. We show that the binding efficiency of HA-binding protein in the ELISA is a function of HA polymer size. Using gel electrophoresis, we show that HA secreted from orbital cells is primarily comprised of polymers more than 500 000. We modified a commercially available ELISA by using 1 million molecular weight HA as standard to accurately measure HA of this size. We demonstrated that IL-1β-stimulated HA secretion is at least 2-fold greater than previously reported, and activation of the TSH receptor by an activating antibody M22 from a patient with Graves' disease led to more than 3-fold increase in HA production in both fibroblasts/preadipocytes and adipocytes. These effects were not consistently detected with the commercial ELISA using rooster comb HA as standard and suggest that fibroblasts/preadipocytes may play a more prominent role in HA remodeling in Graves' ophthalmopathy than previously appreciated.
Design for a Streamlined War Economy
Authors: Lerner Abba P.
Published: December 2013

[Reproduction of the text of a 1942 paper by Abba P. Lerner.]
Adverse Selection and Inertia in Health Insurance Markets: When Nudging Hurts
Authors: Handel Benjamin R
Published: December 2013

This paper investigates consumer inertia in health insurance markets, where adverse selection is a potential concern. We leverage a major change to insurance provision that occurred at a large firm to identify substantial inertia, and develop and estimate a choice model that also quantifies risk preferences and ex ante health risk. We use these estimates to study the impact of policies that nudge consumers toward better decisions by reducing inertia. When aggregated, these improved individual-level choices substantially exacerbate adverse selection in our setting, leading to an overall reduction in welfare that doubles the existing welfare loss from adverse selection. (JEL D82, G22, I13)
Intertemporal Price Discrimination in Storable Goods Markets
Authors: Hendel Igal , Nevo Aviv
Published: December 2013

We study intertemporal price discrimination when consumers can store for future consumption needs. We offer a simple model of demand dynamics, which we estimate using market-level data. Optimal pricing involves temporary price reductions that enable sellers to discriminate between price sensitive consumers, who stockpile for future consumption, and less price-sensitive consumers, who do not stockpile. We empirically quantify the impact of intertemporal price discrimination on profits and welfare. We find that sales (i) capture 25–30 percent of the gap between non-discriminatory profits and (unattainable) third-degree price discrimination profits, (ii) increase total welfare, and (iii) have a modest impact on consumer welfare. (JEL D11, D12, L11, L12, L81)
Two Perspectives on Preferences and Structural Transformation
Authors: Herrendorf Berthold , Rogerson Richard , Valentinyi Ákos
Published: December 2013

We assess the empirical importance of changes in income and relative prices for structural transformation in the postwar United States. We explain two natural approaches to the data: sectors may be categories of final expenditure or value added; e.g., the service sector may be the final expenditure on services or the value added from service industries. We estimate preferences for each approach and find that with final expenditure income effects are the dominant force behind structural transformation, whereas with value-added categories price effects are more important. We show how the input-output structure of the United States can reconcile these findings. (JEL E21, L16)
Information and Quality When Motivation is Intrinsic: Evidence from Surgeon Report Cards
Authors: Kolstad Jonathan T
Published: December 2013

If profit maximization is the objective of a firm, new information about quality should affect firm behavior only through its effects on market demand. I consider an alternate model in which suppliers are motivated by a desire to perform well in addition to profit. The introduction of quality “report cards” for cardiac surgery in Pennsylvania provides an empirical setting to isolate the relative role of extrinsic and intrinsic incentives in determining surgeon response. Information on performance that was new to surgeons and unrelated to patient demand led to an intrinsic response four times larger than surgeon response to profit incentives. (JEL D83, I11, L15)
Time as a Trade Barrier
Authors: Hummels David L , Schaur Georg
Published: December 2013

A large and growing share of world trade travels by air. We model exporters' choice between fast, expensive air cargo and slow, cheap ocean cargo, which depends on the price elasticity of demand and the value that consumers attach to fast delivery. We use US imports data that provide rich variation in the premium paid for air shipping and in time lags for ocean transit to extract consumers' valuation of time. We estimate that each day in transit is equivalent to an advalorem tariff of 0.6 to 2.1 percent. The most time-sensitive trade flows involve parts and components trade. (JEL F13, F14, L93)
The Demand for Youth: Explaining Age Differences in the Volatility of Hours
Authors: Jaimovich Nir , Pruitt Seth , Siu Henry E
Published: December 2013

