bluuebunny/crossref_metadata_2025 huggingface dataset:
The immobilised elephant at Dhauli
Authors: Srinivasan Doris Meth
Published: March 2022

The elephant at Dhauli, site of Aśoka Maurya's inscriptions, is the earliest Indian monumental sculpture. Aśoka reigned between 270–235 BC and the Dhauli elephant is dated c. 257 BC. Only the elephant's forefront is sculpted; about half of the animal's bulk remains within the rock (Figure 1). One art historian claims that Emperor Aśoka is in the vanguard presenting himself to the people of Kaliṅga. Usually, however, the Dhauli elephant is considered symbolic of the Buddha. The well-known story that Māyā dreamt that Siddhārtha entered her womb as a white elephant motivates this view; to wit śeto (i.e. śveta), ʻthe white one’, is inscribed at the end of the 6th Rock Edict.
Reforming to Avoid Reform: Strategic Policy Substitution and the Reform Gap in Policing
Authors: González Yanilda María
Published: March 2022

Institutional reforms often diverge from substantive problems and societal demands that originally prompted reform, raising questions about democratic responsiveness. Such reform gaps are prevalent in policing, wherein some police forces improve capacity and performance, while extrajudicial violence persists. I argue that police evade pressure for reform through strategic policy substitution, pressuring politicians to replace reforms that threaten bureaucratic autonomy with favorable reforms that preserve it. I describe how police act as veto players, thwarting high-threat structural and oversight reforms demanded by advocates to address violence and corruption by enacting low-threat operational and marginal reforms. Drawing on evidence from Colombia and Brazil, I demonstrate that operational reforms, (e.g., body-worn cameras and community policing) preferred by police can produce constrained institutional change. Such reforms may improve performance, but by preserving bureaucratic autonomy, they increase the police’s structural power and ability to resist future structural reforms, complicating efforts to address police violence.
Time Spent in the House: Gender and the Political Careers of U.S. House Members
Authors: Lazarus Jeffrey , Steigerwalt Amy , Clark Micayla
Published: March 2022

More women are running for and serving in the U.S. House of Representatives than ever before, but how does gender influence the careers of House members once they arrive in Congress? We find that gender matters in two important ways: first, freshmen women are older than freshmen men. Second, women are both more likely to lose a reelection race and more likely to retire because of electoral concerns than men. The result is that women have significantly shorter careers in the House than men. Both factors—women's delayed entry and early exit—produce fewer women in the House at any given time than if these disparities did not exist. These findings have significant consequences for the House's demographic makeup, ideological makeup, and policy agenda. The broader implication of our findings is that more women in the electoral arena is a necessary but not sufficient condition to make the representation of women truly equal.
Teaching Quality in Higher Education
Authors: Daumiller Martin , Janke Stefan , Hein Julia , Rinas Raven , Dickhäuser Oliver , Dresel Markus
Published: March 2022

Abstract: Teaching quality is a crucial factor within higher education. Research on this topic often requires assessing teaching quality as a global construct through self-reports. However, such instruments are criticized due to the lack of alignment between teacher and student reports of instructional practices. We argue that while teachers might over- or under-estimate specific dimensions of teaching quality, the aggregation of these dimensions in the form of overarching teaching quality well reflects differences in teaching quality between teachers. Accordingly, we test a ten-item measure that allows faculty to self-report their teaching quality based on the aspects distinguished in the SEEQ ( Marsh, 1982 , 2007 ). Using 15,503 student assessments of teaching quality in 889 sessions taught by 97 faculty members, we conducted Doubly Latent Multi Level Modelling while considering bias and unfairness variables to model overarching teaching quality assessed by students, and simultaneously corrected for measurement error and potential distortions through the assessment situation. This global factor of teaching quality was strongly associated with teacher self-reported teaching quality (ρ = .74), which we interpret as evidence that global teacher reports of teaching quality can serve as sensible indicators of overarching teaching quality for nomothetic research in higher education.
Assessing the Socio‐Economic Effects of Carbon Capture, Utility and Storage Investment From the Perspective of Carbon Neutrality in China
Authors: Chen Danbo , Jiang Mengfei
Published: March 2022

Carbon Capture, Utility and Storage (CCUS) is essential for achieving carbon neutrality and has great development potential in China. CCUS, as a long‐term new investment, can address global warming and has significant social and economic impacts. This paper assessed the socio‐economic effects of CCUS investment based on carbon neutrality in China by combining the dynamic GTAP model and the Input‐output method. The result indicates that: CCUS investment may accumulate US$ 67.09 billion and US$ 776.61 billion from 2026 to 2030 and 2056 to 2060, respectively, based on International Energy Agency (IEA) investment scenario. Moreover, the corresponding value may increase to 8.26 billion and 743.21 billion US dollars from 2026 to 2030 and 2056 to 2060, respectively, based on Asian Development Bank (ADB) investment scenario; CCUS investment may stimulate gross value‐added of US$ 1.2 billion and US$ 10.4 billion based on ADB and IEA investment scenarios, respectively. CCUS investment may mainly promote the machinery industry, metal manufacturing industry, other service industries, power equipment manufacturing industry, and light processing manufacturing industry; Furthermore, ADB and IEA investment scenarios showed that CCUS industrial investment may indirectly create about 12,796 and 103,886 jobs, respectively, and US$ 85 million and US$ 692 million of labor employment income, respectively, in 2030. The corresponding values may increase to 0.82 million and 0.85 million jobs, respectively, and US$ 5,168 and US$ 5,396 million employment income, respectively, in 2060.
The Role of Atmospheric Exchange in False‐Positive Biosignature Detection
Authors: Felton Ryan C. , Bastelberger Sandra T. , Mandt Kathleen E. , Luspay‐Kuti Adrienn , Fauchez Thomas J. , Domagal‐Goldman Shawn D.
Published: March 2022

