bluuebunny/crossref_metadata_2025 huggingface dataset:
Free-swimming northern elephant seals have low field metabolic rates that are sensitive to an increased cost of transport
Authors: Maresh Jennifer L. , Simmons Samantha E. , Crocker Daniel E. , McDonald Birgitte I. , Williams Terrie M. , Costa Daniel P.
Published: April 2014

Widely ranging marine predators often adopt stereotyped, energy-saving behaviours to minimize the energetic cost of transport while maximizing energy gain. Environmental and anthropogenic disturbances can disrupt energy balance by prompting avoidance behaviours that increase transport costs, thereby decreasing foraging efficiency. We examined the ability of 12 free-ranging, juvenile northern elephant seals (Mirounga angustirostris) to mitigate the effects of experimentally increased transport costs by modifying their behaviour and/or energy use in a compensatory manner. Under normal locomotion, elephant seals had low energy requirements (106.5±28.2 kJ kg−1 day−1), approaching or even falling below predictions of basal requirements. Seals responded to a small increase in locomotion costs by spending more time resting between dives (149±44 s) compared with matched control treatments (102±11 s; P<0.01). Despite incurred costs, most other dive and transit behaviours were conserved across treatments, including fixed, rhythmic swimming gaits. Because of this, and because each flipper stroke had a predictable effect on total costs (P<0.001), total energy expenditure was strongly correlated with time spent at sea under both treatments (P<0.0001). These results suggest that transiting elephant seals have a limited capacity to modify their locomotory behaviour without increasing their transport costs. Based on this, we conclude that elephant seals and other ocean predators occupying similar niches may be particularly sensitive to increased transport costs incurred when avoiding unanticipated disturbances.
Deep-diving sea lions exhibit extreme bradycardia in long-duration dives
Authors: McDonald Birgitte I. , Ponganis Paul J.
Published: April 2014

Heart rate and peripheral blood flow distribution are the primary determinants of the rate and pattern of oxygen store utilisation and ultimately breath-hold duration in marine endotherms. Despite this, little is known about how otariids (sea lions and fur seals) regulate heart rate (fH) while diving. We investigated dive fH in five adult female California sea lions (Zalophus californianus) during foraging trips by instrumenting them with digital electrocardiogram (ECG) loggers and time depth recorders. In all dives, dive fH (number of beats/duration; 50±9 beats min−1) decreased compared with surface rates (113±5 beats min−1), with all dives exhibiting an instantaneous fH below resting (<54 beats min−1) at some point during the dive. Both dive fH and minimum instantaneous fH significantly decreased with increasing dive duration. Typical instantaneous fH profiles of deep dives (>100 m) consisted of: (1) an initial rapid decline in fH resulting in the lowest instantaneous fH of the dive at the end of descent, often below 10 beats min−1 in dives longer than 6 min in duration; (2) a slight increase in fH to ~10–40 beats min−1 during the bottom portion of the dive; and (3) a gradual increase in fH during ascent with a rapid increase prior to surfacing. Thus, fH regulation in deep-diving sea lions is not simply a progressive bradycardia. Extreme bradycardia and the presumed associated reductions in pulmonary and peripheral blood flow during late descent of deep dives should (a) contribute to preservation of the lung oxygen store, (b) increase dependence of muscle on the myoglobin-bound oxygen store, (c) conserve the blood oxygen store and (d) help limit the absorption of nitrogen at depth. This fH profile during deep dives of sea lions may be characteristic of deep-diving marine endotherms that dive on inspiration as similar fH profiles have been recently documented in the emperor penguin, another deep diver that dives on inspiration.
Five Facts about Value-Added Exports and Implications for Macroeconomics and Trade Research
Authors: Johnson Robert C.
Published: May 2014

Due to the rise of global supply chains, gross exports do not accurately measure the amount of value added exchanged between countries. I highlight five facts about differences between gross and value-added exports. These differences are large and growing over time, currently around 25 percent, and manufacturing trade looks more important, relative to services, in gross than value-added terms. These differences are also heterogenous across countries and bilateral partners, and changing unevenly across countries and partners over time. Taking these differences into account enables researchers to obtain better quantitative answers to important macroeconomic and trade questions. I discuss how the facts inform analysis of the transmission of shocks across countries; the mechanics of trade balance adjustments; the impact of frictions on trade; the role of endowments and comparative advantage; and trade policy.
Beaches, Sunshine, and Public Sector Pay: Theory and Evidence on Amenities and Rent Extraction by Government Workers
Authors: Brueckner Jan K. , Neumark David
Published: April 2014

Rent extraction by public sector workers may be limited by the ability of taxpayers to vote with their feet. But rent extraction may be higher in regions where high amenities mute the migration response. This paper develops a theoretical model that predicts such a link between public sector wage differentials and local amenities, and the predictions are tested by analyzing variation in these differentials and amenities across states. Public sector wage differentials are, in fact, larger in the presence of high amenities, with the effect stronger for unionized public sector workers, whose political power may allow greater scope for rent extraction. (JEL H75, H76, J31, J32, J45, J51)
The Effect of Disability Insurance Receipt on Labor Supply
Authors: French Eric , Song Jae
Published: April 2014

