bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine D1-like Receptors Regulate Constitutive, μ-Opioid Receptor-Mediated Repression of Use-Dependent Synaptic Plasticity in Dorsal Horn Neurons: More Harm than Good?
Authors: Aira Zigor , Barrenetxea Teresa , Buesa Itsaso , García del Caño Gontzal , Azkue Jon Jatsu 
Published: May 2016

The current study reports on a synaptic mechanism through which D1-like receptors (D1LRs) modulate spinal nociception and plasticity by regulating activation of the μ-opioid receptor (MOR).D1LR stimulation with agonist SKF 38393 concentration-dependently depressed C-fiber-evoked potentials in rats receiving spinal nerve ligation (SNL), but not in uninjured rats. Depression was prevented by MOR- but not GABA-receptor blockade. Neurons expressing the D1 subtype were immunopositive for met-enkephalin and vesicular glutamate transporter VGLUT2, but not for GABAergic marker vGAT.Nerve ligation was followed by increased immunoreactivity for D1 in synaptic compartment (P3) in dorsal horn homogenates and presynaptic met-enkephalin-containing boutons. SNL led to increased immunoreactivity for met-enkephalin in dorsal horn homogenates, which was dose-dependently attenuated by selective D1LR antagonist SCH 23390. During blockade of either D1R or MOR, low-frequency (0.2 or 3 Hz) stimulation (LFS) to the sciatic nerve induced long-term potentiation (LTP) of C-fiber-evoked potentials, revealing a constituent role of both receptors in repressing afferent-induced synaptic plasticity. LFS consistently induced NMDA receptor-dependent LTP in nerve-injured rats. The ability of MOR both to prevent LTP and to modulate mechanical and thermal pain thresholds in behavioral tests was preserved in nerve-ligated rats that were postoperatively treated with SCH 23390. D1LR priming for 30 min sufficed to disrupt MOR function in otherwise naive rats via a mechanism involving receptor overuse.The current data support that, whereas D1LR-modulated MOR activation is instrumental in antinociception and endogenous repression of synaptic plasticity, this mechanism deteriorates rapidly by sustained use, generating increased vulnerability to afferent input.SIGNIFICANCE STATEMENTThe current study shows that dopamine D1-like receptors (D1LRs) and μ-opioid receptors (MOR) in the spinal dorsal horn constitutively repress the expression of synaptic long-term potentiation (LTP) of C-fiber-evoked potentials. Anatomical data are provided supporting that the D1 subtype regulates MOR function by modulating met-enkephalin release. Sustained neuropathic pain induced by spinal nerve ligation is accompanied by D1R and met-enkephalin upregulation, acquired D1LR-mediated antinociception, and a loss of endogenous repression of further synaptic plasticity. We show that the ability of MOR to oppose LTP is rapidly impaired by sustained D1LR activation via a mechanism involving sustained MOR activation.
Cyclic Nucleotide Control of Microtubule Dynamics for Axon Guidance
Authors: Akiyama Hiroki , Fukuda Tetsuko , Tojima Takuro , Nikolaev Viacheslav O. , Kamiguchi Hiroyuki 
Published: May 2016

Graded distribution of intracellular second messengers, such as Ca2+and cyclic nucleotides, mediates directional cell migration, including axon navigational responses to extracellular guidance cues, in the developing nervous system. Elevated concentrations of cAMP or cGMP on one side of the neuronal growth cone induce its attractive or repulsive turning, respectively. Although effector processes downstream of Ca2+have been extensively studied, very little is known about the mechanisms that enable cyclic nucleotides to steer migrating cells. Here, we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance via modulating microtubule dynamics and membrane organelle transport. In embryonic chick dorsal root ganglion neurons in culture, contact of an extending microtubule with the growth cone leading edge induces localized membrane protrusion at the site of microtubule contact. Such a contact-induced protrusion requires exocytosis of vesicle-associated membrane protein 7 (VAMP7)-positive vesicles that have been transported centrifugally along the microtubule. We found that the two cyclic nucleotides counteractively regulate the frequency of microtubule contacts and targeted delivery of VAMP7 vesicles: cAMP stimulates and cGMP inhibits these events, thereby steering the growth cone in the opposite directions. By contrast, Ca2+signals elicit no detectable change in either microtubule contacts or VAMP7 vesicle delivery during Ca2+-induced growth cone turning. Our findings clearly demonstrate growth cone steering machinery downstream of cyclic nucleotide signaling and highlight a crucial role of dynamic microtubules in leading-edge protrusion for cell chemotaxis.SIGNIFICANCE STATEMENTDeveloping neurons can extend long axons toward their postsynaptic targets. The tip of each axon, called the growth cone, recognizes extracellular guidance cues and navigates the axon along the correct path. Here we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance through localized regulation of microtubule dynamics and resulting recruitment of specific populations of membrane vesicles to the growth cone's leading edge. Remarkably, cAMP stimulates microtubule growth and membrane protrusion, whereas cGMP promotes microtubule retraction and membrane senescence, explaining the opposite directional polarities of growth cone turning induced by these cyclic nucleotides. This study reveals a novel microtubule-based mechanism through which cyclic nucleotides polarize the growth cone steering machinery for bidirectional axon guidance.
Neural Coding of Interaural Time Differences with Bilateral Cochlear Implants in Unanesthetized Rabbits
Authors: Chung Yoojin , Hancock Kenneth E. , Delgutte Bertrand 
Published: May 2016

