bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemogenetic Manipulation of Dopamine Neurons Dictates Cocaine Potency at Distal Dopamine Transporters
Authors: Brodnik Zachary D. , Xu Wei , Batra Aashita , Lewandowski Stacia I. , Ruiz Christina M. , Mortensen Ole V. , Kortagere Sandhya , Mahler Stephen V. , España Rodrigo A. 
Published: October 2020

The reinforcing efficacy of cocaine is largely determined by its capacity to inhibit the dopamine transporter (DAT), and emerging evidence suggests that differences in cocaine potency are linked to several symptoms of cocaine use disorder. Despite this evidence, the neural processes that govern cocaine potencyin vivoremain unclear. In male rats, we used chemogenetics with intra-VTA microinfusions of the agonist clozapine-n-oxide to bidirectionally modulate dopamine neurons. Usingex vivofast scan cyclic voltammetry, pharmacological probes of the DAT, biochemical assessments of DAT membrane availability and phosphorylation, and cocaine self-administration, we tested the effects of chemogenetic manipulations on cocaine potency at distal DATs in the nucleus accumbens as well as the behavioral economics of cocaine self-administration. We discovered that chemogenetic manipulation of dopamine neurons produced rapid, bidirectional modulation of cocaine potency at DATs in the nucleus accumbens. We then provided evidence that changes in cocaine potency are associated with alterations in DAT affinity for cocaine and demonstrated that this change in affinity coincides with DAT conformation biases and changes in DAT phosphorylation state. Finally, we showed that chemogenetic manipulation of dopamine neurons alters cocaine consumption in a manner consistent with changes in cocaine potency at distal DATs. Based on the spatial and temporal constraints inherent to our experimental design, we posit that changes in cocaine potency are driven by alterations in dopamine neuron activity. When considered together, these observations provide a novel mechanism through which GPCRs regulate cocaine's pharmacological and behavioral effects.SIGNIFICANCE STATEMENTDifferences in the pharmacological effects of cocaine are believed to influence the development and progression of cocaine use disorder. However, the biological and physiological processes that determine sensitivity to cocaine remain unclear. In this work, we use a combination of chemogenetics, fast scan cyclic voltammetry, pharmacology, biochemistry, and cocaine self-administration with economic demand analysis to demonstrate a novel mechanism by which cocaine potency is determinedin vivo. These studies identify a novel process by which the pharmacodynamics of cocaine are derivedin vivo, and thus this work has widespread implications for understanding the mechanisms that regulate cocaine consumption across stages of addiction.
Dissecting the Role of GABA Neurons in the VTAversusSNr in Opioid Reward
Authors: Galaj Ewa , Han Xiao , Shen Hui , Jordan Chloe J. , He Yi , Humburg Bree , Bi Guo-Hua , Xi Zheng-Xiong 
Published: October 2020

Opioid reward has traditionally been thought to be mediated by GABA-induced disinhibition of dopamine (DA) neurons in the VTA. However, direct behavioral evidence supporting this hypothesis is still lacking. In this study, we found that the μ opioid receptor (MOR) gene,Oprm1, is highly expressed in GABA neurons, with ∼50% of GABA neurons in the substantia nigra pars reticulata (SNr), ∼30% in the VTA, and ∼70% in the tail of the VTA (also called the rostromedial tegmental nucleus) in male rats. NoOprm1mRNA was detected in midbrain DA neurons. We then found that optogenetic inhibition of VTA DA neurons reduced intravenous heroin self-administration, whereas activation of these neurons produced robust optical intracranial self-stimulation in DAT-Cre mice, supporting an important role of DA neurons in opioid reward. Unexpectedly, pharmacological blockade of MORs in the SNr was more effective than in the VTA in reducing heroin reward. Optogenetic activation of VTA GABA neurons caused place aversion and inhibited cocaine, but not heroin, self-administration, whereas optogenetic activation of SNr GABA neurons caused a robust increase in heroin self-administration with an extinction pattern, suggesting a compensatory response in drug intake due to reduced heroin reward. In addition, activation of SNr GABA neurons attenuated heroin-primed, but not cue-induced, reinstatement of drug-seeking behavior, whereas inhibition of SNr GABA neurons produced optical intracranial self-stimulation and place preference. Together, these findings suggest that MORs on GABA neurons in the SNr play more important roles in opioid reward and relapse than MORs on VTA GABA neurons.SIGNIFICANCE STATEMENTOpioid reward has long been believed to be mediated by inhibition of GABA interneurons in the VTA that subsequently leads to disinhibition of DA neurons. In this study, we found that more μ opioid receptors (MORs) are expressed in GABA neurons in the neighboring SNr than in the VTA, and that pharmacological blockade of MORs in the SNr is more effective in reducing heroin reward than blockade of MORs in the VTA. Furthermore, optogenetic activation of VTA GABA neurons inhibited cocaine, but not heroin, self-administration, whereas activation of SNr GABA neurons inhibited heroin reward and relapse. These findings suggest that opioid reward is more likely mediated by stimulation of MORs in GABA afferents from other brain regions than in VTA GABA neurons.
MeCP2 Levels Regulate the 3D Structure of Heterochromatic Foci in Mouse Neurons
Authors: Ito-Ishida Aya , Baker Steven A. , Sillitoe Roy V. , Sun Yaling , Zhou Jian , Ono Yukiteru , Iwakiri Junichi , Yuzaki Michisuke , Zoghbi Huda Y. 
Published: October 2020