Over the business cycle young workers experience much greater volatility of hours worked than prime-aged workers. This can arise from age differences in labor supply or labor demand characteristics. To distinguish between these, we document that, for young workers, both the cyclical volatilities of hours and wages are greater than those of the prime-aged. We argue that a general class of models featuring only age-specific labor supply differences cannot reconcile these facts. We then show that a simple model featuring labor demand differences can. (JEL E32, J13, J22, J23, J31)
News, Noise, and Fluctuations: An Empirical Exploration
Authors: Blanchard Olivier J , L'Huillier Jean-Paul , Lorenzoni Guido
Published: December 2013

We explore empirically models of aggregate fluctuations in which consumers form anticipations about the future based on noisy sources of information and these anticipations affect output in the short run. Our objective is to separate fluctuations due to changes in fundamentals (news) from those due to temporary errors in agents' estimates (noise). We show that structural VARs cannot be used to identify news and noise shocks, but identification is possible via a method of moments or maximum likelihood. Next, we estimate our model on US data. Our results suggest that noise shocks explain a sizable fraction of short-run consumption fluctuations. (JEL D84, E13, E21, E32)
Polarization and Ambiguity
Authors: Baliga Sandeep , Hanany Eran , Klibanoff Peter
Published: December 2013

We offer a theory of polarization as an optimal response to ambiguity. Suppose individual A's beliefs first-order stochastically dominate individual B's. They observe a common signal. They exhibit polarization if A's posterior dominates her prior and B's prior dominates her posterior. Given agreement on conditional signal likelihoods, we show that polarization is impossible under Bayesian updating or after observing extreme signals. However, we also show that polarization can arise after intermediate signals as ambiguity averse individuals implement their optimal prediction strategies. We explore when this polarization will occur and the logic underlying it. (JEL D81, D82, D83)
Social Preferences under Risk: Equality of Opportunity versus Equality of Outcome
Authors: Saito Kota
Published: December 2013

This paper axiomatizes a utility function for social preferences under risk. In the model, a single parameter captures a preference for equality of opportunity (i.e., equality of exante expected payoffs) relative to equality of outcome (i.e., equality of ex-post payoffs). In a deterministic environment, the model reduces to the model of Fehr and Schmidt (1999). The model is consistent with recent experiments on probabilistic dictator games. (JEL C72, D71, D81)
Nigerian secondary school adolescents’ perspective on abstinence-only sexual education as an effective tool for promotion of sexual health
Authors: Inyang Mfrekemfon P , Inyang Obonganyie P
Published: December 2013

The success of any type of sexual education programme depends on the knowledge and preparedness for practice by adolescents. A recent study has found that an ‘abstinence-only’ sexual education programme is effective in reducing sexual activity among adolescents. Knowledge of abstinence-only sexual education and preparedness for practice as an effective tool for promotion of sexual health among Nigerian secondary school adolescents was studied. An analytic descriptive survey design was used for the study. The research population comprised of all public secondary schools in three southern geopolitical zones of the Niger Delta Region of Nigeria. A multistage sampling technique was used to select 2020 senior secondary school (SS1-SS3) students as sample for the study. A partially self-designed and partially adapted questionnaire from an 'abstinence-only versus comprehensive sex education' debate, from debatepedia (http://wiki.idebate.org/), entitled 'Questionnaire on Nigerian Secondary School Adolescents’ Perspective on Abstinence-Only Sexual Education (QNSSAPAOSE)' was used in eliciting information from respondents. Hypotheses were formulated and tested. Frequency counts, percentage and Pearson Product Moment Correlation were used in analysing data. A greater proportion of secondary school adolescents in this study lacked knowledge of sexual education. About 80% of the respondents could not define sexual education. The general perspective on abstinence-only sexual education was negative, as revealed by the larger number of respondents who demonstrated unwillingness to practice abstinence-only sexual education. Specifically, of those who responded in favour of abstinence-only sexual education, the youngest group of adolescents (11-13 years) and the male respondents were more likely to accept this type of education than the other groups. Poor knowledge of sexual education could be responsible for unwillingness to practice abstinence-only sexual education. Sexual education should, therefore, be introduced into the secondary school curriculum and taught by well-prepared teachers to enable an informed decision on practice.
Platform Performance Investment in the Presence of Network Externalities
Authors: Anderson Edward G. , Parker Geoffrey G. , Tan Burcu
Published: December 2013

Managers of emerging platforms must decide what level of platform performance to invest in at each product development cycle in markets that exhibit two-sided network externalities. High performance is a selling point for consumers, but in many cases it requires developers to make large investments to participate. Abstracting from an example drawn from the video game industry, we build a strategic model to investigate the trade-off between investing in high platform performance versus reducing investment in order to facilitate third party content development. We carry out a full analysis of three distinct settings: monopoly, price-setting duopoly, and price-taking duopoly. We provide insights on the optimum investment in platform performance and demonstrate how conventional wisdom about product development may be misleading in the presence of strong cross-network externalities. In particular, we show that, contrary to the conventional wisdom about “winner-take-all” markets, heavily investing in the core performance of a platform does not always yield a competitive edge. We characterize the conditions under which offering a platform with lower performance but greater availability of content can be a winning strategy.
Quality of Life Indicators for Individuals With Intellectual Disabilities: Extending Current Practice
Authors: Brown Ivan , Hatton Chris , Emerson Eric
Published: December 2013

