bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of a Composite Aerogel of Reduced Graphene Oxide Supported by Two-Dimensional Montmorillonite Nanolayers for Methylene Blue Removal
Authors: Ma Qiulin , Wang Wei , Ge Wei , Xia Ling , Song Shaoxian
Published: November 2021

Two-dimensional montmorillonite nanolayers (2D Mnt) are excellent adsorbents for methylene blue due to the fully exposed active sites, but the separation of 2D Mnt from water is difficult. The objective of the present study was to assemble 2D Mnt and graphene oxide sheets into a three-dimensional aerogel (3D Mnt-rGO Gel) to achieve easy solid–liquid separation. Structural characterization demonstrated that the Mnt-rGO Gel has a porous 3D structure with Mnt nanolayers distributed uniformly within; the introduction of 2D Mnt could reduce significantly the degree of restacking of graphene sheets. Adsorption tests indicated that 2D Mnt enhances the methylene blue (MB) removal performance of Mnt-rGO Gel with a large adsorption capacity of 207 mg g–1, which may be attributed to the adsorption of MB onto 2D Mnt and the increased adsorption surface of rGO resulting from the reduced restacking of graphene sheets. The MB was removed completely by 300 mg L–1 of Mnt-rGO Gel-3 in 180 min. The adsorption process of MB onto Mnt-rGO Gel followed the pseudo-second order kinetic model and the Langmuir isotherm model. Mnt-rGO Gel also showed good reusability. Fourier-transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) results suggested that the adsorption of MB onto Mnt-rGO Gel may be attributed to the π–π interactions between aromatic rings of MB and graphene, hydrogen bonding, and the electrostatic interactions between the nitrogen groups on the MB and oxygen-containing groups on the Mnt-rGO Gel.
Negotiating South–South cooperation for mental health: the World Health Organization and the African Mental Health Action Group, 1970s–90s
Authors: Pringle Yolana
Published: November 2021

This article explores the African Mental Health Action Group (AMHAG), one of the earliest examples of the World Health Organization’s (WHO) attempts to promote ‘ownership’ over development through the South–South cooperation envisaged in Technical Cooperation in Developing Countries. Formed in 1978, the AMHAG was intended to guide national and regional policy on mental health, while also fostering national and collective self-reliance. For a short period, between the late 1970s and the early 1990s, it was central to the WHO’s strategy for promoting policies of mental health in primary healthcare in Africa. It was a largely ineffective tool, with national governments having different opinions on the value of mental health, and poor coordination between AMHAG countries. Approaching the AMHAG as a regional project and transnational network, however, the article provides explores the importance of regions and regionalism in international health cooperation, as well as the inequities of participation in health development. Drawing on WHO archival material spanning over twenty countries and two national liberation movements, it argues that participating countries were differently positioned not only to navigate relationships between countries, but also to contend with the shifting landscape of international assistance, as well as – for some – contexts of war, violence and political and economic instability. The article not only serves as a case study of power imbalances in a failed development initiative, but also sheds light on the WHO’s engagement with mental health during a period that historians of psychiatry in Africa have tended to overlook.
Anisotropic Gauss curvature flows and their associated Dual Orlicz-Minkowski problems
Authors: Chen Li , Tu Qiang , Wu Di , Xiang Ni
Published: November 2021

In this paper we study a normalized anisotropic Gauss curvature flow of strictly convex, closed hypersurfaces in the Euclidean space. We prove that the flow exists for all time and converges smoothly to the unique, strictly convex solution of a Monge-Ampère type equation and we obtain a new existence result of solutions to the Dual Orlicz-Minkowski problem for smooth measures, especially for even smooth measures.
THE SCOPE OF STATE SOVEREIGNTY UNDER ARTICLE 194(2) TFEU AND THE EVOLUTION OF EU COMPETENCES IN THE ENERGY SECTOR
Authors: Huhta Kaisa
Published: November 2021

This article analyses the European Union's competences in the energy sector. It focuses on Article 194(2) of the Treaty on the Functioning of the European Union, which affords EU Member States the right to determine the conditions for exploiting their energy resources, the choice between different energy sources and the general structure of their energy supply. This article traces the constitutional development of EU competences in the energy sector to demonstrate the relevance of Article 194(2) TFEU in the current constitutional, international and sector-specific contexts of EU energy law. It analyses the recent case law of the Court of Justice of the European Union, which shows that the scope of Article 194(2) TFEU is considerably narrower in practice than its wording implies. The article concludes by evaluating the implications of this narrow interpretation on the future development of EU energy law and, in a broader context, on the reach of EU energy and climate policy.
THE CJEU AS THE GATEKEEPER OF INTERNATIONAL LAW: THE CASES OF WTO LAW AND THE AARHUS CONVENTION
Authors: Hadjiyianni Ioanna
Published: November 2021

As the gatekeeper of international law, the CJEU determines the effects not only of international agreements but also decisions of compliance review bodies. This article analyses the Court's engagement with rulings of the WTO dispute settlement bodies (DSB) and findings of the Aarhus Convention Compliance Committee (ACCC). These case studies demonstrate the varied toolkit used by the CJEU to forge relationships with external regimes, while maintaining the EU's autonomy. The CJEU considers DSB reports and ACCC findings selectively and implicitly, demonstrating a qualified openness to international law and a reluctance to engage in a meaningful dialogue with international quasi-judicial bodies.
Validity of the DSM-5 craving criterion for alcohol, tobacco, cannabis, cocaine, heroin, and non-prescription use of prescription painkillers (opioids)
Authors: Shmulewitz D. , Stohl M. , Greenstein E. , Roncone S. , Walsh C. , Aharonovich E. , Wall M. M. , Hasin D. S.
Published: November 2021

Background

Although the DSM-5 was adopted in 2013, the validity of the new substance use disorder (SUD) diagnosis and craving criterion has not been investigated systematically across substances.