Methyl-CpG binding protein 2 (MeCP2) is a nuclear protein critical for normal brain function, and both depletion and overexpression of MeCP2 lead to severe neurodevelopmental disease, Rett syndrome (RTT) andMECP2multiplication disorder, respectively. However, the molecular mechanism by which abnormal MeCP2 dosage causes neuronal dysfunction remains unclear. As MeCP2 expression is nearly equivalent to that of core histones and because it binds DNA throughout the genome, one possible function of MeCP2 is to regulate the 3D structure of chromatin. Here, to examine whether and how MeCP2 levels impact chromatin structure, we used high-resolution confocal and electron microscopy and examined heterochromatic foci of neurons in mice. Using models of RTT andMECP2triplication syndrome, we found that the heterochromatin structure was significantly affected by the alteration in MeCP2 levels. Analysis of mice expressing either MeCP2-R270X or MeCP2-G273X, which have nonsense mutations in the upstream and downstream regions of the AT-hook 2 domain, respectively, showed that the magnitude of heterochromatin changes was tightly correlated with the phenotypic severity. Postnatal alteration in MeCP2 levels also induced significant changes in the heterochromatin structure, which underscored importance of correct MeCP2 dosage in mature neurons. Finally, functional analysis of MeCP2-overexpressing mice showed that the behavioral and transcriptomic alterations in these mice correlated significantly with the MeCP2 levels and occurred in parallel with the heterochromatin changes. Taken together, our findings demonstrate the essential role of MeCP2 in regulating the 3D structure of neuronal chromatin, which may serve as a potential mechanism that drives pathogenesis of MeCP2-related disorders.SIGNIFICANCE STATEMENTNeuronal function is critically dependent on methyl-CpG binding protein 2 (MeCP2), a nuclear protein abundantly expressed in neurons. The importance of MeCP2 is underscored by the severe childhood neurologic disorders, Rett syndrome (RTT) andMECP2multiplication disorders, which are caused by depletion and overabundance of MeCP2, respectively. To clarify the molecular function of MeCP2 and to understand the pathogenesis ofMECP2-related disorders, we performed detailed structural analyses of neuronal nuclei by using mouse models and high-resolution microscopy. We show that the level of MeCP2 critically regulates 3D structure of heterochromatic foci, and this is mediated in part by the AT-hook 2 domain of MeCP2. Our results demonstrate that one primary function of MeCP2 is to regulate chromatin structure.
Multivariate Lesion-Behavior Mapping of General Cognitive Ability and Its Psychometric Constituents
Authors: Bowren Mark , Adolphs Ralph , Bruss Joel , Manzel Kenneth , Corbetta Maurizio , Tranel Daniel , Boes Aaron D. 
Published: October 2020