Saturn's Moon Titan receives volatiles into the top of its atmosphere—including atomic oxygen—sourced from cryovolcanoes on Enceladus. Similar types of atmosphere exchange from one body to another, such as O2 and O3 sourced from TRAPPIST‐1 d, could be introduced into the upper atmosphere of TRAPPIST‐1 e and might be interpreted as biosignatures. We simulate this potential false‐positive for life on TRAPPIST‐1 e, by applying an external influx of water and oxygen into the top of the atmosphere using a coupled 1‐D photochemical‐climate model (Atmos), to predict atmospheric composition. In addition, synthetic spectral observations are produced using the Planetary Spectrum Generator for the James Webb Space Telescope, Origins Space Telescope, Habitable Exoplanet Observatory and Large Ultra‐violet/Optical/Infrared Surveyor to test the detectability of abiotic‐generated O2 and O3 in the presence of abiotic and biotic surface fluxes of CH4. We determine that the incoming flux of material needed to trigger detection of abiotic O2/O3 by any of these observatories is more than two orders of magnitude (1 × 1012 molecules/cm2/s) above what is physically plausible.
Probability Distributions of Radiocarbon in Open Linear Compartmental Systems at Steady‐State
Authors: Chanca Ingrid , Trumbore Susan , Macario Kita , Sierra Carlos A.
Published: March 2022

Radiocarbon (14C) is commonly used as a tracer of the carbon cycle to determine how fast carbon moves between different reservoirs such as plants, soils, rivers, or oceans. However such studies mostly emphasize the mean value (as Δ14C) of an unknown probability distribution. We introduce a novel algorithm to compute Δ14C distributions from knowledge of the age distribution of carbon in linear compartmental systems at steady‐state. Our results demonstrate that the shape of the distributions might differ according to the speed of cycling of ecosystem compartments and their connectivity within the system, and might contain multiple peaks and long tails. The distributions are also sensitive to the variations of Δ14C in the atmosphere over time, as influenced by the counteracting anthropogenic effects of fossil‐fuel emissions (14C‐free) and nuclear weapons testing (excess 14C). Lastly, we discuss insights that such distributions can offer for sampling and design of experiments aiming to capture the precise variance of Δ14C values present in the multi‐compartmental ecosystems.
The Diurnal Dynamics of Gross Primary Productivity Using Observations From the Advanced Baseline Imager on the Geostationary Operational Environmental Satellite‐R Series at an Oak Savanna Ecosystem
Authors: Khan A. M. , Stoy P. C. , Joiner J. , Baldocchi D. , Verfaillie J. , Chen M. , Otkin J. A.
Published: March 2022

Gross primary productivity (GPP) is the largest flux in the global carbon cycle and satellite‐based GPP estimates have long been used to study the trends and interannual variability of GPP. With recent updates to geostationary satellites, we can now explore the diurnal variability of GPP at a comparable spatial resolution to polar‐orbiting satellites and at temporal frequencies comparable to eddy covariance (EC) tower sites. We used observations from the Advanced Baseline Imager on the Geostationary Operational Environmental Satellite‐R series (GOES‐R) to test the ability of subdaily satellite data to capture the shifts in the diurnal course of GPP at an oak savanna EC site in California, USA that is subject to seasonal soil moisture declines. We compared three methods to estimate GPP: (a) a light‐use efficiency model, (b) a linear relationship between the product of near‐infrared reflectance of vegetation and photosynthetically active radiation (LIN‐NIRvP) and EC tower GPP, and (c) a light response curve (LRC‐NIRvP) between NIRvP and EC GPP. The LRC‐NIRvP achieved the lowest mean absolute error for winter (2 µmol CO2 m−2 s−1), spring (2.51 µmol CO2 m−2 s−1), summer (1.43 µmol CO2 m−2 s−1), and fall (1.35 µmol CO2 m−2 s−1). The ecosystem experienced the largest shift in daily peak GPP in relation to the peak of incoming solar radiation toward the morning hours during the dry summers. The LRC‐NIRvP and the light‐use efficiency model were in agreement with these patterns of a shift in peak daily GPP toward the morning hours during summer. Our results can help develop diurnal estimates of GPP from geostationary satellites that are sensitive to fluctuating environmental conditions during the day.
A Calibration‐Free Groundwater Module for Improving Predictions of Low Flows
Authors: Tashie Arik , Pavelsky Tamlin , Kumar Mukesh
Published: March 2022

