bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and characterization of apoptotic and necrotic cell death by time-lapse quantitative phase image analysis
Authors: Vicar Tomas , Raudenska Martina , Gumulec Jaromir , Masarik Michal , Balvan Jan 
Published: March 2019

AbstractCell viability and cytotoxicity assays are highly important for drug screening and cytotoxicity tests of antineoplastic or other therapeutic drugs. Even though biochemical-based tests are very helpful to obtain preliminary preview, their results should be confirmed by methods based on direct cell death assessment. In this study, time-dependent changes in quantitative phase-based parameters during cell death were determined and methodology useable for rapid and label-free assessment of direct cell death was introduced. Our method utilizes Quantitative Phase Imaging (QPI) which enables the time-lapse observation of subtle changes in cell mass distribution. According to our results, morphological and dynamical features extracted from QPI micrographs are suitable for cell death detection (76% accuracy in comparison with manual annotation). Furthermore, based on QPI data alone and machine learning, we were able to classify typical dynamical changes of cell morphology during both caspase 3,7-dependent and independent cell death subroutines. The main parameters used for label-free detection of these cell death modalities were cell density (pg/pixel) and average intensity change of cell pixels further designated as Cell Dynamic Score (CDS). To the best of our knowledge, this is the first study introducing CDS and cell density as a parameter typical for individual cell death subroutines with prediction accuracy 75.4 % for caspase 3,7-dependent and -independent cell death.
Contribution of PSD-95 protein to reward location memory
Authors: Cały Anna , Śliwińska Małgorzata Alicja , Ziółkowska Magdalena , Łukasiewicz Kacper , Pagano Roberto , Nowacka Agata , Borczyk Malgorzata , Radwanska Kasia 
Published: March 2019

AbstractThe molecular mechanisms involved in formation of memory are still poorly understood. We focus here on the function of post-synaptic density protein 95 (PSD-95) and its phosphorylation by CaMKII in spontaneous learning about reward location in female mice. We show that formation of reward location memory leads to downregulation of PSD-95 protein in dendritic spines of thestratum radiatum, area CA1, and selective shrinkage of dendritic spines that contain PSD-95. ShRNA-driven, long-term downregulation of PSD-95 in the area CA1 decreases precision of memory. Autophosphorylation deficient CaMKII mutant mice (CaMKII:T286A) need more time than wild-type animals to learn the location of reward. The same impairment is observed after CA1-targeted overexpression of CaMKII phosphorylation-deficient form of PSD-95 (PSD-95:S73A). In contrast to young adult mice, in aged animals reward location learning affects only spines that lack PSD-95. The frequency and size of the spines without PSD-95 are increased, while shRNA targeted to PSD-95 affects neither speed of learning nor precision of memory indicating alternative mechanisms to support successful memory formation in old mice. Altogether, our data suggest that dynamic regulation of PSD-95 expression is a mechanism that accelerates learning and improves precision of reward location memory in young mice. The function of PSD-95 in memory processes changes in aged animals.
Brain connectivity measures improve modeling of functional outcome after acute ischemic stroke
Authors: Ktena Sofia Ira , Schirmer Markus D. , Etherton Mark R. , Giese Anne-Katrin , Tuozzo Carissa , Mills Brittany B , Rueckert Daniel , Wu Ona , Rost Natalia S. 
Published: March 2019