General cognitive ability, or general intelligence (g), is central to cognitive science, yet the processes that constitute it remain unknown, in good part because most prior work has relied on correlational methods. Large-scale behavioral and neuroanatomical data from neurologic patients with focal brain lesions can be leveraged to advance our understanding of the key mechanisms of g, as this approach allows inference on the independence of cognitive processes along with elucidation of their respective neuroanatomical substrates. We analyzed behavioral and neuroanatomical data from 402 humans (212 males; 190 females) with chronic, focal brain lesions. Structural equation models (SEMs) demonstrated a psychometric isomorphism between g and working memory in our sample (which we refer to as g/Gwm), but not between g and other cognitive abilities. Multivariate lesion-behavior mapping analyses indicated that g and working memory localize most critically to a site of converging white matter tracts deep to the left temporo-parietal junction. Tractography analyses demonstrated that the regions in the lesion-behavior map of g/Gwm were primarily associated with the arcuate fasciculus. The anatomic findings were validated in an independent cohort of acute stroke patients (n= 101) using model-based predictions of cognitive deficits generated from the Iowa cohort lesion-behavior maps. The neuroanatomical localization of g/Gwm provided the strongest prediction of observed g in the new cohort (r= 0.42,p< 0.001), supporting the anatomic specificity of our findings. These results provide converging behavioral and anatomic evidence that working memory is a key mechanism contributing to domain-general cognition.SIGNIFICANCE STATEMENTGeneral cognitive ability (g) is thought to play an important role in individual differences in adaptive behavior, yet its core processes remain unknown, in large part because of difficulties in making causal inferences from correlated data. Using data from patients with focal brain damage, we demonstrate that there is a strong psychometric correspondence between g and working memory – the ability to maintain and control mental information, and that the critical neuroanatomical substrates of g and working memory include the arcuate fasciculus. This work provides converging behavioral and neuroanatomical evidence that working memory is a key mechanism contributing to domain-general cognition.
“Wear People’s Faces”
Authors: Smith Jeremy W. 
Published: October 2020

This article discusses fan adaptations of music from The Legend of Zelda: Majora’s Mask (2000), arguing that the creators of these adaptations pick up on semiotic meaning in the game’s original music and maintain this meaning while changing some structural features of the music to place the original pieces into new stylistic and generic contexts. The musical meaning in the works is sometimes subtle, but it can be determined through a combination of semiotic and hermeneutic methods. In both the original soundtrack and the adaptations, the meaning of the music is also tied to the in-game narrative context associated with it, which is often sad or anxious in emotional character. Remaking the music into adaptations helps fans of the game contextualize the meaning in new ways and understand how it relates to their own social and emotional circumstances. The adaptations help fans with “world building” and “organizing social life.”1
After an overview of Majora’s Mask that situates it within Nintendo’s corpus, the Zelda series and its fandom, and composer Koji Kondo’s oeuvre, the article discusses and analyzes multiple adaptations of three specific pieces from the game: “Clock Town,” “Song of Healing,” and “Stone Tower Temple.” The adaptations discussed include amateur remixes and mashups, professional studio productions, covers in different genres, and a full-length opera by composer M. Bulteau. When making this new content, creators “wear people’s faces” (like the protagonist Link does with masks in the game) by taking on the emotional meaning of the works and putting it into new contexts that imitate, but do not replicate, the original music.
SH-synthesis of alumino-manganese alloy based on the Al-MnO3 system
Authors: Boronenko Marina P. , Milyukova Irina V. , Cheklov Sergei A. 
Published: October 2020

The work is devoted to the use of self-propagating high-temperature synthesis for producing aluminum-manganese alloy in the MnО3 AI system. The experiment was carried out in a specially designed SHS reactor at various pressures with and without preliminary heating. The synthesized samples were studied by X-ray diffraction, metallographic, and X-ray spectral analysis; compression tests were performed. X-ray powder diffraction data showed the presence of intermetallic compounds of different stoichiometries: Al8Mn5, Al11Mn4, and Al6Mn. It was established that the main phase is the Al8Mn5 intermetallic compound. The structure of the sample has a needle structure. The alloy has a high hardness of structural components: from 624 HV to 934 HV.
High compressive strength and high hardness are evidence that the synthesized alloy is a direct competitor to hard alloys.
Early Orientation of Preclinical Mbbs Students in Clinicoradiological Skills
Authors: Duara Dr.Bijit Kumar , Banani Dr , Baishya Dr Rupak 
Published: October 2020

