bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusive education and the law in Ireland
Authors: Murphy Muiread , Thompson Stephanie , Doyle David M. , Ferri Delia
Published: May 2022

By ratifying the UN Convention on the Rights of Persons with Disabilities (CRPD) in 2018, Ireland has undertaken inter alia the obligation to implement ‘an inclusive education system at all levels and lifelong learning’, as required by Article 24. However, concerns have been repeatedly expressed about the practice of inclusive education in Ireland in terms of admission policies, funding, school choice and reduced timetabling. This paper investigates whether, and to what extent, the current approach to special educational needs (SEN) in Ireland complies with the aim of ensuring an inclusive educational system in which children with disabilities are valued and empowered. Ireland is an interesting case-study due to its history of marginalisation of children with disabilities and its relatively recent engagement with the concept of inclusive education. By using a socio-legal approach, drawing on qualitative interviews with key stakeholders in education combined with a legal analysis of relevant primary and secondary sources, it examines the current practices relating to the education of children with disabilities in Ireland.
Entwicklung von psychischen Auffälligkeiten bei Mädchen und Jungen in stationären Jugendhilfeeinrichtungen zwischen den Jahren 2008 und 2020
Authors: Rau Thea , Mayer Sophia , Keller Ferdinand , Allroggen Marc
Published: May 2022

Zusammenfassung. Fragestellung: Studien zeigen eine höhere Prävalenz von psychischen Auffälligkeiten bei Kindern und Jugendlichen in stationären Jugendhilfeeinrichtungen im Vergleich zur altersentsprechenden Allgemeinbevölkerung. Es fehlen bislang Untersuchungen zur Entwicklung über die Zeit. In der vorliegenden Studie wurden psychische Auffälligkeiten von Kindern und Jugendlichen in diesen Einrichtungen und die Entwicklung des psychosozialen Funktionsniveaus über die Jahre 2008 bis 2020 untersucht. Methodik: Psychische Auffälligkeiten wurden mittels der Child Behavior Checklist (CBCL) erfasst, das psychosoziale Funktionsniveau mittels der Achse VI des Multiaxialen Klassifikationsschemas (MAS). Insgesamt wurden die Daten von 3269 Kindern und Jugendlichen in Jugendhilfeeinrichtungen analysiert. Ergebnisse: Bei der Betrachtung der Häufigkeit von psychischen Auffälligkeiten bei Kindern und Jugendlichen in stationären Jugendhilfeeinrichtungen über die Jahre 2008 bis 2020 zeigt sich eine Abnahme externalisierender Verhaltensauffälligkeiten, wobei speziell Jungen ab 12 Jahren über die Jahre verglichen weniger auffällig sind. Bei internalisierenden Verhaltensauffälligkeiten gehen die hohen Problemwerte auf die Werte von älteren Mädchen zurück, wobei sich hier kein einheitlicher Trend über die Zeit zeigt. Bei über einem Viertel der Kinder und Jugendlichen ist das psychosoziale Funktionsniveau über die Jahre in etwa gleichbleibend deutlich beeinträchtigt. Schlussfolgerungen: In Anbetracht der Alters- und Geschlechtseffekte im Zusammenhang mit der Entwicklung psychischer Auffälligkeiten über die Zeit ist eine Überprüfung der Betreuungssituation in stationären Jugendhilfeeinrichtungen zu empfehlen.
Redesigning Workplaces by Bridging the Gap Between Analysis and Action
Authors: Metzler Yannick A. , Neuhaus Ciel Alena , Taibi Yacine , Bellingrath Silja , Müller Andreas
Published: May 2022

Abstract. The step from hazard analysis to developing risk-mitigating measures is crucial to improving working conditions but has been scarcely researched to date. We qualitatively investigated protocols of analytical workshops in 33 organizational units that followed a prior hazard analysis with the Copenhagen Psychosocial Questionnaire (COPSOQ, N = 7,257 employees). There was a high degree of agreement between the COPSOQ results and those of the workshops. However, no measures were developed for approximately one-third of the identified work-design problems. A content analysis of the measures revealed the complex interrelationship between the work characteristics, as minimizing one risk factor seems to go hand in hand with the need to redesign others as well. The measures were often simple, indicating either that minimizing psychosocial risks is rather easy, or that the participants within the workshops did not have the authority to develop more complex measures. We discuss the implications to support future psychosocial risk management.
Southern Ocean Phytoplankton Stimulated by Wildfire Emissions and Sustained by Iron Recycling
Authors: Weis Jakob , Schallenberg Christina , Chase Zanna , Bowie Andrew R. , Wojtasiewicz Bozena , Perron Morgane M. G. , Mallet Marc D. , Strutton Peter G.
Published: May 2022

