bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPIN - Species by Proteome INvestigation
Authors: Rüther P.L. , Husic I.M. , Bangsgaard P. , Murphy Gregersen K. , Pantmann P. , Carvalho M. , Godinho R.M. , Friedl L. , Cascalheira J. , Jørkov M.L.S. , Benedetti M.M.. , Haws J. , Bicho N. , Welker F. , Cappellini E. , Olsen J.V. 
Published: February 2021

AbstractGenetic species determination has become an indispensable tool in forensics, archaeology, ecology, and food authentication. The available methods are either suited for detecting a single taxon across many samples or for screening a wide range of species across a few samples. Here, we introduce “Species by Proteome INvestigation” (SPIN), a proteomics workflow capable of querying over 150 mammalian species in 7.2 minutes of mass spectrometry (MS) analysis. Streamlined and automated sample preparation by protein aggregation capture, high-speed chromatography and data-independent acquisition, and a confident species inference algorithm facilitate processing hundreds of samples per day. We demonstrate the correct classification of known references, reproducible species identification in degraded Iron-Age material from Scandinavia, and test the limits of our methods with Middle and Upper Palaeolithic bones from Southern European sites with late Neanderthal occupation. While this initial study is focused on modern and archaeological mammalian bone, SPIN will be open and expandable with other biological tissues and taxa.
Neural correlates of subsequent memory-related gaze reinstatement
Authors: Wynn Jordana S. , Liu Zhong-Xu , Ryan Jennifer D. 
Published: February 2021

AbstractMounting evidence linking gaze reinstatement- the recapitulation of encoding-related gaze patterns during retrieval- to behavioral measures of memory suggests that eye movements play an important role in mnemonic processing. Yet, the nature of the gaze scanpath, including its informational content and neural correlates, has remained in question. In the present study, we examined eye movement and neural data from a recognition memory task to further elucidate the behavioral and neural bases of functional gaze reinstatement. Consistent with previous work, gaze reinstatement during retrieval of freely-viewed scene images was greater than chance and predictive of recognition memory performance. Gaze reinstatement was also associated with viewing of informationally salient image regions at encoding, suggesting that scanpaths may encode and contain high-level scene content. At the brain level, gaze reinstatement was predicted by encoding-related activity in the occipital pole and basal ganglia, neural regions associated with visual processing and oculomotor control. Finally, cross-voxel brain pattern similarity analysis revealed overlapping subsequent memory and subsequent gaze reinstatement modulation effects in the parahippocampal place area and hippocampus, in addition to the occipital pole and basal ganglia. Together, these findings suggest that encoding-related activity in brain regions associated with scene processing, oculomotor control, and memory supports the formation, and subsequent recapitulation, of functional scanpaths. More broadly, these findings lend support to Scanpath Theory’s assertion that eye movements both encode, and are themselves embedded in, mnemonic representations.
FORMATION OF LIPOFUSCIN-LIKE AUTOFLUORESCENT GRANULES IN THE RETINAL PIGMENT EPITHELIUM REQUIRES LYSOSOME DYSFUNCTION
Authors: Escrevente Cristina , Falcão Ana S. , Hall Michael J. , Lopes-da-Silva Mafalda , Antas Pedro , Mesquita Miguel M. , Ferreira Inês S. , Cardoso M. Helena , Fradinho Ana C. , Futter Clare E. , Tenreiro Sandra , Seabra Miguel C. 
Published: February 2021

AbstractPurposeWe aim to characterize the pathways required for autofluorescent granule (AFG) formation by retinal pigment epithelium (RPE) cells using cultured monolayers.MethodsWe fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24h the cells started accumulating AFGs similar to lipofuscinin vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking Cathepsin D by gene editing.ResultsAFGs appear to derive from incompletely digested POS-containing phagosomes and are surrounded after 72h by a single membrane containing lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation but that impairment of lysosomal pH or catalytic activity, particularly Cathepsin D activity, enhances AF accumulation.ConclusionsWe conclude that lysosomal dysfunction results in incomplete POS degradation and AFG accumulation.
Understanding LRRK2 kinase activity in preclinical models and human subjects through quantitative analysis of LRRK2 and pRab10
Authors: Wang Xiang , Negrou Elvira , Maloney Michael T. , Bondar Vitaliy V , Andrews Shan V. , Montalban Manuel , Llapashtica Ceyda , Maciuca Romeo , Nguyen Hoang , Solanoy Hilda , Arguello Annie , Przybyla Laralynne , Moerke Nathan J. , Huntwork-Rodriguez Sarah , Henry Anastasia G. 
Published: February 2021

