bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Bounded Rationality: CEO Reflective Capacity and Firm Sustainability Performance
Authors: Jia Yingya , Tsui Anne S. , Yu Xiaoyu
Published: March 2021

Optimal or rational decision making is not possible due to informational constraints and limits in computation capability of humans (March & Simon, 1958; March, 1978). This bounded rationality serves as a filtering process in decision making among business executives (Hambrick & Mason, 1984). In this study, we propose the concept of CEO reflective capacity as a behavior-oriented cognitive capability that may overcome to some extent the pervasive limitation of bounded rationality in executive decision-making. Following Hinkin's (1998) method and two executive samples, we developed and validated a three-dimensional measure of CEO reflective capacity. Based on two-wave surveys of CEOs and their executive-subordinates in 213 Chinese small-medium sized firms, we tested and confirmed three hypotheses on how CEO reflective capacity is related to a firm's sustainability performance (including economic, societal, and environmental dimensions) through the mediating mechanisms of strategic decision comprehensiveness and CEO behavioral complexity. We discuss the contribution of this study to the literature on the upper echelons and information processing perspectives. We also identify the implications for future research on strategic leadership and managerial cognition in complex and dynamic contexts.
A NOTE ON ARISTOPHANES,KNIGHTS295
Authors: Donelan Jasper F.
Published: March 2021

This note discusses the meaning of the wordκοπροφορεῖνat Aristophanes, Knights (= Eq.)295 and proposes a translation.
NOTES ON SEVEN PASSAGES OF PLUTARCH'S LIVES
Authors: Diggle James
Published: March 2021

This article discusses the text and interpretation of passages in Plutarch's Lives of Romulus, Agis and Cleomenes, Pericles, Brutus, Marcellus, Alexander and Marius.
Understanding Healthcare Social Enterprises: A New Public Governance Perspective
Authors: CHANDRA YANTO , SHANG LIANG , ROY MICHAEL J.
Published: March 2021

In recent years ‘social enterprises’ have become important partners in the delivery of key public services such as healthcare. However, little is known about how healthcare social enterprises contribute to public service provision in the health sector. We analyzed 172 social enterprises from four continents involved in healthcare to assess the types of interventions, processes, and roles they play responding to rapidly evolving healthcare systems. We found that they are engaged broadly in three dimensions of health service provision: improving access to health services; improving the quality of health services; and building public health capacity. We contribute to social policy theory by enhancing understanding of the micro-level interventions of social enterprises in the healthcare sector and articulating new dimensions of NPG that include co-innovation, co-lobbying, and co-integration in the context of healthcare.
SEQUENTIAL MONITORING OF CHANGES IN DYNAMIC LINEAR MODELS, APPLIED TO THE U.S. HOUSING MARKET
Authors: Horváth Lajos , Liu Zhenya , Lu Shanglin
Published: March 2021

We propose a sequential monitoring scheme to find structural breaks in dynamic linear models. The monitoring scheme is based on a detector and a suitably chosen boundary function. If the detector crosses the boundary function, a structural break is detected. We provide the asymptotics for the procedure under the null hypothesis of stability. The consistency of the procedure is also proved. We derive the asymptotic distribution of the stopping time under the change point alternative. Monte Carlo simulation is used to show the size and the power of our method under several conditions. As an example, we study the real estate markets in Boston and Los Angeles, and at the national U.S. level. We find structural breaks in the markets, and we segment the data into stationary segments. It is observed that the autoregressive parameter is increasing but stays below 1.
Trait attributions and threat appraisals explain why an entity theory of personality predicts greater internalizing symptoms during adolescence
Authors: Seo Eunjin , Lee Hae Yeon , Jamieson Jeremy P. , Reis Harry , Josephs Robert A. , Beevers Christopher G. , Yeager David S.
Published: March 2021

Adolescents who hold an entity theory of personality – the belief that people cannot change – are more likely to report internalizing symptoms during the socially stressful transition to high school. It has been puzzling, however, why a cognitive belief about the potential for change predicts symptoms of an affective disorder. The present research integrated three models – implicit theories, hopelessness theories of depression, and the biopsychosocial model of challenge and threat – to shed light on this issue. Study 1 replicated the link between an entity theory and internalizing symptoms by synthesizing multiple datasets (N = 6,910). Study 2 examined potential mechanisms underlying this link using 8-month longitudinal data and 10-day diary reports during the stressful first year of high school (N = 533, 3,199 daily reports). The results showed that an entity theory of personality predicted increases in internalizing symptoms through tendencies to make fixed trait causal attributions about the self and maladaptive (i.e., “threat”) stress appraisals. The findings support an integrative model whereby situation-general beliefs accumulate negative consequences for psychopathology via situation-specific attributions and appraisals.
Comparing Traumatic Brain Injury Symptoms Reported via Questionnaires Versus a Novel Structured Interview
Authors: Emmert Natalie A. , Ristow Georgia , McCrea Michael A. , deRoon-Cassini Terri A. , Nelson Lindsay D.
Published: March 2021

Objective:

Mild traumatic brain injury (mTBI) symptoms are typically assessed via questionnaires in research, yet questionnaires may be more prone to biases than direct clinical interviews. We compared mTBI symptoms reported on two widely used self-report inventories and the novel Structured Interview of TBI Symptoms (SITS). Second, we explored the association between acquiescence response bias and symptom reporting across modes of assessment.

