bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical investigation of the influence of casting techniques on fiber orientation distribution in ECC
Authors: Van Chung Nguyen , Tran Thanh Hai , Nguyen Thuc Nhu , Li Jianchun
Published: December 2022

Engineered cementitious composites (ECC), also known as bendable concrete, were developed based on engineering the interactions between fibers and cementitious matrix. The orientation of fibers, in this regard, is one of the major factors influencing the ductile behavior of this material. In this study, fiber orientation distributions in ECC beams influenced by different casting techniques are evaluated via numerical modeling of the casting process. Two casting directions and two casting positions of the funnel outlet with beam specimens are modeled using a particle-based smoothed particle hydrodynamics (SPH) method. In this SPH approach, fresh mortar and fiber are discretized by separated mortar and fiber particles, which smoothly interact in the computational domain of SPH. The movement of fiber particles is monitored during the casting simulation. Then, the fiber orientations at different sections of specimens are determined after the fresh ECC stops flowing in the formwork. The simulation results show a significant impact of the casting direction on fiber orientation distributions along the longitudinal wall of beams, which eventually influence the flexural strength of beams. In addition, casting positions show negligible influences on the orientation distribution of fibers in the short ECC beam, except under the pouring position.
Associations of preterm and early-term birth with suspected developmental coordination disorder: a national retrospective cohort study in children aged 3–10 years
Authors: Liu Ming-Xia , Li Hai-Feng , Wu Mei-Qin , Geng Shan-Shan , Ke Li , Lou Bi-Wen , Du Wenchong , Hua Jing
Published: December 2022

Background

This study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm (< 34+0 gestational age), late preterm (34+0–36+6 gestational week), and early-term (37+0–38+6 gestational week) children compared to their full-term peers with a national population-based sample in China.

Methods

A total of 1673 children (799 girls, 874 boys) aged 3–10 years old were individually assessed with the Movement Assessment Battery for Children-second edition (MABC-2). The association between gestational age and motor performance of children was analyzed using a multilevel regression model.

Results

The global motor performance [β =  – 5.111, 95% confidence interval (CI) =  – 9.200 to – 1.022; P = 0.015] and balance (β =  – 5.182, 95% CI =  – 5.055 to – 1.158; P = 0.003) for very and moderately preterm children aged 3–6 years old were significantly lower than their full-term peers when adjusting for confounders. Late preterm and early-term children showed no difference. Moreover, very and moderately preterm children aged 3–6 years had a higher risk of suspected developmental coordination disorder (DCD) (≤ 5 percentile of MABC-2 score) when adjusting for potential confounders [odds ratio (OR) = 2.931, 95% CI = 1.067–8.054; P = 0.038]. Late preterm and early-term children showed no difference in motor performance from their full-term peers (each P > 0.05).

Conclusions

Our findings have important implications for understanding motor impairment in children born at different gestational ages. Very and moderately preterm preschoolers have an increased risk of DCD, and long-term follow-up should be provided for early detection and intervention.
Literaturreview zu partizipativer Technologieentwicklung in der Behinderten- und Erziehungshilfe im Kontext Sozialer Arbeit
Authors: Mildenberger Tabea , Schmier Alena , Zorn Isabel
Published: December 2022

Ziel der Literaturstudie war es herauszufinden, welche wissenschaftlichen Projekte zu partizipativer Technikentwicklung in der Erziehungshilfe und jugendbezogener Behindertenhilfe bereits durchgeführt wurden und wie im wissenschaftlichen Diskurs der Sozialen Arbeit die Thematik partizipativer Technologieentwicklung in Einrichtungen der Jugend- und Behindertenhilfe behandelt wird. Ziel ist auch, die angewendete systematische Recherchestrategie zu beschreiben. Methodisch folgt der systematische Literaturreview einem definierten Korpus der relevanten, überwiegend deutschsprachigen wissenschaftlichen Fachzeitschriften Sozialer Arbeit zwischen 1994 und Mai 2020. Durchsucht wurden jene Fachzeitschriften, die sich mit Themengebieten angrenzend zur Forschungsfrage befassen: die Thematik der Jugend(hilfe), Medien, Technologie oder Digitalisierung. Der systematische Literaturreview benennt beforschte Felder und Themen. Die Ergebnisdarstellung erfolgt dabei kategorienbasiert entlang den Forschungslinien Partizipative Forschung, Assistenztechnologien, Handlungsanweisungen für Medienkompetenz von Jugendlichen und Digitalisierung in der Sozialen Arbeit. Der Beitrag zeigt Desiderata für zukünftige Forschung zu partizipativer Technikentwicklung in der Sozialen Arbeit auf.
Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells
Authors: Pérez-Cremades Daniel , Bueno-Betí Carlos , García-Giménez José Luis , Ibañez-Cabellos José Santiago , Pallardó Federico V. , Hermenegildo Carlos , Novella Susana
Published: December 2022

