bluuebunny/crossref_metadata_2025 huggingface dataset:
Populismus versus majoritärer Relativismus: Zu einer wichtigen Unterscheidung zwischen Demokratiekonzeptionen in der Bevölkerung
Authors: König Pascal D.
Published: June 2022

Neben einem populistischen Demokratieverständnis bildet auch ein majoritärer Relativismus Teil der deutschen politischen Kultur. Dieser Aufsatz argumentiert und liefert Evidenz dafür, dass es sich um zwei unterschiedliche, aber zugleich teils miteinander verwandte Demokratieauffassungen handelt und dass es wichtig ist, beide auseinanderzuhalten. Wie der Populismus erwartet der majoritäre Relativismus die möglichst unmittelbare und getreue Verwirklichung der Interessen in der Bevölkerung, er hält dabei jedoch ausdrücklich nicht an der Idee eines wahren und einheitlichen Volkswillens fest. Während beide positiv mit der Unterstützung der rechtspopulistischen Partei Alternative für Deutschland (AfD) zusammenhängen, zeigt nur der Populismus einen negativen Zusammenhang mit optimierendem Problemlösen durch künstliche Intelligenz in der politischen Führung, der majoritäre Relativismus hingegen sogar einen positiven Zusammenhang. Bemerkenswert ist zudem, dass der majoritäre Relativismus Unterstützung für die AfD besser vorhersagt als ein populistisches Demokratieverständnis. Damit leistet der Aufsatz einen wichtigen Beitrag zur Debatte über Populismus als Bestandteil der politischen Kultur in Deutschland.
On mathematical optimization for clustering categories in contingency tables
Authors: Carrizosa Emilio , Guerrero Vanesa , Romero Morales Dolores
Published: June 2022

Many applications in data analysis study whether two categorical variables are independent using a function of the entries of their contingency table. Often, the categories of the variables, associated with the rows and columns of the table, are grouped, yielding a less granular representation of the categorical variables. The purpose of this is to attain reasonable sample sizes in the cells of the table and, more importantly, to incorporate expert knowledge on the allowable groupings. However, it is known that the conclusions on independence depend, in general, on the chosen granularity, as in the Simpson paradox. In this paper we propose a methodology to, for a given contingency table and a fixed granularity, find a clustered table with the highest $$\chi ^2$$

χ
2

statistic. Repeating this procedure for different values of the granularity, we can either identify an extreme grouping, namely the largest granularity for which the statistical dependence is still detected, or conclude that it does not exist and that the two variables are dependent regardless of the size of the clustered table. For this problem, we propose an assignment mathematical formulation and a set partitioning one. Our approach is flexible enough to include constraints on the desirable structure of the clusters, such as must-link or cannot-link constraints on the categories that can, or cannot, be merged together, and ensure reasonable sample sizes in the cells of the clustered table from which trustful statistical conclusions can be derived. We illustrate the usefulness of our methodology using a dataset of a medical study.
Can flipped classroom pedagogy offer promising perspectives for mathematics education on pandemic-related issues? A systematic literature review
Authors: Cevikbas Mustafa , Kaiser Gabriele
Published: June 2022

Educators sometimes effect changes in education through the implementation of new ideas, and sometimes extraordinary circumstances force them to change their educational approaches, as during the COVID-19 crisis. Although we live in a digital age, the limited use of technology in education, particularly prior to the COVID-19 pandemic, and teachers’ insufficient experience with online or hybrid learning and teaching approaches resulted in several countries being unprepared for education during the pandemic. The flipped classroom (FC) is an innovative pedagogy with the potential to engage students in mathematics education using hybrid education combined with online and face-to-face learning, which is especially important during a pandemic. However, despite the high expectations surrounding this innovative approach, to date, no systematic literature review has discussed the opportunities and pitfalls of FCs in mathematics education regarding pandemic-related issues. In the present systematic review, we aim to bridge this gap and highlight the importance of flipping mathematics instruction during the pandemic and beyond. The results, which are based on textual analysis of 97 eligible articles, demonstrate that FC is a promising pedagogy that has numerous benefits for mathematics teaching and learning, although it is not a panacea for pandemic-related issues, as it also has several significant pitfalls. Overall, if the mechanism of mathematics education is to be crisis-ready, we should learn from experiences during the pandemic. In this regard, the current review contributes to research in mathematics education with the aim of gaining insight into successful implementations of FC pedagogy, not only during the pandemic but also beyond the crisis era of a pandemic.
Children’s needs during disclosures of abuse
Authors: Ettinger Tara R.
Published: June 2022

A Narrative Literature Review was conducted providing a comprehensive overview of children’s barriers to disclose during investigations of child abuse. Patterns in the literature were categorized as themes and include: rapport and relationship with the interviewer, feeling in control and prepared, communication, physical abilities, mental health, environment, family dynamics, culture and individual uniqueness. Using a combination of a critical analyses approach and drawing from personal background experiences and knowledge in working with children during disclosures, the themes are expanded upon as a discussion that explores what children may therapeutically need during their disclosures of abuse within the forensic interview. Some practice implications are incorporated with the intent to generate further thinking about addressing children’s needs during investigations of child abuse. Working with multidisciplinary teams in Child and Youth Advocacy Centres is discussed and may be a resource for understanding children’s needs during disclosures of abuse.
Ongoing Positive Selection Drives the Evolution of SARS-CoV-2 Genomes
Authors: Hou Yali , Zhao Shilei , Liu Qi , Zhang Xiaolong , Sha Tong , Su Yankai , Zhao Wenming , Bao Yiming , Xue Yongbiao , Chen Hua
Published: June 2022

