bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytic representation of inhomogeneous-resolution maps of three-dimensional scalar fields
Authors: Urzhumtsev Alexandre G. , Lunin Vladimir Y. 
Published: March 2022

AbstractRefinement of macromolecular atomic models versus experimental maps in cryo-electron microscopy and crystallography is a critical step in structure solution. For an appropriate comparison, model maps should mimic imperfections of the experimental ones, mainly atomic disorder and its limited resolution, often inhomogeneous over the molecule. We construct these model maps as a sum of atomic contributions expressed through a specially designed function describing a solitary spherical wave. Thanks to this function, atomic contributions analytically depend on both an atomic disorder and the local resolution, a value associated now with each atom. Such fully analytic dependence of inhomogeneous-resolution map values on model parameters permits an efficient refinement of all these parameters together and, beyond structural biology, opens a way to solve similar problems in other research domains.One-Sentence SummaryAn analytic decomposition of 3D-oscillating functions results in efficient tools to calculate maps and refine atomic models.
ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2
Authors: Gustavsson Emil K. , Zhang David , Reynolds Regina H. , Garcia-Ruiz Sonia , Ryten Mina 
Published: March 2022

AbstractMotivationThe advent of long-read sequencing technologies has increased demand for the visualisation and interpretation of transcripts. However, tools that perform such visualizations remain inflexible and lack the ability to easily identify differences between transcript structures. Here, we introduce ggtranscript, an R package that provides a fast and flexible method to visualize and compare transcripts. As a ggplot2 extension, ggtranscript inherits the functionality and familiarity of ggplot2 making it easy to use.Availability and implementationggtranscript is available at https://github.com/dzhang32/ggtranscript, DOI: https://doi.org/10.5281/zenodo.6374061
NDR1/2 kinases regulate membrane trafficking, enable efficient autophagy and prevent neurodegeneration
Authors: Roșianu Flavia , Mihaylov Simeon R , Eder Noreen , Martiniuc Antonie , Claxton Suzanne , Flynn Helen R , Jalal Shamsinar , Domart Marie-Charlotte , Collinson Lucy , Skehel Mark , Snijders Ambrosius P , Krause Matthias , Tooze Sharon A , Ultanir Sila K 
Published: March 2022

SummaryAutophagy is essential for neuronal development and its deregulation contributes to neurodegenerative diseases. NDR1 and NDR2 are highly conserved kinases implicated in neuronal development, mitochondrial health and autophagy, but how they affect mammalian brain developmentin vivois not known. Using single and doubleNdr1/2knockout mouse models we show that, dual, but not individual loss ofNdr1/2in neurons causes neurodegeneration during brain development, but also in adult mice. Proteomic and phosphoproteomic comparisons betweenNdr1/2knockout and control brains revealed novel kinase substrates and indicated that endocytosis is significantly affected in the absence of NDR1/2. We validated the endocytic protein, Raph1/Lpd1 as a novel NDR1/2 substrate and showed that both NDR1/2 and Raph1 are critical for endocytosis and membrane recycling. In NDR1/2 knockout brains, we observed prominent accumulation of transferrin receptor, p62 and ubiquitinated proteins, indicative of a major impairment of protein homeostasis. Furthermore, the levels of LC3-positive autophagosomes were reduced in knockout neurons, implying that reduced autophagy efficiency mediates p62 accumulation and neurotoxicity. Mechanistically, pronounced mislocalisation of the transmembrane autophagy protein ATG9A at the neuronal periphery, impaired axonal ATG9A trafficking and increased ATG9A surface levels further confirm defects in membrane trafficking and could underlie the impairment in autophagy. We provide novel insight into the roles of NDR1/2 kinases in maintaining neuronal health.HighlightsDual neuronalNdr1andNdr2knockout during development or in adult mice causes neurodegeneration.Phosphoproteomics comparison ofNdr1/2knockouts with control littermates shows endocytosis and membrane trafficking to be affected and reveals novel substrates.Raph1/Lamellipodin is a novel NDR1/2 substrate that is required for TfR endocytosis.Ndr1/2knockout brains exhibit a severe defect in ubiquitinated protein clearance and reduced autophagy.NDR1/2 and Raph1 are required for the trafficking of the only transmembrane autophagy protein, ATG9A.
Context-independent expression of spatial code in hippocampus
Authors: Kapl S. , Tichanek F. , Zitricky F. , Jezek K. 
Published: March 2022