Extracellular histones have been reported to aggravate different pathophysiological processes by increasing vascular permeability, coagulopathy, and inflammation. In the present study, we elucidate how extracellular histones (10–100 µg/mL) concentration dependently increase cytosolic reactive oxygen species (ROS) production using human umbilical vein endothelial cells (HUVECs). Furthermore, we identify cyclooxygenase (COX) and NADPH oxidase (NOX) activity as sources of ROS production in extracellular histone-treated HUVEC. This COX/NOX-mediated ROS production is also involved in enhanced NF-kB activity and cell adhesion molecules (VCAM1 and ICAM1) expression in histone-treated HUVEC. Finally, by using different toll-like receptor (TLR) antagonists, we demonstrate the role of TLR4 in CAMs overexpression triggered by extracellular histones in endothelial cells. In conclusion, our data suggest that through TLR4 signaling, extracellular histones increase endothelial cell activation, a mechanism involving increased COX- and NOX-mediated ROS. These findings increase our understanding on how extracellular histones enhance systemic inflammatory responses in diseases in which histone release occurs as part of the pathological processes.
Resveratrol ameliorates the behavioural and molecular changes in rats exposed to uninephrectomy: role of hippocampal SIRT1, BDNF and AChE
Authors: Basta Marianne , Saleh Samar. R. , Aly Rania. G. , Dief Abeer. E.
Published: December 2022

Subtle memory and cognitive changes may occur in uninephrectomized (Unix) patients long before the development of chronic kidney disease, such changes may be unnoticed. The dietary polyphenol, Resveratrol, displayed various neuroprotective effects, its role in chronic kidney disease is an area of intense studies. This work was designed to investigate the behavioural and molecular changes that may occur following 7 months of Unix in rats, and to determine whether Resveratrol intake can improve such pathology. Male Wistar rats were divided into three groups: sham operated, Unix and Unix group treated with Resveratrol (20 mg/kg/day). Rats were subjected to series of behavioural testing, different biochemical parameters along with RT-PCR and immunohistochemistry of the hippocampal tissue to track the development of functional or structural brain changes. Anxiety behaviour and reduced spatial memory performance were observed in rats 7 months post-nephrectomy; these deficits were remarkably reversed with Resveratrol. Among the species typical behaviour, burrowing was assessed; it showed significant impairment post-nephrectomy. Resveratrol intake was almost able to increase the burrowing behaviour. Decreased SIRT1 in immune-stained sections, oxidative stress, inflammatory changes, and increased AChE activity in hippocampal homogenates were found in Unix rats, and Resveratrol once more was capable to reverse such pathological changes. This work has investigated the occurrence of behavioural and structural brain changes 7 months following Unix and underlined the importance of Resveratrol to counterbalance the behavioural impairment, biochemical and brain pathological changes after uninephrectomy. These findings may raise the possible protective effects of Resveratrol intake in decreased kidney function.
Diagnostic Relations for the Intercept Parameter of Exponential Raindrop Size Distribution According to Rain Types Derived from Disdrometer Data and Their Impacts on Precipitation Prediction
Authors: Lee Joohyun , Jin Han-Gyul , Baik Jong-Jin
Published: December 2022

The raindrop size distribution observed from ground-based or airborne disdrometers has been widely used to understand the characteristics of clouds and precipitation. However, its variability needs to be studied further and properly considered for improving precipitation prediction. In this study, using disdrometer data, the diagnostic relations for the intercept parameter of the exponential raindrop size distribution N0 are derived for different rain types and the impacts of the diagnostic relations on precipitation prediction are examined. The disdrometer data observed at four sites in South Korea show spatiotemporal variations of N0. Three different derivation methods proposed by previous studies are used to derive the diagnostic relations, and the diagnostic relation that best reproduces the observed N0 is selected. The diagnostic relation is implemented into the WRF single-moment 6-class microphysics (WSM6) scheme, and its impacts are investigated through the simulations of summertime precipitation events in South Korea. Compared to the simulation using the original WSM6 scheme (WSM6-O) where a constant N0 is used, the simulation where N0 is diagnosed by the diagnostic relation using the rainwater content at the lowest level (WSM6-L) yields better precipitation prediction. The WSM6-L simulation represents the variability of N0. Also, the WSM6-L simulation predicts N0 that is on average smaller than the prescribed value in the WSM6-O simulation, agreeing with the observation to some extent. The smaller N0 in the WSM6-L simulation decreases the rainwater production by the accretion of cloud water and the melting of ice hydrometeors, decreasing the rainwater mixing ratio.
Risk-aversion optimal hedging scenarios during droughts
Authors: Shiau Jenq-Tzong
Published: December 2022

The primary purpose of a water supply reservoir is to regular highly fluctuating streamflow for providing reliable water supplies. Reducing water shortage risk for impending droughts is a challenge task in real-time reservoir operation due to future inflow uncertainty. The main aim of this study is to propose risk-aversion optimal hedging scenarios during droughts, which is achieved by a two-stage approach. The water shortage probabilities of future lead times are analytically estimated first, then follows an optimization framework that simultaneously minimizing water shortage probabilities of future lead times and sustaining long-term water supply reliability. With an illustration application of the Nanhua Reservoir located in southern Taiwan, the results indicate that the proposed optimization framework provides an efficient hedging to reduce future water shortage probabilities and mitigate severe water shortages in real-time operation. The proposed optimal hedging scenarios outperforms the rule-curve-based current operation. Further improvements are noted for the time-varying rationing coefficient scenarios than the constant-coefficient scenario and the most favorable scenario is the scenario with the highest time-varying frequency. Using the storage to trigger hedging associated with estimated future lead-time water shortage probabilities as the objective functions, the proposed optimal hedging scenarios are not only risk aversion but also executable in real-time operation during droughts.
A class of diffusive delayed viral infection models with general incidence function and cellular proliferation
Authors: Nangue Alexis , Tacteu Fokam Willy Armel
Published: December 2022

