bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic plasticity in blast crisis-chronic myeloid leukaemia cells under hypoxia reduces the cytotoxic potency of drugs targeting mitochondria
Authors: Salaverry Luciana S. , Lombardo Tomás , Cabral-Lorenzo María C. , Gil-Folgar Martin L. , Rey-Roldán Estela B. , Kornblihtt Laura I. , Blanco Guillermo A.
Published: July 2022

Metabolic reprogramming (MR) influences progression of chronic myeloid leukaemia (CML) to blast crisis (BC), but metabolic programs may change transiently in a second dimension (metabolic plasticity, MP), driven by environments as hypoxia, affecting cytotoxic potency (CPot) of drugs targeting mitochondria or mitochondria-related cell stress responses (MRCSR) such as mitophagy and mitochondrial biogenesis. We assessed mitochondrial membrane potential (MMP), mitochondrial mass (MM), apoptosis, glucose uptake (GU), and CPot of arsenic trioxide (ATO), CCCP, valproic acid (VPA), vincristine (VCR), Mdivi1, and dichloroacetic acid (DCA) in CML BC cells K562 (BC-K562) under hypoxia through flow cytometry, and gene expression from GEO database. About 60% of untreated cells were killed after 72 h under hypoxia, but paradoxically, all drugs but ATO rescued cells and increased survival rates to almost 90%. Blocking mitophagy either with VCR or Mdivi1, or increasing mitochondrial biogenesis with VPA enhanced cell-survival with increased MM. DCA increased MM and rescued cells in spite of its role in activating pyruvate dehydrogenase and Krebs cycle. Cells rescued by DCA, VPA and CCCP showed decreased GU. ATO showed equal CPot in hypoxia and normoxia. MP was evidenced by differential expression of genes (DEG) under hypoxia related to Krebs cycle, lipid synthesis, cholesterol homeostasis, mitophagy, and mitochondrial biogenesis (GSE144527). A 25-gene MP-signature of BC-K562 cells under hypoxia identified BC cases among 113 transcriptomes from CML patients (GSE4170). We concluded that hypoxic environment drove a MP change evidenced by DEG that was reflected in a paradoxical pro-survival, instead of cytotoxic, effect of drugs targeting mitochondria and MRCSR.
Effectiveness of a commercial lure to attract red fox
Authors: Cozzi Francesca , Iacona Elisa , Ferretti Francesco , Corlatti Luca
Published: July 2022

In camera trap studies, attractants may be used to increase detection probabilities of wildlife, which may help to improve estimates of abundance and occupancy. Using a semi-experimental approach, we investigated if a commercial, strawberry scented lure increased detection probability and visiting time duration in red fox Vulpes vulpes, and the potential reasons for variation in these parameters. In September 2020, within the Stelvio National Park, central Italian Alps, 32 camera sites were randomly assigned to 4 different treatments: 8 to commercial lure, the target of our investigation; 8 to orange aroma, to test for the “curiosity” effect; 8 to cat kibble, to test for the “likability” effect; 8 to camera trap only, the control test. Detection probability and duration of visiting time were estimated using hurdle negative binomial regression models. Daily detection probability was significantly higher with lure (0.078), orange aroma (0.086), kibble (0.075) than with camera trap only (0.031); in the first day after treatment, the time an animal spent in front of the cameras significantly increased with orange aroma (16.61 s) and kibble (33.78 s) compared to lure (9.97 s) and camera trap only (0.38 s). Our results support the use of lures to improve detection probability and visit duration in red fox, but we could not disentangle the drivers of increased parameter estimates. When consumable costs are considered, the use of the commercial strawberry scented lure does not appear justified for both detection probability and visit duration, and cheaper alternatives may be preferable.
Teaching as regulated improvisation
Authors: Thomas Matthew Krehl Edward , Skourdoumbis Andrew , Whitburn Ben
Published: July 2022

In this paper, we address the work of teachers at the intersection of educational policy and professional discretion, by undertaking a conceptual reading of Through Growth to Achievement: Report of the Review to Achieve Educational Excellence in Australian Schools, and examining how the report conceptualises teacher practice. Drawing on the Bourdieusian notion of regulated improvisation, the study explores the constraints of pedagogical practices as conceptualised by influential policy reports of this kind, highlighting the paradoxical expectations of the report on teachers whose situational awareness of classrooms is curtailed through regulation. The study examines the tension between teacher autonomy and constraints, negating important considerations to temporalities of learning. The central contribution of the paper is a conceptual understanding of how policy drivers position teacher expertise through standardisation, compliance and performance, a concern not unique only to the Australian context of educational policy, nor schooling.
$$p^\infty $$-Selmer groups and rational points on CM elliptic curves
Authors: Burungale Ashay , Castella Francesc , Skinner Christopher , Tian Ye
Published: July 2022

Let $$E/{\mathbb {Q}}$$

E
/
Q

be a CM elliptic curve and p a prime of good ordinary reduction for E. We show that if $$\text {Sel}_{p^\infty }(E/{\mathbb {Q}})$$

Sel

p
∞

(
E
/
Q
)

has $${\mathbb {Z}}_p$$

Z
p

-corank one, then $$E({\mathbb {Q}})$$

E
(
Q
)

has a point of infinite order. The non-torsion point arises from a Heegner point, and thus $${{\,\textrm{ord}\,}}_{s=1}L(E,s)=1$$

ord

s
=
1

L

(
E
,
s
)

