bluuebunny/crossref_metadata_2025 huggingface dataset:
Embracing the mystery: David Hume's playful religion of wonder
Authors: Lingier Hannah
Published: August 2023

In this article I show how David Hume's works provide the ingredients for a conception of religiosity understood as a feeling of wonder concerning nature or existence, accompanied by a playful attitude regarding the imaginative shapes that can be given to this emotion. Hume serves as an inspiration rather than an object of study: I respect the spirit and values of his work, while going beyond his own explicit points. My reading accounts for Hume's aversion to traditional religions (‘superstition’), and for his acknowledgement of the universal attraction of the idea of invisible intelligent power and his own fascination with it. I argue first that superstition is a natural reaction to existential uncertainty. Second, I argue that uncertainty fuels activity, creativity and morality, and thus may be left untended. Though it always involves a measure of pain, too, human happiness is found in challenge and activity. Traditional monotheist religions respond to this need by generating experiences of wonder, thus, however, stimulating passive devotion and dogmatism. Opposing this, the suggestion of Hume's works is to respect the mystery of nature rather than shrouding it in unfounded convictions. The fictional character Philo illustrates how the longing for an answer by is itself can already be a profoundly religious feeling. Hume's descriptions of ancient polytheism and Philo show how this can be accompanied by a playful, imaginative interaction with the world.
“Workers do not liberate themselves other than with their own hands”—The Political Experience of Workers' Committees in the Industrial District of Beirut (1970–1975)
Authors: Tufaro Rossana
Published: August 2023

From the end of the 1960s until the outbreak of the Civil War (1975), Lebanon experienced a phase of relatively sustained industrial expansion. Albeit the “boom” did not modify significantly Lebanon's tertiarized economic structure, it was anyway sufficient to create the structural conditions for the emergence of a new militant working-class able to become one of the most relevant contentious actors of its time. This new working class was made primarily of very young and recently urbanized unemployed of rural origin, brutally injected in a crude and hyper-exploitative productive cycle where formal labor unions were, for the most part, absent or scarcely effective. The input for their grassroots, transgressive organization into factory-based Workers’ Committees came from the Organization for Communist Action in Lebanon (OACL), i.e. the most important force of the so-called Lebanese New Left, within the framework of a broader process of militant penetration of the “revolutionary classes” produced by the contradictions of Lebanese capitalism. This created the precondition for the Committees to affirm themselves not only as the radical avant-garde of the Lebanese labor movement but also as an integral part of a broader process of contestation of the existing status quo by the subaltern groups emerged from - or activated by - the structural and cultural changes that the country was experiencing. By retrieving the forgotten history of the Workers’ Committees, the article wants to examine the forms and the trajectories whereby such a new working class became an integral part of this process. In particular, by adopting a Gramscian methodology, the article will first expose the structural changes in the Lebanese industrial sector in the examined period and their labor implications. Then, it will focus on the dynamics which superseded the Committees' birth and affirmation, reserving particular attention to the role played by the OACL. Finally, it will conclude by examining the impact of their agency on the political developments that the country was experiencing. The paper contends that the emergence and the affirmation of counter-hegemonical and transformative working-class activism on the eve of the Civil War, along with representing a direct by-product of structural stresses and constraints, was significantly debtor also of the new ideological and militant infrastructures that the emergence of an Arab New Left had contributed to popularize and deploy. The paper wants also to intervene in the historiographical debate on the Lebanese Civil War, stressing the importance of both subaltern actors and class phenomena in its outbreak, which have generally been widely disregarded by the dominant understandings of the conflict.
When resilience is not enough: Imagining novel approaches to supporting Black youth navigating racism
Authors: Jones Shawn C.T. , Simon Carlisa B. , Yadeta Kenna , Patterson Akilah , Anderson Riana E.
Published: August 2023

The narrative surrounding the impact racism has had on the well-being of Black youth has shifted across sociocultural and historical context. Early discourse around these topics were problem-saturated, focusing on deficits “within” Black youth. Over time, an important narrative shift occurred: greater attention was paid to the inherent assets of Black youth, their families, and communities, including how racial-ethnic protective factors such as racial socialization afforded them resilience. What resulted was decades of research seeking to understand the mechanisms that allow Black youth to bounce back in spite of racism-related adversity. Notwithstanding the viable practice and policy implications that have emerged from such inquiry, at what point does our focus on the resilience of Black youth – whether individual or multisystemic – fall short? It is with this question in mind that this paper challenges those committed to the optimal development of Black youth to consider yet another narrative shift: one that stands upon the legacy of cultural ecological frameworks and the seminal models underlying resilience research, and calls us toward not supporting Black youth’s adaptation to racism, but toward collective efforts to transform our approach, pushing back against the perniciousness of racism.
Resilience in development: Neighborhood context, experiences of discrimination, and children’s mental health
Authors: Okuzono Sakurako S. , Wilson Joseph , Slopen Natalie
Published: August 2023