Method:

Level 1 trauma center patients with mTBI (N= 73) were recruited within 2 weeks of injury, assessed at 3 months post-TBI, and produced nonacquiescent profiles. Assessments collected included the SITS (comprising open-ended and closed-ended questions), Rivermead Post Concussion Symptoms Questionnaire (RPQ), Sport Concussion Assessment Tool-3 (SCAT-3) symptom checklist, and Minnesota Multiphasic Personality Inventory-2 Restructured Form True Response Inconsistency (TRIN-r) scale.

Results:

Current mTBI symptom burden and individual symptom endorsement were highly concordant between SITS closed-ended questions, the RPQ, and the SCAT-3. Within the SITS, participants reported significantly fewer mTBI symptoms to open-ended as compared to later closed-ended questions, and this difference was weakly correlated with TRIN-r. Symptom scales were weakly associated with TRIN-r.

Conclusions:

mTBI symptom reporting varies primarily by whether questioning is open- vs. closed-ended but not by mode of assessment (interview, questionnaire). Acquiescence response bias appears to play a measurable but small role in mTBI symptom reporting overall and the degree to which participants report more symptoms to closed- than open-ended questioning. These findings have important implications for mTBI research and support the validity of widely used TBI symptom inventories.
Testing Todd: family types and development
Authors: Gutmann Jerg , Voigt Stefan
Published: March 2021

Many years ago, Emmanuel Todd came up with a classification of family types and argued that the historically prevalent family types in a society have important consequences for its economic, political, and social development. Here, we evaluate Todd's most important predictions empirically. Relying on a parsimonious model with exogenous covariates, we find mixed results. On the one hand, authoritarian family types are, in stark contrast to Todd's predictions, associated with increased levels of the rule of law and innovation. On the other hand, and in line with Todd's expectations, communitarian family types are linked to racism, low levels of the rule of law, and late industrialization. Countries in which endogamy is frequently practiced also display an expectedly high level of state fragility and weak civil society organizations.
Design of an interlocked four-port MIMO antenna for UWB automotive communications
Authors: Saravanan M. , Kalidoss R. , Partibane B. , Vishvaksenan K. S.
Published: March 2021

The design, analysis, fabrication, and testing of a four-port multiple-input multiple-output (MIMO) antenna is reported in this paper for automotive communications. The MIMO antenna is constructed using the basic antenna element exploiting a slot geometry. Two such antennas are developed on the same microwave laminate to develop a two-port MIMO antenna. Two such microwave laminates are interlocked to create the four-port MIMO scheme. The most distinct feature of the proposed architecture is that the inter-port isolation is well-taken care without the need for an external decoupling unit. The four-port MIMO antenna has an overall volume of 32 × 15 × 32 mm3. The prototype MIMO antenna is fabricated and the measurements are carried out to validate the simulation results. The antenna offers ultra-wideband (UWB) characteristics covering the frequency range of 2.8–9.5 GHz. The average boresight gain of the antenna ranges from 3.2 to 5.41 dBi with the peak gain at 8 GHz. The simulated efficiency of the antenna is greater than 73% within the operating bandwidth. The MIMO parameters such as envelope correlation coefficient, diversity gain, and mean effective gain are evaluated and presented. The appropriateness of the proposed antenna for deployment in the shark fin housing of the present-day automobiles is verified using on-car performance estimation.
Can studying a topic through a reception studies approach improve the quality of Year 7 students’ creative responses to the ancient world?
Authors: Sykes Rosie
Published: March 2021

The lessons planned in this essay were designed for a group of Year 7 students in an independent girls’ school in London. Their course of study for Classics in Year 7 was a general introduction, involving beginners’ Greek and the rudiments of Latin, but largely focused on learning about Greek mythology, Homeric epic and Roman culture. Wright'sGreeks & Romanstextbook was often used in class, but the content was chosen and materials designed by the class teacher. I began teaching this class just as they were finishing Greek mythology and beginning to study theIliadandOdyssey. The sequence of four lessons, based around the Underworld was intended to provide a re-cap of the Homeric material after they had studied the two epics, as well as exploring in further detail episodes which I had skipped over for the sake of brevity in the previous sequence, such as theOdyssey'skatabasis. It also looked forward to studying Roman material in the next module by introducing theAeneidin translation.
Elucidating the Effect of Perceived Power on Destructive Responses during Romantic Conflicts
Authors: Alonso-Ferres María , Valor-Segura Inmaculada , Expósito Francisca
Published: March 2021