=
1

, yielding a p-converse to a theorem of Gross–Zagier, Kolyvagin, and Rubin in the spirit of [49, 54]. For $$p>3$$

p
>
3

, this gives a new proof of the main result of [12], which our approach extends to all primes. The approach generalizes to CM elliptic curves over totally real fields [4].
Can Machines Learn Creativity Needs? An Approach Based on Matrix Completion
Authors: Gnecco Giorgio , Landi Sara , Riccaboni Massimo
Published: July 2022

Technological progress has been recently associated with a crowding-out of cognitive-skill intensive jobs in favour of jobs requiring soft skills, such as ones related to social intelligence, flexibility and creativity. The nature of soft skills makes them hardly replaceable by machine work and among subsets of soft skills, creativity is one of the hardest to define and codify. Therefore, creativity-intensive occupations have been shielded from automation. Given this framework, our study contributes to a nascent field on interdisciplinary research to predict the impact of artificial intelligence on work activities and future jobs using machine learning. In our work, we focus on creativity, starting from its possible definitions, then we get significant insights on creativity patterns and dynamics in the Italian labour market, using a machine learning approach. We make use of the INAPP-ISTAT Survey on Occupations (ICP), where we identify 25 skills associated with creativity. Then, we apply matrix completion—a machine learning technique which is often used by recommender systems—to predict the average importance levels of various creative skills for each profession, showing its excellent prediction capability for the specific problem. We also find that matrix completion typically underestimates the average importance levels of soft skills associated with creativity, especially in the case of professions belonging to the major group of legislators, senior officials and managers, as well as intellectual professionals. Conversely, overestimates are typically obtained for other professions, which may be associated with a higher risk of being automated.
Closure scheme for stably stratified turbulence without critical Richardson number
Authors: Caggio Matteo , Schiavon Mario , Tampieri Francesco , Bodnár Tomáš
Published: July 2022

This paper presents a new modification of the second order turbulence closure that removes the critical gradient Richardson number limitation typically found in Mellor-Yamada style models. The mean wind speed and potential temperature profiles are derived for the newly modified model in terms of similarity and structure functions depending on the gradient Richardson number. The derivation is based on a second order boundary layer approximation in neutral to very stable stratification conditions. Some recent closure assumptions for pressure-temperature and heat flux are considered. Variances and covariances of the turbulent fluctuations are also investigated with respect to the gradient Richardson number. The new model predictions are confronted with some well known models.
A critical examination of a community-led ecovillage initiative: a case of Auroville, India
Authors: Koduvayur Venkitaraman Abhishek , Joshi Neelakshi
Published: July 2022

Human settlements across the world are attempting to address climate change, leading to changing paradigms, parameters, and indicators for defining the path to future sustainability. In this regard, the term ecovillage has been increasingly used as models for sustainable human settlements. While the term is new, the concept is an old one: human development in harmony with nature. However, materially realizing the concept of an ecovillage is not without challenges. These include challenges in scaling up and transferability, negative regional impacts and struggles of functioning within larger capitalistic and growth-oriented systems. This paper presents the case of Auroville, an early attempt to establish an ecovillage in Southern India. We draw primarily from the ethnographic living and working experience of the authors in Auroville as well as published academic literature and newspaper articles. We find that Auroville has proven to be a successful laboratory for providing bottom-up, low cost and context-specific ecological solutions to the challenges of sustainability. However, challenges of economic and social sustainability compound as the town attempts to scale up and grow.

Graphical abstract
Three-month Practice Effect of the National Institutes of Health Toolbox Cognition Battery in Young Healthy Adults
Authors: Kuzmuk Leah E. , Rebchuk Alexander D. , Deptuck Halina M. , Cairncross Molly , Silverberg Noah D. , Field Thalia S.
Published: July 2022

The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need clarification if this measure is used to track longitudinal change. We explored the test–retest PEs on NIHTB-CB performance at 3 months in young healthy adults (n = 22). We examined corrected T-scores normalized for demographic factors and calculated PEs using Cohen’s d. There were significant PEs for all NIHTB-CB composite scores and on 4/7 subtests. This work suggests the need to further assess NIHTB-CB PEs as this may affect the interpretation of study results incorporating this battery.
Characteristics of Patients Transported by Doctor-Requested Helicopters After Japan’s 2011 Nuclear Incident
Authors: Sorimachi Kotaro , Muto Kazuya , Sugaya Kazuki , Ueno Satoshi , Onodera Makoto , Ohira Tetsuya , Tsubokura Masaharu , Iseki Ken
Published: July 2022

Objectives:

This study examined the characteristics of severe patients after the Great East Japan Earthquake in 2011.

Methods:

Cases in the Futaba area were extracted using the dispatch database of the doctor helicopter and flight-nurse records from March 11, 2008, till March 10, 2014. The period before March 11, 2011, was defined as ‘pre-earthquake’ and the period after March 11, 2011, as ‘post-earthquake’ to compare the recorded data.

Results:

Of the 128 total recorded cases, 78 were dispatched during the pre-earthquake period and 50 during the post-earthquake period. The number of patients with physical trauma following the earthquake included 4 patients (33.3%) in 2011, 7 patients (43.7%) in 2012, and 13 patients (59.1%) in 2013. However, the increase in number of requests was not statistically significant (P = 0.33). All 4 incidents of physical trauma in 2011, and 3 out of 7 incidents in 2012, occurred at the power plants. A total of 4 incidents occurred at decontamination worksites in 2013.

