bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanocrystals perovskites photocatalyzed singlet oxygen generation for light-driven organic reactions
Authors: Corti Marco , Chiara Rossella , Romani Lidia , Mannucci Barbara , Malavasi Lorenzo , Quadrelli Paolo
Published: October 2021

Lead halide perovskite nanocrystals were prepared and used as photocatalysts for the in situ 1O2 generation to perform hetero Diels–Alder, ene and oxidation reactions with suitable dienes and alkenes. The methodology has been reasonably standardized and made applicable to a variety of olefinic substrates. The scope of the method is finely illustrated by the results in all the tested reactions, which allowed to obtain desymmetrized hydroxy-ketone derivatives, unsaturated ketones and epoxides. Some limitations were also observed especially in the case of the alkene oxidations as well as poor chemoselectivity was somewhere observed.

Graphic abstract

1O2 generated by lead halide perovskite nanocrystals as photocatalyst in organic reactions.
Community-engaged research in translational science: Innovations to improve health in Appalachia
Authors: Rhodes Scott D. , Ballard Parissa J. , Moore Keena R. , Klein Karen , Randall Isaiah , Lischke Michael , Vissman Aaron T. , Lengerich Eugene J. , Daniel Stephanie S. , Skelton Joseph A.
Published: October 2021

Health disparities between Appalachia and the rest of the country are widening. To address this, the Appalachian Translational Research Network (ATRN) organizes an annual ATRN Health Summit. The most recent Summit was held online September 22–23, 2020, and hosted by Wake Forest Clinical and Translational Science Institute in partnership with the Northwest Area Health Education Center. The Summit, titled “Community-Engaged Research in Translational Science: Innovations to Improve Health in Appalachia,” brought together a diverse group of 141 stakeholders from communities, academic institutions, and the National Center for Advancing Translational Science (NCATS) to highlight current research, identify innovative approaches to translational science and community-engaged research, develop cross-regional research partnerships, and establish and disseminate priorities for future Appalachian-focused research. The Summit included three plenary presentations and 39 presentations within 12 concurrent breakout sessions. Here, we describe the Summit planning process and implementation, highlight some of the research presented, and outline nine emergent themes to guide future Appalachian-focused research.
An algebraic treatment of the Askey biorthogonal polynomials on the unit circle
Authors: Vinet Luc , Zhedanov Alexei
Published: October 2021

A joint algebraic interpretation of the biorthogonal Askey polynomials on the unit circle and of the orthogonal Jacobi polynomials is offered. It ties their bispectral properties to an algebra called the meta-Jacobi algebra

$m\mathfrak {J}$

.
Impact of Clostridioides difficile infection on patient-reported quality of life
Authors: Han Zheyi , Lapin Brittany , Garey Kevin W. , Donskey Curtis J. , Deshpande Abhishek
Published: October 2021

Objective:

We investigated the quality of life (QoL) of patients hospitalized with C. difficile infection (CDI).

Design:

Prospective survey study.

Setting:

US tertiary-care referral center, acute-care setting.

Participants:

Adults hospitalized with a diagnosis of CDI, defined as ≥3 episodes of unformed stool in 24 hours and a positive laboratory test for C. difficile.

Methods:

We surveyed patients from July 2019 to March 2020 using the disease-specific Cdiff32 questionnaire and the generic PROMIS GH survey. We compared differences in Cdiff32 scores among demographic and clinical subgroups (including CDI severity, CDI recurrence, and various comorbidities) using 2-sample t tests. We compared PROMIS GH scores to the general population T score of 50 using 1-sample t tests. We performed multivariable linear regression to identify predictors of Cdiff32 scores.

Results:

In total, 100 inpatients (mean age, 58.6 ±17.1 years; 53.0% male; 87.0% white) diagnosed with CDI completed QoL surveys. PROMIS GH physical health summary scores (T = 37.3; P < .001) and mental health summary scores (T = 43.4; P < .001) were significantly lower than those of the general population. In bivariate analysis, recurrent CDI, severe CDI, and number of stools were associated with lower Cdiff32 scores. In multivariable linear regression, recurrent CDI, severe CDI, and each additional stool in the previous 24 hours were associated with significantly decreased Cdiff32 scores.