Quality of life is a social construct that is measured by what are considered to be its most appropriate indicators. Quality of life measurement in intellectual disability reflects a variety of indicators, often grouped under life domains. Subjective and objective methods of measuring indicators each have strengths and drawbacks, but it is currently considered best to use both methods. Indicators of quality of life that are common to all people have been measured to date, although indicators that are unique to individuals are highly useful for enhancing individual development and for applying person-centered practice. Aggregate quality of life data from individuals may not always be the best source of information for evaluating policies and service practices. A case is made for supplementing quality of life frameworks or adopting other frameworks for these purposes, with the Capabilities Framework offered as an example. Further, an argument is made that a pragmatic approach might best be taken to policy and program evaluation, whereby the key criterion for using a conceptual framework and set of indicators is its usefulness in effecting positive change in people's lives.
A Family of Mortality Jump Models Applied to US Data
Authors: Chen Hua
Published: December 2013

Mortality models are fundamental to quantify mortality/longevity risks and provide the basis of pricing and reserving. In this article, we consider a family of mortality jump models and propose a new generalized Lee–Carter model with asymmetric double exponential jumps. It is asymmetric in terms of both time periods of impact and frequency/severity profiles between adverse mortality jumps and longevity jumps. It is mathematically tractable and economically intuitive. It degenerates to a transitory exponential jump model when fitting the US mortality data and is the best fit compared with other jump models.
Das rheinland-pfälzische Digitalisierungsportal dilibri
Authors: Koelges Barbara , Schackmann Elmar
Published: December 2013

Dilibri ist die digitalisierte Sammlung von landeskundlichen Werken zu Rheinland-Pfalz sowie von Beständen aus rheinland-pfälzischen Bibliotheken. Mit dilibri hat das Landesbibliothekszentrum Rheinland-Pfalz eine einheitliche Plattform für Bibliotheken geschaffen, um landesweite Projekte im Bereich der Digitalisierung zu realisieren. Der Artikel beschreibt die Entwicklung des Digitalisierungsportals von der Einführungsphase über die Gewinnung von Kooperationspartnern, die technische und inhaltliche Weiterentwicklung bis hin zu dem von der DFG geförderten Digitalisierungsprojekt, das von 2010 bis 2012 von mehreren rheinland-pfälzischen Bibliotheken realisiert wurde.
CFD Modeling and Experimental Study of a Spray Dryer Performance
Authors: Sadripour Maryam , Rahimi Amir , Hatamipour Mohammad Sadegh
Published: December 2013

The performance of a pilot-scale spray dryer is investigated experimentally and theoretically. The governing equations for flow field, heat and mass transfer, and particle trajectory are solved by applying computational fluid dynamics (CFD). The effects of inlet air temperature and initial particle diameter on the outlet humidity and particle residence time are examined. These parameters should be considered carefully in proper designing of spray dryers especially for the heat-sensitive products. The model is validated with an error of 5.5%.
Quiver Hecke superalgebras
Authors: Kang Seok-Jin , Kashiwara Masaki , Tsuchioka Shunsuke
Published: December 2013

We introduce a new family of superalgebras which should be
considered as a super version of the Khovanov–Lauda–Rouquier
algebras.
Let I be the set of vertices of a Dynkin diagram with a
decomposition

I
=

I
even

⊔

I
odd

$I=I_{{\mathrm {even}}}\sqcup I_{{\mathrm {odd}}}$

.
To this data, we associate a
family of graded superalgebras R
n
, the quiver Hecke
superalgebras. When

I
odd

=
∅

$I_{{\mathrm {odd}}}=\emptyset $

, these algebras are nothing
but the usual Khovanov–Lauda–Rouquier algebras. We then define
another family of graded superalgebras RC
n
, the quiver
Hecke–Clifford superalgebras, and show that the superalgebras R
n

and RC
n
are weakly Morita superequivalent to each other.
Moreover, we
prove that the affine Hecke–Clifford superalgebras, as well as their
degenerate version, the affine Sergeev superalgebras, are isomorphic
to quiver Hecke–Clifford superalgebras RC
n
after a completion.
Hippocampus and Retrosplenial Cortex Combine Path Integration Signals for Successful Navigation
Authors: Sherrill Katherine R. , Erdem Uğur M. , Ross Robert S. , Brown Thackery I. , Hasselmo Michael E. , Stern Chantal E.
Published: December 2013