Groundwater modules are critically important to the simulation of low flows in physically based land surface models (LSMs) and conceptual rainfall‐runoff models (HBV). Here, we develop a Groundwater for Ungauged Basins (GrUB) module that uses only physically based properties for which data are widely available, thus allowing its application without the need for calibration. GrUB is designed to be computationally simple and readily adaptable to a wide variety of LSMs and rainfall‐runoff models. We assess the performance of GrUB in 84 United States watersheds by incorporating it into HBV, a popular rainfall‐runoff model. We compare predictions of low flows by the native (calibrated) HBV groundwater module with those by the (uncalibrated) GrUB module and find that GrUB generates error metrics that are equivalent or superior to those generated by the (calibrated) HBV groundwater module. To assess whether predictions by GrUB are robust to changes in the structure and parameterization of the overlying hydrologic model, we run tests for two artificial scenarios: Slow Recharge with rates of percolation below 0.1 mm/day, and Fast Recharge with rates of percolation of up to 1,000 mm/day. GrUB proves to be robust to these extreme changes, with mean absolute error (MAE) of predictions of low flows only increasing by an average of up to 17%, while average MAE increases by up to 158% when the same tests are performed on HBV without the GrUB module. We suggest GrUB as a potential tool for improving predictions of low flows in LSMs, as well as rainfall‐runoff models when calibration data are sparse.
The Serpukhovian–Bashkirian Amalgamation of Laurussia and the Siberian Continent and Implications for Assembly of Pangea
Authors: Xu Yan , Han Bao‐Fu , Liao Wen , Li Ang
Published: March 2022

The final assembly of Pangea is thought to be marked by the Siberia‐Laurussia amalgamation during the Late Carboniferous–Permian, but there are large uncertainties on the timing of the amalgamation in the previous paleogeographic reconstructions because there are no high‐quality Carboniferous–Permian paleomagnetic data available from the Siberian continent. The Zharma‐Saur area in the junction between the Siberia‐Laurussia amalgamation, involving the Zharma‐Saur arc on the northern margin of the Kazakhstan microcontinent, the South Chinese Altai terrane in the southern margin of the Siberian continent and the Irtysh‐Zaisan suture in between, can provide crucial geological constraints for the assembly of Pangea. In the Zharma‐Saur arc, the Tournaisian–Visean marine sequences are interbedded with thick pillow lavas, which were formed during southward subduction of the Irtysh‐Zaisan Ocean and unconformably covered by the Moscovian terrestrial bimodal volcanic associations and sedimentary successions, in which the basalts are columnar‐jointed in structure and the sandstones also contain the detritus derived from the South Chinese Altai terrane. The Serpukhovian–Bashkirian unconformity was coeval with the transition from the Tournaisian–Visean calc‐alkaline to the Moscovian–Early Permian high alkaline and bimodal volcanism. These dramatic changes in sedimentary environments, provenances and volcanism together indicate the Siberia‐Laurussia amalgamation during the Serpukhovian–Bashkirian and this event was almost simultaneous with the Laurussia‐Gondwana collision and the welding of Laurussia with the Kazakhstan microcontinent, but slightly earlier than the Laurussia‐Tarim collision. Therefore, the final assembly of Pangea could be completed in the Late Carboniferous.
Raindrop energy-powered autonomous wireless hyetometer based on liquid–solid contact electrification
Authors: Xu Chaoqun , Fu Xianpeng , Li Chengyu , Liu Guoxu , Gao Yuyu , Qi Youchao , Bu Tianzhao , Chen Yuanfen , Wang Zhong Lin , Zhang Chi
Published: March 2022

Triboelectric nanogenerators (TENGs) can directly harvest energy via solid–liquid interface contact electrification, making them very suitable for harvesting raindrop energy and as active rainfall sensors. This technology is promising for realizing a fully self-powered system for autonomous rainfall monitoring combined with energy harvesting/sensing. Here, we report a raindrop energy-powered autonomous rainfall monitoring and wireless transmission system (R-RMS), in which a raindrop-TENG (R-TENG) array simultaneously serves as a raindrop energy harvester and rainfall sensor. At a rainfall intensity of 71 mm/min, the R-TENG array can generate an average short-circuit current, open-circuit voltage, and maximum output power of 15 μA, 1800 V, and 325 μW, respectively. The collected energy can be adjusted to act as a stable 2.5 V direct-current source for the whole system by a power management circuit. Meanwhile, the R-TENG array acts as a rainfall sensor, in which the output signal can be monitored and the measured data are wirelessly transmitted. Under a rainfall intensity of 71 mm/min, the R-RMS can be continuously powered and autonomously transmit rainfall data once every 4 min. This work has paved the way for raindrop energy-powered wireless hyetometers, which have exhibited broad prospects in unattended weather monitoring, field surveys, and the Internet of Things.
Cognitive glucose sensitivity—proposing a link between cognitive performance and reliance on external glucose uptake
Authors: Neukirchen Tobias , Radach Ralph , Vorstius Christian
Published: March 2022