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30, 2021, we demonstrate with population genetic evidence that during the course of SARS-CoV-2 pandemic in humans, 1) SARS-CoV-2 genomes are overall conserved under purifying selection, especially for the 14 genes related to viral RNA replication, transcription, and assembly; 2) ongoing positive selection is actively driving the evolution of 6 genes (e.g., S, ORF3a, and N) that play critical roles in molecular processes involving pathogen–host interactions, including viral invasion into and egress from host cells, and viral inhibition and evasion of host immune response, possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution. According to an established haplotype phylogenetic relationship of 138 viral clusters, a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters, of which multiple mutations potentially conferring alterations in viral transmissibility, pathogenicity, and virulence of SARS-CoV-2 are highlighted, warranting attention.
A prospective case series on rhino orbital cerebral mucormycosis in Egypt: Epidemiology, systemic implications, and treatment
Authors: Elmonofy Omar , Ghanem Mohamed , Abdelwahab Mohamed , Mubarak Fahmy A.
Published: June 2022

ABSTRACT

Introduction and importance:

To identify and recognize systemic implications, clinical, characteristics, and management of a group of patients with rhino orbitocerbral mucormycosis infection.

Case presentation:

The study included twenty-five patients aged range (12–71 years) with rhino orbital cerebral mucormycosis infection who were admitted to the oral and maxillofacial department in Cairo, Egypt from January 2016 to January 2021. The diagnosis was based on clinical examination, radiographic evaluation, and histopathological reports. Cases were managed according to severity and extension of the infection.

Clinical discussion:

sixteen (64%) males and 9 (36%) females mean age was 44.17 years in a presented sample. 98% of orbital involvement was unilaterally always related to the Right eye (for unknown cause) mortality rate of about six patients (25%). Identified risk factors included eighteen patients (72%) who had diabetes mellitus of these patients ten were undiagnosed at the time of examination, while seven (18%) patients with the hematological disorder as Hodgkin or non-Hodgkin lymphoma, aplastic anemia, and Wegener's disease. These patients were managed by aggressive surgical debridement, antifungal drugs (Amphotericin B), and adjunctive treatment with hyperbaric oxygen Hyperbaric oxygen was used in five patients post-surgically. All investigations were done with mean values of blood glucose level, hemoglobin and WBC were noticeably abnormal.

Conclusions:

Early identification and reorganization of systemic implications, early clinical diagnosis of patients with mucormycosis infection will facilitate and improve management strategies and outcome of those patients. Understanding this disease will help in rapid and proper management into place to face this lethal opportunistic infection. The most common predisposing factor was diabetes mellitus followed by patients with hematological malignancies.

Highlights
Surface-tension-driven evolution of a viscoplastic liquid coating the interior of a cylindrical tube
Authors: Shemilt James D. , Horsley Alexander , Jensen Oliver E. , Thompson Alice B. , Whitfield Carl A.
Published: June 2022

One mechanism for airway closure in the lung is the surface-tension-driven instability of the mucus layer which lines the airway wall. We study the instability of an axisymmetric layer of viscoplastic Bingham liquid coating the interior of a rigid tube, which is a simple model for an airway that takes into account the yield stress of mucus. An evolution equation for the thickness of the liquid layer is derived using long-wave theory, from which we also derive a simpler thin-film evolution equation. In the thin-film case we show that two branches of marginally yielded static solutions of the evolution equation can be used to both predict the size of the initial perturbation required to trigger instability and quantify how increasing the capillary Bingham number (a parameter measuring yield stress relative to surface tension) reduces the final deformation of the layer. Using numerical solutions of the long-wave evolution equation, we quantify how the critical layer thickness required to form a liquid plug in the tube increases as the capillary Bingham number is increased. We discuss the significance of these findings for modelling airway closure in obstructive conditions such as cystic fibrosis, where the mucus layer is often thicker and has a higher yield stress.
Phonological mergers have systemic phonetic consequences:palm, trees, and the Low Back Merger Shift
Authors: Gardner Matt Hunt , Roeder Rebecca V.
Published: June 2022

This paper provides a unified phonologically motivated explanation for the movement oftrap,dress, andkitfollowing the low-back merger in North American English (i.e., the Canadian Shift, California Shift, Low Back Merger Shift, Third Shift, etc.). The explanation puts forth that the three-way merger oflot,palm, andthoughtresults in the loss of the [+Front] feature specification fortrap, opening the door for dispersion focalization to pulltraptoward the low central region of the vowel space. Analogy then prompts all other [−Peripheral] vowels, includingstrutandfoot, to centralize. Crucial to this explanation is that the low-back merger includespalm, not justlotandthought. Evidence for this requirement is presented in a phonetic analysis of older speakers from conservative Victoria, British Columbia. The explanation presented here reconciles an earlier proposal (Roeder & Gardner, 2013) with Fruehwald's (2017) observation that parallel movement requires a shared feature specification.
A Consistent Framework for Coupling Basal Friction With Subglacial Hydrology on Hard‐Bedded Glaciers
Authors: Gilbert Adrien , Gimbert Florent , Thøgersen Kjetil , Schuler Thomas V. , Kääb Andreas
Published: June 2022

