bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structurally conserved TELR region on shelterin protein TPP1 is essential for telomerase processivity but not recruitment
Authors: Sandhu Ranjodh , Sharma Madhav , Wei Derek , Xu Lifeng 
Published: December 2020

AbstractIn addition to mediating telomerase recruitment, shelterin protein TPP1 also stimulates telomerase processivity. Assessing thein vivosignificance of the latter role of TPP1 has been difficult, as TPP1 mutations that perturb telomerase function tend to abolish both telomerase recruitment and processivity. We sought to separate the two activities of TPP1 in regulating telomerase by considering a structure-guided mutagenesis study on theS. cerevisiaetelomerase-associated Est3 protein, which revealed a TELR surface region on Est3 that regulates telomerase functionviaan unknown mechanism without affecting the interaction between Est3 and telomerase (1). Here, we show that mutations within the structurally conserved TELR region on TPP1 impaired telomerase processivity while leaving telomerase recruitment unperturbed, hence uncoupling the two roles of TPP1 in regulating telomerase. Telomeres in cell lines containing homozygous TELR mutations progressively shortened to a critical length that caused cellular senescence, despite the presence of abundant telomerase in these cells. Our findings not only demonstrate that telomerase processivity can be regulated by TPP1, in a process separable from its role in recruiting telomerase to telomeres, but also establish that thein vivostimulation of telomerase processivity by TPP1 is critical for telomere length homeostasis and long-term cell viability.SignificanceTelomerase directs the synthesis of new telomeric repeats at chromosome ends, enabling cells to overcome the end replication problem and continue to divide. The shelterin protein TPP1 interacts with telomerase, promoting both telomerase recruitment and processivity (the addition of multiple telomeric repeats after a single substrate binding event). Here we show the identification of separation-of-function mutants of TPP1 that eliminate telomerase processivity but leave the telomerase recruitment function intact. When introduced into human cells in a homozygous manner, these mutations can induce critical telomere shortening and cellular senescence. Our observations therefore provide the first demonstration that telomerase processivity, in addition to telomerase recruitment, is a key regulatory stepin vivofor continued human cell proliferation.
Heterogeneity of monocyte subsets and susceptibility to influenza virus contribute to inter-population variability of protective immunity
Authors: O’Neill Mary , Quach Hélène , Pothlichet Julien , Aquino Yann , Bisiaux Aurélie , Zidane Nora , Deschamps Matthieu , Libri Valentina , Hasan Milena , Zhang Shen-Ying , Zhang Qian , Matuozzo Daniela , Cobat Aurélie , Abel Laurent , Casanova Jean-Laurent , Naffakh Nadia , Rotival Maxime , Quintana-Murci Lluis 
Published: December 2020

AbstractThere is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use anex vivomodel to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. Using single-cell RNA-sequencing, we show widespread inter-individual variability in the percentage of IAV-infected monocytes. We show that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. While this host defense strategy is shared betweenCD16+/CD16-monocytes, we also uncoverCD16+-specific mRNA expression ofIL6andTNFin response to IAV, and a stronger resistance ofCD16+monocytes to IAV infection. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such asIFITM3, MX1, andOAS3. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number ofCD16+monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Collectively, our results reveal the effects of IAV infection on the transcriptional landscape of human monocytes and highlight previously unappreciated differences in cellular susceptibility to IAV infection between individuals of African and European ancestry, which may account for the greater susceptibility of Africans to severe influenza.Significance StatementMonocytes may play a critical role during severe viral infections. Our study tackles how heterogeneity in monocyte subsets and activation contributes to shape individual differences in the transcriptional response to viral infections. Using single-cell RNA-sequencing, we reveal heterogeneity in monocyte susceptibility to IAV infection, both betweenCD16+/CD16-monocytes and across individuals, driven by differences in basal activation of an IRF/STAT-induced antiviral program. Furthermore, we show a decreased ability of IAV to infect and replicate in monocytes from African-ancestry individuals, with possible implications for antigen presentation and lymphocyte activation. These results highlight the importance of early cellular activation in determining an individuals’ innate immune response to viral infection.
Joint species distributions reveal the combined effects of host plants, abiotic factors and species competition as drivers of species abundances in fruit flies
Authors: Facon Benoit , Hafsi Abir , de la Masselière Maud Charlery , Robin Stéphane , Massol François , Dubart Maxime , Chiquet Julien , Frago Enric , Chiroleu Frédéric , Duyck Pierre-François , Ravigné Virginie 
Published: December 2020