Large ash plumes emitted by the 2019–2020 Australian wildfires were associated with a widespread phytoplankton bloom in the iron‐limited Pacific sector of the Southern Ocean. In this study, we used satellite observations and aerosol reanalysis products to study the regional phytoplankton community response to wildfire emissions. The bloom was stimulated by pyrogenic iron fertilization and coincided with elevated cellular pigment concentrations, increased photochemical efficiency, and apparent community structural shifts. Physiological anomalies were consistent with previously observed phytoplankton responses to iron stress relief and persisted for up to 9 months. Supported by a regional iron budget, we conclude that the bloom was sustained by iron recycling and episodic inputs of pyrogenic and dust‐borne mineral iron. The continuous regeneration of iron was likely facilitated by the bloom's large size, mitigating edge dilution effects, as well as enhanced bioavailability of pyrogenic and mineral iron due to atmospheric and chemical processing during long‐range transport.
On the Magnetic Dip Ahead of the Dipolarization Fronts
Authors: Huang Hongtao , Yu Yiqun , Chen Zuzheng , Liu Chengming , Cao Jinbin , Yu Tongpu
Published: May 2022

Dipolarization front (DF), a transient structure that is associated with the earthward plasma flow, is widely considered as a result of magnetic reconnection. It is often characterized with a sharp increase in the northward magnetic field Bz preceded by a minor decrease of it. However, the small magnetic dip ahead of the DF is not always present, the reason of which is not well known. By analyzing in site Magnetospheric MultiScale spacecraft measurements at the magnetotail, we present two events of DF with and without a dip ahead of it. It is found that the magnetic dip ahead of DF is accompanied by a guide field By. To investigate the physical mechanism that determines the appearance of the dip, we perform kinetic simulations of symmetric single X line magnetic reconnection under various guide fields. The simulation results show that the dip is generated due to the separation of the gyro‐motion between ions and electrons under the influence of the guide field. Ions are reflected at the DF and further deviated by the guide field away from the neutral sheet, while more electrons remain in the neutral sheet due to their small gyroradius. In the absence of a compensating ion current, a dawnward current thus is formed, carried by the electrons, and generates the dip. Our results bring in a new perspective on the formation of the dip in single X line reconnection.
Performance of a Rotational Sensor to Decipher Volcano Seismic Signals on Etna, Italy
Authors: Eibl Eva P. S. , Rosskopf Martina , Sciotto Mariangela , Currenti Gilda , Di Grazia Giuseppe , Jousset Philippe , Krüger Frank , Weber Michael
Published: May 2022

Volcano‐seismic signals such as long‐period events and tremor are important indicators for volcanic activity and unrest. However, their wavefield is complex and characterization and location using traditional seismological instrumentation is often difficult. In 2019 we recorded the full seismic wavefield using a newly developed 3C rotational sensor co‐located with a 3C traditional seismometer on Etna, Italy. We compare the performance of the rotational sensor, the seismometer and the Istituto Nazionale di Geofisica e Vulcanologia‐Osservatorio Etneo (INGV‐OE) seismic network with respect to the analysis of complex volcano‐seismic signals. We create event catalogs for volcano‐tectonic (VT) and long‐period (LP) events combining a STA/LTA algorithm and cross‐correlations. The event detection based on the rotational sensor is as reliable as the seismometer‐based detection. The LP events are dominated by SH‐type waves. Derived SH phase velocities range from 500 to 1,000 m/s for LP events and 300–400 m/s for volcanic tremor. SH‐waves compose the tremor during weak volcanic activity and SH‐ and SV‐waves during sustained strombolian activity. We derive back azimuths using (a) horizontal rotational components and (b) vertical rotation rate and transverse acceleration. The estimated back azimuths are consistent with the INGV‐OE event location for (a) VT events with an epicentral distance larger than 3 km and some closer events, (b) LP events and tremor in the main crater area. Measuring the full wavefield we can reliably analyze the back azimuths, phase velocities and wavefield composition for VT, LP events and tremor in regions that are difficult to access such as volcanoes.
Survival of the Strong and Dense: Field Evidence for Rapid, Transport‐Dependent Bed Material Abrasion of Heterogeneous Source Lithology
Authors: Pfeiffer Allison M. , Morey Susannah , Karlsson Hannah M. , Fordham Edward M. , Montgomery David R.
Published: May 2022

Bed material abrasion is a major control on the partitioning of basin‐scale sediment fluxes between coarse and fine material. While abrasion is traditionally treated as an exponential function of transport distance and a lithology‐specific abrasion coefficient, experimental studies have demonstrated greater complexity in the abrasion process: the rate of abrasion varies with clast angularity, transport rate, and grain size. Yet, few studies have attempted to assess the importance of these complexities in a field setting. Here, we develop a new method for rapidly quantifying baseline abrasion rate in the field via Schmidt Hammer Rock Strength. We use this method, along with measurements of gravel bar lithology, to quantify abrasion in the Suiattle River, a basin in the North Cascades of Washington State in which sediment supply to the channel is dominated by recurrent debris flows from a tributary draining Glacier Peak stratovolcano. Rapid downstream strengthening of river bar sediment and a preferential loss of weak, low‐density vesicular volcanic clasts relative to non‐vesicular ones suggest that abrasion is extremely effective in this system. The standard exponential model for downstream abrasion, using single‐lithology abrasion rates fails to reproduce observed downstream patterns in lithology and clast strength. Incorporating heterogeneity in source material strength as well as transport rate‐dependent abrasion largely resolves this failure. Further work is needed to develop a comprehensive quantitative framework for the dependence of bed material abrasion on grain size and transport rate.
Chinese-Led Solar Research Is Looking Bright
Authors: Kornei Katherine
Published: May 2022