Conclusions:

Patients hospitalized with CDI reported low scores on the Cdiff32 and PROMIS GH, demonstrating a negative impact of CDI on QoL in multiple health domains. The Cdiff32 questionnaire is particularly sensitive to QoL changes in patients with recurrent or severe disease.
Ostracoda from the Santonian–Campanian (Upper Cretaceous) Nenjiang and Sifangtai formations, Songliao Basin, northeastern China
Authors: Ye Yunqi , Xi Dangpeng , Sun Lixin , Do Carmo Dermeval Aparecido , Antonietto Lucas Silveira , Leite Amanda Moreira , Qin Zuohuan , Wan Xiaoqiao
Published: October 2021

Despite the abundant literature on limnic Cretaceous ostracode faunas, the database on mid-Late Cretaceous taxa is still scarce. The Songliao Basin in northeastern China preserves a diverse assemblage of ostracode fossils from the Santonian–Campanian Nenjiang and Sifangtai formations. This rather unique material is of major importance to comprehend Early to mid-Late Cretaceous (Cenomanian–Campanian) limnic ostracode faunas and therefore the evolution of Late Cretaceous basins in China. A study of this fauna was conducted to detail the taxonomy of ostracode species from members 1 and 2 of the Nenjiang and Sifangtai formations in the Songliao Basin. Well-preserved specimens of 14 ostracode species were recovered from samples of the ZKY2-1 well in southwestern Songliao Basin:Scabriculocypris liaukhenensisLiu in Netchaeva et al., 1959,Ilyocyprimorpha netchaevaeSu in Netchaeva et al., 1959,Cypridea accliniaNetchaeva in Netchaeva et al., 1959,Cypridea cavernosaGaleeva, 1955,Cypridea gracileNetchaeva in Netchaeva et al., 1959,Cypridea lepidaYe in DOFEAD, 1976,Cypridea squalidaSou in Netchaeva et al., 1959,Fabaeformiscandona?Disjuncta(Hao in Hao et al., 1974),Lycopterocypris profundaLübimova, 1956,Mongolocypris magna(Hou, 1958),Mongolocypris tera(Su in Netchaeva et al., 1959),Talicypridea obliquecostae(Szczechura and Błaszyk, 1970),Talicypridea reticulata(Szczechura, 1978) andRenicypris renalata(Su in Hao et al., 1974). Four of the species identified received emended descriptions and diagnoses. Other important results include the first discussion on sexual dimorphism inCypridea accliniaandFabaeformiscandona?disjuncta, the first study on the ontogeny ofIlyocyprimorpha netchaevae, and the reassignment ofCypridea liaukhenensisto the genusScabriculocypris. Several species recorded herein are also found in other continental far-eastern Asian basins, while genera range from worldwide to far-eastern Asian distribution; these results support strong affinities among faunas of Mongolia, China, and Japan.
The New York Daily News and the History of Conservative Media
Authors: Pressman Matthew
Published: October 2021

The media outlets usually identified as building blocks of New Right are niche ideological journals (such as National Review) and radio broadcasts. As crucial as these outlets were, other mainstream publications propagating similar ideas had a far greater reach—foremost among them the New York Daily News, the highest-circulation newspaper in the country. From the 1940s through the 1960s, the Daily News espoused a conservative populism further right than National Review, binding its readers into a community based on anti-elitism and white working-class identity.
‘Highly Civilized, yet Very Simple’: Images of the Czechoslovak State and Nation at Interwar World’s Fairs
Authors: Filipová Marta
Published: October 2021

How does a newly formed state and its newly created nation present itself at world’s fairs? This article focuses on the interwar period and the impact of the political restructuring of Central Europe in order to examine the strategies and motivations of Czechoslovakia for participation in exhibitions around the globe. It takes Czechoslovakia as an example of a country, created in 1918, that constructed and displayed its image in a comprehensible and uncomplicated way to international audiences. World’s fairs that were primarily organized to promote trade relationships thus gave the opportunity to countries like Czechoslovakia to validate its existence, internal composition, and domestic politics through carefully crafted narratives that were showcased. The article primarily addresses the question of who creates these narratives and why, while scrutinizing the transfer of domestic politics into international displays.
“Poles of the World Unite”: The Transnational History of the 1929 World Congress of Poles Abroad in the Context of Interwar Soviet–Polish Rivalries
Authors: Palko Olena
Published: October 2021

By investigating the information and propaganda campaign surrounding the election of delegates to the 1929 World Congress of Poles Abroad, this article seeks to elucidate a complex interplay between foreign policy considerations, security concerns, and nationality policies of the Polish and Soviet governments. It examines the role of national minorities in the Soviet modernization effort and the ongoing Polish-Soviet rivalry of the interwar period. The focused study of the information campaign, and the public discussion surrounding the election process to the congress, contributes also to the debates on mass political culture in the interwar Soviet Union. Party communication, intelligence, and secret reports compiled during the local elections and conferences provide a unique source for sampling public opinion of the Polish population regarding the Soviet regime in the early years of Stalin’s First Five-Year plan. The article argues that despite the considerable efforts of the party to define and promote Polish identity, and thus shift their loyalties closer to the Soviet state, the Polish population in Soviet Ukraine, even at the end of the 1920s, continued to express persistent nonconformity and a lack of faith in the Soviet government.
Diffusion profile embedding as a basis for graph vertex similarity
Authors: Payne Scott , Fuller Edgar , Spirou George , Zhang Cun-Quan
Published: October 2021

We describe here a notion ofdiffusion similarity, a method for defining similarity between vertices in a given graph using the properties of random walks on the graph to model the relationships between vertices. Using the approach of graph vertex embedding, we characterize a vertexviby considering two types of diffusion patterns: the ways in which random walks emanate from the vertexvito the remaining graph and how they converge to the vertexvifrom the graph. We define the similarity of two verticesviandvjas the average of the cosine similarity of the vectors characterizingviandvj. We obtain these vectors by modifying the solution to a differential equation describing a type of continuous time random walk.

