bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of mTOR during a postnatal critical sensitive window rescues deficits in GABAergic PV cell connectivity and social behavior caused by loss ofTSC1
Authors: Choudhury Mayukh , Amegandjin Clara A. , Jadhav Vidya , Carriço Josianne Nunes , Quintal Ariane , Berryer Martin , Snapyan Marina , Chattopadhyaya Bidisha , Saghatelyan Armen , Di Cristo Graziella 
Published: March 2020

ABSTRACTMutations in regulators of the Mechanistic Target Of Rapamycin Complex 1 (mTORC1), such asTsc1/2, lead to neurodevelopmental disorders associated with autism, intellectual disabilities and epilepsy. Whereas the effects of mTORC1 signaling dysfunction within diverse cell types are likely critical for the onset of the diverse neurological symptoms associated with mutations in mTORC1 regulators, they are not well understood. In particular, the effects of mTORC1 dys-regulation in specific types of inhibitory interneurons are unclear.Here, we showed thatTsc1haploinsufficiency in parvalbumin (PV)-positive GABAergic interneurons either in cortical organotypic cultures orin vivocaused a premature increase in their perisomatic innervations, followed by a striking loss in adult mice. This effects were accompanied by alterations of AMPK-dependent autophagy in pre-adolescent but not adult mice. PV cell-restrictedTsc1mutant mice showed deficits in social behavior. Treatment with the mTOR inhibitor Rapamycin restricted to the third postnatal week was sufficient to permanently rescue deficits in both PV cell innervation and social behavior in adult conditional haploinsufficient mice. All together, these findings identify a novel role of Tsc1-mTORC1 signaling in the regulation of the developmental time course and maintenance of cortical PV cell connectivity and provide a mechanistic basis for the targeted rescue of autism-related behaviors in disorders associated with deregulated mTORC1 signaling.
A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamicsin vitroandin vivo
Authors: Chien Jasper Che-Yung , Tabet Elie , Pinkham Kelsey , da Hora Cintia Carla , Chang Jason Cheng-Yu , Lin Steven , Badr Christian Elias , Lai Charles Pin-Kuang 
Published: March 2020

ABSTRACTTracking DNA double strand break (DSB) repair is paramount for the understanding and therapeutic development of various diseases including cancers. Herein, we describe a multiplexed bioluminescent repair reporter (BLRR) for non-invasive monitoring of DSB repair pathways in living cells and animals. The BLRR approach employs secretedGaussiaandVargulaluciferases to simultaneously detect homology-directed repair (HDR) and non-homologous end joining (NHEJ), respectively. BLRR data are consistent with next-generation sequencing results for reporting HDR (R2= 0.9722) and NHEJ (R2= 0.919) events. Moreover, BLRR analysis allows longitudinal tracking of HDR and NHEJ activities in cells, and enables detection of DSB repairs in xenografted tumoursin vivo.Using the BLRR system, we observed a significant difference in the efficiency of CRISPR/Cas9-mediated editing with guide RNAs only 1-10 bp apart. Moreover, BLRR analysis detected altered dynamics for DSB repair induced by small-molecule modulators. Finally, we discovered HDR-suppressing functions of anticancer cardiac glycosides in human glioblastomas and glioma cancer stem-like cellsviainhibition of DNA repair protein RAD51 homolog 1 (RAD51). The BLRR method provides a highly sensitive platform to simultaneously and longitudinally track HDR and NHEJ dynamics that is sufficiently versatile for elucidating the physiology and therapeutic development of DSB repair.
Occipital Alpha-TMS causally modulates Temporal Order Judgements: Evidence for discrete temporal windows in vision
Authors: Chota Samson , Marque Phillipe , VanRullen Rufin 
Published: March 2020

AbstractRecent advances in neuroscience have challenged the view of conscious visual perception as a continuous process. Behavioral performance, reaction times and some visual illusions all undergo periodic fluctuations that can be traced back to oscillatory activity in the brain. These findings have given rise to the idea of a discrete sampling mechanism in the visual system. In this study we seek to investigate the causal relationship between occipital alpha oscillations and Temporal Order Judgements using neural entrainment via rhythmic TMS. We find that certain phases of the entrained oscillation facilitate temporal order perception of two visual stimuli, whereas others hinder it. Our findings support the idea that the visual system periodically compresses information into discrete packages within which temporal order information is lost.Significance StatementCorrelational evidence for a relationship between brain states and perception is abundant. However, in order to truly understand the causal relationship between the two, we need to be able to manipulate one and observe changes in the other. Neural entrainment via TMS serves as a valuable tool to interfere with cortical rhythms and observe changes in perception. Here, using rhythmic TMS-pulses at 10 Hz, we investigate the effect of the phase of entrained oscillations on performance in a temporal order judgement (TOJ) task. We observe that the causally entrained oscillation indeed modulates time perception rhythmically. On top of previous work on discrete perception we were able to 1. causally influence brain rhythms in a far more direct fashion using TMS, and 2. show that previous work on discrete perception cannot simply be explained by rhythmic fluctuations in visibility. In conclusion our findings support the long discussed idea that the temporal organization of visual processing is discrete rather than continuous, and is causally modulated by cortical rhythms. To our knowledge, this is the first study providing causal evidence via TMS for an endogenous periodic modulation of time perception.
Mapping the forest disturbance regimes of Europe
Authors: Senf Cornelius , Seidl Rupert 
Published: March 2020