As per GMER 2019, the goal of medical education is to creat IMG , who is clinician of first contact ,leader ,communicator,Life long learner and Professional .Basic science (Anatomy ) is the corner stone of Radiodiagnostic principles .Early Clinico Diagnostic (Radiological) Exposure (ECDE ) ensures well integrated knowledge of applied Anatomy. Aims of the study were to assess influence of ECDE on students ,perception of students and faculties about utility of ECDE and to improve self directed learning in students. After obtaining administrative approval ,participating Faculties were selected and sensitized. 156 willing first year students were selected and divided in two groups by Random Selection .Group A (ECDE GROUP) and Group B (NON ECDE GROUP ). ECDE Group was exposed with Radiological films and videos of Cardiopulmonary system in addition to TLM methods in Anatomy, which was not done with Non ECDE Group. Assessment was made with MCQ and OSPE. After completion of assessment, feedback of faculties and students were taken for assessing perception on ECDE . In MCQ test 79% (n=62) of ECDE Group scored higher marks in comparison to Non ECDE Group .P value <0.001. In OSPE Test 89% (n=70) of ECDE Group scored higher marks compared to Non ECDE Group .p value <0.0001.
ECDE has significant impact on knowledge and skill acquisition of students.90% students expressed positively that ECDE increases their interest in basic Science (Anatomy) .86% students and 100% faculties expressed positively that ECDE should be one of the teaching methods in Anatomy. ECDE motivated students to do SDL.
Research on the Application Value of Comfort Nursing Intervention in the Nursing of Senile Chronic Heart Failure
Authors: Yan Fengjiao , Wang Chao , Pan Peizhen , Wang Shuang , Lv Lishan 
Published: October 2020

<p><strong>Objective</strong><strong>:</strong> To analyze the application value of comfort nursing intervention in senile chronic heart failure nursing. <strong>Methods:</strong> The 120 heart failures discharged from our hospital in 2018 and 2019 were selected. The changes in nursing satisfaction, specialty nursing quality indicators and the incidence of pressure ulcers in hospitalized patients were compared and analyzed between the two groups. <strong>Results:</strong> The average satisfaction degree of the two groups was 97.48% and 97.22% respectively, and the difference between the groups was statistically significant (P&lt;0.05). The correct rates of acute left heart failure in the two groups were 99.56% and 98.13%, and the difference between the groups was statistically significant (P&lt;0.05), and two groups of patients with cardiac Ⅲ class above intake control accuracy was 99.95% and 99.99%, and the difference between groups was statistically significant (P&gt;0.05), and the incidence of pressure ulcer was 0.18‰ and 0, and there was no significant difference between the two groups. <strong>Conclusion:</strong> Comfort nursing intervention has achieved good nursing satisfaction and clinical effect in elderly patients with heart failure.</p>
Chichen-Itzá y Tula
Authors: Kubler George A. 
Published: October 2020

El gran parecido que existe entre algunos de los edificios de Chichen-Itzá y y los de Tula en el altiplano de México, fue notado por primera vez por D. Charnay hacia 1800 depués de visitar ambos sitios. Las observaciones de Charnay se confirmaron en 1940 cuando el gobierno mexicano inició excavaciones en Tula.
Un modelo de tecnología mesoamericana de la obsidiana basada en derechos de un taller preclasico en El Salvador
Authors: Sheets Payson D. 
Published: October 2020

Se propone un modelo de procedimientos y productos líticos para tratar de explicar artefactos y desechos de obsidiana que se encuentran en horizontes sedentarios agrícolas en casi coda Mesoamérica. Por método de percusión se crearon nódulos de forma ligeramente hemisférica, partiendo un nódulo ovoide en dos hemisferios o quitándole una lasca plana de un extrema, para crear plataforma.1 El paso siguiente fue el desprendimiento también por percusión, de lascas grandes en la periferia del núcleo para regularizar su contorno e iniciar la formación de aristas que se extienden desde la plataforma hasta el extremo distal (la punta) del núcleo. Después de quitar la cornisa 2 o sobrante de la plataforma, se separaron por percusión navajas grandes; luego, se cambió el método de percusión por el de presión y se obtuvieron navajas prismáticas del núcleo preparado. Muchos núcleos fueron rejuvenecidos (o reavivados) antes de que se agotaran y se les desechara. Tanto las navajas grandes como las prismáticas fueron usadas sin otra modificación o sirvieron de base para manufacturar gran variedad de artefactos. Presento en detalle el material del taller, del cual se derivó el modelo, y también hago la comparación de este con otros materiales de piedra tallada, pertenecientes a otros periodos en El Salvador.
NOTAS SOBRE LOS YACIMIENTOS DE ALBITA Y JADE1TA DE SAN CRISTOBAL ACASAGUASTLAN, GUATEMALA
Authors: Becquelin Pierre , Bose Eric 
Published: October 2020