The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals.
Long-Term Antagonism of κ Opioid Receptors Prevents Escalation of and Increased Motivation for Heroin Intake
Authors: Schlosburg Joel E. , Whitfield Timothy W. , Park Paula E. , Crawford Elena F. , George Olivier , Vendruscolo Leandro F. , Koob George F.
Published: December 2013

The abuse of opioid drugs, both illicit and prescription, is a persistent problem in the United States, accounting for >1.2 million users who require treatment each year. Current treatments rely on suppressing immediate withdrawal symptoms and replacing illicit drug use with long-acting opiate drugs. However, the mechanisms that lead to preventing opiate dependence are still poorly understood. We hypothesized that κ opioid receptor (KOR) activation during chronic opioid intake contributes to negative affective states associated with withdrawal and the motivation to take increasing amounts of heroin. Using a 12 h long-access model of heroin self-administration, rats showed escalation of heroin intake over several weeks. This was prevented by a single high dose (30 mg/kg) of the long-acting KOR antagonist norbinaltorphimine (nor-BNI), paralleled by reduced motivation to respond for heroin on a progressive-ratio schedule of reinforcement, a measure of compulsive-like responding. Systemic nor-BNI also significantly decreased heroin withdrawal-associated anxiety-like behavior. Immunohistochemical analysis showed prodynorphin content increased in the nucleus accumbens core in all heroin-exposed rats, but selectively increased in the nucleus accumbens shell in long-access rats. Local infusion of nor-BNI (4 μg/side) into accumbens core altered the initial intake of heroin but not the rate of escalation, while local injection into accumbens shell selectively suppressed increases in heroin intake over time without altering initial intake. These data suggest that dynorphin activity in the nucleus accumbens mediates the increasing motivation for heroin taking and compulsive-like responding for heroin, suggesting that KOR antagonists may be promising targets for the treatment of opioid addiction.
Regulation of Spine Formation by ErbB4 in PV-Positive Interneurons
Authors: Yin Dong-Min , Sun Xiang-Dong , Bean Jonathan C. , Lin Thiri W. , Sathyamurthy Anupama , Xiong Wen-Cheng , Gao Tian-Ming , Chen Yong-Jun , Mei Lin
Published: December 2013

The trophic factor neuregulin 1 (Nrg1) and its receptorErbB4are schizophrenia candidate genes. NRG1-ErbB4 signaling was thought to regulate spine formation and function in a cell-autonomous manner. Yet, recent studies indicate that ErbB4 expression is largely restricted to GABAergic interneurons and is very low or absent in pyramidal cells. Here, we generated and characterized cell type-specificErbB4mutant and transgenic mice. Spine density and the number of excitatory synapses were unaltered by neither deletion nor overexpression of ErbB4 in pyramidal neurons. However, spine density and excitatory synapse number were reduced in PV-ErbB4−/−mice where ErbB4 was selectively ablated in parvalbumin-positive GABAergic interneurons. Concurrently, basal glutamate transmission was impaired in PV-ErbB4−/−mice, but not in mice where ErbB4 was deleted or overexpressed in pyramidal neurons. Our results demonstrate a role of ErbB4 in PV-positive interneurons for spine formation in excitatory neurons.
Integration over Multiple Timescales in Primary Auditory Cortex
Authors: David Stephen V. , Shamma Shihab A.
Published: December 2013

Speech and other natural vocalizations are characterized by large modulations in their sound envelope. The timing of these modulations contains critical information for discrimination of important features, such as phonemes. We studied how depression of synaptic inputs, a mechanism frequently reported in cortex, can contribute to the encoding of envelope dynamics. Using a nonlinear stimulus-response model that accounted for synaptic depression, we predicted responses of neurons in ferret primary auditory cortex (A1) to stimuli with natural temporal modulations. The depression model consistently performed better than linear and second-order models previously used to characterize A1 neurons, and it produced more biologically plausible fits. To test how synaptic depression can contribute to temporal stimulus integration, we used nonparametricmaximum a posterioridecoding to compare the ability of neurons showing and not showing depression to reconstruct the stimulus envelope. Neurons showing evidence for depression reconstructed stimuli over a longer range of latencies. These findings suggest that variation in depression across the cortical population supports a rich code for representing the temporal dynamics of natural sounds.
FAIM-L Is an IAP-Binding Protein That Inhibits XIAP Ubiquitinylation and Protects from Fas-Induced Apoptosis
Authors: Moubarak Rana S. , Planells-Ferrer Laura , Urresti Jorge , Reix Stéphanie , Segura Miguel F. , Carriba Paulina , Marqués-Fernàndez Fernando , Sole Carme , Llecha-Cano Nuria , Lopez-Soriano Joaquin , Sanchis Daniel , Yuste Victor J. , Comella Joan X.
Published: December 2013