Existing evidence on the effects of glucose supplementation on cognitive performance appears inconclusive. Metabolic switching offers an approach to explain such incoherent findings based on differences in cognitive functioning after fasting. We propose a new construct, cognitive glucose sensitivity (CGS), which quantifies individual performance gain due to glucose supplementation. We tested the hypothesis that the effects of glucose ingestion depend on CGS, cognitive task domain, and sex. In addition, the relationship between CGS and body mass index (BMI) was examined. Seventy-one participants (48 female) were tested in two conditions each (deprivation baseline vs. glucose supplementation), performing tasks from different cognitive domains (memory and executive functioning). We found significant evidence for a correlation of deprivation baseline performance and CGS across domains (Corsi-Block-Tapping Task: r = −0.57, p < 0.001; Go-No-Go Task: r = 0.39, p = 0.001; word list recall: r = −0.50, p < 0.001). Moreover, individual CGS differed significantly between tasks (p = 0.018). Only in men, BMI was significantly related to CGS in a word recall paradigm (r = 0.49, p = 0.017). Our findings support the notion that the effects of glucose depend on CGS, task domain, and sex. The effort to reduce performance impairment (short-term) might sacrifice independence from external glucose (long term), possibly via declining blood glucose regulation. Therefore, CGS could be regarded as a candidate to enhance our understanding of the etiology of unhealthy eating.
Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial
Authors: Tiwari Arun K. , Zai Clement C. , Altar C. Anthony , Tanner Julie-Anne , Davies Paige E. , Traxler Paul , Li James , Cogan Elizabeth S. , Kucera Matthew T. , Gugila Ana , Braganza Nicole , Emmerson Heather , Zai Gwyneth , Müller Daniel J. , Levitan Robert , Kloiber Stefan , Daskalakis Zafiris J. , Frey Benicio N. , Bowen James M. , Tarride Jean-Eric , Tytus Richard , Chandrasena Ranjith , Voudouris Nicholas , Taylor Valerie H. , Tempier Raymond , Sharma Verinder , Vasudev Akshya , Dzongowski Peter , Pliamm Lew , Greenspoon Todd , Dechairo Bryan M. , Kennedy James L.
Published: March 2022

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. (“GUIDED”), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian “GAPP-MDD” RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).
Distinct contributions of GluA1-containing AMPA receptors of different hippocampal subfields to salience processing, memory and impulse control
Authors: Kilonzo Kasyoka , Strahnen Daniel , Prex Vivien , Gems John , van der Veen Bastiaan , Kapanaiah Sampath K. T. , Murthy Bhargavi K. B. , Schulz Stefanie , Sprengel Rolf , Bannerman David , Kätzel Dennis
Published: March 2022

Schizophrenia is associated with a broad range of severe and currently pharmacoresistant cognitive deficits. Prior evidence suggests that hypofunction of AMPA-type glutamate receptors (AMPARs) containing the subunit GLUA1, encoded by GRIA1, might be causally related to impairments of selective attention and memory in this disorder, at least in some patients. In order to clarify the roles of GluA1 in distinct cell populations, we investigated behavioural consequences of selective Gria1-knockout in excitatory neurons of subdivisions of the prefrontal cortex and the hippocampus, assessing sustained attention, impulsivity, cognitive flexibility, anxiety, sociability, hyperactivity, and various forms of short-term memory in mice. We found that virally induced reduction of GluA1 across multiple hippocampal subfields impaired spatial working memory. Transgene-mediated ablation of GluA1 from excitatory cells of CA2 impaired short-term memory for conspecifics and objects. Gria1 knockout in CA3 pyramidal cells caused mild impairments of object-related and spatial short-term memory, but appeared to partially increase social interaction and sustained attention and to reduce motor impulsivity. Our data suggest that reduced hippocampal GluA1 expression—as seen in some patients with schizophrenia—may be a central cause particularly for several short-term memory deficits. However, as impulse control and sustained attention actually appeared to improve with GluA1 ablation in CA3, strategies of enhancement of AMPAR signalling likely require a fine balance to be therapeutically effective across the broad symptom spectrum of schizophrenia.
Rubicon-deficiency sensitizes mice to mixed lineage kinase domain-like (MLKL)-mediated kidney ischemia-reperfusion injury
Authors: Tonnus Wulf , Locke Sophie , Meyer Claudia , Maremonti Francesca , Eggert Lena , von Mässenhausen Anne , Bornstein Stefan R. , Green Douglas R. , Linkermann Andreas
Published: March 2022

The cytosolic protein rubicon (RUBCN) has been implicated in the removal of necrotic debris and autoimmunity. However, the role of RUBCN in models of acute kidney injury (AKI), a condition that typically involves necrotic kidney tubules, was not investigated. Here, we demonstrate that RUBCN-deficient mice are hypersensitive to renal damage induced by ischemia-reperfusion injury (IRI) and cisplatin-induced AKI. Combined deficiency of RUBCN and mixed lineage kinase domain-like (MLKL) partially reversed the sensitivity in the IRI model suggesting that the absence of RUBCN sensitizes to necroptosis in that model. Necroptosis is known to contribute to TNFα-induced severe inflammatory response syndrome (SIRS), but we detected no statistically significant difference in overall survival following injection of TNFα in RUBCN-deficient mice. We additionally generated RUBCN-deficient mice which lack gasdermin D (GSDMD), the terminal mediator of pyroptosis, but no reversal of the AKI phenotype was observed. Finally, and in contrast to the previous understanding of the role of RUBCN, we did not find a significant autoimmune phenotype in RUBCN-deficient mice, but detected chronic kidney injury (CKD) in aged RUBCN-deficient mice of both sexes. In summary, our data indicate that RUBCN-deficient mice are hypersensitive to kidney injury.
An integrated bioinformatic investigation of mitochondrial solute carrier family 25 (SLC25) in colon cancer followed by preliminary validation of member 5 (SLC25A5) in tumorigenesis
Authors: Chen Yan-Jie , Hong Wei-Feng , Liu Meng-Ling , Guo Xi , Yu Yi-Yi , Cui Yue-Hong , Liu Tian-Shu , Liang Li
Published: March 2022