We propose and analyze a new class of three dimensional space models that describes infectious diseases caused by viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV). This work constructs a Reaction–Diffusion-Ordinary Differential Equation model of virus dynamics, including absorption effect, cell proliferation, time delay, and a generalized incidence rate function. By constructing suitable Lyapunov functionals, we show that the model has threshold dynamics: if the basic reproduction number $$\mathcal {R}_{0}(\tau ) \le 1 $$

R
0

(
τ
)

≤
1

, then the uninfected equilibrium is globally asymptotically stable, whereas if $$\mathcal {R}_{0}(\tau ) > 1$$

R
0

(
τ
)

>
1

, and under certain conditions, the infected equilibrium is globally asymptotically stable. This precedes a careful study of local asymptotic stability. We pay particular attention to prove boundedness, positivity, existence and uniqueness of the solution to the obtained initial and boundary value problem. Finally, we perform some numerical simulations to illustrate the theoretical results obtained in one-dimensional space. Our results improve and generalize some known results in the framework of virus dynamics.
Uterine Fibroids, Perceived Stress, and Menstrual Distress: a Key Role of Heavy Menstrual Bleeding
Authors: Vannuccini Silvia , Clemenza Sara , Cassioli Emanuele , Rossi Eleonora , Castellini Giovanni , Ricca Valdo , Petraglia Felice
Published: December 2022

Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age, frequently associated with pain symptoms and heavy menstrual bleeding (HMB), leading to impaired quality of life. Thus, the aim of the study was to evaluate the global perception of stress and the menstrual distress in patients with UFs. A cross-sectional observational study was conducted on a group (n = 69) of fertile age women with UFs compared to age-matched controls, by administering two questionnaires: the perceived stress scale (PSS) and the Menstrual Distress Questionnaire (MEDI-Q). The PSS, MEDI-Q Total Score and 3 subscales—menstrual symptoms (MS), menstrual symptoms distress (MSD), and menstrual specificity index (MESI)—were evaluated. Patients with UFs showed higher PSS than controls (18.5 ± 5.0 vs. 13.8 ± 5.0, p < 0.001) and PSS values were very high in those with HMB, severe dysmenorrhea, and impaired social and working life. Patients with UFs also showed significantly higher score for MEDI-Q Total Score (16.51 ± 12.99 vs. 10.86 ± 12.36) (p < 0.01) as well as for the subscales MSD (2.54 ± 1.07 vs. 1.57 ± 0.98) (p < 0.001) and MESI (0.76 ± 0.30 vs 0.60 ± 0.39) (p < 0.05). The menstrual distress was associated to being uncomfortable about uterine bleeding; in fact, MEDI-Q Total Score was significantly higher in women with HMB compared to those with moderate/normal bleeding. UF characteristics (number, type, and size) did not correlate with perceived stress or menstrual distress. In conclusion, women with UFs have significantly higher levels of perceived stress and menstrual distress than controls and HMB plays a major role in determining such conditions.
Closing the concern-action gap through relational climate conversations: insights from US climate activists
Authors: Fine Julia Coombs
Published: December 2022

Several studies have found that relational climate conversations can be an effective method of increasing conversational participants’ concern about the climate crisis and encouraging them to take collective action. However, little work has yet examined how such conversations are practiced by climate activists, a group with expertise in relational organizing. Drawing on surveys and semi-structured interviews with climate activists across the USA, this analysis finds that activists frequently have climate conversations with friends and family, most of whom are politically progressive and somewhat to very concerned about the climate crisis. These findings might seem to suggest that climate activists only have climate conversations with like-minded others, producing an echo chamber effect that could entrench the political polarization of the issue. However, climate activists report strategic reasons for choosing like-minded audiences, such as personal response efficacy. Additionally, they report that one of their primary conversational goals is to move people who are already concerned about the climate crisis to take collective action in accordance with values of climate justice. The results identify obstacles to collective climate action even among concerned audiences and suggest that relational climate conversations can be useful in overcoming these obstacles.

Graphical Abstract
Cryogenic ultrasonic vibration assisted turning to texturize AZ31 magnesium alloy surfaces
Authors: Bertolini R. , Ghiotti A. , Bruschi S.
Published: December 2022

Magnesium alloys are increasingly used in the biomedical field thanks to their biocompatibility. However, poor corrosion resistance greatly limits their applications. Coating the devices is known to represent the most efficient way to increase the corrosion performances of magnesium alloys, but it requires specific surface preparation of the metal substrate. In the present paper, a hybrid machining technology, namely cryogenic–ultrasonic-assisted turning, is applied to generate magnesium alloy texturized surfaces with enhanced surface integrity characteristics. Results showed that the application of liquid nitrogen led to a harder and more complex surface texture than in the case of ultrasonic-assisted turning under dry conditions.
ASSESSING THE 14C MARINE RESERVOIR EFFECT IN ARCHAEOLOGICAL CONTEXTS: DATA FROM THE CABEÇUDA SHELL MOUND IN SOUTHERN BRAZIL
Authors: Alves Eduardo Q , Macario Kita D , Scheel-Ybert Rita , Oliveira Fabiana M , Colonese André Carlo , Giannini Paulo César Fonseca , Guimarães Renato , Fallon Stewart , Muniz Marcelo , Chivall David , Bronk Ramsey Christopher
Published: December 2022