The neuronal long isoform of Fas Apoptotic Inhibitory Molecule (FAIM-L) protects from death receptor (DR)-induced apoptosis, yet its mechanism of protection remains unknown. Here, we show that FAIM-L protects rat neuronal Type II cells from Fas-induced apoptosis. XIAP has previously emerged as a molecular discriminator that is upregulated in Type II and downregulated in Type I apoptotic signaling. We demonstrate that FAIM-L requires sustained endogenous levels of XIAP to protect Type II cells as well as murine cortical neurons from Fas-induced apoptosis. FAIM-L interacts with the BIR2 domain of XIAP through an IAP-binding motif, the mutation of which impairs the antiapoptotic function of FAIM-L. Finally, we report that FAIM-L inhibits XIAP auto-ubiquitinylation and maintains its stability, thus conferring protection from apoptosis. Our results bring new understanding of the regulation of endogenous XIAP by a DR antagonist, pointing out at FAIM-L as a promising therapeutic tool for protection from apoptosis in pathological situations where XIAP levels are decreased.
Nitric Oxide Mediates Activity-Dependent Plasticity of Retinal Bipolar Cell Output via S-Nitrosylation
Authors: Tooker Ryan E. , Lipin Mikhail Y. , Leuranguer Valerie , Rozsa Eva , Bramley Jayne R. , Harding Jacqueline L. , Reynolds Melissa M. , Vigh Jozsef
Published: December 2013

Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a “weighted potentiation” that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input–output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (ICa) to more negative potentials. The process depended upon glutamate-evoked retrograde nitric oxide (NO) signaling as it was eliminated by pretreatment with an NO synthase blocker, TRIM. The NO-dependent ICamodulation was cGMP independent but could be blocked byN-ethylmaleimide (NEM), indicating that NO acted via an S-nitrosylation mechanism. Importantly, the NO action resulted in a weighted potentiation of Mb output in response to small (≤−30 mV) depolarizations. Coincidentally, light flashes with intensity ≥2.4 × 108photons/cm2/s lowered the latency of scotopic (≤2.4 × 108photons/cm2/s) light-evoked calcium spikes in Mb axon terminals in an NEM-sensitive manner, but light responses above cone threshold (≥3.5 × 109photons/cm2/s) were unaltered. Under bright scotopic/mesopic conditions, this novel form of Mb output potentiation selectively amplifies dim retinal inputs at Mb → ganglion cell synapses. We propose that this process might counteract decreases in retinal sensitivity during light adaptation by preventing the loss of visual information carried by dim scotopic signals.
β-Hydroxybutyrate Modulates N-Type Calcium Channels in Rat Sympathetic Neurons by Acting as an Agonist for the G-Protein-Coupled Receptor FFA3
Authors: Won Yu-Jin , Lu Van B. , Puhl Henry L. , Ikeda Stephen R.
Published: December 2013

Free fatty acids receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43), for which the short-chain fatty acids (SCFAs) acetate and propionate are agonist, have emerged as important G-protein-coupled receptors influenced by diet and gut flora composition. A recent study (Kimura et al., 2011) demonstrated functional expression of FFA3 in the rodent sympathetic nervous system (SNS) providing a potential link between nutritional status and autonomic function. However, little is known of the source of endogenous ligands, signaling pathways, or effectors in sympathetic neurons. In this study, we found that FFA3 and FFA2 are unevenly expressed in the rat SNS with higher transcript levels in prevertebral (e.g., celiac-superior mesenteric and major pelvic) versus paravertebral (e.g., superior cervical and stellate) ganglia. FFA3, whether heterologously or natively expressed, coupled via PTX-sensitive G-proteins to produce voltage-dependent inhibition of N-type Ca2+channels (Cav2.2) in sympathetic neurons. In addition to acetate and propionate, we show that β-hydroxybutyrate (BHB), a metabolite produced during ketogenic conditions, is also an FFA3 agonist. This contrasts with previous interpretations of BHB as an antagonist at FFA3. Together, these results indicate that endogenous BHB levels, especially when elevated under certain conditions, such as starvation, diabetic ketoacidosis, and ketogenic diets, play a potentially important role in regulating the activity of the SNS through FFA3.
Independent Population Coding of Speech with Sub-Millisecond Precision
Authors: Garcia-Lazaro Jose A. , Belliveau Lucile A. C. , Lesica Nicholas A.
Published: December 2013