Below hard‐bedded glaciers, both basal friction and distributed subglacial drainage are thought to be controlled by a network of cavities. Previous coupled hydro‐mechanical models, however, describe cavity‐driven friction and hydraulic transmissivity independently, resulting in a physically inconsistent cavity evolution between the two components of the models. Here, we overcome this issue by describing the hydro‐mechanical system using a common cavity‐evolution description, that governs both transient friction and hydraulic transmissivity. We show that our coupling approach is superior to previous formulations in explaining a unique observation record of glacier sliding speed from the French Alps. We find that, at multi‐day to multi‐decadal timescales, sliding speed can be expressed as a direct function of basal shear stress and water discharge, without accounting for water pressure, which simply adjusts to maintain the cavitation ratio needed to accommodate the water supply.
Detecting Volcano‐Related Underground Mass Changes With a Quantum Gravimeter
Authors: Antoni‐Micollier Laura , Carbone Daniele , Ménoret Vincent , Lautier‐Gaud Jean , King Thomas , Greco Filippo , Messina Alfio , Contrafatto Danilo , Desruelle Bruno
Published: June 2022

We present the world's first time series acquired in the summit area of an active volcano with an absolute atom interferometry gravimeter. The device was installed ∼2.5 km from the active craters of Mt. Etna volcano and produced a continuous high–quality gravity time series, despite the unfavorable environmental conditions at the installation site and the occurrence of phases of high volcanic tremor during the acquisition interval. Comparison with data from superconducting gravimeters installed elsewhere on Mt. Etna highlights correlated anomalies, demonstrating that the quantum device measured gravity variations driven by bulk mass changes. The latter are reflective of volcanic processes, involving the dynamics of magma and exsolved gas in the upper part of Mt. Etna's plumbing system. Our results confirm the operational possibilities of quantum gravimetry and open new horizons for the application of the gravity method in geophysics.
Strong Ocean/Sea‐Ice Contrasts Observed in Satellite‐Derived Ice Crystal Number Concentrations in Arctic Ice Boundary‐Layer Clouds
Authors: Papakonstantinou‐Presvelou Iris , Sourdeval Odran , Quaas Johannes
Published: June 2022

The Arctic climate changes at a faster rate than the rest of the globe. Boundary‐layer clouds may play an important role in this change. At temperatures below 0°C, mixed‐phase clouds exist and their phase and longevity is influenced by the abundance of ice crystals, which in turn is a function of aerosols serving as ice nucleating particles (INPs). Previous in situ studies suggested a local source of INPs due to biological activity over open ocean. Here we investigate ice crystal concentrations in clouds below 2 km at a large scale, by exploiting a newly developed data set—DARDAR‐Nice—retrieved from active satellite remote sensing. The data set spans from 2006 to 2016. Contrary to previous expectation, we find that at a given latitude and temperature, there are more ice crystals over sea ice than over open ocean. This enhancement is particularly found in clouds south of 70°N, and also at temperatures between 0°C and −10°C.
Observed Equatorward Propagation and Chimney Effect of Near‐Inertial Waves in the Midlatitude Ocean
Authors: Yu Xiaolong , Naveira Garabato Alberto C. , Vic Clément , Gula Jonathan , Savage Anna C. , Wang Jinbo , Waterhouse Amy F. , MacKinnon Jennifer A.
Published: June 2022

The propagation characteristics of near‐inertial waves (NIWs) and how mesoscale and submesoscale processes affect the waves' vertical penetration are investigated using observations from a mooring array located in the northeast Atlantic. The year‐long observations show that near‐inertial motions are mainly generated by local wind forcing, and that they radiate equatorward and downward following several strong wind events (wind stress ≳0.5 N m−2). Observational estimates of horizontal group speed typically exceed those of vertical group speed by two orders of magnitude, consistent with predictions from the dispersion relation. Enhanced near‐inertial kinetic energy and vertical shear are found only in mesoscale anticyclones with Rossby number of O(0.1). By contrast, submesoscale motions with order one Rossby number have little effect on the trapping and vertical penetration of NIWs, due to their smaller horizontal scales, shorter time scales, and confined vertical extent compared to mesoscale eddies.
The Beaufort Gyre’s Diffusive Staircase: Finescale Signatures of Gyre‐Scale Transport
Authors: Shibley Nicole C. , Timmermans Mary‐Louise
Published: June 2022

