bluuebunny/crossref_metadata_2025 huggingface dataset:
Human and computer estimations of Predictability of words in written language
Authors: Bianchi Bruno , Bengolea Monzón Gastón , Ferrer Luciana , Fernández Slezak Diego , Shalom Diego E. , Kamienkowski Juan E.
Published: March 2020

When we read printed text, we are continuously predicting upcoming words to integrate information and guide future eye movements. Thus, the Predictability of a given word has become one of the most important variables when explaining human behaviour and information processing during reading. In parallel, the Natural Language Processing (NLP) field evolved by developing a wide variety of applications. Here, we show that using different word embeddings techniques (like Latent Semantic Analysis, Word2Vec, and FastText) and N-gram-based language models we were able to estimate how humans predict words (cloze-task Predictability) and how to better understand eye movements in long Spanish texts. Both types of models partially captured aspects of predictability. On the one hand, our N-gram model performed well when added as a replacement for the cloze-task Predictability of the fixated word. On the other hand, word embeddings were useful to mimic Predictability of the following word. Our study joins efforts from neurolinguistic and NLP fields to understand human information processing during reading to potentially improve NLP algorithms.
Publisher Correction: Research on oral microbiota of monozygotic twins with discordant caries experience - in vitro and in vivo study
Authors: Wu Hongle , Zeng Benhua , Li Bolei , Ren Biao , Zhao Jianhua , Li Mingyun , Peng Xian , Feng Mingye , Li Jiyao , Wei Hong , Cheng Lei , Zhou Xuedong
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Comparison of electrocatalytic activity of Pt1−xPdx/C catalysts for ethanol electro-oxidation in acidic and alkaline media
Authors: Zhang Qiang , Chen Ting , Jiang Rongyan , Jiang Fengxing
Published: March 2020

The Pt1−xPdx/C catalysts exhibit much higher electrocatalytic activity in alkaline media than in acid media.
An umpolung reaction of α-iminothioesters possessing a cyclopropyl group
Authors: Shimizu Makoto , Morimoto Takayoshi , Yanagi Yusuke , Mizota Isao , Zhu Yusong
Published: March 2020

Tandem N-alkylation/oxidation/second addition reaction to α-cyclopropyl α-imino(thio)esters gave N-alkylated ring-opened products in good yields.
Role of microvascular endothelial cells on proliferation, migration and adhesion of hematopoietic stem cells
Authors: Lin Fanli , Wang Shuyue , Xiong Hao , Liu Yang , Li Xiaoming , Huang Chunlan
Published: March 2020

Background: The present study investigated the effects of microvascular endothelial cells (MECs) on the chemotaxis, adhesion and proliferation of bone marrow hematopoietic stem cells (HSCs) ex vivo. Methods and Results: MECs were collected from the lung tissue of C57BL/6 mice, and HSCs were isolated with immunomagnetic beads from bone marrow of GFP mice. MECs and HSCs were co-cultured with or without having direct cell–cell contact in Transwell device for the measurement of chemotaxis and adhesion of MECs to HSCs. Experimental results indicate that the penetration rate of HSCs from the Transwell upper chamber to lower chamber in ‘co-culture’ group was significantly higher than that of ‘HSC single culture’ group. Also, the HSCs in co-culture group were all adherent at 24 h, and the co-culture group with direct cell–cell contact had highest proliferation rate. The HSC number was positively correlated with vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) levels in supernatants of the culture. Conclusions: Our study reports that MECs enhance the chemotaxis, adhesion and proliferation of HSCs, which might be related to cytokines SDF-1 and VEGF secreted by MECs, and thus MECs enhance the HSC proliferation through cell–cell contact. The present study revealed the effect of MECs on HSCs, and provided a basis and direction for effective expansion of HSCs ex vivo.
The OTELO survey
Authors: Nadolny Jakub , Lara-López Maritza A. , Cerviño Miguel , Bongiovanni Ángel , Cepa Jordi , de Diego José A. , Pérez García Ana María , Pérez Martínez Ricardo , Sánchez-Portal Miguel , Alfaro Emilio , Castañeda Héctor O. , Gallego Jesús , González J. Jesús , González-Serrano J. Ignacio , Padilla Torres Carmen P. , Pintos-Castro Irene , Pović Mirjana
Published: March 2020

Context. A sample of low-mass Hα emission line sources at z ∼ 0.4 was studied in the context of the mass-metallicty relation (MZR) and its possible evolution. We drew our sample from the OSIRIS Tunable Emission Line Object (OTELO) survey, which exploits the red tunable filter of OSIRIS at the Gran Telescopio Canarias to perform a blind narrow-band spectral scan in a selected field of the Extended Groth Strip. We were able to directly measure emission line fluxes and equivalent widths from the analysis of OTELO pseudo-spectra.