Methods

Adults (N= 588) who engaged in binge drinking or illicit drug use and endorsed at least one DSM-5 SUD criterion were included. DSM-5 SUD criteria were assessed for alcohol, tobacco, cannabis, cocaine, heroin, and opioids. Craving was considered positive if “wanted to use so badly that could not think of anything else” (severe craving) or “felt a very strong desire or urge to use” (moderate craving) was endorsed. Baseline information on substance-related variables and psychopathology was collected, and electronic daily assessment queried substance use for the following 90 days. For each substance, logistic regression estimated the association between craving and validators, i.e. variables expected to be related to craving/SUD, and whether association with the validators differed for DSM-5 SUD diagnosed with craving as a criterionv.without.

Results

Across substances, craving was associated with most baseline validators (pvalues<0.05); neither moderate nor severe craving consistently showed greater associations. Baseline craving predicted subsequent use [odds ratios (OR): 4.2 (alcohol) – 234.3 (heroin);p's ⩽ 0.0001], with stronger associations for moderate than severe craving (p's < 0.05). Baseline DSM-5 SUD showed stronger associations with subsequent use when diagnosed with craving than without (p's < 0.05).

Conclusion

The DSM-5 craving criterion as operationalized in this study is valid. Including craving improves the validity of DSM-5 SUD diagnoses, and clinical relevance, since craving may cause impaired control over use and development and maintenance of SUD.
The Caravana of Central American Mothers in Mexico: Performances of Devotional and Saintly Motherhood on a Transnational Stage-in-Motion
Authors: PUGA ANA ELENA
Published: November 2021

Like earlier mother activism in Latin America, the annual Caravana de Madres Centroamericanas (Caravan of Central American Mothers) through Mexico strategically activates the traditional archetype of mothers as passive, pious, suffering victims whose self-abnegation forces them, almost against their will, out of their supposedly natural domestic sphere. Three elements, however, distinguish the caravana from earlier protests staged by mothers. First, this protest crosses national borders, functioning as a transnational pilgrimage to the memory of the disappeared relative. This stage-in-motion temporarily spotlights and claims the spaces traversed by undocumented Central American migrants in Mexico, attempting to recast those migrants as victims of violence rather than as criminals. Second, through performances of both devotional motherhood and saintly motherhood, the caravana's mother-based activism de-normalizes violence related to drugs and migration. Third, performances of family reunification staged by the caravana organizers take place in the few cases in which they manage to locate family members who have not fallen prey to violence but have simply resettled in Mexico and abandoned or lost touch with families left behind in Central America. These performances of family reunification serve important functions: they shift the performance of motherhood from devotion to saintly tolerance, patience and forgiveness – even toward prodigal offspring who were ‘lost’ for years; they provide a chance for other mothers to vicariously feel joy and hope that their children are still alive; they exemplify world citizens challenging incompetent or indifferent nation state authorities; and they enact a symbolic unification of Central America and Mexico in defiance of contemporary nation state borders.
Kinderschutz und Schutzkonzepte im klinischen und ambulanten Bereich
Authors: Fegert Jörg M. , Hoffmann Ulrike
Published: November 2021

Zusammenfassung. Die Auseinandersetzung mit Fällen von (sexualisierter) Gewalt gegen Kinder und Jugendliche sowie die Entwicklung von Schutzkonzepten war in den Institutionen des medizinisch-therapeutischen Bereiches über lange Zeit ein eher marginalisiertes Thema. Mit der Verankerung der Verpflichtung zur Erstellung von Schutzkonzepten gegen (sexualisierte) Gewalt in der Qualitätsmanagement-Richtlinie des Gemeinsamen Bundesausschusses (G-BA) müssen sich jedoch nun alle Kliniken und Praxen dieser Thematik stellen. Der vorliegende Themenschwerpunkt gibt einen Überblick über Daten und Zahlen (sexueller) Übergriffe gegen Kinder und Jugendliche in medizinischen Institutionen und beschäftigt sich mit den Ursachen von Übergriffen durch Angehörige der Heilberufe sowie den daraus folgenden notwendigen Interventionen. Weiteres Thema ist die Entwicklung von Schutzkonzepten gegen (sexuelle) Gewalt. Es werden Hinweise zum Aufbau sowie zur praktischen Umsetzung im klinischen und ambulanten Bereich gegeben.
Häufigkeiten von Übergriffen auf Kinder und Jugendliche durch Angehörige der Heil- und Pflegeberufe
Authors: Rassenhofer Miriam , Korger Simone , Fegert Jörg M. , Hoffmann Ulrike
Published: November 2021