Arctic Ocean waters sourced from the Atlantic contain a vast amount of heat. In the Arctic’s Beaufort Gyre, diffusive convection is the primary mechanism by which this heat is transported vertically. This mixing process is characterized by a “staircase” where convective layers are separated by interfaces in temperature and salinity. It is not well‐understood what governs layer thickness, which is an important parameter in heat transport. Here we relate staircase properties to the background water‐mass structure of the Beaufort Gyre via analysis of Ice‐Tethered Profiler observations. We find that staircase layer thicknesses vary with intrusive features below the staircase and the stratification overlying the staircase. We relate these features to the pathway of anomalously warm Atlantic Water in the Beaufort Gyre. Results suggest that intrusive features in context with the Gyre’s large‐scale geostrophic flow may be key to understanding layer thicknesses and the propagation of warm waters into the Gyre.
Sound Velocities of Superhydrous Phase B up to 21 GPa and 900 K
Authors: Xu Chaowen , Gréaux Steeve , Inoue Toru , Noda Masamichi , Gao Jing , Li Ying
Published: June 2022

Sound velocities and density of Mg10Si3H4O18 superhydrous phase B (SuB) were investigated by synchrotron X‐rays combined with ultrasonic interferometry techniques in a multi‐anvil apparatus, up to 21 GPa and 900 K. Our data show that SuB has compressional (VP) and shear velocities (VS) lower than major anhydrous minerals but higher than majorite garnet. Our data combined with those of other mantle minerals allowed estimation of VP and VS of hydrated mantle regions at depths of the mantle transition zone and upper lower mantle. The local hydration of pyrolitic mantle with SuB as the main water host could explain low VP and low VS anomalies near cold subduction zones while it would be associated with low VP and high VS anomalies in hot mantle regions. The anomalies may be particularly strong in the ∼30 km beneath the 660 km discontinuity, due to the discrepancy of post‐spinel transition between hydrous and dry pyrolite lithologies.
Melting of the Fe‐C‐H System and Earth's Deep Carbon‐Hydrogen Cycle
Authors: Lai Xiaojing , Zhu Feng , Gao Jing , Greenberg Eran , Prakapenka Vitali B. , Meng Yue , Chen Bin
Published: June 2022

The occurrences and cycling of slab‐originated carbon and hydrogen are considered to be controlled by their reactions with metallic iron from mantle disproportionation and slab serpentinization, to form Fe alloys containing carbon and hydrogen. Here we show experimental results on the phase relations and melting of the Fe‐C‐H system using laser‐heated diamond anvil cell and X‐ray diffraction techniques up to 72 GPa. The incorporation of hydrogen was found to lower the eutectic melting temperatures of Fe‐C alloy by ∼50–178 K at 20–70 GPa, facilitating the formation of metallic liquids in the deep mantle and thus enhancing the mobility and deep cycling of subducted carbon and hydrogen. Hydrogen also substitutes with carbon in Fe‐C metal to form hydride and diamond at relatively high‐temperature conditions (e.g., 42.6 GPa, >1885 K and 71.8 GPa, >1798 K). The hydrogen‐carbon‐enriched metallic liquids provide the necessary fluid environment for superdeep diamond growth.
Buried Paleo‐Channel Detection With a Groundwater Model, Tracer‐Based Observations, and Spatially Varying, Preferred Anisotropy Pilot Point Calibration
Authors: Schilling O. S. , Partington D. J. , Doherty J. , Kipfer R. , Hunkeler D. , Brunner P.
Published: June 2022

Alluvial sand and gravel (ASG) aquifers are highly heterogeneous and exhibit strong, spatially variable anisotropy, often interspersed by buried paleo‐channels of increased hydraulic conductivity. Groundwater flow and solute transport is often characterized by preferential flow caused by anisotropic properties in ASG aquifers. Connected ASG subsurface structures such as buried paleo‐channels, however, are difficult to reproduce with commonly used techniques, and anisotropy is rarely considered in applied groundwater models. To ease the notoriously difficult problem of how to consider anisotropy, we propose a novel modeling framework based on calibration of an integrated surface‐subsurface hydrological model via spatially varying, preferred anisotropy pilot point inversion. The inversion leverages hydraulic and tracer‐based observations representing multiple spatial and temporal scales. We demonstrate the applicability of the framework on a real‐world ASG site used for drinking water production, and we quantify the information content of observations to identify connected paleo‐channels and provide guidance for optimal field‐data acquisition.
Landslide Sensitivity and Response to Precipitation Changes in Wet and Dry Climates
Authors: Handwerger Alexander L. , Fielding Eric J. , Sangha Simran S. , Bekaert David P. S.
Published: June 2022

Slow‐moving landslides are hydrologically driven. Yet, landslide sensitivity to precipitation, and in particular, precipitation extremes, is difficult to constrain because landslides occur under diverse hydroclimatological conditions. Here we use standardized open‐access satellite radar interferometry data to quantify the sensitivity of 38 landslides to both a record drought and extreme rainfall that occurred in California between 2015 and 2020. These landslides are hosted in similar rock types, but span more than ∼2 m/yr in mean annual rainfall. Despite the large differences in hydroclimate, we found these landslides exhibited surprisingly similar behaviors and hydrologic sensitivity, which was characterized by faster (slower) than average velocities during wetter (drier) than average years, once the impact of the drought diminished. Our findings may be representative of future landslide behaviors in California where precipitation extremes are predicted to become more frequent with climate change.
Fast Nocturnal Heterogeneous Chemistry in a Coastal Background Atmosphere and Its Implications for Daytime Photochemistry
Authors: Niu Ying‐Bo , Zhu Bo , He Ling‐Yan , Wang Zhe , Lin Xiao‐Yu , Tang Meng‐Xue , Huang Xiao‐Feng
Published: June 2022