Conclusions:

It is of primary importance for hospitals to anticipate physical trauma cases during the reconstruction phase following a disaster, and develop a system for patients with physical trauma in the short- and long-term.
On supercritical branching processes with emigration
Authors: Braun Georg
Published: July 2022

We study supercritical branching processes under the influence of an independent and identically distributed (i.i.d.) emigration component. We provide conditions under which the lifetime of the process is finite or has a finite expectation. A theorem of Kesten–Stigum type is obtained, and the extinction probability for a large initial population size is related to the tail behaviour of the emigration.
Homogeneous and curvature homogeneous Lorentzian critical metrics
Authors: Brozos-Vázquez M. , Caeiro-Oliveira S. , García-Río E.
Published: July 2022

We determine all three-dimensional homogeneous and $1$-curvature homogeneous Lorentzian metrics which are critical for a quadratic curvature functional. As a result, we show that any quadratic curvature functional admits different non-Einstein homogeneous critical metrics and that there exist homogeneous metrics which are critical for all quadratic curvature functionals without being Einstein.
(Inequality in) Interest Group Involvement and the Legitimacy of Policy Making
Authors: Rasmussen Anne , Reher Stefanie
Published: July 2022

While interest groups are consulted at different stages of policy making to provide expertise and legitimacy, their influence is often criticized as being undemocratic. Yet, we know little about how their participation in policy making affects citizen perceptions of the legitimacy of governance. Based on survey experiments conducted in the UK, the United States and Germany, our study shows that unequal participation between group types reduces the benefits of interest group consultation for citizens' perceived legitimacy of decision-making processes. Importantly, these legitimacy losses cannot be compensated for by policies that represent the opinion of the under-represented groups and are even greater when policy decisions favour the over-represented groups. Moreover, we show that citizen perceptions of how economically powerful and representative of society different types of interest groups are act as important drivers of legitimacy evaluations. Our results provide important new theoretical and empirical insights into when and why interest groups affect democratic legitimacy.
LACTANTIUS BEFORE LACTANTIUS? A HEXAMETER FROM THE CARMINA XII SAPIENTVM IN AN INSCRIPTION ON SAMIAN WARE FROM BELSINON (HISPANIA TARRACONENSIS)
Authors: Aguilera Aragón Isidro , Díaz Ariño Borja
Published: July 2022

This paper presents a graffito written after firing on a Samian-ware bowl dated to the turn of the first and second centuries c.e., which seems to contain part of a hexameter included in the well-known anthology Carmina XII sapientum, the composition of which has recently been attributed to the Christian author Lactantius.
Coinage in the Roman Provinces: the RPC and CHRE projects
Authors: Hekster Olivier , Manders Erika
Published: July 2022

Roman coinage forms an astoundingly rich body of material. That applies to coins struck by the centre as much as so-called provincial coinage. The latter can be roughly categorised as 1) coins struck by cities in the east of the Roman Empire, and for the Julio-Claudian period also in the west (in the western provinces, cities stopped issuing coins around the end of Claudius’ reign); 2) coinages issued in the name of federations of cities (koina) or coins celebrating alliances between cities (so-called homonoia-coins); 3) coins struck by ‘friendly kings’; and 4) so-called ‘provincial issues’ — mainly drachms, didrachms and tetradrachms, but also bronzes — that were mostly struck by important mints such as Alexandria, Antioch and Caesarea (in Cappadocia), probably under the supervision of Roman magistrates, to circulate in specific provinces.1
Sīyaḍoṇi: an unplanned town of the Gurjara-Pratīhāra times
Authors: Mishra Aman
Published: July 2022

Between the sixth and the tenth century, India passed through a new phase of urbanization. This has been identified as the third urbanization in India, setting it apart from two earlier phases. The focus of historical investigations for this period has generally been on capital cities and royal centres, or centres of pilgrimage. Port cities have also received some attention. There are no exclusive studies on unplanned cities from this period other than the overview that a few historians provide. In this article, I am focusing on one of them, Sīyaḍoṇi in central India, in order to understand how urban centres developed in this period without being royal centres, places of pilgrimage or hubs of maritime trade. I propose that Sīyaḍoṇi emerged as a merchant town on an important trade route and its commerce-centred economy was reinforced by deep-seated practices of rent-seeking involving generation of income through ground rent, taxation and interest on loans.
Bayesian approach for genetic analysis of production and reproduction traits in Jersey crossbred cattle
Authors: Ratwan Poonam , Kumar Manoj , Mandal Ajoy
Published: July 2022