Solute carrier family 25 (SLC25) encodes transport proteins at the inner mitochondrial membrane and functions as carriers for metabolites. Although SLC25 genetic variants correlate with human metabolic diseases, their roles in colon cancer remain unknown. Cases of colon cancer were retrieved from The Cancer Genome Atlas, and the transcriptionally differentially expressed members (DEMs) of SLC25 were identified. DNA level alterations, clinicopathological characteristics, and clinical survival were also investigated. A risk score model based on the DEMs was constructed to further evaluate their prognostic values in a clinical setting. The results were preliminarily validated using bioinformatic analysis of datasets from the Gene Expression Omnibus, immunohistochemical evaluations in clinical specimens, and functional experiments in colon cancer-derived cell lines. Thirty-seven DEMs were identified among 53 members of SLC25. Eight of 37 DEMs were introduced into a risk score model using integrated LASSO regression and multivariate Cox regression. Validated by GSE395282 and GSE175356, DEMs with high-risk scores were associated with the phenotypes of increasing tumor immune infiltration and decreasing glycolysis and apoptosis contents. SLC25A5 was downregulated in cancer, and its upregulation was related to better overall survival in patients from public datasets and in clinical cases. High SLC25A5 expression was an independent prognostic factor for 79 patients after surgical treatment. A negative correlation between CD8 and SLC25A5 was determined in specimens from 106 patients with advanced colon cancer. SLC25A5 attenuated cell proliferation, upregulated the expression of programmed cell death-related signatures, and exerted its biological function by inhibiting the MAPK signaling pathway. Our study reveals that mitochondrial SLC25 has prognostic value in patients with colon cancer. The bioinformatic analyses by following verification in situ and in vitro provide direction for further functional and mechanistic studies on the identified member of SLC25.
Hyperglycemia-triggered ATF6-CHOP pathway aggravates acute inflammatory liver injury by β-catenin signaling
Authors: Yang Chao , Wang Zeng , Hu Yuanchang , Yang Shikun , Cheng Feng , Rao Jianhua , Wang Xuehao
Published: March 2022

Although hyperglycemia has been documented as an unfavorable element that can further induce liver ischemia–reperfusion injury (IRI), the related molecular mechanisms remain to be clearly elaborated. This study investigated the effective manner of endoplasmic reticulum (ER) stress signaling in hyperglycemia-exacerbated liver IRI. Here we demonstrated that in the liver tissues and Kupffer cells (KCs) of DM patients and STZ-induced hyperglycemic mice, the ER stress-ATF6-CHOP signaling pathway is activated. TLR4-mediated pro-inflammatory activation was greatly attenuated by the addition of 4-phenylbutyrate (PBA), one common ER stress inhibitor. The liver IRI in hyperglycemic mice was also significantly reduced after PBA treatment. In addition, deficiency of CHOP (CHOP−/−) obviously alleviates the hepatic IRI, and pro-inflammatory effects deteriorated by hyperglycemia. In hyperglycemic mice, β-catenin expression was suppressed while the ATF6-CHOP signal was activated. In the liver tissues of PBA-treated or CHOP−/− hyperglycemic mice, the expression of β-catenin was restored. Furthermore, CHOP deficiency can induce protection against hyperglycemia-related liver IRI, which was disrupted by the knockdown of β-catenin will cause this protection to disappear. High glucose (HG) treatment stimulated ATF6-CHOP signaling, reduced cellular β-catenin accumulation, and promoted the TLR4-related inflammation of BMDMs. But the above effects were partially rescued in BMDMs with CHOP deficiency or by PBA treatment. In BMDMs cultured in HG conditions, the anti-inflammatory functions of CHOP−/− were destroyed by the knockdown of β-catenin. Finally, chimeric mice carrying WT or CHOP−/− BMDMs by bone marrow transplantation were adopted to verify the above conclusion. The current study suggested that hyperglycemia could trigger ER stress-ATF6-CHOP axis, inhibit β-catenin activation, accelerate inflammation, and deteriorate liver IRI, thus providing the treatment potential for management of sterile liver inflammation in DM patients.
A specialized bone marrow microenvironment for fetal haematopoiesis
Authors: Liu Yang , Chen Qi , Jeong Hyun-Woo , Koh Bong Ihn , Watson Emma C. , Xu Cong , Stehling Martin , Zhou Bin , Adams Ralf H.
Published: March 2022

