bluuebunny/crossref_metadata_2025_split huggingface dataset:
REST Protects Dopaminergic Neurons from Mitochondrial and α-Synuclein Oligomer Pathology in an Alpha Synuclein Overexpressing BAC-Transgenic Mouse Model
Authors: Ryan Brent J. , Bengoa-Vergniory Nora , Williamson Matthew , Kirkiz Ecem , Roberts Rosalind , Corda Gabriele , Sloan Maximilian , Saqlain Saba , Cherubini Marta , Poppinga Josse , Bogetofte Helle , Cioroch Milena , Hester Svenja , Wade-Martins Richard 
Published: February 2021

Alpha-synuclein pathology is associated with dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's patients. Working across human and mouse models, we investigated mechanisms by which the accumulation of soluble α-synuclein oligomers leads to neurodegeneration. Biochemical analysis of the midbrain of α-synuclein overexpressing BAC-transgenic male and female mice revealed age- and region-dependent mitochondrial dysfunction and accumulation of damaged proteins downstream of the RE1 Silencing Transcription Factor (REST). Vulnerable SN dopaminergic neurons displayed low REST levels compared with neighboring protected SN GABAergic neurons, which correlated with the accumulation of α-synuclein oligomers and disrupted mitochondrial morphology. Consistent with a protective role, REST levels were reduced in patient induced pluripotent stem cell-derived dopaminergic neurons carrying theSNCA-Triplicationmutation, which accumulated α-synuclein oligomers and mitochondrial damage, and displayed REST target gene dysregulation. Furthermore, CRISPR-mediated REST KO induced mitochondrial dysfunction and impaired mitophagyin vitro. Conversely, REST overexpression attenuated mitochondrial toxicity and mitochondrial morphology disruption through the transcription factor PGC-1α. Finally, decreased α-synuclein oligomer accumulation and mitochondrial dysfunction in mice correlated with nuclear REST and PGC-1α in protected SN GABAergic neurons compared with vulnerable dopaminergic neurons. Our findings show that increased levels of α-synuclein oligomers cause dopaminergic neuronal-specific dysfunction through mitochondrial toxicity, which can be attenuated by REST in an early model of Parkinsonian pathology. These findings highlight REST as a mediator of dopaminergic vulnerability in PD.SIGNIFICANCE STATEMENTUnderstanding early Parkinsonian pathophysiology through studies of advanced preclinical models is fundamental to the translation of disease-modifying therapies. Here we show disease-relevant levels of α-synuclein expression in mice leads to accumulation of α-synuclein oligomers in the absence of overt aggregation, and mitochondrial dysfunction in dopaminergic neurons lacking the RE1 Silencing Transcription Factor. Our findings identify the mechanism of action of RE1 Silencing Transcription Factor and PGC-1α as mediators of dopaminergic vulnerability in α-synuclein BAC-transgenic mice and induced pluripotent stem cell-derived dopaminergic cultures, highlighting their potential as therapeutic targets.
Expert Tool Users Show Increased Differentiation between Visual Representations of Hands and Tools
Authors: Schone Hunter R. , Maimon-Mor Roni O. , Baker Chris I. , Makin Tamar R. 
Published: February 2021

