bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro analysis of RNA polymerase II elongation complex dynamics
Authors: Joo Yoo Jin , Ficarro Scott B. , Chun Yujin , Marto Jarrod A. , Buratowski Stephen 
Published: January 2019

AbstractRNA polymerase II elongation complexes (ECs) were assembled from nuclear extract on immobilized DNA templates and analyzed by quantitative mass spectrometry. Time course experiments showed that initiation factor TFIIF can remain bound to early ECs, while levels of core elongation factors Spt4-Spt5, Paf1C, Spt6-Spn1, and Elf1 levels remain steady. Importantly, the dynamic phosphorylation patterns of the Rpb1 C-terminal domain (CTD), and the factors that recognize them, change as a function of post-initiation time, rather than distance elongated. Chemical inhibition of Kin28/Cdk7 blocks both Serine 5 and Serine 2 phosphorylation, affects initiation site choice, and inhibits elongation efficiency. EC components dependent on CTD phosphorylation include capping enzyme, Cap Binding Complex, Set2, and the PAF1 complex. By recapitulating many known features ofin vivoelongation, this system reveals new details that clarify how EC-associated core elongation factors, chromatin regulators, and RNA processing factors change at each step of transcription.
The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity
Authors: Jevtić Predrag , Schibler Andria C. , Pegoraro Gianluca , Misteli Tom , Levy Daniel L. 
Published: January 2019

ABSTRACTHow intracellular organelles acquire their characteristic sizes is a fundamental cell biological question. Given the stereotypical changes in nuclear size in cancer, it is particularly important to understand the mechanisms that control nuclear size in human cells. Here we use a high-throughput imaging RNAi screen to identify and mechanistically characterize ELYS, a nucleoporin required for postmitotic nuclear pore complex (NPC) assembly, as a determinant of nuclear size in mammalian cells. We show that ELYS knockdown results in small nuclei, the accumulation of cytoplasmic lamin aggregates, reduced nuclear lamin B2 localization, lower NPC density, and decreased nuclear import. Increasing nuclear import by importin α overexpression rescues nuclear size and lamin B2 import, while inhibiting importin α/β nuclear import decreases nuclear size. Conversely, ELYS overexpression leads to increased nuclear size, enrichment of nuclear lamin B2 staining at the nuclear periphery, and elevated NPC density and nuclear import. Consistent with these observations, knockdown or inhibition of exportin 1 increases nuclear size. In summary, we identify ELYS and NPC density as novel positive effectors of mammalian nuclear size and propose that nuclear size is controlled by nuclear import capacity.
Altering nuclear import in early Xenopus laevis embryos affects later development
Authors: Jevtić Predrag , Levy Daniel L. 
Published: January 2019

ABSTRACTMore than just a container for DNA, the nucleus carries out a wide variety of critical and highly regulated cellular functions. One of these functions is nuclear import, and in this study we investigate how altering nuclear import impacts developmental progression and organismal size. During early Xenopus laevis embryogenesis, the timing of a key developmental event, the midblastula transition (MBT), is sensitive to nuclear import factor levels. How might altering nuclear import and MBT timing in the early embryo affect downstream development of the organism? We microinjected X.laevis two-cell embryos to increase levels of importin α or NTF2, resulting in differential amounts of nuclear import factors in the two halves of the embryo. Compared to controls, these embryos exhibited delayed gastrulation, curved neural plates, and bent tadpoles with different sized eyes. Furthermore, embryos microinjected with NTF2 developed into smaller froglets compared to control microinjected embryos. We propose that altering nuclear import and size affects MBT timing, cell size, and cell number, subsequently disrupting later development. Thus, altering nuclear import early in development can affect function and size at the organismal level.
Left anterior temporal lobe is necessary for efficient lateralised processing of spoken word identity
Authors: Cope Thomas , Shtyrov Yury , MacGregor Lucy , Holland Rachel , Pulvermüller Friedemann , Rowe James B , Patterson Karalyn 
Published: January 2019

