bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental Novelty Differentially Affects c-fosmRNA Expression Induced by Amphetamine or Cocaine in Subregions of the Bed Nucleus of the Stria Terminalis and Amygdala
Authors: Day Heidi E. W. , Badiani Aldo , Uslaner Jason M. , Oates Matthew M. , Vittoz Nicole M. , Robinson Terry E. , Watson Stanley J. , Akil Huda 
Published: April 2018

The environmental context in which amphetamine or cocaine are administered modulates both their acute psychomotor activating effects and their ability to induce sensitization. Here we report that environmental context differentially affects patterns of amphetamine- and cocaine-induced c-fosmRNA expression in the bed nucleus of the stria terminalis (BST) and amygdala of male rats.In the medial amygdala and medial posterior BST, exposure to novelty resulted in a marked increase in c-fosmRNA. Amphetamine given at home did not induce c-fosmRNA, and when given in the novel environment, did not increase levels beyond that observed for novelty alone. In the basolateral and lateral amygdala, amphetamine or cocaine at home or exposure to novelty induced c-fosmRNA. When amphetamine or cocaine was given in a novel environment the c-fosmRNA response was significantly enhanced. In the central nucleus of the amygdala (CEA) and oval subnucleus of the BST (BSTov), amphetamine administration at home produced a robust increase in c-fosmRNA expression, whereas exposure to novelty had little effect. In contrast to other brain regions examined, the c-fosmRNA response to amphetamine in a novel versus home environment was significantly smaller. In both “home” and “novel” amphetamine groups, c-fosmRNA in the BSTov and CEA was predominantly expressed in enkephalin-containing cells; coexpression with corticotropin-releasing hormone was rare.These data suggest that the context in which psychostimulants are given powerfully and differentially alters the response of limbic structures that have been functionally implicated in drug reinforcement and emotional behaviors.
Pyruvate Released by Astrocytes Protects Neurons from Copper-Catalyzed Cysteine Neurotoxicity
Authors: Wang Xue Feng , Cynader Max S. 
Published: April 2018

We have found previously that astrocytes can provide cysteine to neurons. However, cysteine has been reported to be neurotoxic although it plays a pivotal role in regulating intracellular levels of glutathione, the major cellular antioxidant. Here, we show that cysteine toxicity is a result of hydroxyl radicals generated during cysteine autoxidation. Transition metal ions are candidates to catalyze this process. Copper substantially accelerates the autoxidation rate of cysteine even at submicromolar levels, whereas iron and other transition metal ions, including manganese, chromium, and zinc, are less efficient. The autoxidation rate of cysteine in rat CSF is equal to that observed in the presence of ∼0.2 μmcopper. In tissue culture tests, we found that cysteine toxicity depends highly on its autoxidation rate and on the total amount of cysteine being oxidized, suggesting that the toxicity can be attributed to the free radicals produced from cysteine autoxidation, but not to cysteine itself.We have also explored thein vivomechanisms that protect against cysteine toxicity. Catalase and pyruvate were each found to inhibit the production of hydroxyl radicals generated by cysteine autoxidation. In tissue culture, they both protected primary neurons against cysteine toxicity catalyzed by copper. This protection is attributed to their ability to react with hydrogen peroxide, preventing the formation of hydroxyl radicals. Pyruvate, but not catalase or glutathione peroxidase, was detected in astrocyte-conditioned medium and CSF. Our data therefore suggest that astrocytes can prevent cysteine toxicity by releasing pyruvate.
Complex Trait Analysis of the Hippocampus: Mapping and Biometric Analysis of Two Novel Gene Loci with Specific Effects on Hippocampal Structure in Mice
Authors: Lu Lu , Airey David C. , Williams Robert W. 
Published: April 2018