This method can be applied to any dataset that can be assigned a graph structure that is weighted or unweighted, directed or undirected. It can be used to represent similarity of vertices within community structures of a network while at the same time representing similarity of vertices within layered substructures (e.g., bipartite subgraphs) of the network. To validate the performance of our method, we apply it to synthetic data as well as the neural connectome of theC. elegansworm and a connectome of neurons in the mouse retina. A tool developed to characterize the accuracy of the similarity values in detecting community structures,the uncertainty index, is introduced in this paper as a measure of the quality of similarity methods.
The psychophysiological correlates of cognitive dissonance
Authors: Ploger Gavin W. , Dunaway Johnanna , Fournier Patrick , Soroka Stuart
Published: October 2021

Abstract

This preregistered study uses a combination of physiological measures to explore both the activation and reduction components of cognitive dissonance theory. More precisely, we use skin conductance to identify dissonance arousal, a short-term affective response to counter-attitudinal stimuli, and then use heart rate variability to measure dissonance reduction, which reflects longer-term patterns of emotional regulation and information processing. Our preliminary tests find weak evidence of dissonance arousal and no evidence of dissonance reduction using this physiological approach. We consequently reconsider (albeit optimistically) the use of physiology in future work on cognitive dissonance. We also discuss the implications of our findings for selective exposure and motivated reasoning.
Evaluation of co-cultured spermatogonial stem cells encapsulated in alginate hydrogel with Sertoli cells and their transplantation into azoospermic mice
Authors: Veisi Mohammad , Mansouri Kamran , Assadollahi Vahideh , Jalili Cyrus , Pirnia Afshin , Salahshoor Mohammad Reza , Hoseinkhani Zohreh , Gholami Mohammad Reza
Published: October 2021

Anin vitrospermatogonial stem cell (SSC) culture can serve as an effective technique to study spermatogenesis and treatment for male infertility. In this research, we compared the effect of a three-dimensional alginate hydrogel with Sertoli cells in a 3D culture and co-cultured Sertoli cells. After harvest of SSCs from neonatal mice testes, the SSCs were divided into two groups: SSCs on a 3D alginate hydrogel with Sertoli cells and a co-culture of SSCs with Sertoli cells for 1 month. The samples were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays and bromodeoxyuridine (BrdU) tracing, haematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining after transplantation into an azoospermic testis mouse. The 3D group showed rapid cell proliferation and numerous colonies compared with the co-culture group. Molecular assessment showed significantly increasedintegrin alpha-6,integrin beta-1,Nanog,Plzf,Thy-1,Oct4andBcl2expression levels in the 3D group and decreased expression levels ofP53,Fas, andBax. BrdU tracing, and H&E and PAS staining results indicated that the hydrogel alginate improved spermatogenesis after transplantationin vivo. This finding suggested that cultivation of SSCs on alginate hydrogel with Sertoli cells in a 3D culture can lead to efficient proliferation and maintenance of SSC stemness and enhance the efficiency of SSC transplantation.
A Scoping Review on Category A Agents as Bioweapons
Authors: Beale Sarah L. , Zolnikov Tara Rava , Firebaugh Casey Mace
Published: October 2021

Category A agents are biological pathogens that could pose a threat to health and human safety if used as bioweapons. The exploration and possibility of these threats must be comprehensively reviewed to create a preparedness plan to recognize outbreaks, to educate the public, and to offer vaccinations and/or treatment options, if available. A scoping review using PRISMA guidelines was performed to categorize current information on Category A biological agents as well as understand their potential for future threats. The results used 34 articles and found that while botulin neurotoxins were the most lethal, anthrax posed the most likely threat for use as a bioweapon. Most research was conducted on plague, though it is not the most likely threat. Smallpox is the most likely agent to vaccinate against as there is already a working vaccine that has proven effective and the issue at hand is the need for a larger stockpile. Ultimately, preparedness efforts should include vaccinations and continued research and development of them. Category A agents are a serious public health concern; updated and reformed bioterrorism preparedness plans could greatly minimize panic and mortality.
Gut leben zuhause mit Multimorbidität
Authors: Jenkins Rachel , Jähnke Anke , Bischofberger Iren
Published: October 2021