AbstractForest disturbances shape ecosystem composition and structure, and changes in disturbance regimes can have strong consequences for forest ecosystem services. Yet we currently lack consistent quantitative data on Europe’s forest disturbance regimes and their changes over time. Here we used satellite data to map three decades (1986-2016) of forest disturbances across continental Europe, covering 35 countries and a forest area of 210 million ha at a spatial grain of 30 m, and analyzed the patterns and trends in disturbance size, frequency and severity. Between 1986 and 2016, 17% of Europe’s forest area was disturbed by anthropogenic and/or natural causes. The 25 million individual disturbance patches had a mean patch size of 1.09 ha (range between 1stand 99thpercentile 0.18 – 10.10 ha). On average 0.52 (0.02 – 3.01) disturbances occurred per km2every year, removing 77% (22 – 100%) of the canopy. While trends in disturbance size were highly variable, disturbance frequency increased and disturbance severity decreased since 1986. Changes in disturbance rates observed for Europe’s forests are thus primarily driven by changes in disturbance frequency (i.e., more disturbances), and only to a lesser extent by increasing disturbance size. We here present the first continental-scale characterization of Europe’s forest disturbance regimes and their changes over time, providing spatially explicit information that is critical for understanding the ongoing changes in forest ecosystems across Europe.
Biochemical profile and bioactive potential of wild folk medicinal plants of Zygophyllaceae from Balochistan, Pakistan
Authors: Ahmed Alia , Hameed Amjad , Saeed Shazia 
Published: March 2020

AbstractRecent focus is on analysis of biological activities of extracts from plant species. Zygophyllaceae is exceedingly important angiosperm family with many taxa being used in folk medicines widely dispersed in arid and semi-arid zones of Balochistan, Pakistan. Only a small proportion of them have been scientifically analyzed and many species are nearly facing extinction. Therefore present investigation explores the biochemical and bioactive potential of fourteen folk medicinal plants usually used for treatments of different ailments. Fresh aerial parts of nine taxa and two fruit samples were collected from plants growing in arid and semi-arid zones of Balochistan and analyzed for enzymatic, non-enzymatic and other biochemical activities. Higher phytochemical activities were detected in the aerial parts. Superoxide dismutase was detected maximum inFagonia indica, (184.7±5.17 units/g), ascorbate peroxidase inTribulus longipetalussubsp.longipetalus(947.5±12.5 Units/g), catalase and peroxidase was higher inPeganum harmala(555.0±5.0 and 2597.8±0.4 units/g respectively). Maximum esterase and alpha amylase activity was found inZygophyllum fabago(14.3±0.44 and 140±18.8 mg/g respectively). Flavonoid content was high inT. longipetalussubsp.longipetalus(666.1±49 μg/ml). The highest total phenolic content and tannin was revealed inF. olivieri(72125±425 and 37050±1900 μM/g. respectively). Highest value of ascorbic acid was depicted inF. bruguierivar.rechingeri(448±1.5 μg/g). Total soluble Proteins and reducing sugars were detected higher inP. harmala(372.3±54 and 5.9±0.1 mg/g respectively). Maximum total antioxidant capacity (TAC) was depicted in Z. simplex(16.9±0.01 μM/g). Pigment analysis exhibited the high value of lycopene and total carotenoids inT. terrestris(7.44±0.2 and 35.5±0.0 mg/g respectively). Chlorophyll a, b and total chlorophyll content was found maximum inT. longipetalussubsp.pterophorus(549.1±9.9, 154.3±10 and 703.4±20.2 ug/g respectively). All taxa exhibited anti-inflammatory activity as well as anti-diabetic inhibitory potential. Seed extracts ofZygophyllum eurypterum(96%) exhibited highest inhibitory potential, along with twelve other taxa of Zygophyllaceae indicated (96-76%) activity when compared with the standard drug diclofenac sodium (79%). Seeds ofT. longipetalussubsp.longipetalus(85%) exhibited the highest anti-diabetic activity; other eleven taxa also exhibited inhibitory activity of α-amylase ranging from (85-69%) compared with Metformin (67%) standard drug. Phytochemical screening revealed that selected taxa proved to be the potential source of natural antioxidants and could further be explored for in-vivo studies and utilized in pharmaceutical industries as potent therapeutic agents validating their ethno-pharmacological uses.
In silicoanalysis of DNA re-replication across a complete genome reveals cell-to-cell heterogeneity and genome plasticity
Authors: Rapsomaniki Maria Anna , Maxouri Stella , Garrastacho Manuel Ramirez , Nathanailidou Patroula , Giakoumakis Nickolaos Nikiforos , Taraviras Stavros , Lygeros John , Lygerou Zoi 
Published: March 2020