Notable differences in hippocampal structure are associated with intriguing differences in development and behavioral capabilities. We explored genetic and environmental factors that modulate hippocampal size, structure, and cell number using sets of C57BL/6J (B6) and DBA/2J (D2) mice; their F1 and F2 intercrosses (n= 180); and 35 lines of BXD recombinant inbred (RI) strains. Hippocampal weights of the parental strains differ by 20%. Estimates of granule cell number also differ by ∼20%. Hippocampal weights of RI strains range from 21 to 31 mg, and those of individual F2 mice range from 23 to 36 mg (bilateral weights). Volume and granule cell number are well correlated (r= 0.7–0.8). Significant variation is associated with differences in age and sex. The hippocampus increases in weight by 0.24 mg per month, and those of males are 0.55 mg heavier (bilateral) than those of females.Heritability of variation is ∼50%, and half of this genetic variation is generated by two quantitative trait loci that map to chromosome 1 (Hipp1a: genome-widep< 0.005, between 65 and 100 cM) and to chromosome 5 (Hipp5a,p< 0.05, between 15 and 40 cM). These are among the first gene loci known to produce normal variation in forebrain structure.Hipp1aandHipp5aindividually modulate hippocampal weight by 1.0–2.0 mg, an effect size greater than that generated by age or sex. TheHippgene loci modulate neuron number in the dentate gyrus, collectively shifting the population up or down by as much as 200,000 cells. Candidate genes for theHipploci includeRxrgandFgfr3.
Differential Contribution of Substance P and Neurokinin A to Spinal Cord Neurokinin-1 Receptor Signaling in the Rat
Authors: Trafton Jodie A. , Abbadie Catherine , Basbaum Allan I. 
Published: April 2018

Although the tachykinins substance P (SP) and neurokinin A (NKA) are coreleased from primary afferent nociceptors and act via neurokinin (NK) receptors, their differential effectsin vivoare not known. Despite pharmacological evidence that NKA preferentially binds NK-2 receptors, this receptor is not found in spinal cord neurons. Thus, in the present studies, we compared the extent to which SP and NKA contribute to spinal nociceptive processing via the NK-1 receptor.We found that SP and NKA induce NK-1 receptor internalization with identical dose dependence and induce increases in intracellular calcium at the same concentrations, suggesting that SP and NKA equally activate the NK-1 receptor. We found, however, that the selective NK-1 receptor antagonist GR 205171 blocked NKA but not SP-induced NK-1 receptor internalization in the rat spinal cordin vivoand in embryonic day 19 rat spinal neuronsin vitro. Using this selectivity of GR 205171 for NKA-induced NK-1 receptor activation, we examined the relative contribution of SP and NKA to noxious stimulus-induced activation of spinal NK-1 receptors. We estimate that NKA contributes to at least 50% of the NK-1 receptor activation in lamina I. Under inflammatory conditions, all noxious stimulus-induced NK-1 receptor internalization in deep dorsal horn neurons was blocked by GR 205171, suggesting that it is entirely NKA-mediated. Substance P-mediated NK-1 receptor internalization was focused at the site of termination of stimulated nociceptors but NKA also activated NK-1 receptors at more distant sites. We conclude that NKA not only targets the NK-1 receptor but may be a predominant pronociceptive primary afferent neurotransmitter.
Susceptibility to Kindling and Neuronal Connections of the Anterior Claustrum
Authors: Zhang Xia , Hannesson Darren K. , Saucier Deborah M. , Wallace Amy E. , Howland John , Corcoran Michael E. 
Published: April 2018

The claustrum has been implicated in the kindling of generalized seizures from limbic sites. We examined the susceptibility of the anterior claustrum itself to kindling and correlated this with an anatomical investigation of its afferent and efferent connections.Electrical stimulation of the anterior claustrum resulted in a pattern of rapid kindling with two distinct phases. Early kindling involved extremely rapid progression to bilaterally generalized seizures of short duration. With repeated daily kindling stimulations, early-phase generalized seizures abruptly became more elaborate and prolonged, resembling limbic-type seizures as triggered from the amygdala. We suggest that the rapid rate of kindling from the anterior claustrum is an indication that the claustrum is functionally close to the mechanisms of seizure generalization.In support of our hypothesis, we found significant afferent, efferent, and often reciprocal connections between the anterior claustrum and areas that have been implicated in the generation of generalized seizures, including frontal and motor cortex, limbic cortex, amygdala, and endopiriform nucleus. Additional connections were found with various other structures, including olfactory areas, nucleus accumbens, midline thalamus, and brainstem nuclei including the substantia nigra and the dorsal raphe nucleus. The anatomical connections of the anterior claustrum are consistent with its very high susceptibility to kindling and support the view that the claustrum is part of a forebrain network of structures participating in the generalization of seizures.
Psychological Stress Increases Hippocampal Mineralocorticoid Receptor Levels: Involvement of Corticotropin-Releasing Hormone
Authors: Gesing Angela , Bilang-Bleuel Alicia , Droste Susanne K. , Linthorst Astrid C. E. , Holsboer Florian , Reul Johannes M. H. M. 
Published: April 2018