Zusammenfassung. Hintergrund: Immer mehr ältere Menschen leben mit Multimorbidität, reduzierter Autonomie und Lebensqualität, komplexen Therapieregimes und erhöhten Komplikations- und Hospitalisationsraten. Bei funktionalen Einschränkungen oder zur Unterstützung des Therapiemanagements ist die professionelle häusliche Pflege unerlässlich. In der stationären Versorgung verbessern Advanced Practice Nurses (APN) aufgrund ihrer erweiterten Kompetenzen die Versorgungsqualität. Für mehrfach erkrankte Klient_innen zuhause ist die Rolle der APN hingegen neu. Ziel: Ausgehend von international etablierten APN-Kernkompetenzen sollte die APN-Rolle in einem häuslichen Pflegedienst für Menschen mit Multimorbidität entwickelt werden. Methoden: Das Praxisprojekt orientierte sich am PDCA-Zyklus. Merkmale von zugewiesenen Klient_innen sowie Fallsituationen wurden analysiert und so der Mehrwert der APN für die Klient_innen, deren Angehörige, die Pflegeteams und die interprofessionelle Zusammenarbeit herausgearbeitet. Ergebnisse: Im Projektzeitraum wurden 40 Klient_innen durch die APN begleitet. Durch ihre Interventionen stabilisierten sich vielschichtige Lebens- und Krankheitssituationen, und sie vermittelten den Beteiligten Sicherheit im Gesundheitsmanagement. Diskussion: Leadership in der Praxisentwicklung und interprofessionelle Zusammenarbeit waren zentrale Erfolgsfaktoren. Die APN nahm eine wichtige Koordinationsrolle innerhalb der zahlreichen Akteure wahr. Grenzen und Transfer: Diese Rolle muss für die häusliche Pflege konsolidiert und ihre Wirksamkeit auf die Versorgungsqualität empirisch erforscht werden.
circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3
Authors: Huang Yizhen , Zhang Zhenlei , Wang Jianle , Shen Shuying , Yao Teng , Xu Yining , Chen Zizheng , Fang Bin , Ma Jianjun
Published: October 2021

The abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene (ATP1B3) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3. The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.
An adaptive microscope for the imaging of biological surfaces
Authors: Abouakil Faris , Meng Huicheng , Burcklen Marie-Anne , Rigneault Hervé , Galland Frédéric , LeGoff Loïc
Published: October 2021

Scanning fluorescence microscopes are now able to image large biological samples at high spatial and temporal resolution. This comes at the expense of an increased light dose which is detrimental to fluorophore stability and cell physiology. To highly reduce the light dose, we designed an adaptive scanning fluorescence microscope with a scanning scheme optimized for the unsupervised imaging of cell sheets, which underly the shape of many embryos and organs. The surface of the tissue is first delineated from the acquisition of a very small subset (~0.1%) of sample space, using a robust estimation strategy. Two alternative scanning strategies are then proposed to image the tissue with an improved photon budget, without loss in resolution. The first strategy consists in scanning only a thin shell around the estimated surface of interest, allowing high reduction of light dose when the tissue is curved. The second strategy applies when structures of interest lie at the cell periphery (e.g. adherens junctions). An iterative approach is then used to propagate scanning along cell contours. We demonstrate the benefit of our approach imaging live epithelia from Drosophila melanogaster. On the examples shown, both approaches yield more than a 20-fold reduction in light dose -and up to more than 80-fold- compared to a full scan of the volume. These smart-scanning strategies can be easily implemented on most scanning fluorescent imaging modality. The dramatic reduction in light exposure of the sample should allow prolonged imaging of the live processes under investigation.
Light People: Professor John Dudley spoke about supercontinuum generation and International Day of Light
Authors: Guo Chenzi
Published: October 2021

Editorial

The extreme spectral broadening of light in supercontinuum generation (SCG) is considered by many as the ultimate legacy of nonlinear optics. In this interview, Light: Science & Applications invited John Dudley [see the “Short Bio” section]—pioneer of supercontinuum generation, rogue waves, and ultrafast lasers—to share insight on how supercontinuum generation have evolved over the past decades and where it is heading. Also as the Steering Chair of UNESCO’s International Day of Light & International Year of Light (IDL & IYL), John is asked to share his comments on how light may influence post-pandemic World.
Quantifying ERK activity in response to inhibition of the BRAFV600E-MEK-ERK cascade using mathematical modelling
Authors: Hamis Sara J. , Kapelyukh Yury , McLaren Aileen , Henderson Colin J. , Roland Wolf C. , Chaplain Mark A. J.
Published: October 2021

Background

Simultaneous inhibition of multiple components of the BRAF-MEK-ERK cascade (vertical inhibition) has become a standard of care for treating BRAF-mutant melanoma. However, the molecular mechanism of how vertical inhibition synergistically suppresses intracellular ERK activity, and consequently cell proliferation, are yet to be fully elucidated.

Methods

We develop a mechanistic mathematical model that describes how the mutant BRAF inhibitor, dabrafenib, and the MEK inhibitor, trametinib, affect BRAFV600E-MEK-ERK signalling. The model is based on a system of chemical reactions that describes cascade signalling dynamics. Using mass action kinetics, the chemical reactions are re-expressed as ordinary differential equations that are parameterised by in vitro data and solved numerically to obtain the temporal evolution of cascade component concentrations.