AbstractVariants in theleucine-rich repeat kinase 2(LRRK2) gene are associated with increased risk for familial and sporadic Parkinson’s disease (PD). Pathogenic variants in LRRK2, including the common variant G2019S, result in increased LRRK2 kinase activity, supporting the therapeutic potential of LRRK2 kinase inhibitors for PD. To better understand the role of LRRK2 in disease and to support the clinical development of LRRK2 inhibitors, quantitative and high-throughput assays to measure LRRK2 levels and activity are needed. We developed and applied such assays to measure the levels of LRRK2 as well as the phosphorylation of LRRK2 itself or one of its substrates, Rab10 (pT73 Rab10). We observed increased LRRK2 activity in various cellular models of disease, including iPSC-derived microglia, as well as in human subjects carrying disease-linked variant in LRRK2 (G2019S). Capitalizing on the high-throughput and sensitive nature of these assays, we detected a significant reduction in LRRK2 activity in subjects carrying missense variants in LRRK2 associated with reduced disease risk. Finally, we optimized these assays to enable analysis of LRRK2 activity following inhibition in human peripheral blood mononuclear cells (PBMCs) and whole blood, demonstrating their potential utility as biomarkers to assess changes in LRRK2 expression and activity in the clinic.
Altered environmental perception by parental stress and depression vulnerability: impact on mothers and offspring
Authors: Alves Renata L. , Portugal Camila C. , Lopes Igor M. , Oliveira Pedro , Alves Cecília J. , Barbosa Fernando , Summavielle Teresa , Magalhães Ana 
Published: February 2021

AbstractDepressive mothers often find the mother-child interaction to be challenging. Parental stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depression (Wistar and Kyoto) to investigate the impact of stress (maternal separation-MS) on maternal behaviour and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behaviour after weaning, while worsening their adolescent offspring cognitive behaviour. Whereas MS in Wistar dams elicited higher quality of pup-directed behaviour, increasing Brain-Derived Neurotrophic Factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to impact the salience of the social environment cues (as negative for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behaviour and stress regulatory processes.
Genes with Specificity for Expression in the Round Cell Layer of the Growth Plate are Enriched in GWAS of Human Height
Authors: Renthal Nora E. , Nakka Priyanka , Baronas John M. , Kronenberg Henry M. , Hirschhorn Joel N. 
Published: February 2021

ABSTRACTHuman adult height reflects the outcome of childhood skeletal growth. Growth plate (epiphyseal) chondrocytes are key determinants of height. As epiphyseal chondrocytes mature and proliferate, they pass through three developmental stages, which are organized into three distinct layers in the growth plate: 1) resting (round), 2) proliferative (flat), and 3) hypertrophic. Recent genome-wide association studies (GWAS) of human height identified numerous associated loci, which are enriched for genes expressed in growth plate chondrocytes. However, it remains unclear which specific genes expressed in which layers of the growth plate regulate skeletal growth and human height.To connect the genetics of height and growth plate biology, we analyzed GWAS data through the lens of gene expression in the three dissected layers of murine newborn tibial growth plate. For each gene, we derived a specificity score for each growth plate layer and regressed these scores against gene-level p-values from recent height GWAS data. We found that specificity for expression in the round cell layer, which contains chondrocytes early in maturation, is significantly associated with height GWAS p-values (p=8.5×10−9); this association remains after conditioning on specificity for the other cell layers. The association also remains after conditioning on membership in an “OMIM gene set” (genes known to cause monogenic skeletal growth disorders,p<9.7×10−6). We replicated the association in RNA-seq data from maturing chondrocytes sampled at early and late time points during differentiationin vitro: we found that expression early in differentiation is significantly associated withp-values from height GWAS (p=6.1×10−10) and that this association remains after conditioning on expression at 10 days in culture and on the OMIM gene set (p<0.006). These findings newly implicate genes highlighted by GWAS of height and specifically expressed in the round cell layer as being potentially important regulators of skeletal biology.
Control of Ca2+signals by astrocyte nanoscale morphology at tripartite synapses
Authors: Denizot Audrey , Arizono Misa , Nägerl Valentin U. , Berry Hugues , De Schutter Erik 
Published: February 2021