We investigated whether acute stressors regulate functional properties of the hippocampal mineralocorticoid receptor (MR), which acts inhibitory on hypothalamic-pituitary-adrenocortical activity. Exposure of rats to forced swimming or novelty evoked a significant rise in density of MR immunoreactivity in all hippocampal subfields after 24 hr, whereas exposure to a cold environment was ineffective. Time course analysis revealed that the effect of forced swimming on MR peaked at 24 hr and returned to control levels between 24 and 48 hr. In pyramidal neurons of CA2 and CA3, marked rises were already observed after 8 hr. Radioligand binding assays showed that corticotropin-releasing hormone (CRH) injected intracerebroventricularly into adrenalectomized rats also produced a rise in hippocampal MR levels; an effect for which the presence of corticosterone, but not dexamethasone, at the time of injection was a prerequisite. Moreover, pretreatment with the CRH receptor antagonist (d-Phe12,Nle21,38,α-Me-Leu37)-CRH12–41blocked the effect of forced swimming on hippocampal MR levels. To investigate whether the rise in MR levels had any functional consequences for HPA regulation, 24 hr after forced swimming, a challenge test with the MR antagonist RU 28318 was conducted. The forced swimming exposed rats showed an enhanced MR-mediated inhibition of HPA activity.This study identifies CRH as an important regulator of MR, a pathway with marked consequence for HPA axis regulation. We conclude that the interaction between CRH and MR presents a novel mechanism involved in the adaptation of the brain to psychologically stressful events.
The Role of Activity-Dependent Network Depression in the Expression and Self-Regulation of Spontaneous Activity in the Developing Spinal Cord
Authors: Tabak Joël , Rinzel John , O'Donovan Michael J. 
Published: April 2018

Spontaneous episodic activity occurs throughout the developing nervous system because immature circuits are hyperexcitable. It is not fully understood how the temporal pattern of this activity is regulated. Here, we study the role of activity-dependent depression of network excitability in the generation and regulation of spontaneous activity in the embryonic chick spinal cord. We demonstrate that the duration of an episode of activity depends on the network excitability at the beginning of the episode. We found a positive correlation between episode duration and the preceding inter-episode interval, but not with the following interval, suggesting that episode onset is stochastic whereas episode termination occurs deterministically, when network excitability falls to a fixed level. This is true over a wide range of developmental stages and under blockade of glutamatergic or GABAergic/glycinergic synapses.We also demonstrate that during glutamatergic blockade the remaining part of the network becomes more excitable, compensating for the loss of glutamatergic synapses and allowing spontaneous activity to recover. This compensatory increase in the excitability of the remaining network reflects the progressive increase in synaptic efficacy that occurs in the absence of activity. Therefore, the mechanism responsible for the episodic nature of the activity automatically renders this activity robust to network disruptions. The results are presented using the framework of our computational model of spontaneous activity in the developing cord. Specifically, we show how they follow logically from a bistable network with a slow activity-dependent depression switching periodically between the active and inactive states.
Short-Term Retrograde Inhibition of GABAergic Synaptic Currents in Rat Purkinje Cells Is Mediated by Endogenous Cannabinoids
Authors: Diana Marco A. , Levenes Carole , Mackie Ken , Marty Alain 
Published: April 2018