Results

The model provides a quantitative method to compute how dabrafenib and trametinib can be used in combination to synergistically inhibit ERK activity in BRAFV600E-mutant melanoma cells. The model elucidates molecular mechanisms of vertical inhibition of the BRAFV600E-MEK-ERK cascade and delineates how elevated BRAF concentrations generate drug resistance to dabrafenib and trametinib. The computational simulations further suggest that elevated ATP levels could be a factor in drug resistance to dabrafenib.

Conclusions

The model can be used to systematically motivate which dabrafenib–trametinib dose combinations, for treating BRAFV600E-mutated melanoma, warrant experimental investigation.
Sulforaphane downregulated fatty acid synthase and inhibited microtubule-mediated mitophagy leading to apoptosis
Authors: Yan Yuting , Zhou Yan , Li Juntao , Zheng Zhongnan , Hu Yabin , Li Lei , Wu Wei
Published: October 2021

We previously demonstrated that sulforaphane (SFN) inhibited autophagy leading to apoptosis in human non-small cell lung cancer (NSCLC) cells, but the underlying subcellular mechanisms were unknown. Hereby, high-performance liquid chromatography-tandem mass spectrometry uncovered that SFN regulated the production of lipoproteins, and microtubule- and autophagy-associated proteins. Further, highly expressed fatty acid synthase (FASN) contributed to cancer malignancy and poor prognosis. Results showed that SFN depolymerized microtubules, downregulated FASN, and decreased its binding to α-tubulin; SFN downregulated FASN, acetyl CoA carboxylase (ACACA), and ATP citrate lyase (ACLY) via activating proteasomes and downregulating transcriptional factor SREBP1; SFN inhibited the interactions among α-tubulin and FASN, ACACA, and ACLY; SFN decreased the amount of intracellular fatty acid (FA) and mitochondrial phospholipids; and knockdown of FASN decreased mitochondrial membrane potential (ΔΨm) and increased reactive oxygen species, mitochondrial abnormality, and apoptosis. Further, SFN downregulated mitophagy-associated proteins Bnip3 and NIX, and upregulated mitochondrial LC3 II/I. Transmission electron microscopy showed mitochondrial abnormality and accumulation of mitophagosomes in response to SFN. Combined with mitophagy inducer CCCP or autophagosome–lysosome fusion inhibitor Bafilomycin A1, we found that SFN inhibited mitophagosome–lysosome fusion leading to mitophagosome accumulation. SFN reduced the interaction between NIX and LC3 II/I, and reversed CCCP-caused FA increase. Furthermore, knockdown of α-tubulin downregulated NIX and BNIP3 production, and upregulated LC3 II/I. Besides, SFN reduced the interaction and colocalization between α-tubulin and NIX. Thus, SFN might cause apoptosis via inhibiting microtubule-mediated mitophagy. These results might give us a new insight into the mechanisms of SFN-caused apoptosis in the subcellular level.
SOD1 D91A variant in the southernmost tip of Europe: a heterozygous ALS patient resident on the island of Gozo
Authors: Farrugia Wismayer Maia , Farrugia Wismayer Andrew , Pace Adrian , Vassallo Neville , Cauchi Ruben J.
Published: October 2021

Amyotrophic lateral sclerosis (ALS) is frequently caused by mutations in the SOD1 gene. Here, we report the first SOD1 variant in Malta, an archipelago of three inhabited islands in southern Europe. We describe a patient with a sporadic form of ALS living on the island of Gozo in which the heterozygous SOD1 c.272A>C; p.(Asp91Ala) variant was detected. The patient had a late onset (79 years), sensory impairments and rapid disease progression culminating in respiratory failure. ALS has not yet developed in any of the three additional family members in which the D91A variant was identified. None of the healthy controls from the Maltese population were found to carry this variant. This report underscores the high prevalence of the D91A variant in Europe, despite the presence of a North-South gradient in its frequency, and confirms that this variant can be associated with dominant cases in Mediterranean countries.
Robust charge-density wave strengthened by electron correlations in monolayer 1T-TaSe2 and 1T-NbSe2
Authors: Nakata Yuki , Sugawara Katsuaki , Chainani Ashish , Oka Hirofumi , Bao Changhua , Zhou Shaohua , Chuang Pei-Yu , Cheng Cheng-Maw , Kawakami Tappei , Saruta Yasuaki , Fukumura Tomoteru , Zhou Shuyun , Takahashi Takashi , Sato Takafumi
Published: October 2021