Nitryl chloride (ClNO2) is an important chlorine reservoir in the atmosphere that affects the oxidation capacity by producing first‐ and second‐generation radicals, but it has been rarely observed in the world. Here, online measurements of both N2O5 and ClNO2 at a coastal background site in the Pearl River Delta (PRD) in southern China, a region with high atmospheric oxidation capacity in the daytime, are presented. We observed continuous accumulation of elevated ClNO2 at night, while N2O5 was generally low. The maximum concentrations of N2O5 and ClNO2 were 1.4 and 1.7 ppbv, respectively, associated with a transported urban plume with high levels of O3 and NO2. The average product of N2O5 uptake coefficient and ClNO2 yield (γ × f = 0.02, with average γ of 0.027 and f of 0.71) was roughly twice those in urban areas in China, indicating active N2O5 heterogenous chemistry and effective ClNO2 formation in the background atmosphere. The production rate of Cl radicals (pCl) from the photolysis of ClNO2 was estimated to be an order of magnitude higher than those at coastal and rural sites in the literature. Such levels of Cl radical production could have considerable contribution to the atmospheric oxidation capacity after sunrise. In addition, NO2 produced by ClNO2 photolysis in the morning accounted for approximately 10% of the NO2 increase within several hours after sunrise. Thus, high nocturnal ClNO2 production and its following daytime photochemistry should be considered seriously in regional air quality modeling in the PRD and regions with similar conditions.
Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants
Authors: Sun Cong , Xie Chu , Bu Guo-Long , Zhong Lan-Yi , Zeng Mu-Sheng
Published: June 2022

The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.
Microbiomes of bloom-forming Phaeocystis algae are stable and consistently recruited, with both symbiotic and opportunistic modes
Authors: Mars Brisbin Margaret , Mitarai Satoshi , Saito Mak A , Alexander Harriet
Published: June 2022

Phaeocystis is a cosmopolitan, bloom-forming phytoplankton genus that contributes significantly to global carbon and sulfur cycles. During blooms, Phaeocystis species produce large carbon-rich colonies, creating a unique interface for bacterial interactions. While bacteria are known to interact with phytoplankton—e.g., they promote growth by producing phytohormones and vitamins—such interactions have not been shown for Phaeocystis. Therefore, we investigated the composition and function of P. globosa microbiomes. Specifically, we tested whether microbiome compositions are consistent across individual colonies from four P. globosa strains, whether similar microbiomes are re-recruited after antibiotic treatment, and how microbiomes affect P. globosa growth under limiting conditions. Results illuminated a core colonial P. globosa microbiome—including bacteria from the orders Alteromonadales, Burkholderiales, and Rhizobiales—that was re-recruited after microbiome disruption. Consistent microbiome composition and recruitment is indicative that P. globosa microbiomes are stable-state systems undergoing deterministic community assembly and suggests there are specific, beneficial interactions between Phaeocystis and bacteria. Growth experiments with axenic and nonaxenic cultures demonstrated that microbiomes allowed continued growth when B-vitamins were withheld, but that microbiomes accelerated culture collapse when nitrogen was withheld. In sum, this study reveals symbiotic and opportunistic interactions between Phaeocystis colonies and microbiome bacteria that could influence large-scale phytoplankton bloom dynamics and biogeochemical cycles.
Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery
Authors: Vaney Marie-Christine , Dellarole Mariano , Duquerroy Stéphane , Medits Iris , Tsouchnikas Georgios , Rouvinski Alexander , England Patrick , Stiasny Karin , Heinz Franz X. , Rey Félix A.
Published: June 2022

The flavivirus envelope glycoproteins prM and E drive the assembly of icosahedral, spiky immature particles that bud across the membrane of the endoplasmic reticulum. Maturation into infectious virions in the trans-Golgi network involves an acid-pH-driven rearrangement into smooth particles made of (prM/E)2 dimers exposing a furin site for prM cleavage into “pr” and “M”. Here we show that the prM “pr” moiety derives from an HSP40 cellular chaperonin. Furthermore, the X-ray structure of the tick-borne encephalitis virus (pr/E)2 dimer at acidic pH reveals the E 150-loop as a hinged-lid that opens at low pH to expose a positively-charged pr-binding pocket at the E dimer interface, inducing (prM/E)2 dimer formation to generate smooth particles in the Golgi. Furin cleavage is followed by lid-closure upon deprotonation in the neutral-pH extracellular environment, expelling pr while the 150-loop takes the relay in fusion loop protection, thus revealing the elusive flavivirus mechanism of fusion activation.
A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery
Authors: Tan Hayden Weng Siong , Lu Guang , Dong Han , Cho Yik-Lam , Natalia Auginia , Wang Liming , Chan Charlene , Kappei Dennis , Taneja Reshma , Ling Shuo-Chien , Shao Huilin , Tsai Shih-Yin , Ding Wen-Xing , Shen Han-Ming
Published: June 2022