The idea that when we use a tool we incorporate it into the neural representation of our body (embodiment) has been a major inspiration for philosophy, science, and engineering. While theoretically appealing, there is little direct evidence for tool embodiment at the neural level. Using functional magnetic resonance imaging (fMRI) in male and female human subjects, we investigated whether expert tool users (London litter pickers:n= 7) represent their expert tool more like a hand (neural embodiment) or less like a hand (neural differentiation), as compared with a group of tool novices (n= 12). During fMRI scans, participants viewed first-person videos depicting grasps performed by either a hand, litter picker, or a non-expert grasping tool. Using representational similarity analysis (RSA), differences in the representational structure of hands and tools were measured within occipitotemporal cortex (OTC). Contrary to the neural embodiment theory, we find that the experts group represent their own tool less like a hand (not more) relative to novices. Using a case-study approach, we further replicated this effect, independently, in five of the seven individual expert litter pickers, as compared with the novices. An exploratory analysis in left parietal cortex, a region implicated in visuomotor representations of hands and tools, also indicated that experts do not visually represent their tool more similar to hands, compared with novices. Together, our findings suggest that extensive tool use leads to an increased neural differentiation between visual representations of hands and tools. This evidence provides an important alternative framework to the prominent tool embodiment theory.SIGNIFICANCE STATEMENTIt is commonly thought that tool use leads to the assimilation of the tool into the neural representation of the body, a process referred to as embodiment. Here, we demonstrate that expert tool users (London litter pickers) neurally represent their own tool less like a hand (not more), compared with novices. Our findings advance our current understanding for how experience shapes functional organization in high-order visual cortex. Further, this evidence provides an alternative framework to the prominent tool embodiment theory, suggesting instead that experience with tools leads to more distinct, separable hand and tool representations.
Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context
Authors: Cho Jounhong Ryan , Chen Xinhong , Kahan Anat , Robinson J. Elliott , Wagenaar Daniel A. , Gradinaru Viviana 
Published: February 2021

The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRNDAneurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues. The DRNDAresponse to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRNDAactivity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRNDAneurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that head-fixation itself abolished the neural response to aversive cues, indicating its modulation by behavioral context. Overall, these results suggest that DRNDAneurons encode motivational salience, dependent on internal and external factors.SIGNIFICANCE STATEMENTDopamine (DA) contributes to motivational control, composed of at least two functional cell types, one signaling for motivational value and another for motivational salience. Here, we demonstrate that DA neurons in the dorsal raphe nucleus (DRN) encode the motivational salience in associative learning tasks. Neural responses were dynamic and modulated by the animal's internal state. The majority of single-cells developed responses to reward or paired cues, but not to shock-predicting cues. Additional experiments with freely-moving and head-fixed mice showed that head-fixation abolished the development of cue responses during fear learning. This work provides further characterization on the functional roles of overlooked DRNDApopulations and an example that neural responses can be altered by head-fixation, which is commonly used in neuroscience.
MAPK signaling regulates c‐MYC for melanoma cell adaptation to asparagine restriction
Authors: Pathria Gaurav , Verma Sachin , Yin Jun , Scott David A , Ronai Ze’ev A 
Published: February 2021

AbstractAmino acid restriction is among promising potential cancer treatment strategies. However, cancer cells employ a multitude of mechanisms to mount resistance to amino acid restriction, which impede the latter’s clinical development. Here we show that MAPK signaling activation in asparagine‐restricted melanoma cells impairs GSK3‐β‐mediated c‐MYC degradation. In turn, elevated c‐MYC supports ATF4 translational induction by enhancing the expression of the amino acid transporter SLC7A5, increasing the uptake of essential amino acids, and the subsequent maintenance of mTORC1 activity in asparagine‐restricted melanoma cells. Blocking the MAPK‐c‐MYC‐SLC7A5 signaling axis cooperates with asparagine restriction to effectively suppress melanoma cell proliferation. This work reveals a previously unknown axis of cancer cell adaptation to asparagine restriction and informs mechanisms that may be targeted for enhanced therapeutic efficacy of asparagine limiting strategies.
Application of the Problem Based-Fishbone Model on Reproductive System Material in SMA N 1 Dempet
Authors: Subekti Arum , WH Nugrahaningsih , . Lisdiana 
Published: February 2021