The knowledge of genetic parameters of performance traits is crucial for any breeding programme in dairy animals. The present study was conducted to use a Bayesian approach for estimation of genetic parameters of production and reproduction traits in Jersey crossbred cattle. Data of Jersey crossbred cattle maintained at Eastern Regional Station, National Dairy Research Institute, West Bengal spread over a span of 41 years were utilized. The marginal posterior medians of heritability for 305-day milk yield (305MY), total milk yield (TMY), peak yield (PY), lactation length (LL), calving interval (CI), total milk yield per day of lactation length (TMY/LL) and total milk yield per day of calving interval (TMY/CI) were 0.31 ± 0.07, 0.29 ± 0.07, 0.27 ± 0.06, 0.16 ± 0.05, 0.15 ± 0.05, 0.29 ± 0.06, 0.27 ± 0.06, respectively. Moderate heritability estimates for 305MY, TMY, PY and production efficiency traits indicate the presence of adequate additive genetic variance in these traits to respond to selection combined with better herd management. Repeatability estimates for 305MY, TMY, PY, LL, CI, TMY/LL and TMY/CI were 0.57 ± 0.08, 0.58 ± 0.08, 0.51 ± 0.07, 0.34 ± 0.06, 0.31 ± 0.06, 0.54 ± 0.07 and 0.49 ± 0.07, respectively. Repeatability estimates for 305MY, TMY and PY were high in the current study, suggesting the use of first lactation records for early evaluation of Jersey crossbred cattle for future selection. Genetic correlations varied from 0.21 to 0.97 and maximum genetic correlation was observed between 305MY and TMY indicating that consideration of 305MY instead of TMY in breeding programmes would suffice. Positive genetic correlations of CI with 305MY and TMY indicated the antagonistic association between production and reproduction traits.
Chiari network as a cause of neonatal hypoxemia
Authors: Takahashi Manabu , Sotodate Genichiro , Kajiwara Waka
Published: July 2022

The Chiari network is an embryonic remnant of the right venosus, consisting of a thin, mobile structure connected to the right atrium. Neonates with the Chiari network may present with hypoxemia. We report a case of a neonate with persistent hypoxemia despite improvement in respiratory distress symptoms and increased supplemental oxygen that was diagnosed using real-time telemedicine.
Curbing the fruitfulness of self-replicating machines
Authors: Ellery Alex
Published: July 2022

The self-replicating machine has high utility by virtue of its universal construction properties and its productive capacity for exponential growth. Their capacity is unrivalled. They can be deployed to the Moon to industrialize it using local in-situ resources in the short term to open up the solar system and thence deployed on interstellar spacecraft to explore the entire Galaxy by exploiting in-situ stellar system resources. Nevertheless, there are significant concerns regarding the inherent safety of self-replicating machines. We consider the general problem of runaway population growth in physical self-replicating machines to prevent the grey goo problem, the number of offspring spawned by self-replicating machines may be controlled at a genetic level. We adopt a biologically-inspired approach based on telomeres, DNA endcaps that are progressively shortened during cellular replication. This acts as a counter that imposes a limit to the number of replication cycles (Hayflick limit). By examining the biological process in detail, we can obtain some insights in implementing similar mechanisms in self-replicating machines. In particular, we find that counting mechanisms are vulnerable to cancerous runaway.
Directive Principles, Political Constitutionalism, and Constitutional Culture: the Case of Ireland’s failed Directive Principles of Social Policy
Authors: Kenny David , Musgrove McCann Lauryn
Published: July 2022

Directive principles of social or state policy – use of constitutional provisions in parliamentary debates – economic, social and cultural rights – political constitutionalism – Article 45 of the Constitution of Ireland – constitutional culture – constitutional narrative – failure of constitutional culture to take hold – limits of constitutional text
Social Reactions After Disclosing Suicide Loss Among Women
Authors: Mayer Lea , Puschner Nadja , Votruba Nicole , Rüsch Nicolas , Oexle Nathalie
Published: July 2022

Abstract: Background: Suicide loss is often concealed. While initial evidence suggests that disclosure is important for healthy grieving, observed beneficial effects may depend on social reactions. Aim: The current study aimed to identify social reactions and associated consequences experienced by persons who lost a loved one to suicide (i.e., suicide loss survivors). Method: We conducted qualitative interviews with 22 female adult suicide loss survivors focusing on social reactions after suicide loss. Interviews were transcribed and analyzed using qualitative content analysis. Results: When talking about their loss with others, suicide loss survivors experienced a broad range of social reactions including compassionate and supportive responses, speechlessness and insecurity, curiosity and gossip, stigmatization, and grieving expectations. Depending on these social reactions, disclosing suicide loss was associated with both negative and positive long-term effects. Limitations: The findings are limited to the current female sample. Conclusion: Interventions that help suicide loss survivors in finding supportive confidants, combined with public interventions to decrease public suicide stigma and improve the public’s readiness to provide helpful support to suicide loss survivors, could improve grieving outcomes among this group.
Faculty clinical articles: a regular update for the oral healthcare team
Authors: Cobourne Martyn T. , Porter Stephen R. , Escudier Michael , Garrett Matthew
Published: July 2022

The Faculty of Dental Surgery of the Royal College of Surgeons of England and British Dental Journal have teamed up to provide a regular series of short articles on different aspects of clinical and academic dentistry. This series will provide concise insight into a diverse range of topics with the aim of providing regular ongoing professional development for all members of the oral healthcare team. We begin here, with a short update on the Faculty and overview of the series' aims.
Constructing a multi-bishelled cobalt-based electrocatalyst for the oxygen evolution reaction in CO2 electrolysis
Authors: Zhang Yu , Zheng Penglun , Qin Xueping , Yang Jun , Dinh Khang Ngoc , Zheng Yun , Shao Minhua , Yan Qingyu
Published: July 2022