Aims. This study aims to explore the MZR in the very low-mass regime. Our sample reaches stellar masses (M*) as low as 106.8 M⊙, where 63% of the sample have M* <  109 M⊙. We also explore the relation of the star formation rate (SFR) and specific SFR with M* and gas-phase oxygen abundances, as well as the M*-size relation and the morphological classification.

Methods. The M* were estimated using synthetic rest-frame colours. Using an χ2 minimization method, we separated the contribution of [N II]λ6583 to the Hα emission lines. Using the N2 index, we separated active galactic nuclei from star-forming galaxies (SFGs) and estimated the gas metallicity. We studied the morphology of the sampled galaxies qualitatively (visually) and quantitatively (automatically) using high-resolution data from the Hubble Space Telescope-ACS. The physical size of the galaxies was derived from the morphological analysis using GALAPAGOS2/GALFIT, where we fit a single-Sérsic 2D model to each source.

Results. We find no evidence for an MZR evolution from comparing our very low-mass sample with local SFGs from the Sloan Digital Sky Survey. Furthermore, the same is true for M*-size and M*-SFR relations, as we deduce from comparison with recent literature. Morphologically, our sample is mostly (63%) populated by late-type galaxies, with 13% of early-type sources. For the first time, we identify one possible candidate outlier in the MZR at z = 0.4. The stellar-mass, metallicity, colour, morphology, and SFR of this source suggest that it is compatible with a transitional dwarf galaxy.
Comment favoriser l’engagement dans les tâches pédagogiques du clinicien enseignant de médecine d’urgence ?
Authors: Perrin Céline , Poteaux Nicole
Published: March 2020

Contexte : La naissance récente de la médecine d’urgence comme spécialité place le clinicien enseignant de médecine d’urgence au centre des enjeux de l’enseignement clinique de sa spécialité. Une formation aux compétences requises par cet enseignement pourrait ne pas suffire s’il ne rencontre pas les conditions d’engagement dans les tâches pédagogiques sur le terrain. But : Identifier les leviers et les freins de l’engagement dans les tâches pédagogiques du clinicien enseignant de médecine d’urgence, selon le modèle « exigences-ressources » de l’engagement. Méthodes : Douze cliniciens enseignants du Département Hospitalo-Universitaire de Médecine d’Urgence du Centre Hospitalier Universitaire de Nice ont participé à un entretien en re-situ subjectif suivant l’enregistrement vidéo en perspective subjective d’un dispositif pédagogique en milieu clinique. Les verbatims obtenus par la retranscription des entretiens ont été analysés selon une approche interprétative et confrontés à une grille d’analyse thématique. Résultats : L’analyse des entretiens a permis de caractériser l’activité pédagogique mise en œuvre et d’identifier cinq ressources qui la soutiennent, et cinq exigences qui lui font obstacle et peuvent conduire à son abandon pur et simple. Elle a aussi porté l’emphase sur l’intérêt pédagogique de la méthode de recueil, génératrice de rétro-action équilibrée et centrée sur le clinicien enseignant. Conclusion : Favoriser l’engagement dans les tâches pédagogiques nécessite d’identifier des axes d’action prioritaires et réalisables. L’entretien en re situ subjectif, en permettant l’analyse du point de vue du clinicien enseignant pendant l’activité pédagogique, serait un moyen d’approcher cet objectif.
Étude des connaissances, des attitudes et des pratiques des enseignants à la Faculté de médecine et de pharmacie de Marrakech en vue de l’implantation de l’approche par compétences
Authors: Sebbani Majda , Adarmouch Latifa , Amine Mohamed , Bouskraoui Mohamed
Published: March 2020

Contexte :La formation médicale basée sur une approche de développement des compétences est un impératif au Maroc à l’ère de la réforme des études médicales et de l’accréditation des facultés de médecine. L’implication et l’engagement des enseignants sont indispensables pour la réussite de l’implantation du changement de paradigme.But :Explorer les connaissances, les attitudes et les pratiques des enseignants et recueillir leurs besoins afin de formuler des recommandations à l’égard de l’adoption de l’approche par compétences (APC).Méthodes :Une étude quantitative a été menée auprès des enseignants de la Faculté de médecine et de pharmacie de Marrakech puis complétée par une enquête qualitative par entretiens au cours de l’année 2018. Les données ont été collectées par questionnaire anonyme informatisé auto administré. Les entretiens ont été conduits à l’aide d’un guide d’entretien, enregistrés et retranscrits. Les données quantitatives ont été analysées de manière descriptive à l’aide du logiciel SPSS.Résultats :Au total, 69 enseignants ont participé à l’étude quantitative et 6 entretiens ont été menés. Près de 12 % des répondants n’avaient pas entendu parler de l’approche par compétences auparavant. Les méthodes d’enseignement adoptées en pratique par les répondants étaient en majorité influencées par l’approche par objectifs (78,3 %) et les connaissances à propos de l’APC étaient seulement basiques. Toutefois, la majorité a exprimé sa réceptivité au changement de l’enseignement en adoptant l’APC, tout en réclamant la nécessité d’une formation homogène et continue ainsi qu’une implantation progressive appuyée par l’encouragement institutionnel.Conclusion :Les résultats nous permettent de conclure que les facteurs prédisposant à la réussite de l’implantation de l’approche par compétences sont présents tout en mettant en évidence les leviers d’actions pour une meilleure transition.
Cognitive-Communication Interventions for Youth with Traumatic Brain Injury
Authors: Laane Sarah A. , Cook Lori G.
Published: March 2020