Combination of low-dimensionality and electron correlation is vital for exotic quantum phenomena such as the Mott-insulating phase and high-temperature superconductivity. Transition-metal dichalcogenide (TMD) 1T-TaS2 has evoked great interest owing to its unique nonmagnetic Mott-insulator nature coupled with a charge-density-wave (CDW). To functionalize such a complex phase, it is essential to enhance the CDW-Mott transition temperature TCDW-Mott, whereas this was difficult for bulk TMDs with TCDW-Mott < 200 K. Here we report a strong-coupling 2D CDW-Mott phase with a transition temperature onset of ~530 K in monolayer 1T-TaSe2. Furthermore, the electron correlation derived lower Hubbard band survives under external perturbations such as carrier doping and photoexcitation, in contrast to the bulk counterpart. The enhanced Mott-Hubbard and CDW gaps for monolayer TaSe2 compared to NbSe2, originating in the lattice distortion assisted by strengthened correlations and disappearance of interlayer hopping, suggest stabilization of a likely nonmagnetic CDW-Mott insulator phase well above the room temperature. The present result lays the foundation for realizing monolayer CDW-Mott insulator based devices operating at room temperature.
Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction
Authors: Eeftens Jorine M. , Kapoor Manya , Michieletto Davide , Brangwynne Clifford P.
Published: October 2021

Organization of the genome into transcriptionally active euchromatin and silenced heterochromatin is essential for eukaryotic cell function. Phase-separation has been implicated in heterochromatin formation, but it is unclear how phase-separated condensates can contribute to stable repression, particularly for heritable epigenetic changes. Polycomb complex PRC1 is key for heterochromatin formation, but the multitude of Polycomb proteins has hindered our understanding of their collective contribution to chromatin repression. Here, we show that PRC1 forms multicomponent condensates through hetero-oligomerization. They preferentially seed at H3K27me3 marks, and subsequently write H2AK119Ub marks. We show that inducing Polycomb phase-separation can cause chromatin compaction, but polycomb condensates are dispensable for maintenance of the compacted state. Our data and simulations are consistent with a model in which the time integral of Polycomb phase-separation is progressively recorded in repressive histone marks, which subsequently drive compaction. These findings link the equilibrium thermodynamics of phase-separation with the fundamentally non-equilibrium concept of epigenetic memory.
Evolution of the electronic structure in open-shell donor-acceptor organic semiconductors
Authors: Chen Zhongxin , Li Wenqiang , Sabuj Md Abdus , Li Yuan , Zhu Weiya , Zeng Miao , Sarap Chandra S. , Huda Md Masrul , Qiao Xianfeng , Peng Xiaobin , Ma Dongge , Ma Yuguang , Rai Neeraj , Huang Fei
Published: October 2021

Most organic semiconductors have closed-shell electronic structures, however, studies have revealed open-shell character emanating from design paradigms such as narrowing the bandgap and controlling the quinoidal-aromatic resonance of the π-system. A fundamental challenge is understanding and identifying the molecular and electronic basis for the transition from a closed- to open-shell electronic structure and connecting the physicochemical properties with (opto)electronic functionality. Here, we report donor-acceptor organic semiconductors comprised of diketopyrrolopyrrole and naphthobisthiadiazole acceptors and various electron-rich donors commonly utilized in constructing high-performance organic semiconductors. Nuclear magnetic resonance, electron spin resonance, magnetic susceptibility measurements, single-crystal X-ray studies, and computational investigations connect the bandgap, π-extension, structural, and electronic features with the emergence of various degrees of diradical character. This work systematically demonstrates the widespread diradical character in the classical donor-acceptor organic semiconductors and provides distinctive insights into their ground state structure-property relationship.
ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7
Authors: Fischer Robert J. , van Doremalen Neeltje , Adney Danielle R. , Yinda Claude Kwe , Port Julia R. , Holbrook Myndi G. , Schulz Jonathan E. , Williamson Brandi N. , Thomas Tina , Barbian Kent , Anzick Sarah L. , Ricklefs Stacy , Smith Brian J. , Long Dan , Martens Craig , Saturday Greg , de Wit Emmie , Gilbert Sarah C. , Lambe Teresa , Munster Vincent J.
Published: October 2021

We investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observe a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 do not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals do not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus can be detected in lungs of vaccinated animals. Histopathological evaluation shows extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.
GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
Authors: Li Xiaolin , Liu Sixuan , Chen Xuan , Huang Run , Ma Lisi , Weng Huaiyu , Yu Yang , Zong Xiangyun
Published: October 2021