Prior research has indicated that the people one loves the most, such as their romantic partners, ironically, are also the people toward whom they often direct destructive behaviors in times of conflict, and such destructive responses become one of the most challenging relationship problems. Identifying the conditions that promote destructive (vs. constructive) conflict-resolution strategies is a crucial gap requiring study to help individuals build healthier and happier relationships. Across three studies (total N = 728), we examined whether (a) power is related to direct destructive (vs. constructive) responses during romantic conflicts; (b) this effect was moderated by the seriousness of the conflict and the relationship’s inclusiveness. In Study 1, participants involved in romantic relationships completed scales assessing interpersonal power, the conflict’s seriousness, their relationship’s inclusiveness, and conflict-resolution responses. In Studies 2-3, the participants were randomly assigned to complete an essay in which the conflict’s seriousness and power were experimentally manipulated. Findings from hierarchical regression analyses consistently showed that power led to destructive (and lower constructive) responses. However, this only occurred when the participants faced severe conflicts and their partner was not central to their self-concept. An internal meta-analysis of the studies confirmed the reliability and significance of these relationships; |r’s| =.13-37. Together, these results support the proposition that power asymmetries can threaten relationships by driving destructive responses during romantic conflicts, and untangle the conditions under which this happens. The conflict’s seriousness and the inclusiveness of the relationship may be considered to provide skills that help individuals navigate their relationships’ life challenges.
In Situ Observations of Whistler‐Mode Chorus Waves Guided by Density Ducts
Authors: Chen Rui , Gao Xinliang , Lu Quanming , Chen Lunjin , Tsurutani Bruce T. , Li Wen , Ni Binbin , Wang Shui
Published: March 2021

In this paper, we report the proof of the existence of density ducts in the Earth's magnetosphere by studying in situ observations of whistler‐mode chorus waves using NASA's Van Allen Probe‐A data. Chorus waves, originally excited inside the density ducts with wave normal angles (WNAs) smaller than the Gendrin angle at the near‐equatorial region, are efficiently confined to a limited area inside density ducts (i.e., ducted regions), and remain with small WNAs as they propagate toward higher latitudes. The ducted region becomes narrower for the higher‐frequency waves. Chorus waves with WNAs larger than the Gendrin angle are not guided by density ducts. Our study reveals that density ducts can effectively control the property and distribution of chorus waves, and may ultimately regulate electron dynamics in the Earth's or other planetary radiation belts.
Asymmetric Wave Distributions of Tropical Cyclones Based on CFOSAT Observations
Authors: Shi Yanping , Du Yan , Chu Xiaoqing , Tang Shilin , Shi Ping , Jiang Xingwei
Published: March 2021

Observations of the China‐France oceanography satellite are used to investigate the wave distribution's asymmetry during tropical cyclone (TC) from August 2019 to August 2020. The spatial distribution of TC waves is analyzed based on an individual case, six ocean basins, and TCs categories. A study of super typhoon Hagibis shows that the highest significant wave height (SWH) appears on the typhoon track's right side. Further analysis reveals that the highest SWH is located on the right (left) side of TC tracks in the Northern Hemisphere (Southern Hemisphere). In the Western North Pacific, North Atlantic, Eastern North Pacific, and North Indian Ocean, the highest SWH is on the right side of TCs of 251, 260, 130, and 118 km, respectively. In the South Pacific and South Indian Ocean, the highest SWH is on the left side of 70 and 128 km. According to the TC categories, the largest (smallest) departure happens during the weakest (strongest) TC. The intensifying of TC favors the wavefield's growth and reduces the asymmetry of the wave height's distribution. Both the asymmetric wind fields and the land's orographic effects impact the TC wave's distribution. In the Eastern North Pacific, the TC wind is the weakest, but the departure is not the smallest, probably due to the left continent bounding the wave energy's propagation.
Roles of Semivolatile/Intermediate‐Volatility Organic Compounds on SOA Formation Over China During a Pollution Episode: Sensitivity Analysis and Implications for Future Studies
Authors: Wu Liqing , Ling Zhenhao , Shao Min , Liu Huan , Lu Sihua , Zhou Shengzhen , Guo Junchen , Mao Jingying , Hang Jian , Wang Xuemei
Published: March 2021

To improve the performance of SOA simulations and to evaluate the roles of semivolatile/intermediate‐volatility organic compounds (S/IVOCs) on SOA formation with focus on a winter pollution episode, an updated S/IVOC emission inventory over China and optimized reaction parameterization were incorporated into a regional air quality model (i.e., the WRF‐Chem model). The simulation on atmospheric concentrations of SOA was improved with the inclusion of S/IVOC emissions and their degradation, wherein, the temporal mean bias between simulated and observed SOA concentrations decreased by 25%. With the updated S/IVOC emissions and chemical evolution parameterization, the fraction of observed SOA resolved by the model increased from 18% to 40%, of which 21% was attributed to the updated emissions while the remaining 1% was attributed to parameterization. The existence of discrepancy between observation and simulation indicated that other improvements are still needed for better simulation of SOA by the WRF‐Chem model. Using updated OH reactivity coefficient for polycyclic aromatic hydrocarbons and adding the O3‐initiated and NO3‐initiated oxidation of S/IVOCs did not significantly impact SOA formation. Model results further suggested that high SOA concentrations were mainly distributed in the Sichuan Basin, the eastern and southern China, with higher concentrations observed at night rather than during daytime. Compared with the contributions of all precursors, SOA concentrations in China were dominated by those formed from S/IVOCs, which were more sensitive to S/IVOC emissions than other parameterizations. These findings highlight the roles of S/IVOCs in SOA formation over China and provide valuable insights for future SOA simulations.
Markers of adipose tissue hypoxia are elevated in subcutaneous adipose tissue of severely obese patients with obesity hypoventilation syndrome but not in the moderately obese
Authors: Todorčević Marijana , Manuel Ari R. , Austen Luke , Michailidou Zoi , Hazlehurst Jonathan M. , Neville Matt , Stradling John R. , Karpe Fredrik
Published: March 2021

