bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium
Authors: Johnson NM , Parham LR , Na J , Monaghan KE , Kolev HM , Klochkova A , Kim MS , Danan CH , Cramer Z , Simon LA , Naughton KE , Adams-Tzivelekidis S , Tian Y , Williams PA , Leu NA , Sidoli S , Whelan KA , Li N , Lengner CJ , Hamilton KE 
Published: April 2022

SummaryThe intestinal epithelium exhibits a rapid and efficient regenerative response to injury. Emerging evidence supports a model where plasticity of differentiated cells, particularly those in the secretory lineages, contributes to epithelial regeneration upon ablation of injury-sensitive stem cells. However, such facultative stem cell activity is rare within secretory populations. Here we ask whether specific functional properties predict facultative stem cell activity. We utilize in vivo labeling combined with ex vivo organoid formation assays to evaluate how cell age and autophagic state contribute to facultative stem cell activity within secretory lineages. Strikingly, we find that cell age (time elapsed since cell cycle exit) does not correlate with secretory cell plasticity. Instead, high autophagic activity predicts plasticity and resistance to DNA damaging injury independently of cell lineage. Our findings indicate that autophagic status prior to injury serves as a lineageagnostic marker for the prospective identification of facultative stem cells.
Multiple distinct evolutionary mechanisms govern the dynamics of selfish mitochondrial genomes
Authors: Gitschlag Bryan L. , Pereira Claudia V. , Held James P. , McCandlish David M. , Patel Maulik R. 
Published: April 2022

ABSTRACTCells possess multiple mitochondrial DNA (mtDNA) copies, which undergo semi-autonomous replication and stochastic inheritance. This enables mutant mtDNA variants to arise and selfishly compete with cooperative (wildtype) mtDNA. Selfish mitochondrial genomes are subject to selection at different levels: they compete against wildtype mtDNA directly within hosts and indirectly through organismal selection. However, determining the relative contributions of selection at different levels has proven challenging. We overcome this challenge by combining mathematical modeling with experiments designed to isolate the levels of selection. Applying this approach to many selfish mitochondrial genotypes inCaenorhabditis elegansrevealed an unexpected diversity of evolutionary mechanisms. Some mutant genomes persist at high frequency for many generations, despite a host fitness cost, by aggressively outcompeting cooperative genomes within hosts. Conversely, some mutant genomes persist by evading organismal selection. Strikingly, the mutant genomes vary dramatically in their susceptibility to neutral drift. Although different mechanisms can cause high frequency of selfish mtDNA, we show how they give rise to characteristically different distributions of mutant frequency among individuals. Given that heteroplasmic frequency represents a key determinant of phenotypic severity, this work outlines an evolutionary theoretic framework for predicting the distribution of phenotypic consequences among individuals carrying a selfish mitochondrial genome.
Diversity and evolution of telomere and subtelomere DNA sequences in insects
Authors: Lukhtanov Vladimir A. 
Published: April 2022