An understanding of child psychopathology and resilience requires attention to the nested and interconnected systems and contexts that shape children’s experiences and health outcomes. In this study, we draw on data from the National Survey of Children’s Health, 2016 to 2021 (n = 182,375 children, ages 3– to 17 years) to examine associations between community social capital and neighborhood resources and children’s internalizing and externalizing problems, and whether these associations were moderated by experiences of racial discrimination. Study outcomes were caregiver-report of current internalizing and externalizing problems. Using logistic regression models adjusted for sociodemographic characteristics of the child and household, higher levels of community social capital were associated with a lower risk of children’s depression, anxiety, and behaviors. Notably, we observed similar associations between neighborhood resources and child mental health for depression only. In models stratified by the child’s experience of racial/ethnic discrimination, the protective benefits of community social capital were specific to those children who did not experience racial discrimination. Our results illustrate heterogeneous associations between community social capital and children’s mental health that differ based on interpersonal experiences of racial/ethnic discrimination, illustrating the importance of a multilevel framework to promote child wellbeing.
Human–environment interactions at Ta'ab Nuk Na, a submerged Maya salt works site in Belize
Authors: Foster Cheryl M. , McKillop Heather , Sills E. Cory
Published: August 2023

Sea-level rise and settlement are investigated at Ta'ab Nuk Na, an ancient Maya salt works in Belize, by examining samples from wooden posts and marine sediment. The samples included Post 145 of Building B and the Nunavut beam, along with marine sediment columns cut from beside both wooden posts. The sediment columns were sampled at 2 cm intervals. Loss-on ignition confirmed the presence of organic material. Identifying the organic content involved removing nonorganic material from the sediment and sorting the organic material under magnification. This procedure established that most of the organic material was red mangrove (Rhizophora mangle). Red mangroves tolerate salt water, but under conditions of sea-level rise, the plants grow vertically to keep their leaves above water. Sediment, leaves, and detritus trapped in the prop roots form mangrove peat, which serves as a proxy for sea-level rise. AMS dating of fine red mangrove roots determined that the local sea levels rose at Ta'ab Nuk Na throughout the Late Classic period and continued into the Postclassic period. Radiocarbon dates obtained from the wood-post samples yielded Late Classic–period dates. Comparing the radiocarbon dates from the wooden posts and the sediment core samples determined that the site was abandoned before the rising seas flooded the area. Evidently, sea-level rise did not play a role in site abandonment.
Evaluation of phenological development and agronomic traits in exotic common bean germplasm across multiple environments
Authors: Basavaraja T. , Tripathi Anupam , Chandora Rahul , Pratap Aditya , Manjuanatha L. , Gurumurthy S. , Singh Mohar , Rana J. C. , Kumar S. D. Nitesh , Katiyar P. K. , Singh Bansa
Published: August 2023

Twenty-nine exotic common bean germplasms and three elite cultivars were examined for phenotypic diversity in two bean-producing environments (Kanpur and Shimla) across three winter seasons and one rainy season. The estimate of genetic variability parameters revealed that the exotic bean germplasm has enough diversity for all the evaluated features. The highest genotypic and phenotypic coefficients of variation were found in seed yield, followed by 100-seed weight, pods per plant and pod length. Furthermore, seed yield was the most heritable and genetically advanced quantitative feature, followed by 100-seed weight, pod length and pods per plant. According to a trait association study, the days to maturity of phenological traits have a strong positive correlation with the days to initial flowering and the days to 50% flowering. Pods per plant and seeds per pod most strongly influence increased grain yield. The first two principal components accounted for 63.3% of the variation and demonstrated significant diversity among exotic bean lines for the traits studied, according to the principal component analysis. According to the hierarchical clustering analysis, 29 accessions and three cultivars were divided into three groups. Cluster I contains early flowering and maturing accessions, while cluster III contains high pods per plant and an increased grain yield of germplasms. The fundamental source of phenological fluctuations in both environmental circumstances is temperature. This study found four genetically divergent and stable performance accessions, including EC932021, EC932189 (earliness), and EC931452, EC931971 (high grain yield), which may aid in the establishment of a bean breeding programme.
Use of narratives to communicate organics with commodity grain farmers
Authors: Zebrowski Wesley , Farmer James , Bruce Analena , Giroux Stacey , Dickinson Stephanie , Chen Xiwei , O'Donnell Michael , Benjamin Tamara
Published: August 2023