AbstractDNA replication is a complex and remarkably robust process: despite its inherent uncertainty, manifested through stochastic replication timing at a single-cell level, multiple control mechanisms ensure its accurate and timely completion across a population. Disruptions in these mechanisms lead to DNA re-replication, closely connected to genomic instability and oncogenesis. We present a stochastic hybrid model of DNA re-replication that accurately portrays the interplay between discrete dynamics, continuous dynamics, and uncertainty. Using experimental data on the fission yeast genome, model simulations show how different regions respond to re-replication, and permit insight into the key mechanisms affecting re-replication dynamics. Simulated and experimental population-level profiles exhibit good correlation along the genome, which is robust to model parameters, validating our approach. At a single-cell level, copy numbers of individual loci are affected by intrinsic properties of each locus,in ciseffects from adjoining loci andin transeffects from distant loci.In silicoanalysis and single-cell imaging reveal that cell-to-cell heterogeneity is inherent in re-replication and can lead to a plethora of genotypic variations. Our thoroughin silicoanalysis of DNA re-replication across a complete genome reveals that heterogeneity at the single cell level and robustness at the population level are emerging and co-existing principles of DNA re-replication. Our results indicate that re-replication can promote genome plasticity by generating many diverse genotypes within a population, potentially offering an evolutionary advantage in cells with aberrations in replication control mechanisms.
Analysis of antecedent factors in academic achievement and student retention
Authors: Setiawan Rony , Aprillia Ariesya , Magdalena Nonie 
Published: March 2020

PurposeStudent achievement and retention are two important components that indicate the quality of a university. This is in line with one of the standards of university accreditations regarding the quality of students and graduates, which are set by BAN-PT, an institution that guarantees the quality of National Education Service delivery at every university in Indonesia. The purpose of this paper is analyzing the internal and external factors that contribute to academic achievement and student retention.Design/methodology/approachThis paper is a causal explanatory-based study, using multiple regression analysis among five independent variables and two dependent variables separately. Several sequential tests are conducted to maintain the proper research results, such as reliability, normality, multi-collinearity and heteroscedasticity.FindingsThis paper provides empirical facts that student motivation has a significant positive impact on the level of student academic achievement, and the quality of lecturers has a significant positive impact both on student academic achievement and retention rates.Research limitations/implicationsThis study is conducted within the context of a university. The generalization in the study is low. Researchers are encouraged to explore further.Practical implicationsThis paper is expected to provide constructive feedback to university management in setting policies that are oriented toward strategic actions to optimize academic achievement and maintain their students.Originality/valueThis paper provides insights of good university governance concerning in higher education management.
Exploring potentials of digital nudging for business processes
Authors: Bammert Sandra , König Ulrich Matthias , Roeglinger Maximilian , Wruck Tabitha 
Published: March 2020

PurposeBusiness process improvement is vital for organizations as business environments are becoming ever more volatile, uncertain, complex and ambiguous. Process improvement methods help organizations sustain competitiveness. Many existing methods, however, do not fit emerging business environments as they entail initiatives with long implementation times, high investments and limited involvement of process participants. What is needed are agile process improvement approaches. The purpose of this paper is to explore the potential of digital nudging – a concept offering tools that lead individuals to better decisions – to improve business processes.Design/methodology/approachUsing process deviance as theoretical lens, an online experiment with 473 participants is conducted. Within the experiment, business processes and digital nudges are implemented to examine whether digital nudging can mitigate the weaknesses of existing process improvement methods.FindingsDigital nudging can influence the decisions of process participants and entail positive process deviance that leads to process improvement opportunities. Further, the research gives a first hint on the effectiveness of different digital nudges and lays the foundation for future research.Research limitations/implicationsSince exploring a completely new field of research and conducting the experiment in a synthetic environment, the paper serves as a first step toward the combination of digital nudging, business process improvements and positive process deviance.Originality/valueThe major achievement reported in this paper is the exploration of a new field of research. Thus, digital nudging shapes up as a promising foundation for agile process improvement, a discovery calling for future research at the intersection of digital nudging and business process management.
Adoption of blockchain in supply chain: an analysis of influencing factors
Authors: Ghode Dnyaneshwar , Yadav Vinod , Jain Rakesh , Soni Gunjan 
Published: March 2020