AbstractIn the healthy human brain, the processing of spoken words is strongly left-lateralised, while the processing of complex non-linguistic sounds recruits brain regions bilaterally. Here we asked whether the left anterior temporal lobe, strongly implicated in semantic processing, is critical to this special treatment of linguistic stimuli. Nine patients with semantic dementia (SD) and fourteen age-matched controls underwent magnetoencephalography and structural MRI. Voxel based morphometry demonstrated the stereotypical pattern of SD: severe grey matter loss restricted to the left anterior temporal lobe. During magnetoencephalography, participants listened to word sets in which identity and meaning were ambiguous until utterance completion, for exampleplayedvsplate. Whereas left-hemispheric responses were similar across groups, patients demonstrated increased right hemisphere activity 174-294ms after stimulus disambiguation. Source reconstructions confirmed recruitment of right-sided analogues of language regions in SD: atrophy of left anterior temporal lobe was associated with increased activity in right temporal pole, middle temporal gyrus, inferior frontal gyrus and supramarginal gyrus. Moreover only healthy controls had differential responses to wordsversusnon-words in right auditory cortex and planum temporale. Overall, the results indicate that anterior temporal lobe is necessary for normal and efficient processing of word identity in the rest of the language network.
Meta-analysis of the human brain transcriptome identifies heterogeneity across human AD coexpression modules robust to sample collection and methodological approach
Authors: Logsdon Benjamin A. , Perumal Thanneer M. , Swarup Vivek , Wang Minghui , Funk Cory , Gaiteri Chris , Allen Mariet , Wang Xue , Dammer Eric , Srivastava Gyan , Mukherjee Sumit , Sieberts Solveig K. , Omberg Larsson , Dang Kristen D. , Eddy James A. , Snyder Phil , Chae Yooree , Amberkar Sandeep , Wei Wenbin , Hide Winston , Preuss Christoph , Ergun Ayla , Ebert Phillip J , Airey David C. , Carter Gregory W. , Mostafavi Sara , Yu Lei , Klein Hans-Ulrich ,   the AMP-AD Consortium, Collier David A. , Golde Todd , Levey Allan , Bennett David A. , Estrada Karol , Decker Michael , Liu Zhandong , Shulman Joshua M. , Zhang Bin , Schadt Eric , De Jager Phillip L. , Price Nathan D. , Ertekin-Taner Nilüfer , Mangravite Lara M. 
Published: January 2019

SUMMARYAlzheimer’s disease (AD) is a complex and heterogenous brain disease that affects multiple inter-related biological processes. This complexity contributes, in part, to existing difficulties in the identification of successful disease-modifying therapeutic strategies. To address this, systems approaches are being used to characterize AD-related disruption in molecular state. To evaluate the consistency across these molecular models, a consensus atlas of the human brain transcriptome was developed through coexpression meta-analysis across the AMP-AD consortium. Consensus analysis was performed across five coexpression methods used to analyze RNA-seq data collected from 2114 samples across 7 brain regions and 3 research studies. From this analysis, five consensus clusters were identified that described the major sources of AD-related alterations in transcriptional state that were consistent across studies, methods, and samples. AD genetic associations, previously studied AD-related biological processes, and AD targets under active investigation were enriched in only three of these five clusters. The remaining two clusters demonstrated strong heterogeneity between males and females in AD-related expression that was consistently observed across studies. AD transcriptional modules identified by systems analysis of individual AMP-AD teams were all represented in one of these five consensus clusters except ROS/MAP-identified Module 109, which was specific for genes that showed the strongest association with changes in AD-related gene expression across consensus clusters. The other two AMP-AD transcriptional analyses reported modules that were enriched in one of the two sex-specific Consensus Clusters. The fifth cluster has not been previously identified and was enriched for genes related to proteostasis. This study provides an atlas to map across biological inquiries of AD with the goal of supporting an expansion in AD target discovery efforts.
Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation
Authors: Albadri Shahad , Naso Federica , Gauron Carole , Parolin Carola , Duroure Karine , Fiori Jessica , Boga Carla , Vriz Sophie , Calonghi Natalia , Del Bene Filippo 
Published: January 2019