To understand the strategies used by the brain to analyze complex environments, we must first characterize how the features of sensory stimuli are encoded in the spiking of neuronal populations. Characterizing a population code requires identifying the temporal precision of spiking and the extent to which spiking is correlated, both between cells and over time. In this study, we characterize the population code for speech in the gerbil inferior colliculus (IC), the hub of the auditory system where inputs from parallel brainstem pathways are integrated for transmission to the cortex. We find that IC spike trains can carry information about speech with sub-millisecond precision, and, consequently, that the temporal correlations imposed by refractoriness can play a significant role in shaping spike patterns. We also find that, in contrast to most other brain areas, the noise correlations between IC cells are extremely weak, indicating that spiking in the population is conditionally independent. These results demonstrate that the problem of understanding the population coding of speech can be reduced to the problem of understanding the stimulus-driven spiking of individual cells, suggesting that a comprehensive model of the subcortical processing of speech may be attainable in the near future.
Circadian Variation in Gastric Vagal Afferent Mechanosensitivity
Authors: Kentish Stephen J. , Frisby Claudine L. , Kennaway David J. , Wittert Gary A. , Page Amanda J.
Published: December 2013

Food intake is coordinated to cellular metabolism by clock gene expression with a master clock in the suprachiasmatic nucleus synchronized by light exposure. Gastric vagal afferents play a role in regulating food intake, but it is unknown whether they exhibit circadian variation in their mechanosensitivity. We aimed to determine whether gastric vagal afferents express clock genes and whether their response to mechanical stimuli oscillates throughout the light/dark cycle. Nodose ganglia were collected from 8-week-old female C57BL/6 mice every 3 h starting at lights off (1800 h) to quantifyBmal1,Per1,Per2, andNr1d1mRNA by qRT-PCR. Additionallyin vitrosingle-fiber recordings of gastric vagal mechanoreceptors were taken at all time points.Per1,Per2,Bmal1, andNr1d1mRNA is expressed in the nodose ganglia and levels oscillated over a 24 h period. In mice fedad libitum, gastric content was 3 times higher at 0000 h and 0300 h than 1200 h. The response of tension receptors to 3 g stretch was reduced by up to 70% at 2100 h, 0000 h, and 0300 h compared with 1200 h. Gastric mucosal receptor response to stroking with a 50 mg von Frey hair was 3 times greater at 1200 h and 1500 h than the response at 0000 h. Similar findings were obtained in mice fasted for 6 h or maintained in darkness for 3 d before study. Therefore, these changes do not result from food intake or the light/dark cycle. Thus, gastric vagal mechanoreceptors display circadian rhythm, which may act to control food intake differentially at different times of the day.
The Curious Case of Hoàng Thị Thế
Authors: Keith Charles P.
Published: December 2013

Hoàng Thị Thế, the daughter of a famous figure in the resistance to the French conquest of Vietnam, was glamorous; a self-proclaimed princess and later a film star, she captured the imaginations and attention of those around her. But her life was also sad, full of loss and hardship. And because of who she was, official interest in her, documented in French surveillance files and the propaganda of the revolutionary Vietnamese state, makes her life an unusually rich example of the possibilities of biography to illuminate the everyday struggles, unlikely networks and trajectories, and powerful ironies and sadnesses of the colonial era in Vietnamese history. This article tells her life story.
NRF2 immunolocalization in human breast cancer patients as a prognostic factor
Authors: Onodera Yoshiaki , Motohashi Hozumi , Takagi Kiyoshi , Miki Yasuhiro , Shibahara Yukiko , Watanabe Mika , Ishida Takanori , Hirakawa Hisashi , Sasano Hironobu , Yamamoto Masayuki , Suzuki Takashi
Published: December 2013

Nuclear factor erythroid 2-related factor 2 (NRF2 (NFE2L2)) is an important transcriptional activator involved in the cellular defense mechanisms against electrophilic and oxidative stress. Recent studies have demonstrated that the expression of NRF2 protein is upregulated in several human malignancies and is associated with worse prognosis in these patients. However, the pathological and clinical significance of NRF2 has remained largely unknown in breast cancer patients. Therefore, in this study, we immunolocalized NRF2 in 106 breast carcinoma cases. NRF2 immunoreactivity was mainly detected in the nucleus of the breast carcinoma cells and it was positive in 44% of the cases. NRF2 status was significantly associated with histological grade, Ki-67 labeling index, p62 immunoreactivity, and NAD(P)H:quinone oxidoreductase 1 (NQO1) immunoreactivity, and the results of multivariate analyses revealed that NRF2 status was an independent adverse prognostic factor for both recurrence and disease-free survival of the patients. Subsequent in vitro studies demonstrated that the expression of NRF2 significantly increased the proliferation activity of MCF7 and SK-BR-3 breast carcinoma cells. These results indicate that nuclear NRF2 protein plays important roles in the proliferation and/or progression of breast carcinoma, and nuclear NRF2 immunoreactivity is therefore considered a potent prognostic factor in breast cancer patients.
The role of the inflammatory microenvironment in thyroid carcinogenesis
Authors: Cunha Lucas Leite , Marcello Marjory Alana , Ward Laura Sterian
Published: December 2013