AbstractThe relative importance of ecological factors and species interactions for phytophagous insect species distributions has long been a controversial issue. Using field abundances of eight sympatric Tephritid fruit flies on 21 host plants, we inferred flies’ realized niches using joint species distribution modelling and network inference, on the community as a whole and separately on three groups of host plants. These inferences were then confronted to flies’ fundamental niches estimated through laboratory-measured fitnesses on host plants. Species abundances were mainly determined by host plants followed by climatic factors, with a minor role for competition between species sharing host plants. The relative importance of these factors mildly changed when we focused on particular host plant groups. Despite overlapping fundamental niches, specialists and generalists had almost distinct realized niches, with possible competitive exclusion of generalists by specialists on Cucurbitaceae, and different assembly rules: specialists were mainly influenced by their adaptation to host plants while generalist abundances varied regardless of their fundamental host use.
DNA sequence-dependent positioning of the linker histone in a nucleosome: a single-pair FRET study
Authors: De Madhura , Öztürk Mehmet Ali , Isbaner Sebastian , Tóth Katalin , Wade Rebecca C. 
Published: December 2020

AbstractLinker histones (LH) bind to nucleosomes with their globular domain (gH) positioned in either an on- or an off-dyad binding mode. Here, we study the effect of the linker DNA (L-DNA) sequence on the binding of a full-length LH, Xenopus laevis H1.0b, to a Widom 601 nucleosome core particle (NCP) flanked by two 40 bp long L-DNA arms, by single-pair FRET spectroscopy. We varied the sequence of the 11 bp of L-DNA adjoining the NCP on either side, making the sequence either A-tract, purely GC, or mixed, with 64% AT. The labelled gH consistently exhibited higher FRET efficiency with the labelled L-DNA containing the A-tract, than that with the pure-GC stretch, even when the stretches were swapped. However, it did not exhibit higher FRET efficiency with the L-DNA containing 64% AT-rich mixed DNA when compared to the pure-GC stretch. We explain our observations with a model that shows that the gH binds on-dyad and that two arginines mediate recognition of the A-tract via its characteristically narrow minor groove. To investigate whether this on-dyad minor groove-based recognition was distinct from previously identified off-dyad major groove-based recognition, a nucleosome was designed with A-tracts on both the L-DNA arms. One A-tract was complementary to thymine and the other to deoxyuridine. The major groove of the thymine-tract was lined with methyl groups that were absent from the major groove of the deoxyuridine tract. The gH exhibited similar FRET for both these A-tracts, suggesting that it does not interact with the thymine methyl groups exposed on the major groove. Our observations thus complement previous studies that suggest that different LH isoforms may employ different ways of recognizingff AT-rich DNA and A-tracts. This adaptability may enable the LH to universally compact scaffold-associated regions and constitutive heterochromatin, which are rich in such sequences.Statement of SignificanceLinker histones (LHs) associate with the smallest repeat unit of chromatin, the nucleosome. They have been observed to have affinity for AT-rich DNA, which is found in constitutive heterochromatin and scaffold-associated regions (SAR), which could explain how the LHs can compact such parts of the chromatin. How the LH recognizes such sequences is poorly understood. Using single-pair FRET and modelling, we provide experimental evidence of DNA-sequence-induced changes in the orientation of a LH bound to a nucleosome, and thereby reveal a new mechanism by which the LH can recognize A-tract sequences that are abundantly present in the SAR. Our results show that, depending on how the LH associates with the nucleosome, it can employ more than one mechanism to recognize AT-rich DNA.
Pharmacological rescue of impaired mitophagy in Parkinson’s disease-related LRRK2 G2019S knock-in mice
Authors: Singh Francois , Prescott Alan R. , Ball Graeme , Reith Alastair D. , Ganley Ian G. 
Published: December 2020

AbstractParkinson’s disease (PD) is a major and progressive neurodegenerative disorder, yet the biological mechanisms involved in its aetiology are poorly understood. Evidence links this disorder with mitochondrial dysfunction and/or impaired lysosomal degradation – key features of the autophagy of mitochondria, known as mitophagy. Here we investigated the role of LRRK2, a protein kinase frequently mutated in PD, on this process in vivo. Using mitophagy and autophagy reporter mice, bearing either knockout of LRRK2 or expressing the pathogenic kinase-activating G2019S LRRK2 mutation, we found that basal mitophagy was specifically altered in clinically relevant cells and tissues. Our data show that basal mitophagy inversely correlates with LRRK2 kinase activity in vivo. In support of this, use of distinct LRRK2 kinase inhibitors in cells increased basal mitophagy, and a CNS penetrant LRRK2 kinase inhibitor, GSK3357679A, rescued the mitophagy defects observed in LRRK2 G2019S mice. This study provides the first in vivo evidence that pathogenic LRRK2 directly impairs basal mitophagy, a process with strong links to idiopathic Parkinson’s disease, and demonstrates that pharmacological inhibition of LRRK2 is a rational mitophagy-rescue approach and potential PD therapy.
Discovery of Fibrillar Adhesins across Bacterial Species
Authors: Monzon Vivian , Lafita Aleix , Bateman Alex 
Published: December 2020

