bluuebunny/crossref_metadata_2025 huggingface dataset:
When Can Benefit–Cost Analyses Ignore Secondary Markets?
Authors: Kotchen Matthew J. , Levinson Arik
Published: December 2022

We make four main contributions in this paper related to the theory and practice of benefit–cost analysis (BCA). First, we show that most BCAs of policy interventions do not consider the welfare consequences in secondary markets, where goods or services can be complements or substitutes to those in the directly regulated markets. Second, we provide a general theoretical analysis for examining the sign of welfare effects in secondary markets, showing how the results depend on the welfare measure of interest and on whether the goods are complements or substitutes. We conclude that the welfare effects in secondary markets will typically be negative in cases most relevant for policy analysis. Third, we develop a straightforward tool that BCA analysts can use to evaluate the potential magnitude of secondary-market effects in particular applications. The tool itself highlights how secondary markets are likely to be relatively small in most circumstances. Finally, we illustrate use of the tool in different applications that provide further evidence that secondary-market effects are likely to be small.
Potential host range of Cotesia vanessae (Hymenoptera: Braconidae), a parasitoid new to North America and a possible biological control agent of noctuid pest species
Authors: Hervet V. A. D. , Laird R. A. , Floate K. D.
Published: December 2022

The likelihood of parasitoids establishing in new geographic regions depends upon the availability of suitable host species. Identifying these hosts and the degree of their suitability is particularly important when they include species that are economically important as pests. In laboratory studies, we examined the suitability of 47 species of Lepidoptera as potential hosts of a parthenogenetic strain of the gregarious parasitoid Cotesia vanessae (Hymenoptera: Braconidae). Previously known from Eurasia and northern Africa, the first known recovery of C. vanessae in North America was in 2009. C. vanessae completed development in 34 species, of which three were known hosts (Noctuidae) and 31 (30 Noctuidae, 1 Nymphalidae) were not. Many of these noctuid species are economic pests. Parasitoid fitness was generally highest on species of Plusiinae (Noctuidae), measured as either percentage of successful parasitism, developmental time, or number and mass of F1 progeny. Closely related species were generally similar in their suitability as hosts. In some cases, parasitoid eggs or larvae were killed by the immune system of the parasitized host, but the host eventually failed to excrete food waste, did not pupate, and ultimately died. Such cases reached up to 100% mortality depending upon the lepidopteran species. The suitability of many species of noctuid pests as hosts for C. vanessae suggests that this parasitoid will become established widely throughout North America and may help to suppress populations of some pest species.
Childbirth and Emerging Missionary Information Networks in Britain and the South Pacific
Authors: TILSON KATE
Published: December 2022

This article explores how childbirth shaped the information networks that London Missionary Society missionaries helped develop between Britain and the South Pacific from the late eighteenth century. As Evangelical missionaries experienced challenging births in the South Pacific, they sought new forms of cultural knowledge, which they recorded in their reports to the society. Part of these knowledge networks included books on medicine and midwifery that the missionaries ordered from Britain. From the 1820s, moreover, some missionaries came to collate early forms of ethnographical and anthropological research on Pacific peoples, which examined indigenous ways of birth and postnatal care.
Revisiting epidemiology of leishmaniasis in central Asia: lessons learnt
Authors: Yurchenko Vyacheslav , Chistyakov Daniil S. , Akhmadishina Lyudmila V. , Lukashev Alexander N. , Sádlová Jovana , Strelkova Margarita V.
Published: December 2022

In this work we reviewed historical and recent data onLeishmaniaspp. infection combining data collected in Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Iran, China and Mongolia. We specifically focused on a complex of co-existing species (Leishmania major,Leishmania turanicaandLeishmania gerbilli) sharing the same animal reservoirs and vectors. In addition, we analysed the presence of dsRNA viruses in these species and discussed future research directions to identify species-specific traits, which may determine susceptibility of differentLeishmaniaspp. to viral infection.
Solidarity in Place? Hope and Despair in Postpandemic Membership
Authors: Shachar Ayelet
Published: December 2022

Initially portrayed as the “great equalizer,” the COVID-19 pandemic has proved anything but. This essay recounts the sobering social disparities and vulnerabilities that the pandemic has exposed, especially when it comes to the inequalities that are baked into existing membership regimes, before turning to narratives of hope and democratic renewal. My discussion shines a spotlight on the relationship between borders, (im)mobility, and struggles for recognition and inclusion that have long been central to the practice of citizenship. Focusing on pathways to the acquisition of full membership status for those who are currently denied it, I will deploy logics and policies that have already begun to take shape in different parts of the world, with the goal of amplifying their effects and multiplying their scale. I identify three possible trajectories for postpandemic recovery, two of which offer ways to enhance equality of status and public standing by enlarging the circle of membership: first, through contribution (or what I will term “jus contribuere”), and second, by highlighting what we might call “solidarity in place.” The third reaction, which we might call the “stratification of membership,” pulls in the opposite direction by sharply redrawing the lines—legal, economic, social—that have distinguished insiders from outsiders, and exacerbated patterns of stratification and inequality of status and opportunity that predate the pandemic.
Parties, Democracy, and the Ideal of Anti-factionalism: Past Anxieties and Present Challenges
Authors: Ragazzoni David
Published: December 2022