AbstractIn insects, two types of telomere length maintenance are known: telomerase-dependent, resulting in chromosome ends consisting of short nucleotide repeats (typically TTAGG), and telomerase-independent, resulting in chromosome ends consisting of long nucleotide repeats or transposon-like elements. However, only a few species have been previously studied with regard to their telomere DNA sequences. Here, based on analysis of chromosome-level genome assemblies, I present the data on telomere and subtelomere organization for 180 species from 148 genera, 53 families and 8 orders of insects.Analysis of these taxa reveals that in fact chromosome ends of most insect species have an intermediate structure and consist of numerous arrays of short telomeric repeats interspersed with telomere-specific non-LTR retrotransposons. An unexpectedly high level of diversity of short telomeric motifs (22 variants ranging in length from 1 to 17 nucleotides) is documented. Telomeres consisting of long repeats (from 173 to 374 bp) are confirmed for flies (the order Diptera) and also found in the orders Odonata and Hymenoptera. The most unusual telomere structure is found in the bee Lasioglossum lativentre, in which the chromosomes possess the short telomeric repeat TTAGGTCTGGG at only one end, whereas opposing ends terminate with medium and long repeats.I conclude that different types of telomere organization and numerous variants of long and short T-containing motifs, including the (T)n mononucleotide sequence, are compatible with the performance of telomere functions. I argue that both telomerase-dependent and telomerase-independent mechanisms for maintaining telomere length operate simultaneously in many insects. The balance between them and the exchange of sequences between telomeres and subtelomeres are most likely the key factors that determine the structure and evolution of telomeres.SignificanceMultilayer telomeres, resulted from numerous, site-specific insertions of retrotransposons into the region of short telomeric repeats, are not an aberrant type of organization, as previously thought. They are widely distributed among insects and can represent up to 30-40 % of eukaryotic species diversity. Accordingly, the telomere maintenance mechanism based on the joint work of telomerase-dependent and telomerase-independent mechanisms can also be extremely widespread in nature.
Unexpected proteinopathies in hippocampal PDE11A4 promote age-related cognitive decline of social associative memories
Authors: Pilarzyk K , Porcher L , Capell WR , Burbano SD , Davis J , Fisher JL , Gorny N , Petrolle S , Kelly MP 
Published: April 2022

ABSTRACTIn humans, associative memories are more susceptible to age-related cognitive decline (ARCD) than are recognition memories. Reduced cAMP/cGMP signaling in the hippocampus may contribute to ARCD. Here, we found that both aging and traumatic brain injury-associated dementia increased expression of the cAMP/cGMP-degrading enzyme phosphodiesterase 11A (PDE11A) in the human hippocampus. Further, age-related increases in hippocampal PDE11A4 mRNA and protein were conserved in mice, as was the increased vulnerability of associative versus recognition memories to ARCD. Interestingly, mouse PDE11A4 protein in the aged ventral hippocampus (VHIPP) ectopically accumulated in the membrane fraction and filamentous structures we term “ghost axons”. These age-related increases in expression were driven by reduced exoribonuclease-mediated degradation of PDE11A mRNA and increased PDE11A4-pS117/pS124, the latter of which also drove the punctate accumulation of PDE11A4. In contrast, PDE11A4-pS162 caused dispersal. Importantly, preventing age-related increases in PDE11 expression via genetic deletion protected mice from ARCD of short-term and remote long-term associative memory (aLTM) in the social transmission of food preference assay, albeit at the expense of recent aLTM. Further, mimicking age-related overexpression of PDE11A4 in CA1 of old KO mice caused aging-like impairments in CREB function and remote social—but not non-social—LTMs. RNA sequencing and phosphoproteomic analyses of VHIPP identified cGMP-PKG—as opposed to cAMP-PKA—as well as circadian entrainment, glutamatergic/cholinergic synapses, calcium signaling, oxytocin, and retrograde endocannabinoid signaling as mechanisms by which PDE11A deletion protects against ARCD. Together, these data suggest that PDE11A4 proteinopathies acutely impair signaling in the aged brain and contribute to ARCD of social memories.
Evolutionary history mediates population response to rapid environmental change through within-generational and transgenerational plasticity
Authors: Clement Dale , Neylan Isabelle P. , Roberts Nicholas J. , Schreiber Sebastian , Trimmer Pete C. , Sih Andrew 
Published: April 2022

AbstractRapid environmental change is affecting many organisms; some are coping well but many species are in decline. A key mechanism for facilitating success following environmental change is phenotypic plasticity. Organisms use cues to respond phenotypically to environmental conditions; many incorporate recent information (within-generation plasticity) and information from previous generations (transgenerational plasticity). We extend an existing evolutionary model where organisms utilize within-generational plasticity, transgenerational plasticity, rapid evolution, and bet-hedging. We show how, when rapid evolution of plasticity is not possible, the effect of environmental change (altering the environment mean, variance, or autocorrelation, or cue reliability) on population growth rate depends on selection for within-generation plasticity and transgenerational plasticity under historical environmental conditions. We then evaluate the predictions that populations adapted to highly variable environments, or with greater within-generational plasticity, are more likely to successfully respond to environmental change. We identify when these predictions fail, and show environmental change is most detrimental when previously reliable cues become unreliable. When multiple cues become unreliable, environmental change can cause deleterious effects regardless of the population’s evolutionary history. Overall, this work provides a general framework for understanding the role of plasticity in population responses to rapid environmental change.
THEMIS: A Framework for Cost-Benefit Analysis of COVID-19 Non-Pharmaceutical Interventions
Authors: Bertsimas Dimitris , Li Michael Lingzhi , Soni Saksham 
Published: April 2022