While grain farming has seen a major shift toward organic production in recent years, the USA continues to lag behind with domestic demand continuing to outpace domestic supply, making the USA an all-around net importer. The Midwestern USA is poised to help remedy this imbalance; however, farmers continue to slowly transition to organic production systems. Existing literature has identified three prevalent narratives that farmers use to frame their organic transition: environmentalism, farm-family legacy and economic factors, in addition to a four and untested religiosity narrative. This study sought to better understand how these different narratives frame grain farmers’ thought processes for transitioning from conventional production systems to certified organic production systems. We co-created narratives around organic production with farmers, which resulted in four passages aligned with the literature: farm-family legacy, economic values, environmental values and Christianity and stewarding Eden. Then, we mailed a paper survey to conventional, in transition and certified organic Indiana grain farmers in order to test how these different narratives motivated organic production. We found that the most prevalent narrative around organic production is the farm-family legacy, which specifically resonated with midsize farmers. We also found that the religious stewardship narrative resonated with a substantial number of organic and mixed practice farmers, which is likely due to Amish farmers within the sample. These results shed light on the role that narratives and associated values play in organic practice use and can inform the organic efforts of agricultural professionals.
When do voters perceive intra-party conflict? A democratic life cycle perspective
Authors: Klingelhöfer Tristan , Müller Jochen
Published: August 2023

Political parties commonly experience internal disagreements. Recently, evidence is accumulating that outright internal discord makes a party much less attractive to voters. However, we do not understand well when citizens perceive a party to be internally conflicted in the first place. We here explain citizens’ perceptions from a democratic life cycle perspective: Factors related to the periodic conduct of elections induce higher levels of intra-party conflict and make it more visible to citizens. To test this argument, we combine survey data on citizens’ perceptions of political parties in Germany spanning 16 years with indicators moderating (the visibility of) intra-party conflict. The analysis shows that citizens perceive more internal conflict when parties are heterogenous, when they are governing, when election day is distant, and when electoral losses accumulate. This demonstrates the recurring patterns in citizens’ perceptions of political parties and suggests self-reinforcing dynamics between citizen assessments and election outcomes.
Teaching Latin and ancient Greek in the 21st-century Primary School: Framing local approaches to international challenges
Authors: Bracke Evelien
Published: August 2023

The idea for this special issue of Journal of Classics Teaching arose from the conference ‘Monsters in the classroom: Latin and Greek at primary school’ which Steve Hunt (Cambridge), Lidewij Van Gils (Amsterdam), and myself (Ghent) co-organised in January of 2022.1 This conference gathered teaching expertise from eight countries and attracted more than 120 participants from 20 countries to discuss both the successes and challenges related to current international practice in the teaching of Classical languages at primary school. It became a constructive and fruitful event, where participants from different countries shared good practice in order to learn from each other and formulate steps forward.
Designing Vocabulous: a Case Study in Classics, EdTech and English Literacy
Authors: Huelin Lucy
Published: August 2023

This article examines the website Vocabulous, an innovative resource that combines Classics and English literacy. The aim of Vocabulous is to improve students' English vocabulary knowledge and skills using Latin and Greek root patterns. For example, the root ‘scrip’ meaning ‘write’ can help students understand that ‘inscription’, ‘manuscript’ and ‘transcription’ are all related to writing. Students use these roots to work out the meaning of unfamiliar vocabulary, so that by the end of the programme, they have the skills they need to decipher new words on their own. As Alex Quigley notes, ‘over 90% of the vocabulary of academic texts in school has Latin and Greek origins and therefore teaching etymology has positive implications for learning and cracking the academic code of school’ (Quigley, 2018: 71). This article discusses the pedagogy behind the site, the selection of Latin and Greek roots, the design of the questions (based on vocabulary acquisition research) and the use of animated videos to engage students. The article concludes by outlining the current Vocabulous trial with 10–13-year-olds in 50 schools across the UK, combining teacher testimonies with ideas for practical application in the classroom1. Vocabulous is funded by The SHINE Trust and is part of a research trial led by Professor Arlene Holmes-Henderson and Christ Church, Oxford. It will be available for school subscriptions from September 2023.
Simulation of Ground Motion From Finite‐Fault Modeling Incorporating the Influence of Duration
Authors: Dang Pengfei , Cui Jie , Li Yi , Wang Wenbo
Published: August 2023