Zusammenfassung. Theoretischer Hintergrund: Kindesmisshandlung, -missbrauch und Vernachlässigung stellen ein gesamtgesellschaftliches Entwicklungsrisiko für Kinder in Deutschland dar. Zweithäufigster Kontext des Geschehens nach dem familiären Umfeld sind Institutionen. Fragestellung: Der vorliegende Artikel gibt eine Übersicht zu Häufigkeiten von Übergriffen durch Angehörige der Heil- und Pflegeberufe mit Schwerpunkt auf dem kinder- und jugendpsychiatrischen/-psychotherapeutischen Bereich. Methode: Mittels Literaturrecherche wird der Forschungsstand zum Thema dargestellt. Ergebnisse: Neben Auswertungen zu Zwangsmaßnahmen, welche von Betroffenen häufig als viktimisierend erlebt werden, existieren für Deutschland zwei repräsentative retrospektive Befragungen zum medizinischen Bereich. Hier ergaben sich Prävalenzen zwischen einem Fünftel und einem Drittel der Befragten, die mindestens eine Form von Gewalt oder Vernachlässigung bejahten. Diskussion und Schlussfolgerung: Neben alarmierenden Zahlen zeigt sich der große Bedarf an weiterer Forschung zum Thema.
Schulbasiertes Training für Jugendliche zur Emotionsregulation
Authors: Merkle Nadja , Ullrich Janice , Gfrörer Thomas , Brown Rebecca C.
Published: November 2021

Zusammenfassung. Theoretischer Hintergrund: Trainingsprogramme zur Emotionsregulation für Jugendliche sind notwendig, da eine Dysregulation der Emotionen die Entwicklung von psychischen Störungen begünstigen kann. Fragestellung: Ziel dieser systematischen Literaturübersicht ist es, einen Überblick über aktuelle Publikationen zu Trainingsprogrammen von 2015 – 2020 zu geben. Methode: Im Rahmen der Literaturrecherche konnten sechs Publikationen eingeschlossen werden. Ergebnisse: Es zeigten sich positive Effekte bei der Programmdurchführung durch externe Personen, vor allem durch Fachpersonen und keine bis negative Effekte bei der Durchführung durch das Schulpersonal. Ein positiver Einfluss durch die Einbeziehung der Eltern konnte in einem Trainingsprogramm vermutet werden, wobei die Ergebnisse statistisch nicht signifikant waren. Schlussfolgerung: Es zeigt sich die Notwendigkeit weiterer Evaluation von Trainingsprogrammen, welche sich vor allem auch mit dem Einbezug der Bezugspersonen beschäftigen und untersuchen, inwiefern Trainer_inneneffekte auch bei Studien mit einer besseren Vergleichbarkeit vorliegen.
Effect of Topographic Degradation on Small Lunar Craters: Implications for Regolith Thickness Estimation
Authors: Yang Xi , Fa Wenzhe , Du Jun , Xie Minggang , Liu Tiantian
Published: November 2021

Small crater morphology method has been used extensively in lunar regolith thickness estimation. However, topographic degradation can change crater morphology and thus bias regolith thickness estimation. In this study, we first developed a shape model for small fresh craters with normal, central mound, flat‐bottomed, and concentric geometry. We then simulated their degradation processes by using a topographic diffusion model. Simulation results show that as a small crater degrades, its morphology changes from concentric/central mound to flat‐bottomed, from flat‐bottomed to normal, and from normal to invisible, depending on its initial morphology. Upon the time a crater becomes invisible, its diameter can be enlarged by a factor of ∼70%. We proposed a revised small crater morphology method and applied it to the Apollo 11 and 14 landing sites. Our revised method permits a more accurate estimate of regolith thickness, and our results are helpful in understanding the evolution of the Moon's surface.
Machine‐Learning Characterization of Tectonic, Hydrological and Anthropogenic Sources of Active Ground Deformation in California
Authors: Hu Xie , Bürgmann Roland , Xu Xiaohua , Fielding Eric , Liu Zhen
Published: November 2021

Tectonic, hydrological and industrial processes coexist in the dynamic natural environments. However, our knowledge of ground deformation associated with tectonic, hydrological and anthropogenic processes and their interactions remains limited. California represents a natural laboratory that hosts the San Andreas fault system, Central Valley and other aquifer systems, and extensive human extraction of natural resources. The attendant multi‐scale ground deformation that has been mapped using Copernicus Sentinel‐1 Synthetic Aperture Radar (SAR)‐satellite constellation from four ascending and five descending tracks during 2015–2019. We consider the secular horizontal surface velocities and strain rates, constrained from GNSS measurements and tectonic models, as proxies for tectonic processes, and seasonal displacement amplitudes from interferometric SAR (InSAR) time series as proxies for hydrological processes. We synergize 23 types of multidisciplinary datasets, including ground deformation, sedimentary basins, precipitation, soil moisture, topography, and hydrocarbon production fields, using a machine learning algorithm–random forest, and we succeed in predicting 86%–95% of the representative data sets. High strain rates along the SAF system mainly occur in areas with a low‐to‐moderate vegetation fraction (∼0.3), suggesting a correlation of rough/high‐relief coastal range morphology and topography with the active faulting, seasonal and orographic rainfall, and vegetation growth. Linear discontinuities in the long‐term, seasonal amplitude and phase of the surface displacement fields coincide with some fault strands, the boundary zone between the sediment‐fill Central Valley and bedrock‐dominated Sierra Nevada, and the margins of the inelastically deforming aquifer in the San Joaquin Valley, suggesting groundwater flow interruptions, contrasting elastic properties, and heterogeneous hydrological units.
Energy Partitioning, Dynamic Fragmentation, and Off‐Fault Damage in the Earthquake Source Volume
Authors: Johnson Scott E. , Song Won Joon , Vel Senthil S. , Song Bo Ra , Gerbi Christopher C.
Published: November 2021