This paper exploits the effectively random assignment of judges to Disability Insurance cases to estimate the causal impact of Disability Insurance receipt on labor supply. We find that benefit receipt reduces labor force participation by 26 percentage points three years after a disability determination decision, although the reduction is smaller for older people, college graduates, and those with mental illness. OLS and instrumental variables estimates are similar. Furthermore, over 60 percent of those denied benefits by an administrative law judge are subsequently allowed benefits within ten years, showing that most applicants apply, reapply, and appeal until they get benefits. (JEL H55, J14, J22, K23)
Civil Service Rules and Policy Choices: Evidence from US State Governments
Authors: Ujhelyi Gergely
Published: April 2014

This paper studies the policy impact of civil service regulations, exploiting reforms undertaken by US state governments throughout the twentieth century. These reforms replaced political patronage with a civil service recruited based on merit and protected from politics. I find that state politicians respond to these changes by spending relatively less through the reformed state-level bureaucracies. Instead, they allocate more funds to lower level governments. The reallocation of expenditures leads to reduced long-term investment by state governments. (JEL D73, H72, H77, H79)
The person-oriented approach: A short theoretical and practical guide
Authors: Bergman Lars R. , Wångby Margit
Published: April 2014

Lühike ülevaade indiviidile suunatud käsitlusviisist (person-oriented approach) koostati juhendmaterjaliks selle meetodi kasutamisest huvitatud uurijatele. Artiklis arutletakse meetodi teoreetiliste, metodoloogiliste ja praktiliste kaalutluste üle. Esiteks osutatakse mõningatele ajaloolistele juurtele. Sellele järgneb lühiülevaade holistlik-interaktsioonilisest uurimisparadigmast, mis moodustab indiviidikeskse käsitlusviisi üldise raami. Sellel käsitlusviisil on olemas nii teoreetiline kui ka metodoloogiline pool. Peale peamiste teoreetiliste tõekspidamiste tutvustatakse ka enam levinud indiviidikeskseid meetodeid. Indiviidile suunatud käsitlusviisi tuumaks on süsteemne vaade, mille kohaselt moodustavad süsteemi komponendid mustri, mida võiks pidada jagamatuks. Seda mustrit tuleks mõista ja uurida ühe tervikuna, mitte jagada tükkideks (variaabliteks/muutujateks), et neid tükke seejärel eraldiseisvate ühikutena uurida. Seega kasutatakse selliseid metodoloogilisi vahendeid, mis võimaldavad analüüsida tervikut (nt klasteranalüüs). Samuti esitatakse empiiriline näide koolihinnete arengumustrite uurimise kohta.
Full text
Relationships between self-reflection ability and social adjustment among mono and bilingual children
Authors: Arro Grete
Published: April 2014

Üks võrdlemisi vähe koolis tähelepanu saanud tegur, mis tõenäoliselt on seotud psühhosotsiaalse toimetulekuga, seostub lapsele kättesaadavate keeleliste vahenditega, sealhulgas võimega mitmekesiseid sotsiaalseid situatsioone ja iseend nendes paindlikult reflekteerida. Enesepeegeldus- ja eneseanalüüsioskus on uuringute põhjal seotud paremate suhete ja subjektiivse heaoluga. Iseäranis suurt huvi võiks see omadus pakkuda mitmekeelsuse kontekstis ehk laste puhul, kes on sotsialiseeritud korraga mitmesse keelekeskkonda ning peavad sotsiaalses kontekstis end sageli võõrkeeles väljendama. On leitud, et mitmekeelsetel õpilastel esineb sotsiaalse ja akadeemilise kohanemisega seotud arengulisi erinevusi võrreldes nende laste rühmadega, kes õpivad oma emakeeles. Sealjuures avaldab mitmekeelsus lapse toimetulekule kahetist mõju: mõnedes uurimustes on mitmekeelsetel täheldatud vähem probleemkäitumisi ning kiiremat kognitiivset ja lingvistilist arengut, kuid ka suuremat akadeemilise mahajäämuse riskirühma sattumise tõenäosust ning akulturatsiooniprobleeme. Negatiivsed tulemid võivad olla muu hulgas seotud eneserefleksioonivõime teistsuguse arenguga mitmekeelses kontekstis. Siinses uurimuses leiti, et enesepeegeldusoskus on erinevate kognitiivsete võimetega seotud omadus ning parema enesepeegeldusvõimega lastel on paremad sotsiaalse ja psühholoogilise heaolu näitajad. Samuti ilmnes, et mitme- ja ühekeelsete laste enesepeegeldusvõime areng on erinev, ent erinevus vanuse kasvades kaob. Indiviiditasandi analüüsid osutasid, et enesepeegeldusvõime näib olevat mitme- ja ühekeelsete laste rühmades kohanemisega erinevalt seotud.
Summary
Bilingual and Estonian-speaking children studying in the same classes: relation of academic achievement to the pupil’s mental ability and classroom learning environment
Authors: Seepter Kristina
Published: April 2014