Traumatic brain injuries (TBIs) are relatively common in the pediatric population, yielding several potential challenges across a wide range of skills and abilities. Cognitive-communication disorders are particularly prevalent, with implications for long-term academic and social outcomes. While considerable evidence exists for identifying and characterizing the effects of cognitive-communication deficits, evidence informing effective interventions is still emerging. This review includes discussion of individual factors that affect treatment needs and outcomes as well as evidence that supports cognitive-communication intervention approaches at both a fundamental/discrete and integrated level. Also addressed is the need for modifying contextual factors that may be barriers as well as augmenting facilitators of successful communication and participation, including collaboration with everyday communication partners and identification and use of appropriate accommodations. Overall, research suggests a growing trend toward interventions that are individualized, dynamic, and combine multiple approaches for cognitive-communication treatment after pediatric TBI.
Higher-rank zeta functions and
SL

n

-zeta functions for curves
Authors: Weng Lin , Zagier Don
Published: March 2020

Significance

Almost 100 years ago, Artin defined an analog of the famous Riemann zeta function for curves (one-dimensional varieties) over a finite field. In 2005, L.W. defined two different series of “higher zeta functions” for curves over finite fields that both generalized Artin’s zeta functions, one being defined geometrically and the other using advanced concepts from group representation theory, and conjectured that they always coincide. In this paper this conjecture is proved by giving a formula for one of the two series and showing that it agrees with the formula for the other series proved a few years ago by Sergey Mozgovoy and Markus Reineke.
Imaginal dialogue as a method of narrative inquiry
Authors: Fang Nini
Published: March 2020

This paper joins the discussions on imaginal dialogue with references to the relational turn in psychoanalysis. It explores imaginal dialogue as a creative, relational endeavour in evoking the unconscious materials. By describing my own imaginal dialogue with Virginia Woolf, it exemplifies the potentiality of reading as an embodied, co-constructed interplay between the reader and the text. The deepening of relational and dialogical engagement with the text not only stirs the affective depth in the reader, but also brings the reader to conjure the presence of the author as an object for relatedness in the process of narrative inquiry. Imaginal dialogue transgresses beyond the poststructuralist allowance of interpretive pluralism to relational processes ofworking withthe encounters with the presence of the author as their imaginary co-inquirer. Imaginal dialogue, I argue, not only provides an alternative kind of narrative framing, but the imaginal relationship becomes the very locus of knowledge creation.
Storying the heartbreak
Authors: Harake Nicole R. , Dunlop William L.
Published: March 2020

We examined narratives of romantic breakups (i.e., breakup accounts) in relation to romantic attachment tendencies. In Study 1, participants provided accounts of difficult breakups and indicated who in the relationship initiated its dissolution. In Study 2, participants provided breakup accounts from the perspective of the initiator and the non-initiator. Breakup accounts were coded for levels of exploration (active reflection of the narrated experience) and resolution (emotional closure and a sense of resiliency). Across studies, levels of resolution were highest in self-initiated, when compared to other-initiated, breakup accounts. In Study 2, avoidant attachment correlated negatively with levels of resolution in self-initiated, but not other-initiated, breakup accounts. These results suggest that avoidantly attached individuals narrate self-initiated breakups in a less thoroughly processed manner than their secure peers, and that these differences in transformational processing may carry implications for romantic domain functioning.
Historians and Native American and Indigenous Studies: A Reply
Authors: Silverman David J.
Published: March 2020

David Silverman offers a critical appraisal of two prizewinning works in Native American and Indigenous studies (NAIS), Our Beloved Kin: A New History of King Philip’s War, by Lisa Brooks, and Memory Lands: King Philip’s War and the Place of Violence in the Northeast, by Christine M. DeLucia. Silverman’s review treats the methodology associated with NAIS with some skepticism, offering the opportunity for a lively discussion about the merits and perils of community-engaged history scholarship. Four scholars of Native American history, including DeLucia, respond, defending new approaches to Indigenous history represented by these recent works.
Recognition and the Other in Social Work
Authors: Niemi Petteri
Published: March 2020