With new missions underway and planned, China is stepping up to observe our nearest stellar neighbor.
Turbidity Currents Can Dictate Organic Carbon Fluxes Across River‐Fed Fjords: An Example From Bute Inlet (BC, Canada)
Authors: Hage S. , Galy V. V. , Cartigny M. J. B. , Heerema C. , Heijnen M. S. , Acikalin S. , Clare M. A. , Giesbrecht I. , Gröcke D. R. , Hendry A. , Hilton R. G. , Hubbard S. M. , Hunt J. E. , Lintern D. G. , McGhee C. , Parsons D. R. , Pope E. L. , Stacey C. D. , Sumner E. J. , Tank S. , Talling P. J.
Published: May 2022

The delivery and burial of terrestrial particulate organic carbon (OC) in marine sediments is important to quantify, because this OC is a food resource for benthic communities, and if buried it may lower the concentrations of atmospheric CO2 over geologic timescales. Analysis of sediment cores has previously shown that fjords are hotspots for OC burial. Fjords can contain complex networks of submarine channels formed by seafloor sediment flows, called turbidity currents. However, the burial efficiency and distribution of OC by turbidity currents in river‐fed fjords had not been investigated previously. Here, we determine OC distribution and burial efficiency across a turbidity current system within Bute Inlet, a fjord in western Canada. We show that 62% ± 10% of the OC supplied by the two river sources is buried across the fjord surficial (30–200 cm) sediment. The sandy subenvironments (channel and lobe) contain 63% ± 14% of the annual terrestrial OC burial in the fjord. In contrast, the muddy subenvironments (overbank and distal basin) contain the remaining 37% ± 14%. OC in the channel, lobe, and overbank exclusively comprises terrestrial OC sourced from rivers. When normalized by the fjord’s surface area, at least 3 times more terrestrial OC is buried in Bute Inlet, compared to the muddy parts of other fjords previously studied. Although the long‐term (>100 years) preservation of this OC is still to be fully understood, turbidity currents in fjords appear to be efficient at storing OC supplied by rivers in their near‐surface deposits.
Virtual Height Characteristics of Ionospheric and Ground Scatter Observed by Mid‐Latitude SuperDARN HF Radars
Authors: Thomas E. G. , Shepherd S. G.
Published: May 2022

Propagation of high‐frequency (HF) radio signals is strongly dependent on the ionospheric electron density structure along a communications link. The ground‐based, HF space weather radars of the Super Dual Auroral Radar Network (SuperDARN) utilize the ionospheric refraction of transmitted signals to monitor the global circulation of E‐ and F‐region plasma irregularities. Previous studies have assessed the propagation characteristics of backscatter echoes from ionospheric irregularities in the auroral and polar regions of the Earth's ionosphere. By default, the geographic location of these echoes are found using empirical models which estimate the virtual backscattering height from the measured range along the radar signal path. However, the performance of these virtual height models has not yet been evaluated for mid‐latitude SuperDARN radar observations or for ground scatter (GS) propagation modes. In this study, we derive a virtual height model suitable for mid‐latitude SuperDARN observations using 5 years of data from the Christmas Valley East and West radars. This empirical model can be applied to both ionospheric and GS observations and provides an improved estimate of the ground range to the backscatter location compared to existing high‐latitude virtual height models. We also identify a region of overlapping half‐hop F‐region ionospheric scatter and one‐hop E‐region GS where the measured radar parameters (e.g., velocity, spectral width, elevation angle) are insufficient to discriminate between the two scatter types. Further studies are required to determine whether these backscatter echoes of ambiguous origin are observed by other mid‐latitude SuperDARN radars and their potential impact on scatter classification schemes.
Tunable structural colors on display
Authors: Tittl Andreas
Published: May 2022

Structural coloration takes inspiration from the bright hues found in nature to control the reflection and transmission of light from artificially structured materials. Combining them with active electrical tuning heralds breakthrough applications in optical displays.
Characterization of raloxifene as a potential pharmacological agent against SARS-CoV-2 and its variants
Authors: Iaconis Daniela , Bordi Licia , Matusali Giulia , Talarico Carmine , Manelfi Candida , Cesta Maria Candida , Zippoli Mara , Caccuri Francesca , Bugatti Antonella , Zani Alberto , Filippini Federica , Scorzolini Laura , Gobbi Marco , Beeg Marten , Piotti Arianna , Montopoli Monica , Cocetta Veronica , Bressan Silvia , Bucci Enrico M. , Caruso Arnaldo , Nicastri Emanuele , Allegretti Marcello , Beccari Andrea R.
Published: May 2022