AbstractSince December 2019, the world has been ravaged by the COVID-19 pandemic, with over 150 million confirmed cases and 3 million confirmed deaths worldwide. To combat the spread of COVID-19, governments have issued unprecedented non-pharmaceutical interventions (NPIs), ranging from mass gathering restrictions to complete lockdowns. Despite their proven effectiveness in reducing virus transmission, the policies often carry significant economic and humanitarian cost, ranging from unemployment to depression, PTSD, and anxiety. In this paper, we create a data-driven system dynamics framework, THEMIS, that allows us to compare the costs and benefits of a large class of NPIs in any geographical region across different cost dimensions. As a demonstration, we analyzed thousands of alternative policies across 5 countries (United States, Germany, Brazil, Singapore, Spain) and compared with the actual implemented policy.Our results show that moderate NPIs (such as restrictions on mass gatherings) usually produce the worst results, incurring significant cost while unable to sufficiently slow down the pandemic to prevent the virus from becoming endemic. Short but severe restrictions (complete lockdown for 4-5 weeks) generally produced the best results for developed countries, but only if the speed of reopening is slow enough to prevent a resurgence. Developing countries exhibited very different trade-off profiles from developed countries, and suggests that severe NPIs such as lockdowns might not be as suitable for developing countries in general.
Comparative analysis of high- and low-level deep learning approaches in microsatellite instability prediction
Authors: Park Jeonghyuk , Chung Yul Ri , Nose Akinao 
Published: April 2022

ABSTRACTDeep learning-based approaches in histopathology can be largely divided into two categories: a high-level approach using an end-to-end model and a low-level approach using feature extractors. Although the advantages and disadvantages of both approaches are empirically well known, there exists no scientific basis for choosing a specific approach in research, and direct comparative analysis of the two approaches has rarely been performed. Using the Cancer Genomic Atlas (TCGA)-based dataset, we compared these two different approaches in microsatellite instability (MSI) prediction and analyzed morphological image features associated with MSI. Our high-level approach was based solely on EfficientNet, while our low-level approach relied on LightGBM and multiple deep learning models trained on publicly available multiclass tissue, nuclei, and gland datasets. We compared their performance and important image features. Our high-level approach showed superior performance compared to our low-level approach. In both approaches, debris, lymphocytes, and necrotic cells were revealed as important features of MSI, which is consistent with clinical knowledge. Then, during qualitative analysis, we discovered the weaknesses of our low-level approach and demonstrated that its performance can be improved by using different image features in a complementary way. We performed our study using open-access data, and we believe this study can serve as a useful basis for discovering imaging biomarkers for clinical application.
A distributed and efficient population code of mixed selectivity neurons for flexible navigation decisions
Authors: Kira Shinichiro , Safaai Houman , Morcos Ari S. , Panzeri Stefano , Harvey Christopher D. 
Published: April 2022