This essay weaves together the history of political and legal thought, contemporary democratic theory, and recent debates in legal scholarship to examine the ambivalent relationship between political parties and democracy. Celebrated as a structural necessity for the mechanics of democratic government, political parties are also handled with suspicion for their hybrid nature—neither entirely public nor completely private—and for their always-possible regression into factions. Anti-factionalism, I show, has been a powerful ideal driving constitutional imagination and practice over the centuries, from antiquity (with its emphasis on parts and its horror over factions), to the age of democratic revolutions (with its signature anxieties about divisions), up through the present. However, this long historical process has not extinguished the long-lived concern with the nature and implications of party spirit, nor has it made party democracy completely safe from revamped forms of factionalism. Two manifestations of factional politics stand out in the contemporary political landscape: authoritarian regime changes and populist constitutionalism. While the former is easy to diagnose but hard to prevent, the latter exemplifies a torsion of the constitutional and democratic imagination from within. Despite their differences, both scenarios remind us that constitutions need to envision mechanisms to prevent parties from undermining the liberal democratic order they have been designed to serve. At the same time, they call for renewed attention to the study of parties in the domains of democratic theory and constitutional scholarship.
Teaching Undergraduates Research Methods: A “Methods Lab” Approach
Authors: Sullivan Heather , De Bruin Erica
Published: December 2022

This article introduces a “methods lab” approach to teaching undergraduates about different types of research in political science. In this approach, students are given explicit instruction on what a specific research method entails and the opportunity to practice it before conducting their own research. Methods labs can help students craft more creative research designs as well as understand the strengths and potential pitfalls associated with each method, making the subsequent process of writing a research paper or thesis easier. We provide two sample methods labs focused on conducting archival research and developing survey and interview questions. We discuss our experiences in implementing the labs in a thesis course, describe how the modular lab approach could fit into multiple types of courses, and offer suggestions for those interested in developing labs for other types of research methods.
European interprofessional postgraduate curriculum in palliative care: A narrative synthesis of field interviews in the region of Middle, Eastern, and Southeastern Europe and Central and West Asia
Authors: Paal Piret , Brandstötter Cornelia , Elsner Frank , Lorenzl Stefan , Osterbrink Jürgen , Stähli Andreas
Published: December 2022

Objectives

In 2018, a study was conducted in the Eastern and South-eastern Europe and Central Asia. National leaders of palliative care were asked to describe developments in postgraduate education in their region. They were asked whether the introduction of a European curriculum would be useful in their country. The aim was to explore the structures of postgraduate education at country level in order to define the barriers and opportunities.

Methods

This is an ethnographic study based on semi-structured field interviews. A thematic analysis was chosen for data extraction and a narrative synthesis for the systematic presentation and critical discussion of the results.

Results

Thirty-two interviews were recorded in 23 countries. The analysis revealed 4 main themes: (1) general barriers to access, (2) necessary to improve palliative care education, (3) palliative care core curriculum – the theoretical framework, and (4) challenges in implementation. These main themes were complemented by 19 subthemes.

Significance of results

Palliative care is understood as a universal idea, which in practice means accepting social pluralism and learning to respect unique individual needs. This makes teaching palliative care a very special task because there are no golden standards for dealing with each individual as they are. In theory, a European curriculum recommendation is useful to convince governments and other key stakeholders of the importance of postgraduate education. In practice, such a curriculum needs to be adapted to the constraints of health services and human resources. Validated quality assessment criteria for palliative care education are crucial to advance postgraduate education.
Frühkindliche religiöse Bildung in den Bildungsplänen
Authors: Knoblauch Christoph
Published: December 2022

Zusammenfassung. Frühkindliche religiöse Bildung wird unter vielfältigen Perspektiven diskutiert und von unterschiedlichen Interessengruppen geprägt. Dabei befindet sich religiöse Bildung in einer dynamischen Gemengelage, die unterschiedliche Verständnisgrundlagen sowie Herausforderungen durch gesellschaftliche Transformationen beinhaltet. Eine Analyse der Bildungspläne der Länder untersucht Darstellung, Verortung, zugrunde liegende Religionsbegriffe und Zielvorstellungen religiöser Bildung, um Gemeinsamkeiten und Unterschiede identifizieren und Tendenzen erkennen zu können.
Perceived Economic Inequality Measures and Their Association With Objective Inequality and Redistributive Preferences
Authors: García-Castro Juan Diego , García-Sánchez Efraín , Willis Guillermo B. , Castillo Juan Carlos , Rodríguez-Bailón Rosa
Published: December 2022