The new coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic, which so far has caused over 6 million deaths in 2 years, despite new vaccines and antiviral medications. Drug repurposing, an approach for the potential application of existing pharmaceutical products to new therapeutic indications, could be an effective strategy to obtain quick answers to medical emergencies. Following a virtual screening campaign on the most relevant viral proteins, we identified the drug raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a new potential agent to treat mild-to-moderate COVID-19 patients. In this paper we report a comprehensive pharmacological characterization of raloxifene in relevant in vitro models of COVID-19, specifically in Vero E6 and Calu-3 cell lines infected with SARS-CoV-2. A large panel of the most common SARS-CoV-2 variants isolated in Europe, United Kingdom, Brazil, South Africa and India was tested to demonstrate the drug’s ability in contrasting the viral cytopathic effect (CPE). Literature data support a beneficial effect by raloxifene against the viral infection due to its ability to interact with viral proteins and activate protective estrogen receptor-mediated mechanisms in the host cells. Mechanistic studies here reported confirm the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies, and show that the drug treatment does not directly affect Spike/ACE2 interaction or viral internalization in infected cell lines. Interestingly, raloxifene can counteract Spike-mediated ADAM17 activation in human pulmonary cells, thus providing new insights on its mechanism of action. A clinical study in mild to moderate COVID-19 patients (NCT05172050) has been recently completed. Our contribution to evaluate raloxifene results on SARS-CoV-2 variants, and the interpretation of the mechanisms of action will be key elements to better understand the trial results, and to design new clinical studies aiming to evaluate the potential development of raloxifene in this indication.
Assessing the stability of Pd-exchanged sites in zeolites with the aid of a high throughput quantum chemistry workflow
Authors: Aljama Hassan A. , Head-Gordon Martin , Bell Alexis T.
Published: May 2022

Cation exchanged-zeolites are functional materials with a wide range of applications from catalysis to sorbents. They present a challenge for computational studies using density functional theory due to the numerous possible active sites. From Al configuration, to placement of extra framework cation(s), to potentially different oxidation states of the cation, accounting for all these possibilities is not trivial. To make the number of calculations more tractable, most studies focus on a few active sites. We attempt to go beyond these limitations by implementing a workflow for a high throughput screening, designed to systematize the problem and exhaustively search for feasible active sites. We use Pd-exchanged CHA and BEA to illustrate the approach. After conducting thousands of explicit DFT calculations, we identify the sites most favorable for the Pd cation and discuss the results in detail. The high throughput screening identifies many energetically favorable sites that are non-trivial. Lastly, we employ these results to examine NO adsorption in Pd-exchanged CHA, which is a promising passive NOx adsorbent (PNA) during the cold start of automobiles. The results shed light on critical active sites for NOx capture that were not previously studied.
Synergy of Pd atoms and oxygen vacancies on In2O3 for methane conversion under visible light
Authors: Luo Lei , Fu Lei , Liu Huifen , Xu Youxun , Xing Jialiang , Chang Chun-Ran , Yang Dong-Yuan , Tang Junwang
Published: May 2022

Methane (CH4) oxidation to high value chemicals under mild conditions through photocatalysis is a sustainable and appealing pathway, nevertheless confronting the critical issues regarding both conversion and selectivity. Herein, under visible irradiation (420 nm), the synergy of palladium (Pd) atom cocatalyst and oxygen vacancies (OVs) on In2O3nanorods enables superior photocatalytic CH4activation by O2. The optimized catalyst reaches ca. 100 μmol h−1of C1 oxygenates, with a selectivity of primary products (CH3OH and CH3OOH) up to 82.5%. Mechanism investigation elucidates that such superior photocatalysis is induced by the dedicated function of Pd single atoms and oxygen vacancies on boosting hole and electron transfer, respectively. O2is proven to be the only oxygen source for CH3OH production, while H2O acts as the promoter for efficient CH4activation through ·OH production and facilitates product desorption as indicated by DFT modeling. This work thus provides new understandings on simultaneous regulation of both activity and selectivity by the synergy of single atom cocatalysts and oxygen vacancies.
Serotonin limits generation of chromaffin cells during adrenal organ development
Authors: Kameneva Polina , Melnikova Victoria I. , Kastriti Maria Eleni , Kurtova Anastasia , Kryukov Emil , Murtazina Aliia , Faure Louis , Poverennaya Irina , Artemov Artem V. , Kalinina Tatiana S. , Kudryashov Nikita V. , Bader Michael , Skoda Jan , Chlapek Petr , Curylova Lucie , Sourada Lukas , Neradil Jakub , Tesarova Marketa , Pasqualetti Massimo , Gaspar Patricia , Yakushov Vasily D. , Sheftel Boris I. , Zikmund Tomas , Kaiser Jozef , Fried Kaj , Alenina Natalia , Voronezhskaya Elena E. , Adameyko Igor
Published: May 2022

Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor “bridge” cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3Ahigh human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in “bridge” progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies.
Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury
Authors: Francos-Quijorna Isaac , Sánchez-Petidier Marina , Burnside Emily R. , Badea Smaranda R. , Torres-Espin Abel , Marshall Lucy , de Winter Fred , Verhaagen Joost , Moreno-Manzano Victoria , Bradbury Elizabeth J.
Published: May 2022

Chondroitin sulfate proteoglycans (CSPGs) act as potent inhibitors of axonal growth and neuroplasticity after spinal cord injury (SCI). Here we reveal that CSPGs also play a critical role in preventing inflammation resolution by blocking the conversion of pro-inflammatory immune cells to a pro-repair phenotype in rodent models of SCI. We demonstrate that enzymatic digestion of CSPG glycosaminoglycans enhances immune cell clearance and reduces pro-inflammatory protein and gene expression profiles at key resolution time points. Analysis of phenotypically distinct immune cell clusters revealed CSPG-mediated modulation of macrophage and microglial subtypes which, together with T lymphocyte infiltration and composition changes, suggests a role for CSPGs in modulating both innate and adaptive immune responses after SCI. Mechanistically, CSPG activation of a pro-inflammatory phenotype in pro-repair immune cells was found to be TLR4-dependent, identifying TLR4 signalling as a key driver of CSPG-mediated immune modulation. These findings establish CSPGs as critical mediators of inflammation resolution failure after SCI in rodents, which leads to prolonged inflammatory pathology and irreversible tissue destruction.
Risk caused by the propagation of earthquake losses through the economy
Authors: León J. A. , Ordaz M. , Haddad E. , Araújo I. F.
Published: May 2022