Seismological fracture or breakdown energy represents energy expended in a volume surrounding the advancing rupture front and the slipping fault surface. Estimates are commonly obtained by inverting ground motions and using the results to model slip on the fault surface. However, this practice cannot identify contributions from different energy‐consumption processes, so our understanding of the importance of these processes comes largely from field‐ and laboratory‐based studies. Here, we use garnet fragment size data to estimate surface‐area energy density with distance from the fault core in the damage zone of a deeply exhumed strike‐slip fault/shear zone. Estimated energy densities per fragmentation event range from 2.87 × 103 to 2.72 × 105 J/m3 in the outer and inner portions of the dynamic damage zone, respectively, with the dynamic zone being inferred from the fractal dimensions of fragment size distributions and other indicators. Integrating over the ∼105 m width of the dynamic damage zone gives fracture surface‐area energy per unit fault area ranging from a lower bound of 6.63 × 105 J/m2 to an upper bound of 1.63 × 107 J/m2 per event. This range overlaps with most geological, theoretical, and kinematic slip‐model estimates of energy expenditure in the source volume for earthquakes characterized by seismic moments >1017 N·m. We employ physics‐based fragmentation models to estimate equivalent tensile strain rates associated with garnet fragmentation, which range from 5.42 × 102 to 1.04 × 104 s−1 per earthquake in the outer and inner portions of the dynamic damage zone, respectively. Our results suggest that surface‐energy generation is a nonnegligible component of the earthquake energy budget.
Intraseasonal Variability of the North Equatorial Current Bifurcation Off the Philippines
Authors: Zhou Hui , Liu Xueqi , Li Ruixiang , Wang Yonggang , Yang Guang
Published: November 2021

Characteristics of the intraseasonal variability (ISV) of the North Equatorial Current bifurcation latitude (NBL) are analyzed by using both observations and reanalysis data. The maximum amplitude of the ISV of the NBL can reach about 6° of latitude, which almost triples its annual excursion. The NBL shows a broad spectral peak around 50–140 days with the highest peak occurring around 73 days. Both the Madden‐Julian oscillation and mesoscale eddies have a significant impact on its ISV. A case study for a cyclonic eddy indicates that it can transport about 1.5 Sv (1 Sv–106 m3 s−1) waters to the NBL, and the bifurcation shifts northward with an amplitude of about 8° of latitude in 1 month. Meanwhile, the influence of mesoscale eddies on the ISV of the NBL is highly modulated by the interannual variations of the eddy field. Active eddy activities associated with enhanced barotropic and baroclinic instabilities show a large influence on the NBL. The eddy kinetic energy level around the NBL showed a quite diverse character for the 1997–1998 and the 2015–2016 extreme El Niños, with the latter being double or triple that of the former due to the much stronger vertical and horizontal shears. Given the significant impact on the NBL by the individual eddies and the unevenly distributed cyclonic and anticyclonic eddies around the NBL, the effect of mesoscale eddies on the bifurcation latitude may not cancel each other on seasonal or interannual time scales.
Paradoxical implication of BAX/BAK in the persistence of tetraploid cells
Authors: Deng Jiayin , Gutiérrez Lucía G. , Stoll Gautier , Motiño Omar , Martins Isabelle , Núñez Lucía , Bravo-San Pedro José Manuel , Humeau Juliette , Bordenave Chloé , Pan Juncheng , Fohrer-Ting Hélène , Souquere Sylvie , Pierron Gerard , Hetz Claudio , Villalobos Carlos , Kroemer Guido , Senovilla Laura
Published: November 2021