AbstractDecision-making requires flexibility to rapidly switch sensorimotor associations depending on behavioral goals stored in memory. We identified cortical areas and neural activity patterns that mediate this flexibility during virtual-navigation, where mice switched navigation toward or away from a visual cue depending on its match to a remembered cue. An optogenetics screen identified V1, posterior parietal cortex (PPC), and retrosplenial cortex (RSC) as necessary for accurate decisions. Calcium imaging revealed neurons that can mediate rapid sensorimotor switching by encoding a conjunction of a current and remembered visual cue that predicted the mouse’s navigational choice from trial-to-trial. Their activity formed efficient population codes before correct, but not incorrect, choices. These neurons were distributed across posterior cortex, even V1, but were densest in RSC and sparsest in PPC. We propose the flexibility of navigation decisions arises from neurons that mix visual and memory information within a visual-parietal-retrosplenial network, centered in RSC.
T-cell Abca1 and Abcg1 cholesterol efflux pathways suppress T-cell apoptosis and senescence and increase atherosclerosis in middle-agedLdlr-/-mice
Authors: Bazioti Venetia , La Rose Anouk M. , Maassen Sjors , Bianchi Frans , de Boer Rinse , Guilbaud Emma , Flohr-Svendsen Arthur , Groenen Anouk G. , Marmolejo-Garza Alejandro , Koster Mirjam H. , Kloosterhuis Niels J. , Pranger Alle T. , Langelaar-Makkinje Miriam , de Bruin Alain , van de Sluis Bart , Kohan Alison B. , Yvan-Charvet Laurent , van den Bogaart Geert , Westerterp Marit 
Published: April 2022

ABSTRACTAtherosclerosis is a chronic inflammatory disease driven by hypercholesterolemia. During aging, T-cells accumulate cholesterol, which could lead to a pro-inflammatory phenotype. However, the role of cholesterol efflux pathways mediated by ATP-binding cassette A1 and G1 (ABCA1/ABCG1) in T-cell-dependent age-related inflammation and atherosclerosis remains poorly understood. In this study, we generated mice with T-cell-specificAbca1/Abcg1-deficiency on the low-density-lipoprotein-receptor deficient (Ldlr-/-) background. T-cellAbca1/Abcg1-deficiency decreased blood, lymph node, and splenic T-cells, and increased T-cell activation and apoptosis. T-cellAbca1/Abcg1-deficiency induced a premature T-cell aging phenotype in middle-aged (12-13 months)Ldlr-/-mice, reflected by upregulation of senescence markers. Despite T-cell senescence and enhanced T-cell activation, T-cellAbca1/Abcg1-deficiency decreased atherosclerosis and aortic inflammation in middle-agedLdlr-/-mice, accompanied by decreased T-cells in atherosclerotic plaques. We attribute these effects to T-cell apoptosis downstream of T-cell activation. Collectively, T-cell cholesterol efflux pathways are critical for maintaining T-cell numbers, suppress senescence, and induce atherosclerosis in middle-agedLdlr-/-mice.
Polerovirus N-terminal readthrough domain structures reveal novel molecular strategies for mitigating virus transmission by aphids
Authors: Schiltz Carl J. , Wilson Jennifer R. , Hosford Christopher J. , Adams Myfanwy C. , Preising Stephanie E. , DeBlasio Stacy L. , MacLeod Hannah J. , Van Eck Joyce , Heck Michelle L. , Chappie Joshua S. 
Published: April 2022

AbstractPoleroviruses, enamoviruses, and lutoeviruses are icosahedral, positive sense RNA viruses that cause economically important diseases in food and fiber crops. They are transmitted by phloem-feeding aphids in a circulative manner that involves the movement across and within insect tissues. The N-terminal portion of the viral readthrough domain (NRTD) has been implicated as a key determinant of aphid transmission in each of these genera. Here, we report crystal structures of the NRTDs from the poleroviruses turnip yellow virus (TuYV) and potato leafroll virus (PLRV) at 1.53-Å and 2.22-Å resolution, respectively. These adopt a two-domain arrangement with a unique interdigitated topology and form highly conserved dimers that are stabilized by a C-terminal peptide that is critical for proper folding. We demonstrate that the PLRV NRTD can act as an inhibitor of virus transmission and identify NRTD mutant variants that are lethal to aphids. Sequence conservation argues that enamovirus and luteovirus NRTDs will follow the same structural blueprint, which affords a novel approach to block the spread of these agricultural pathogens in a generalizable manner.
Weighted Kernels Improve Multi-Environment Genomic Prediction
Authors: Hu Xiaowei , Carver Brett F. , El-Kassaby Yousry A. , Zhu Lan , Chen Charles 
Published: April 2022