Chemotherapy-induced ovarian dysfunction is a serious adverse effect in premenopausal patients with cancer. Gonadotrophin-releasing hormone analogs (GnRHa) protect ovarian function, but its molecular mechanisms have not yet been determined. In this study, we attempted to determine the previously unknown molecular mechanism by which such protection occurs. Serum anti-Müllerian hormone (AMH) levels were tested in tumor-bearing nude mice, a series of exploratory experiments were conducted. We discovered that GnRHa protects granulosa cells from chemotherapeutic toxicity in vivo and in vitro. We also showed that CTX-induced endoplasmic reticulum stress inhibits the secretion of AMH, and treatment with GnRHa relieves ER stress and the subsequent unfolded-protein response by modulating mTOR signaling to induce autophagy. The results of mechanistic studies indicated that GnRHa-modulated mTOR signaling to induce autophagy, which alleviated CTX-induced ER stress and promoted the secretion of AMH.
Haplotyping-based preimplantation genetic testing reveals parent-of-origin specific mechanisms of aneuploidy formation
Authors: Tšuiko Olga , Vanneste Michiel , Melotte Cindy , Ding Jia , Debrock Sophie , Masset Heleen , Peters Maire , Salumets Andres , De Leener Anne , Pirard Céline , Kluyskens Candice , Hostens Katleen , van de Vijver Arne , Peeraer Karen , Denayer Ellen , Vermeesch Joris Robert , Dimitriadou Eftychia
Published: October 2021

Chromosome instability is inherent to human IVF embryos, but the full spectrum and developmental fate of chromosome anomalies remain uncharacterized. Using haplotyping-based preimplantation genetic testing for monogenic diseases (PGT-M), we mapped the parental and mechanistic origin of common and rare genomic abnormalities in 2300 cleavage stage and 361 trophectoderm biopsies. We show that while single whole chromosome aneuploidy arises due to chromosome-specific meiotic errors in the oocyte, segmental imbalances predominantly affect paternal chromosomes, implicating sperm DNA damage in segmental aneuploidy formation. We also show that postzygotic aneuploidy affects multiple chromosomes across the genome and does not discriminate between parental homologs. In addition, 6% of cleavage stage embryos demonstrated signatures of tripolar cell division with excessive chromosome loss, however hypodiploid blastomeres can be excluded from further embryo development. This observation supports the selective-pressure hypothesis in embryos. Finally, considering that ploidy violations may constitute a significant proportion of non-viable embryos, using haplotyping-based approach to map these events might further improve IVF success rate.
Single-cell epigenomics reveals mechanisms of human cortical development
Authors: Ziffra Ryan S. , Kim Chang N. , Ross Jayden M. , Wilfert Amy , Turner Tychele N. , Haeussler Maximilian , Casella Alex M. , Przytycki Pawel F. , Keough Kathleen C. , Shin David , Bogdanoff Derek , Kreimer Anat , Pollard Katherine S. , Ament Seth A. , Eichler Evan E. , Ahituv Nadav , Nowakowski Tomasz J.
Published: October 2021

During mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes in the gene regulatory landscape1. In the developing brain, cell fate specification and topographic identity are important for defining cell identity2 and confer selective vulnerabilities to neurodevelopmental disorders3. Here, to identify cell-type-specific chromatin accessibility patterns in the developing human brain, we used a single-cell assay for transposase accessibility by sequencing (scATAC-seq) in primary tissue samples from the human forebrain. We applied unbiased analyses to identify genomic loci that undergo extensive cell-type- and brain-region-specific changes in accessibility during neurogenesis, and an integrative analysis to predict cell-type-specific candidate regulatory elements. We found that cerebral organoids recapitulate most putative cell-type-specific enhancer accessibility patterns but lack many cell-type-specific open chromatin regions that are found in vivo. Systematic comparison of chromatin accessibility across brain regions revealed unexpected diversity among neural progenitor cells in the cerebral cortex and implicated retinoic acid signalling in the specification of neuronal lineage identity in the prefrontal cortex. Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development.
Epigenomic diversity of cortical projection neurons in the mouse brain
Authors: Zhang Zhuzhu , Zhou Jingtian , Tan Pengcheng , Pang Yan , Rivkin Angeline C. , Kirchgessner Megan A. , Williams Elora , Lee Cheng-Ta , Liu Hanqing , Franklin Alexis D. , Miyazaki Paula Assakura , Bartlett Anna , Aldridge Andrew I. , Vu Minh , Boggeman Lara , Fitzpatrick Conor , Nery Joseph R. , Castanon Rosa G. , Rashid Mohammad , Jacobs Matthew W. , Ito-Cole Tony , O’Connor Carolyn , Pinto-Duartec António , Dominguez Bertha , Smith Jared B. , Niu Sheng-Yong , Lee Kuo-Fen , Jin Xin , Mukamel Eran A. , Behrens M. Margarita , Ecker Joseph R. , Callaway Edward M.
Published: October 2021

Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the thalamus, superior colliculus and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.
Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination
Authors: Cho Alice , Muecksch Frauke , Schaefer-Babajew Dennis , Wang Zijun , Finkin Shlomo , Gaebler Christian , Ramos Victor , Cipolla Melissa , Mendoza Pilar , Agudelo Marianna , Bednarski Eva , DaSilva Justin , Shimeliovich Irina , Dizon Juan , Daga Mridushi , Millard Katrina G. , Turroja Martina , Schmidt Fabian , Zhang Fengwen , Tanfous Tarek Ben , Jankovic Mila , Oliveria Thiago Y. , Gazumyan Anna , Caskey Marina , Bieniasz Paul D. , Hatziioannou Theodora , Nussenzweig Michel C.
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern1. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested1,2. Here we examine memory B cell evolution five months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccine in a cohort of SARS-CoV-2-naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge five months after vaccination of naive individuals express antibodies that are similar to those that dominate the initial response. While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with equivalent breadth to those obtained by vaccinating convalescent individuals.
An independently validated, portable algorithm for the rapid identification of COPD patients using electronic health records
Authors: Chu Su H. , Wan Emily S. , Cho Michael H. , Goryachev Sergey , Gainer Vivian , Linneman James , Scotty Erica J. , Hebbring Scott J. , Murphy Shawn , Lasky-Su Jessica , Weiss Scott T. , Smoller Jordan W. , Karlson Elizabeth
Published: October 2021

Electronic health records (EHR) provide an unprecedented opportunity to conduct large, cost-efficient, population-based studies. However, the studies of heterogeneous diseases, such as chronic obstructive pulmonary disease (COPD), often require labor-intensive clinical review and testing, limiting widespread use of these important resources. To develop a generalizable and efficient method for accurate identification of large COPD cohorts in EHRs, a COPD datamart was developed from 3420 participants meeting inclusion criteria in the Mass General Brigham Biobank. Training and test sets were selected and labeled with gold-standard COPD classifications obtained from chart review by pulmonologists. Multiple classes of algorithms were built utilizing both structured (e.g. ICD codes) and unstructured (e.g. medical notes) data via elastic net regression. Models explicitly including and excluding spirometry features were compared. External validation of the final algorithm was conducted in an independent biobank with a different EHR system. The final COPD classification model demonstrated excellent positive predictive value (PPV; 91.7%), sensitivity (71.7%), and specificity (94.4%). This algorithm performed well not only within the MGBB, but also demonstrated similar or improved classification performance in an independent biobank (PPV 93.5%, sensitivity 61.4%, specificity 90%). Ancillary comparisons showed that the classification model built including a binary feature for FEV1/FVC produced substantially higher sensitivity than those excluding. This study fills a gap in COPD research involving population-based EHRs, providing an important resource for the rapid, automated classification of COPD cases that is both cost-efficient and requires minimal information from unstructured medical records.
A proof of concept for machine learning-based virtual knapping using neural networks
Authors: Orellana Figueroa Jordy Didier , Reeves Jonathan Scott , McPherron Shannon P. , Tennie Claudio
Published: October 2021

Prehistoric stone tools are an important source of evidence for the study of human behavioural and cognitive evolution. Archaeologists use insights from the experimental replication of lithics to understand phenomena such as the behaviours and cognitive capacities required to manufacture them. However, such experiments can require large amounts of time and raw materials, and achieving sufficient control of key variables can be difficult. A computer program able to accurately simulate stone tool production would make lithic experimentation faster, more accessible, reproducible, less biased, and may lead to reliable insights into the factors that structure the archaeological record. We present here a proof of concept for a machine learning-based virtual knapping framework capable of quickly and accurately predicting flake removals from 3D cores using a conditional adversarial neural network (CGAN). We programmatically generated a testing dataset of standardised 3D cores with flakes knapped from them. After training, the CGAN accurately predicted the length, volume, width, and shape of these flake removals using the intact core surface information alone. This demonstrates the feasibility of machine learning for investigating lithic production virtually. With a larger training sample and validation against archaeological data, virtual knapping could enable fast, cheap, and highly-reproducible virtual lithic experimentation.
Avian influenza transmission risk along live poultry trading networks in Bangladesh
Authors: Moyen Natalie , Hoque Md. Ahasanul , Mahmud Rashed , Hasan Mahmudul , Sarkar Sudipta , Biswas Paritosh Kumar , Mehedi Hossain , Henning Joerg , Mangtani Punam , Flora Meerjady Sabrina , Rahman Mahmudur , Debnath Nitish C. , Giasuddin Mohammad , Barnett Tony , Pfeiffer Dirk U. , Fournié Guillaume
Published: October 2021

Live animal markets are known hotspots of zoonotic disease emergence. To mitigate those risks, we need to understand how networks shaped by trading practices influence disease spread. Yet, those practices are rarely recorded in high-risk settings. Through a large cross-sectional study, we assessed the potential impact of live poultry trading networks’ structures on avian influenza transmission dynamics in Bangladesh. Networks promoted mixing between chickens sourced from different farming systems and geographical locations, fostering co-circulation of viral strains of diverse origins in markets. Viral transmission models suggested that the observed rise in viral prevalence from farms to markets was unlikely explained by intra-market transmission alone, but substantially influenced by transmission occurring in upstream network nodes. Disease control interventions should therefore alter the entire network structures. However, as networks differed between chicken types and city supplied, standardised interventions are unlikely to be effective, and should be tailored to local structural characteristics.