On 21 May 2021 (local time), an Mw 6.1 earthquake struck the Yangbi County, Yunnan Province, China. The finite fault stochastic simulation approach is usually used to simulate ground motions in high‐frequency band (f > 1 Hz). Model parameters needed for earthquake ground motion simulation mainly include source, path, and site. In the high‐frequency ground motion simulation program widely used in earthquake engineering, the reciprocal of corner frequency is typically used to define the source rise time; however, the complete step‐wise derivation process is unavailable. In deriving the static corner frequency f0, source rise time is typically estimated to be the time required for the rupture to reach 50% of the final location, and the source rise time then can be obtained as 0.27/f0, which is consistent with the hypothesis of corner frequency and rupture velocity, and the correlation and integrity between parameters are established. This study also focuses on the influence of different source rise times and path durations on the simulation results, such as Fourier acceleration spectrum, pseudo‐spectral acceleration, and peak ground acceleration. The results show that the source rise time recommended in this simulation can improve the accuracy of near‐fault ground motion simulations. This study provides suggestions for a reasonable selection of path duration in different engineering applications.
Concepts Toward a Global Mechanistic Mapping of Ocean Carbon Export
Authors: Laurenceau‐Cornec Emmanuel C. , Mongin Mathieu , Trull Thomas W. , Bressac Matthieu , Cavan Emma L. , Bach Lennart T. , Le Moigne Frédéric A. C. , Planchon Frédéric , Boyd Philip W.
Published: August 2023

The gravitational sinking of organic debris from ocean ecosystems is a dominant mechanism of the biological carbon pump (BCP) that regulates the global climate. The fraction of primary production exported downward, the e‐ratio, is an important but poorly constrained BCP metric. In mid‐ and high‐latitude oceans, seasonal and local variations of sinking particle fluxes strongly modulate the e‐ratio. These locally specific e‐ratio variations and their ecological foundations are here encapsulated in the term “export systems” (ES). ES have been partly characterized for a few ocean locations but remain largely ignored over most of the ocean surface. Here, in a fully conceptual approach and with the primary aim to understand rather than to estimate ocean carbon export, we combine biogeochemical (BGC) modeling with satellite observations to map ES at fine spatio‐temporal scales. We identify four plausible ES with distinct e‐ratio seasonalities across mid‐ and high‐latitude oceans. The ES map confirms the outlines of traditional BGC provinces and unveils new boundaries indicating where (and how) the annual relationship between carbon export and production changes markedly. At six sites where ES features can be partially inferred from in situ data, we test our approach and propose key ecological processes driving carbon export. In the light of our findings, a re‐examination of 1,841 field‐based e‐ratios could challenge the conventional wisdom that e‐ratios change strongly with latitude, suggesting a possible seasonal artifact caused by the timing of observations. By deciphering carbon export mechanistically, our conceptual ES map provides timely directions to emergent ocean robotic explorations of the BCP.
Gulf Stream Sea Surface Temperature Anomalies Associated With the Extratropical Transition of North Atlantic Tropical Cyclones
Authors: Jones Evan , Parfitt Rhys , Wing Allison A. , Hart Robert
Published: August 2023

This study investigates Gulf Stream (GS) sea surface temperature (SST) anomalies associated with the extratropical transition (ET) of tropical cyclones (TCs) in the North Atlantic. Composites of western North Atlantic TCs indicate that GS SSTs are warmer, and both large‐ and fine‐scale SST gradients are weaker than average, for TCs that begin the ET process but do not complete it, compared with TCs that do. Further analysis suggests that the associated fine‐scale GS SST gradient anomalies are related to atmospheric processes but not the same as those that are typically associated with the onset of ET. As sensible heat flux gradients and surface diabatic frontogenesis are shown to generally scale with the local SST gradient strength, these results suggest that knowledge of the fine‐scale GS SST gradient in the weeks prior to the arrival of a TC might potentially provide additional information regarding the likelihood of that system completing ET.
Snow Cover on the Tibetan Plateau and Lake Baikal Intensifies the Winter North Atlantic Oscillation
Authors: Zhang Chao , Duan Anmin , Jia XiaoJing , Hu Jun , Liu Shizuo
Published: August 2023

This paper revealed a physical connection between the antiphase variation in the preceding autumn Tibetan Plateau (TP) and Lake Baikal snow cover anomalies (TBSA) and the following winter North Atlantic Oscillation (NAO) on interannual time scales during 1979–2021. The antiphase variation in TBSA, accounting for 44% of the total years, has a dipole structure in autumn, which prolonged into the following winter. The persistent antiphase TBSA associated diabatic forcing, disturbances and transient eddies favor a double wave train structure spanning the TP (east of Baikal) and North Atlantic from autumn to winter. Amid the wave train, the circulation anomalies over the North Atlantic extract more energy from the basic flow due to the seasonal increase in the westerly jet, which further evolves into the winter NAO pattern. Our results provide new insights into the formation and projection of winter NAO from the perspective of subtropical and extratropical Eurasia snow.
Southern Ocean Low Cloud and Precipitation Phase Observed During the Macquarie Island Cloud and Radiation Experiment (MICRE)
Authors: Tansey Emily , Marchand Roger , Alexander Simon P. , Klekociuk Andrew R. , Protat Alain
Published: August 2023