Axel Honneth’s recognition theory is a useful ethical framework for social work. Stephen Webb connects it straightforwardly with the relativistic ethical tradition that arguably emphasises the role of differences too much. However, this article shows that an alternative objectivist reading of recognition theory evades Webb’s critique and describes a balanced attitude towards otherness, fitting the practical field of social work. A detailed picture of recognition theory also reveals how it can be utilised in macro-level social critique. Contrary to what Webb claims, it is important that social workers generally respect differences in their work. Unfortunately, every attempt to understand a client inevitably also involves the risk of misunderstanding that might harm the client. This cannot be avoided because helping typically requires understanding. Fortunately, recognitive attitudes and work practices help to minimise risks of that kind. Finally, we have to acknowledge that there are differences that we cannot tolerate, like physical violence against children in the form of physical discipline.
A Comparative Study on the Clinical Features of Coronavirus 2019 (COVID-19) Pneumonia With Other Pneumonias
Authors: Zhao Dahai , Yao Feifei , Wang Lijie , Zheng Ling , Gao Yongjun , Ye Jun , Guo Feng , Zhao Hui , Gao Rongbao
Published: March 2020

Background

A novel coronavirus (COVID-19) has raised world concern since it emerged in Wuhan, China in December 2019. The infection may result in severe pneumonia with clusters of illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias.

Methods

Nineteen COVID-19 and 15 other patients with pneumonia (non-COVID-19) in areas outside of Hubei were involved in this study. Both COVID-19 and non-COVID-19 patients were confirmed to be infected using throat swabs and/or sputa with/without COVID-2019 by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the differences between COVID-19 and non-COVID-19.

Results

All patients had a history of exposure to confirmed cases of COVID-19 or travel to Hubei before illness. The median (IQR) duration was 8 (6–11) and 5 (4–11) days from exposure to onset in COVID-19 and non-COVID-19 cases, respectively. The clinical symptoms were similar between COVID-19 and non-COVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) COVID-19 but 4 (26.67%) non-COVID-19 patients had bilateral involvement while 17 COVID-19 patients (89.47%) but 1 non-COVID-19 patient (6.67%) had multiple mottling and ground-glass opacity on chest CT images. Compared with non-COVID-19, COVID-19 presents remarkably more abnormal laboratory tests, including AST, ALT, γ-GT, LDH, and α-HBDH.

Conclusions

The COVID-19 infection has onsets similar to other pneumonias. CT scan may be a reliable test for screening COVID-19 cases. Liver function damage is more frequent in COVID-19 than non-COVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of COVID-19.
Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory
Authors: Chen Zongwei , Zhu Shaoyuan , Kindig Kayla , Wang Shengxuan , Chou Shih-Wei , Davis Robin Woods , Dercoli Michael R , Weaver Hannah , Stepanyan Ruben , McDermott Brian M
Published: March 2020

Perception of sound is initiated by mechanically gated ion channels at the tips of stereocilia. Mature mammalian auditory hair cells require transmembrane channel-like 1 (TMC1) for mechanotransduction, and mutations of the cognate genetic sequences result in dominant or recessive heritable deafness forms in humans and mice. In contrast, zebrafish lateral line hair cells, which detect water motion, require Tmc2a and Tmc2b. Here, we use standard and multiplex genome editing in conjunction with functional and behavioral assays to determine the reliance of zebrafish hearing and vestibular organs on Tmc proteins. Surprisingly, our approach using multiple mutant alleles demonstrates that hearing in zebrafish is not dependent on Tmc1, nor is it fully dependent on Tmc2a and Tmc2b. Hearing however is absent in triple-mutant zebrafish that lack Tmc1, Tmc2a and Tmc2b. These outcomes reveal a striking resemblance of Tmc protein reliance in the vestibular sensory epithelia of mammals to the maculae of zebrafish. Moreover, our findings disclose a logic of Tmc use where hearing depends on a complement of Tmc proteins beyond those employed to sense water motion.
Different bottom trawl fisheries have a differential impact on the status of the North Sea seafloor habitats
Authors: Rijnsdorp A D , Hiddink J G , van Denderen P D , Hintzen N T , Eigaard O R , Valanko S , Bastardie F , Bolam S G , Boulcott P , Egekvist J , Garcia C , van Hoey G , Jonsson P , Laffargue P , Nielsen J R , Piet G J , Sköld M , van Kooten T
Published: March 2020

Fisheries using bottom trawls are the most widespread source of anthropogenic physical disturbance to seafloor habitats. To mitigate such disturbances, the development of fisheries-, conservation-, and ecosystem-based management strategies requires the assessment of the impact of bottom trawling on the state of benthic biota. We explore a quantitative and mechanistic framework to assess trawling impact. Pressure and impact indicators that provide a continuous pressure–response curve are estimated at a spatial resolution of 1 × 1 min latitude and longitude (∼2 km2) using three methods: L1 estimates the proportion of the community with a life span exceeding the time interval between trawling events; L2 estimates the decrease in median longevity in response to trawling; and population dynamic (PD) estimates the decrease in biomass in response to trawling and the recovery time. Although impact scores are correlated, PD has the best performance over a broad range of trawling intensities. Using the framework in a trawling impact assessment of ten métiers in the North Sea shows that muddy habitats are impacted the most and coarse habitats are impacted the least. Otter trawling for crustaceans has the highest impact, followed by otter trawling for demersal fish and beam trawling for flatfish and flyshooting. Beam trawling for brown shrimps, otter trawling for industrial fish, and dredging for molluscs have the lowest impact. Trawling is highly aggregated in core fishing grounds where the status of the seafloor is low but the catch per unit of effort (CPUE) per unit of impact is high, in contrast to peripheral grounds, where CPUE per unit of impact is low.
Patient characteristics associated with objective measures of digital health tool use in the United States: A literature review
Authors: Nouri Sarah S , Adler-Milstein Julia , Thao Crishyashi , Acharya Prasad , Barr-Walker Jill , Sarkar Urmimala , Lyles Courtney
Published: March 2020