Pro-apoptotic multi-domain proteins of the BCL2 family such as BAX and BAK are well known for their important role in the induction of mitochondrial outer membrane permeabilization (MOMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. Human or mouse cells lacking both BAX and BAK (due to a double knockout, DKO) are notoriously resistant to MOMP and cell death induction. Here we report the surprising finding that BAX/BAK DKO cells proliferate less than control cells expressing both BAX and BAK (or either BAX or BAK) when they are driven into tetraploidy by transient exposure to the microtubule inhibitor nocodazole. Mechanistically, in contrast to their BAX/BAK-sufficient controls, tetraploid DKO cells activate a senescent program, as indicated by the overexpression of several cyclin-dependent kinase inhibitors and the activation of β-galactosidase. Moreover, DKO cells manifest alterations in ionomycin-mobilizable endoplasmic reticulum (ER) Ca2+ stores and store-operated Ca2+ entry that are affected by tetraploidization. DKO cells manifested reduced expression of endogenous sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (Serca2a) and transfection-enforced reintroduction of Serca2a, or reintroduction of an ER-targeted variant of BAK into DKO cells reestablished the same pattern of Ca2+ fluxes as observed in BAX/BAK-sufficient control cells. Serca2a reexpression and ER-targeted BAK also abolished the tetraploidy-induced senescence of DKO cells, placing ER Ca2+ fluxes downstream of the regulation of senescence by BAX/BAK. In conclusion, it appears that BAX/BAK prevent the induction of a tetraploidization-associated senescence program. Speculatively, this may contribute to the low incidence of cancers in BAX/BAK DKO mice and explain why human cancers rarely lose the expression of both BAX and BAK.
Identification of a novel variant of the ciliopathic gene FUZZY associated with craniosynostosis
Authors: Barrell William B. , Adel Al-Lami Hadeel , Goos Jacqueline A. C. , Swagemakers Sigrid M. A. , van Dooren Marieke , Torban Elena , van der Spek Peter J. , Mathijssen Irene M. J. , Liu Karen J.
Published: November 2021

Craniosynostosis is a birth defect occurring in approximately one in 2000 live births, where premature fusion of the cranial bones inhibits growth of the skull during critical periods of brain development. The resulting changes in skull shape can lead to compression of the brain, causing severe complications. While we have some understanding of the molecular pathology of craniosynostosis, a large proportion of cases are of unknown genetic aetiology. Based on studies in mouse, we previously proposed that the ciliopathy geneFuzshould be considered a candidate craniosynostosis gene. Here, we report a novel variant ofFUZ(c.851 G > C, p.(Arg284Pro)) found in monozygotic twins presenting with craniosynostosis. To investigate whetherFuzhas a direct role in regulating osteogenic fate and mineralisation, we cultured primary osteoblasts and mouse embryonic fibroblasts (MEFs) fromFuzmutant mice. Loss ofFuzresulted in increased osteoblastic mineralisation. This suggests that FUZ protein normally acts as a negative regulator of osteogenesis. We then usedFuzmutant MEFs, which lose functional primary cilia, to test whether the FUZ p.(Arg284Pro) variant could restore FUZ function during ciliogenesis. We found that expression of the FUZ p.(Arg284Pro) variant was sufficient to partially restore cilia numbers, but did not mediate a comparable response to Hedgehog pathway activation. Together, this suggests the osteogenic effects of FUZ p.(Arg284Pro) do not depend upon initiation of ciliogenesis.
N-glucosyltransferase GbNGT1 from ginkgo complements the auxin metabolic pathway
Authors: Yin Qinggang , Zhang Jing , Wang Shuhui , Cheng Jintang , Gao Han , Guo Cong , Ma Lianbao , Sun Limin , Han Xiaoyan , Chen Shilin , Liu An
Published: November 2021

As auxins are among the most important phytohormones, the regulation of auxin homeostasis is complex. Generally, auxin conjugates, especially IAA glucosides, are predominant at high auxin levels. Previous research on terminal glucosylation focused mainly on the O-position, while IAA-N-glucoside and IAA-Asp-N-glucoside have been neglected since their discovery in 2001. In our study, IAA-Asp-N-glucoside was found to be specifically abundant (as high as 4.13 mg/g) in the seeds of 58 ginkgo cultivars. Furthermore, a novel N-glucosyltransferase, termed GbNGT1, was identified via differential transcriptome analysis and in vitro enzymatic testing. It was found that GbNGT1 could catalyze IAA-Asp and IAA to form their corresponding N-glucosides. The enzyme was demonstrated to possess a specific catalytic capacity toward the N-position of the IAA-amino acid or IAA from 52 substrates. Docking and site-directed mutagenesis of this enzyme confirmed that the E15G mutant could almost completely abolish its N-glucosylation ability toward IAA-Asp and IAA in vitro and in vivo. The IAA modification of GbNGT1 and GbGH3.5 was verified by transient expression assay in Nicotiana benthamiana. The effect of GbNGT1 on IAA distribution promotes root growth in Arabidopsis thaliana.
Integrating full-length transcriptomics and metabolomics reveals the regulatory mechanisms underlying yellow pigmentation in tree peony (Paeonia suffruticosa Andr.) flowers
Authors: Luo Xiaoning , Sun Daoyang , Wang Shu , Luo Sha , Fu Yaqi , Niu Lixin , Shi Qianqian , Zhang Yanlong
Published: November 2021