Uurimuse eesmärk oli analüüsida, kuidas arenevad eesti koolis koos õppivad eesti- ja kakskeelsed lapsed. Selleks analüüsiti, kas õpilase vaimne baasvõimekus oli realiseerunud akadeemilises plaanis nii matemaatikas kui ka eesti keele mõistmises. Lisaks kirjeldati, millised klassi õpikeskkonnad toetavad õpilaste arengut ja millised laste akadeemilised tulemused olid vastavuses nende võimekusega ning millistes õpikeskkondades oli õpilastel probleeme ja nende vaimne potentsiaal ei realiseerunud.
Analüüsiti 25 klassikomplekti, kus õppisid koos nii eesti- kui ka kakskeelsed lapsed. Arvesse läks õpilase vaimse võimekuse tase 3. klassis ja tema edaspidised tulemused 5. klassi matemaatikas ja eesti keele mõistmises. Klassi õpikeskkonda kirjeldasid klassikaaslaste keskmine IQ tase ja selle varieeruvus klassis ning õpetaja üldine toimetulek selle klassikomplekti õpetamisel. Andmeanalüüsimeetoditest kasutati nii rühmatasandi meetodeid (nt dispersioon- ja hulgiregressioonanalüüsi) kui ka indiviiditasandi meetodeid (nt konfiguratsioonilist sagedusanalüüsi).
Tulemused osutasid, et aineõppele ülemineku perioodi alguseks (5. klass) olid matemaatikateadmised kakskeelsetel õpilastel jõudnud sarnasele tasemele kui samas õpikeskkonnas õppivatel eestikeelsetel lastel, ent eesti keele mõistmises püsis kakskeelsete rühm kõigil kolmel aastal (3.–5. klass) oluliselt kehvemal tasemel võrreldes eestikeelsetega. Oluline on märkida, et väiksem akadeemiline edukus ei iseloomustanud ühtmoodi kõiki muukeelseid õpilasi. Võimekusele mittevastav madalam akadeemiline tase oli iseloomulik just keskpärase võimekusega kakskeelsetele lastele. Need õpilased moodustavad kakskeelsete hulgas riskirühma, kes tuleks õpetajatel ära tunda, et nende arengut paremini toetada. Uurimistulemustest ilmnes, et keskpäraste võimetega kakskeelsetel lastel oli probleeme klassi õppekeskkonnas, mis oli võimete poolest ühtlane, kuid keskmisest madalama IQ tasemega. Lisaks näitasid andmed, et vaimse võimekuse mõttes heterogeensetes klassikomplektides õppis andekaid lapsi, nii eesti- kui ka kakskeelseid, kelle vaimne potentsiaal akadeemilises plaanis ei realiseerunud.
Erinevused õpilaste arengumustrites eri tüüpi klassi õpikeskkondades võivad olla tingitud õpetaja toimetuleku erinevustest. Näiteks ei suuda heterogeenses klassikeskkonnas suur hulk õpetajaid (ja ka koolikorraldusi) piisavalt toetada kõigi klassis koos õppivate lasterühmade arengut. Tavaliselt kannatavad kõige rohkem keskpärase ja kõrge võimekuse tasemega lapsed, kelle akadeemilised tulemused jäävad alla nende vaimsele potentsiaalile.
Summary
Computability and human symbolic output
Authors: Megill Jason , Melvin Tim
Published: April 2014

This paper concerns “human symbolic output,” or strings of characters produced by humans in our various symbolic systems; e.g., sentences in a natural language, mathematical propositions, and so on. One can form a set that consists of all of the strings of characters that have been produced by at least one human up to any given moment in human history. We argue that at any particular moment in human history, even at moments in the distant future, this set is finite. But then, given fundamental results in recursion theory, the set will also be recursive, recursively enumerable, axiomatizable, and could be the output of a Turing machine. We then argue that it is impossible to produce a string of symbols that humans could possibly produce but no Turing machine could. Moreover, we show that any given string of symbols that we could produce could also be the output of a Turing machine. Our arguments have implications for Hilbert’s sixth problem and the possibility of axiomatizing particular sciences, they undermine at least two distinct arguments against the possibility of Artificial Intelligence, and they entail that expert systems that are the equals of human experts are possible, and so at least one of the goals of Artificial Intelligence can be realized, at least in principle.
‘Beat the cheat’: portrayals of disability benefit claimants in print media
Authors: McEnhill Libby , Byrne Victoria
Published: April 2014

The Welfare Reform Act (2012) brought about changes to benefit entitlement and assessment for disabled people, with measures to reduce the budget in this area justified within parts of the Conservative Party and right-wing media through the use of narratives of deserving and undeserving citizens. Using a case study of the Sun newspaper's publications on disability in 2012, this paper illustrates that increasingly negative perceptions of disabled people in society are congruent with dominant portrayals of disability benefit recipients as undeserving in the right-wing press. In line with previous research, this supports the idea of a level of media influence on the public.
Access to and Experience of Later Abortion: Accounts from Women in Scotland
Authors: Purcell Carrie , Cameron Sharon , Caird Lucy , Flett Gillian , Laird George , Melville Catriona , McDaid Lisa M.
Published: April 2014

Context

Except in the presence of significant medical indications, the legal limit for abortion in Great Britain is 24 weeks’ gestation. Nevertheless, abortion for nonmedical reasons is not usually provided in Scotland after 18–20 weeks, meaning women have to travel to England for the procedure.

Methods

In‐depth interviews were conducted with 23 women presenting for “later” abortions (i.e., at 16 or more weeks’ gestation) in Scotland. Participants were women who sought an abortion at a participating National Health Service clinic between January and July 2013. Interviews addressed reasons for and consequences of later presentation, as well as women's experiences of abortion. Thematic analysis attended to emerging issues and employed the conceptual tool of candidacy.

Results

Delayed recognition of pregnancy, changed life circumstances and conflicting candidacies for motherhood and having an abortion were common reasons for women's presentation for later abortion. Women perceived that the resources required to travel to England for a later abortion were potential barriers to access, and felt that such travel was distressing and stigmatizing. Participants who continued their pregnancy did so after learning they were at a later gestational age than expected or after receiving assurances of support from partners, friends or family.