Students achievement that are less than optimal indicate the students thinking skills are not maximal. To improve students thinking skills can be done in several ways among others, students further deepen the concept of material, to provide further explanation and to provide alternative solutions to problems, so that students in the future are expected to solve problems in the environment. One learning model that can improve students thinking skills is problem based learning. Problem-based learning models can encourage students ability to conduct investigations and be able to provide alternative solutions to problems. This study aims to analyze the model problem based -fishbone on reproductive system material influencing learning outcomes and the health care attitude of high school students. This study used a quasi experimental design with pretest-posttest control group design. The sample of this study was students of class XI MIPA 2 and XI MIPA 6 in SMA N 1 Dempet which were determined using purposive sampling technique. The independent variable is a model problem based-fishbone on reproductive system material. Dependent variables are student learning outcomes and student health care attitudes. How to retrieve data using test and observation sheet questions. The results of data analysis showed that student learning outcomes could increase after learning activities were completed with completeness for both classes in a row 79.54% and 90.48%, and students had good health care attitudes. Based on the results of the study it can be concluded that the application of the model problem based- fishbone influences learning outcomes and health care attitudes in high school students.
HUBUNGAN VARIASI MENGAJAR GURU DAN MOTIVASI BELAJAR SISWA DENGAN HASIL BELAJAR MATEMATIKA
Authors: Setiyaningsih Suhelin 
Published: February 2021

Tujuan penelitian ini adalah menguji hubungan variasi mengajar guru dan motivasi belajar siswa dengan hasil belajar matematika siswa kelas IV SD Gugus Kenanga Kecamatan Pejagoan Kabupaten Kebumen. Penelitian ini menggunakan metode kuantitatif dengan jenis penelitian korelasi. Populasi dalam penelitian ini yaitu 112 siswa. Pengambilan sampel menggunakan metode Nonprobability Sampling, sedangkan cara pengambilan sampel yang digunakan adalah sampling jenuh sejumlah populasi. Teknik pengumpulan data menggunakan angket, dokumentasi, observasi, dan wawancara. Hasil penelitian menunjukkan adanya hubungan positif dan siginifikan antara variasi mengajar guru dan motivasi belajar siswa dengan hasil belajar matematika dengan rhitung= 0,8023 (kategori sangat kuat) dan Fhitung = 98,5023 serta berkontribusi sebesar 64,4%. Dari hasil penelitian dapat disimpulkan bahwa ada hubungan yang positif dan signifikan antara variasi mengajar guru dan motivasi belajar siswa dengan hasil belajar Matematika siswa kelas IV SD Gugus Kenanga Kecamatan Pejagoan Kabupaten Kebumen.

The purpose of this study was to examine the correlation between teacher teaching variations and student learning motivation with mathematics learning outcomes the 4th grade students in Cluster Kenanga Elementary School Pejagoan Kebumen. This research used quantitative method with the type of correlation research. The population in this study were 112 students. Sampling used Nonprobability Sampling method, while the sampling method used was saturated sampling. Data collection technique were questionnaires, documentation, observation, and interview. The results showed a positive and significant relationship between teacher teaching variation and student learning motivation with mathematics learning outcomes with rcount = 0.8023 (very strong category) and Fcount = 98.5023 and contributed 64.4%. From the results of the study it can be concluded that there was a positive and significant correlation between teacher teaching variations and student learning motivation and mathematics learning outcomes the 4th grade students in Cluster Kenanga Elementary School Pejagoan Kebumen.
Formando professores de Português como Língua Adicional (PLA) para a superdiversidade
Authors: Bessa Mariana de Camargo , Weiss Denise Barros 
Published: February 2021

Este artigo tem como objetivo refletir sobre as lacunas que precisam ser equacionadas no que tange à institucionalização na área de Português como Língua Adicional (PLA) e sobre ações glotopolíticas nesse campo. Pretendemos discutir sobre alguns efeitos da ausência de documentos que orientam o ensino em salas de aula que refletem a realidade superdiversa em que estamos inseridos. Analisamos como o Exame Celpe-Bras - Certificado de Proficiência em Língua Portuguesa para Estrangeiros - tem norteado políticas de ensino de PLA e, por fim, observamos os impactos dessa influência na formação de professores de PLA. Mobilizamos, para este estudo, os conceitos de superdiversidade; de saberes locais e saberes globais; de políticas linguísticas e ações glotopolíticas. Com base nesses conceitos, mostramos alguns dos saberes necessárias para o professor dar conta desses desafios que se impõem no trabalho hoje.
Palavras-chave: Política linguística. Superdiversidade. Formação de professores de PLA.
Que nostalgia!
Authors: Bordulis da Silva Suaidy Viviane , Pilatti Telles Luciana 
Published: February 2021