Prehistoric shell mounds can be useful for the quantification of the radiocarbon marine reservoir effect (MRE) and, at the same time, knowledge about the MRE allows for the establishment of robust chronologies for these sites. This creates a loop in which the archaeological setting has a dual role: it is part of both the method and the application. Therefore, it is paramount to address these sites from both archaeological and environmental perspectives, investigating their origin and diagenesis in order to overcome biases caused by post-depositional alterations. In this study, samples of bone, charcoal and shell from a Late Holocene shell mound in Southern Brazil, the Sambaqui de Cabeçuda, were analyzed following a multidisciplinary approach to disentangle the complex relationships between archaeology and the environment. We performed X-ray diffraction, radiocarbon dating, stable isotopes (δ13C, δ18O, δ15N) and anthracology analyses as well as Bayesian Chronological Models and Isotope Mixing Models to assess the local MRE and to reconstruct the diet of Cabeçuda builders. Our results reveal a negative local correction for the MRE (ΔR = –263 ± 46 14C yr), expected for the lagoon next to the site, and diets with considerable intakes of marine proteins. We examine the implications of these results for the chronology of the site and discuss a series of complications when performing MRE studies using shell mound sites.
Towards a Buddhist theism
Authors: Zappulli Davide Andrea
Published: December 2022

My claim in this article is that the thesis that Buddhism has no God, insofar as it is taken to apply to Buddhism universally, is false. I defend this claim by interpreting a central text in East-Asian Buddhism – The Awakening of Faith in Mahāyāna – through the lenses of perfect being theology (PBT), a research programme in philosophy of religion that attempts to provide a description of God through a two-step process: (1) defining God in terms of maximal greatness; (2) inferring the properties or attributes that God must have in virtue of satisfying the definition. My argument comprises two steps. First, I argue that, since PBT is a method for providing a description of God starting from a definition of God, any text that contains a PBT ipso facto contains a notion of God. Second, I argue through textual evidence that The Awakening articulates a PBT, concluding that it contains a notion of God. Since the method of PBT leaves open what descriptions are to be inferred, my argument allows me to conclude that a text contains a notion of God without previously committing to any particular conception of the divine, which makes it particularly versatile and powerful.
Coronavirus rhyming slang
Authors: Lillo Antonio
Published: December 2022

Most people are remarkably calm. I was in my local last night and the mood was, “if I get it, I get it”. The most heated thing said about covid19 was whether to call it the Miley or the Billy Ray! (Twitter user from Manchester, March 14, 2020)
Anything Goes? Analyzing Varied Understandings of Assent
Authors: Birchley Giles
Published: December 2022

Assent to medical research or treatment may be an intuitively attractive way to address the area between incapacity and capacity that might otherwise be subject to a best interests assessment. Assent has become a widely disseminated concept in law, research, and clinical ethics, but little conceptual work on assent has so far occurred. An exploration of use of assent in treatment and research in children and people with dementia suggests that at least five claims are made on behalf of assent. Since at least some of these may lead to tensions with others, assent requires firmer conceptual underpinning. Whether assent remains primarily a local approach to research in children in the United States, where it appears to fit with legal background conditions, or develops its promise to overturn the dominant, binary, approach to (in)capacity will depend on the strength of future philosophical work to improve the theoretical foundations to assent.
FUNDC1 protects against doxorubicin-induced cardiomyocyte PANoptosis through stabilizing mtDNA via interaction with TUFM
Authors: Bi Yaguang , Xu Haixia , Wang Xiang , Zhu Hong , Ge Junbo , Ren Jun , Zhang Yingmei
Published: December 2022

Doxorubicin (DOX) is an effective anthracycline chemotherapeutic anticancer drug with its life-threatening cardiotoxicity severely limiting its clinical application. Mitochondrial damage-induced cardiomyocyte death is considered an essential cue for DOX cardiotoxicity. FUN14 domain containing 1 (FUNDC1) is a mitochondrial membrane protein participating in the regulation of mitochondrial integrity in multiple diseases although its role in DOX cardiomyopathy remains elusive. Here, we examined whether PANoptosis, a novel type of programmed cell death closely associated with mitochondrial damage, was involved in DOX-induced heart injury, and FUNDC1-mediated regulation of cardiomyocyte PANoptosis, if any. FUNDC1 was downregulated in heart tissues in patients with dilated cardiomyopathy (DCM) and DOX-challenged mice. FUNDC1 deficiency aggravated DOX-induced cardiac dysfunction, mitochondrial injury, and cardiomyocyte PANoptosis. Further examination revealed that FUNDC1 countered cytoplasmic release of mitochondrial DNA (mtDNA) and activation of PANoptosome through interaction with mitochondrial Tu translation elongation factor (TUFM), a key factor in the translational expression and repair of mitochondrial DNA, via its 96–133 amino acid domain. TUFM intervention reversed FUNDC1-elicited protection against DOX-induced mtDNA cytosolic release and cardiomyocyte PANoptosis. Our findings shed light toward a beneficial role of FUNDC1 in DOX cardiotoxicity and cardiomyocyte PANoptosis, thus offering therapeutic promises in DOX-induced cardiotoxicity.
Extracellular CIRP dysregulates macrophage bacterial phagocytosis in sepsis
Authors: Zhou Mian , Aziz Monowar , Yen Hao-Ting , Ma Gaifeng , Murao Atsushi , Wang Ping
Published: December 2022