AbstractMuch of the Ca2+activity in astrocytes is spatially restricted to microdomains and occurs in fine processes that form a complex anatomical meshwork, the so-called spongiform domain. A growing body of literature indicates that those astrocytic Ca2+signals can influence the activity of neuronal synapses and thus tune the flow of information through neuronal circuits. Because of technical difficulties in accessing the small spatial scale involved, the role of astrocyte morphology on Ca2+microdomain activity remains poorly understood. Here, we use computational tools and idealized 3D geometries of fine processes based on recent super-resolution microscopy data to investigate the mechanistic link between astrocytic nanoscale morphology and local Ca2+activity. Simulations demonstrate that the nano-morphology of astrocytic processes powerfully shapes the spatio-temporal properties of Ca2+signals and promotes local Ca2+activity. The model predicts that this effect is attenuated upon astrocytic swelling, hallmark of brain diseases, which we confirm experimentally in hypo-osmotic conditions. Upon repeated neurotransmitter release events, the model predicts that swelling hinders astrocytic signal propagation. Overall, this study highlights the influence of the complex morphology of astrocytes at the nanoscale and its remodeling in pathological conditions on neuron-astrocyte communication at so-called tripartite synapses, where astrocytic processes come into close contact with pre- and postsynaptic structures.Table of ContentsMain PointsAstrocyte nano-morphology favors the compartmentalization of biochemical signalsThis compartmentalization promotes local Ca2+activity and signal propagation robustnessIn contrast, its pathological remodeling upon swelling attenuates Ca2+activityTable of Contents ImageFigure 1:Proposed mechanisms that regulate astrocytic Ca2+activity in perisynaptic astrocytic processes.Our simulation results demonstrate that the nano-morphology of astrocytic processes, consisting in the alternation of nodes and shafts, favors the compartmentalization of biochemical signals. This compartmentalization promotes local Ca2+activity and signal propagation robustness. Astrocyte swelling, observed in pathological conditions such as brain injury, stroke and epilepsy, results in an increased shaft width without altering node size. Our results suggest that such pathological alterations of the nanoscale morphology of astrocytes result in a decreased local Ca2+activity, which we confirm experimentally in hypo-osmotic conditions. Upon repeated neuronal stimuli, we predict that swelling hinders astrocytic signal propagation. Overall, this study highlights the impact of astrocyte nano-morphology on astrocyte activity at tripartite synapses, in health and disease.
The developing mouse coronal suture at single-cell resolution
Authors: Farmer D’Juan T. , Mlcochova Hana , Zhou Yan , Koelling Nils , Wang Guanlin , Ashley Neil , Maxson Robert E , Wilkie Andrew O. M. , Crump J Gage , Twigg Stephen R.F. 
Published: February 2021

AbstractSutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. To uncover the cellular diversity within sutures, we generated single-cell transcriptomes and performed extensive expression validation of the embryonic murine coronal suture. We identifyErgandPthlhas markers of osteogenic progenitors in sutures, and distinct pre-osteoblast signatures between the bone fronts and periosteum. In the ectocranial layers above the suture, we observe a ligament-like population spanning the frontal and parietal bones. In the dura mater underlying the suture, we detect a chondrocyte-like signature potentially linked to cartilage formation under pathological conditions. Genes mutated in coronal synostosis are preferentially expressed in proliferative osteogenic cells, as well as meningeal layers, suggesting discrete cell types that may be altered in different syndromes. This single-cell atlas provides a resource for understanding development of the coronal suture, the suture most commonly fused in monogenic craniosynostosis.
Reliance of neuronal gene expression on cohesin scales with chromatin loop length
Authors: Calderon Lesly , Weiss Felix D , Beagan Jonathan A , Oliveira Marta S , Wang Yi-Fang , Carroll Thomas , Dharmalingam Gopuraja , Gong Wanfeng , Tossell Kyoko , de Paola Vincenzo , Whilding Chad , Ungless Mark A. , Fisher Amanda G , Phillips-Cremins Jennifer E , Merkenschlager Matthias 
Published: February 2021

AbstractCohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here we show a prominent role for cohesin in the expression of genes that facilitate neuronal maturation and homeostasis. Unexpectedly, we observed two major classes of activity-regulated genes with distinct reliance on cohesin in primary cortical neurons. Immediate early genes remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the Immediate early geneFosformed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterised by long-range chromatin contacts. Cohesin-dependence of constitutive neuronal genes with key functions in synaptic transmission and neurotransmitter signaling also scaled with chromatin loop length. Our data demonstrate that key genes required for the maturation and activation of primary cortical neurons depend cohesin for their full expression, and that the degree to which these genes rely on cohesin scales with the genomic distance traversed by their chromatin contacts.
MYC promotes immune-suppression in TNBC via inhibition of IFN signaling
Authors: Zimmerli Dario , Brambillasca Chiara S , Talens Francien , Bhin Jinhyuk , Bhattacharya Arkajyoti , Joosten Stacey E.P. , Da Silva Ana Moises , Wellenstein Max D. , Kersten Kelly , de Boo Mart , Roorda Maurits , Henneman Linda , de Bruijn Roebi , Annunziato Stefano , van der Burg Eline , Drenth Anne Paulien , Lutz Catrin , van de Ven Marieke , Wessels Lodewyk , de Visser Karin , Zwart Wilbert , Fehrmann Rudolf S.N. , van Vugt Marcel A.T.M. , Jonkers Jos 
Published: February 2021

