bluuebunny/crossref_metadata_2025 huggingface dataset:
Art and linguistic bodies: a transformative view
Authors: Finke Ståle , Netland Thomas , Solli Mattias
Published: November 2023

This article takes its point of departure from the second (embodied) linguistic turn represented by the enactivist notion of humans as linguistic bodies, using resources from Hans Georg Gadamer in order to propose a view of the relation between art and everyday experience as one of symbolic transformation. Conceiving art as a form of linguistic phenomenon wherein one can engage in original situations of communication, this view rejects both autonomist and direct continuity views of the art-everyday relation. We start by situating the idea of linguistic bodies within the enactive approach, spelling out relevant aspects concerning the significance of language for human life and perception (Sect. 2). Then we embark on a discussion of aspects of Shaun Gallagher’s and Alva Noë’s enactivist perspectives on art experience, highlighting places where their views align with and depart from ours (Sect. 3). The last two sections aim to lay out the transformative view in more detail, proposing a pluralistic understanding of art media and a view of art and art experience as modes of ideational, embodied thought (Sects. 4 and 5).
Ecotoxicology of Polystyrene Microplastic Fragments: Oxidative Stress Effects in Neonate Versus Adult Daphnia magna
Authors: Esterhuizen Maranda , Lee Sang-Ah , Järvinen Riikka , Kim Youngsam , Pflugmacher Stephan , Kim Young Jun
Published: November 2023

Polystyrene is an inert polymer; however, sublethal effects have been observed in aquatic organisms exposed to microparticles of this plastic. Information on microplastic-related oxidative stress and related antioxidative responses as adverse effects and the underlying mechanisms of toxicity are limited. Daphnids are key contributors in aquatic ecosystems, linking primary producers to consumers and predators, facilitating energy transfer and thus being considered an ideal bioindicator organism to study the adverse effects of polystyrene fragments on the oxidative stress status and subsequent enzymatic antioxidant response. In the present study, neonates (≤ 24 h) and adult daphnids were acutely exposed to polystyrene fragments sieved to three size factions (< 25 µm, 45—63 µm, and 100—500 µm), and adverse effects were evaluated after 24 and 48 h. In adults, larger particles elicited reactive oxygen species by 61%, which was met with elevated superoxide dismutase (17%) and catalase activities (98%), restoring redox homeostasis within 48 h. However, in neonates, the reactive oxygen species increased with exposure to all polystyrene sizes within 24 h, and homeostasis was regained within 48 h without eliciting the enzymatic antioxidant defense. The adverse effects were associated with size fractions that were too large to be consumed, suggesting that leached additives may be involved. Further studies are needed to determine whether nonenzymatic antioxidants were responsible for neutralizing excess reactive oxygen species in neonates.
The Importance of Body Acceptance in Exploring the Relationships of Mindfulness-Based Constructs to Eating Behaviours among Gay and Bisexual Men
Authors: Regan Harvey , Keyte Rebecca , Mantzios Michael , Egan Helen
Published: November 2023

Introduction

Mindfulness and mindfulness-based constructs (e.g. self-compassion and mindful eating) have been negatively associated with problematic eating and body-related issues in general and other specific populations. Exploration of mindfulness-based concepts in relation to problematic eating would provide novel insight into the relationships of these elements among gay and bisexual men. The present research aimed to identify the role of body acceptance in exploring previous relationships between mindfulness-based constructs and eating behaviours.

Methods

Participants completed an online questionnaire, comprising measures assessing mindfulness, self-compassion, mindful eating, body acceptance, grazing, emotional eating, restrained eating and external eating (data collection occurred in 2022). Correlation and further mediation analysis was employed to assess the relationships of these constructs within the present sample (n = 164).

Results

Positive associations between body acceptance and mindfulness-based concepts and negative associations to problematic eating (grazing; emotional, restrained, and external eating) were found within a sample of self-identified gay and bisexual men. Mediation analysis showed the importance of body acceptance in exploring relationships between mindfulness, self-compassion, and mindful eating to grazing, emotional, restrained and external eating.

Conclusions

Findings highlight the importance of body acceptance when considering the development of mindfulness- and/or compassion-based interventions to attenuate problematic eating among gay and bisexual men.