SummaryReactive oxygen species (ROS) and downstream products of lipid oxidation are emerging as important secondary messengers in tissue homeostasis. However their regulation and mechanism of action remain poorly studiedin vivoduring normal development. Here we reveal that the fine regulation of hydrogen peroxide (H2O2) levels at the degradation step by its scavenger Catalase is crucial to mediate the switch from proliferation to differentiation in retinal progenitor cells (RPCs). We further show that altering the levels of downstream products of the Redox signaling can also affect this switch. Indeed, we identify9-hydroxystearic acid (9-HSA), an endogenous downstream lipid peroxidation product, as a mediator of this effect in the zebrafish retina. In fact, RPCs exposed to higher amounts of9-HSA failed to differentiate and remained proliferative. We found that9-HSA exerts its biological functionin vivoby inhibiting the activity of histone deacetylase 1. We finally show that the local and temporal manipulation of H2O2levels bycatalaseoverexpression in RPCs was sufficient to trigger their premature differentiation. Therefore the amount of H2O2in RPCs is instructive of their ability to switch from proliferation to differentiation. We propose a mechanism that acts in RPC and linking H2O2homeostasis and neuronal differentiationviathe modulation of lipid peroxidation.
Construction of synthetic microbiota for reproducible flavor metabolism in Chinese light aroma type liquor produced by solid-state fermentation
Authors: Wang Shilei , Wu Qun , Nie Yao , Xu Yan 
Published: January 2019

ABSTRACTNatural microbiota plays an essential role in flavor compounds producing for traditional food fermentation. Whereas, the fluctuation of natural microbiota results in the inconstancy of food quality. Thus, it is critical to reveal the core microbiota for flavor compounds producing and construct a synthetic core microbiota for constant food fermentation. Here, we revealed the core microbiota based on their flavor-producing and co-occurrence performance, using Chinese light aroma type liquor as a model system. Five genera were identified to be the core microbiota, includingLactobacillus, Saccharomyces, Pichia, Geotrichum, andCandida. The synthetic core microbiota of these five genera presented a reproducible dynamic profile with that in the natural microbiota. Monte Carlo test showed that the interpretation of five environmental factors (lactic acid, ethanol and acetic acid contents, moisture and pH) on the synthetic microbiota distribution were highly significant (P< 0.01), which was similar with that in the natural fermentation system. In addition, 77.27% of the flavor compounds produced by the synthetic core microbiota showed a similar dynamic profile (ρ> 0) with that in the natural liquor fermentation process, and the flavor profile presented a similar composition. It indicated that the synthetic core microbiota is efficient for reproducible flavor metabolism. This work established a method for identifying core microbiota and constructing a synthetic microbiota for reproducible flavor compounds. It is of great significance for the tractable and constant production of various fermented foods.IMPORTANCEThe transformation from natural fermentation to synthetic fermentation is essential to construct a constant food fermentation process, which is the premise for stably making high-quality food. According to the functions of flavor-producing and co-occurring in dominant microbes, we provided a system-level approach to identify the core microbiota in Chinese light aroma type liquor fermentation. In addition, we successfully constructed a synthetic core microbiota to simulate the microbial community succession and flavor compounds production in thein vitrosystem. The constructed synthetic core microbiota could not only facilitate a mechanistic understanding of the structure and function of the microbiota, but also be beneficial for constructing a tractable and reproducible food fermentation process.
Multi-ATOM: Ultrahigh-throughput single-cell quantitative phase imaging with subcellular resolution
Authors: Lee Kelvin C. M. , Lau Andy K. S. , Tang Anson H. L. , Wang Maolin , Mok Aaron T. Y. , Chung Bob M. F. , Yan Wenwei , Shum Ho Cheung , Cheah Kathryn S. E. , Chan Godfrey C. F. , So Hayden K. H. , Wong Kenneth K. Y. , Tsia Kevin K. 
Published: January 2019