AbstractBackgroundThe ability to model long-term functional outcomes after acute ischemic stroke (AIS) represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brain’s connectivity as a graph, whose topological properties have helped uncover underlying mechanisms of brain function in health and disease. Specifically, we assessed the impact of stroke lesions on rich club (RC) organization, a high capacity backbone system of brain function.MethodsIn a hospital-based cohort of 41 AIS patients, we investigated the effect of acute infarcts on the brain’s pre-stroke RC backbone and post-stroke functional connectomes with respect to post-stroke outcome. Functional connectomes were created utilizing three anatomical atlases and characteristic path-length (L) was calculated for each connectome. The number of RC regions (NRC) affected were manually determined using each patient’s diffusion weighted image (DWI). We investigated differences inLwith respect to outcome (modified Rankin Scale score (mRS); 90-days; poor: mRS>2) and the National Institutes of Health Stroke Scale (NIHSS; early: 2-5 days; late: 90-day follow-up). Furthermore, we assessed the effect of including NRCandLin ‘outcome’ models, using linear regression and assessing the explained variance (R2).ResultsOf 41 patients (mean age (range): 70 (45-89) years), 61% were male. There were differences inLbetween patients with good and poor outcome (mRS). Including NRC in the backward selection models of outcome, R2increased between 1.3- and 2.6-fold beyond that of traditional markers (age and acute lesion volume) for NIHSS and mRS.ConclusionIn this proof-of-concept study, we showed that information on network topology can be leveraged to improve modeling of post-stroke functional outcome. Future studies are warranted to validate this approach in larger prospective studies of outcome prediction in stroke.
Single chromosome gains can function as metastasis suppressors and metastasis promoters in colon cancer
Authors: Vasudevan Anand , Baruah Prasamit S. , Smith Joan C. , Wang Zihua , Sayles Nicole M. , Andrews Peter , Kendall Jude , Leu Justin E. , Chunduri Narendra Kumar , Levy Dan , Wigler Michael , Storchová Zuzana , Sheltzer Jason M. 
Published: March 2019

AbstractMost human tumors display chromosome-scale copy number alterations, and high levels of aneuploidy are frequently associated with advanced disease and poor patient prognosis. To examine the relationship between aneuploidy and cancer progression, we generated and analyzed a series of congenic human cell lines that harbor single extra chromosomes. We find that different aneuploidies can have distinct effects on invasive behavior: across 13 different cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior by triggering a partial epithelial-mesenchymal transition. In contrast, chromosomal instability, which can lead to the development of aneuploidy, uniformly suppressed cellular invasion. By analyzing genomic copy number and survival data from 10,133 cancer patients, we demonstrate that specific aneuploidies are associated with distinct clinical outcomes, and the acquisition of certain aneuploidies is in fact linked with a favorable prognosis. Thus, aneuploidy is not a uniform driver of malignancy, and different chromosome copy number changes can uniquely influence tumor progression. At the same time, the gain of a single chromosome is capable of inducing a profound cell state transition, underscoring how genomic plasticity can engender phenotypic plasticity and lead to the acquisition of enhanced metastatic properties.
White Matter Extension of the Melbourne Children’s Regional Infant Brain Atlas: M-CRIB-WM
Authors: Wen Yao Sarah Hui , Yang Joseph Yuan-Mou , Alexander Bonnie , Wu Michelle Hao , Kelly Claire E. , Ball Gareth , Seal Marc L. , Anderson Peter J. , Doyle Lex W. , Cheong Jeanie L.Y. , Spittle Alicia J. , Thompson Deanne K. 
Published: March 2019