Abstract. Perceptions of economic inequality (PEI) play a central role in people’s responses to inequality. We aim to examine the consistency between different PEI measures (income gaps, diagrammatic figures, experienced downward and upward disparities), their relationship with objective inequality, and their association with redistributive preferences. Using data from the International Social Survey Programme 2019 ( N = 34,387, 22 countries), we performed multilevel regression analyses and found that PEI indicators were weakly and positively correlated, suggesting that they represent different dimensions of the same construct. Furthermore, objective inequality was not related to PEI measures. Finally, all PEI measures were positively associated with support for redistribution, except for experienced upward inequality. We discuss the multidimensional nature of PEI and its implications on redistributive preferences.
Deep Mantle Influence on the Cameroon Volcanic Line
Authors: Saeidi Hesam , Hansen Samantha E. , Nyblade Andrew A.
Published: December 2022

The origin of the Cameroon Volcanic Line (CVL), which is difficult to explain with traditional plate tectonics and mantle convection models because the volcanism does not display clear age progression, remains widely debated. Existing seismic tomography models show anomalously slow structure beneath the CVL, which some have interpreted to reflect upper mantle convective processes, possibly associated with edge‐driven flow related to the neighboring Congo Craton. However, mid‐ and lower mantle depths are generally not well resolved in these models, making it difficult to determine the extent of the anomalous CVL structure. Here, we present a new P‐wave velocity model for the African mantle, developed with the largest collection of travel‐time residuals recorded across the continent to date and an adaptive model parameterization. Our extensive data set and inversion method yield high resolution images of the mantle structure beneath western Africa, particularly at the critical mid‐ and lower mantle depths needed to further evaluate processes associated with the formation of the CVL. Our new model provides strong evidence for a connection between the African Large Low Velocity Province, centered in the lower mantle beneath southern Africa, and the continental portion of the CVL. We suggest that seismically slow material generated near the core‐mantle boundary beneath southern Africa moves northwestward under the Congo Craton. At the northern edge of the craton, the hot, buoyant material rises through the upper mantle, causing the CVL volcanism. Consequently, CVL magmatism can be linked to large‐scale mantle processes rooted in the deep mantle.
The “New Core Paradox”: Challenges and Potential Solutions
Authors: Driscoll P. , Davies C.
Published: December 2022

The “new core paradox” suggests that the persistence of the geomagnetic field over nearly all of Earth history is in conflict with the core being highly thermally conductive, which makes convection and dynamo action in the core much harder prior to the nucleation of the inner core. Here we revisit this issue by exploring the influence of six important parameters on core evolution: upper/lower mantle viscosity ratio, core thermal conductivity, core radiogenic heat rate, mantle radiogenic heating rate, central core melting temperature, and initial core‐mantle boundary (CMB) temperature. Each parameter is systematically explored by the model, which couples mantle energy and core energy‐entropy evolution. A model is “successful” if the correct present‐day inner core size is achieved and the dynamo remains alive, as implied by the paleomagnetic record. In agreement with previous studies, we do not find successful thermal evolutions using nominal parameters, which includes a core thermal conductivity of 70 Wm−1K−1, zero core radioactivity, and an initial CMB temperature of 5,000 K. The dynamo can be kept alive by assuming an unrealistically low thermal conductivity of 20 Wm−1K−1 or an unrealistically high core radioactive heat flow of 3 TW at present‐day, which are considered “unsuccessful” models. We identify a third scenario to keep the dynamo alive by assuming a hot initial CMB temperature of ∼6,000 K and a central core liquidus of ∼5,550 K. These temperatures are on the extreme end of typical estimates, but should not be ruled out and deserve further scrutiny.
The publication quality of laboratory values in clinical studies in neonates
Authors: Allegaert Karel , Hildebrand Heidrun , Singh Kanwaljit , Turner Mark A.
Published: December 2022

Background

There are no generally accepted age-appropriate reference ranges for laboratory values in neonates. This also matters for drug development. The International Neonatal Consortium (INC) is engaged to define actionable reference ranges of commonly used laboratory values in neonates.

Methods

A structured literature search was performed to identify standards or recommendations for publications that present neonatal laboratory data to assess the publication quality of laboratory values in neonates. Using a modified Delphi approach, an assessment and data extraction instrument to screen on completeness of information was developed.

Results

On 2908 hits, 281 papers were retained for full reading and 257 for data extraction. None of the papers reported a publication standard. Using the extraction instrument, most papers presented single country or unit findings. The median number of neonates was 120, with uncertainty on single or repeated measurements. Clinically meaningful information on age, sex, and medical conditions was commonly provided. Information on pharmacotherapy, equipment, analytical method, or laboratory location was rarely mentioned.

Conclusions

Published information on laboratory values for neonates is sparse, not systematic, and incomplete. This undermines efforts to compare treatments, safety monitoring, or clinical management. Furthermore, there appears to be no standard yet to report laboratory values in neonates.

Impact

There are no generally accepted age-appropriate reference ranges for laboratory values in neonates, leading to a significant knowledge gap, also for safety reporting and drug development in neonates.