Although bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs, bilateral CI users' sensitivity to interaural time differences (ITDs) is still poorer than normal. In particular, ITD sensitivity of most CI users degrades with increasing stimulation rate and is lacking at the high carrier pulse rates used in CI processors to deliver speech information. To gain a better understanding of the neural basis for this degradation, we characterized ITD tuning of single neurons in the inferior colliculus (IC) for pulse train stimuli in an unanesthetized rabbit model of bilateral CIs. Approximately 73% of IC neurons showed significant ITD sensitivity in their overall firing rates. On average, ITD sensitivity was best for pulse rates near 80–160 pulses per second (pps) and degraded for both lower and higher pulse rates. The degradation in ITD sensitivity at low pulse rates was caused by strong, unsynchronized background activity that masked stimulus-driven responses in many neurons. Selecting synchronized responses by temporal windowing revealed ITD sensitivity in these neurons. With temporal windowing, both the fraction of ITD-sensitive neurons and the degree of ITD sensitivity decreased monotonically with increasing pulse rate. To compare neural ITD sensitivity to human performance in ITD discrimination, neural just-noticeable differences (JNDs) in ITD were computed using signal detection theory. Using temporal windowing at lower pulse rates, and overall firing rate at higher pulse rates, neural ITD JNDs were within the range of perceptual JNDs in human CI users over a wide range of pulse rates.SIGNIFICANCE STATEMENTMany profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears [interaural time difference (ITD)] to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors. This study provides a better understanding of ITD processing with bilateral CIs and shows a parallel between human performance in ITD discrimination and neural responses in the auditory midbrain. The present study is the first report on binaural properties of auditory neurons with CIs in unanesthetized animals.
Sensory Cortical Activity Is Related to the Selection of a Rhythmic Motor Action Pattern
Authors: Li Jennifer X. , Maier Joost X. , Reid Emily E. , Katz Donald B. 
Published: May 2016

Rats produce robust, highly distinctive orofacial rhythms in response to taste stimuli—responses that aid in the consumption of palatable tastes and the ejection of aversive tastes, and that are sourced in a multifunctional brainstem central pattern generator. Several pieces of indirect evidence suggest that primary gustatory cortex (GC) may be a part of a distributed forebrain circuit involved in the selection of particular consumption-related rhythms, although not in the production of individual mouth movements per se. Here, we performed a series of tests of this hypothesis. We first examined the temporal relationship between GC activity and orofacial behaviors by performing paired single-neuron and electromyographic recordings in awake rats. Using a trial-by-trial analysis, we found that a subset of GC neurons shows a burst of activity beginning before the transition between nondistinct and taste-specific (i.e., consumption-related) orofacial rhythms. We further showed that shifting the latency of consumption-related behavior by selective cueing has an analogous impact on the timing of GC activity. Finally, we showed the complementary result, demonstrating that optogenetic perturbation of GC activity has a modest but significant impact on the probability that a specific rhythm will be produced in response to a strongly aversive taste. GC appears to be a part of a distributed circuit that governs the selection of taste-induced orofacial rhythms.SIGNIFICANCE STATEMENTIn many well studied (typically invertebrate) sensorimotor systems, top-down modulation helps motor-control regions “select” movement patterns. Here, we provide evidence that gustatory cortex (GC) may be part of the forebrain circuit that performs this function in relation to oral behaviors (“gapes”) whereby a substance in the mouth is rejected as unpalatable. We show that GC palatability coding is well timed to play this role, and that the latency of these codes changes as the latency of gaping shifts with learning. We go on to show that by silencing these neurons, we can change the likelihood of gaping. These data help to break down the sensory/motor divide by showing a role for sensory cortex in the selection of motor behavior.
Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade
Authors: Mills Holly , Ortega Amanda , Law Wenjing , Hapiak Vera , Summers Philip , Clark Tobias , Komuniecki Richard 
Published: May 2016