In sepsis, macrophage bacterial phagocytosis is impaired, but the mechanism is not well elucidated. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that causes inflammation. However, whether eCIRP regulates macrophage bacterial phagocytosis is unknown. Here, we reported that the bacterial loads in the blood and peritoneal fluid were decreased in CIRP−/− mice and anti-eCIRP Ab-treated mice after sepsis. Increased eCIRP levels were correlated with decreased bacterial clearance in septic mice. CIRP−/− mice showed a marked increase in survival after sepsis. Recombinant murine CIRP (rmCIRP) significantly decreased the phagocytosis of bacteria by macrophages in vivo and in vitro. rmCIRP decreased the protein expression of actin-binding proteins, ARP2, and p-cofilin in macrophages. rmCIRP significantly downregulated the protein expression of βPIX, a Rac1 activator. We further demonstrated that STAT3 and βPIX formed a complex following rmCIRP treatment, preventing βPIX from activating Rac1. We also found that eCIRP-induced STAT3 phosphorylation was required for eCIRP’s action in actin remodeling. Inhibition of STAT3 phosphorylation prevented the formation of the STAT3-βPIX complex, restoring ARP2 and p-cofilin expression and membrane protrusion in rmCIRP-treated macrophages. The STAT3 inhibitor stattic rescued the macrophage phagocytic dysfunction induced by rmCIRP. Thus, we identified a novel mechanism of macrophage phagocytic dysfunction caused by eCIRP, which provides a new therapeutic target to ameliorate sepsis.
Constraining surface properties of asteroid (162173) Ryugu from numerical simulations of Hayabusa2 mission impact experiment
Authors: Jutzi Martin , Raducan Sabina D. , Zhang Yun , Michel Patrick , Arakawa Masahiko
Published: December 2022

The Hayabusa2 mission impact experiment on asteroid Ryugu created an unexpectedly large crater. The associated regime of low-gravity, low-strength cratering remained largely unexplored so far, because these impact conditions cannot be re-created in laboratory experiments on Earth. Here we show that the target cohesion may be very low and the impact probably occurred in the transitional cratering regime, between strength and gravity. For such conditions, our numerical simulations are able to reproduce the outcome of the impact on Ryugu, including the effects of boulders originally located near the impact point. Consistent with most recent analysis of Ryugu and Bennu, cratering scaling-laws derived from our results suggest that surfaces of small asteroids must be very young. However, our results also show that the cratering efficiency can be strongly affected by the presence of a very small amount of cohesion. Consequently, the varying ages of different geological surface units on Ryugu may be due to the influence of cohesion.
Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
Authors: Krohn Lynne , Heilbron Karl , Blauwendraat Cornelis , Reynolds Regina H. , Yu Eric , Senkevich Konstantin , Rudakou Uladzislau , Estiar Mehrdad A. , Gustavsson Emil K. , Brolin Kajsa , Ruskey Jennifer A. , Freeman Kathryn , Asayesh Farnaz , Chia Ruth , Arnulf Isabelle , Hu Michele T. M. , Montplaisir Jacques Y. , Gagnon Jean-François , Desautels Alex , Dauvilliers Yves , Gigli Gian Luigi , Valente Mariarosaria , Janes Francesco , Bernardini Andrea , Högl Birgit , Stefani Ambra , Ibrahim Abubaker , Šonka Karel , Kemlink David , Oertel Wolfgang , Janzen Annette , Plazzi Giuseppe , Biscarini Francesco , Antelmi Elena , Figorilli Michela , Puligheddu Monica , Mollenhauer Brit , Trenkwalder Claudia , Sixel-Döring Friederike , Cochen De Cock Valérie , Monaca Christelle Charley , Heidbreder Anna , Ferini-Strambi Luigi , Dijkstra Femke , Viaene Mineke , Abril Beatriz , Boeve Bradley F. ,   23andMe Research Team, Aslibekyan Stella , Auton Adam , Babalola Elizabeth , Bell Robert K. , Bielenberg Jessica , Bryc Katarzyna , Bullis Emily , Coker Daniella , Partida Gabriel Cuellar , Dhamija Devika , Das Sayantan , Elson Sarah L. , Filshtein Teresa , Fletez-Brant Kipper , Fontanillas Pierre , Freyman Will , Gandhi Pooja M. , Hicks Barry , Hinds David A. , Jewett Ethan M. , Jiang Yunxuan , Kukar Katelyn , Lin Keng-Han , Lowe Maya , McCreight Jey C. , McIntyre Matthew H. , Micheletti Steven J. , Moreno Meghan E. , Mountain Joanna L. , Nandakumar Priyanka , Noblin Elizabeth S. , O’Connell Jared , Petrakovitz Aaron A. , Poznik G. David , Schumacher Morgan , Shastri Anjali J. , Shelton Janie F. , Shi Jingchunzi , Shringarpure Suyash , Tran Vinh , Tung Joyce Y. , Wang Xin , Wang Wei , Weldon Catherine H. , Wilton Peter , Hernandez Alejandro , Wong Corinna , Tchakouté Christophe Toukam , Scholz Sonja W. , Ryten Mina , Bandres-Ciga Sara , Noyce Alastair , Cannon Paul , Pihlstrøm Lasse , Nalls Mike A. , Singleton Andrew B. , Rouleau Guy A. , Postuma Ronald B. , Gan-Or Ziv
Published: December 2022