We performed a literature search to identify standards or recommendations for publications on neonatal laboratory data and to assess the publication quality of laboratory values in clinical studies involving neonates.

Standards or recommendations for publications that present neonatal laboratory data were not identified, while published information on laboratory values for neonates is sparse, not systematic, and incomplete.
Clinical utility of liquid biopsy and integrative genomic profiling in early-stage and oligometastatic cancer patients treated with radiotherapy
Authors: Cifuentes Guadalupe A. , Santiago Adrián , Méndez Blanco Lucía , Fueyo María , López Martínez Esther , Soria Raquel , Martín López Irene , Cucarella Beltrán Pepa , Pardo-Coto Pablo , Rodriguez-Rubi David , Urquilla Karla , Durán Noelia S. , Álvarez Rebeca , Lago Claudia G. , Otero Andrea , Diñeiro Marta , Capín Raquel , Cadiñanos Juan , Cabanillas Rubén
Published: December 2022

Background

Liquid biopsy and Integrative Genomic Profiling (IGP) are yet to be implemented into routine Radiation Oncology. Here we assess the utility of germline, tumour and circulating cell-free DNA-based genomic analyses for the clinical management of early-stage and oligometastatic cancer patients treated by precision radiotherapy.

Methods

We performed germline, tissue- and liquid biopsy NGS panels on 50 early-stage/oligometastatic cancer patients undergoing radiotherapy. We also monitored ctDNA variants in serial liquid biopsies collected during radiotherapy and follow-up and evaluated the clinical utility of such comprehensive approach.

Results

The integration of different genomic studies revealed that only 1/3 of the liquid biopsy variants are of tumour origin. Altogether, 55 tumour variants (affecting 3/4 of the patients) were considered potentially actionable (for treatment and prognosis), whereas potential follow-up biomarkers were identified in all cases. Germline cancer-predisposing variants were present in three patients, which would have not been eligible for hereditary cancer testing according to clinical guidelines. The presence of detectable ctDNA variants before radiotherapy was associated with progression-free survival both in oligometastatic patients and in those with early-stage.

Conclusions

IGP provides both valuable and actionable information for personalised decision-making in Radiation Oncology.
Human leukocyte antigen super-locus: nexus of genomic supergenes, SNPs, indels, transcripts, and haplotypes
Authors: Kulski Jerzy K. , Suzuki Shingo , Shiina Takashi
Published: December 2022

The human Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) super-locus is a highly polymorphic genomic region that encodes more than 140 coding genes including the transplantation and immune regulatory molecules. It receives special attention for genetic investigation because of its important role in the regulation of innate and adaptive immune responses and its strong association with numerous infectious and/or autoimmune diseases. In recent years, MHC genotyping and haplotyping using Sanger sequencing and next-generation sequencing (NGS) methods have produced many hundreds of genomic sequences of the HLA super-locus for comparative studies of the genetic architecture and diversity between the same and different haplotypes. In this special issue on ‘The Current Landscape of HLA Genomics and Genetics’, we provide a short review of some of the recent analytical developments used to investigate the SNP polymorphisms, structural variants (indels), transcription and haplotypes of the HLA super-locus. This review highlights the importance of using reference cell-lines, population studies, and NGS methods to improve and update our understanding of the mechanisms, architectural structures and combinations of human MHC genomic alleles (SNPs and indels) that better define and characterise haplotypes and their association with various phenotypes and diseases.
Tiltable objective microscope visualizes selectivity for head motion direction and dynamics in zebrafish vestibular system
Authors: Tanimoto Masashi , Watakabe Ikuko , Higashijima Shin-ichi
Published: December 2022

Spatio-temporal information about head orientation and movement is fundamental to the sense of balance and motion. Hair cells (HCs) in otolith organs of the vestibular system transduce linear acceleration, including head tilt and vibration. Here, we build a tiltable objective microscope in which an objective lens and specimen tilt together. With in vivo Ca2+imaging of all utricular HCs and ganglion neurons during 360° static tilt and vibration in pitch and roll axes, we reveal the direction- and static/dynamic stimulus-selective topographic responses in larval zebrafish. We find that head vibration is preferentially received by striolar HCs, whereas static tilt is preferentially transduced by extrastriolar HCs. Spatially ordered direction preference in HCs is consistent with hair-bundle polarity and is preserved in ganglion neurons through topographic innervation. Together, these results demonstrate topographically organized selectivity for direction and dynamics of head orientation/movement in the vestibular periphery.
A space-based quantum gas laboratory at picokelvin energy scales
Authors: Gaaloul Naceur , Meister Matthias , Corgier Robin , Pichery Annie , Boegel Patrick , Herr Waldemar , Ahlers Holger , Charron Eric , Williams Jason R. , Thompson Robert J. , Schleich Wolfgang P. , Rasel Ernst M. , Bigelow Nicholas P.
Published: December 2022