Objective

The study sought to determine which patient characteristics are associated with the use of patient-facing digital health tools in the United States.

Materials and Methods

We conducted a literature review of studies of patient-facing digital health tools that objectively evaluated use (eg, system/platform data representing frequency of use) by patient characteristics (eg, age, race or ethnicity, income, digital literacy). We included any type of patient-facing digital health tool except patient portals. We reran results using the subset of studies identified as having robust methodology to detect differences in patient characteristics.

Results

We included 29 studies; 13 had robust methodology. Most studies examined smartphone apps and text messaging programs for chronic disease management and evaluated only 1-3 patient characteristics, primarily age and gender. Overall, the majority of studies found no association between patient characteristics and use. Among the subset with robust methodology, white race and poor health status appeared to be associated with higher use.

Discussion

Given the substantial investment in digital health tools, it is surprising how little is known about the types of patients who use them. Strategies that engage diverse populations in digital health tool use appear to be needed.

Conclusion

Few studies evaluate objective measures of digital health tool use by patient characteristics, and those that do include a narrow range of characteristics. Evidence suggests that resources and need drive use.
GenomegaMap: Within-Species Genome-Wide dN/dS Estimation from over 10,000 Genomes
Authors: Wilson Daniel J ,   The CRyPTIC Consortium, Crook Derrick W , Peto Timothy E A , Walker A Sarah , Hoosdally Sarah J , Gibertoni Cruz Ana L , Carter Joshua , Grazian Clara , Earle Sarah G , Kouchaki Samaneh , Lachapelle Alexander , Yang Yang , Clifton David A , Fowler Philip W , Iqbal Zamin , Hunt Martin , Knaggs Jeffrey , Smith E Grace , Rathod Priti , Jarrett Lisa , Matias Daniela , Cirillo Daniela M , Borroni Emanuele , Battaglia Simone , Ghodousi Arash , Spitaleri Andrea , Cabibbe Andrea , Tahseen Sabira , Nilgiriwala Kayzad , Shah Sanchi , Rodrigues Camilla , Kambli Priti , Surve Utkarsha , Khot Rukhsar , Niemann Stefan , Kohl Thomas A , Merker Matthias , Hoffmann Harald , Todt Katharina , Plesnik Sara , Ismail Nazir , Omar Shaheed Vally , Joseph Lavania , Thwaites Guy , Thuong Thuong Nguyen Thuy , Ngoc Nhung Hoang , Srinivasan Vijay , Walker Timothy M , Moore David , Coronel Jorge , Solano Walter , Gao George F , He Guangxue , Zhao Yanlin , Liu Chunfa , Ma Aijing , Zhu Baoli , Laurenson Ian , Claxton Pauline , Koch Anastasia , Wilkinson Robert , Lalvani Ajit , Posey James , Gardy Jennifer , Werngren Jim , Paton Nicholas , Jou Ruwen , Wu Mei-Hua , Lin Wan-Hsuan , Ferrazoli Lucilaine , de Oliveira Rosangela Siqueira , Arandjelovic Irena , Chaiprasert Angkana , Comas Iñaki , Roig Calle Jaime , Drobniewski Francis A , Farhat Maha R , Gao Qian , Hee Rick Ong Twee , Sintchenko Vitali , Supply Philip , van Soolingen Dick
Published: March 2020

The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap’s simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species.
Abnormal Cullin1 neddylation-mediated p21 accumulation participates in the pathogenesis of recurrent spontaneous abortion by regulating trophoblast cell proliferation and differentiation
Authors: Sun Xiaohe , Tong Xiaomei , Hao Yanqing , Li Chao , Zhang Yinli , Pan Yibin , Dai Yongdong , Liu Liu , Zhang Tai , Zhang Songying
Published: March 2020