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.
Spatially resolved proteomics via tissue expansion
Authors: Li Lu , Sun Cuiji , Sun Yaoting , Dong Zhen , Wu Runxin , Sun Xiaoting , Zhang Hanbin , Jiang Wenhao , Zhou Yan , Cen Xufeng , Cai Shang , Xia Hongguang , Zhu Yi , Guo Tiannan , Piatkevich Kiryl D.
Published: December 2022

Spatially resolved proteomics is an emerging approach for mapping proteome heterogeneity of biological samples, however, it remains technically challenging due to the complexity of the tissue microsampling techniques and mass spectrometry analysis of nanoscale specimen volumes. Here, we describe a spatially resolved proteomics method based on the combination of tissue expansion with mass spectrometry-based proteomics, which we call Expansion Proteomics (ProteomEx). ProteomEx enables quantitative profiling of the spatial variability of the proteome in mammalian tissues at ~160 µm lateral resolution, equivalent to the tissue volume of 0.61 nL, using manual microsampling without the need for custom or special equipment. We validated and demonstrated the utility of ProteomEx for streamlined large-scale proteomics profiling of biological tissues including brain, liver, and breast cancer. We further applied ProteomEx for identifying proteins associated with Alzheimer’s disease in a mouse model by comparative proteomic analysis of brain subregions.
Impact of international travel and diarrhea on gut microbiome and resistome dynamics
Authors: Boolchandani Manish , Blake Kevin S. , Tilley Drake H. , Cabada Miguel M. , Schwartz Drew J. , Patel Sanket , Morales Maria Luisa , Meza Rina , Soto Giselle , Isidean Sandra D. , Porter Chad K. , Simons Mark P. , Dantas Gautam
Published: December 2022

International travel contributes to the global spread of antimicrobial resistance. Travelers’ diarrhea exacerbates the risk of acquiring multidrug-resistant organisms and can lead to persistent gastrointestinal disturbance post-travel. However, little is known about the impact of diarrhea on travelers’ gut microbiomes, and the dynamics of these changes throughout travel. Here, we assembled a cohort of 159 international students visiting the Andean city of Cusco, Peru and applied next-generation sequencing techniques to 718 longitudinally-collected stool samples. We find that gut microbiome composition changed significantly throughout travel, but taxonomic diversity remained stable. However, diarrhea disrupted this stability and resulted in an increased abundance of antimicrobial resistance genes that can remain high for weeks. We also identified taxa differentially abundant between diarrheal and non-diarrheal samples, which were used to develop a classification model that distinguishes between these disease states. Additionally, we sequenced the genomes of 212 diarrheagenic Escherichia coli isolates and found those from travelers who experienced diarrhea encoded more antimicrobial resistance genes than those who did not. In this work, we find the gut microbiomes of international travelers’ are resilient to dysbiosis; however, they are also susceptible to colonization by multidrug-resistant bacteria, a risk that is more pronounced in travelers with diarrhea.
The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing
Authors: Cervantes-Silva Mariana P. , Carroll Richard G. , Wilk Mieszko M. , Moreira Diana , Payet Cloe A. , O’Siorain James R. , Cox Shannon L. , Fagan Lauren E. , Klavina Paula A. , He Yan , Drewinski Tabea , McGinley Alan , Buel Sharleen M. , Timmons George A. , Early James O. , Preston Roger J. S. , Hurley Jennifer M. , Finlay David K. , Schoen Ingmar , Javier Sánchez-García F. , Mills Kingston H. G. , Curtis Annie M.
Published: December 2022

Dendritic cells play a key role in processing and presenting antigens to naïve T cells to prime adaptive immunity. Circadian rhythms are known to regulate many aspects of immunity; however, the role of circadian rhythms in dendritic cell function is still unclear. Here, we show greater T cell responses when mice are immunised in the middle of their rest versus their active phase. We find a circadian rhythm in antigen processing that correlates with rhythms in both mitochondrial morphology and metabolism, dependent on the molecular clock gene,Bmal1. Using Mdivi-1, a compound that promotes mitochondrial fusion, we are able to rescue the circadian deficit in antigen processing and mechanistically link mitochondrial morphology and antigen processing. Furthermore, we find that circadian changes in mitochondrial Ca2+are central to the circadian regulation of antigen processing. Our results indicate that rhythmic changes in mitochondrial calcium, which are associated with changes in mitochondrial morphology, regulate antigen processing.
Air pollution disparities and equality assessments of US national decarbonization strategies
Authors: Goforth Teagan , Nock Destenie
Published: December 2022

Energy transitions and decarbonization require rapid changes to a nation’s electricity generation mix. There are many feasible decarbonization pathways for the electricity sector, yet there is vast uncertainty about how these pathways will advance or derail the nation’s energy equality goals. We present a framework for investigating how decarbonization pathways, driven by a least-cost paradigm, will impact air pollution inequality across vulnerable groups (e.g., low-income, minorities) in the US. We find that if no decarbonization policies are implemented, Black and high-poverty communities may be burdened with 0.19–0.22 μg/m3 higher PM2.5 concentrations than the national average during the energy transition. National mandates requiring more than 80% deployment of renewable or low-carbon technologies achieve equality of air pollution concentrations across all demographic groups. Thus, if least-cost optimization capacity expansion models remain the dominant decision-making paradigm, strict low-carbon or renewable energy technology mandates will have the greatest likelihood of achieving national distributional energy equality. Decarbonization is essential to achieving climate goals, but myopic decarbonization policies that ignore co-pollutants may leave Black and high-poverty communities up to 26–34% higher PM2.5 exposure than national averages over the energy transition.
Pexophagy suppresses ROS-induced damage in leaf cells under high-intensity light
Authors: Oikawa Kazusato , Goto-Yamada Shino , Hayashi Yasuko , Takahashi Daisuke , Kimori Yoshitaka , Shibata Michitaro , Yoshimoto Kohki , Takemiya Atsushi , Kondo Maki , Hikino Kazumi , Kato Akira , Shimoda Keisuke , Ueda Haruko , Uemura Matsuo , Numata Keiji , Ohsumi Yoshinori , Hara-Nishimura Ikuko , Mano Shoji , Yamada Kenji , Nishimura Mikio
Published: December 2022