Conclusions

Reasons for seeking later abortion are complex and varied among women in Scotland, and suggest that reducing barriers to access and improving local provision of such abortions are a necessity. The candidacy framework allows for a fuller understanding of the difficulties involved in obtaining abortions.
Understanding the Underutilization of Urban Bicycle Commuting: A Behavioral Reasoning Perspective
Authors: Claudy Marius C. , Peterson Mark
Published: April 2014

In an effort to make urban transportation more sustainable, policy makers and social marketers have turned increased attention to bicycling. The authors apply behavioral reasoning theory to investigate consumers' mental processing of bicycle commuting to better understand why such an active mode of transportation is underutilized in many urban areas. Using a large-scale sample of commuters in Dublin, Ireland, the study offers insights into the psychological antecedents of bicycling adoption. The structural equation modeling results confirm the main premise of behavioral reasoning theory, in that reasons serve as important linkages between people's values and their attitudes and behavior. In particular, the findings suggest that commuters have reasons not to engage in bicycling (e.g., inconvenience, perceived danger), which account for most of the variance in bicycle-commuting behavior. The findings challenge interventions that emphasize the role of information campaigns and one-time infrastructural changes in encouraging voluntary change in travel behavior. Instead, the findings suggest that transportation planners and social marketers would be better off addressing consumers' reasons for and against bicycling through community-based initiatives.
Acetylcholine Controls GABA-, Glutamate-, and Glycine-Dependent Giant Depolarizing Potentials that Govern Spontaneous Motoneuron Activity at the Onset of Synaptogenesis in the Mouse Embryonic Spinal Cord
Authors: Czarnecki Antonny , Le Corronc Hervé , Rigato Chiara , Le Bras Barbara , Couraud François , Scain Anne-Laure , Allain Anne-Emilie , Mouffle Christine , Bullier Erika , Mangin Jean-Marie , Branchereau Pascal , Legendre Pascal
Published: April 2014

A remarkable feature of early neuronal networks is their endogenous ability to generate spontaneous rhythmic electrical activity independently of any external stimuli. In the mouse embryonic SC, this activity starts at an embryonic age of ∼12 d and is characterized by bursts of action potentials recurring every 2–3 min. Although these bursts have been extensively studied using extracellular recordings and are known to play an important role in motoneuron (MN) maturation, the mechanisms driving MN activity at the onset of synaptogenesis are still poorly understood. Because only cholinergic antagonists are known to abolish early spontaneous activity, it has long been assumed that spinal cord (SC) activity relies on a core network of MNs synchronized via direct cholinergic collaterals. Using a combination of whole-cell patch-clamp recordings and extracellular recordings in E12.5 isolated mouse SC preparations, we found that spontaneous MN activity is driven by recurrent giant depolarizing potentials. Our analysis reveals that these giant depolarizing potentials are mediated by the activation of GABA, glutamate, and glycine receptors. We did not detect direct nAChR activation evoked by ACh application on MNs, indicating that cholinergic inputs between MNs are not functional at this age. However, we obtained evidence that the cholinergic dependency of early SC activity reflects a presynaptic facilitation of GABA and glutamate synaptic release via nicotinic AChRs. Our study demonstrates that, even in its earliest form, the activity of spinal MNs relies on a refined poly-synaptic network and involves a tight presynaptic cholinergic regulation of both GABAergic and glutamatergic inputs.
Brain White Matter Development Is Associated with a Human-Specific Haplotype Increasing the Synthesis of Long Chain Fatty Acids
Authors: Peters Bart D. , Voineskos Aristotle N. , Szeszko Philip R. , Lett Tristram A. , DeRosse Pamela , Guha Saurav , Karlsgodt Katherine H. , Ikuta Toshikazu , Felsky Daniel , John Majnu , Rotenberg David J. , Kennedy James L. , Lencz Todd , Malhotra Anil K.
Published: April 2014

The genetic and molecular pathways driving human brain white matter (WM) development are only beginning to be discovered. Long chain polyunsaturated fatty acids (LC-PUFAs) have been implicated in myelination in animal models and humans. The biosynthesis of LC-PUFAs is regulated by the fatty acid desaturase (FADS) genes, of which a human-specific haplotype is strongly associated with ω-3 and ω-6 LC-PUFA concentrations in blood. To investigate the relationship between LC-PUFA synthesis and human brain WM development, we examined whether this FADS haplotype is associated with age-related WM differences across the life span in healthy individuals 9–86 years of age (n= 207). Diffusion tensor imaging was performed to measure fractional anisotropy (FA), a putative measure of myelination, of the cerebral WM tracts. FADS haplotype status was determined with a single nucleotide polymorphism (rs174583) that tags this haplotype. Overall, normal age-related WM differences were observed, including higher FA values in early adulthood compared with childhood, followed by lower FA values across older age ranges. However, individuals homozygous for the minor allele (associated with lower LC-PUFA concentrations) did not display these normal age-related WM differences (significant age × genotype interactions,pcorrected< 0.05). These findings suggest that LC-PUFAs are involved in human brain WM development from childhood into adulthood. This haplotype and LC-PUFAs may play a role in myelin-related disorders of neurodevelopmental origin.
Axonal Targeting of the Serotonin Transporter in Cultured Rat Dorsal Raphe Neurons Is Specified by SEC24C-Dependent Export from the Endoplasmic Reticulum
Authors: Montgomery Therese R. , Steinkellner Thomas , Sucic Sonja , Koban Florian , Schüchner Stefan , Ogris Egon , Sitte Harald H. , Freissmuth Michael
Published: April 2014