AbstractBackgroundUnderstanding typically developing infant brain structure is crucial in investigating neurological disorders of early childhood. Brain atlases providing standardised identification of neonatal brain regions are key in such investigations. Our previously developed Melbourne Children’s Regional Infant Brain (M-CRIB) and M-CRIB 2.0 neonatal brain atlases provide standardised parcellation of 100 and 94 brain regions respectively, including cortical, subcortical, and cerebellar regions. The aim of this study was to extend the M-CRIB atlas coverage to include 54 white matter regions.MethodsParticipants were ten healthy term-born neonates who comprised the sample for the M-CRIB and M-CRIB 2.0 atlases. WM regions were manually segmented on T2 images and co-registered diffusion tensor imaging-based, direction-encoded colour maps. Our labelled regions are based on those in the JHU-neonate-SS atlas, but differ in the following ways: 1) we included five corpus callosum subdivisions instead of a left / right division; 2) we included a left / right division for the middle cerebellar peduncle; and 3) we excluded the three brainstem divisions. All segmentations were reviewed and approved by a paediatric radiologist and a neurosurgery research fellow for anatomical accuracy.ResultsThe resulting neonatal WM atlas comprises 54 WM regions: 24 paired regions, and six unpaired regions comprising five corpus callosum subdivisions and one pontine crossing tract. Detailed protocols for manual WM parcellations are provided, and the M-CRIB-WM atlas is presented together with the existing M-CRIB and M-CRIB 2.0 cortical, subcortical and cerebellar parcellations in ten individual neonatal MRI datasets.ConclusionThe updated M-CRIB atlas including the WM parcellations will be made publicly available. The atlas will be a valuable tool that will help facilitate neuroimaging research into neonatal WM development in both healthy and diseased states.
Identification of a human adult cardiac stem cell population with neural crest origin
Authors: Höving Anna , Merten Madlen , Schmidt Kazuko Elena , Faust Isabel , Ruiz-Perera Lucia Mercedes , Hachmeister Henning , Sommer Sebastian-Patrick , Fujita Buntaro , Pühler Thomas , Huser Thomas , Greiner Johannes , Kaltschmidt Barbara , Gummert Jan , Knabbe Cornelius , Kaltschmidt Christian 
Published: March 2019

ABSTRACTCardiovascular diseases are the major cause of death worldwide, emphasizing the necessity to better understand adult human cardiac cell biology and development. Although the adult heart was considered as a terminally differentiated organ, rare populations of cardiac stem cells (CSCs) have been described so far, with their developmental origin and endogenous function still being a matter of debate.Here, we identified a Nestin+/S100+/CD105+/Sca1+/cKit-population of CSCs in the myocardium of the adult human heart auricle. Isolated cells showed expression of characteristic neural crest-derived stem cell (NCSC) markers and kept their genetic stability during cultivationin vitro. Cultivated hCSCs efficiently gave rise to functional, beating cardiomyocytes, osteoblasts, adipocytes and neurons. Global transcriptome analysis via RNAseq showed a high similarity between the expression profiles of Nestin+/S100+/CD105+/Sca1+/cKit-hCSCs and adult human NCSCs from the nasal cavity (inferior turbinate stem cells, ITSCs). In detail, 88.1 % of all genes were significantly expressed in both stem cell populations particularly including common NCSC-markers. Based on these observations, we suggest a similar developmental origin of both stem cell populations.In summary, we identified a human adult cardiac stem cell population with neural crest-origin, which may also contribute to endogenous cardiac tissue homeostasis and tissue repairin vivo.
AMPK-independent LKB1 activity is required for efficient epithelial ovarian cancer metastasis
Authors: Buensuceso Adrian , Valdes Yudith Ramos , DiMattia Gabriel E. , Shepherd Trevor G. 
Published: March 2019

ABSTRACTEpithelial ovarian cancer (EOC) spreads by direct dissemination of malignant cells and multicellular clusters, known as spheroids, into the peritoneum followed by implantation and growth on abdominal surfaces. Using a spheroid model system of EOC metastasis, we discovered that Liver kinase B1 (LKB1), encoded by theSTK11gene, and its canonical substrate AMP-activated protein kinase (AMPK) are activated in EOC spheroids, yet only LKB1 is required for cell survival. We have now generatedSTK11-knockout cell lines using normal human FT190 cells and three EOC cell lines, OVCAR8, HeyA8, and iOvCa147.STK11KO did not affect growth and viability in adherent culture, but it decreased anchorage-independent growth of EOC cells. EOC spheroids lacking LKB1 had markedly impaired growth and viability, whereas there was no difference in normal FT190 spheroids. To test whether LKB1 loss affects EOC metastasis, we performed intraperitoneal injections of OVCAR8-, HeyA8-, and iOvCa147-STK11KO cells, and respective controls. LKB1 loss exhibited a dramatic reduction on tumour burden and metastatic potential; in particular, OVCAR8-STK11KO tumours had evidence of extensive necrosis, apoptosis and hypoxia. Interestingly, LKB1 loss did not affect AMPKα phosphorylation in EOC spheroids and tumour xenografts, indicating that LKB1 signaling to support EOC cell survival in spheroids and metastatic tumour growth occurs via other downstream mediators. We identified the dual-specificity phosphatase DUSP4 as a commonly upregulated protein due to LKB1 loss; indeed,DUSP4knockdown in HeyA8-STK11KO cells restored spheroid formation and viability. Our results strongly indicate that intact LKB1 activity independent of downstream AMPK signaling is required during EOC metastasis.
Resting networks and personality predict attack speed in social spiders
Authors: Hunt Edmund R. , Mi Brian , Geremew Rediet , Fernandez Camila , Wong Brandyn M. , Pruitt Jonathan N. , Pinter-Wollman Noa 
Published: March 2019