In adult mammalian bone marrow (BM), vascular endothelial cells and perivascular reticular cells control the function of haematopoietic stem and progenitor cells (HSPCs). During fetal development, the mechanisms regulating the de novo haematopoietic cell colonization of BM remain largely unknown. Here, we show that fetal and adult BM exhibit fundamental differences in cellular composition and molecular interactions by single cell RNA sequencing. While fetal femur is largely devoid of leptin receptor-expressing cells, arterial endothelial cells (AECs) provide Wnt ligand to control the initial HSPC expansion. Haematopoietic stem cells and c-Kit+ HSPCs are reduced when Wnt secretion by AECs is genetically blocked. We identify Wnt2 as AEC-derived signal that activates β-catenin-dependent proliferation of fetal HSPCs. Treatment of HSPCs with Wnt2 promotes their proliferation and improves engraftment after transplantation. Our work reveals a fundamental switch in the cellular organization and molecular regulation of BM niches in the embryonic and adult organism.
Texture is encoded in precise temporal spiking patterns in primate somatosensory cortex
Authors: Long Katie H. , Lieber Justin D. , Bensmaia Sliman J.
Published: March 2022

Humans are exquisitely sensitive to the microstructure and material properties of surfaces. In the peripheral nerves, texture information is conveyed via two mechanisms: coarse textural features are encoded in spatial patterns of activation that reflect their spatial layout, and fine features are encoded in highly repeatable, texture-specific temporal spiking patterns evoked as the skin moves across the surface. Here, we examined whether this temporal code is preserved in the responses of neurons in somatosensory cortex. We scanned a diverse set of everyday textures across the fingertip of awake macaques while recording the responses evoked in individual cortical neurons. We found that temporal spiking patterns are highly repeatable across multiple presentations of the same texture, with millisecond precision. As a result, texture identity can be reliably decoded from the temporal patterns themselves, even after information carried in the spike rates is eliminated. However, the combination of rate and timing is more informative than either code in isolation. The temporal precision of the texture response is heterogenous across cortical neurons and depends on the submodality composition of their input and on their location along the somatosensory neuraxis. Furthermore, temporal spiking patterns in cortex dilate and contract with decreases and increases in scanning speed, respectively, and this systematic relationship between speed and patterning may contribute to the observed perceptual invariance to speed. Finally, we find that the quality of a texture percept can be better predicted when these temporal patterns are taken into consideration. We conclude that high-precision spike timing complements rate-based signals to encode texture in somatosensory cortex.
Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress
Authors: Park Kihyoun , Lim Hyejin , Kim Jinyoung , Hwang Yeseong , Lee Yu Seol , Bae Soo Han , Kim Hyeongseok , Kim Hail , Kang Shin-Wook , Kim Joo Young , Lee Myung-Shik
Published: March 2022

Although autophagy is critical for pancreatic β-cell function, the role and mechanism of mitophagy in β-cells are unclear. We studied the role of lysosomal Ca2+ in TFEB activation by mitochondrial or metabolic stress and that of TFEB-mediated mitophagy in β-cell function. Mitochondrial or metabolic stress induced mitophagy through lysosomal Ca2+ release, increased cytosolic Ca2+ and TFEB activation. Lysosomal Ca2+ replenishment by ER- > lysosome Ca2+ refilling was essential for mitophagy. β-cell-specific Tfeb knockout (TfebΔβ-cell) abrogated high-fat diet (HFD)-induced mitophagy, accompanied by increased ROS and reduced mitochondrial cytochrome c oxidase activity or O2 consumption. TfebΔβ-cell mice showed aggravation of HFD-induced glucose intolerance and impaired insulin release. Metabolic or mitochondrial stress induced TFEB-dependent expression of mitophagy receptors including Ndp52 and Optn, contributing to the increased mitophagy. These results suggest crucial roles of lysosomal Ca2+ release coupled with ER- > lysosome Ca2+ refilling and TFEB activation in mitophagy and maintenance of pancreatic β-cell function during metabolic stress.
An achromatic X-ray lens
Authors: Kubec Adam , Zdora Marie-Christine , Sanli Umut T. , Diaz Ana , Vila-Comamala Joan , David Christian
Published: March 2022

Diffractive and refractive optical elements have become an integral part of most high-resolution X-ray microscopes. However, they suffer from inherent chromatic aberration. This has to date restricted their use to narrow-bandwidth radiation, essentially limiting such high-resolution X-ray microscopes to high-brightness synchrotron sources. Similar to visible light optics, one way to tackle chromatic aberration is by combining a focusing and a defocusing optic with different dispersive powers. Here, we present the first successful experimental realisation of an X-ray achromat, consisting of a focusing diffractive Fresnel zone plate (FZP) and a defocusing refractive lens (RL). Using scanning transmission X-ray microscopy (STXM) and ptychography, we demonstrate sub-micrometre achromatic focusing over a wide energy range without any focal adjustment. This type of X-ray achromat will overcome previous limitations set by the chromatic aberration of diffractive and refractive optics and paves the way for new applications in spectroscopy and microscopy at broadband X-ray tube sources.
Phylogenomic analyses highlight innovation and introgression in the continental radiations of Fagaceae across the Northern Hemisphere
Authors: Zhou Biao-Feng , Yuan Shuai , Crowl Andrew A. , Liang Yi-Ye , Shi Yong , Chen Xue-Yan , An Qing-Qing , Kang Ming , Manos Paul S. , Wang Baosheng
Published: March 2022