Export of the serotonin transporter (SERT) from the endoplasmic reticulum (ER) is mediated by the SEC24C isoform of the coatomer protein-II complex. SERT must enter the axonal compartment and reach the presynaptic specialization to perform its function, i.e., the inward transport of serotonin. Refilling of vesicles is contingent on the operation of an efficient relay between SERT and the vesicular monoamine transporter-2 (VMAT2). Here, we visualized the distribution of both endogenously expressed SERT and heterologously expressed variants of human SERT in dissociated rat dorsal raphe neurons to examine the role of SEC24C-dependent ER export in axonal targeting of SERT. We conclude that axonal delivery of SERT is contingent on recruitment of SEC24C in the ER. This conclusion is based on the following observations. (1) Both endogenous and heterologously expressed SERT were delivered to the extensive axonal arborizations and accumulated in bouton-like structures. (2) In contrast, SERT–607RI608–AA, in which the binding site of SEC24C is disrupted, remained confined to the microtubule-associated protein 2-positive somatodendritic compartment. (3) The overexpression of dominant-negative SEC24C–D796V/D797N (but not of the corresponding SEC24D mutant) redirected both endogenous SERT and heterologously expressed yellow fluorescent protein–SERT from axons to the somatodendritic region. (4) SERT–K610Y, which harbors a mutation converting it into an SEC24D client, was rerouted from the axonal to the somatodendritic compartment by dominant-negative SEC24D. In contrast, axonal targeting of the VMAT2 was disrupted by neither dominant-negative SEC24C nor dominant-negative SEC24D. This suggests that SERT and VMAT2 reach the presynaptic specialization by independent routes.
Terminal Schwann Cells Participate in Neuromuscular Synapse Remodeling during Reinnervation following Nerve Injury
Authors: Kang Hyuno , Tian Le , Mikesh Michelle , Lichtman Jeff W. , Thompson Wesley J.
Published: April 2014

Schwann cells (SCs) at neuromuscular junctions (NMJs) play active roles in synaptic homeostasis and repair. We have studied how SCs contribute to reinnervation of NMJs using vital imaging of mice whose motor axons and SCs are transgenically labeled with different colors of fluorescent proteins. Motor axons most commonly regenerate to the original synaptic site by following SC-filled endoneurial tubes. During the period of denervation, SCs at the NMJ extend elaborate processes from the junction, as shown previously, but they also retract some processes from territory they previously occupied within the endplate. The degree of this retraction depends on the length of the period of denervation. We show that the topology of the remaining SC processes influences the branching pattern of regenerating axon terminals and the redistribution of acetylcholine receptors (AChRs). Upon arriving at the junction, regenerating axons follow existing SC processes within the old synaptic site. Some of the AChR loss that follows denervation is correlated with failure of portions of the old synaptic site that lack SC coverage to be reinnervated. New AChR clustering is also induced by axon terminals that follow SC processes extended during denervation. These observations show that SCs participate actively in the remodeling of neuromuscular synapses following nerve injury by their guidance of axonal reinnervation.
Optogenetic Stimulation of Locus Ceruleus Neurons Augments Inhibitory Transmission to Parasympathetic Cardiac Vagal Neurons via Activation of Brainstem α1 and β1 Receptors
Authors: Wang Xin , Piñol Ramón A. , Byrne Peter , Mendelowitz David
Published: April 2014

Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. In this study, we test directly whether activation of noradrenergic neurons in the LC influences brainstem parasympathetic cardiac vagal neurons (CVNs). CVNs were identified in transgenic mice that express channel-rhodopsin-2 (ChR2) in LC tyrosine hydroxylase neurons. Photoactivation evoked a rapid depolarization, increased firing, and excitatory inward currents in ChR2-expressing neurons in the LC. Photostimulation of LC neurons did not alter excitatory currents, but increased inhibitory neurotransmission to CVNs. Optogenetic activation of LC neurons increased the frequency of isolated glycinergic IPSCs by 27 ± 8% (p= 0.003,n= 26) and augmented GABAergic IPSCs in CVNs by 21 ± 5% (p= 0.001,n= 26). Inhibiting α1, but not α2, receptors blocked the evoked responses. Inhibiting β1 receptors prevented the increase in glycinergic, but not GABAergic, IPSCs in CVNs. This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, α1 and/or β1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.
Global Ca2+Signaling Drives Ribbon-Independent Synaptic Transmission at Rod Bipolar Cell Synapses
Authors: Mehta Bhupesh , Ke Jiang-Bin , Zhang Lei , Baden Alexander D. , Markowitz Alexander L. , Nayak Subhashree , Briggman Kevin L. , Zenisek David , Singer Joshua H.
Published: April 2014