The economy of a country is exposed to disruptions caused by natural and man-made disasters. Here we present a set of probabilistic risk indicators, the Average Annual Loss (AAL) and the Loss Exceedance Curve (LEC), regarding to production, employment, Gross Domestic Product (GDP), Gross Regional Product (GRP), export volume, inflation, tariff revenue, among others, due to earthquakes. All indicators are computed using a systematic probabilistic approach, which integrates the seismic risk assessment with spatial computable general equilibrium models, both robust and well-known frameworks used worldwide in their respective fields. Our approach considers the induced damage and frequency of occurrence of a vast collection of events that collectively describe the entire seismic hazard of a country, giving us a better and more complete understanding of the full consequence of earthquakes. We illustrate this approach with an example developed for Chile.
Modulating inherent lewis acidity at the intergrowth interface of mortise-tenon zeolite catalyst
Authors: Wang Huiqiu , Shen Boyuan , Chen Xiao , Xiong Hao , Wang Hongmei , Song Wenlong , Cui Chaojie , Wei Fei , Qian Weizhong
Published: May 2022

The acid sites of zeolite are important local structures to control the products in the chemical conversion. However, it remains a great challenge to precisely design the structures of acid sites, since there are still lack the controllable methods to generate and identify them with a high resolution. Here, we use the lattice mismatch of the intergrown zeolite to enrich the inherent Lewis acid sites (LASs) at the interface of a mortise-tenon ZSM-5 catalyst (ZSM-5-MT) with a 90° intergrowth structure. ZSM-5-MT is formed by two perpendicular blocks that are atomically resolved by integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM). It can be revealed by various methods that novel framework-associated Al (AlFR) LASs are generated in ZSM-5-MT. Combining the iDPC-STEM results with other characterizations, we demonstrate that the partial missing of O atoms at interfaces results in the formation of inherent AlFRLASs in ZSM-5-MT. As a result, the ZSM-5-MT catalyst shows a higher selectivity of propylene and butene than the single-crystal ZSM-5 in the steady conversion of methanol. These results provide an efficient strategy to design the Lewis acidity in zeolite catalysts for tailored functions via interface engineering.
Biogenesis of a bacterial metabolosome for propanediol utilization
Authors: Yang Mengru , Wenner Nicolas , Dykes Gregory F. , Li Yan , Zhu Xiaojun , Sun Yaqi , Huang Fang , Hinton Jay C. D. , Liu Lu-Ning
Published: May 2022

Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential for understanding their significance in cellular metabolism and pathogenesis. Here we investigate the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and characterize the roles of the key constituents in generation and intracellular positioning of functional metabolosomes. Our results demonstrate that the Pdu metabolosome undertakes both “Shell first” and “Cargo first” assembly pathways, unlike the β-carboxysome structural analog which only involves the “Cargo first” strategy. Shell and cargo assemblies occur independently at the cell poles. The internal cargo core is formed through the ordered assembly of multiple enzyme complexes, and exhibits liquid-like properties within the metabolosome architecture. Our findings provide mechanistic insight into the molecular principles driving bacterial metabolosome assembly and expand our understanding of liquid-like organelle biogenesis.
Chirality locking charge density waves in a chiral crystal
Authors: Li Geng , Yang Haitao , Jiang Peijie , Wang Cong , Cheng Qiuzhen , Tian Shangjie , Han Guangyuan , Shen Chengmin , Lin Xiao , Lei Hechang , Ji Wei , Wang Ziqiang , Gao Hong-Jun
Published: May 2022

In Weyl semimetals, charge density wave (CDW) order can spontaneously break the chiral symmetry, gap out the Weyl nodes, and drive the material into the axion insulating phase. Investigations have however been limited since CDWs are rarely seen in Weyl semimetals. Here, using scanning tunneling microscopy/spectroscopy (STM/S), we report the discovery of a novel unidirectional CDW order on the (001) surface of chiral crystal CoSi – a unique Weyl semimetal with unconventional chiral fermions. The CDW is incommensurate with both lattice momentum and crystalline symmetry directions, and exhibits an intra unit cell π phase shift in the layer stacking direction. The tunneling spectrum shows a particle-hole asymmetric V-shaped energy gap around the Fermi level that modulates spatially with the CDW wave vector. Combined with first-principle calculations, we identify that the CDW is locked to the crystal chirality and is related by a mirror reflection between the two enantiomers of the chiral crystal. Our findings reveal a novel correlated topological quantum state in chiral CoSi crystals and raise the potential for exploring the unprecedented physical behaviors of unconventional chiral fermions.
Cell type-specific biotin labeling in vivo resolves regional neuronal and astrocyte proteomic differences in mouse brain
Authors: Rayaprolu Sruti , Bitarafan Sara , Santiago Juliet V. , Betarbet Ranjita , Sunna Sydney , Cheng Lihong , Xiao Hailian , Nelson Ruth S. , Kumar Prateek , Bagchi Pritha , Duong Duc M. , Goettemoeller Annie M. , Oláh Viktor János , Rowan Matt , Levey Allan I. , Wood Levi B. , Seyfried Nicholas T. , Rangaraju Srikant
Published: May 2022