Tree peony (Paeonia suffruticosa Andr.) is a popular ornamental plant in China due to its showy and colorful flowers. However, yellow-colored flowers are rare in both wild species and domesticated cultivars. The molecular mechanisms underlying yellow pigmentation remain poorly understood. Here, petal tissues of two tree peony cultivars, “High Noon” (yellow flowers) and “Roufurong” (purple–red flowers), were sampled at five developmental stages (S1–S5) from early flower buds to full blooms. Five petal color indices (brightness, redness, yellowness, chroma, and hue angle) and the contents of ten different flavonoids were determined. Compared to “Roufurong,” which accumulated abundant anthocyanins at S3–S5, the yellow-colored “High Noon” displayed relatively higher contents of tetrahydroxychalcone (THC), flavones, and flavonols but no anthocyanin production. The contents of THC, flavones, and flavonols in “High Noon” peaked at S3 and dropped gradually as the flower bloomed, consistent with the color index patterns. Furthermore, RNA-seq analyses at S3 showed that structural genes such as PsC4Hs, PsDFRs, and PsUFGTs in the flavonoid biosynthesis pathway were downregulated in “High Noon,” whereas most PsFLSs, PsF3Hs, and PsF3’Hs were upregulated. Five transcription factor (TF) genes related to flavonoid biosynthesis were also upregulated in “High Noon.” One of these TFs, PsMYB111, was overexpressed in tobacco, which led to increased flavonols but decreased anthocyanins. Dual-luciferase assays further confirmed that PsMYB111 upregulated PsFLS. These results improve our understanding of yellow pigmentation in tree peony and provide a guide for future molecular-assisted breeding experiments in tree peony with novel flower colors.
Direct copolymerization of ethylene with protic comonomers enabled by multinuclear Ni catalysts
Authors: Ji Gang , Chen Zhou , Wang Xiao-Yan , Ning Xiao-Shan , Xu Chong-Jie , Zhang Xing-Min , Tao Wen-Jie , Li Jun-Fang , Gao Yanshan , Shen Qi , Sun Xiu-Li , Wang Hao-Yang , Zhao Jun-Bo , Zhang Bo , Guo Yin-Long , Zhao Yanan , Sun Jiajie , Luo Yi , Tang Yong
Published: November 2021

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.
Atomic scale crystal field mapping of polar vortices in oxide superlattices
Authors: Susarla Sandhya , García-Fernández Pablo , Ophus Colin , Das Sujit , Aguado-Puente Pablo , McCarter Margaret , Ercius Peter , Martin Lane W. , Ramesh Ramamoorthy , Junquera Javier
Published: November 2021

Polar vortices in oxide superlattices exhibit complex polarization topologies. Using a combination of electron energy loss near-edge structure analysis, crystal field multiplet theory, and first-principles calculations, we probe the electronic structure within such polar vortices in [(PbTiO3)16/(SrTiO3)16] superlattices at the atomic scale. The peaks in Ti $$L$$
L
-edge spectra shift systematically depending on the position of the Ti4+ cations within the vortices i.e., the direction and magnitude of the local dipole. First-principles computation of the local projected density of states on the Ti $$3d$$
3
d
orbitals, together with the simulated crystal field multiplet spectra derived from first principles are in good agreement with the experiments.
Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes
Authors: Lehmann Brian D. , Colaprico Antonio , Silva Tiago C. , Chen Jianjiao , An Hanbing , Ban Yuguang , Huang Hanchen , Wang Lily , James Jamaal L. , Balko Justin M. , Gonzalez-Ericsson Paula I. , Sanders Melinda E. , Zhang Bing , Pietenpol Jennifer A. , Chen X. Steven
Published: November 2021

Triple-negative breast cancer (TNBC) is a collection of biologically diverse cancers characterized by distinct transcriptional patterns, biology, and immune composition. TNBCs subtypes include two basal-like (BL1, BL2), a mesenchymal (M) and a luminal androgen receptor (LAR) subtype. Through a comprehensive analysis of mutation, copy number, transcriptomic, epigenetic, proteomic, and phospho-proteomic patterns we describe the genomic landscape of TNBC subtypes. Mesenchymal subtype tumors display high mutation loads, genomic instability, absence of immune cells, low PD-L1 expression, decreased global DNA methylation, and transcriptional repression of antigen presentation genes. We demonstrate that major histocompatibility complex I (MHC-I) is transcriptionally suppressed by H3K27me3 modifications by the polycomb repressor complex 2 (PRC2). Pharmacological inhibition of PRC2 subunits EZH2 or EED restores MHC-I expression and enhances chemotherapy efficacy in murine tumor models, providing a rationale for using PRC2 inhibitors in PD-L1 negative mesenchymal tumors. Subtype-specific differences in immune cell composition and differential genetic/pharmacological vulnerabilities suggest additional treatment strategies for TNBC.
A live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters
Authors: Frantz Phanramphoei N. , Barinov Aleksandr , Ruffié Claude , Combredet Chantal , Najburg Valérie , de Melo Guilherme Dias , Larrous Florence , Kergoat Lauriane , Teeravechyan Samaporn , Jongkaewwattana Anan , Billon-Denis Emmanuelle , Tournier Jean-Nicolas , Prot Matthieu , Levillayer Laurine , Conquet Laurine , Montagutelli Xavier , Tichit Magali , Hardy David , Fernandes Priyanka , Strick-Marchand Hélène , Di Santo James , Simon-Lorière Etienne , Bourhy Hervé , Tangy Frédéric
Published: November 2021

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.
Long-term priors influence visual perception through recruitment of long-range feedback
Authors: Hardstone Richard , Zhu Michael , Flinker Adeen , Melloni Lucia , Devore Sasha , Friedman Daniel , Dugan Patricia , Doyle Werner K. , Devinsky Orrin , He Biyu J.
Published: November 2021