Northern Hemisphere forests changed drastically in the early Eocene with the diversification of the oak family (Fagaceae). Cooling climates over the next 20 million years fostered the spread of temperate biomes that became increasingly dominated by oaks and their chestnut relatives. Here we use phylogenomic analyses of nuclear and plastid genomes to investigate the timing and pattern of major macroevolutionary events and ancient genome-wide signatures of hybridization across Fagaceae. Innovation related to seed dispersal is implicated in triggering waves of continental radiations beginning with the rapid diversification of major lineages and resulting in unparalleled transformation of forest dynamics within 15 million years following the K-Pg extinction. We detect introgression at multiple time scales, including ancient events predating the origination of genus-level diversity. As oak lineages moved into newly available temperate habitats in the early Miocene, secondary contact between previously isolated species occurred. This resulted in adaptive introgression, which may have further amplified the diversification of white oaks across Eurasia.
DNA methylation-free Arabidopsis reveals crucial roles of DNA methylation in regulating gene expression and development
Authors: He Li , Huang Huan , Bradai Mariem , Zhao Cheng , You Yin , Ma Jun , Zhao Lun , Lozano-Durán Rosa , Zhu Jian-Kang
Published: March 2022

A contribution of DNA methylation to defense against invading nucleic acids and maintenance of genome integrity is uncontested; however, our understanding of the extent of involvement of this epigenetic mark in genome-wide gene regulation and plant developmental control is incomplete. Here, we knock out all five known DNA methyltransferases in Arabidopsis, generating DNA methylation-free plants. This quintuple mutant exhibits a suite of developmental defects, unequivocally demonstrating that DNA methylation is essential for multiple aspects of plant development. We show that CG methylation and non-CG methylation are required for a plethora of biological processes, including pavement cell shape, endoreduplication, cell death, flowering, trichome morphology, vasculature and meristem development, and root cell fate determination. Moreover, we find that DNA methylation has a strong dose-dependent effect on gene expression and repression of transposable elements. Taken together, our results demonstrate that DNA methylation is dispensable for Arabidopsis survival but essential for the proper regulation of multiple biological processes.
Deciphering the mechanism of the Ni-photocatalyzed C‒O cross-coupling reaction using a tridentate pyridinophane ligand
Authors: Na Hanah , Mirica Liviu M.
Published: March 2022

Photoredox nickel catalysis has emerged as a powerful strategy for cross-coupling reactions. Although the involvement of paramagnetic Ni(I)/Ni(III) species as active intermediates in the catalytic cycle has been proposed, a thorough spectroscopic investigation of these species is lacking. Herein, we report the tridentate pyridinophane ligandsRN3 that allow for detailed mechanistic studies of the photocatalytic C–O coupling reaction. The derived (RN3)Ni complexes are active catalysts under mild conditions and without an additional photocatalyst. We also provide direct evidence for the key steps involving paramagnetic Ni species in the proposed catalytic cycle: the oxidative addition of an aryl halide to a Ni(I) species, the ligand exchange/transmetalation at a Ni(III) center, and the C–O reductive elimination from a Ni(III) species. Overall, the present work suggests theRN3 ligands are a practical platform for mechanistic studies of Ni-catalyzed reactions and for the development of new catalytic applications.
Catalyst-controlled functionalization of carboxylic acids by electrooxidation of self-assembled carboxyl monolayers
Authors: Hintz Heather A. , Sevov Christo S.
Published: March 2022

While the electrooxidative activation of carboxylic acids is an attractive synthetic methodology, the resulting transformations are generally limited to either homocoupling or further oxidation followed by solvent capture. These reactions require extensive electrolysis at high potentials, which ultimately renders the methodology incompatible with metal catalysts that could possibly provide new and complementary product distributions. This work establishes a proof-of-concept for a rare and synthetically-underutilized strategy for selective electrooxidation of carboxylic acids in the presence of oxidatively-sensitive catalysts that control reaction selectivity. We leverage the formation of self-adsorbed monolayers of carboxylate substrates at the anode to promote selective oxidation of the adsorbed carboxylate over a more easily-oxidized catalyst. Consequently, reactions operate at lower potentials, greater faradaic efficiencies, and improved catalyst compatibility over conventional approaches, which enables reactions to be performed with inexpensive Fe complexes that catalyze selective radical additions to olefins.
Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas
Authors: Brastianos Priscilla K. , Kim Albert E. , Giobbie-Hurder Anita , Lee Eudocia Quant , Wang Nancy , Eichler April F. , Chukwueke Ugonma , Forst Deborah A. , Arrillaga-Romany Isabel C. , Dietrich Jorg , Corbin Zachary , Moliterno Jennifer , Baehring Joachim , White Michael , Lou Kevin W. , Larson Juliana , de Sauvage Magali A. , Evancic Kathryn , Mora Joana , Nayyar Naema , Loeffler Jay , Oh Kevin , Shih Helen A. , Curry William T. , Cahill Daniel P. , Barker Fred G. , Gerstner Elizabeth R. , Santagata Sandro
Published: March 2022