AbstractA growing body of evidence has substantiated the significance of quantitative phase imaging (QPI) in enabling cost-effective and label-free cellular assay, which provides useful insights into understanding biophysical properties of cells and their roles in cellular functions. However, available QPI modalities are limited by the loss of imaging resolution at high throughput and thus run short of sufficient statistical power at the single cell precision to define cell identities in a large and heterogeneous population of cells – hindering their utility in mainstream biomedicine and biology. Here we present a new QPI modality, coined multi-ATOM that captures and processes quantitative label-free single-cell images at ultra-high throughput without compromising sub-cellular resolution. We show that multi-ATOM, based upon ultrafast phase-gradient encoding, outperforms state-of-the-art QPI in permitting robust phase retrieval at a QPI throughput of >10,000 cell/sec, bypassing the need for interferometry which inevitably compromises QPI quality under ultrafast operation. We employ multi-ATOM for large-scale, label-free, multi-variate, cell-type classification (e.g. breast cancer sub-types, and leukemic cells versus peripheral blood mononuclear cells) at high accuracy (>94%). Our results suggest that multi-ATOM could empower new strategies in large-scale biophysical single-cell analysis with applications in biology and enriching disease diagnostics.
Assessment of gibberellin (GA4+7) mediated changes on grain filling, hormonal behaviour and antioxidants in high-density maize (Zea Mays L.)
Authors: Cui Wenwen , Zuo Bingyun , Song Quanhao , Kamran Muhammad , Ali Shahzad , Han Qingfang , Jia Zhikuan 
Published: January 2019

AbstractDense plant cultivation is an efficient approach to improve the maize production by maximizing the utilization of energy and nutrient. However, dense plant populations may aggravate the abortion rate of young grains and result in fewer number of kernels per ear. Grain filling rate and duration play a decisive role in maize grain yield. Therefore, increasing plant density, consideration of enhancing the grain filling rate and duration of individual maize plant and regulating crop senescence would be the first priority. In this study, we examined the regulatory effects of GA4+7 under two application methods (shank-smearing and silk-smearing). Shank-soaking with GA4+7 at the rate of 0 (CK1), 10 (T1), 60 (T2), and 120 (T3) mg L-1, while silk-smearing at the rate of 0 (CK2), 10 (S1), 60 (S2), and 120 (S3) mg L-1 were used. The results showed that GA4+7 improved the grain filling rate by increasing the content of auxin, gibberellin and zeatin and abscisic acid in grains compared to control plants. In addition, The auxin, gibberellin and zeatin contents in the grains were positively and significantly correlated with the maximum grain weight and the maximum and mean grain-filling rates; the abscisic acid level was positively correlated with the maximum grain weight and the maximum and mean grain-filling rates. Moreover, GA4+7 increased the activities of superoxide dismutases, catalases, peroxidases, and reduced the malondialdehyde content in leaves compared with untreated plants. At the rate of 60 mg L-1, GA4+7 showed the greatest effect for shank-smearing and silk-smearing (T2 and S2), followed by 10 mg L-1 (T1) for shank-smearing and 120 mg L-1 (S3) for silk-smearing. Our results suggest that application of 60 mg L-1 GA4+7 for smearing application could efficiently be used for changed the level of hormones in grains and antioxidant enzymes in ear leaf, would be useful for enhancing grain filling rate and delaying leaves senescence, and resulting in an increasing of maize grain yield.
Inclusive medical rehabilitation for persons with disability due to leprosy, lymphatic filariasis, and diabetes mellitus: Mapping the gap in three leprosy endemic districts in Indonesia
Authors: Denny Hanifa Maher , Dharmawan Yudhy , Ginandjar Praba , Widjanarko Bagoes , Sriatmi Ayun , Umamah Aizzatul , Sakundarno Mateus , Prasetyanti Widya 
Published: January 2019