The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. InCaenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued innpr-17-null animals by the expression ofnpr-17or a human κ opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by bothnlp-3andnlp-24, and eithernlp-3ornlp-24overexpression mimics morphine and suppresses withdrawal. Peptides encoded bynlp-3act differentially, with only NLP-3.3 mimicking morphine, whereas othernlp-3peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception inCaenorhabditis elegansthrough a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals.SIGNIFICANCE STATEMENTOpiates are used extensively to treat chronic pain. InCaenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a α-adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human κ opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate signaling in mammals.
Circulating makorin ring finger protein 3 levels decline in boys before the clinical onset of puberty
Authors: Varimo Tero , Dunkel Leo , Vaaralahti Kirsi , Miettinen Päivi J , Hero Matti , Raivio Taneli 
Published: May 2016

ObjectiveMakorin ring finger protein 3 (MKRN3) gene restrains the hypothalamic–pituitary–gonadal axis. In girls, peripheral levels of MKRN3 decline prior to the onset of puberty. We described longitudinal changes in serum MKRN3 levels in boys before and during puberty and assessed the effect of inhibition of estrogen biosynthesis on MKRN3 levels.DesignLongitudinal serum samples from a double-blind, randomized controlled study in 30 boys (age range: 9.1–14.2years) with idiopathic short stature who received placebo (Pl;n=14) or aromatase inhibitor letrozole (Lz; 2.5mg/day;n=16) for 2years.MethodsWe analyzed the relationships between serum MKRN3 and clinical and biochemical markers of puberty by using summary measures.ResultsSerum MKRN3 declined by 669±713 pg/mL per year (P<0.001). This change was biphasic, as the levels decreased during Tanner genital stage G1 (–2931±2750 pg/mL per year) and plateaued thereafter (–560±1510 pg/mL per year) (P<0.05). During G1, MKRN3 levels in Lz-treated subjects decreased slower than in Pl-treated boys (–782±3190 vs –2030±821 pg/mL per year,P<0.05). The decrease in serum MKRN3 levels in G1 was associated with increases in LH (r=–0.5,P<0.01), testosterone (r=–0.6,P<0.01), and inhibin B (r=–0.44,P<0.05) (n=26).ConclusionPeripheral MKRN3 levels in boys appear to serve as a readout of the diminishing central inhibition that controls the onset of puberty.
‘Incidental’ and ‘non-incidental’ thyroid papillary microcarcinomas are two different entities
Authors: Provenzale Maria Annateresa , Fiore Emilio , Ugolini Clara , Torregrossa Liborio , Morganti Riccardo , Molinaro Eleonora , Miccoli Paolo , Basolo Fulvio , Vitti Paolo 
Published: May 2016

Objective
Papillary thyroid microcarcinomas (microPTC) may be ’incidental’ (Inc-microPTC), occasionally found at histology after surgery for benign disease or ‘non-incidental’ (Non-Inc-microPTC), diagnosed on clinical grounds. It is unclear whether these different microPTC reflect the same disease. The aim of the study was to compare Inc-microPTC and Non-Inc-microPTC for clinical and histological features as well as for serum TSH, a known factor involved in PTC development.

Design
We evaluated histology and serum TSH levels of consecutive patients submitted to thyroidectomy for goiter with compressive symptoms or for cytological diagnosis suspicious/indicative of PTC.

Methods
In total, 665 consecutive patients (259 with a single thyroid nodule, SN and 406 with a multinodular gland, MN) were included in the study. According to histology, patients were classified as: benign nodular goiter (Benign, n=291); Inc-microPTC (n=92); Non-Inc-microPTC (n=67) and PTC≥1cm (macroPTC, n=215).

Results
Inc-microPTC were significantly more frequent in MN than in SN (66/406, 16.2% vs 26/259, 10.0%, P=0.02). Patients with Inc-microPTC compared with Non-Inc-microPTC were older (mean age±s.d. 53.3±13.2 years vs 44.9±14.8 years, P=0.0002), had a smaller tumor size (median 4mm vs 9mm, P<0.0001), a higher frequency of multifocality (70/92, 76.1% vs 35/67, 52.2% P=0.001) and lower levels of TSH (median 0.6mIU/L, IR: 0.4–1.0mIU/L vs value 1. mIU/L, IR: 0.6–1.4mIU/L vs P=0.0001).