High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31–0.66) and a median PFS of 7.6 months (90% CI: 3.4–12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.
Forecasting and modeling of the COVID-19 pandemic in the USA with a timed intervention model
Authors: Hachtel Gary D. , Stack John D. , Hachtel Jordan A.
Published: March 2022

We propose a novel Timed InterventionS, P, E, I, Q, R, D model for projecting the possible futures of the COVID-19 pandemic in the USA. The proposed model introduces a series of timed interventions that can account for the influence of real time changes in government policy and social norms. We consider three separate types of interventions: (i) Protective interventions: Where population moves from susceptible to protected corresponding to mask mandates, stay-at-home orders and/or social distancing. (ii) Release interventions: Where population moves from protected to susceptible corresponding to social distancing mandates and practices being lifted by policy or pandemic fatigue. (iii) Vaccination interventions: Where population moves from susceptible, protected, and exposed to recovered (meaning immune) corresponding to the mass immunization of the U.S. Population. By treating the pandemic with timed interventions, we are able to model the pandemic extremely effectively, as well as directly predicting the course of the pandemic under differing sets of intervention schedules. We show that without prompt effective protective/vaccination interventions the pandemic will be extended significantly and result in many millions of deaths in the U.S.
Preparation of Thymus vulgaris (L.) essential oil nanoemulsion and its chitosan encapsulation for controlling mosquito vectors
Authors: Gupta Parisa , Preet Shabad , Ananya  , Singh Navneet
Published: March 2022

Here, we report a novel comparative assessment of preparation and characterization of thyme oil nanoemulsion and its chitosan encapsulation using high energy approach for the management of three major mosquito species viz., Anopheles stephensi (Liston,1901), Aedes aegypti (Linn., 1762) and Culex tritaeniorhynchus (Giles, 1901). The synthesized formulations were analysed for thermodynamic stability, indicating 1:0.5 (oil: surfactant) ratio to be the most stable of thyme oil nanoemulsion while 1:1 (nanoemulsion: chitosan solution) ratio of its chitosan encapsulation. These were further characterized by dynamic light scattering and transmission electron microscopy which revealed the size and morphology of the droplets which measured 52.18 ± 4.53 nm for thyme oil nanoemulsion and 50.18 ± 2.32 nm for its chitosan encapsulation. All the droplets were well dispersed with distinct flower-shaped nanoemulsion and somewhat mitochondria like chitosan encapsulation. In-vitro release study of thyme essential oil from its nanoemulsion and chitosan encapsulation showed that 91.68% and 73.41% of the total oil concentration in water was released respectively to the environment after 48 h clearly depicting controlled release in the encapsulation. Assessment of insecticidal potential against selected mosquito species revealed that both the nanoemulsion and its chitosan encapsulation were effective on the major mosquito species. Maximum activity of thyme oil nanoemulsion was noticed against C. tritaeniorhynchus (LC50—22.58 ppm) after 24 h of exposure while it was observed that its chitosan encapsulation was most effective on A. stephensi (LC50—18.88 ppm) after 24 h of exposure. Consistent morphological alterations could be noticed in the larvae of mosquito species. Hence, these nanoemulsions and encapsulations could be further tested for their applications against other insect pests in agriculture.
Media-multitasking and cognitive control across the lifespan
Authors: Matthews Natasha , Mattingley J. B. , Dux P. E.
Published: March 2022

The exponential rise in technology use over the past decade, and particularly during the COIVD-19 pandemic, has been accompanied by growing concern regarding the consequences of this technology use for our cognition. Previous studies on the influence of technology-multitasking (the use of two or more technologies simultaneously) on cognitive performance have provided mixed results. However, these past studies have generally ignored the considerable developmental trajectories that cognitive abilities undergo across the lifespan. In a large community-based science project we investigated the relationship between media-multitasking and cognitive flexibility (multitasking ability) in participants aged 7–70 years. Higher levels of every-day technology multitasking were associated with higher levels of multitasking performance across an age range in which multitasking ability undergoes developmental change. These findings suggest that age is an important moderator of the relationship between technology use and cognition.
A hybrid approach to enhance the lifespan of WSNs in nuclear power plant monitoring system
Authors: Haque Md Ershadul , Hossain Tanvir , Sarker Mahidur R. , Paul Manoranjan , Hoque Md Samiul , Uddin Salah , Suman Abdulla Al , Md Saad Mohamad Hanif , Ul Huque Tanvir
Published: March 2022

In recent years, the nuclear power plant has received huge attention as it generates vast amounts of power at a lower cost. However, its creation of radioactive wastes is a major environmental concern. Therefore, the nuclear power plant requires a reliable and uninterrupted monitoring system as an essential part of it. Monitoring a nuclear power plant using wireless sensor networks is a convenient and popular practice now. This paper proposes a hybrid approach for monitoring wireless sensor networks in the context of a nuclear power plant in Bangladesh. Our hybrid approach enhances the lifespan of wireless sensor networks reducing power consumption and offering better connectivity of sensors. To do so, it uses both the topology maintenance and topology construction algorithms. We found that the HGETRecRot topology maintenance algorithm enhances the network lifetime compared to other algorithms. This algorithm increases the communication and sensing coverage area but decreases the network performance. We also propose a prediction model, based on linear regression algorithm, that predicts the best combination of topology maintenance and topology construction algorithms.