Although light is essential for photosynthesis, it has the potential to elevate intracellular levels of reactive oxygen species (ROS). Since high ROS levels are cytotoxic, plants must alleviate such damage. However, the cellular mechanism underlying ROS-induced leaf damage alleviation in peroxisomes was not fully explored. Here, we show that autophagy plays a pivotal role in the selective removal of ROS-generating peroxisomes, which protects plants from oxidative damage during photosynthesis. We present evidence that autophagy-deficient mutants show light intensity-dependent leaf damage and excess aggregation of ROS-accumulating peroxisomes. The peroxisome aggregates are specifically engulfed by pre-autophagosomal structures and vacuolar membranes in both leaf cells and isolated vacuoles, but they are not degraded in mutants. ATG18a-GFP and GFP-2×FYVE, which bind to phosphatidylinositol 3-phosphate, preferentially target the peroxisomal membranes and pre-autophagosomal structures near peroxisomes in ROS-accumulating cells under high-intensity light. Our findings provide deeper insights into the plant stress response caused by light irradiation.
Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus
Authors: Zheng Meiling , Hu Zhi , Mei Xiaole , Ouyang Lianlian , Song Yang , Zhou Wenhui , Kong Yi , Wu Ruifang , Rao Shijia , Long Hai , Shi Wei , Jing Hui , Lu Shuang , Wu Haijing , Jia Sujie , Lu Qianjin , Zhao Ming
Published: December 2022

Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are both types of lupus, yet the characteristics, and differences between them are not fully understood. Here we show single-cell RNA sequencing data of cutaneous lesions from DLE and SLE patients and skin tissues from healthy controls (HCs). We find significantly higher proportions of T cells, B cells and NK cells in DLE than in SLE. Expanded CCL20+ keratinocyte, CXCL1+ fibroblast, ISGhiCD4/CD8 T cell, ISGhi plasma cell, pDC, and NK subclusters are identified in DLE and SLE compared to HC. In addition, we observe higher cell communication scores between cell types such as fibroblasts and macrophage/dendritic cells in cutaneous lesions of DLE and SLE compared to HC. In summary, we clarify the heterogeneous characteristics in cutaneous lesions between DLE and SLE, and discover some specific cell subtypes and ligand-receptor pairs that indicate possible therapeutic targets of lupus erythematosus.
High-throughput screening of 2D van der Waals crystals with plastic deformability
Authors: Gao Zhiqiang , Wei Tian-Ran , Deng Tingting , Qiu Pengfei , Xu Wei , Wang Yuecun , Chen Lidong , Shi Xun
Published: December 2022

Inorganic semiconductors exhibit multifarious physical properties, but they are prevailingly brittle, impeding their application in flexible and hetero-shaped electronics. The exceptional plasticity discovered in InSe crystal indicates the existence of abundant plastically deformable two-dimensional van der Waals (2D vdW) materials, but the conventional trial-and-error method is too time-consuming and costly. Here we report on the discovery of tens of potential 2D chalcogenide crystals with plastic deformability using a nearly automated and efficient high-throughput screening methodology. Seven candidates e.g., famous MoS2, GaSe, and SnSe2 2D materials are carefully verified to show largely anisotropic plastic deformations, which are contributed by both interlayer and cross-layer slips involving continuous breaking and reconstruction of chemical interactions. The plasticity becomes a new facet of 2D materials for deformable or flexible electronics.
Toward economical application of carbon capture and utilization technology with near-zero carbon emission
Authors: Langie Kezia Megagita Gerby , Tak Kyungjae , Kim Changsoo , Lee Hee Won , Park Kwangho , Kim Dongjin , Jung Wonsang , Lee Chan Woo , Oh Hyung-Suk , Lee Dong Ki , Koh Jai Hyun , Min Byoung Koun , Won Da Hye , Lee Ung
Published: December 2022

Carbon capture and utilization technology has been studied for its practical ability to reduce CO2 emissions and enable economical chemical production. The main challenge of this technology is that a large amount of thermal energy must be provided to supply high-purity CO2 and purify the product. Herein, we propose a new concept called reaction swing absorption, which produces synthesis gas (syngas) with net-zero CO2 emission through direct electrochemical CO2 reduction in a newly proposed amine solution, triethylamine. Experimental investigations show high CO2 absorption rates (>84%) of triethylamine from low CO2 concentrated flue gas. In addition, the CO Faradaic efficiency in a triethylamine supplied membrane electrode assembly electrolyzer is approximately 30% (@−200 mA cm−2), twice higher than those in conventional alkanolamine solvents. Based on the experimental results and rigorous process modeling, we reveal that reaction swing absorption produces high pressure syngas at a reasonable cost with negligible CO2 emissions. This system provides a fundamental solution for the CO2 crossover and low system stability of electrochemical CO2 reduction.
Quantum coherence tomography of light-controlled superconductivity
Authors: Luo L. , Mootz M. , Kang J. H. , Huang C. , Eom K. , Lee J. W. , Vaswani C. , Collantes Y. G. , Hellstrom E. E. , Perakis I. E. , Eom C. B. , Wang J.
Published: December 2022