Perception results from the interplay of sensory input and prior knowledge. Despite behavioral evidence that long-term priors powerfully shape perception, the neural mechanisms underlying these interactions remain poorly understood. We obtained direct cortical recordings in neurosurgical patients as they viewed ambiguous images that elicit constant perceptual switching. We observe top-down influences from the temporal to occipital cortex, during the preferred percept that is congruent with the long-term prior. By contrast, stronger feedforward drive is observed during the non-preferred percept, consistent with a prediction error signal. A computational model based on hierarchical predictive coding and attractor networks reproduces all key experimental findings. These results suggest a pattern of large-scale information flow change underlying long-term priors’ influence on perception and provide constraints on theories about long-term priors’ influence on perception.
A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
Authors: Bateman Thomas J. , Shah Megha , Ho Timothy Pham , Shin Hyejin Esther , Pan Chuxi , Harris Greg , Fegan Jamie E. , Islam Epshita A. , Ahn Sang Kyun , Hooda Yogesh , Gray-Owen Scott D. , Chen Wangxue , Moraes Trevor F.
Published: November 2021

Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
A deep learning approach for complex microstructure inference
Authors: Durmaz Ali Riza , Müller Martin , Lei Bo , Thomas Akhil , Britz Dominik , Holm Elizabeth A. , Eberl Chris , Mücklich Frank , Gumbsch Peter
Published: November 2021

Automated, reliable, and objective microstructure inference from micrographs is essential for a comprehensive understanding of process-microstructure-property relations and tailored materials development. However, such inference, with the increasing complexity of microstructures, requires advanced segmentation methodologies. While deep learning offers new opportunities, an intuition about the required data quality/quantity and a methodological guideline for microstructure quantification is still missing. This, along with deep learning’s seemingly intransparent decision-making process, hampers its breakthrough in this field. We apply a multidisciplinary deep learning approach, devoting equal attention to specimen preparation and imaging, and train distinct U-Net architectures with 30–50 micrographs of different imaging modalities and electron backscatter diffraction-informed annotations. On the challenging task of lath-bainite segmentation in complex-phase steel, we achieve accuracies of 90% rivaling expert segmentations. Further, we discuss the impact of image context, pre-training with domain-extrinsic data, and data augmentation. Network visualization techniques demonstrate plausible model decisions based on grain boundary morphology.
Post-translational insertion of boron in proteins to probe and modulate function
Authors: Mollner Tim A. , Isenegger Patrick G. , Josephson Brian , Buchanan Charles , Lercher Lukas , Oehlrich Daniel , Hansen D. Flemming , Mohammed Shabaz , Baldwin Andrew J. , Gouverneur Véronique , Davis Benjamin G.
Published: November 2021

Boron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) in proteins. Precise anchoring of boron within complex biomolecular systems allows dative bond-mediated, site-dependent protein Lewis acid–base-pairing (LABP) by Bal. Dynamic protein-LABP creates tunable inter- and intramolecular ligand–host interactions, while reactive protein-LABP reveals reactively accessible sites through migratory boron-to-oxygen Cβ–Oγ covalent bond formation. These modes of dative bonding can also generate de novo function, such as control of thermo- and proteolytic stability in a target protein, or observation of transient structural features via chemical exchange. These results indicate that controlled insertion of boron facilitates stability modulation, structure determination, de novo binding activities and redox-responsive ‘mutation’.
Metabolomic profiling of Burkholderia cenocepacia in synthetic cystic fibrosis sputum medium reveals nutrient environment-specific production of virulence factors
Authors: Jaiyesimi Olakunle A. , McAvoy Andrew C. , Fogg David N. , Garg Neha
Published: November 2021

Infections by Burkholderia cenocepacia lead to life-threatening disease in immunocompromised individuals, including those living with cystic fibrosis (CF). While genetic variation in various B. cenocepacia strains has been reported, it remains unclear how the chemical environment of CF lung influences the production of small molecule virulence factors by these strains. Here we compare metabolomes of three clinical B. cenocepacia strains in synthetic CF sputum medium (SCFM2) and in a routine laboratory medium (LB), in the presence and absence of the antibiotic trimethoprim. Using a mass spectrometry-based untargeted metabolomics approach, we identify several compound classes which are differentially produced in SCFM2 compared to LB media, including siderophores, antimicrobials, quorum sensing signals, and various lipids. Furthermore, we describe that specific metabolites are induced in the presence of the antibiotic trimethoprim only in SCFM2 when compared to LB. Herein, C13-acyl-homoserine lactone, a quorum sensing signal previously not known to be produced by B. cenocepacia as well as pyochelin-type siderophores were exclusively detected during growth in SCFM2 in the presence of trimethoprim. The comparative metabolomics approach described in this study provides insight into environment-dependent production of secondary metabolites by B. cenocepacia strains and suggests future work which could identify personalized strain-specific regulatory mechanisms involved in production of secondary metabolites. Investigations into whether antibiotics with different mechanisms of action induce similar metabolic alterations will inform development of combination treatments aimed at effective clearance of Burkholderia spp. pathogens.
Redesigning an antibody H3 loop by virtual screening of a small library of human germline-derived sequences
Authors: Corbeil Christopher R. , Manenda Mahder Seifu , Sulea Traian , Baardsnes Jason , Picard Marie-Ève , Hogues Hervé , Gaudreault Francis , Deprez Christophe , Shi Rong , Purisima Enrico O.
Published: November 2021