The study explores the role of neddylation in early trophoblast development and its alteration during the pathogenesis of recurrent spontaneous abortion (RSA). Immunofluorescence and western blot were conducted to evaluate the expression pattern of NEDD8 protein in the first-trimester placentas of healthy control and RSA patients. Neddylated-cullins, especially neddylated-cullin1, were downregulated and their substrate, p21, was accumulated in RSA samples. NEDD8 cytoplasmic recruitment was observed in extravillous trophoblast (EVT) progenitors of RSA placentas. Consistent with the results of clinical samples, neddylation inhibition using MLN4924 in trophoblast cell lines caused obvious p21 accumulation and free NEDD8 cytoplasmic recruitment. Further in vitro study demonstrated neddylation inhibition attenuated proliferation of Jeg-3 cells via p21 accumulation. Moreover, when trophoblast stem (TS) cells derived from first-trimester placentas were cultured for differentiation analyses. MLN4924 impaired the differentiation of TS cells towards EVTs by downregulating HLA-G and GATA3. p21 knockdown could partly rescue MLN4924-suppressed HLA-G and GATA3 expression. In conclusion, cullin1 neddylation-mediated p21 degradation is required for trophoblast proliferation and can affect trophoblast plasticity by affecting HLA-G and GATA3 expression. The results provide insights into the pathological mechanism of RSA and the biological regulation of trophoblast development.
SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics
Authors: Cabello-Aguilar Simon , Alame Mélissa , Kon-Sun-Tack Fabien , Fau Caroline , Lacroix Matthieu , Colinge Jacques
Published: March 2020

Single-cell transcriptomics offers unprecedented opportunities to infer the ligand–receptor (LR) interactions underlying cellular networks. We introduce a new, curated LR database and a novel regularized score to perform such inferences. For the first time, we try to assess the confidence in predicted LR interactions and show that our regularized score outperforms other scoring schemes while controlling false positives. SingleCellSignalR is implemented as an open-access R package accessible to entry-level users and available from https://github.com/SCA-IRCM. Analysis results come in a variety of tabular and graphical formats. For instance, we provide a unique network view integrating all the intercellular interactions, and a function relating receptors to expressed intracellular pathways. A detailed comparison of related tools is conducted. Among various examples, we demonstrate SingleCellSignalR on mouse epidermis data and discover an oriented communication structure from external to basal layers.
Timing of organ initiation is crucial for robust organ size
Authors: Zhu Mingyuan , Chen Weiwei , Mirabet Vincent , Hong Lilan , Bovio Simone , Strauss Soeren , Schwarz Erich M. , Tsugawa Satoru , Wang Zhou , Smith Richard S. , Li Chun-Biu , Hamant Olivier , Boudaoud Arezki , Roeder Adrienne H. K.
Published: March 2020

Organs precisely regulate their size and shape to ensure proper function1–6. The contribution of organ initiation timing to final organ size and shape is often masked by compensatory adjustments to growth later in development7–9. Here we show that DEVELOPMENT RELATED MYB-LIKE1 (DRMY1) is required for both proper organ initiation timing and growth leading to robust sepal size inArabidopsis.Within eachdrmy1flower, the initiation of some sepals is variably delayed. Late-initiating sepals indrmy1mutants remain smaller throughout development resulting in variability in sepal size. DRMY1 focuses the spatiotemporal signaling patterns of the plant hormones auxin and cytokinin, which jointly control the timing of sepal initiation. Contrary to expectation, our findings demonstrate that timing of organ initiation contributes to robust organ size throughout development.
Mathematically Modeling Inflammation as a Promoter of Tumour Growth
Authors: Wilkie Kathleen P. , Aktar Farjana
Published: March 2020

Inflammation is now known to play a significant role in tumour growth and progression. It is also difficult to adequately quantify systemic inflammation and the resulting localized effects in cancer. Here we use experimental data to infer the possible contributions of inflammation in a mouse model of cancer. The model is validated by predicting tumour growth under anti-inflammatory treatments, and combination cancer therapies are explored. We then extend the model to consider simultaneous tumour implants at two distinct sites, which experimentally was shown to result in one large and one small tumour. We use this model to examine the role inflammation may play in the growth rate separation. Finally, we use this predictive two-tumour model to explore implications of inflammation on metastases, surgical removal of the primary, and adjuvant anti-inflammatory treatments. This work suggests that improved tumour control can be obtained by targeting both the cancer and host, through anti-inflammatory treatments, including reduced metastatic burden post-surgical removal of primary tumours.
Massive rhizobial genomic variations associated with partner quality inLotus–Mesorhizobiumsymbiosis
Authors: Bamba Masaru , Aoki Seishiro , Kajita Tadashi , Setoguchi Hiroaki , Watano Yasuyuki , Sato Shusei , Tsuchimatsu Takashi
Published: March 2020