Ribbon-type presynaptic active zones are a hallmark of excitatory retinal synapses, and the ribbon organelle is thought to serve as the organizing point of the presynaptic active zone. Imaging of exocytosis from isolated retinal neurons, however, has revealed ectopic release (i.e., release away from ribbons) in significant quantities. Here, we demonstrate in anin vitromouse retinal slice preparation that ribbon-independent release from rod bipolar cells activates postsynaptic AMPARs on AII amacrine cells. This form of release appears to draw on a unique, ribbon-independent, vesicle pool. Experimental, anatomical, and computational analyses indicate that it is elicited by a significant, global elevation of intraterminal [Ca2+] arising following local buffer saturation. Our observations support the conclusion that ribbon-independent release provides a read-out of the average behavior of all of the active zones in a rod bipolar cell's terminal.
miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3
Authors: Boufraqech Myriem , Zhang Lisa , Jain Meenu , Patel Dhaval , Ellis Ryan , Xiong Yin , He Mei , Nilubol Naris , Merino Maria J , Kebebew Electron
Published: April 2014

The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targetedAKT3.In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.
Application of microRNAs in diabetes mellitus
Authors: Chen Haiyong , Lan Hui-Yao , Roukos Dimitrios H , Cho William C
Published: April 2014

MicroRNAs (miRNAs) are small molecules negatively regulating gene expression by diminishing their target mRNAs. Emerging studies have shown that miRNAs play diverse roles in diabetes mellitus. Type 1 diabetes (T1D) and T2D are two major types of diabetes. T1D is characterized by a reduction in insulin release from the pancreatic β-cells, while T2D is caused by islet β-cell dysfunction in response to insulin resistance. This review describes the miRNAs that control insulin release and production by regulating cellular membrane electrical excitability (ATP:ADP ratio), insulin granule exocytosis, insulin synthesis in β-cells, and β-cell fate and islet mass formation. This review also examines miRNAs involved the insulin resistance of liver, fat, and skeletal muscle, which change insulin sensitivity pathways (insulin receptors, glucose transporter type 4, and protein kinase B pathways). This review discusses the potential application of miRNAs in diabetes, including the use of gene therapy and therapeutic compounds to recover miRNA function in diabetes, as well as the role of miRNAs as potential biomarkers for T1D and T2D.
Preferential expression of PAPPA in human preadipocytes from omental fat
Authors: Davidge-Pitts Caroline , Escande Carlos J , Conover Cheryl A
Published: April 2014

Fat distribution differs between individuals, and those with visceral fat predominance develop metabolic profiles that increase the risk of adverse cardiovascular events. This is due, in part, to the proinflammatory state associated with visceral obesity as well as depot-specific adipogenesis. The IGF system is important in adipose tissue development and metabolic function. Pregnancy-associated plasma protein A (PAPPA) is a novel zinc metalloproteinase that regulates local IGF availability. The first aim of this study was to characterize PAPPA mRNA and protein expression in primary cultures of human preadipocytes isolated from omental, mesenteric, and subcutaneous depots. PAPPA expression was significantly increased in omental preadipocytes compared with mesenteric and subcutaneous preadipocytes. The second aim of this study was to investigate the factors regulating PAPPA expression, focusing on proinflammatory cytokines and resveratrol that have been shown to have negative and positive effects, respectively, on metabolism and diet-induced obesity. Treatment of cultured primary human preadipocytes with tumor necrosis factor α and interleukin 1β led to significant increases in PAPPA expression. Activated pathways mediating cytokine-induced PAPPA expression include the nuclear factor κB pathway and the MAPK family, particularly c-Jun NH2-terminal kinase and p38 MAPK. Resveratrol, a polyphenolic compound with beneficial cardiometabolic effects, significantly downregulated PAPPA expression under basal and stimulated conditions. Effects of resveratrol on PAPPA appeared to be mediated through pathways independent of silent mating type information regulation 2 homolog 1 (SIRT1) and AMP kinase activation. Depot-specific PAPPA expression in human preadipocytes may contribute to a depot-specific function.
Advances in understanding the role of cardiac glycosides in control of sodium transport in renal tubules
Authors: Khundmiri Syed Jalal
Published: April 2014

Cardiotonic steroids have been used for the past 200 years in the treatment of congestive heart failure. As specific inhibitors of membrane-bound Na+/K+ATPase, they enhance cardiac contractility through increasing myocardial cell calcium concentration in response to the resulting increase in intracellular Na concentration. The half-minimal concentrations of cardiotonic steroids required to inhibit Na+/K+ATPase range from nanomolar to micromolar concentrations. In contrast, the circulating levels of cardiotonic steroids under physiological conditions are in the low picomolar concentration range in healthy subjects, increasing to high picomolar levels under pathophysiological conditions including chronic kidney disease and heart failure. Little is known about the physiological function of low picomolar concentrations of cardiotonic steroids. Recent studies have indicated that physiological concentrations of cardiotonic steroids acutely stimulate the activity of Na+/K+ATPase and activate an intracellular signaling pathway that regulates a variety of intracellular functions including cell growth and hypertrophy. The effects of circulating cardiotonic steroids on renal salt handling and total body sodium homeostasis are unknown. This review will focus on the role of low picomolar concentrations of cardiotonic steroids in renal Na+/K+ATPase activity, cell signaling, and blood pressure regulation.
The Insertion Green Monster (iGM) Method for Expression of Multiple Exogenous Genes in Yeast
Authors: Labunskyy Vyacheslav M , Suzuki Yo , Hanly Timothy J , Murao Ayako , Roth Frederick P , Gladyshev Vadim N
Published: April 2014