AbstractCrucial to variety improvement programs is the reliable and accurate prediction of genotype’s performance across environments. However, due to the impactful presence of genotype by environment (G×E) interaction that dictates how changes in expression and function of genes influence target traits, prediction performance of genomic selection (GS) using single-environment models often falls short. Furthermore, despite the successes of genome-wide association studies (GWAS), the genetic insights derived from genome-to-phenome mapping have not yet been incorporated in predictive analytics, making GS models that use Gaussian kernel primarily an estimator of genomic similarity, instead of the underlying genetics characteristics of the populations. Here, we developed a GS framework that, in addition to capturing the overall genomic relationship, can capitalize on the signal of genetic associations of the phenotypic variation as well as the genetic characteristics of the populations. The capacity of predicting the performance of populations across environments was demonstrated by an overall gain in predictability up to 31% for the winter wheat DH population. Compared to Gaussian kernels, we showed that our multienvironment weighted kernels could better leverage the significance of genetic associations and yielded a marked improvement of 4-33% in prediction accuracy for half-sib families. Furthermore, the flexibility incorporated in our Bayesian implementation provides the generalizable capacity required for predicting multiple highly genetic heterogeneous populations across environments, allowing reliable GS for genetic improvement programs that have no access to genetically uniform material.
Numerical study of the yaw control of flapless aircraft
Authors: Li Ling-Xiao , Xu He-Yong , Fu Zhi-Jie , Huang Zeng-Chun 
Published: April 2022

Purpose
The purpose of this paper is to study the yaw control of the flapless aircraft and investigate the equivalent control effect (ECE) and the power consumption of the pneumatic control.

Design/methodology/approach
The control effects of the mechanical control and the pneumatic control are calculated and the ECE curves are obtained. The power consumption of the pneumatic control is analyzed. A new pneumatic drag-type yaw control method is proposed. The mechanisms of the drag-type yaw control and the conventional thrust-type yaw control are explored. The drag-type yaw control is divided into two combined blowing forms: inner-top outer-bottom blowing and inner-bottom outer-top blowing. The differences between two kinds of the drag-type yaw control at a small angle of attack and a large angle of attack are explored.

Findings
The ECE curves of the pneumatic control are obtained. The power consumption of the drag-type yaw control is much lower than that of the thrust type. The lift coefficient of the inner-top outer-bottom blowing is higher than that of the inner-bottom outer-top blowing, but the inner-bottom outer-top blowing has higher efficiency of the yaw control at a large angle of attack.

Practical implications
This paper contributes to the research of the flapless aircraft.

Originality/value
A new pneumatic drag-type yaw control method of the flapless aircraft is proposed.
The maturity of open government data maturity: a multivocal literature review
Authors: Çaldağ Murat Tahir , Gökalp Ebru 
Published: April 2022

PurposeThe aim of this study is to provide administrators in government institutions a roadmap to achieve benefits of open government data (OGD) by reviewing and classifying studies with assessment or maturity models (MMs) in the OGD domain with a Multivocal Literature Review (MLR).Design/methodology/approachTo achieve this goal, the authors conducted an MLR that includes data from not only the formal literature but also the grey literature (e.g. white papers and online documents).FindingsOut of 3,569 sources, 81 studies were selected by following the elimination scheme and assessing sources by relevance and methodology. As a result of the quality assessment of the identified MMs based on predefined criteria, unambiguity, comparability, repeatability, completeness, clearness and objectivity, it was observed that there are a limited number of MMs in this domain and none of them fully satisfies the requirements.Originality/valueThis study is likely the first MLR on OGD domain. This MLR serves as a first step for future research on OGD assessment and MMs by presenting the need to establish a holistic approach covering all OGD dimensions, creation of an objective assessment method, prescriptive properties, and empirical evaluation demonstrating the applicability and usefulness at different scope levels.