In diverse mutualistic relationships, genetic variations in impact on the growth of interacting partners—variations in partner quality—are common, despite the theoretical prediction that selection favoring high-quality partners should eliminate such variations. Here, we investigated how variations in partner quality could be maintained in the nitrogen-fixing mutualism betweenLotus japonicusandMesorhizobiumbacteria. We reconstructedde novoassembled full-genome sequences from nine rhizobial symbionts, finding massive variations in the core genome and the contrastingly similar symbiotic islands, indicating recent horizontal gene transfer (HGT) of the symbiosis islands into diverseMesorhizobiumlineages. A cross-inoculation experiment using nine sequenced rhizobial symbionts and 15L. japonicusaccessions revealed extensive quality variations represented by plant growth phenotypes, including genotype-by-genotype interactions. Quality variations were not associated with the presence/absence variations of known symbiosis-related genes in the symbiosis island, but rather, showed significant correlations with the core genome variations, supported by SNP- and kinship matrix-based association analyses. These findings highlight the novel role of HGT of symbiosis islands, which indirectly supply mutations of core genomes intoL. japonicus-associated bacteria, thereby contributing to the maintenance of variations in partner quality.
Identification of Conserved Evolutionary Trajectories in Tumors
Authors: Hodzic Ermin , Shrestha Raunak , Malikic Salem , Collins Colin C. , Litchfield Kevin , Turajlic Samra , Sahinalp S. Cenk
Published: March 2020

Motivation

As multi-region, time-series, and single cell sequencing data become more widely available, it is becoming clear that certain tumors share evolutionary characteristics with others. In the last few years, several computational methods have been developed with the goal of inferring the subclonal composition and evolutionary history of tumors from tumor biopsy sequencing data. However, the phylogenetic trees that they report differ significantly between tumors (even those with similar characteristics).

Results

In this paper, we present a novel combinatorial optimization method, CONETT, for detection of recurrent tumor evolution trajectories. Our method constructs a consensus tree of conserved evolutionary trajectories based on the information about temporal order of alteration events in a set of tumors. We apply our method to previously published datasets of 100 clear-cell renal cell carcinoma and 99 non-small-cell lung cancer patients and identify both conserved trajectories that were reported in the original studies, as well as new trajectories.

Availability

CONETT is implemented in C++ and available athttps://github.com/ehodzic/CONETT.
Systemic mutational rescue inEscherichia colielicited by a valency dependent, high affinity protein DNA interaction
Authors: Hurd P.J. , Al-Swailem A. M. , Bin Dukhyil A.A.A. , Sheikh Q.I. , Al-Ghanim A. A. , Alfageih L. , Matin M. , Lu Yueh Ting , Abdalgelel A. , Florence J. , Al-Shemirti Mohammed , Al Harbi S. , Brown P.E. , Hornby D.P.
Published: March 2020

The controlled formation of sequence specific DNA protein complexes is a fundamental feature of most genetic transactions. Studies of the impact of point mutations on the function of individual components, such as repressors, remains a key aspect of many Systems and Synthetic Biology research programmes. One of the most dramatic systemic consequences of a point mutation is exhibited by the monomeric DNA methyltransferases M.HhaI and M.EcoRII, where substitution of a single, catalytic cysteine by either glycine or alanine, creates a lethal gain of function phenotype.

In vivoexpression of these point mutants promotes the deposition of high affinity nucleoprotein complexes that arrest replicationin vivo, causing cell death. Interestingly, it appears that a systemic response to expression of these mutant enzymes is dramatically enhanced when they are expressed as synthetic dimers. A previously unreported form of “mutational rescue” appears to be triggered as a result of networked crosslinking of host cell DNA resulting from an increased valency of nucleoprotein complex formation. This finding may have significance for developing molecular interventions for the controlled regulation of genome function and for the development of novel antimicrobial and anticancer strategies.
Prion Protein Folding Mechanism Revealed by Pulling Force Studies
Authors: Kriegler Theresa , Lang Sven , Notari Luigi , Hessa Tara
Published: March 2020

The mammalian prion protein (PrP) engages with the ribosome-Sec61 translocation channel complex to generate different topological variants that are either physiological, or involved in neurodegenerative diseases. Here, we describe cotranslational folding and translocation mechanisms of PrP coupled to a Xbp1-based arrest peptide (AP) as folding sensor, to measure forces acting on PrP nascent chain. Our data reveal two main pulling events followed by a minor third one exerted on the nascent chains during their translocation.

Using those force landscapes, we show that a specific sequence within an intrinsically disordered region, containing a polybasic and glycine-proline rich residues, modulates the second pulling event by interacting with TRAP complex. This work also delineates the sequence of events involved in generation of PrP toxic transmembrane topologies during its synthesis. Our results shed new insight into the folding of such topological complex protein, where marginal pulling by the signal sequence, together with the downstream sequence in the mature domain, primarily drives an overall inefficient translocation resulting in the nascent chain to adopt other topologies.
A Systematic Protein Turnover Map for Decoding Protein Degradation
Authors: Christiano R. , Kabatnik S. , Mejhert N. , Farese R.V. , Walther T.C.
Published: March 2020

Protein degradation is mediated by an expansive and complex network of protein modification and degradation enzymes. Matching degradation enzymes with their targets and determining globally which proteins are degraded by the proteasome or lysosome/vacuole has been a major challenge. Further, an integrated view of protein degradation for cellular pathways has been lacking. Here we present a novel analytical platform that combines systematic gene deletions with quantitative measures of protein turnover to deconvolve protein degradation pathways forS. cerevisiae. The resulting turnover map (T-MAP) reveals target candidates of nearly all E2 and E3 ubiquitin ligases and identifies the primary degradation routes for most proteins. We further mined this T-MAP to identify new substrates of ER-associated Degradation (ERAD) involved in sterol biosynthesis and to uncover novel regulatory nodes for sphingolipid biosynthesis. The T-MAP approach should be broadly applicable to the study of other cellular processes and systems, including mammalian systems.