Shallow cloud decks residing in or near the boundary layer cover a large fraction of the Southern Ocean (SO) and play a major role in determining the amount of shortwave radiation reflected back to space from this region. In this article, we examine the macrophysical characteristics and thermodynamic phase of low clouds (tops <3 km) and precipitation using ground‐based ceilometer, depolarization lidar and vertically‐pointing W‐band radar measurements collected during the Macquarie Island Cloud and Radiation Experiment (MICRE) from April 2016 to March 2017. During MICRE, low clouds occurred ∼65% of the time on average (slightly more often in austral winter than summer). About 2/3 of low clouds were cold‐topped (temperatures ≤0°C). These were thicker and had higher bases on average than warm‐topped clouds. 83%–88% of cold‐topped low clouds were liquid phase at cloud base (depending on the season). The majority of low clouds had precipitation in the vertical range 150–250 m below cloud base, a significant fraction of which did not reach the surface. Phase characterization is limited to the period between April 2016 and November 2016. Small‐particle (low‐radar‐reflectivity) precipitation (which dominates precipitation occurrence) was mostly liquid below‐cloud, while large‐particle precipitation (which dominates total accumulation) was predominantly mixed/ambiguous or ice phase. Approximately 40% of cold‐topped clouds had mixed/ambiguous or ice phase precipitation below (with predominantly liquid phase cloud droplets at cloud base). Below‐cloud precipitation with radar reflectivity factors below about −10 dBZ were predominantly liquid, while reflectivity factors above about 0 dBZ were predominantly ice.
Tracing Low‐CO2 Fluxes in Soil Incubation and 13C Labeling Experiments: A Simplified Gas Sampling System for Respiration and Photosynthesis Measurements
Authors: Witzgall K. , Hesse B. D. , Seguel O. , Oses R. , Grams T. E. E. , Mueller C. W.
Published: August 2023

Quantifying carbon dioxide (CO2) fluxes between soil and atmosphere is key in understanding net ecosystem C exchange and biogeochemical C cycling in plant‐soil systems. In ecosystems with low primary production and sparse vegetation, for example, dry lands or subpolar regions where C fluxes are small, measurement sensitivity is key—even so when measurements are combined with isotopic labeling. Here, we present a simplified gas sampling system developed to facilitate sampling and measurement of low soil CO2 fluxes as well as in situ 13CO2 labeling in the same setup. The capacity of the system was tested in a set of feature tests along with gas measurements of dryland soil‐biocrust systems. The system's sensitivity to capture minor changes in CO2 concentration was confirmed in respiration and photosynthesis measurements of soil‐biocrust systems, where fluxes down to 0.1 μmol CO2 m−2 s−1 were quantified. A balloon, implemented to counterbalance underpressure build‐up during gas withdrawal, mitigated 72% of pressure differences at sampling. The overall system volume was reduced to a minimum to limit contamination caused by residual air, and the design enabled one‐step flushing and evacuation of system compartments and gas sample bags, successfully ruling out cross‐contamination between samples. Ultimately, this system offers a flexible and accessible solution for CO2 measurements that can be applied not only on arid soils with low biological activity and turnover rates, but also on plant‐soil systems. The modifications enabled larger, and thereby more representative, sample volumes to be collected while limiting incubation, contamination, and pressure effects on the intact soil system.
Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses
Authors: Banaj Nerisa , Vecchio Daniela , Piras Fabrizio , De Rossi Pietro , Bustillo Juan , Ciufolini Simone , Dazzan Paola , Di Forti Marta , Dickie Erin W. , Ford Judith M. , Fuentes-Claramonte Paola , Gruber Oliver , Guerrero-Pedraza Amalia , Hamilton Holly K. , Howells Fleur M. , Kraemer Bernd , Lawrie Stephen M. , Mathalon Daniel H. , Murray Robin , Pomarol-Clotet Edith , Potkin Steven G. , Preda Adrian , Radua Joaquim , Richter Anja , Salvador Raymond , Sawa Akira , Scheffler Freda , Sim Kang , Spaniel Filip , Stein Dan J. , Temmingh Henk S. , Thomopoulos Sophia I. , Tomecek David , Uhlmann Anne , Voineskos Aristotle , Yang Kun , Jahanshad Neda , Thompson Paul M. , Van Erp Theo G. M. , Turner Jessica A. , Spalletta Gianfranco , Piras Federica
Published: August 2023