AbstractHippocampus plays a crucial role in formation and retrieval of spatial memory across mammals and episodic memory in humans. Episodic as well as spatial memories can be retrieved irrespectively of subject’s awake behavioral state and independently of its actual spatial context. The nature of hippocampal network activity during such out-context retrieval has not been described so far, though. Theoretically, context-independent spatial memory retrieval suggests a shift from the hippocampal spatial representations coding the actual- to the remembered context. In this study we show in rats that CA3 neuronal population can switch spontaneously across representations and transiently activate another stored familiar spatial pattern without a direct external sensory cuing. This phenomenon qualitatively differs from the well described sharp wave-related pattern reactivations during immobility. Here it occurred under theta oscillatory state during an active exploration and reflected the preceding experience of sudden environment change. The respective out-context coding spikes appeared later in the theta cycle than the in-context ones. Finally, the experience induced as well an emergence of population vectors with a co-expression of both codes segregated into different phases of the theta cycle.
Deciphering the fibre-orientation independent component of R2* (R2,iso*) in the human brain with a single multi-echo gradient-recalled-echo measurement under varying microstructural conditions
Authors: Fritz Francisco J. , Mordhorst Laurin , Ashtarayeh Mohammad , Periquito Joao , Pohlmann Andreas , Morawski Markus , Jaeger Carsten , Niendorf Thoralf , Pine Kerrin J. , Callaghan Martina F. , Weiskopf Nikolaus , Mohammadi Siawoosh 
Published: March 2022

AbstractThe effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain, e.g. the g-ratio characterising the relative myelination of axons. However, R2* depends on the orientation of the fibres relative to the main magnetic field degrading its reproducibility and that of any microstructural derivative measure. To decipher its orientation-independent part (R2,iso*), a second-order polynomial in time (M2) can be applied to single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientation. The linear-time dependent parameter,β1, of M2 can be biophysically related to R2,iso* when neglecting the signal from the myelin water (MW) in the hollow cylinder fibre model (HCFM). Here, we examined the effectiveness of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We showed that the fittedβ1effectively estimates R2,iso*when using meGRE with long maximum echo time (TEmax≈ 54 ms) but its microscopic dependence on the g-ratio was not accurately captured. This error was reduced to less than 12% when accounting for the MW contribution in a newly introduced biophysical expression forβ1. We further used this new expression to estimate the MW fraction (0.14) and g-ratio (0.79) in a human optic chiasm. However, the proposed method failed to estimate R2,iso* for a typicalin-vivomeGRE protocol (TEmax≈ 18 ms). At this TEmaxand around the magic angle, the HCFM-based simulations failed to explain the R2*-orientation-dependence. In conclusion, estimation of R2,iso* with M2in vivorequires meGRE protocols with very long TEmax≈ 54 ms.
Genotype by microbiome interactions have large effects on growth in Lotus japonicus
Authors: Bamba Masaru , Akyol Turgut Yigit , Azuma Yusuke , Quilbe Johan , Andersen Stig Uggerhøj , Sato Shusei 
Published: March 2022

AbstractBiological interactions between plants and their root microbiomes are pivotal for plant growth. Even though the plant genotype [G], soil microbiome [C], and growth conditions (environment) [E] are core factors shaping the root microbiome, their relationships remain unclear. We disentangled the effects of G, C, E, and their interactions on the Lotus root microbiome and plant growth using a cross-inoculation approach that reconstructed the interactions between nine Lotus accessions and four soil microbiomes under two different environmental conditions. We found that a large proportion of the root microbiome composition was determined by C and E and that G-related (G, G × C, and G × E) effects were significant but small. In contrast, the interactions between G and C had a more pronounced effect on plant shoot growth than C alone. Our findings indicate that most microbiome variations controlled by C have little effect on the plant phenotype, whereas G × C interactions have more significant effects. Plant genotype-dependent interactions with soil microbes warrant more attention in efforts to optimize crop yield and resilience.
Resistance of mitochondrial DNA to chemical-induced germline mutations is independent of mitophagy in C. elegans
Authors: Leuthner Tess C , Benzing Laura , Kohrn Brendan F , Bergemann Christina M , Hipp Michael J , Hershberger Kathleen A , Mello Danielle F , Sokolskyi Tymofii , Merutka Ilaria R , Seay Sarah A , Kennedy Scott R , Meyer Joel N 
Published: March 2022