AbstractGroups of social predators capture large prey items collectively, and their social interaction patterns may impact how quickly they can respond to time-sensitive predation opportunities. We investigated whether various organizational levels of resting interactions (individual, sub-group, group), observed at different intervals leading up to a collective prey attack, impacted the predation speed of colonies of the social spiderStegodyphus dumicola. We found that in adult spiders overall group connectivity (average degree) increased group attack speed. However, this effect was detected only immediately before the predation event; connectivity two and four days before prey capture had little impact on the collective dynamics. Significantly, lower social proximity of the group’s boldest individual to other group members (closeness centrality) immediately prior and two days before prey capture was associated with faster attack speeds. These results suggest that for adult spiders, the long-lasting effects of the boldest individual on the group’s attack dynamics are mediated by its role in the social network, and not only by its boldness. This suggests that behavioural traits and social network relationships should be considered together when defining keystone individuals in some contexts. By contrast, for subadult spiders, while the group maximum boldness was negatively correlated with latency to attack, no significant resting network predictors of latency to attack were found. Thus, separate behavioural mechanisms might play distinctive roles in determining collective outcomes at different developmental stages, timescales, and levels of social organization.Significance statementCertain animals in a group, such as leaders, may have a more important role than other group members in determining their collective behavior. Often these individuals are defined by their behavioral attributes, for example, being bolder than others. We show that in social spiders both the behavioral traits of the influential individual, and its interactions with other group members, shape its role in affecting how quickly the group collectively attacks prey.
Precision timing with α-β oscillatory coupling: stopwatch or motor control?
Authors: Kononowicz Tadeusz W. , Sander Tillman , Van Rijn Hedderik , van Wassenhove Virginie 
Published: March 2019

AbstractPrecise timing is crucial for many behaviors ranging from street crossing, conversational speech, to athletic performance. The precision of motor timing has been suggested to result from the strength of phase-amplitude coupling (PAC) between the phase of alpha oscillations (α, 8-12 Hz) and the power of beta activity (β, 14-30 Hz), herein referred to as α-β PAC. The amplitude of β oscillations has been proposed to code for temporally relevant information, and the locking of β power to the phase of α oscillations to maintain timing precision. Motor timing precision has at least two sources of variability: variability of timekeeping mechanism and variability of motor control. There is ambiguity to with of these two factors α-β PAC could be ascribed to. Whether α-β PAC indexes precision of internal timekeeping mechanisms like a stopwatch, or α-β PAC indexes motor control precision is unclear. To disentangle these two hypotheses, we tested how oscillatory coupling at different stages of time reproduction related to temporal precision. Human participants perceived, and subsequently reproduced, a time interval while magnetoencephalography was recorded. The data show a robust α-β PAC during both the encoding and the reproduction of a temporal interval, a pattern which could not be predicted for by the motor control account. Specifically, we found that timing precision resulted from the tradeoff between the strength of α-β PAC during the encoding and during the reproduction of intervals. We interpret these results as supporting evidence for the hypothesis that α-β PAC codes for precision of temporal representations in the human brain.Highlights-Encoding and reproducing temporal intervals implicate α-β PAC.-α-β PAC does not represent solely motor control.-α-β PAC maintains the precision of temporal representations.
Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
Authors: Cundiff Mary D. , Hurley Christina M. , Wong Jeremy D. , Bashyal Aarti , Rosenberg Jake , Reichard Eden L. , Nassif Nicholas D. , Brodbelt Jennifer S. , Kraut Daniel A. 
Published: March 2019