It has been suggested that metabolic dysfunction in obesity is at least in part driven by adipose tissue (AT) hypoxia. However, studies on AT hypoxia in humans have shown conflicting data. Therefore we aimed to investigate if markers of AT hypoxia were present in the subcutaneous AT of severly obese individuals (class III obesity) with and without hypoventilation syndrome (OHS) in comparison to moderately obese (class I obesity) and lean controls. To provide a proof-of-concept study, we quantified AT hypoxia by hypoxia inducible factor 1 A (HIF1A) protein abundance in human participants ranging from lean to severly obese (class III obesity). On top of that nightly arterial O2 saturation in individuals with obesity OHS was assessed. Subjects with class III obesity (BMI > 40 kg/m2) and OHS exhibited significantly higher adipose HIF1A protein levels versus those with class I obesity (BMI 30–34.9 kg/m2) and lean controls whereas those with class III obesity without OHS showed an intermediate response. HIF1A gene expression was not well correlated with protein abundance. Although these data demonstrate genuine AT hypoxia in the expected pathophysiological context of OHS, we did not observe a hypoxia signal in lesser degrees of obesity suggesting that adipose dysfunction may not be driven by hypoxia in moderate obesity.
Recurrent neural network-based volumetric fluorescence microscopy
Authors: Huang Luzhe , Chen Hanlong , Luo Yilin , Rivenson Yair , Ozcan Aydogan
Published: March 2021

Volumetric imaging of samples using fluorescence microscopy plays an important role in various fields including physical, medical and life sciences. Here we report a deep learning-based volumetric image inference framework that uses 2D images that are sparsely captured by a standard wide-field fluorescence microscope at arbitrary axial positions within the sample volume. Through a recurrent convolutional neural network, which we term as Recurrent-MZ, 2D fluorescence information from a few axial planes within the sample is explicitly incorporated to digitally reconstruct the sample volume over an extended depth-of-field. Using experiments on C. elegans and nanobead samples, Recurrent-MZ is demonstrated to significantly increase the depth-of-field of a 63×/1.4NA objective lens, also providing a 30-fold reduction in the number of axial scans required to image the same sample volume. We further illustrated the generalization of this recurrent network for 3D imaging by showing its resilience to varying imaging conditions, including e.g., different sequences of input images, covering various axial permutations and unknown axial positioning errors. We also demonstrated wide-field to confocal cross-modality image transformations using Recurrent-MZ framework and performed 3D image reconstruction of a sample using a few wide-field 2D fluorescence images as input, matching confocal microscopy images of the same sample volume. Recurrent-MZ demonstrates the first application of recurrent neural networks in microscopic image reconstruction and provides a flexible and rapid volumetric imaging framework, overcoming the limitations of current 3D scanning microscopy tools.
Wnt/β-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients
Authors: Qi Han-zhou , Ye Yi-ling , Suo Yuan , Qu Hong , Zhang Hai-yan , Yang Kai-bo , Fan Zhi-ping , Huang Fen , Xuan Li , Chen Yan-qiu , Jin Hua , Liu Qi-fa
Published: March 2021

Chronic graft-versus-host disease (cGVHD) is the main cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mesenchymal stem cells (MSCs) in bone marrow (BM) remain unclear in the pathophysiology of cGVHD. In this study, we analyzed BM-MSCs from 66 patients after allo-HSCT, including 33 with active cGVHD and 33 without cGVHD. BM-MSCs showed similar morphology, frequency, phenotype, and proliferation in patients with or without cGVHD. MSCs from the active cGVHD group showed a decreased apoptosis rate (P < 0.01). Osteogenic capacity was increased while adipogenic capacity was decreased in the active cGVHD MSCs compared with no-cGVHD MSCs. The expressions of osteogenic gene RUNX2 and COL1A1 were higher (P < 0.001) while adipogenic gene PPAR-γ and FABP4 were lower (P < 0.001) in the active cGVHD MSCs than no-cGVHD MSCs. These changes were associated with the severity of cGVHD (P < 0.0001; r = 0.534, r = 0.476, r = −0.796, and r = −0.747, respectively in RUNX2, COL1A1, PPAR-γ, and FABP4). The expression of Wnt/β-catenin pathway ligand Wnt3a was increased in cGVHD-MSCs. The dysfunction of cGVHD-MSCs could be reversed by Dickkopf related protein 1(DKK1) to inhibit the binding of Wnt3a. In summary, the differentiation of BM-MSCs was abnormal in active cGVHD, and its underlying mechanism is the upregulated of Wnt3a through Wnt/β-catenin signaling pathway of MSCs.
Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events
Authors: Kapuy Orsolya , Holczer Marianna , Márton Margita , Korcsmáros Tamás
Published: March 2021