Electrochemical reduction of CO2into value-added chemicals has been envisioned as a promising strategy to alleviate the issue of increasing CO2emissions. However, the sluggish oxygen evolution reaction (OER), as the anodic reaction, typically consumes approximately 90% of the electricity input, necessitating the development of an efficient OER for energy-saving purposes. Herein, we developed a unique heterostructure of multi-double (bi)-shelled Co-based spheres via a facile template-free method, in which each bi-shelled structure is composed of Co9Se8/Co9S8/CoO (Co-S-Se) with a symmetric configuration. These heterogeneous nanospheres possess both sufficient heterointerfaces and a high density of active sites and exhibit excellent OER activity in alkaline media with a low overpotential of 226 mV at 10 mA cm−2, a small Tafel slope of 46.5 mV dec−1, and long-term durability over 15 h. As a proof and concept, when coupled with a cathodic CO2reduction reaction, the electrochemical performance of Pd nanosheets (NSs) for CO2reduction can be significantly enhanced in terms of product selectivity and energy input. Our study might provide insight into the development of efficient OER electrocatalysts for practical CO2reduction reactions.
Observation of Néel-type skyrmions in acentric self-intercalated Cr1+δTe2
Authors: Saha Rana , Meyerheim Holger L. , Göbel Börge , Hazra Binoy Krishna , Deniz Hakan , Mohseni Katayoon , Antonov Victor , Ernst Arthur , Knyazev Dmitry , Bedoya-Pinto Amilcar , Mertig Ingrid , Parkin Stuart S. P.
Published: July 2022

Transition-metal dichalcogenides intercalated with 3d-transition metals within the van der Waals (vdW) gaps have been the focus of intense investigations owing to their fascinating structural and magnetic properties. At certain concentrations the intercalated atoms form ordered superstructures that exhibit ferromagnetic or anti-ferromagnetic ordering. Here we show that the self-intercalated compound Cr1+δTe2 with δ ≈ 0.3 exhibits a new, so far unseen, three-dimensionally ordered (2×2×2) superstructure. Furthermore, high resolution X-ray diffraction reveals that there is an asymmetric occupation of the two inequivalent vdW gaps in the unit cell. The structure thus lacks inversion symmetry, which, thereby, allows for chiral non-collinear magnetic nanostructures. Indeed, Néel-type skyrmions are directly observed using Lorentz transmission electron microscopy. The skyrmions are stable within the accessible temperature range (100–200 K) as well as in zero magnetic field. The diameter of the Néel skyrmions increases with lamella thickness and varies with applied magnetic field, indicating the role of long-range dipole fields. Our studies show that self-intercalation in vdW materials is a novel route to the formation of synthetic non-collinear spin textures.
Cation-selective two-dimensional polyimine membranes for high-performance osmotic energy conversion
Authors: Zhang Zhen , Bhauriyal Preeti , Sahabudeen Hafeesudeen , Wang Zhiyong , Liu Xiaohui , Hambsch Mike , Mannsfeld Stefan C. B. , Dong Renhao , Heine Thomas , Feng Xinliang
Published: July 2022

Two-dimensional (2D) membranes are emerging candidates for osmotic energy conversion. However, the trade-off between ion selectivity and conductivity remains the key bottleneck. Here we demonstrate a fully crystalline imine-based 2D polymer (2DPI) membrane capable of combining excellent ionic conductivity and high selectivity for osmotic energy conversion. The 2DPI can preferentially transport cations with Na+ selectivity coefficient of 0.98 (Na+/Cl− selectivity ratio ~84) and K+ selectivity coefficient of 0.93 (K+/Cl− ratio ~29). Moreover, the nanometer-scale thickness (~70 nm) generates a substantially high ionic flux, contributing to a record power density of up to ~53 W m−2, which is superior to most of nanoporous 2D membranes (0.8~35 W m−2). Density functional theory unveils that the oxygen and imine nitrogen can both function as the active sites depending on the ionization state of hydroxyl groups, and the enhanced interaction of Na+ versus K+ with 2DPI plays a significant role in directing the ion selectivity.
Energy-selective confinement of fusion-born alpha particles during internal relaxations in a tokamak plasma
Authors: Bierwage A. , Shinohara K. , Kazakov Ye.O. , Kiptily V. G. , Lauber Ph. , Nocente M. , Štancar Ž. , Sumida S. , Yagi M. , Garcia J. , Ide S. ,   JET Contributors
Published: July 2022

Long-pulse operation of a self-sustained fusion reactor using toroidal magnetic containment requires control over the content of alpha particles produced by D-T fusion reactions. On the one hand, MeV-class alpha particles must stay confined to heat the plasma. On the other hand, decelerated helium ash must be expelled before diluting the fusion fuel. Here, we report results of kinetic-magnetohydrodynamic hybrid simulations of a large tokamak plasma that confirm the existence of a parameter window where such energy-selective confinement can be accomplished by exploiting internal relaxation events known as sawtooth crashes. The physical picture — a synergy between magnetic geometry, optimal crash duration and rapid particle motion — is completed by clarifying the role of magnetic drifts. Besides causing asymmetry between co- and counter-going particle populations, magnetic drifts determine the size of the confinement window by dictating where and how much reconnection occurs in particle orbit topology.
Upper airway gene expression shows a more robust adaptive immune response to SARS-CoV-2 in children
Authors: Mick Eran , Tsitsiklis Alexandra , Spottiswoode Natasha , Caldera Saharai , Serpa Paula Hayakawa , Detweiler Angela M. , Neff Norma , Pisco Angela Oliveira , Li Lucy M. , Retallack Hanna , Ratnasiri Kalani , Williamson Kayla M. , Soesanto Victoria , Simões Eric A. F. , Smith Christiana , Abuogi Lisa , Kistler Amy , Wagner Brandie D. , DeRisi Joseph L. , Ambroggio Lilliam , Mourani Peter M. , Langelier Charles R.
Published: July 2022