PINK1-Parkin mediated mitophagy, a selective form of autophagy, represents one of the most important mechanisms in mitochondrial quality control (MQC) via the clearance of damaged mitochondria. Although it is well known that the conjugation of mammalian ATG8s (mATG8s) to phosphatidylethanolamine (PE) is a key step in autophagy, its role in mitophagy remains controversial. In this study, we clarify the role of the mATG8-conjugation system in mitophagy by generating knockouts of the mATG8-conjugation machinery. Unexpectedly, we show that mitochondria could still be cleared in the absence of the mATG8-conjugation system, in a process independent of lysosomal degradation. Instead, mitochondria are cleared via extracellular release through a secretory autophagy pathway, in a process we define as Autophagic Secretion of Mitochondria (ASM). Functionally, increased ASM promotes the activation of the innate immune cGAS-STING pathway in recipient cells. Overall, this study reveals ASM as a mechanism in MQC when the cellular mATG8-conjugation machinery is dysfunctional and highlights the critical role of mATG8 lipidation in suppressing inflammatory responses.
Nanoscale self-organization and metastable non-thermal metallicity in Mott insulators
Authors: Ronchi Andrea , Franceschini Paolo , De Poli Andrea , Homm Pía , Fitzpatrick Ann , Maccherozzi Francesco , Ferrini Gabriele , Banfi Francesco , Dhesi Sarnjeet S. , Menghini Mariela , Fabrizio Michele , Locquet Jean-Pierre , Giannetti Claudio
Published: June 2022

Mott transitions in real materials are first order and almost always associated with lattice distortions, both features promoting the emergence of nanotextured phases. This nanoscale self-organization creates spatially inhomogeneous regions, which can host and protect transient non-thermal electronic and lattice states triggered by light excitation. Here, we combine time-resolved X-ray microscopy with a Landau-Ginzburg functional approach for calculating the strain and electronic real-space configurations. We investigate V2O3, the archetypal Mott insulator in which nanoscale self-organization already exists in the low-temperature monoclinic phase and strongly affects the transition towards the high-temperature corundum metallic phase. Our joint experimental-theoretical approach uncovers a remarkable out-of-equilibrium phenomenon: the photo-induced stabilisation of the long sought monoclinic metal phase, which is absent at equilibrium and in homogeneous materials, but emerges as a metastable state solely when light excitation is combined with the underlying nanotexture of the monoclinic lattice.
MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma
Authors: Tao Ling , Mohammad Mahmoud A. , Milazzo Giorgio , Moreno-Smith Myrthala , Patel Tajhal D. , Zorman Barry , Badachhape Andrew , Hernandez Blanca E. , Wolf Amber B. , Zeng Zihua , Foster Jennifer H. , Aloisi Sara , Sumazin Pavel , Zu Youli , Hicks John , Ghaghada Ketan B. , Putluri Nagireddy , Perini Giovanni , Coarfa Cristian , Barbieri Eveline
Published: June 2022

Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and pharmacological SLC27A2 inhibition selectively suppresses tumor growth, prolongs animal survival, and exerts synergistic anti-tumor effects when combined with conventional chemotherapies in multiple preclinical NB models. This study identifies FA uptake as a critical metabolic dependency for MYCN-amplified tumors. Inhibiting FA uptake is an effective approach for improving current treatment regimens.
Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency
Authors: De Ravin Suk See , Liu Siyuan , Sweeney Colin L. , Brault Julie , Whiting-Theobald Narda , Ma Michelle , Liu Taylor , Choi Uimook , Lee Janet , O’Brien Sandra Anaya , Quackenbush Priscilla , Estwick Tyra , Karra Anita , Docking Ethan , Kwatemaa Nana , Guo Shuang , Su Ling , Sun Zhonghe , Zhou Sheng , Puck Jennifer , Cowan Morton J. , Notarangelo Luigi D. , Kang Elizabeth , Malech Harry L. , Wu Xiaolin
Published: June 2022

X-linked Severe Combined Immunodeficiency (SCID-X1) due to IL2RG mutations is potentially fatal in infancy where ‘emergency’ life-saving stem cell transplant may only achieve incomplete immune reconstitution following transplant. Salvage therapy SCID-X1 patients over 2 years old (NCT01306019) is a non-randomized, open-label, phase I/II clinical trial for administration of lentiviral-transduced autologous hematopoietic stem cells following busulfan (6 mg/kg total) conditioning. The primary and secondary objectives assess efficacy in restoring immunity and safety by vector insertion site analysis (VISA). In this ongoing study (19 patients treated), we report VISA in blood lineages from first eight treated patients with longer follow up found a > 60-fold increase in frequency of forward-orientated VIS within intron 3 of the High Mobility Group AT-hook 2 gene. All eight patients demonstrated emergence of dominant HMGA2 VIS clones in progenitor and myeloid lineages, but without disturbance of hematopoiesis. Our molecular analysis demonstrated a cryptic splice site within the chicken β-globin hypersensitivity 4 insulator element in the vector generating truncated mRNA transcripts from many transcriptionally active gene containing forward-oriented intronic vector insert. A two base-pair change at the splice site within the lentiviral vector eliminated splicing activity while retaining vector functional capability. This highlights the importance of functional analysis of lentivectors for cryptic splicing for preclinical safety assessment and a redesign of clinical vectors to improve safety.
Surface plasmons induce topological transition in graphene/α-MoO3 heterostructures
Authors: Ruta Francesco L. , Kim Brian S. Y. , Sun Zhiyuan , Rizzo Daniel J. , McLeod Alexander S. , Rajendran Anjaly , Liu Song , Millis Andrew J. , Hone James C. , Basov D. N.
Published: June 2022