AbstractImmune checkpoint inhibitor (ICI) treatment has thus far shown limited efficacy in triple-negative breast cancer (TNBC) patients, presumably due to sparse or unresponsive tumor-infiltrating lymphocytes. We reveal a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of BRCA1-proficient and -deficient TNBC, MYC overexpression dramatically decreased lymphocyte infiltration in tumors, along with immune signature loss. Likewise, MYC overexpression suppressed inflammatory signaling induced by BRCA1/2 inactivation in human TNBC cell lines. Moreover, MYC overexpression prevented the recruitment and activation of lymphocytes in co-cultures with human and mouse TNBC models. Chromatin immunoprecipitation (ChIP)-sequencing revealed that MYC directly binds promoters of multiple interferon-signaling genes, which were downregulated upon MYC expression. Finally, MYC overexpression suppressed induction of interferon signaling and tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist. Together, our data reveal that MYC suppresses innate immunity and facilitates immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs.Statement of SignificanceMYC suppresses recruitment and activation of immune cells in TNBC by repressing the transcription of interferon genes. These findings provide a mechanistic rationale for the association of high MYC expression levels with immune exclusion in human TNBCs, which might underlie the relatively poor response of many TNBCs to ICI.
Impact of epidemics and pandemics on consumption pattern: evidence from Covid-19 pandemic in rural-urban India
Authors: Kumar Rahul , Abdin Md. Shahnawaz 
Published: February 2021

Purpose
The present world is crippled with the pandemic coronavirus (Covid-19). The pandemic that originated in Wuhan city of China has sent every country in the world in an unprecedented situation that has social and economic impacts. This paper aims to explore whether epidemics and pandemics have any impact on consumption patterns among rural and urban consumers in India. Taking pandemic Covid-19 as a case study, it was explored how this pandemic impacted the consumption pattern of consumers in India; what are the similarities and/or differences between rural and urban consumers that are found in their consumption habits in the wake of Covid-19 pandemic.

Design/methodology/approach
The required data was collected through questionnaires sent to respondents. Approximately 500 respondents were contacted through the mail to fill in the survey questionnaire. Despite the sincere efforts, a total of 175 complete survey questionnaires were filled in by respondents. The study used SPSS Statistics version 25 software for the analysis of data.

Findings
It was found that epidemics and pandemics have a profound impact on the pattern of consumption in India. The study reveals that consumers resort to panic buying in the initial stages of epidemics and pandemics. It was found that consumption habits of consumers went a sea change and they were spending largely on essentials only. The study also reveals that the majority of consumers would like to continue in the same consumption habits as that of during COVID-19. The consumption pattern of urban consumers witnessed more change than the consumption pattern of rural consumers. It is due to the closure of eateries and restaurants, shopping malls, movie theatres, etc., in urban areas that forced the change in the consumption pattern of urban consumers.

Research limitations/implications
The research has a limitation of using a less sample size. For the generalizations, more robust studies can be conducted with more data.

Practical implications
The findings of the study will give marketers an insight for framing their policies in the wake of epidemics and pandemics.

Originality/value
The research adds to the existing body of knowledge. There are plenty of studies on the behaviour of consumers. However, there are no major studies that focus on the behaviour of consumers during the outbreak of a pandemic. So, this study fills this gap in the existing body of knowledge.
Application of a bottom-up approach to estimate economic impacts of building maintenance projects: cladding rectification program in Australia
Authors: Teo Pauline , Gajanayake Akvan , Jayasuriya Sajani , Izaddoost Ali , Perera Treshani , Naderpajouh Nader , Wong Peter S.P. 
Published: February 2021

PurposeThis paper critically reviews economic impact assessment methods adopted in construction-related projects, to develop and present a novel bottom-up approach suitable to estimate regional economic impacts of building maintenance projects.Design/methodology/approachA thorough literature review of economic impact assessment in construction projects is carried out to identify the most relevant approach to estimate wider economic impacts of building maintenance projects. Based on these findings, a model based on the bottom-up approach to estimate wider economic impacts is developed. The applicability and face validity of the developed model is demonstrated through a case of cladding replacement program in Australia.FindingsThe literature review revealed that bottom-up models are better suited for estimating regional economic impacts of maintenance projects, given the challenges of obtaining micro-level economic data in the maintenance sector. In relation to the total economic impacts (direct and indirect), the results show that for every $1 of government spending on similar projects the Gross State Product would increase by $1.34. In terms of employment impact, over 70% of the direct economic value addition is driven by the increase in labour, where close to 3 FTE jobs will be required for each $1 million of spending on cladding replacement projects.Originality/valueThis paper presents a model to estimate the wider economic impacts of building maintenance projects, which is typically overlooked in the construction management field. The proposed model is developed to incorporate the variability of different building maintenance projects so that the economic impact resulting from these projects could be estimated more accurately. This model can be used by local government decision-makers to justify and prioritise maintenance projects in a similar manner to new construction projects.