Although autophagy is a type of programmed cell death, it is also essential for cell survival upon tolerable level of various stress events. For the cell to respond adequately to an external and/or internal stimulus induced by cellular stress, autophagy must be controlled in a highly regulated manner. By using systems biology techniques, here we explore the dynamical features of autophagy induction. We propose that the switch-like characteristic of autophagy induction is achieved by a control network, containing essential feedback loops of four components, so-called autophagy inducer, autophagy controller, mTORC1 and autophagy executor, respectively. We show how an autophagy inducer is capable to turn on autophagy in a cellular stress-specific way. The autophagy controller acts as a molecular switch and not only promotes autophagy but also blocks the permanent hyperactivation of the process via downregulating the autophagy inducer. In this theoretical analysis, we explore in detail the properties of all four proposed controlling elements and their connections. Here we also prove that the kinetic features of this control network can be considered accurate in various stress processes (such as starvation, endoplasmic reticulum stress and oxidative stress), even if the exact components may be different. The robust response of the resulting control network is essential during cellular stress.
Strain rate dependency of dislocation plasticity
Authors: Fan Haidong , Wang Qingyuan , El-Awady Jaafar A. , Raabe Dierk , Zaiser Michael
Published: March 2021

Dislocation glide is a general deformation mode, governing the strength of metals. Via discrete dislocation dynamics and molecular dynamics simulations, we investigate the strain rate and dislocation density dependence of the strength of bulk copper and aluminum single crystals. An analytical relationship between material strength, dislocation density, strain rate and dislocation mobility is proposed, which agrees well with current simulations and published experiments. Results show that material strength displays a decreasing regime (strain rate hardening) and then increasing regime (classical forest hardening) as the dislocation density increases. Accordingly, the strength displays universally, as the strain rate increases, a strain rate-independent regime followed by a strain rate hardening regime. All results are captured by a single scaling function, which relates the scaled strength to a coupling parameter between dislocation density and strain rate. Such coupling parameter also controls the localization of plasticity, fluctuations of dislocation flow and distribution of dislocation velocity.
Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice
Authors: Yoshida Tomoyuki , Yamagata Atsushi , Imai Ayako , Kim Juhyon , Izumi Hironori , Nakashima Shogo , Shiroshima Tomoko , Maeda Asami , Iwasawa-Okamoto Shiho , Azechi Kenji , Osaka Fumina , Saitoh Takashi , Maenaka Katsumi , Shimada Takashi , Fukata Yuko , Fukata Masaki , Matsumoto Jumpei , Nishijo Hisao , Takao Keizo , Tanaka Shinji , Okabe Shigeo , Tabuchi Katsuhiko , Uemura Takeshi , Mishina Masayoshi , Mori Hisashi , Fukai Shuya
Published: March 2021

Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.
Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level
Authors: Clark Helen R. , McKenney Connor , Livingston Nathan M. , Gershman Ariel , Sajjan Seema , Chan Isaac S. , Ewald Andrew J. , Timp Winston , Wu Bin , Singh Abhyudai , Regot Sergi
Published: March 2021

To prevent damage to the host or its commensal microbiota, epithelial tissues must match the intensity of the immune response to the severity of a biological threat. Toll-like receptors allow epithelial cells to identify microbe associated molecular patterns. However, the mechanisms that mitigate biological noise in single cells to ensure quantitatively appropriate responses remain unclear. Here we address this question using single cell and single molecule approaches in mammary epithelial cells and primary organoids. We find that epithelial tissues respond to bacterial microbe associated molecular patterns by activating a subset of cells in an all-or-nothing (i.e. digital) manner. The maximum fraction of responsive cells is regulated by a bimodal epigenetic switch that licenses the TLR2 promoter for transcription across multiple generations. This mechanism confers a flexible memory of inflammatory events as well as unique spatio-temporal control of epithelial tissue-level immune responses. We propose that epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses.
Common Era sea-level budgets along the U.S. Atlantic coast
Authors: Walker Jennifer S. , Kopp Robert E. , Shaw Timothy A. , Cahill Niamh , Khan Nicole S. , Barber Donald C. , Ashe Erica L. , Brain Matthew J. , Clear Jennifer L. , Corbett D. Reide , Horton Benjamin P.
Published: March 2021