Ultracold quantum gases are ideal sources for high-precision space-borne sensing as proposed for Earth observation, relativistic geodesy and tests of fundamental physical laws as well as for studying new phenomena in many-body physics during extended free fall. Here we report on experiments with the Cold Atom Lab aboard the International Space Station, where we have achieved exquisite control over the quantum state of single 87Rb Bose-Einstein condensates paving the way for future high-precision measurements. In particular, we have applied fast transport protocols to shuttle the atomic cloud over a millimeter distance with sub-micrometer accuracy and subsequently drastically reduced the total expansion energy to below 100 pK with matter-wave lensing techniques.
Machine learning assisted interferometric structured illumination microscopy for dynamic biological imaging
Authors: Ward Edward N. , Hecker Lisa , Christensen Charles N. , Lamb Jacob R. , Lu Meng , Mascheroni Luca , Chung Chyi Wei , Wang Anna , Rowlands Christopher J. , Schierle Gabriele S. Kaminski , Kaminski Clemens F.
Published: December 2022

Structured Illumination Microscopy, SIM, is one of the most powerful optical imaging methods available to visualize biological environments at subcellular resolution. Its limitations stem from a difficulty of imaging in multiple color channels at once, which reduces imaging speed. Furthermore, there is substantial experimental complexity in setting up SIM systems, preventing a widespread adoption. Here, we present Machine-learning Assisted, Interferometric Structured Illumination Microscopy, MAI-SIM, as an easy-to-implement method for live cell super-resolution imaging at high speed and in multiple colors. The instrument is based on an interferometer design in which illumination patterns are generated, rotated, and stepped in phase through movement of a single galvanometric mirror element. The design is robust, flexible, and works for all wavelengths. We complement the unique properties of the microscope with an open source machine-learning toolbox that permits real-time reconstructions to be performed, providing instant visualization of super-resolved images from live biological samples.
Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion
Authors: Kawai Hiroyuki , Bouchekioua Youcef , Nishitani Naoya , Niitani Kazuhei , Izumi Shoma , Morishita Hinako , Andoh Chihiro , Nagai Yuma , Koda Masashi , Hagiwara Masako , Toda Koji , Shirakawa Hisashi , Nagayasu Kazuki , Ohmura Yu , Kondo Makoto , Kaneda Katsuyuki , Yoshioka Mitsuhiro , Kaneko Shuji
Published: December 2022

Appropriate processing of reward and aversive information is essential for survival. Although a critical role of serotonergic neurons in the dorsal raphe nucleus (DRN) in reward processing has been shown, the lack of rewarding effects with selective serotonin reuptake inhibitors (SSRIs) implies the presence of a discrete serotonergic system playing an opposite role to the DRN in the processing of reward and aversive stimuli. Here, we demonstrated that serotonergic neurons in the median raphe nucleus (MRN) of mice process reward and aversive information in opposite directions to DRN serotonergic neurons. We further identified MRN serotonergic neurons, including those projecting to the interpeduncular nucleus (5-HTMRN→IPN), as a key mediator of reward and aversive stimuli. Moreover, 5-HT receptors, including 5-HT2A receptors in the interpeduncular nucleus, are involved in the aversive properties of MRN serotonergic neural activity. Our findings revealed an essential function of MRN serotonergic neurons, including 5-HTMRN→IPN, in the processing of reward and aversive stimuli.
Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice
Authors: Institoris Adam , Vandal Milène , Peringod Govind , Catalano Christy , Tran Cam Ha , Yu Xinzhu , Visser Frank , Breiteneder Cheryl , Molina Leonardo , Khakh Baljit S. , Nguyen Minh Dang , Thompson Roger J. , Gordon Grant R.
Published: December 2022

Functional hyperemia occurs when enhanced neuronal activity signals to increase local cerebral blood flow (CBF) to satisfy regional energy demand. Ca2+ elevation in astrocytes can drive arteriole dilation to increase CBF, yet affirmative evidence for the necessity of astrocytes in functional hyperemia in vivo is lacking. In awake mice, we discovered that functional hyperemia is bimodal with a distinct early and late component whereby arteriole dilation progresses as sensory stimulation is sustained. Clamping astrocyte Ca2+ signaling in vivo by expressing a plasma membrane Ca2+ ATPase (CalEx) reduces sustained but not brief sensory-evoked arteriole dilation. Elevating astrocyte free Ca2+ using chemogenetics selectively augments sustained hyperemia. Antagonizing NMDA-receptors or epoxyeicosatrienoic acid production reduces only the late component of functional hyperemia, leaving brief increases in CBF to sensory stimulation intact. We propose that a fundamental role of astrocyte Ca2+ is to amplify functional hyperemia when neuronal activation is prolonged.
Cross-kingdom synthetic microbiota supports tomato suppression of Fusarium wilt disease
Authors: Zhou Xin , Wang Jinting , Liu Fang , Liang Junmin , Zhao Peng , Tsui Clement K. M. , Cai Lei
Published: December 2022