Depolarization-induced suppression of inhibition (DSI) is a form of short-term plasticity of GABAergic synaptic transmission that is found in cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. DSI involves the release of a calcium-dependent retrograde messenger by the somatodendritic compartment of the postsynaptic cell. Both glutamate and endogenous cannabinoids have been proposed as retrograde messenger.Here we show that, in cerebellar parasagittal slices, type 1 cannabinoid receptors (CB1Rs) are expressed at high levels in axons of GABAergic interneurons and in presynaptic terminals onto Purkinje cells. Application of the cannabinoid antagonist AM-251 (500 nm) leads to the abolition of the DSI of evoked currents (eIPSCs) recorded in paired recordings and to a strong reduction of the DSI of TTX-insensitive miniature events (mIPSCs) recorded from Purkinje cells. Furthermore, the CB1R agonist WIN 55–212,2 (5 μm) induces a presynaptic inhibition of synaptic currents similar to that occurring during DSI, as well as an occlusion of DSI after stimulation of Purkinje cells. Moreover, WIN 55–212,2 reduces the calcium transients evoked in presumed presynaptic varicosities by short trains of action potentials.Our results indicate that DSI is mediated by the activation of presynaptic CB1Rs and that an endogenous cannabinoid is a likely candidate retrograde messenger in this preparation. They further suggest that DSI involves distinct presynaptic modifications for eIPSCs and mIPSCs, including an inhibition of action potential-evoked calcium rises.
Çene Yüz Kırıklarının Demografik Özellikleri ve Etiyolojik Faktörleri: Retrospektif Çalışma
Authors: Özgül Özkan 
Published: April 2018

Amaç:
Bu çalışmanın amacı bölgemizde görülen çene yüz kırıklarının demografik ve
klinik özelliklerini, etiyolojik faktörlerini ve tedavi protokollerini
retrospektif olarak analiz etmektir. Gereç ve Yöntemler:
Çalışmamızda Nisan 2015- Kasım 2017 tarihleri arasında
kliniğimizde çene yüz kırık tanısı ile tedavi edilmiş hastaların medikal
kayıtları değerlendirmeye
alındı. Yaş, cinsiyet, etiyolojik neden, kırığın lokalizasyonu, uygulanan
tedavi yöntemi
belirlenerek veri dağılımı analiz edildi.Bulgular: Medikal
kayıtların incelenmesi ile, 40’ı erkek (%77), 12’si kadın olan 52 hastada 62 çene yüz kırığı tespit
edildi. Ortalama yaş 33.3 (9- 67), etiyolojik faktörler sırasıyla darp (%42),
trafik kazası (%33), düşme (%25) olarak bulundu. 62 kırığın %92’si mandibulada;
lokalizasyonlarına göre sırasıyla angulus (%34), simfiz (%31), kondil (%14), korpus (%8), ramus (%5)
ve %8’i de maksillada görüldü. Sonuç: Çene yüz kırıklarının
etiyolojisi ve insidansı; sosyal, kültürel, ekonomik ve çevresel şartlara bağımlıdır. Farklı
coğrafik, ekonomik ve sosyal özelliklere sahip olan ülkemizde yapılacak çok merkezli çalışmalara ihtiyaç
bulunmaktadır.

Anahtar Kelime:
Travma; Çene yüz Kırıkları; Etiyoloji
Flower Development in Walnut: Altering the Flowering Pattern by Gibberellic Acid Application
Authors: HASSANKHAH Amin , RAHEMI Majid , MOZAFARI Mohamad Reza , VAHDATI Kourosh 
Published: April 2018

The pattern of walnut flowering varies depending on genetic and environmental factors. This research was carried out to study the patterns by which pistillate flowers develop as a result of applying gibberellic acid (GA3). To study the effect of gibberellin on flowering, we used a factorial test. Factor A was the diameter of the tree trunks, and three levels were considered (10 to 12 cm, 12 to 14 cm and 14 to 16 cm). Factor B was comprised of four levels of GA3 (0, 50,100 and 200 mg/lit). Different levels of GA3 were sprayed twice on the ‘Chandler’ cultivar, i.e. 2 and 4 weeks after flowering. Also, a new (without using a microtome or scanning electron microscopy) method was used to study the development of pistillate flower buds. Different stages of development included induction, initiation and differentiation of the pistillate flower bud which were observed respectively in late May, early June, September and March. The results of GA3 application showed that GA3 treatment can alter the flowering pattern of walnut. GA3 application significantly increased the number of male flowers, total flowers, and male: female flower ratio per branch. The number of female flowers increased as the diameter of the tree trunk increased. The highest number of female flowers (62.3) was observed in trees with trunk diameters between 14-16 cm and when GA3 was applied at 100 mg/liter. Also, a linear regression model was used in order to find a relationship between GA3 levels and the diameter of the trunk with flowering pattern.
FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome
Authors: Le Robert Q. , Li Liang , Yuan Weishi , Shord Stacy S. , Nie Lei , Habtemariam Bahru A. , Przepiorka Donna , Farrell Ann T. , Pazdur Richard 
Published: April 2018