Immune responses against thyroid carcinomas have long been demonstrated and associations between inflammatory microenvironment and thyroid carcinomas repeatedly reported. This scenario has prompted scientists throughout the world to unveil how the inflammatory microenvironment is established in thyroid tumors and what is its influence on the outcome of patients with thyroid carcinoma. Many studies have reported the role of evasion from the immune system in tumor progression and reinforced the weakness of the innate immune response toward thyroid cancer spread in advanced stages. Translational studies have provided evidence that an increased density of tumor-associated macrophages in poorly differentiated thyroid carcinoma (DTC) is associated with an aggressive phenotype at diagnosis and decreased cancer-related survival, whereas well-DTC microenvironment enriched with macrophages is correlated with improved disease-free survival. It is possible that these different results are related to different microenvironments. Several studies have provided evidence that patients whose tumors are not infiltrated by lymphocytes present a high recurrence rate, suggesting that the presence of lymphocytes in the tumor microenvironment may favor the prognosis of patients with thyroid carcinoma. However, the effect of lymphocytes and other immune cells on patient outcome seems to result from complex interactions between the tumor and immune system, and the molecular pattern of cytokines and chemokines helps to explain the involvement of the immune system in thyroid tumor progression. The inflammatory microenvironment may help to characterize aggressive tumors and to identify patients who would benefit from a more invasive approach, probably sparing the vast majority of patients with an indolent disease from unnecessary procedures.
Expression of chemerin and its receptors in rat testes and its action on testosterone secretion
Authors: Li Lei , Ma Ping , Huang Chen , Liu Yongjun , Zhang Ye , Gao Chen , Xiao Tianxia , Ren Pei-Gen , Zabel Brian A , Zhang Jian V
Published: December 2013

The novel adipokine chemerin plays a role in the regulation of lipid and carbohydrate metabolism, and recent reports of elevated chemerin levels in polycystic ovarian syndrome and preeclampsia have pointed to an emerging role of chemerin in reproduction. We hypothesised that chemerin, like other adipokines, may function to regulate male gonadal steroidogenesis. In this study, we show that chemerin and its three receptors chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and chemokine (C-C motif) receptor-like 2 were expressed in male reproductive tracts, liver and white adipose tissue. CMKLR1 and GPR1 proteins were localised specifically in the Leydig cells of human and rat testes by immunohistochemistry. The expression ofchemerinand its receptors in rat testes was developmentally regulated and highly expressed in Leydig cells.In vitrotreatment with chemerin suppressed the human chorionic gonadotropin (hCG)-induced testosterone production from primary Leydig cells, which was accompanied by the inhibition of 3β-hydroxysteroid dehydrogenase gene and protein expression. The hCG-activated p44/42 MAPK (Erk1/2) pathway in Leydig cells was also inhibited by chemerin cotreatment. Together, these data suggest that chemerin is a novel regulator of male gonadal steroidogenesis.
Angiotensin-II promotes Na+ uptake in larval zebrafish, Danio rerio, in acidic and ion-poor water
Authors: Kumai Yusuke , Bernier Nicholas J , Perry Steve F
Published: December 2013

The contribution of the renin–angiotensin system (RAS) to Na+uptake was investigated in larval zebrafish (Danio rerio). At 4 days post fertilization (dpf), the level of whole-body angiotensin-II (ANG-II) was significantly increased after 1- or 3-h exposure to acidic (pH=4.0) or ion-poor water (20-fold dilution of Ottawa tapwater), suggesting rapid activation of the RAS. Long-term (24 h) treatment of 3 dpf larvae with ANG-I or ANG-II significantly increased Na+uptake which was accompanied by an increase in mRNA expression of the Na+-Cl−cotransporter (zslc12a10.2). Induction of Na+uptake by exposure to ANG-I was blocked by simultaneously treating larvae with lisinopril (an angiotensin-converting enzyme inhibitor). Acute (2 h) exposure to acidic water or ion-poor water led to significant increase in Na+uptake which was partially blocked by the ANG-II receptor antagonist, telmisartan. Consistent with these data, translational knockdown of renin prevented the stimulation of Na+uptake following exposure to acidic or ion-poor water. The lack of any effects of pharmacological inhibition (using RU486), or knockdown of glucocorticoid receptors on the stimulation of Na+uptake during acute exposure to acidic or ion-poor environments, indicates that the acute effects of RAS occur independently of cortisol signaling. The results of this study demonstrate that the RAS is involved in Na+homeostasis in larval zebrafish.
Suppression of Expression Between Adjacent Genes Within Heterologous Modules in Yeast
Authors: Lee Tae J , Parikh Rasesh Y , Weitz Joshua S , Kim Harold D
Published: December 2013