PurposeBlockchain technology (BT) is setting world-shattering standard in all type of transactions in business. BT has the prospective to drastically transform supply chain (SC). The main challenge is to enhance trust among the SC stakeholders. This paper aims to identify and prioritize the factors and its challenges that influence the adoptability of BT in SC. The prioritization of these factors will be helpful to the practitioners to decide the strategy of implementing the BT in SC.Design/methodology/approachThe factors influencing adoption of BT are identified from the review of literature and expert opinion is used to rank the factors influencing the adoptability of BT in SC using grey relational analysis (GRA).FindingsWe identified and prioritized key factors: inter-organizational trust and relational governance as organizational challenge, data transparency and data immutability as technological challenge, interoperability and product type as operational challenge and social influence and behavioral intention as social challenge that influences adoptability of BT in SC.Originality/valueThe priority of these factors will guide future researchers and industry practitioners to plan rational and financial strategy for implementing BT in SC.
Offense is the best defense: the impact of workplace bullying on knowledge hiding
Authors: Yao Zhu , Zhang Xianchun , Luo Jinlian , Huang Hui 
Published: March 2020

PurposeWorkplace bullying is a common negative event suffered by employees in the workplace. The harm it brings to the organization has become the focus of the field of organizational behavior. The purpose of this study was to explore whether workplace bullying has an impact on employee knowledge hiding and to discover the underlying mechanism between the two.Design/methodology/approachBased on the conservation of resource theory and the cognitive-affective personality system theory, this paper surveys 327R&D employees of Chinese technological corporations at two time points and explores the relationship between workplace bullying and knowledge hiding as well as the underlying mechanism. This study used confirmatory factor analysis, bootstrapping method and structural equation model to validate the research hypothesis.FindingsThe results show that workplace bullying positively correlates with knowledge hiding; emotional exhaustion and organizational identification play a mediation role between workplace bullying and knowledge hiding, and both variables play a chain mediation role in that relationship; and forgiveness climate moderates the positive impact of workplace bullying on emotional exhaustion, further moderating the chain mediation role of emotional exhaustion and organizational identification.Originality/valueThe findings of this study can not only complement the existing researches on the influence of negative workplace events on employees’ knowledge hiding behaviors but also strengthen scholars’ attention and understanding of the internal mechanism between workplace bullying and knowledge hiding.
The impact of servant leadership and transformational leadership on learning organization: a comparative analysis
Authors: Xie Lei 
Published: March 2020

PurposeLeadership has a powerful influence on learning and development in today's organizations. Various types of leadership have been found to be conducive to building a learning organization. This empirical study compared the effect of transformational and servant leadership on a learning organization (an organization that constantly transforms itself using learning and development techniques) in the context of Chinese small- and medium-sized enterprises (SMEs).Design/methodology/approachFour proposed hypotheses were tested using structural equation modeling.FindingsThe results show that servant leadership has no significant relationship to learning organization, whereas transformational leadership is a strong predictor.Originality/valueThis research compares two different leadership styles and presents theoretical and practical implications for scholars and practitioners. In particular, this study advances our understanding of how and which leadership style relates to learning organization by examining a structural model with three latent variables: servant leadership, transformational leadership, and learning organization.
Demystifying organisational embeddedness of leadership – a multi-method approach to validate a new construct
Authors: Busse Ronald , Winnen Lothar , Wilms Rafael , Lanwehr Ralf 
Published: March 2020

PurposeSince the dawn of leadership research, generations of scholars have looked at the topic through the lenses of leader personalities and traits, their behaviour, the situation they are in and their relations with co-workers. Same as with ideology waves in managerial discourse and though sailing under different flags, many of the above “classical” foci reverberate in “modern” organisational literature. The authors argue, however, that relatively little effort has been put into what we label as “organisational embeddedness of leadership” (OEL). The authors here focus on the role of institutionalising leadership within the setting of “poly-contextual” organisational frameworks.Design/methodology/approachAddressing the ambiguity of previous OEL research with fresh primary data from Germany, the authors present a clear-cut five-dimensional, 15-items construct. The authors’ empirical validation rests on (1) two independent qualitative studies and (2) three independent quantitative investigations computing exploratory (N = 61) and confirmatory (N = 172) factor analysis as well as a regression analysis (N = 131).FindingsStructural equation modelling results indicate a single-factor model with five sub-dimensions consisting of leadership training and career development, leadership alignment, evaluation and feedback, implementation of employee interviews and supporting resources for leadership.Originality/valueThis work contributes to a broader understanding of “leadership emergence and development” (LED) from an organisational perspective. The limitations of the present article call for a lively debate on OEL and may illuminate some promising future research avenues.