No presente estudo, refletimos sobre o desenvolvimento de atividades de consciência fonológica em uma tarefa sobre produção de desenhos animados brasileiros. Mobilizamos as noções de tarefa como plano de trabalho (ELLIS et al. 2020). Nas atividades propostas, constituintes da fase de foco na língua (WILLIS, 1996), apresentamos e discutimos oportunidades de compreensão, reflexão e manipulação da variação da lateral pós-vocálica (COLLISCHONN e QUEDNAU, 2009; HAHN-NONNENMACHER, 2019; CALLOU, 2009; LEITE, CALLOU e MORAES, 2007; BATTISTI e MORAS, 2016; MORAS, 2017) pelos participantes, a partir de nomes de personagens de cinco obras de animação brasileiras. No uso das atividades com três grupos de estudantes na Universidade Federal do Rio Grande, percebemos que os discentes (a) reconheceram as diferentes pronúncias da lateral em português brasileiro, conforme a sua posição na sílaba, (b) refletiram sobre a produção da lateral em coda em variedades do português e em variedades do espanhol e (c) experimentaram a aplicação da regra variável.
Optimisation of modification parameters for amaranth starch for the development of pudding and study of the quality traits of developed pudding
Authors: Gupta A.K. , Jha A.K. , Singhal S. 
Published: February 2021

AbstractAmaranth is considered to be a part of “superfood”, however, due to multiple restricting properties, its functionality in the food industry is still not explored to its fullest. The present study investigated the effect of almond gum concentration (3–10 g), temperature (50–90 °C), and quantity of water (30–70 mL) on the functional properties of amaranth starch. A central composite rotatable design (CCRD) showed that the 6.9 g of almond gum, 64.43 mL of water, and temperature maintained at 90 °C, were the optimised conditions to attain 16.77 g g−1of swelling power, 12.97% of solubility index, and 20.13% freeze-thaw stability. Moreover, the modified amaranth starch was further employed to develop pudding as a value-added product. The findings concluded that the developed pudding using modified amaranth starch exhibited enhanced sensorial attributes due to an increase in cohesiveness, chewiness, and resilience of starch gel.
Tooth contact analysis of the effect of the addendum modification coefficient of helical gears having modified teeth
Authors: Bodzás Sándor 
Published: February 2021

AbstractThe helical gear pair is widely used in different mechanical constructions such as vehicle industry and working machine industry. The main property of them is the skew tooth direction with which better tooth connections could be available than in case of straight tooth direction. The analysis of the effect of the addendum modification coefficient for the normal stress and the normal deformation is the aim of the research which could be determined by finite element analysis. Five helical gear types are designed and modelled. The difference among them is only the different addendum modification coefficients. All of the other initial parameters are constant. After the result we determine the conclusions based on the diagram's results which are received by the mechanical parameters and the addendum modification coefficients.
Comparison of bus driving cycles elaborated for vehicle dynamic simulation
Authors: Vámosi Attila , Czégé Levente , Kocsis Imre 
Published: February 2021

AbstractDue to the technological progress, new approaches such as model-based design are spreading in the development process in the automotive industry to meet the increased requirements related to lower fuel consumption and reduced emission. This work is part of a research project which focuses on dynamic modeling of vehicles aimed at analyzing and optimizing the emission and fuel consumption. To model the driver behavior, the simulation control algorithm requires a predetermined speed-time curve as an input. The completeness of this driving cycle is a crucial factor in the simulation, and as far as the legislative driving cycles are not accurate enough, it is indispensable to develop our own one representing our narrower area and driving conditions. This article considers two common drive cycle design methods, comparing the micro-trip-based approach and the Markov-chain approach. The new driving cycle has been developed applying the Markov-chain approach and compared to a driving cycle introduced in our recent paper using the micro-trip method. The comparison basis is the Speed-Acceleration Probability Distribution, which sufficiently reflects the dynamic behavior of the vehicle, and the root mean square error, including parameters such as the average speed, average cruising speed, average acceleration, average deceleration, root mean square acceleration, and idle time percentage. The representative Bus Driving Cycle for Debrecen is prepared to be applied in the vehicle dynamics simulation for evaluating and improving the fuel economy of vehicles, selecting the proper power source for various applications and the optimization of the powertrain and the energy consumption in researches to be continued.
Problematic Internet Use in early adolescence: The role of attachment and negative beliefs about worry
Authors: Marci Tatiana , Marino Claudia , Sacchi Chiara , Lan Xiaoyu , Spada Marcantonio M. 
Published: February 2021