Abstract

On August 30, 2017, the U.S. Food and Drug Administration approved Actemra (tocilizumab, Genentech, Inc., South San Francisco, CA) for the treatment of severe or life-threatening chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) in adults and in pediatric patients 2 years of age and older. The approval was based on a retrospective analysis of data for patients who developed CRS after treatment with CTL019 and KTE-C19 on prospective clinical trials. Evaluable patients had been treated with intravenous tocilizumab 8 mg/kg (12 mg/kg for patients &lt;30 kg) for severe or life-threatening CRS; only the first episode of CRS was included in the analysis. The efficacy population for the CTL019 cohort included 24 male and 21 female patients (total 45 patients) of median age 12 years. The median time from the start of CRS to the first dose of tocilizumab was 4 days (range, 0–18 days). Patients were considered responders if CRS resolved within 14 days of the first dose of tocilizumab, if no more than 2 doses of tocilizumab were needed, and if no drugs other than tocilizumab and corticosteroids were used for treatment. Thirty-one patients (69%; 95% confidence interval, 53%–82%) achieved a response as defined. In an independent cohort of 15 patients with KTE-C19-induced CRS, 53% responded. Further study is needed to determine the optimal dose of tocilizumab and to confirm the safety of its use for treatment of patients with CAR T cell-induced CRS.

Implications for Practice
Severe or life-threatening chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) requires urgent treatment to prevent fatal outcomes. In two independent cohorts, the majority of patients with severe or life-threatening CAR T cell-induced CRS responded to treatment with one or two doses of tocilizumab in addition to advanced supportive care. More research is needed to determine the optimal dose and schedule of tocilizumab for treatment of CAR T cell-induced CRS.
TEORÍA CONTABLE: FUNDAMENTO DE ANÁLISIS EN EL EJERCICIO PROFESIONAL Y LA PRÁCTICA PEDAGÓGICA
Authors: Ariza Angarita Yuleida , Villasmil Molero Milagros 
Published: April 2018

El presente artículo de revisión bibliográfica, se realizó con el objetivo de analizar la teoría contable con fundamento en el análisis del ejercicio profesional y la práctica pedagógica en la formación integral del contador público. En su elaboración, se utilizó el método analítico, con una visión descriptiva, y la técnica investigativa de la revisión documental. Entre los hallazgos obtenidos, se destaca que en el proceso formativo del contador aún se encuentran poco desarrolladas las competencias de observación, reflexión analítica y predicción, por cuanto, al momento de tomar decisiones se le da más importancia a la parte cuantitativa de la información que a la parte cualitativa . Las razones obedecen en gran parte a débiles bases conceptuales acerca de su valor y su contribución al desarrollo de nuevas prácticas y pensamiento contable. Se concluyó que para que a la teoría contable le sea reconocido su valor proyectivo y predictivo, es imperativo una pedagogía particular para estudiarla, comprenderla e introducirla como fundamento de soporte esencial para el análisis financiero en el ejercicio de la profesión contable; ello es así porque las cambiantes visiones de la realidad exigen nuevas formas de observación fenoménica, que favorezcan la solución a problemas complejos que le son inherentes. Asimismo, se espera que el estudio bibliográfico constituya un asidero epistemológico para futuras investigaciones. ABSTRACTThis article literature review was conducted with the aim of analyzing accounting theory as a foundation in the analysis of professional practice and pedagogical practice in the formation of the CPA, in drafting the analytical method was used, with a descriptive view technical research is the literature review. Among the findings from the formative process of the counter are still lagging skills of observation, analysis and reflection-prediction, in that he gives more importance to the quantitative portion of the information that highlights the qualitative part for decision making , the reasons are due largely to weak conceptual basis about its value against the correct usage you have and its contribution to the development of new practices and accounting thought. It was concluded that for accounting theory is recognized its projective and predictive value, it is imperative to study a particular pedagogy understand and enter it as essential foundation for financial analysis support in the performance of the accounting profession; considering that this paradigmatic changing views of reality require new forms of phenomenal observation that favors the solution to complex problems that are inherent, also is expected to constitute an epistemological journey bibliographic handle foundation for future research.