AbstractMedical rehabilitation for person with disability in Indonesia is still an issue. This research aimed to explore Inclusive medical rehabilitation for persons with disability due to leprosy, lymphatic filariasis, and diabetes mellitus in three regions in Indonesia. The qualitative study was employed to gather data from disability patients, health workers in PHCs, medical rehabilitation services for leprosy, DM, and LF in hospitals.The results indicated that the gap on medical rehabilitation for person with disability due to leprosy, lymphatic filariasis and diabetes mellitus in three regions were due to some differences in their geographical aspects, availability of referral hospital for treating leprosy and filariasis, supervision, human resource competencies.
Influence of Gurney flaps on aerodynamic characteristics of a canard-configuration aircraft
Authors: Wei Zhongcheng , Zhan Jingxia , He Xi , Wang Jinjun 
Published: January 2019

Purpose
The purpose of this paper is to mount Gurney flaps at the trailing edges of the canards and investigate their influence on aerodynamic characteristics of a simplified canard-configuration aircraft model.

Design/methodology/approach
A force measurement experiment was conducted in a low-speed wind tunnel. Hence, the height and shape effects of the Gurney flaps on the canards were investigated.

Findings
Gurney flaps can increase the lift and pitching-up moment for the aircraft model tested, thereby increasing the lift when trimming the aircraft. The dominant parameter to influence aerodynamic characteristics is the height of Gurney flaps. When the flap heights are the same, the aerodynamic efficiency of the triangular Gurney flaps is higher than that of the rectangular ones. Moreover, the canard deflection efficiency will be reduced with Gurney flaps equipped, but the total aerodynamic increment is considerable.

Practical implications
This paper helps to solve the key technical problem of increasing take-off and landing lift coefficients, thus improving the aerodynamic performance of the canard-configuration aircraft.

Originality/value
This paper recommends to adopt triangular Gurney flaps with the height of 3 per cent chord length of the canard root (c) for engineering application.
Does academic major matter in mobile assisted language learning? A quasi-experimental study
Authors: Thongsri Nattaporn , Shen Liang , Yukun Bao 
Published: January 2019

Purpose
The purpose of this paper is to investigate the use of mobile assisted language learning (MALL) in vocabulary learning among English foreign language learners in China with a lens on academic major difference. This study hypothesizes that academic majors including Science, Technology, Engineering and Mathematics (STEM) and non-STEM differentiate the learners’ perception of computer self-efficacy (CSE) and MALL learning performance as well as moderate the effect of CSE on language learning performance.

Design/methodology/approach
Sample data for this study were collected from 200 university students enrolled in both STEM and non-STEM majors. Under the quasi-experiment, this study had been conducted vocabulary training, pre-test, post-test and a questionnaire. The Statistical Package for the Social Sciences, a statistical analysis technique based on ANOVA and regression were used to analyze the data.

Findings
The results support hypotheses that CSE, learning score and satisfaction are rated higher for STEM students than non-STEM ones and indicate the effect of CSE on language learning performance is stronger for STEM students than non-STEM ones in using MALL.

Originality/value
This paper addressed important issues in language learning on the academic major difference. The findings would be the guidelines for educational organizations to motivate and stimulate students with sustainable self-confidence important not only for improvement in students’ language learning achievements and outcomes but also for the advancement of mobile technology in language learning.
Does work engagement mediate the perceived career support- and career adaptability- work performance relationship?
Authors: Gupta Manish 
Published: January 2019

PurposeThe purpose of this paper is to examine the mediating role of work engagement between the relationship of perceived career support and work performance as well as between the relationship of career adaptability and work performance.Design/methodology/approachData were collected form 606 i-generation liquid knowledge workers. They had completed their internship program in the industry for a period of at least one month. Regression analysis was carried out to test the hypothesized framework.FindingsMost of the results indicated support for the hypotheses. Work engagement was found to be mediating the perceived career support and work performance relationship fully. However, work engagement was found to be mediating the career adaptability and work performance relationship only partially.Research limitations/implicationsEngaging liquid workers plays a crucial role in passing the positive effects of perceived career support and career adaptability to work performance.Practical implicationsThe findings suggest that managers may take steps to enhance engagement levels of the employees so that it can help the interns high on perceived career support and career adaptability perform well at work.Originality/valueTo the best of the authors’ knowledge, this study is unique that tests and finds the intervening role of work engagement between work performance and the two career-related constructs.