The role of rhizosphere microbiota in the resistance of tomato plant against soil-borne Fusarium wilt disease (FWD) remains unclear. Here, we showed that the FWD incidence was significantly negatively correlated with the diversity of both rhizosphere bacterial and fungal communities. Using the microbiological culturomic approach, we selected 205 unique strains to construct different synthetic communities (SynComs), which were inoculated into germ-free tomato seedlings, and their roles in suppressing FWD were monitored using omics approach. Cross-kingdom (fungi and bacteria) SynComs were most effective in suppressing FWD than those of Fungal or Bacterial SynComs alone. This effect was underpinned by a combination of molecular mechanisms related to plant immunity and microbial interactions contributed by the bacterial and fungal communities. This study provides new insight into the dynamics of microbiota in pathogen suppression and host immunity interactions. Also, the formulation and manipulation of SynComs for functional complementation constitute a beneficial strategy in controlling soil-borne disease.
Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice
Authors: Dufour Damien , Dumontet Typhanie , Sahut-Barnola Isabelle , Carusi Aude , Onzon Méline , Pussard Eric , Wilmouth James Jr , Olabe Julie , Lucas Cécily , Levasseur Adrien , Damon-Soubeyrand Christelle , Pointud Jean-Christophe , Roucher-Boulez Florence , Tauveron Igor , Bossis Guillaume , Yeh Edward T. , Breault David T. , Val Pierre , Lefrançois-Martinez Anne-Marie , Martinez Antoine
Published: December 2022

SUMOylation is a dynamic posttranslational modification, that provides fine-tuning of protein function involved in the cellular response to stress, differentiation, and tissue development. In the adrenal cortex, an emblematic endocrine organ that mediates adaptation to physiological demands, the SUMOylation gradient is inversely correlated with the gradient of cellular differentiation raising important questions about its role in functional zonation and the response to stress. Considering that SUMO-specific protease 2 (SENP2), a deSUMOylating enzyme, is upregulated by Adrenocorticotropic Hormone (ACTH)/cAMP-dependent Protein Kinase (PKA) signalling within the zonafasciculata, we generated mice with adrenal-specific Senp2 loss to address these questions. Disruption of SENP2 activity in steroidogenic cells leads to specific hypoplasia of the zona fasciculata, a blunted reponse to ACTH and isolated glucocorticoid deficiency. Mechanistically, overSUMOylation resulting from SENP2 loss shifts the balance between ACTH/PKA and WNT/β-catenin signalling leading to repression of PKA activity and ectopic activation of β-catenin. At the cellular level, this blocks transdifferentiation of β-catenin-positive zona glomerulosa cells into fasciculata cells and sensitises them to premature apoptosis. Our findings indicate that the SUMO pathway is critical for adrenal homeostasis and stress responsiveness.
Ampere-level current density ammonia electrochemical synthesis using CuCo nanosheets simulating nitrite reductase bifunctional nature
Authors: Fang Jia-Yi , Zheng Qi-Zheng , Lou Yao-Yin , Zhao Kuang-Min , Hu Sheng-Nan , Li Guang , Akdim Ouardia , Huang Xiao-Yang , Sun Shi-Gang
Published: December 2022

The development of electrocatalysts capable of efficient reduction of nitrate (NO3−) to ammonia (NH3) is drawing increasing interest for the sake of low carbon emission and environmental protection. Herein, we present a CuCo bimetallic catalyst able to imitate the bifunctional nature of copper-type nitrite reductase, which could easily remove NO2−via the collaboration of two active centers. Indeed, Co acts as an electron/proton donating center, while Cu facilitates NOx−adsorption/association. The bio-inspired CuCo nanosheet electrocatalyst delivers a 100 ± 1% Faradaic efficiency at an ampere-level current density of 1035 mA cm−2at −0.2 Vvs. Reversible Hydrogen Electrode. The NH3production rate reaches a high activity of 4.8 mmol cm−2h−1(960 mmol gcat−1h−1). A mechanistic study, using electrochemical in situ Fourier transform infrared spectroscopy and shell-isolated nanoparticle enhanced Raman spectroscopy, reveals a strong synergy between Cu and Co, with Co sites promoting the hydrogenation of NO3−to NH3via adsorbed *H species. The well-modulated coverage of adsorbed *H and *NO3led simultaneously to high NH3selectivity and yield.
Clay hydroxyl isotopes show an enhanced hydrologic cycle during the Paleocene-Eocene Thermal Maximum
Authors: Walters Gregory L. , Kemp Simon J. , Hemingway Jordon D. , Johnston David T. , Hodell David A.
Published: December 2022