The coupling between superconductors and oscillation cycles of light pulses, i.e., lightwave engineering, is an emerging control concept for superconducting quantum electronics. Although progress has been made towards terahertz-driven superconductivity and supercurrents, the interactions able to drive non-equilibrium pairing are still poorly understood, partially due to the lack of measurements of high-order correlation functions. In particular, the sensing of exotic collective modes that would uniquely characterize light-driven superconducting coherence, in a way analogous to the Meissner effect, is very challenging but much needed. Here we report the discovery of parametrically driven superconductivity by light-induced order-parameter collective oscillations in iron-based superconductors. The time-periodic relative phase dynamics between the coupled electron and hole bands drives the transition to a distinct parametric superconducting state out-of-equalibrium. This light-induced emergent coherence is characterized by a unique phase–amplitude collective mode with Floquet-like sidebands at twice the Higgs frequency. We measure non-perturbative, high-order correlations of this parametrically driven superconductivity by separating the terahertz-frequency multidimensional coherent spectra into pump–probe, Higgs mode and bi-Higgs frequency sideband peaks. We find that the higher-order bi-Higgs sidebands dominate above the critical field, which indicates the breakdown of susceptibility perturbative expansion in this parametric quantum matter.
Cohesin and CTCF control the dynamics of chromosome folding
Authors: Mach Pia , Kos Pavel I. , Zhan Yinxiu , Cramard Julie , Gaudin Simon , Tünnermann Jana , Marchi Edoardo , Eglinger Jan , Zuin Jessica , Kryzhanovska Mariya , Smallwood Sebastien , Gelman Laurent , Roth Gregory , Nora Elphège P. , Tiana Guido , Giorgetti Luca
Published: December 2022

In mammals, interactions between sequences within topologically associating domains enable control of gene expression across large genomic distances. Yet it is unknown how frequently such contacts occur, how long they last and how they depend on the dynamics of chromosome folding and loop extrusion activity of cohesin. By imaging chromosomal locations at high spatial and temporal resolution in living cells, we show that interactions within topologically associating domains are transient and occur frequently during the course of a cell cycle. Interactions become more frequent and longer in the presence of convergent CTCF sites, resulting in suppression of variability in chromosome folding across time. Supported by physical models of chromosome dynamics, our data suggest that CTCF-anchored loops last around 10 min. Our results show that long-range transcriptional regulation might rely on transient physical proximity, and that cohesin and CTCF stabilize highly dynamic chromosome structures, facilitating selected subsets of chromosomal interactions.
Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
Authors: Tamman Hedvig , Ernits Karin , Roghanian Mohammad , Ainelo Andres , Julius Christina , Perrier Anthony , Talavera Ariel , Ainelo Hanna , Dugauquier Rémy , Zedek Safia , Thureau Aurelien , Pérez Javier , Lima-Mendez Gipsi , Hallez Régis , Atkinson Gemma C. , Hauryliuk Vasili , Garcia-Pino Abel
Published: December 2022

Stringent factors orchestrate bacterial cell reprogramming through increasing the level of the alarmones (p)ppGpp. In Beta- and Gammaproteobacteria, SpoT hydrolyzes (p)ppGpp to counteract the synthetase activity of RelA. However, structural information about how SpoT controls the levels of (p)ppGpp is missing. Here we present the crystal structure of the hydrolase-only SpoT from Acinetobacter baumannii and uncover the mechanism of intramolecular regulation of ‘long’-stringent factors. In contrast to ribosome-associated Rel/RelA that adopt an elongated structure, SpoT assumes a compact τ-shaped structure in which the regulatory domains wrap around a Core subdomain that controls the conformational state of the enzyme. The Core is key to the specialization of long RelA-SpoT homologs toward either synthesis or hydrolysis: the short and structured Core of SpoT stabilizes the τ-state priming the hydrolase domain for (p)ppGpp hydrolysis, whereas the longer, more dynamic Core domain of RelA destabilizes the τ-state priming the monofunctional RelA for efficient (p)ppGpp synthesis.
Defectronics based photoelectrochemical properties of Cu2+ ion doped hematite thin film
Authors: Kim Chang Woo , Pawar Amol U. , Hawari Thomi , Ahn Na Hyeon , Lee Don Keun , Yang Long , Sivasankaran Ramesh Poonchi , Tang Jun , Zhuo Zhongbiao , Kang Young Soo
Published: December 2022

The concentration of guest elements (dopants) into host materials play an important role in changing their intrinsic electrical and optical properties. The existence of hetero-element induce defect in crystal structure, affecting conductivity. In the current work, we report Cu2+ ion into hematite in the defectronics point of view and their photoelectrochemical properties. Crystal distortion in the structure of hematite is observed as the amount of dopant increases. Among 1, 3 and 5 mol% of Cu2+ doped hematite, the existence of 1 mol% of Cu2+ ion into hematite crystal structure produce photocurrent value of 0.15 mA/cm2, IPCE value of ~ 4.7% and EIS value of ~ 2000 Ω/cm2 as best performances. However, further increasing dopants increases the number of interstitial defects, which cause the deformation of intrinsic lattice structure.