ABSTRACTMitochondrial DNA (mtDNA) is prone to mutation in aging and over evolutionary time, yet the processes that regulate the accumulation of de novo mtDNA mutations and modulate mtDNA heteroplasmy are not fully elucidated. Mitochondria lack certain DNA repair processes, which could contribute to polymerase error-induced mutations and increase susceptibility to chemical-induced mtDNA mutagenesis. We conducted error-corrected, ultra-sensitive Duplex Sequencing to investigate the effects of two known nuclear genome mutagens, cadmium and Aflatoxin B1, on germline mtDNA mutagenesis in Caenorhabditis elegans. After 1,750 generations, we detected 2,270 single nucleotide mutations. Heteroplasmy is pervasive in C. elegans and mtDNA mutagenesis is dominated by C:G → A:T mutations generally attributed to oxidative damage, yet there was no effect of either exposure on mtDNA mutation frequency, spectrum, or trinucleotide context signature. Mitophagy may play a role in eliminating mtDNA damage or deleterious mutations, and mitophagy-deficient mutants pink-1 and dct-1 accumulated significantly higher levels of mtDNA damage compared to wild-type C. elegans after exposures. However, there were only small differences in overall mutation frequency, spectrum, or trinucleotide context signature compared to wild-type after 3,050 generations, across all treatments. These findings suggest mitochondria harbor additional previously uncharacterized mechanisms that regulate mtDNA mutational processes across generations.
High Quality Phasing Using Linked-Read Whole Genome Sequencing of Patient Cohorts Informs Genetic Understanding of Complex Traits
Authors: Mastromatteo Scott , Chen Angela , Gong Jiafen , Lin Fan , Thiruvahindrapuram Bhooma , Sung Wilson WL , Whitney Joe , Wang Zhuozhi , Patel Rohan V , Keenan Katherine , Halevy Anat , Panjwani Naim , Avolio Julie , Wang Cheng , Côté-Maurais Guillaume , Bégin Stéphanie , Adam Damien , Brochiero Emmanuelle , Bjornson Candice , Chilvers Mark , Price April , Parkins Michael , van Wylick Richard , Mateos-Corral Dimas , Hughes Daniel , Smith Mary Jane , Morrison Nancy , Tullis Elizabeth , Stephenson Anne L , Wilcox Pearce , Quon Bradley S , Leung Winnie M , Solomon Melinda , Sun Lei , Ratjen Felix , Strug Lisa J 
Published: March 2022

AbstractPhasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. For population studies, phase is often inferred from external data but read-based phasing approaches that span long genomic distances would be more accurate because they enable both genotype and phase to be obtained from a single dataset. To demonstrate how read-based phasing can provide functional insights, we sequenced 477 individuals with Cystic Fibrosis (CF) using linked-read sequencing. We benchmark read-based phasing with different short- and long-read sequencing technologies, prioritize linked-read technology as the most informative and produce a benchmark phase call set from reference sample HG002 for the community. The 477 samples display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, which facilitates understanding of complex CF alleles. Fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus demonstrates a 20 kb deletion and a PRSS2 missense variant p.Thr8Ile (rs62473563) independently contribute to meconium ileus risk (p=0.0028, p=0.011, respectively) and are PRSS2 pancreas eQTLs (p=9.5e-7 and p=1.4e-4, respectively), explaining the mechanism by which these polymorphisms contribute to CF. Phase enables access to haplotypes that can be used for genome graph or reference panel construction, identification of cis-effects, and for understanding disease associated loci. The phase information from linked-reads provides a causal explanation for variation at a CF-relevant locus which also has implications for the genetic basis of non-CF pancreatitis to which this locus has been reported to contribute.
Primate dopamine neurons activated in rewarding environment by tonic disinhibition from amygdala
Authors: Maeda Kazutaka , Inoue Ken-ichi , Takada Masahiko , Hikosaka Okihide 
Published: March 2022

SummarySeeking out good and avoiding bad objects is critical for survival. In practice, objects are rarely good every time or everywhere, but only at the right time or place. Whereas the basal ganglia (BG) are known to mediate goal-directed behavior, for example, saccades to rewarding objects, it remains unclear how such simple behaviors are rendered contingent on higher-order factors, including environmental context. Here we show that amygdala neurons are sensitive to environments and regulate dopamine (DA) neurons via an inhibitory projection to substantia nigra pars reticulata (SNr) neurons. We combined optogenetics and multi-channel recording to demonstrate that rewarding environments induce tonic firing changes in DA neurons. These tonic responses are mediated by disinhibition via GABAergic projection onto DA neurons from SNr, which in turn are suppressed by inhibitory projection from the amygdala. Thus, the amygdala provides an additional source of learning to BG circuits, namely contingencies imposed by the environment.
Multimodal microscale mechanical mapping of cancer cells in complex microenvironments
Authors: Nikolić Miloš , Scarcelli Giuliano , Tanner Kandice 
Published: March 2022