The Paleocene-Eocene Thermal Maximum (PETM) was an abrupt global warming event associated with a large injection of carbon into the ocean-atmosphere system, as evidenced by a diagnostic carbon isotope excursion (CIE). Evidence also suggests substantial hydrologic perturbations, but details have been hampered by a lack of appropriate proxies. To address this shortcoming, here we isolate and measure the isotopic composition of hydroxyl groups (OH−) in clay minerals from a highly expanded PETM section in the North Sea Basin, together with their bulk oxygen isotope composition. At this location, we show that hydroxyl O- and H-isotopes are less influenced than bulk values by clay compositional changes due to mixing and/or inherited signals and thus better track hydrologic variability. We find that clay OH− hydrogen-isotope values (δ2HOH) decrease slowly prior to the PETM and then abruptly by ∼8‰ at the CIE onset. Coincident with an increase in relative kaolinite content, this indicates increased rainfall and weathering and implies an enhanced hydrologic cycle response to global warming, particularly during the early stages of the PETM. Subsequently, δ2HOH returns to pre-PETM values well before the end of the CIE, suggesting hydrologic changes in the North Sea were short-lived relative to carbon-cycle perturbations.
Memory for nonadjacent dependencies in the first year of life and its relation to sleep
Authors: Friedrich Manuela , Mölle Matthias , Born Jan , Friederici Angela D.
Published: December 2022

Grammar learning requires memory for dependencies between nonadjacent elements in speech. Immediate learning of nonadjacent dependencies has been observed in very young infants, but their memory of such dependencies has remained unexplored. Here we used event-related potentials to investigate whether 6- to 8-month-olds retain nonadjacent dependencies and if sleep after learning affects this memory. Infants were familiarised with two rule-based morphosyntactic dependencies, presented in sentences of an unknown language. Brain responses after a retention period reveal memory of the nonadjacent dependencies, independent of whether infants napped or stayed awake. Napping, however, altered a specific processing stage, suggesting that memory evolves during sleep. Infants with high left frontal spindle activity show an additional brain response indicating memory of individual speech phrases. Results imply that infants as young as 6 months are equipped with memory mechanisms relevant to grammar learning. They also suggest that during sleep, consolidation of highly specific information can co-occur with changes in the nature of generalised memory.
Benchmarking tools for detecting longitudinal differential expression in proteomics data allows establishing a robust reproducibility optimization regression approach
Authors: Välikangas Tommi , Suomi Tomi , Chandler Courtney E. , Scott Alison J. , Tran Bao Q. , Ernst Robert K. , Goodlett David R. , Elo Laura L.
Published: December 2022

Quantitative proteomics has matured into an established tool and longitudinal proteomics experiments have begun to emerge. However, no effective, simple-to-use differential expression method for longitudinal proteomics data has been released. Typically, such data is noisy, contains missing values, and has only few time points and biological replicates. To address this need, we provide a comprehensive evaluation of several existing differential expression methods for high-throughput longitudinal omics data and introduce a Robust longitudinal Differential Expression (RolDE) approach. The methods are evaluated using over 3000 semi-simulated spike-in proteomics datasets and three large experimental datasets. In the comparisons, RolDE performs overall best; it is most tolerant to missing values, displays good reproducibility and is the top method in ranking the results in a biologically meaningful way. Furthermore, RolDE is suitable for different types of data with typically unknown patterns in longitudinal expression and can be applied by non-experienced users.
A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1
Authors: Hou Yun Nan , Cai Yang , Li Wan Hua , He Wei Ming , Zhao Zhi Ying , Zhu Wen Jie , Wang Qiang , Mai Xinyi , Liu Jun , Lee Hon Cheung , Stjepanovic Goran , Zhang Hongmin , Zhao Yong Juan
Published: December 2022

Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation.
Simultaneous capturing phonon and electron dynamics in MXenes
Authors: Zhang Qi , Li Jiebo , Wen Jiao , Li Wei , Chen Xin , Zhang Yifan , Sun Jingyong , Yan Xin , Hu Mingjun , Wu Guorong , Yuan Kaijun , Guo Hongbo , Yang Xueming
Published: December 2022

Plasmonic MXenes are of particular interest, because of their unique electron and phonon structures and multiple surface plasmon effects, which are different from traditional plasmonic materials. However, to date, how electronic energy damp to lattice vibrations (phonons) in MXenes has not been unraveled. Here, we employed ultrafast broadband impulsive vibrational spectroscopy to identify the energy damping channels in MXenes (Ti3C2Tx and Mo2CTx). Distinctive from the well-known damping pathways, our results demonstrate a different energy damping channel, in which the Ti3C2Tx plasmonic electron energy transfers to coherent phonons by nonthermal electron mediation after Landau damping, without involving electron-electron scattering. Moreover, electrons are observed to strongly couple with A1g mode (~60 fs, 85–100%) and weakly couple with Eg mode (1–2 ps, 0–15%). Our results provide new insight into the electron-phonon interaction in MXenes, which allows the design of materials enabling efficient manipulation of electron transport and energy conversion.
Graph-based pangenomics maximizes genotyping density and reveals structural impacts on fungal resistance in melon
Authors: Vaughn Justin N. , Branham Sandra E. , Abernathy Brian , Hulse-Kemp Amanda M. , Rivers Adam R. , Levi Amnon , Wechter William P.
Published: December 2022