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 older adults (>40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.
Signal-processing and adaptive prototissue formation in metabolic DNA protocells
Authors: Samanta Avik , Hörner Maximilian , Liu Wei , Weber Wilfried , Walther Andreas
Published: July 2022

The fundamental life-defining processes in living cells, such as replication, division, adaptation, and tissue formation, occur via intertwined metabolic reaction networks that process signals for downstream effects with high precision in a confined, crowded environment. Hence, it is crucial to understand and reenact some of these functions in wholly synthetic cell-like entities (protocells) to envision designing soft materials with life-like traits. Herein, we report on all-DNA protocells composed of a liquid DNA interior and a hydrogel-like shell, harboring a catalytically active DNAzyme, that converts DNA signals into functional metabolites that lead to downstream adaptation processes via site-selective strand displacement reactions. The downstream processes include intra-protocellular phenotype-like changes, prototissue formation via multivalent interactions, and chemical messenger communication between active sender and dormant receiver cell populations for sorted heteroprototissue formation. The approach integrates several tools of DNA-nanoscience in a synchronized way to mimic life-like behavior in artificial systems for future interactive materials.
Synthetic phosphoethanolamine-modified oligosaccharides reveal the importance of glycan length and substitution in biofilm-inspired assemblies
Authors: Tyrikos-Ergas Theodore , Gim Soeun , Huang Jhih-Yi , Pinzón Martín Sandra , Varón Silva Daniel , Seeberger Peter H. , Delbianco Martina
Published: July 2022

Bacterial biofilm matrices are nanocomposites of proteins and polysaccharides with remarkable mechanical properties. Efforts understanding and tuning the protein component have been extensive, whereas the polysaccharide part remained mostly overlooked. The discovery of phosphoethanolamine (pEtN) modified cellulose in E. coli biofilms revealed that polysaccharide functionalization alters the biofilm properties. To date, the pattern of pEtN cellulose and its mode of interactions with proteins remains elusive. Herein, we report a model system based on synthetic epitomes to explore the role of pEtN in biofilm-inspired assemblies. Nine pEtN-modified oligosaccharides were synthesized with full control over the length, degree and pattern of pEtN substitution. The oligomers were co-assembled with a representative peptide, triggering the formation of fibers in a length dependent manner. We discovered that the pEtN pattern modulates the adhesion of biofilm-inspired matrices, while the peptide component controls its stiffness. Unnatural oligosaccharides tune or disrupt the assembly morphology, revealing interesting targets for polysaccharide engineering to develop tunable bio-inspired materials.
Widespread increasing vegetation sensitivity to soil moisture
Authors: Li Wantong , Migliavacca Mirco , Forkel Matthias , Denissen Jasper M. C. , Reichstein Markus , Yang Hui , Duveiller Gregory , Weber Ulrich , Orth Rene
Published: July 2022

Global vegetation and associated ecosystem services critically depend on soil moisture availability which has decreased in many regions during the last three decades. While spatial patterns of vegetation sensitivity to global soil water have been recently investigated, long-term changes in vegetation sensitivity to soil water availability are still unclear. Here we assess global vegetation sensitivity to soil moisture during 1982-2017 by applying explainable machine learning with observation-based leaf area index (LAI) and hydro-climate anomaly data. We show that LAI sensitivity to soil moisture significantly increases in many semi-arid and arid regions. LAI sensitivity trends are associated with multiple hydro-climate and ecological variables, and strongest increasing trends occur in the most water-sensitive regions which additionally experience declining precipitation. State-of-the-art land surface models do not reproduce this increasing sensitivity as they misrepresent water-sensitive regions and sensitivity strength. Our sensitivity results imply an increasing ecosystem vulnerability to water availability which can lead to exacerbated reductions in vegetation carbon uptake under future intensified drought, consequently amplifying climate change.
Increased Indian Ocean-North Atlantic Ocean warming chain under greenhouse warming
Authors: Yang Young-Min , Park Jae-Heung , An Soon-Il , Yeh Sang-Wook , Zhu Zhiwei , Liu Fei , Li Juan , Lee June-Yi , Wang Bin
Published: July 2022

Over the past half a century, both the Indian Ocean (IO) and the North Atlantic Ocean (NA) exhibit strong warming trends like a global mean surface temperature (SST). Here, we show that not only simply as a result of increased greenhouse gases, but the IO-NA interaction through atmospheric teleconnection boosts up their warming trends. Climate model simulations demonstrate that the IO warming increases the NA SST by enhancing the longwave radiation through atmospheric teleconnection, subsequently, the warmer NA SST-induced atmospheric teleconnection leads to IO warming by reducing evaporative cooling with weakened surface winds. This two-way interaction (i.e., IO-NA warming chain) acts as positive feedback that reinforces warming over both ocean basins. The Pacific Ocean is partly involved in this warming chain as a modulator in an interdecadal timescale. These results highlight the importance of understanding ocean-basin interactions that may provide a more accurate future projection of warming.
GLI3 regulates muscle stem cell entry into GAlert and self-renewal
Authors: Brun Caroline E. , Sincennes Marie-Claude , Lin Alexander Y. T. , Hall Derek , Jarassier William , Feige Peter , Le Grand Fabien , Rudnicki Michael A.
Published: July 2022