AbstractBackground and aimsProblematic Internet Use (PIU) might be a potential mental health problem. Few studies have investigated the relative contribution of individual and family factors in the development of PIU in early adolescence. The aim of the current study was to model the relationship between attachment styles, negative beliefs about worry, and PIU in early adolescence.MethodsFive hundred and thirty-eight Italian early adolescents (51% females, M age = 12.7 years, SD = 0.87) were included in this study. The pattern of relationships specified by the theoretical model was examined through path analysis.ResultsResults showed that avoidance (mother) and anxiety (father) were directly associated with PIU. Anxiety (mother) and avoidance (father) were indirectly associated with PIU via negative beliefs about worry.Discussion and conclusionsOverall, our findings show that attachment toward mother and father are differently linked to PIU and that negative beliefs about worry may play a mediating role in the association between attachment and PIU. Findings are discussed within clinical and preventive implications.
Impact of determinants on nutritional status among children up to five years at tertiary care hospital, HIMS, Sitapur, Uttar Pradesh
Authors: Pachori Ravi , Sillapasuwan Jiratithigan 
Published: February 2021

Background: Malnutrition in children occurs as a complex interplay among various factors like maternal health, dietary practices, hand washing and other hygiene practices, low birth weight, episode of diarrhoea and acute respiratory infection within the last 6 months are often associated with undernutrition in most developing nations including India. Objective of the study were to assess the determinants of maternal and child health, hygienic practice, health services for underweight and their association among apparently healthy children. Methods: The present study was hospital based descriptive cross-sectional study conducted from June 2019 to December 2019. The sample size calculated was 410, and accounting for 10% nonresponsive, the sample size calculated was 451. The data obtained were compiled and entered in MS-excel 2010 and analysed by using institutional SPSS (22.0). Results: Mother’s age at marriage <18 years belong to 68 (15.1%) children significantly low proportion as compared to marriage >18 years 383 (84.9%) including underweight 41 (22.5%) and mother’s age at child birth <18 years belong to 46 (10.2%) children significantly very low proportion in comparison to child birth >18 years including underweight 30 (16.6%). Birth weight <2.5 kg belongs to significantly 136 (30.1%) children including underweight 72 (39.8%) and significantly birth order >2 belong to 135 (29.9%) children including underweight 39 (21.6%). Exclusive breast feeding belongs to 149 (33.0%) children including underweight 62 (34.2%)Conclusions: Health education and its reinforcement especially in the area of maternal & child health care services is required.
Transformational Leadership, Knowledge Management, Work Motivation, and Employee Performance among Construction Employees in Jakarta
Authors: Baskoro Bimmo Dwi , Sudarmadji Sudarmadji , Suherman Suherman , Yani Ahmad , Simanjuntak Robby 
Published: February 2021

This study aims to analyze the influence of transformational leadership (TL) and knowledge management (KM) on employee performance (EP) through work motivation (WM) at construction companies in Jakarta, Indonesia. The data was collected from construction firms that have grade high qualification in Jakarta, Indonesia. A sample of 138 companies representatives was drawn from 138 construction firms in Jakarta. The structural equation modelling – partial least squares (SEM-PLS) was used to test the proposed hypothesizes. TL has a significant effect on EP through WM. KM has a significant effect on EP through WM. The relevance of the research stems from the context of a major city in Jakarta, Indonesia. Furthermore, this research is one of the initial attempts to investigate EP by considering TL and KM and its applicability to Jakarta construction firms.