ABSTRACTThe ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasome’s unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasome’s unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.
Individual social entrepreneurship orientation: towards development of a measurement scale
Authors: Satar Mir Shahid , Natasha Saqib 
Published: March 2019

Purpose
While the literature has described social entrepreneurs as overwhelmingly occupying a pivotal role in social entrepreneurship (S-ENT) process, there is a high inconsistency prevailing with respect to entrepreneurial traits, attitudes and skills of social entrepreneurs. One explanation for this may be the lack of a suitable scale measuring entrepreneurship orientation of social entrepreneurial individuals. The purpose of this study is to address this gap by proposing an initial assessment tool for individual S-ENT orientation (ISEO).

Design/methodology/approach
A mixed methods research design, along with a two-stage Delphi process, helped in generating appropriate constructs for ISEO. While the items for the first dimension of scale were directly derived from the Delphi study, the items of the remaining dimensions were mainly found based on the three individual entrepreneurial orientation dimensions presented by Bolton and Lane. By means of exploratory factor analysis, the final examination of the ISEO items was undertaken through a survey of 71 social entrepreneurs across India. The process eventually resulted in reliable and valid measures for four dimensions of ISEO.

Findings
The scale-development process eventually resulted in a 13-item scale, measuring four dimensions of ISEO (social passion, innovativeness, risk-taking and pro-activeness). By developing a set of relevant ISEO indicators, the study answers the call for a scale development of ISEO in S-ENT literature.

Research limitations/implications
There is a need to further validate this instrument among other stakeholders (students) as well as in samples with different demographic characteristics across different regions of the country and the world. To further evaluate the reliability and validity properties and to confirm the newly established subscales and their relationship with the ISEO construct, there is need for conducting a confirmatory factor analysis using larger sample sizes.

Practical implications
The measurement of SEO at an individual level will assist in S-ENT education, training and development of present and prospective social entrepreneurs, as well as assist individuals who want to assess the strength of their orientation towards S-ENT. The understanding of ISEO at the individual level will be equally useful for S-ENT incubators, the government and other S-ENT stakeholders who are considering supporting S-ENT proposals.

Originality/value
The paper is the first to develop an ISEO scale which is based on empirical data in S-ENT field.
Contradictory results on environmental concern while re-visiting green purchase awareness and behavior
Authors: Malik Muhammad Imran , Nawaz Mir Faisal , Hussain Saddam , Hyder Shabir , Anwar Asim , Khan Zia Ullah , Nawab Noman , Shah Syed Farjad Ali , Waseem Muhammad 
Published: March 2019

PurposeThis paper aims to examine the mediating role of environmental concern in the relationship of green purchase awareness and purchasing behavior of fast food consumers keeping in view the theory of planned behavior.Design/methodology/approachA quantitative, cross-sectional design is used by collecting primary responses through a validated questionnaire. In all, 1,008 male and female buyers of fast food were sampled. Structural equation modeling is applied.FindingsThe results revealed that green purchase awareness has a positive relationship with green purchase behavior, and environmental concern has no mediation in the relationship. Upon having awareness, the respondents adopted green or pro-environmental behavior, but at the same time, they were found having least concern for the protection of environment.Research limitations/implicationsThis is a cross-sectional study with questionnaire. Multiple sources of data collection results in weakening self-reporting bias.Practical implicationsImplications count toward individuals, enterprises and society at general.Originality/valueThe study highlights the issue of not having concern for the protection of the environment even after having green purchase awareness. This is the first time the environmental concern is examined as a mediator in the selected relationship. The contradictory results of having no environmental concern differentiate this study from others.