Satellite cells are required for the growth, maintenance, and regeneration of skeletal muscle. Quiescent satellite cells possess a primary cilium, a structure that regulates the processing of the GLI family of transcription factors. Here we find that GLI3 processing by the primary cilium plays a critical role for satellite cell function. GLI3 is required to maintain satellite cells in a G0 dormant state. Strikingly, satellite cells lacking GLI3 enter the GAlert state in the absence of injury. Furthermore, GLI3 depletion stimulates expansion of the stem cell pool. As a result, satellite cells lacking GLI3 display rapid cell-cycle entry, increased proliferation and augmented self-renewal, and markedly enhanced regenerative capacity. At the molecular level, we establish that the loss of GLI3 induces mTORC1 signaling activation. Therefore, our results provide a mechanism by which GLI3 controls mTORC1 signaling, consequently regulating muscle stem cell activation and fate.
Mast4 determines the cell fate of MSCs for bone and cartilage development
Authors: Kim Pyunggang , Park Jinah , Lee Dong-Joon , Mizuno Seiya , Shinohara Masahiro , Hong Chang Pyo , Jeong Yealeen , Yun Rebecca , Park Hyeyeon , Park Sujin , Yang Kyung-Min , Lee Min-Jung , Jang Seung Pil , Kim Hyun-Yi , Lee Seung-Jun , Song Sun U. , Park Kyung-Soon , Tanaka Mikako , Ohshima Hayato , Cho Jin Won , Sugiyama Fumihiro , Takahashi Satoru , Jung Han-Sung , Kim Seong-Jin
Published: July 2022

Mesenchymal stromal cells (MSCs) differentiation into different lineages is precisely controlled by signaling pathways. Given that protein kinases play a crucial role in signal transduction, here we show that Microtubule Associated Serine/Threonine Kinase Family Member 4 (Mast4) serves as an important mediator of TGF-β and Wnt signal transduction in regulating chondro-osteogenic differentiation of MSCs. Suppression of Mast4 by TGF-β1 led to increased Sox9 stability by blocking Mast4-induced Sox9 serine 494 phosphorylation and subsequent proteasomal degradation, ultimately enhancing chondrogenesis of MSCs. On the other hand, Mast4 protein, which stability was enhanced by Wnt-mediated inhibition of GSK-3β and subsequent Smurf1 recruitment, promoted β-catenin nuclear localization and Runx2 activity, increasing osteogenesis of MSCs. Consistently,Mast4−/−mice demonstrated excessive cartilage synthesis, while exhibiting osteoporotic phenotype. Interestingly, Mast4 depletion in MSCs facilitated cartilage formation and regeneration in vivo. Altogether, our findings uncover essential roles of Mast4 in determining the fate of MSC development into cartilage or bone.
TRIM24 is an insulin-responsive regulator of P-bodies
Authors: Wei Wen , Chen Qiaoli , Liu Minjun , Sheng Yang , OuYang Qian , Feng Weikuan , Yang Xinyu , Ding Longfei , Su Shu , Zhang Jingzi , Fang Lei , Vidal-Puig Antonio , Wang Hong-Yu , Chen Shuai
Published: July 2022

Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability through the processing body (P-body) molecular machinery. However, whether and how insulin regulates mRNA stability via P-bodies is not clear. Here we show that the E3-ligase TRIM24 is a critical factor linking insulin signalling to P-bodies. Upon insulin stimulation, protein kinase B (PKB, also known as Akt) phosphorylates TRIM24 and stimulates its shuttling from the nucleus into the cytoplasm. TRIM24 interacts with several critical components of P-bodies in the cytoplasm, promoting their polyubiquitylation, which consequently stabilises Pparγ mRNA. Inactivation of TRIM24 E3-ligase activity or prevention of its phosphorylation via knockin mutations in mice promotes hepatic Pparγ degradation via P-bodies. Consequently, both knockin mutations alleviate hepatosteatosis in mice fed on a high-fat diet. Our results demonstrate the critical role of TRIM24 in linking insulin signalling to P-bodies and have therapeutic implications for the treatment of hepatosteatosis.
Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway
Authors: Li Jingwen , Liu Hanshu , Wang Xinyi , Xia Yun , Huang Jinsha , Wang Tao , Lin Zhicheng , Xiong Nian
Published: July 2022

An important pathophysiological component of Parkinson’s Disease (PD) is circadian rhythm disorder, closely related to a decrease in circulated melatonin (MLT) level. It has been reported recently that retinoic acid-associated orphan nuclear receptor (RORα), for the potentiallyendogenous ligand MLT, plays an important role in various diseases. However, the function of RORα in the pathogenesis of neurodegenerative diseases remains much unclear. Here, we showed in a cellular PD model that RORα expression was down-regulated in 1 methyl 4 phenyl pyridinium ion (MPP+)-treated BV2 cells but up-regulated by MLT. Of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - induced mouse model with RORα levels reduced in the midbrain tissue, MLT treatment (intraperitoneal 20 mg/kg/d for 7 days) significantly increased the RORα levels and protected dopamine neurons, with decreased inflammation and increased anti-inflammatory M2-like phenotype in the microglia. Furthermore, siRNA-mediated knockdown implied the involvement of signal transducer and activator of transcription (STAT) pathway. In conclusion, MLT ameliorates neuroinflammation by inhibiting STAT-related pro-inflammatory (M1-like) polarization of microglia, revealing alternative options for neuroprotective treatment of PD.
HistoML, a markup language for representation and exchange of histopathological features in pathology images
Authors: Lou Peiliang , Wang Chunbao , Guo Ruifeng , Yao Lixia , Zhang Guanjun , Yang Jun , Yuan Yong , Dong Yuxin , Gao Zeyu , Gong Tieliang , Li Chen
Published: July 2022