Proteomic profiling of brain cell types using isolation-based strategies pose limitations in resolving cellular phenotypes representative of their native state. We describe a mouse line for cell type-specific expression of biotin ligase TurboID, for in vivo biotinylation of proteins. Using adenoviral and transgenic approaches to label neurons, we show robust protein biotinylation in neuronal soma and axons throughout the brain, allowing quantitation of over 2000 neuron-derived proteins spanning synaptic proteins, transporters, ion channels and disease-relevant druggable targets. Next, we contrast Camk2a-neuron and Aldh1l1-astrocyte proteomes and identify brain region-specific proteomic differences within both cell types, some of which might potentially underlie the selective vulnerability to neurological diseases. Leveraging the cellular specificity of proteomic labeling, we apply an antibody-based approach to uncover differences in neuron and astrocyte-derived signaling phospho-proteins and cytokines. This approach will facilitate the characterization of cell-type specific proteomes in a diverse number of tissues under both physiological and pathological states.
The 3′ Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies’ association with histone locus bodies
Authors: Suzuki Hidefumi , Abe Ryota , Shimada Miho , Hirose Tomonori , Hirose Hiroko , Noguchi Keisuke , Ike Yoko , Yasui Nanami , Furugori Kazuki , Yamaguchi Yuki , Toyoda Atsushi , Suzuki Yutaka , Yamamoto Tatsuro , Saitoh Noriko , Sato Shigeo , Tomomori-Sato Chieri , Conaway Ronald C. , Conaway Joan W. , Takahashi Hidehisa
Published: May 2022

Non-polyadenylated mRNAs of replication-dependent histones (RDHs) are synthesized by RNA polymerase II (Pol II) at histone locus bodies (HLBs). HLBs frequently associate with Cajal bodies (CBs), in which 3′-end processing factors for RDH genes are enriched; however, this association’s role in transcription termination of RDH genes remains unclear. Here, we show that Pol II pauses immediately upstream of transcript end sites of RDH genes and Mediator plays a role in this Pol II pausing through CBs’ association with HLBs. Disruption of the Mediator docking site for Little elongation complex (LEC)–Cap binding complex (CBC)–Negative elongation factor (NELF), components of CBs, interferes with CBs’ association with HLBs and 3′ Pol II pausing, resulting in increased aberrant unprocessed RDH gene transcripts. Our findings suggest Mediator’s involvement in CBs’ association with HLBs to facilitate 3′ Pol II pausing and subsequent 3′-end processing of RDH genes by supplying 3′-end processing factors.
Peptide nano-blanket impedes fibroblasts activation and subsequent formation of pre-metastatic niche
Authors: Zhou Yi , Ke Peng , Bao Xiaoyan , Wu Honghui , Xia Yiyi , Zhang Zhentao , Zhong Haiqing , Dai Qi , Wu Linjie , Wang Tiantian , Lin Mengting , Li Yaosheng , Jiang Xinchi , Yang Qiyao , Lu Yiying , Zhong Xincheng , Han Min , Gao Jianqing
Published: May 2022

There is evidence to suggest that the primary tumor induces the formation of a pre-metastatic niche in distal organs by stimulating the production of pro-metastatic factors. Given the fundamental role of the pre-metastatic niche in the development of metastases, interruption of its formation would be a promising strategy to take early action against tumor metastasis. Here we report an enzyme-activated assembled peptide FR17 that can serve as a “flame-retarding blanket” in the pre-metastatic niche specifically to extinguish the “fire” of tumor-supportive microenvironment adaption. We show that the in-situ assembled peptide nano-blanket inhibits fibroblasts activation, suppressing the remodeling of the metastasis-supportive host stromal tissue, and reversing vascular destabilization and angiogenesis. Furthermore, we demonstrate that the nano-blanket prevents the recruitment of myeloid cells to the pre-metastatic niche, regulating the immune-suppressive microenvironment. We show that FR17 administration effectively inhibits the formation of the pulmonary pre-metastatic niche and postoperative metastasis, offering a therapeutic strategy against pre-metastatic niche formation.
Seeking patterns of antibiotic resistance in ATLAS, an open, raw MIC database with patient metadata
Authors: Catalán Pablo , Wood Emily , Blair Jessica M. A. , Gudelj Ivana , Iredell Jonathan R. , Beardmore Robert E.
Published: May 2022