Being a simple eukaryotic organism, Saccharomyces cerevisiae provides numerous advantages for expression and functional characterization of proteins from higher eukaryotes, including humans. However, studies of complex exogenous pathways using yeast as a host have been hampered by the lack of tools to engineer strains expressing a large number of genetic components. In addition to inserting multiple genes, it is often desirable to knock out or replace multiple endogenous genes that might interfere with the processes studied. Here, we describe the “insertion Green Monster” (iGM) set of expression vectors that enable precise insertion of many heterologous genes into the yeast genome in a rapid and reproducible manner and permit simultaneous replacement of selected yeast genes. As a proof of principle, we have used the iGM method to replace components of the yeast pathway for methionine sulfoxide reduction with genes encoding the human selenoprotein biosynthesis machinery and generated a single yeast strain carrying 11 exogenous components of the selenoprotein biosynthetic pathway in precisely engineered loci.
Mapping Small Effect Mutations inSaccharomyces cerevisiae: Impacts of Experimental Design and Mutational Properties
Authors: Duveau Fabien , Metzger Brian P H , Gruber Jonathan D , Mack Katya , Sood Natasha , Brooks Tiffany E , Wittkopp Patricia J
Published: April 2014

Genetic variants identified by mapping are biased toward large phenotypic effects because of methodologic challenges for detecting genetic variants with small phenotypic effects. Recently, bulk segregant analysis combined with next-generation sequencing (BSA-seq) was shown to be a powerful and cost-effective way to map small effect variants in natural populations. Here, we examine the power of BSA-seq for efficiently mapping small effect mutations isolated from a mutagenesis screen. Specifically, we determined the impact of segregant population size, intensity of phenotypic selection to collect segregants, number of mitotic generations between meiosis and sequencing, and average sequencing depth on power for mapping mutations with a range of effects on the phenotypic mean and standard deviation as well as relative fitness. We then used BSA-seq to map the mutations responsible for three ethyl methanesulfonate−induced mutant phenotypes in Saccharomyces cerevisiae. These mutants display small quantitative variation in the mean expression of a fluorescent reporter gene (−3%, +7%, and +10%). Using a genetic background with increased meiosis rate, a reliable mating type marker, and fluorescence-activated cell sorting to efficiently score large segregating populations and isolate cells with extreme phenotypes, we successfully mapped and functionally confirmed a single point mutation responsible for the mutant phenotype in all three cases. Our simulations and experimental data show that the effects of a causative site not only on the mean phenotype, but also on its standard deviation and relative fitness should be considered when mapping genetic variants in microorganisms such as yeast that require population growth steps for BSA-seq.
Perfil das exposições a medicamentos por mulheres em idade reprodutiva atendidas por um Centro de Informações Toxicológicas
Authors: Takahama Carina Harumi , Turini Conceição Aparecida , Girotto Edmarlon
Published: April 2014

O objetivo deste artigo é descrever os dados epidemiológicos referentes às exposições a medicamentos por mulheres em idade fértil atendidas por um Centro de Informações Toxicológicas. Realizou-se um estudo com mulheres em idade fértil, expostas a medicamentos entre 2007 e 2011. Foram estudadas variáveis relacionadas às pacientes, à ocorrência e ao medicamento envolvido, totalizando 777 notificações. Os dados foram obtidos do Sistema de Informação de Agravos de Notificação e processadas com o uso do programa Epi Info. A maioria das ocorrências (90,5%) foi intencional, em 33,7% dos casos foram utilizados de dois a três medicamentos e a frequência de hospitalização foi de 35,6%. Os medicamentos com atuação no Sistema Nervoso Central foram responsáveis por 59,9% das ocorrências, destacando-se os antiepilépticos (21,2%) e os antidepressivos (20,7%). Os principais fatores associados à hospitalização das pacientes foram: demora no atendimento após a ocorrência da exposição, pacientes com nível superior, contato com dois ou mais medicamentos e exposições a antiepilépticos e antidepressivos. Os resultados obtidos mostraram que as exposições a medicamentos representam um grave problema à saúde de mulheres em idade fértil e contribuem para o aumento das internações hospitalares.
Atrasos nos encaminhamentos de pacientes com câncer bucal: avaliação qualitativa da percepção dos cirurgiões-dentistas
Authors: Lombardo Eduardo Madruga , Cunha Amanda Ramos da , Carrard Vinicius Coelho , Bavaresco Caren Serra
Published: April 2014

O objetivo deste estudo é verificar, na percepção dos cirurgiões-dentistas atuantes em Atenção Primária em Saúde (APS) em Porto Alegre (RS), quais as possíveis razões que justifiquem o atraso da chegada do paciente com câncer bucal aos setores de atenção em saúde de maior complexidade. O presente estudo teve como público-alvo cirurgiões-dentistas atuantes em cinco diferentes realidades laborais em APS em Porto Alegre. Foram utilizados como critérios de inclusão profissionais com formação em APS e que estivessem atuando na Atenção Básica. O instrumento para coleta de dados foi a técnica de grupo focal com aplicação de questionário estruturado. Uma vez coletados os dados, foi realizada análise interpretativa e categorização das informações em quatro eixos centrais: profissional, equipe, comunidade e rede de serviços. Os resultados sugerem que os seguintes fatores estão associados ao atraso da chegada do paciente com câncer bucal aos setores de atenção em saúde de maior complexidade: falha na identificação precoce, ausência de trabalho multidisciplinar, desvalorização da necessidade de corresponsabilização pela própria saúde por parte da comunidade e a deficiência da rede de atenção no que tange a qualidade da comunicação entre profissionais de diferentes níveis de atenção.
Fatores associados à procura por serviços de saúde numa perspectiva relacional de gênero
Authors: Levorato Cleice Daiana , Mello Luane Marques de , Silva Anderson Soares da , Nunes Altacílio Aparecido
Published: April 2014