The study of histopathological phenotypes is vital for cancer research and medicine as it links molecular mechanisms to disease prognosis. It typically involves integration of heterogenous histopathological features in whole-slide images (WSI) to objectively characterize a histopathological phenotype. However, the large-scale implementation of phenotype characterization has been hindered by the fragmentation of histopathological features, resulting from the lack of a standardized format and a controlled vocabulary for structured and unambiguous representation of semantics in WSIs. To fill this gap, we propose the Histopathology Markup Language (HistoML), a representation language along with a controlled vocabulary (Histopathology Ontology) based on Semantic Web technologies. Multiscale features within a WSI, from single-cell features to mesoscopic features, could be represented using HistoML which is a crucial step towards the goal of making WSIs findable, accessible, interoperable and reusable (FAIR). We pilot HistoML in representing WSIs of kidney cancer as well as thyroid carcinoma and exemplify the uses of HistoML representations in semantic queries to demonstrate the potential of HistoML-powered applications for phenotype characterization.
Anesthetic modulations dissociate neuroelectric characteristics between sensory-evoked and spontaneous activities across bilateral rat somatosensory cortical laminae
Authors: Baek Kwangyeol , Park Chae Ri , Jang Siwan , Shim Woo Hyun , Kim Young Ro
Published: July 2022

Spontaneous neural activity has been widely adopted to construct functional connectivity (FC) amongst distant brain regions. Although informative, the functional role and signaling mechanism of the resting state FC are not intuitive as those in stimulus/task-evoked activity. In order to bridge the gap, we investigated anesthetic modulation of both resting-state and sensory-evoked activities. We used two well-studied GABAergic anesthetics of varying dose (isoflurane: 0.5–2.0% and α-chloralose: 30 and 60 mg/kg∙h) and recorded changes in electrophysiology using a pair of laminar electrode arrays that encompass the entire depth of the bilateral somatosensory cortices (S1fl) in rats. Specifically, the study focused to describe how varying anesthesia conditions affect the resting state activities and resultant FC between bilateral hemispheres in comparison to those obtained by evoked responses. As results, isoflurane decreased the amplitude of evoked responses in a dose-dependent manner mostly due to the habituation of repetitive responses. However, α-chloralose rather intensified the amplitude without exhibiting habituation. No such diverging trend was observed for the spontaneous activity, in which both anesthetics increased the signal power. For α-chloralose, overall FC was similar to that obtained with the lowest dose of isoflurane at 0.5% while higher doses of isoflurane displayed increased FC. Interestingly, only α-chloralose elicited relatively much greater increases in the ipsi-stimulus evoked response (i.e., in S1fl ipsilateral to the stimulated forelimb) than those associated with the contra-stimulus response, suggesting enhanced neuronal excitability. Taken together, the findings demonstrate modulation of the FC profiles by anesthesia is highly non-linear, possibly with a distinct underlying mechanism that affects either resting state or evoked activities differently. Further, the current study warrants thorough investigation of the basal neuronal states prior to the interpretation of resting state FC and evoked activities for accurate understanding of neural signal processing and circuitry.
Long-term posterolateral spinal fusion in rabbits induced by rhBMP6 applied in autologous blood coagulum with synthetic ceramics
Authors: Stokovic Nikola , Ivanjko Natalia , Pecin Marko , Erjavec Igor , Smajlović Ana , Milesevic Marina , Karlovic Sven , Capak Hrvoje , Vrbanac Zoran , Maticic Drazen , Vukicevic Slobodan
Published: July 2022

Autologous bone graft substitute (ABGS) containing rhBMP6 in autologous blood coagulum (Osteogrow) is a novel therapeutic solution for bone regeneration. This study is aimed to investigate the long-term outcome of ABGS with synthetic ceramics (Osteogrow-C) in rabbit posterolateral spinal fusion (PLF) model. Osteogrow-C implants were implanted bilaterally between rabbit lumbar transverse processes. We compared the outcome following implantation of ABGS with ceramic particles of different chemical composition (TCP and biphasic ceramics containing both TCP and HA) and size (500–1700 µm and 74–420 µm). Outcome was analyzed after 14 and 27 weeks by microCT, histology, and biomechanical analyses. Successful bilateral spinal fusion was observed in all animals at the end of observation period. Chemical composition of ceramic particles has impact on the PLF outcome via resorption of TCP ceramics, while ceramics containing HA were only partially resorbed. Moreover, persistence of ceramic particles subsequently resulted with an increased bone volume in implants with small particles containing high proportion of HA. ABGS (rhBMP6/ABC) with various synthetic ceramic particles promoted spinal fusion in rabbits. This is the first presentation of BMP-mediated ectopic bone formation in rabbit PLF model with radiological, histological, and biomechanical features over a time course of up to 27 weeks.