Sea-level budgets account for the contributions of processes driving sea-level change, but are predominantly focused on global-mean sea level and limited to the 20th and 21st centuries. Here we estimate site-specific sea-level budgets along the U.S. Atlantic coast during the Common Era (0–2000 CE) by separating relative sea-level (RSL) records into process-related signals on different spatial scales. Regional-scale, temporally linear processes driven by glacial isostatic adjustment dominate RSL change and exhibit a spatial gradient, with fastest rates of rise in southern New Jersey (1.6 ± 0.02 mm yr−1). Regional and local, temporally non-linear processes, such as ocean/atmosphere dynamics and groundwater withdrawal, contributed between −0.3 and 0.4 mm yr−1 over centennial timescales. The most significant change in the budgets is the increasing influence of the common global signal due to ice melt and thermal expansion since 1800 CE, which became a dominant contributor to RSL with a 20th century rate of 1.3 ± 0.1 mm yr−1.
Vegetation feedback causes delayed ecosystem response to East Asian Summer Monsoon Rainfall during the Holocene
Authors: Cheng Jun , Wu Haibin , Liu Zhengyu , Gu Peng , Wang Jingjing , Zhao Cheng , Li Qin , Chen Haishan , Lu Huayu , Hu Haibo , Gao Yu , Yu Miao , Song Yaoming
Published: March 2021

One long-standing issue in the paleoclimate records is whether East Asian Summer Monsoon peaked in the early Holocene or mid-Holocene. Here, combining a set of transient earth system model simulations with proxy records, we propose that, over northern China, monsoon rainfall peaked in the early Holocene, while soil moisture and tree cover peaked in the mid-Holocene. The delayed ecosystem (soil moisture and tree cover) response to rainfall is caused by the vegetation response to winter warming and the subsequent feedback with soil moisture. Our study provides a mechanism for reconciling different evolution behaviors of monsoon proxy records; it sheds light on the driving mechanism of the monsoon evolution and monsoon-ecosystem feedback over northern China, with implications to climate changes in other high climate sensitivity regions over the globe.
NAC blocks Cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients
Authors: March Michael E. , Gutierrez-Uzquiza Alvaro , Snorradottir Asbjorg Osk , Matsuoka Leticia S. , Balvis Noelia Fonseca , Gestsson Thorgeir , Nguyen Kenny , Sleiman Patrick M. A. , Kao Charlly , Isaksson Helgi J. , Bragason Birkir Thor , Olafsson Elias , Palsdottir Astridur , Hakonarson Hakon
Published: March 2021

Hereditary cystatin C amyloid angiopathy is a dominantly inherited disease caused by a leucine to glutamine variant of human cystatin C (hCC). L68Q-hCC forms amyloid deposits in brain arteries associated with micro-infarcts, leading ultimately to paralysis, dementia and death in young adults. To evaluate the ability of molecules to interfere with aggregation of hCC while informing about cellular toxicity, we generated cells that produce and secrete WT and L68Q-hCC and have detected high-molecular weight complexes formed from the mutant protein. Incubations of either lysate or supernatant containing L68Q-hCC with reducing agents glutathione or N-acetyl-cysteine (NAC) breaks oligomers into monomers. Six L68Q-hCC carriers taking NAC had skin biopsies obtained to determine if hCC deposits were reduced following NAC treatment. Remarkably, ~50–90% reduction of L68Q-hCC staining was observed in five of the treated carriers suggesting that L68Q-hCC is a clinical target for reducing agents.
Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis
Authors: Liu Xiaonan , Chai Yu , Liu Guanqiao , Su Weiping , Guo Qiaoyue , Lv Xiao , Gao Peisong , Yu Bin , Ferbeyre Gerardo , Cao Xu , Wan Mei
Published: March 2021

Synthetic glucocorticoids (GCs), one of the most effective treatments for chronic inflammatory and autoimmune conditions in children, have adverse effects on the growing skeleton. GCs inhibit angiogenesis in growing bone, but the underlying mechanisms remain unclear. Here, we show that GC treatment in young mice induces vascular endothelial cell senescence in metaphysis of long bone, and that inhibition of endothelial cell senescence improves GC-impaired bone angiogenesis with coupled osteogenesis. We identify angiogenin (ANG), a ribonuclease with pro-angiogenic activity, secreted by osteoclasts as a key factor for protecting the neighboring vascular cells against senescence. ANG maintains the proliferative activity of endothelial cells through plexin-B2 (PLXNB2)-mediated transcription of ribosomal RNA (rRNA). GC treatment inhibits ANG production by suppressing osteoclast formation in metaphysis, resulting in impaired endothelial cell rRNA transcription and subsequent cellular senescence. These findings reveal the role of metaphyseal blood vessel senescence in mediating the action of GCs on growing skeleton and establish the ANG/PLXNB2 axis as a molecular basis for the osteoclast-vascular interplay in skeletal angiogenesis.
Author Correction: Paternal grandfather’s access to food predicts all-cause and cancer mortality in grandsons
Authors: Vågerö Denny , Pinger Pia R. , Aronsson Vanda , van den Berg Gerard J.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22367-x
Multiple analyses of various factors affecting the plantlet regeneration of Picea mongolica (H. Q. Wu) W.D. Xu from somatic embryos
Authors: Yan Jia , Peng Peng , Duan Guozhen , Lin Tao , Bai Yu´e
Published: March 2021