Polaritons in hyperbolic van der Waals materials—where principal axes have permittivities of opposite signs—are light-matter modes with unique properties and promising applications. Isofrequency contours of hyperbolic polaritons may undergo topological transitions from open hyperbolas to closed ellipse-like curves, prompting an abrupt change in physical properties. Electronically-tunable topological transitions are especially desirable for future integrated technologies but have yet to be demonstrated. In this work, we present a doping-induced topological transition effected by plasmon-phonon hybridization in graphene/α-MoO3 heterostructures. Scanning near-field optical microscopy was used to image hybrid polaritons in graphene/α-MoO3. We demonstrate the topological transition and characterize hybrid modes, which can be tuned from surface waves to bulk waveguide modes, traversing an exceptional point arising from the anisotropic plasmon-phonon coupling. Graphene/α-MoO3 heterostructures offer the possibility to explore dynamical topological transitions and directional coupling that could inspire new nanophotonic and quantum devices.
The impact of rare germline variants on human somatic mutation processes
Authors: Vali-Pour Mischan , Park Solip , Espinosa-Carrasco Jose , Ortiz-Martínez Daniel , Lehner Ben , Supek Fran
Published: June 2022

Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. We perform a gene-based rare variant association study with diverse mutational processes, using human cancer genomes from over 11,000 individuals of European ancestry. By combining burden and variance tests, we identify 207 associations involving 15 somatic mutational phenotypes and 42 genes that replicated in an independent data set at a false discovery rate of 1%. We associate rare inherited deleterious variants in genes such as MSH3, EXO1, SETD2, and MTOR with two phenotypically different forms of DNA mismatch repair deficiency, and variants in genes such as EXO1, PAXIP1, RIF1, and WRN with deficiency in homologous recombination repair. In addition, we identify associations with other mutational processes, such as APEX1 with APOBEC-signature mutagenesis. Many of the genes interact with each other and with known mutator genes within cellular sub-networks. Considered collectively, damaging variants in the identified genes are prevalent in the population. We suggest that rare germline variation in diverse genes commonly impacts mutational processes in somatic cells.
Dual topological states in the layered titanium-based oxypnictide superconductor BaTi2Sb2O
Authors: Huang Z. , Liu W. L. , Wang H. Y. , Su Y. L. , Liu Z. T. , Shi X. B. , Gao S. Y. , Chen Z. Y. , Yan Y. J. , Jiang Z. C. , Liu Z. H. , Liu J. S. , Lu X. L. , Yang Y. C. , Zhou R. X. , Xia W. , Huang Y. B. , Qiao S. , Zhao W. W. , Guo Y. F. , Li G. , Shen D. W.
Published: June 2022

Topological superconductors have long been predicted to host Majorana zero modes which obey non-Abelian statistics and have potential for realizing non-decoherence topological quantum computation. However, material realization of topological superconductors is still a challenge in condensed matter physics. Utilizing high-resolution angle-resolved photoemission spectroscopy and first-principles calculations, we predict and then unveil the coexistence of topological Dirac semimetal and topological insulator states in the vicinity of Fermi energy (EF) in the titanium-based oxypnictide superconductor BaTi2Sb2O. Further spin-resolved measurements confirm its spin-helical surface states around EF, which are topologically protected and give an opportunity for realization of Majorana zero modes and Majorana flat bands in one material. Hosting dual topological states, the intrinsic superconductor BaTi2Sb2O is expected to be a promising platform for further investigation of topological superconductivity.
Instructor-learner body coupling reflects instruction and learning
Authors: Pan Yafeng , Dikker Suzanne , Zhu Yi , Yang Cuirong , Hu Yi , Goldstein Pavel
Published: June 2022

It is widely accepted that nonverbal communication is crucial for learning, but the exact functions of interpersonal coordination between instructors and learners remain unclear. Specifically, it is unknown what role instructional approaches play in the coupling of physical motion between instructors and learners, and crucially, how such instruction-mediated Body-to-Body Coupling (BtBC) might affect learning. We used a video-based, computer-vision Motion Energy Analysis (MEA) to quantify BtBC between learners and instructors who used two different instructional approaches to teach psychological concepts. BtBC was significantly greater when the instructor employed a scaffolding approach than when an explanation approach was used. The importance of the instructional approach was further underscored by the fact that an increase in motion in the instructor was associated with boosted BtBC, but only during scaffolding; no such relationship between the instructor movements and BtBC was found during explanation interactions. Finally, leveraging machine learning approaches (i.e., support vector and logistic regression models), we demonstrated that both learning outcome and instructional approaches could be decoded based on BtBC. Collectively, these results show that the real-time interaction of teaching and learning bodies is important for learning and that the instructional approach matters, with possible implications for both in-person and online learning.
Unprecedented frequency of mitochondrial introns in colonial bilaterians
Authors: Jenkins Helen Louise , Graham Rachael , Porter Joanne Sara , Vieira Leandro Manzoni , de Almeida Ana Carolina Sousa , Hall Andrea , O’Dea Aaron , Coppard Simon Edward , Waeschenbach Andrea
Published: June 2022