The genomic sequences segregating in experimental populations are often highly divergent from the community reference and from one another. Such divergence is problematic under various short-read-based genotyping strategies. In addition, large structural differences are often invisible despite being strong candidates for causal variation. These issues are exacerbated in specialty crop breeding programs with fewer, lower-quality sequence resources. Here, we examine the benefits of complete genomic information, based on long-read assemblies, in a biparental mapping experiment segregating at numerous disease resistance loci in the non-model crop, melon (Cucumis melo). We find that a graph-based approach, which uses both parental genomes, results in 19% more variants callable across the population and raw allele calls with a 2 to 3-fold error-rate reduction, even relative to single reference approaches using a parent genome. We show that structural variation has played a substantial role in shaping two Fusarium wilt resistance loci with known causal genes. We also report on the genetics of powdery mildew resistance, where copy number variation and local recombination suppression are directly interpretable via parental genome alignments. Benefits observed, even in this low-resolution biparental experiment, will inevitably be amplified in more complex populations.
Genetically engineered mesenchymal stem cells with dopamine synthesis for Parkinson’s disease in animal models
Authors: Li Jun , Li Nan , Wei Jingkuan , Feng Chun , Chen Yanying , Chen Tingwei , Ai Zongyong , Zhu Xiaoqing , Ji Weizhi , Li Tianqing
Published: December 2022

Although striatal delivery of three critical genes for dopamine synthesis by viruses is a potential clinical approach for treating Parkinson’s disease (PD), the approach makes it difficult to finely control dopamine secretion amounts and brings safety concerns. Here, we generate genetically engineered mesenchymal stem cells encoding three critical genes for dopamine synthesis (DOPA-MSCs). DOPA-MSCs retain their MSC identity and stable ability to secrete dopamine during passaging. Following transplantation, DOPA-MSCs reinstate striatal dopamine levels and correct motor function in PD rats. Importantly, after grafting into the caudate and putamen, DOPA-MSCs provide homotopic reconstruction of midbrain dopamine pathways by restoring striatal dopamine levels, and safely and long-term (up to 51 months) correct motor disorders and nonmotor deficits in acute and chronic PD rhesus monkey models of PD even with advanced PD symptoms. The long-term benefits and safety results support the idea that the development of dopamine-synthesized engineered cell transplantation is an important strategy for treating PD.
Qualitative study of user perspectives and experiences of digital inhaler technology
Authors: Adejumo Ireti , Patel Mitesh , McKeever Tricia M. , Shaw Dominick E. , Bains Manpreet
Published: December 2022

Electronic monitoring devices (EMDs) have been trialled in interventions to improve inhaled corticosteroid adherence and clinical outcomes. This study sought to understand the perceptions and experiences of EMD end-users. Participants recruited into a six-month EMD study were invited to a semi-structured interview. Interviews were audio-recorded, transcribed verbatim and analysed using the framework approach. Twenty-eight participants (68% female, median age 47) were interviewed. Individuals described feeling responsible for their asthma control. Recent attacks motivated a desire to maintain control. Study participation led to increased awareness of asthma status and medication use. Several individuals were open to integrating digital monitoring data with other mHealth inputs, perceiving the potential to enhance communication with clinicians and empower self-management. Openness to data sharing was tied to expectations of transparent data use. Data supported integrating beliefs and habit formation to achieve behaviour change. There was a willingness for an integrated, platform-based approach to digital self-management.
Preparation of metrological states in dipolar-interacting spin systems
Authors: Zheng Tian-Xing , Li Anran , Rosen Jude , Zhou Sisi , Koppenhöfer Martin , Ma Ziqi , Chong Frederic T. , Clerk Aashish A. , Jiang Liang , Maurer Peter C.
Published: December 2022

Spin systems are an attractive candidate for quantum-enhanced metrology. Here we develop a variational method to generate metrological states in small dipolar-interacting spin ensembles with limited qubit control. For both regular and disordered spatial spin configurations the generated states enable sensing beyond the standard quantum limit (SQL) and, for small spin numbers, approach the Heisenberg limit (HL). Depending on the circuit depth and the level of readout noise, the resulting states resemble Greenberger-Horne-Zeilinger (GHZ) states or Spin Squeezed States (SSS). Sensing beyond the SQL holds in the presence of finite spin polarization and a non-Markovian noise environment. The developed black-box optimization techniques for small spin numbers (N ≤ 10) are directly applicable to diamond-based nanoscale field sensing, where the sensor size limits N and conventional squeezing approaches fail.
Recovery from microplastic-induced marine deoxygenation may take centuries
Authors: Kvale Karin , Oschlies Andreas
Published: December 2022

Climate change and plastics pollution are dual threats to marine environments. Here we use biogeochemical and microplastic modelling to show that even if there is complete removal of microplastics and cessation of deposition in the oceans in 2022, regional recovery from microplastic-induced remineralization and water column deoxygenation could take hundreds of years for coastal upwelling zones, the North Pacific and Southern Ocean. Surface stratification and reduced sea ice cover further impede regional recovery, highlighting the importance of aggressive mitigation of plastic pollution.