Antibiotic resistance represents a growing medical concern where raw, clinical datasets are under-exploited as a means to track the scale of the problem. We therefore sought patterns of antibiotic resistance in the Antimicrobial Testing Leadership and Surveillance (ATLAS) database. ATLAS holds 6.5M minimal inhibitory concentrations (MICs) for 3,919 pathogen-antibiotic pairs isolated from 633k patients in 70 countries between 2004 and 2017. We show most pairs form coherent, although not stationary, timeseries whose frequencies of resistance are higher than other databases, although we identified no systematic bias towards including more resistant strains in ATLAS. We sought data anomalies whereby MICs could shift for methodological and not clinical or microbiological reasons and found artefacts in over 100 pathogen-antibiotic pairs. Using an information-optimal clustering methodology to classify pathogens into low and high antibiotic susceptibilities, we used ATLAS to predict changes in resistance. Dynamics of the latter exhibit complex patterns with MIC increases, and some decreases, whereby subpopulations’ MICs can diverge. We also identify pathogens at risk of developing clinical resistance in the near future.
Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes
Authors: Wang Chunyan , Hesketh Emma L. , Shamorkina Tatiana M. , Li Wentao , Franken Peter J. , Drabek Dubravka , van Haperen Rien , Townend Sarah , van Kuppeveld Frank J. M. , Grosveld Frank , Ranson Neil A. , Snijder Joost , de Groot Raoul J. , Hurdiss Daniel L. , Bosch Berend-Jan
Published: May 2022

Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1A domain, but, remarkably, also to S1B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1B epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.
A high-throughput multiparameter screen for accelerated development and optimization of soluble genetically encoded fluorescent biosensors
Authors: Koveal Dorothy , Rosen Paul C. , Meyer Dylan J. , Díaz-García Carlos Manlio , Wang Yongcheng , Cai Li-Heng , Chou Peter J. , Weitz David A. , Yellen Gary
Published: May 2022

Genetically encoded fluorescent biosensors are powerful tools used to track chemical processes in intact biological systems. However, the development and optimization of biosensors remains a challenging and labor-intensive process, primarily due to technical limitations of methods for screening candidate biosensors. Here we describe a screening modality that combines droplet microfluidics and automated fluorescence imaging to provide an order of magnitude increase in screening throughput. Moreover, unlike current techniques that are limited to screening for a single biosensor feature at a time (e.g. brightness), our method enables evaluation of multiple features (e.g. contrast, affinity, specificity) in parallel. Because biosensor features can covary, this capability is essential for rapid optimization. We use this system to generate a high-performance biosensor for lactate that can be used to quantify intracellular lactate concentrations. This biosensor, named LiLac, constitutes a significant advance in metabolite sensing and demonstrates the power of our screening approach.
O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine
Authors: Kim Kibum , Yoo Hee Chan , Kim Byung Gyu , Kim Sulhee , Sung Yulseung , Yoon Ina , Yu Ya Chun , Park Seung Joon , Kim Jong Hyun , Myung Kyungjae , Hwang Kwang Yeon , Kim Sunghoon , Han Jung Min
Published: May 2022

All living organisms have the ability to sense nutrient levels to coordinate cellular metabolism. Despite the importance of nutrient-sensing pathways that detect the levels of amino acids and glucose, how the availability of these two types of nutrients is integrated is unclear. Here, we show that glucose availability regulates the central nutrient effector mTORC1 through intracellular leucine sensor leucyl-tRNA synthetase 1 (LARS1). Glucose starvation results in O-GlcNAcylation of LARS1 on residue S1042. This modification inhibits the interaction of LARS1 with RagD GTPase and reduces the affinity of LARS1 for leucine by promoting phosphorylation of its leucine-binding site by the autophagy-activating kinase ULK1, decreasing mTORC1 activity. The lack of LARS1 O-GlcNAcylation constitutively activates mTORC1, supporting its ability to sense leucine, and deregulates protein synthesis and leucine catabolism under glucose starvation. This work demonstrates that LARS1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine.
Rhodium-catalyzed selective direct arylation of phosphines with aryl bromides
Authors: Wang Dingyi , Li Mingjie , Shuang Chengdong , Liang Yong , Zhao Yue , Wang Minyan , Shi Zhuangzhi
Published: May 2022

The widespread use of phosphine ligand libraries is frequently hampered by the challenges associated with their modular preparation. Here, we report a protocol that appends arenes to arylphosphines to access a series of biaryl monophosphines via rhodium-catalyzed P(III)-directedorthoC–H activation, enabling unprecedented one-fold, two-fold, and three-fold direct arylation. Our experimental and theoretical findings reveal a mechanism involving oxidative addition of aryl bromides to the Rh catalyst, furtherorthoC–H metalation viaafour-membered cyclometalated ring. Given the ready availability of substrates, our approach opens the door to developing more general methods for the construction of phosphine ligands.
The macular inner plexiform layer thickness as an early diagnostic indicator for Parkinson’s disease
Authors: Wang Xin , Jiao Bin , Jia Xiaoliang , Wang Yaqin , Liu Hui , Zhu Xiangyu , Hao Xiaoli , Zhu Yuan , Xu Bei , Zhang Sizhe , Xu Qian , Wang Junling , Guo Jifeng , Yan Xinxiang , Tang Beisha , Zhao Rongchang , Shen Lu
Published: May 2022