Animal mitogenomes are typically devoid of introns. Here, we report the largest number of mitochondrial introns ever recorded from bilaterian animals. Mitochondrial introns were identified for the first time from the phylum Bryozoa. They were found in four species from three families (Order Cheilostomatida). A total of eight introns were found in the complete mitogenome of Exechonella vieirai, and five, 17 and 18 introns were found in the partial mitogenomes of Parantropora penelope, Discoporella cookae and Cupuladria biporosa, respectively. Intron-encoded protein domains reverse transcriptase and intron maturase (RVT-IM) were identified in all species. Introns in E. vieirai and P. penelope had conserved Group II intron ribozyme domains V and VI. Conserved domains were lacking from introns in D. cookae and C. biporosa, preventing their further categorization. Putative origins of metazoan introns were explored in a phylogenetic context, using an up-to-date alignment of mitochondrial RVT-IM domains. Results confirmed previous findings of multiple origins of annelid, placozoan and sponge RVT-IM domains and provided evidence for common intron donor sources across metazoan phyla. Our results corroborate growing evidence that some metazoans with regenerative abilities (i.e. placozoans, sponges, annelids and bryozoans) are susceptible to intron integration, most likely via horizontal gene transfer.
Single-cell transcriptional profiling reveals cellular and molecular divergence in human maternal–fetal interface
Authors: Wang Quanlei , Li Jinlu , Wang Shengpeng , Deng Qiuting , An Yanru , Xing Yanan , Dai Xi , Li Zelong , Ma Qiwang , Wang Kuixing , Liu Chuanyu , Yuan Yue , Dong Guoyi , Zhang Tao , Yang Huanming , Du Yutao , Hou Yong , Ke Weilin , Shang Zhouchun
Published: June 2022

Placenta plays essential role in successful pregnancy, as the most important organ connecting and interplaying between mother and fetus. However, the cellular characteristics and molecular interaction of cell populations within the fetomaternal interface is still poorly understood. Here, we surveyed the single-cell transcriptomic landscape of human full-term placenta and revealed the heterogeneity of cytotrophoblast cell (CTB) and stromal cell (STR) with the fetal/maternal origin consecutively localized from fetal section (FS), middle section (Mid_S) to maternal section (Mat_S) of maternal–fetal interface. Then, we highlighted a subpopulation of CTB, named trophoblast progenitor-like cells (TPLCs) existed in the full-term placenta and mainly distributed in Mid_S, with high expression of a pool of putative cell surface markers. Further, we revealed the putative key transcription factor PRDM6 that might promote the differentiation of endovascular extravillous trophoblast cells (enEVT) by inhibiting cell proliferation, and down-regulation of PRDM6 might lead to an abnormal enEVT differentiation process in PE. Together, our study offers important resources for better understanding of human placenta and stem cell-based therapy, and provides new insights on the study of tissue heterogeneity, the clinical prevention and control of PE as well as the maternal–fetal interface.
Orthologs of human circulating miRNAs associated with hepatocellular carcinoma are elevated in mouse plasma months before tumour detection
Authors: Ding Liang-Hao , Fallgren Christina M. , Yu Yongjia , McCarthy Maureen , Edmondson Elijah F. , Ullrich Robert L. , Weil Michael. M. , Story Michael D.
Published: June 2022

Research examining the potential for circulating miRNA to serve as markers for preneoplastic lesions or early-stage hepatocellular carcinoma (HCC) is hindered by the difficulties of obtaining samples from asymptomatic individuals. As a surrogate for human samples, we identified hub miRNAs in gene co-expression networks using HCC-bearing C3H mice. We confirmed 38 hub miRNAs as associated with HCC in F2 hybrid mice derived from radiogenic HCC susceptible and resistant founders. When compared to a panel of 12 circulating miRNAs associated with human HCC, two had no mouse ortholog and 7 of the remaining 10 miRNAs overlapped with the 38 mouse HCC hub miRNAs. Using small RNA sequencing data generated from serially collected plasma samples in F2 mice, we examined the temporal levels of these 7 circulating miRNAs and found that the levels of 4 human circulating markers, miR-122-5p, miR-100-5p, miR-34a-5p and miR-365-3p increased linearly as the time approaching HCC detection neared, suggesting a correlation of miRNA levels with oncogenic progression. Estimation of change points in the kinetics of the 4 circulating miRNAs suggested the changes started 17.5 to 6.8 months prior to HCC detection. These data establish these 4 circulating miRNAs as potential sentinels for preneoplastic lesions or early-stage HCC.