AbstractThe mechanical phenotype of the cell is critical for survival following deformations due to confinement and fluid flow. One idea is that cancer cells are plastic and adopt different mechanical phenotypes under different geometries that aid in their survival. Thus, an attractive goal, is to disrupt the cancer cells’ ability to adopt multiple mechanical states. To begin to address this question, we aimed to quantify the diversity of these mechanical states usingin vitrobiomimetics to mimicin vivo2D and 3D extracellular matrix environments. Here, we used two modalities Brillouin microscopy (∼GHz) and broadband frequency (3-15kHz) optical tweezer microrheology to measure microscale cell mechanics. We measured the response of intracellular mechanics of cancer cells cultured in 2D and 3D environments where we modified substrate stiffness, dimensionality (2D versus 3D), and presence of fibrillar topography. We determined that there was good agreement between two modalities despite the difference in timescale of the two measurements. These findings on cell mechanical phenotype in different environments confirm a correlation between modalities that employ different mechanisms at different temporal scales (Hz-kHz vs. GHz). We also determined that observed heterogeneity in cell shape that is more closely linked to the cells’ mechanical state. We also determined that individual cells in multicellular spheroids exhibit a lower degree of mechanical heterogeneity when compared to single cells cultured in monodisperse 3D cultures. Moreover, the observed decreased heterogeneity among cells in spheroids suggested that there is mechanical cooperativity between cells that make up a single spheroid.
Learning of probabilistic punishment as a model of anxiety produces changes in action but not punishment encoding in the dmPFC and VTA
Authors: Jacobs David S. , Allen Madeleine C. , Park Junchol , Moghaddam Bita 
Published: March 2022

AbstractPreviously, we developed a novel model for anxiety during motivated behavior by training rats to perform a task where actions executed to obtain a reward were probabilistically punished and observed that after learning, neuronal activity in the ventral tegmental area (VTA) and dorsomedial prefrontal cortex (dmPFC) encode the relationship between action and punishment risk (Park & Moghaddam, 2017). Here we used male and female rats to expand on the previous work by focusing on neural changes in the dmPFC and VTA that were associated with the learning of probabilistic punishment, and with anxiolytic treatment with diazepam after learning. We find that adaptive neural responses of dmPFC and VTA during the learning of anxiogenic contingencies are independent from the punishment experience and occur primarily during the peri-action period. Our results further identify peri-action ramping of VTA neural activity, and VTA-dmPFC correlated activity, as potential markers for the anxiolytic properties of diazepam.
Forgetting to learn and learning to forget: the call for organizational unlearning
Authors: Mull Mandolen , Duffy Clayton , Silberman Dave 
Published: March 2022

Purpose
The purpose of this conceptual paper is to provide a foundation for human resource development (HRD) scholars in attempts to devise mechanisms for establishing and facilitating actionable pathways through which unlearning can be acknowledged and serve as a contributing agent for HRD interventions. This paper concludes with a call to action for our HRD colleagues to join us in further examination of unlearning interventions within the organizational context.

Design/methodology/approach
This paper narratively details the literature associated with the myriad social science domains that have investigated the unlearning process. Additionally, a cross-disciplinary literature review provides the basis for an operational definition of unlearning provided herein.

Findings
The field of HRD is devoted to creating learning organizations as well as utilizing change initiatives to develop organizations. However, unlearning has been largely ignored within the field of HRD.

Originality/value
The first contribution is by answering the call of scholars across varied disciplines to further investigate unlearning within the organizational context (Bettis and Prahalad, 1995; Hedberg, 1981; Nystrom and Starbuck, 1984). Additionally, this paper seeks to specifically address the role that unlearning holds within the field of HRD as it builds upon the definition provided by Wang et al. (2017) and offers its own operational definition. Finally, this paper provides the only known review of cross-disciplinary research pertaining to unlearning.
Impacts and restoration strategy of the tourism industry post-COVID-19 pandemic: evidence from Vietnam
Authors: Vu Hoa Dinh , Nguyen Anh Thi Ngoc , Nguyen Nga Thi Phuong , Tran Duy Ba 
Published: March 2022

PurposeThis paper presents the impact of the COVID-19 pandemic on Vietnam's tourism industry to propose appropriate recovery strategies in the future.Design/methodology/approachThis study uses a combination of research methods. Data were collected from the Ministry of Culture, Sports and Tourism, General Statistics Office, Vietnam National Administration of Tourism and Ministry of Health. Non-parametric statistical methods were applied to analyze the differences between epidemic and non-epidemic periods and find correlations between the number of infections and data related to the performance of the tourism industry. In-depth interviews with 20 people linked to tourism activities were conducted to analyze the impacts and propose strategies for future recovery.FindingsThe results demonstrate the severe impact of the pandemic on Vietnam's tourism industry based on a decrease in the number of visitors, business activities, revenue and employment rate. Therefore, to recover tourism – Vietnam's key economic sector in the future – developing reasonable strategies to build a safe tourism environment, building a sustainable tourist market, diversifying and improving tourism high-quality tourism products, marketing, human resources, digital transformation and sustainable tourism are necessary, along with the development trend of the industry after COVID-19.Originality/valueThis paper synchronously and systematically presents the effects of COVID-19 on Vietnam's tourism industry based on official data. Strategies are proposed to handle these effects on a reliable scientific basis. This study can be considered a valuable reference for researchers and managers of tourism in developing countries, such as Vietnam.