The design of superior biologic therapeutics, including antibodies and engineered proteins, involves optimizing their specific ability to bind to disease-related molecular targets. Previously, we developed and applied the Assisted Design of Antibody and Protein Therapeutics (ADAPT) platform for virtual affinity maturation of antibodies (Vivcharuk et al. in PLoS One 12(7):e0181490,https://doi.org/10.1371/journal.pone.0181490, 2017). However, ADAPT is limited to point mutations of hot-spot residues in existing CDR loops. In this study, we explore the possibility of wholesale replacement of the entire H3 loop with no restriction to maintain the parental loop length. This complements other currently published studies that sample replacements for the CDR loops L1, L2, L3, H1 and H2. Given the immense sequence space theoretically available to H3, we focused on the virtual grafting of over 5000 human germline-derived H3 sequences from the IGMT/LIGM database increasing the diversity of the sequence space when compared to using crystalized H3 loop sequences. H3 loop conformations are generated and scored to identify optimized H3 sequences. Experimental testing of high-ranking H3 sequences grafted into the framework of the bH1 antibody against human VEGF-A led to the discovery of multiple hits, some of which had similar or better affinities relative to the parental antibody. In over 75% of the tested designs, the re-designed H3 loop contributed favorably to overall binding affinity. The hits also demonstrated good developability attributes such as high thermal stability and no aggregation. Crystal structures of select re-designed H3 variants were solved and indicated that although some deviations from predicted structures were seen in the more solvent accessible regions of the H3 loop, they did not significantly affect predicted affinity scores.
Local adaptations of Mediterranean sheep and goats through an integrative approach
Authors: Serranito Bruno , Cavalazzi Marco , Vidal Pablo , Taurisson-Mouret Dominique , Ciani Elena , Bal Marie , Rouvellac Eric , Servin Bertrand , Moreno-Romieux Carole , Tosser-Klopp Gwenola , Hall Stephen J. G. , Lenstra Johannes A. , Pompanon François , Benjelloun Badr , Da Silva Anne
Published: November 2021

Small ruminants are suited to a wide variety of habitats and thus represent promising study models for identifying genes underlying adaptations. Here, we considered local Mediterranean breeds of goats (n = 17) and sheep (n = 25) from Italy, France and Spain. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original cradle (i.e., the geographical area in which the breed has emerged), including transhumant pastoral areas. We then used the programs PCAdapt and LFMM to identify signatures of artificial and environmental selection. Considering cradles instead of current GPS coordinates resulted in a greater number of signatures identified by the LFMM analysis. The results, combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles in relation to the gradient of aridity and altitude. Some of these genes have been previously implicated in lipid metabolism (SUCLG2, BMP2), hypoxia stress/lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). Selection signatures involving the PCDH9 and KLH1 genes, as well as NBEA/NBEAL1, were identified in both species and thus could play an important adaptive role.
Motion and Sash Height (MASH) alarms for efficient fume hood use
Authors: Kongoletos Johnathan , Munden Ethan , Ballew Jennifer , Preston Daniel J.
Published: November 2021

Ventilation, including fume hoods, consumes 40–70% of the total energy used by modern laboratories. Energy-conscious fume hood usage—for example, closing the sash when a hood is unused—can significantly reduce energy expenditures due to ventilation. Prior approaches to promote such behaviors among lab users have primarily relied on passive feedback methods. In this work, we developed a low-cost fume hood monitoring device with active feedback to alert lab users when a fume hood is left open and unused. Using data collected by the building management system, we observed a 75.6% decrease in the average sash height after installation of these “Motion and Sash Height” (MASH) alarms, which would result in a reduction roughly equal to 43% of the annual carbon emissions of a typical American vehicle, for each fume hood. The MASH alarm presented here reduced energy costs by approximately $1,159 per year, per hood, at MIT.
Identification of the first highly selective inhibitor of human lactate dehydrogenase B
Authors: Shibata Sachio , Sogabe Satoshi , Miwa Masanori , Fujimoto Takuya , Takakura Nobuyuki , Naotsuka Akihiko , Kitamura Shuji , Kawamoto Tomohiro , Soga Tomoyoshi
Published: November 2021

Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate and NADH to NAD+; it has two isoforms, LDHA and LDHB. LDHA is a promising target for cancer therapy, whereas LDHB is necessary for basal autophagy and cancer cell proliferation in oxidative and glycolytic cancer cells. To the best of our knowledge, selective inhibitors for LDHB have not yet been reported. Here, we developed a high-throughput mass spectrometry screening system using an LDHB enzyme assay by detecting NADH and NAD+. As a result, we identified a small-molecule LDHB selective inhibitor AXKO-0046, an indole derivative. This compound exhibited uncompetitive LDHB inhibition (EC50 = 42 nM). X-ray crystallography revealed that AXKO-0046 bound to the potential allosteric site away from the LDHB catalytic active site, suggesting that targeting the tetramerisation interface of the two dimers is critical for the enzymatic activity. AXKO-0046 and its derivatives can be used to validate LDHB-associated pathways in cancer metabolism.