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.
Dynorphin / kappa-opioid receptor regulation of excitation-inhibition balance toggles afferent control of prefrontal cortical circuits in a pathway-specific manner
Authors: Yarur Hector E. , Casello Sanne M. , Tsai Valerie S. , Enriquez-Traba Juan , Kore Rufina , Wang Huikun , Arenivar Miguel , Tejeda Hugo A.
Published: August 2023

The medial prefrontal cortex (mPFC) controls behavior via connections with limbic excitatory afferents that engage various inhibitory motifs to shape mPFC circuit function. The dynorphin (Dyn) / kappa-opioid receptor (KOR) system is highly enriched in the mPFC, and its dysregulation is implicated in neuropsychiatric disorders. However, it is unclear how the Dyn / KOR system modulates excitatory and inhibitory circuits that are integral for mPFC information processing and behavioral control. Here, we provide a circuit-based framework wherein mPFC Dyn / KOR signaling regulates excitation-inhibition balance by toggling which afferents drive mPFC neurons. Dyn / KOR regulation of afferent inputs is pathway-specific. Dyn acting on presynaptic KORs inhibits glutamate release from afferent inputs to the mPFC, including the basolateral amygdala (BLA), paraventricular nucleus of the thalamus, and contralateral cortex. The majority of excitatory synapses to mPFC neurons, including those from the ventral hippocampus (VH), do not express presynaptic KOR, rendering them insensitive to Dyn / KOR modulation. Dyn / KOR signaling also suppresses afferent-driven recruitment of specific inhibitory sub-networks, providing a basis for Dyn to disinhibit mPFC circuits. Specifically, Dyn / KOR signaling preferentially suppresses SST interneuron- relative to PV interneuron-mediated inhibition. Selective KOR action on afferents or within mPFC microcircuits gates how distinct limbic inputs drive spiking in mPFC neurons. Presynaptic Dyn / KOR signaling decreases KOR-positive input-driven (e.g. BLA) spiking of mPFC neurons. In contrast, KOR-negative input recruitment of mPFC neurons is enhanced by Dyn / KOR signaling via suppression of mPFC inhibitory microcircuits. Thus, by acting on distinct circuit elements, Dyn / KOR signaling shifts KOR-positive and negative afferent control of mPFC circuits, providing mechanistic insights into the role of neuropeptides in shaping mPFC function. Together, these findings highlight the utility of targeting the mPFC Dyn / KOR system as a means to treat neuropsychiatric disorders characterized by dysregulation in mPFC integration of long-range afferents with local inhibitory microcircuits.
Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix
Authors: Smail Marissa A. , Smith Brittany L. , Shukla Rammohan , Alganem Khaled , Eby Hunter M. , Bollinger Justin L. , Parikh Ria K. , Chambers James B. , Reigle James K. , Moloney Rachel D. , Nawreen Nawshaba , Wohleb Eric S. , Pantazopoulos Harry , McCullumsmith Robert E. , Herman James P.
Published: August 2023

Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats. The basolateral amygdala (BLA) was identified as a region of interest, demonstrating differential Fos responsivity to ER and having an established role in stress processing and adaptation. A comprehensive multi-omics investigation of the BLA, spanning multiple cohorts, platforms, and analyses, revealed alterations in microglia and the extracellular matrix (ECM). Follow-up studies indicated that ER decreased microglia size, complexity, and phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, suggesting decreased plasticity and increased inhibition within the BLA following loss. Behavioral analyses suggest that these molecular effects are linked to impaired BLA salience evaluation, leading to a mismatch between stimulus and reaction intensity. These loss-like behaviors could be rescued by depleting BLA ECM during the removal period, helping us understand the mechanisms underlying loss and revealing novel molecular targets to ameliorate its impact.
SCARB1 in extracellular vesicles promotes NPC metastasis by co-regulating M1 and M2 macrophage function
Authors: Chen Wenhui , Bao Lili , Ren Qianqian , Zhang Zixiang , Yi Lu , Lei Wei , Yang Zhiyuan , Lu Yingna , You Bo , You Yiwen , Gu Miao
Published: August 2023