Os valores da cultura masculina envolvem comportamentos de risco à saúde, sendo que a forma como os homens constroem e vivenciam a sua masculinidade torna-se uma das matrizes dos modos de adoecer e morrer. O objetivo deste estudo foi identificar os fatores associados à procura por serviços de saúde e diferenças entre os sexos, selecionando usuários de serviços de saúde, investigando como variável dependente o sexo do usuário (indicador cultural) e a não procura pelo serviço de saúde e variáveis independentes: características sóciodemográficas e clínico-epidemiológicas. Para a análise de associação entre variáveis empregou-se a Razão de Prevalência através de análises univariadas e multivariada. Os fatores associados à não procura por serviços de saúde foram: sexo masculino, horário de funcionamento das unidades de saúde, horário de trabalho do usuário e não possuir nenhuma doença. Pela análise multivariada, os fatores facilitadores da procura por serviços de saúde (proteção) foram: sexo feminino entre 26 e 49 anos de idade. É relevante a efetiva consolidação de um modelo de atenção à saúde que questiona a contradição existente entre os dados epidemiológicos quanto à saúde masculina e a posição dos serviços de saúde de permanecerem no senso comum da invulnerabilidade dos homens ao adoecimento.
Clinical and epidemiological aspects of scorpion stings in the northeast region of Brazil
Authors: Barros Rafaella Moreno , Pasquino Jackeline Araujo , Peixoto Laisla Rangel , Targino Isabely Tamarys Gomes , Sousa Jorge Alves de , Leite Renner de Souza
Published: April 2014

Scorpion stings are a serious public health issue in tropical and subtropical countries. This is a descriptive and retrospective study of the clinical-epidemiological characteristics of scorpion sting cases registered in the Health System in the city of Campina Grande, Paraíba state, from 2007 to 2012. Data was collected from the Injury Notification Information System data banks of the Ministry of Health. A total of 2,283 records, provided by the Third Health Sector of Campina Grande, were analyzed. Data revealed that the majority of the victims are female aged between 20 and 29 years, and the highest incidence of stings was in the urban area. Victims were mostly stung on the feet and hand. Serotherapy was not administered in most cases. The majority of the victims received medical assistance within 1 to 3 hours after the sting. The most prevalent clinical manifestations were pain, edema and paresthesias. Most cases were classified as mild, though seven deaths were reported. The high incidence rate suggests that this town may be an endemic area of scorpion stings, supporting the need to develop strategies to control and prevent scorpion stings.
Método de mineração de dados para identificação de câncer de mama baseado na seleção de variáveis
Authors: Holsbach Nicole , Fogliatto Flávio Sanson , Anzanello Michel Jose
Published: April 2014

Na maioria dos países, o câncer de mama entre as mulheres é predominante. Se diagnosticado precocemente, apresenta alta probabilidade de cura. Diversas abordagens baseadas em Estatística foram desenvolvidas para auxiliar na sua detecção precoce. Este artigo apresenta um método para a seleção de variáveis para classificação dos casos em duas classes de resultado, benigno ou maligno, baseado na análise citopatológica de amostras de célula da mama de pacientes. As variáveis são ordenadas de acordo com um novo índice de importância de variáveis que combina os pesos de importância da Análise de Componentes Principais e a variância explicada a partir de cada componente retido. Observações da amostra de treino são categorizadas em duas classes através das ferramentas k-vizinhos mais próximos e Análise Discriminante, seguida pela eliminação da variável com o menor índice de importância. Usa-se o subconjunto com a máxima acurácia para classificar as observações na amostra de teste. Aplicando ao Wisconsin Breast Cancer Database, o método proposto apresentou uma média de 97,77% de acurácia de classificação, retendo uma média de 5,8 variáveis.
Yoga e promoção da saúde
Authors: Barros Nelson Filice de , Siegel Pamela , Moura Soraia Maria de , Cavalari Thaís Adriana , Silva Luis Geraldo da , Furlanetti Maria Renata , Gonçalves Andrea Vasconcelos
Published: April 2014

O objetivo deste trabalho é analisar os sintomas e o estado de bem-estar autodeclarados dos participantes do programa "Yoga e Promoção da Saúde", que consistiu em aulas de hatha yoga, utilizando técnicas corporais e respiratórias e conteúdo ético-filosófico, ministradas a dois grupos de docentes, funcionários e alunos, de uma universidade pública do Estado de São Paulo, entre agosto/dezembro de 2011 e março/junho de 2012. Os participantes preencheram um instrumento adaptado do Measure Yourself Medical Outcome Profile nos momentos iniciais e finais do programa. Dos 20 participantes do Grupo 1, oito preencheram o instrumento e a metade apresentou melhora do sintoma declarado; concernente ao estado de bem-estar houve uma melhora para três deles. No Grupo 2, também com 20 participantes, nove completaram o programa e todos tiveram melhoras nos sintomas autodeclarados e melhora da percepção de bem-estar. Conclui-se que o yoga é uma prática mente-corpo que atua como importante terapêutica para a maior parte das pessoas, bem como promove saúde para a maioria dos praticantes, inclusive ampliando sua capacidade de autopercepção e autocuidado corporal. Porém, destaca-se que não alcança o mesmo efeito positivo para todos que a praticam, como preconizam algumas tradições de yoga.