Picea mongolica, a native species with excellent industrial wood quality and strong sand-fixing capacity, may be utilized in construction of urban green spaces in arid areas in China. However, now the sustainability of the ecosystems where this species grows is at serious risk due to a lack of natural regeneration. In this study, we developed an efficient regeneration system and comprehensively analyzed various factors affecting somatic embryogenesis (SE) using zygotic embryos as explants. We identified the optimal plant growth regulators (PGRs) performance and the best donor trees (k81) for the generation of somatic embryos (SEMs). Additionally, we confirmed that the positive developmental window of SEMs initiation was at the end of July to early August, which is when zygotic embryos was at the late embryogeny. In this time period, specific transcripts associated with the regulation of epigenetic modifications, plant hormone-related genes, and embryonic development-related transcription factors play important roles for early SEMs initiation. These results may provide a valuable resource for vegetative propagation of Picea mongolica. Our results may help to establish a reliable protocol for plantlet regeneration, which may facilitate urban greening applications and industrialization in arid areas.
PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons
Authors: Brown Sarah J. , Boussaad Ibrahim , Jarazo Javier , Fitzgerald Julia C. , Antony Paul , Keatinge Marcus , Blechman Janna , Schwamborn Jens C. , Krüger Rejko , Placzek Marysia , Bandmann Oliver
Published: March 2021

Recent evidence suggests neurogenesis is on-going throughout life but the relevance of these findings for neurodegenerative disorders such as Parkinson’s disease (PD) is poorly understood. Biallelic PINK1 mutations cause early onset, Mendelian inherited PD. We studied the effect of PINK1 deficiency on adult neurogenesis of dopaminergic (DA) neurons in two complementary model systems. Zebrafish are a widely-used model to study neurogenesis in development and through adulthood. Using EdU analyses and lineage-tracing studies, we first demonstrate that a subset of ascending DA neurons and adjacent local-projecting DA neurons are each generated into adulthood in wild type zebrafish at a rate that decreases with age. Pink1-deficiency impedes DA neurogenesis in these populations, most significantly in early adult life. Pink1 already exerts an early effect on Th1+ progenitor cells rather than on differentiated DA neurons only. In addition, we investigate the effect of PINK1 deficiency in a human isogenic organoid model. Global neuronal differentiation in PINK1-deficient organoids and isogenic controls is similar, but PINK1-deficient organoids display impeded DA neurogenesis. The observation of impaired adult dopaminergic neurogenesis in Pink1 deficiency in two complementing model systems may have significant consequences for future therapeutic approaches in human PD patients with biallelic PINK1 mutations.
Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
Authors: Baliga Madhurima M. , Klawitter Jost , Christians Uwe , Hopp Katharina , Chonchol Michel , Gitomer Berenice Y. , Cadnapaphornchai Melissa A. , Klawitter Jelena
Published: March 2021

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. Although children with ADPKD show normal renal function, cyst development is already occurring. In this study, we aimed to identify markers and associated molecular pathways of disease progression in children and young adults with ADPKD. Plasma samples were collected during a 3-year randomized, double-blind, placebo-controlled, phase III clinical trial that was designed to test the efficacy of pravastatin on slowing down ADPKD progression in pediatric patients. Samples from 58 patients were available at baseline and at the 3-year endpoint of the study, respectively. Furthermore, plasma samples from 98 healthy children were used as controls. Metabolomic analysis was performed using liquid chromatography-tandem mass spectrometry and differences in metabolic profiles over time and within study groups were evaluated. While pravastatin therapy led to a decrease in a percent change of total kidney volume (HtTKV) in ADPKD patients, it had minimal effects on metabolite changes. Oxidative stress, endothelial dysfunction, inflammation and immune response were the most affected signaling pathways that distinguished healthy from diseased children. Pathway analysis revealed that metabolites in the arginine metabolism (urea and nitric oxide cycles), asparagine and glutamine metabolism, in the methylation cycle and kynurenine pathway were significantly changed between healthy and children with ADPDK and continued to diverge from the control levels while the disease progressed. Detected metabolite changes were primarily governed by disease progression, and less by pravastatin treatment. Identified metabolic pathways, from arginine and asparagine to kynurenine metabolism could present therapeutic targets and should be further investigated for potential to treat ADPKD progression at an early stage.
MTH1 and OGG1 maintain a low level of 8-oxoguanine in Alzheimer's brain, and prevent the progression of Alzheimer's pathogenesis
Authors: Oka Sugako , Leon Julio , Sakumi Kunihiko , Abolhassani Nona , Sheng Zijing , Tsuchimoto Daisuke , LaFerla Frank M. , Nakabeppu Yusaku
Published: March 2021