AbstractBackgroundFibrillar adhesins are long multidomain proteins attached at the cell surface and composed of at least one adhesive domain and multiple tandemly repeated domains, which build an elongated stalk that projects the adhesive domain beyond the bacterial cell surface. They are an important yet understudied class of proteins that mediate interactions of bacteria with their environment. This study aims to characterize fibrillar adhesins in a wide range of bacterial phyla and to identify new fibrillar adhesin-like proteins to improve our understanding of host-bacteria interactions.ResultsBy careful search for fibrillar adhesins in the literature and by computational analysis we identified 75 stalk domains and 24 adhesive domains. Based on the presence of these domains in the UniProt Reference Proteomes database, we identified and analysed 3,388 fibrillar adhesin-like proteins across species of the most common bacterial phyla. We found that the bacterial proteomes with the highest fraction of fibrillar adhesins include several known pathogens. We further enumerate the adhesive and stalk domain combinations found in nature and demonstrate that fibrillar adhesins have complex and variable domain architectures, which differ across species. By analysing the domain architecture of fibrillar adhesins we show that in Gram positive bacteria adhesive domains are mostly positioned at the N-terminus of the protein with the cell surface anchor at the C-terminus, while their positions are more variable in Gram negative bacteria. We provide an open repository of fibrillar adhesin-like proteins and domains to facilitate downstream studies of this class of bacterial surface proteins.ConclusionThis study provides a domain-based characterization of fibrillar adhesins and demonstrates that they are widely found across the main bacterial phyla. We have discovered numerous novel fibrillar adhesins and improved the understanding of how pathogens might adhere to and subsequently invade into host cells.
Oscillatory tracking of pseudo-rhythmic speech is constrained by linguistic predictions
Authors: Oever Sanne Ten , Martin Andrea E. 
Published: December 2020

AbstractNeuronal oscillations putatively track speech in order to optimize sensory processing. However, it is unclear how isochronous brain oscillations can track pseudo-rhythmic speech input. Here we propose that oscillations can track pseudo-rhythmic speech when considering that speech time is dependent on predictions flowing from internal language models. We show that the temporal dynamics of speech are dependent on the predictability of words in a sentence. A computational model including oscillations, feedback, and inhibition is able to track the natural pseudo-rhythmic speech input. As the model processes, it generates temporal phase codes, which are a candidate mechanism for carrying information forward in time. The model is optimally sensitive to the natural temporal speech dynamics and can explain empirical data on temporal speech illusions. Our results reveal that speech tracking does not only rely on the input acoustics but instead entails an interaction between oscillations and constraints flowing from internal language models.
Acculturation stressors and academic adjustment among Nepalese students in South Korean higher education institutions
Authors: Atteraya Madhu S. 
Published: December 2020

AbstractIntroductionInternational students are steadily increasing in South Korean higher education institutions. How well international students in South Korea are adjusted academically and the relationship between acculturation stressors and academic adjustment has not yet been determined. The study aimed to fill this research gap by examining the relationship between acculturation stressors and academic adjustment among Nepalese international students in South Korean higher education institutions.MethodsThe sample of the study consisted of Nepalese international students who enrolled in 36 universities in South Korea. Students’ background characteristics and acculturation stressors (e.g., discrimination, homesickness, hate/rejection, fear, cultural shock, and guilt) were selected to assess the association of these characteristics and stressors with academic adjustment. Pearson correlation and hierarchical multiple regression were utilized to examine the association between acculturation stressors and academic adjustment.ResultsThe results from the Pearson correlation revealed the negative correlation of perceived discrimination (r = -.23, p< 0.01), perceived hate/rejection (r = -.18, p< 0.05), perceived fear (r = -.24, p< 0.01), and perceived cultural shock (r = -.17, p< 0.05) with academic adjustment. Further, the hierarchical regression model revealed that marital status (β= .223,p <.01) had a positive association with academic adjustment, whereas perceived fear (β= -.206,p <.05) had a negative association with academic adjustment even after including students’ background characteristics and other acculturation stressors.ConclusionAddressing acculturation stressors among international students in higher education institutions is essential to facilitate positive academic adjustment. Mainly, perceived fear has negatively affected students’ academic adjustment. Based on these findings, tailored programs must be developed to curtail students’ perceived fear in order to enhance their academic performance in South Korean higher education institutions.
Rapid evolution of bacterial mutualism in the plant rhizosphere
Authors: Li Erqin , de Jonge Ronnie , Liu Chen , Jiang Henan , Friman Ville-Petri , Pieterse Corné M.J. , Bakker Peter A.H.M. , Jousset Alexandre 
Published: December 2020