One Sentence Summary

A systematic, global map of protein turnover for a large set of yeast mutants reveals scope and specificity of degradation pathways and identifies novel regulatory nodes for lipid metabolism.
Spontaneous Cell Fusions as a Mechanism of Parasexual Recombination in Tumor Cell Populations
Authors: Miroshnychenko Daria , Baratchart Etienne , Ferrall-Fairbanks Meghan C. , Vander Velde Robert , Laurie Mark A , Bui Marilyn M. , Tan Aik Choon , Altrock Philipp M. , Basanta David , Marusyk Andriy
Published: March 2020

Initiation and progression of cancers reflect the underlying process of somatic evolution, which follows a Darwinian logic,i.e., diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination – a key diversification mechanism throughout all strata of life. Based on observations of spontaneous fusions involving cancer cells, reported genetic instability of polypoid cells, and precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions could serve as a source of parasexual recombination in cancer cell populations. Using differentially labelled tumor cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer bothin vitroandin vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modeling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumor cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape, relative to strictly asexual populations, which may substantially accelerate a tumor’s ability to adapt to new selective pressures.
Information outreach interventions to promote the information access, use and exchange in the rural areas of Pakistan
Authors: Naeem Salman Bin , Bhatti Rubina , Ahmad Khurshid
Published: March 2020

Purpose

This study is a part of the doctoral dissertation that proposes concrete measures to improve health-care information outreach program for rural health-care professionals in primary and secondary health care in Punjab, Pakistan. This study aims to report on the barriers to accessing and using online health-care information from rural settings of the Punjab province of Pakistan.

Design/methodology/approach

A cross-sectional survey was conducted in primary and secondary health-care settings in the Punjab province of Pakistan. The study’s population consisted of the rural primary care physicians (PCPs), who were geographically dispersed across 2,873 different remote health-care settings across Punjab. These practice settings included 2,455 basic health units, 293 rural health centers, 89 tehsil headquarter hospitals and 36 district headquarter hospitals.

Findings

Limited internet access, non-availability of required equipment and lack of training facilities were identified as the main barriers. PCPs’ gender, previous enrollment in post-graduation programs and type of health-care facility were significant factors in the perceived barriers related to both “non-availability of required equipment” and “inadequate training facilities on the use of information resources”.

Practical implications

The findings of the study hold some important practical implications for different stakeholders. This study identifies and addresses the barriers to accessing and using health-care information for PCPs in rural settings. The success of the health-care information outreach program in Punjab, Pakistan, should rely on the eradication of these barriers.

Originality/value

To the best of the authors’ knowledge, this is the first large-scale study in Pakistan that assesses the barriers and proposes ways to overcome these barriers to effectively access and use health-care information.
On the asymmetric response of the exchange rate to shocks in the crude oil market
Authors: Alqaralleh Huthaifa
Published: March 2020

Purpose

This paper aims to investigate the nonlinear dynamics in the effects of oil price shocks on the exchange rate for a sample from the Group of Twenty (G20) over the period 1994:1-2019:1.

Design/methodology/approach

Using monthly time series data covering the period1994:1-2019:1, the author first use the non-parametric triples test of Randles et al. (1980) to ascertain the existence of asymmetric properties in the sample of exchange rates. Then the author used the nonlinear ARDL cointegration approach developed by Shin et al. (2014) to examine the reaction of these exchange rates to the oil price shocks.

Findings

This study has identified significant evidence that the exchange rate is asymmetrically distributed, with the effect that high appreciation of the exchange rate is followed by slower depreciation. The NARDL results support such asymmetry even more strongly because in the test the exchange rate is shown to react differently in the long term to positive and negative shocks in oil prices. Another major finding was that the speed of adjustment differed over the sample, as the cumulative dynamic multipliers effect highlighted.

Research limitations/implications

This change in direction and the employment of non-linear technique can be to obtain better insight into the model specification, which the author believes, will not only enhance the findings in the literature but also enhance forecasting and decision-making.

Practical implications

A practical implication of this change is the possibility that policymakers and participants concerned with exchange rate stability should intervene in the market to alleviate the unfavourable impact of oil price shocks on the exchange rate.

Originality/value

Addressing this nonlinear dynamic in the effects of oil price shocks on the exchange rate have at least the following two important reasons: asymmetry and regime change are types of nonlinearities that affect the market dynamics, especially, over marked sample period with such financial crises as the global financial crises of 2007, thereby violating the linear models. Adopting an asymmetric cointegration technique permits to incorporate cointegrated positive and negative components of the considered series.