Conclusion
Incidental and non-incidental papillary thyroid microcarcinomas appear to be two different entities.
Reseña del artículo “Activities and Programs That Improve Children’s Executive Functions”
Authors: Cortés Saavedra Daniela , Marques Daniela 
Published: May 2016

La presente reseña desarrolla una línea argumentativa que describe la relevancia del estudio de las funciones ejecutivas en el contexto de la evaluación e intervención. Se describen los principales tópicos discutidos en el artículo, tales como la conceptualización de función ejecutiva, los principios generales de intervención y la eficacia de algunos programas de entrenamiento. Se concluye enfatizando la necesidad de estudiar diferentes métodos de intervención para elegir el que más se adecúe a la individualidad de cada sujeto. De igual forma, se apuntan críticas al interés de la gran mayoría de investigadores en el estudio de métodos de entrenamiento dirigidos a niños escolarizados, poniendo de parte los que no se encuentran vinculados a un proceso de educación formal.
Legal Ethics, Rules of Conduct and the Moral Compass – Considerations from a Law Student's Perspective
Authors: Van Zyl IV Christoffel Hendrik , Visser Jo-Marí 
Published: May 2016

When young law graduates enter the legal profession they will undoubtedly be exposed to difficult situations that will demand of them to make difficult decisions, often having to balance conflicting systems of belief and ideas on what ethical behaviour entails. Legal ethics training in law faculties the world over often neglects teaching aspects of morality to focus on reviews of rules of professional legal conduct. This article argues that if legal education is to adequately prepare law graduates for legal practice, it must offer more than reviews of these codes of conduct. To properly assist law students in avoiding pitfalls which may lead to disciplinary action, they must be taught to appropriately use their moral compasses.
This narrative aims to show that the metaphorical moral compass, with the cardinal virtues as possible main points, may serve as the crucial and underlying guide in the avoidance of the pitfalls which may result in a person being struck from the roll, but more than that, that it may aid in the pursuit of personal dreams or goals. The article contributes to the literature on legal ethics by foregrounding the virtues that pertain to sound conduct in a lawyer, as opposed to the rules and codes, in the hope that this may help legal practitioners to decide on what is right and what is wrong.
A MASTECTOMIA E A RESSIGNIFICAÇÃO DO CORPO NO FEMININO
Authors: Pereira Dayane , Martinelli Braga Ana Aparecida 
Published: May 2016

O câncer de mama é o segundo tipo de câncer mais frequente no mundo e o mais comum entre as mulheres. A cirurgia de mastectomia é o mais invasivo dos tratamentos cirúrgicos para esta patologia, e traz sérias implicações para a paciente. Este trabalho visa abordar questões referentes às estratégias de enfrentamento utilizadas no processo de adoecimento, bem como a percepção das pacientes sobre sua autoimagem pré e pós cirúrgica; identificar impactos psicológicos, físicos e sociais causados pela cirurgia e pelo tratamento quimioterápico; avaliar as percepções referentes à temática da morte e às dimensões do medo que este tema desperta. O estudo contou com levantamento bibliográfico e pesquisa de campo, na qual a coleta de dados foi feita através de entrevista semiestruturada, aplicada em dois momentos – antes e depois da cirurgia – em quatro participantes que estavam em tratamento oncológico em clínica particular de Salvador - BA. Com os dados obtidos, foram selecionadas quatro categorias de análise. Como resultado, concluiu-se que o recebimento do diagnóstico de câncer fez com que a paciente refletisse sobre questões como o sentido da sua vida e o medo da morte; para elas a estética não diz respeito apenas ao que é belo, mas se refere à identificação com o feminino; observou-se também que a crença em Deus é algo que possibilita e potencializa o estabelecimento da confiança no tratamento e na possibilidade de cura; e que a atuação da equipe multidisciplinar de assistência pode otimizar o tratamento quando esta trabalha de forma humanizada.
The NICU Mom Who Rarely Visits and What You Can Do About It
Authors: Discenza Deborah 
Published: May 2016

ABSTRACTNICU nurses often worry about NICU moms who are not able to visit their babies regularly and rightfully so. The mother is key to not only the baby’s ability to survive but also thrive, and spare visits do little to help with the bonding process. This article provides solid tips on increasing the NICU mom’s visits using strengths and positives instead of guilt.
Patient-Centered Care and Population Health
Authors: Harwood Jared L. , Butler Craig A. , Page Alexandra E. 
Published: May 2016

Abstract:
As health care increasingly emphasizes high value, the terms “population health” and “patient-centered care” have become common, but their application is less clear. Patient-centered care encourages using data to optimize care for an individual. Population health offers a framework to consider how to efficiently and effectively manage a condition for a population, how prevention affects large groups, and the specific distribution of a given disorder. Integrating both concepts into practice can facilitate required outcome-measure reporting and potentially improve patient outcomes. Clinical practice guidelines and appropriate use criteria are examples of reconciliation of these topics. By embracing attempts to decrease variation in treating musculoskeletal disorders while personalizing delivery to individual patients, surgeons may benefit from the improvement of both efficiency and patient experience.