Distant metastasis is currently the main factor affecting the prognosis of nasopharyngeal carcinoma (NPC), and understanding the mechanisms of metastasis and identifying reliable therapeutic targets are critical for improving prognosis and achieving clinical translation. Macrophages, as important immune cells in the tumor microenvironment (TME), have been shown to regulate metastasis. And extracellular vesicles (EVs) secreted by stromal cells and tumor cells play the important role in intercellular communication in the tumor microenvironment. However, the role of NPC-EVs on macrophages and their function in regulating macrophages to affect metastasis has not been fully clarified. In this study, we report that NPC-EVs can be uptake by macrophages and alter macrophage polarization, for the first time, we identified the genes implicated in these regulatory functions: SCARB1, HAAO, and CYP1B1. Moreover, we found that SCARB1 was positively associated with metastasis and poor prognosis of NPC. Interestingly, we found that SCARB1-rich EVs promoted M1 macrophages ferroptosis to decrease M1 macrophages infiltration by upregulating the HAAO level while decreasing phagocytosis of M2 macrophages by upregulating the CYP1B1 level. Finally, we identified the SCARB1-binding gene KLF9, which is involved in the transcription of HAAO and CYP1B1. Our findings showed that SCARB1-EVs promoted metastasis by co-regulating M1 and M2 macrophage function. The related mechanism will provide a new therapeutic strategy to help patients with NPC improve their prognosis.
Igneous meteorites suggest Aluminium-26 heterogeneity in the early Solar Nebula
Authors: Krestianinov Evgenii , Amelin Yuri , Yin Qing-Zhu , Cary Paige , Huyskens Magdalena H. , Miller Audrey , Dey Supratim , Hibiya Yuki , Tang Haolan , Young Edward D. , Pack Andreas , Di Rocco Tommaso
Published: August 2023

The short-lived radionuclide aluminium-26 (26Al) isotope is a major heat source for early planetary melting. The aluminium-26 – magnesium-26 (26Al-26Mg) decay system also serves as a high-resolution relative chronometer. In both cases, however, it is critical to establish whether 26Al was homogeneously or heterogeneously distributed throughout the solar nebula. Here we report a precise lead-207 – lead-206 (207Pb-206Pb) isotopic age of 4565.56 ± 0.12 million years (Ma) for the andesitic achondrite Erg Chech 002. Our analysis, in conjunction with published 26Al-26Mg data, reveals that the initial 26Al/27Al in the source material of this achondrite was notably higher than in various other well-preserved and precisely dated achondrites. Here we demonstrate that the current data clearly indicate spatial heterogeneity of 26Al by a factor of 3-4 in the precursor molecular cloud or the protoplanetary disk of the Solar System, likely associated with the late infall of stellar materials with freshly synthesized radionuclides.
Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease
Authors: Hoskinson Courtney , Dai Darlene L. Y. , Del Bel Kate L. , Becker Allan B. , Moraes Theo J. , Mandhane Piushkumar J. , Finlay B. Brett , Simons Elinor , Kozyrskyj Anita L. , Azad Meghan B. , Subbarao Padmaja , Petersen Charisse , Turvey Stuart E.
Published: August 2023

Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (βindirect = −2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance
Authors: Rasool Reyaz ur , O’Connor Caitlin M. , Das Chandan Kanta , Alhusayan Mohammed , Verma Brijesh Kumar , Islam Sehbanul , Frohner Ingrid E. , Deng Qu , Mitchell-Velasquez Erick , Sangodkar Jaya , Ahmed Aqila , Linauer Sarah , Mudrak Ingrid , Rainey Jessica , Zawacki Kaitlin P. , Suhan Tahra K. , Callahan Catherine G. , Rebernick Ryan , Natesan Ramakrishnan , Siddiqui Javed , Sauter Guido , Thomas Dafydd , Wang Shaomeng , Taylor Derek J. , Simon Ronald , Cieslik Marcin , Chinnaiyan Arul M. , Busino Luca , Ogris Egon , Narla Goutham , Asangani Irfan A.
Published: August 2023

Loss of the tumor suppressive activity of the protein phosphatase 2A (PP2A) is associated with cancer, but the underlying molecular mechanisms are unclear. PP2A holoenzyme comprises a heterodimeric core, a scaffolding A subunit and a catalytic C subunit, and one of over 20 distinct substrate-directing regulatory B subunits. Methylation of the C subunit regulates PP2A heterotrimerization, affecting B subunit binding and substrate specificity. Here, we report that the leucine carboxy methyltransferase (LCMT1), which methylates the L309 residue of the C subunit, acts as a suppressor of androgen receptor (AR) addicted prostate cancer (PCa). Decreased methyl-PP2A-C levels in prostate tumors is associated with biochemical recurrence and metastasis. Silencing LCMT1 increases AR activity and promotes castration-resistant prostate cancer growth. LCMT1-dependent methyl-sensitive AB56αCme heterotrimers target AR and its critical coactivator MED1 for dephosphorylation, resulting in the eviction of the AR-MED1 complex from chromatin and loss of target gene expression. Mechanistically, LCMT1 is regulated by S6K1-mediated phosphorylation-induced degradation requiring the β-TRCP, leading to acquired resistance to anti-androgens. Finally, feedforward stabilization of LCMT1 by small molecule activator of phosphatase (SMAP) results in attenuation of AR-signaling and tumor growth inhibition in anti-androgen refractory PCa. These findings highlight methyl-PP2A-C as a prognostic marker and that the loss of LCMT1 is a major determinant in AR-addicted PCa, suggesting therapeutic potential for AR degraders or PP2A modulators in prostate cancer treatment.
Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
Authors: Sturm Ádám , Saskői Éva , Hotzi Bernadette , Tarnóci Anna , Barna János , Bodnár Ferenc , Sharma Himani , Kovács Tibor , Ari Eszter , Weinhardt Nóra , Kerepesi Csaba , Perczel András , Ivics Zoltán , Vellai Tibor
Published: August 2023

Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.
γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
Authors: Quintana Juan F. , Sinton Matthew C. , Chandrasegaran Praveena , Lestari Agatha Nabilla , Heslop Rhiannon , Cheaib Bachar , Ogunsola John , Ngoyi Dieudonne Mumba , Kuispond Swar Nono-Raymond , Cooper Anneli , Mabbott Neil A. , Coffelt Seth B. , MacLeod Annette
Published: August 2023

African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.
Functionalization and higher-order organization of liposomes with DNA nanostructures
Authors: Zhang Zhao , Feng Zhaomeng , Zhao Xiaowei , Jean Dominique , Yu Zhiheng , Chapman Edwin R.
Published: August 2023

Small unilamellar vesicles (SUVs) are indispensable model membranes, organelle mimics, and drug and vaccine carriers. However, the lack of robust techniques to functionalize or organize preformed SUVs limits their applications. Here we use DNA nanostructures to coat, cluster, and pattern sub-100-nm liposomes, generating distance-controlled vesicle networks, strings and dimers, among other configurations. The DNA coating also enables attachment of proteins to liposomes, and temporal control of membrane fusion driven by SNARE protein complexes. Such a convenient and versatile method of engineering premade vesicles both structurally and functionally is highly relevant to bottom-up biology and targeted delivery.
Next generation synthetic memory via intercepting recombinase function
Authors: Short Andrew E. , Kim Dowan , Milner Prasaad T. , Wilson Corey J.
Published: August 2023

Here we present a technology to facilitate synthetic memory in a living system via repurposing Transcriptional Programming (i.e., our decision-making technology) parts, to regulate (intercept) recombinase function post-translation. We show that interception synthetic memory can facilitate programmable loss-of-function via site-specific deletion, programmable gain-of-function by way of site-specific inversion, and synthetic memory operations with nested Boolean logical operations. We can expand interception synthetic memory capacity more than 5-fold for a single recombinase, with reconfiguration specificity for multiple sites in parallel. Interception synthetic memory is ~10-times faster than previous generations of recombinase-based memory. We posit that the faster recombination speed of our next-generation memory technology is due to the post-translational regulation of recombinase function. This iteration of synthetic memory is complementary to decision-making via Transcriptional Programming – thus can be used to develop intelligent synthetic biological systems for myriad applications.
Hippocampal subfield vulnerability to α-synuclein pathology precedes neurodegeneration and cognitive dysfunction
Authors: Dues Dylan J. , Nguyen An Phu Tran , Becker Katelyn , Ma Jiyan , Moore Darren J.
Published: August 2023

Cognitive dysfunction is a salient feature of Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). The onset of dementia reflects the spread of Lewy pathology throughout forebrain structures. The mere presence of Lewy pathology, however, provides limited indication of cognitive status. Thus, it remains unclear whether Lewy pathology is the de facto substrate driving cognitive dysfunction in PD and DLB. Through application of α-synuclein fibrils in vivo, we sought to examine the influence of pathologic inclusions on cognition. Following stereotactic injection of α-synuclein fibrils within the mouse forebrain, we measured the burden of α-synuclein pathology at 1-, 3-, and 6-months post-injection within subregions of the hippocampus and cortex. Under this paradigm, the hippocampal CA2/3 subfield was especially susceptible to α-synuclein pathology. Strikingly, we observed a drastic reduction of pathology in the CA2/3 subfield across time-points, consistent with the consolidation of α-synuclein pathology into dense somatic inclusions followed by neurodegeneration. Silver-positive degenerating neurites were observed prior to neuronal loss, suggesting that this might be an early feature of fibril-induced neurotoxicity and a precursor to neurodegeneration. Critically, mice injected with α-synuclein fibrils developed progressive deficits in spatial learning and memory. These findings support that the formation of α-synuclein inclusions in the mouse forebrain precipitate neurodegenerative changes that recapitulate features of Lewy-related cognitive dysfunction.