Recent studies have shown that proximal arrangement of multiple genes can have complex effects on gene expression. For example, in the case of heterologous gene expression modules, certain arrangements of the selection marker and the gene expression cassette may have unintended consequences that limit the predictability and interpretability of module behaviors. The relationship between arrangement and expression has not been systematically characterized within heterologous modules to date. In this study, we quantitatively measured gene expression patterns of the selection marker (KlURA3 driven by the promoter, pKlURA) and the gene expression cassette (GFP driven by the galactose-inducible GAL1 promoter, pGAL1) in all their possible relative arrangements in Saccharomyces cerevisiae. First, we observed that pKlURA activity depends strongly on the relative arrangement and the activity of pGAL1. Most notably, we observed transcriptional suppression in the case of divergent arrangements: pKlURA activity was reduced when pGAL1 was inactive. Based on our nucleosome occupancy data, we attribute the observed transcriptional reduction to nucleosome repositioning. Second, we observed that pGAL1 activity also depends on the relative arrangement of pKlURA. In particular, strains with divergent promoters showed significantly different pGAL1 activation patterns from other strains, but only when their growth was compromised by lack of uracil. We reasoned that this difference in pGAL1 activation patterns arises from arrangement-dependent pKlURA activity that can affect the overall cell physiology (i.e., cell growth and survival in the uracil-depleted condition). Our results underscore the necessity to consider ramifications of promoter arrangement when using synthetic gene expression modules.
Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria VectorAnopheles arabiensis
Authors: Marsden Clare Diana , Lee Yoosook , Kreppel Katharina , Weakley Allison , Cornel Anthony , Ferguson Heather M , Eskin Eleazar , Lanzaro Gregory C
Published: December 2013

Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples can result in spurious associations if not accounted for. As such, it is useful to have a detailed understanding of these factors before conducting association mapping experiments. Here we conducted whole-genome sequencing on 24 specimens of the malaria mosquito vector, Anopheles arabiensis, to further understanding of patterns of genetic diversity, population subdivision and linkage disequilibrium in this species. We found high levels of genetic diversity within the An. arabiensis genome, with ~800,000 high-confidence, single- nucleotide polymorphisms detected. However, levels of nucleotide diversity varied significantly both within and between chromosomes. We observed lower diversity on the X chromosome, within some inversions, and near centromeres. Population structure was absent at the local scale (Kilombero Valley, Tanzania) but detected between distant populations (Cameroon vs. Tanzania) where differentiation was largely restricted to certain autosomal chromosomal inversions such as 2Rb. Overall, linkage disequilibrium within An. arabiensis decayed very rapidly (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium was observed within some inversions, suggesting that recombination is reduced in those regions. The overall low levels of linkage disequilibrium suggests that association studies in this taxon will be very challenging for all but variants of large effect, and will require large sample sizes.
Generation of a UsefulroX1Allele by Targeted Gene Conversion
Authors: Apte Manasi S , Moran Victoria A , Menon Debashish U , Rattner Barbara P , Barry Kathryn Hughes , Zunder Rachel M , Kelley Richard , Meller Victoria H
Published: December 2013

Methods for altering the sequence of endogenous Drosophila melanogaster genes remain labor-intensive. We have tested a relatively simple strategy that enables the introduction of engineered mutations in the vicinity of existing P-elements. This method was used to generate useful alleles of the roX1 gene, which produces a noncoding RNA involved in dosage compensation. The desired change was first introduced into a genomic clone of roX1 and transgenic flies were generated that carry this sequence in a P-element. Targeted transposition was then used to move the P-element into roX1. Remobilization of the targeted insertion produced large numbers of offspring carrying chromosomes that had precisely introduced the engineered sequences into roX1. We postulate that this occurred by gap repair, using the P-element on the sister chromatid as template. This strategy was used to introduce six MS2 loops into the roX1 gene (roX1MS2-6), enabling detection of roX1 RNA by a MCP-GFP fusion protein in embryos. The roX1MS2-6 remains under the control of the authentic promoter and within the correct genomic context, features expected to contribute to normal roX1 function. The ability to replace relatively large blocks of sequence suggests that this method will be of general use.