Hasta el presente los únicos depósitos de jadeíta conocidos en Mesoamérica se ubican al norte de Manzanotal, poblado que se encuentra al este de San Cristóbal Acasaguastlán en el curso medio del valle del río Motagua (Foshag y Leslie 1955, Barbour 1957). Nuevos yacimientos fueron descubiertos por E. Bose durante un periodo de estudios geológicos efectuado en la región, y visitada por los autores en julio de 1965. La mayor parte de estos yacimientos de albita y jadeíta se encuentran al norte de la carretera asfaltada Guatemala-Puerto Barrios entre los ríos El Cintillo y Uyus (ver figura 1) como inclusiones tectónicas de dimensiones variables en afloramientos de serpentinas foliadas. La vegetación es característica de climas semiáridos y esta formada principalmente por arbustos como el brazil (Haematoxylon brasiletto Karst), quebracho (Quebracha Lorentzii), guayacan (Gua.yacum sanctum L.), guachipilin (Diphysa floribtmda Peyritsh), chichicaste (Urtica dioica), manzanotal (Olmediella Betschleriana), etcétera, siendo el maíz el único cultivo en esta área, sembrado en milpas pequeñas con un rendimiento muy reducido debido a la pobreza de los suelos desarrollados en serpentinas. El área consiste en una serie de colinas bajas que gradualmente se levantan hacia el norte hasta una línea de cresta situada aproximadamente a dos y tres mil metros de la carretera arriba mencionada; cerca de esta cresta existe un campo de maíz o milpa, en el cual se han podido observar excavaciones consistentes en pozos de poca profundidad (0.25 a 2 m) y de diámetro variable (promedio 2 m) rodeados en la superficie por escombros con fragmentos angulares de albita y jadeíta.
A Cost-Effectiveness Analysis of Smoking-Cessation Interventions Prior to Posterolateral Lumbar Fusion
Authors: Zhuang Thompson , Ku Seul , Shapiro Lauren M. , Hu Serena S. , Cabell Akaila , Kamal Robin N. 
Published: October 2020

Background:
Smoking cessation represents an opportunity to reduce both short and long-term effects of smoking on complications after lumbar fusion and smoking-related morbidity and mortality. However, the cost-effectiveness of smoking-cessation interventions prior to lumbar fusion is not fully known.

Methods:
We created a decision-analytic Markov model to evaluate the cost-effectiveness of 5 smoking-cessation strategies (behavioral counseling, nicotine replacement therapy [NRT], bupropion or varenicline monotherapy, and a combined intervention) prior to single-level, instrumented lumbar posterolateral fusion (PLF) from the health payer perspective. Probabilities, costs, and utilities were obtained from published sources. We calculated the costs and quality-adjusted life years (QALYs) associated with each strategy over multiple time horizons and accounted for uncertainty with probabilistic sensitivity analyses (PSAs) consisting of 10,000 second-order Monte Carlo simulations.

Results:
Every smoking-cessation intervention was more effective and less costly than usual care at the lifetime horizon. In the short term, behavioral counseling, NRT, varenicline monotherapy, and the combined intervention were also cost-saving, while bupropion monotherapy was more effective but more costly than usual care. The mean lifetime cost savings for behavioral counseling, NRT, bupropion monotherapy, varenicline monotherapy, and the combined intervention were $3,291 (standard deviation [SD], $868), $2,571 (SD, $479), $2,851 (SD, $830), $6,767 (SD, $1,604), and $34,923 (SD, $4,248), respectively. The minimum efficacy threshold (relative risk for smoking cessation) for lifetime cost savings varied from 1.01 (behavioral counseling) to 1.15 (varenicline monotherapy). A PSA revealed that the combined smoking-cessation intervention was always more effective and less costly than usual care.

Conclusions:
Even brief smoking-cessation interventions yield large short-term and long-term cost savings. Smoking-cessation interventions prior to PLF can both reduce costs and improve patient outcomes as health payers/systems shift toward value-based reimbursement (e.g., bundled payments) or population health models.

Level of Evidence:
Economic Level II. See Instructions for Authors for a complete description of levels of evidence.