SummaryEven though beneficial plant-microbe interactions are commonly observed in nature, direct evidence for the evolution of bacterial mutualism in the rhizosphere remains elusive. Here we use experimental evolution to causally show that initially plant-antagonisticPseudomonas protegensbacterium evolves into mutualists in the rhizosphere ofArabidopsis thalianawithin six plant growth cycles (6 months). This evolutionary transition was accompanied with increased mutualist fitness via two mechanisms:i)improved competitiveness for root exudates andii)enhanced capacity for activating the root-specific transcription factor geneMYB72, which triggers the production of plant-secreted scopoletin antimicrobial for which the mutualists evolved relatively higher tolerance to. Genetically, mutualism was predominantly associated with different mutations in the GacS/GacA two-component regulator system, which conferred high fitness benefits only in the presence of plants. Together, our results show that bacteria can rapidly evolve along the parasitism-mutualism continuum in the plant rhizosphere at an agriculturally relevant evolutionary timescale.
Pre-Implantation Alcohol Exposure Induces Lasting Sex-Specific DNA Methylation Programming Errors in the Developing Forebrain
Authors: Legault LM , Doiron K , Breton-Larrivée M , Langford-Avelar A , Lemieux A , Caron M , Jerome-Majewska LA , Sinnett D , McGraw S 
Published: December 2020

ABSTRACTBackgroundPrenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program.ResultsUsing a pre-clinicalin vivomouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormalde novoDNA methylation profiles in various biological pathways (e.g., neural/brain development).ConclusionThese findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.
Role of threading dislocations on the growth of HgCdTe epilayers investigated using monochromatic X-ray Bragg diffraction imaging
Authors: Yildirim Can , Ballet Philippe , Santailler Jean-Louis , Giotta Dominique , Obrecht Rémy , Tran Thi Thu Nhi , Baruchel José , Brellier Delphine 
Published: December 2020

High-quality Hg1–x
Cd
x
Te (MCT) single crystals are essential for two-dimensional infrared detector arrays. Crystal quality plays an important role on the performance of these devices. Here, the dislocations present at the interface of CdZnTe (CZT) substrates and liquid-phase epitaxy grown MCT epilayers are investigated using X-ray Bragg diffraction imaging (XBDI). The diffraction contributions coming from the threading dislocations (TDs) of the CZT substrate and the MCT epilayers are separated using weak-beam conditions in projection topographs. The results clearly suggest that the lattice parameter of the growing MCT epilayer is, at the growth inception, very close to that of the CZT substrate and gradually departs from the substrate's lattice parameter as the growth advances. Moreover, the relative growth velocity of the MCT epilayer around the TDs is found to be faster by a factor of two to four compared with the matrix. In addition, a fast alternative method to the conventional characterization methods for probing crystals with low dislocation density such as atomic force microscopy and optical interferometry is introduced. A 1.5 mm × 1.5 mm area map of the epilayer defects with sub-micrometre spatial resolution is generated, using section XBDI, by blocking the diffraction contribution of the substrate and scanning the sample spatially.
May you live in interesting times: a reflection on academic integrity and accounting assessment during COVID19 and online learning
Authors: White Amanda 
Published: December 2020

Purpose
The purpose of this paper is to reflect on the shift of assessments online and the potential impact on academic integrity and misconduct. The rapid pivot to online teaching as a result of COVID19 and our experiences in the accounting academy is the embodiment of the phrase “may you live in interesting times”. As teaching and learning activities shifted online, so did assessment of student learning. A topic of great discussion amongst faculty is whether accounting exams should be invigilated online and whether exams should be used at all to assess student learning.

Design/methodology/approach
This paper uses personal reflections and experiences to analyse the tensions between the risk of academic misconduct, maintaining assessment security and accreditation requirements of professional accounting bodies during the shift of assessment tasks online in 2020. These tensions are analysed using the fraud triangle framework (Cressey, 1973).

Findings
Students face incentives and pressures to engage in misconduct, opportunities that arise from online learning and assessment, and hold complex perceptions around their attitudes towards academic integrity and rationalisations of misconduct behaviour.

Originality/value
Suggestions are made as to how the accounting academy can move forward, taking advantages of online assessment, while still ensuring that our graduates are meeting the competencies required to join the accounting profession.