Whether structural alterations of intraretinal layers are indicators for the early diagnosis of Parkinson’s disease (PD) remains unclear. We assessed the retinal layer thickness in different stages of PD and explored whether it can be an early diagnostic indicator for PD. In total, 397 [131, 146, and 120 with Hoehn-Yahr I (H-Y I), H-Y II, and H-Y III stages, respectively] patients with PD and 427 healthy controls (HCs) were enrolled. The peripapillary retinal nerve fiber layer (pRNFL), total macular retinal thickness (MRT), and macular volume (TMV) were measured by high-definition optical coherence tomography, and the macular intraretinal thickness was analyzed by the Iowa Reference Algorithms. As a result, the PD group had a significantly lower average, temporal quadrant pRNFL, MRT, and TMV than the HCs group (all p < 0.001). Moreover, the ganglion cell layer (GCL), inner plexiform layer (IPL), and outer nuclear layer were thinner in patients with PD with H-Y I, and significantly decreased as the H-Y stage increased. In addition, we observed that GCL and IPL thicknesses were both correlated with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS III) scores and non-motor symptoms assessment scores. Furthermore, macular IPL thickness in the superior inner (SI) quadrant (IPL-SI) had the best diagnostic performance in patients with PD with H-Y I versus HCs, with a sensitivity and specificity of 75.06% and 81.67%, respectively. In conclusion, we confirmed the retinal structure was significantly altered in patients with PD in different clinical stages, and that GCL and IPL changes occurred during early PD disease and were correlated with MDS-UPDRS III scores and non-motor symptoms assessment scores. Furthermore, macular IPL-SI thickness might be performed as an early diagnostic indicator for PD.
Dataset of solution-based inorganic materials synthesis procedures extracted from the scientific literature
Authors: Wang Zheren , Kononova Olga , Cruse Kevin , He Tanjin , Huo Haoyan , Fei Yuxing , Zeng Yan , Sun Yingzhi , Cai Zijian , Sun Wenhao , Ceder Gerbrand
Published: May 2022

The development of a materials synthesis route is usually based on heuristics and experience. A possible new approach would be to apply data-driven approaches to learn the patterns of synthesis from past experience and use them to predict the syntheses of novel materials. However, this route is impeded by the lack of a large-scale database of synthesis formulations. In this work, we applied advanced machine learning and natural language processing techniques to construct a dataset of 35,675 solution-based synthesis procedures extracted from the scientific literature. Each procedure contains essential synthesis information including the precursors and target materials, their quantities, and the synthesis actions and corresponding attributes. Every procedure is also augmented with the reaction formula. Through this work, we are making freely available the first large dataset of solution-based inorganic materials synthesis procedures.
Cross-reactive immunity potentially drives global oscillation and opposed alternation patterns of seasonal influenza A viruses
Authors: Gatti Lorenzo , Koenen Mischa H. , Zhang Jitao David , Anisimova Maria , Verhagen Lilly M. , Schutten Martin , Osterhaus Ab , van der Vries Erhard
Published: May 2022

Several human pathogens exhibit distinct patterns of seasonality and circulate as pairs. For instance, influenza A virus subtypes oscillate and peak during winter seasons of the world’s temperate climate zones. Alternation of dominant strains in successive influenza seasons makes epidemic forecasting a major challenge. From the start of the 2009 influenza pandemic we enrolled influenza A virus infected patients (n = 2980) in a global prospective clinical study. Complete hemagglutinin sequences were obtained from 1078 A/H1N1 and 1033 A/H3N2 viruses. We used phylodynamics to construct high resolution spatio-temporal phylogenetic hemagglutinin trees and estimated global influenza A effective reproductive numbers (R) over time (2009–2013). We demonstrate that R oscillates around R = 1 with a clear opposed alternation pattern between phases of the A/H1N1 and A/H3N2 subtypes. Moreover, we find a similar alternation pattern for the number of global viral spread between the sampled geographical locations. Both observations suggest a between-strain competition for susceptible hosts on a global level. Extrinsic factors that affect person-to-person transmission are a major driver of influenza seasonality. The data presented here indicate that cross-reactive host immunity is also a key intrinsic driver of influenza seasonality, which determines the influenza A virus strain at the onset of each epidemic season.
Exploring 3D elastic-wave scattering at interfaces using high-resolution phased-array system
Authors: Ohara Yoshikazu , Remillieux Marcel C. , Ulrich Timothy James , Ozawa Serina , Tsunoda Kosuke , Tsuji Toshihiro , Mihara Tsuyoshi
Published: May 2022

The elastic-wave scattering at interfaces, such as cracks, is essential for nondestructive inspections, and hence, understanding the phenomenon is crucial. However, the elastic-wave scattering at cracks is very complex in three dimensions since microscopic asperities of crack faces can be multiple scattering sources. We propose a method for exploring 3D elastic-wave scattering based on our previously developed high-resolution 3D phased-array system, the piezoelectric and laser ultrasonic system (PLUS). We describe the principle of PLUS, which combines a piezoelectric transmitter and a 2D mechanical scan of a laser Doppler vibrometer, enabling us to resolve a crack into a collection of scattring sources. Subsequently, we show how the 3D elastic-wave scattering in the vicinity of each response can be extracted. Here, we experimentally applied PLUS to a fatigue-crack specimen. We found that diverse 3D elastic-wave scattering occurred in a manner depending on the responses within the fatigue crack. This is significant because access to such information will be useful for optimizing inspection conditions, designing ultrasonic measurement systems, and characterizing cracks. More importantly, the described methodology is very general and can be applied to not only metals but also other materials such as composites, concrete, and rocks, leading to progress in many fields.