8-Oxoguanine (8-oxoG), a major oxidative base lesion, is highly accumulated in Alzheimer’s disease (AD) brains during the pathogenic process. MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby avoiding 8-oxo-dG incorporation into DNA. 8-OxoG DNA glycosylase-1 (OGG1) excises 8-oxoG paired with cytosine in DNA, thereby minimizing 8-oxoG accumulation in DNA. Levels of MTH1 and OGG1 are significantly reduced in the brains of sporadic AD cases. To understand how 8-oxoG accumulation in the genome is involved in AD pathogenesis, we established an AD mouse model with knockout of Mth1 and Ogg1 genes in a 3xTg-AD background. MTH1 and OGG1 deficiency increased 8-oxoG accumulation in nuclear and, to a lesser extent, mitochondrial genomes, causing microglial activation and neuronal loss with impaired cognitive function at 4–5 months of age. Furthermore, minocycline, which inhibits microglial activation and reduces neuroinflammation, markedly decreased the nuclear accumulation of 8-oxoG in microglia, and inhibited microgliosis and neuronal loss. Gene expression profiling revealed that MTH1 and OGG1 efficiently suppress progression of AD by inducing various protective genes against AD pathogenesis initiated by Aß/Tau accumulation in 3xTg-AD brain. Our findings indicate that efficient suppression of 8-oxoG accumulation in brain genomes is a new approach for prevention and treatment of AD.
Distinct cortical thickness patterns link disparate cerebral cortex regions to select mobility domains
Authors: Maidan Inbal , Mirelman Anat , Hausdorff Jeffrey M. , Stern Yaakov , Habeck Christian G.
Published: March 2021

The cortical control of gait and mobility involves multiple brain regions. Therefore, one could speculate that the association between specific spatial patterns of cortical thickness may be differentially associated with different mobility domains. To test this possibility, 115 healthy participants aged 27–82 (mean 60.5 ± 13.8) underwent a mobility assessment (usual-walk, dual-task walk, Timed Up and Go) and MRI scan. Ten mobility domains of relatively simple (e.g., usual-walking) and complex tasks (i.e., dual task walking, turns, transitions) and cortical thickness of 68 ROIs were extracted. All associations between mobility and cortical thickness were controlled for age and gender. Scaled Subprofile Modelling (SSM), a PCA-regression, identified thickness patterns that were correlated with the individual mobility domains, controlling for multiple comparisons. We found that lower mean global cortical thickness was correlated with worse general mobility (r = − 0.296, p = 0.003), as measured by the time to complete the Timed Up and Go test. Three distinct patterns of cortical thickness were associated with three different gait domains during simple, usual-walking: pace, rhythm, and symmetry. In contrast, cortical thickness patterns were not related to the more complex mobility domains. These findings demonstrate that robust and topographically distinct cortical thickness patterns are linked to select mobility domains during relatively simple walking, but not to more complex aspects of mobility. Functional connectivity may play a larger role in the more complex aspects of mobility.
Emergence of novel SARS-CoV-2 variants in the Netherlands
Authors: Urhan Aysun , Abeel Thomas
Published: March 2021

Coronavirus disease 2019 (COVID-19) has emerged in December 2019 when the first case was reported in Wuhan, China and turned into a pandemic with 27 million (September 9th) cases. Currently, there are over 95,000 complete genome sequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, in public databases, accompanying a growing number of studies. Nevertheless, there is still much to learn about the viral population variation when the virus is evolving as it continues to spread. We have analyzed SARS-CoV-2 genomes to identify the most variant sites, as well as the stable, conserved ones in samples collected in the Netherlands until June 2020. We identified the most frequent mutations in different geographies. We also performed a phylogenetic study focused on the Netherlands to detect novel variants emerging in the late stages of the pandemic and forming local clusters. We investigated the S and N proteins on SARS-CoV-2 genomes in the Netherlands and found the most variant and stable sites to guide development of diagnostics assays and vaccines. We observed that while the SARS-CoV-2 genome has accumulated mutations, diverging from reference sequence, the variation landscape is dominated by four mutations globally, suggesting the current reference does not represent the virus samples circulating currently. In addition, we detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters and region-specific sub-populations indicating community spread. We explored SARS-CoV-2 variants in the Netherlands until June 2020 within a global context; our results provide insight into the viral population diversity for localized efforts in tracking the transmission of COVID-19, as well as sequenced-based approaches in diagnostics and therapeutics. We emphasize that little diversity is observed globally in recent samples despite the increased number of mutations relative to the established reference sequence. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed to speed up diagnostics and vaccine design.
Analysis of residents’ food safety satisfaction from the perspective of income heterogeneity
Authors: Li Xianmei , Li Xiandong , Liao Yuanlin , Zhu Guanghui , Yu Guoxin
Published: March 2021

Food is the paramount necessity of the people, while food safety is the priority. Facing the increasingly serious food safety problems in China, how to improve food safety has become the responsibility of the whole society, and also the obligation of social development. Based on the 8000 residents’ survey data, the ordinal logistic model was used to analyze the residents’ satisfaction with food safety. The results show that residents are generally worried about food safety, and there is a strong demand for safe food. Gender, age, educational background, supervision, publicity, and complaint handling significantly affect residents’ food safety satisfaction. In terms of income heterogeneity, low-income residents have the highest degree of satisfaction with food safety. With the improvement of income level, their degree of satisfaction is decreasing. The high-income class residents have a strong consciousness of rights safeguarding after purchasing unsafe food. For low-income residents, their awareness of rights protection is declining due to insufficient income. In the way of rights protection, most respondents choose to return or refund money after negotiation with the seller. The lack of punishment for unscrupulous sellers is one of the main reasons for the frequent occurrence of food safety problems in China.