Policy Implications

This research consolidates the importance of mindfulness and related constructs when considering problematic eating, which should be reflected in policy aiming to attenuate unhealthy eating in specific populations.
Technology and Neutrality
Authors: Heyndels Sybren
Published: November 2023

This paper clarifies and answers the following question: is technology morally neutral? It is argued that the debate between proponents and opponents of the Neutrality Thesis depends on different underlying assumptions about the nature of technological artifacts. My central argument centres around the claim that a mere physicalistic vocabulary does not suffice in characterizing technological artifacts as artifacts, and that the concepts of function and intention are necessary to describe technological artifacts at the right level of description. Once this has been established, I demystify talk about the possible value-ladenness of technological artifacts by showing how these values can be empirically identified. I draw from examples in biology and the social sciences to show that there is a non-mysterious sense in which functions and values can be empirically identified. I conclude from this that technology can be value-laden and that its value-ladenness can both derive from the intended functions as well as the harmful non-intended functions of technological artifacts.
Clusters in light nuclei: history and recent developments
Authors: Lombardo Ivano , Dell’Aquila Daniele
Published: November 2023

In this review, we discuss recent advancements in the study of clustering phenomena occurring in light nuclei, and their influence on nuclear structure, dynamics, and astrophysics. In the introduction, we outline the historical steps leading to the concept of$$\alpha $$α-clusterization in nuclei and provide a comprehensive description of the evolution of nuclear models capable to describe clustering aspects in nuclear systems and of the main experiments and discoveries leading to the development of this research field. We also describe some spectroscopic techniques that are used to establish the clustered nature of a given nuclear state. Some relevant experimental and theoretical findings recently reported both in experimental and theoretical works are discussed in the text. We put emphasis on recent achievements and remaining problems in the description of the structure of light isotopes, from helium to neon, including both self- and non-self-conjugate nuclei. Particular attention to the implication in the nuclear astrophysics context and to clustering effects in the dynamics of nuclear reactions is pursued all along the review.
Incoherence, inquiry, and suspension
Authors: McHugh Conor
Published: November 2023

I consider two possible evidentialist responses to Schmidt. According to the first, all of the reason-giving work in the relevant cases is being done by evidence. According to the second, even if the ‘incoherence fact’ sometimes provides a reason, what it provides a reason for is not a doxastic attitude, or at least not one that is an alternative to belief. I argue that the first response is not satisfying, but the second is defensible.
A Concept of Balance of Interest in the Context of Active Assisted Living
Authors: Kuźmicz Maksymilian Michał
Published: November 2023

This paper explores the concept of balancing interests within the context of Active Assisted Living (AAL). AAL technologies hold great promise for addressing the care and support needs of older adults. However, they also raise ethical and social considerations that necessitate a careful balance of interests among various stakeholders. The objective of this study is to comprehensively examine the notion of balance shedding light on its multifaceted dimensions and discuss practical implications for the AAL. Drawing on a thorough literature review and interdisciplinary insights, the research unfolds in three stages. First, it recognizes four key dimensions of balance: equilibrium, avoidance of extremes, proportion, and compromise. Subsequently, the study explores arguments both in favor of and against balancing, addressing issues such as absolute values, methodological concerns, benefits of imbalances, and alternative approaches. This examination offers a comprehensive perspective on the complexities surrounding the concept of balance. Finally, the paper investigates the implications of the conceptual framework within the AAL context, examining what the process of balancing interests could mean from this perspective.
DlMYB113 mutation affects anthocyanin accumulation in red pericarp longan (Dimocarpus longan Lour.)
Authors: Huang Ying-Hua , Liu Li-Qin , Yi De-Bao , Lu Yi-Ying , Zhu Li-Fei , Chen Meng-Ya , Wang Yi-Cheng , Zhou Jian-Nan , Hu Xiao-Wen , Wei Yong-Zan , Shi Sheng-You
Published: November 2023

Fruit color influences fruit quality and commodity value. Most longan (Dimocarpus longan Lour.) varieties have a yellowish-brown or grayish-yellow pericarp, and the discovery of red pericarp (RP) longan expanded the color varieties of longan fruit. Our previous research showed that the red pericarp of RP fruit was mainly caused by anthocyanin accumulation; however, its underlying regulatory mechanism remains unknown. Herein, DlMYB113, an R2R3-MYB transcription factor, was discovered by examining differentially expressed genes in two longan cultivars. Dimocarpus longan MYB (v-myb avian myeloblastosis viral) 113 (DlMYB113) expression was significantly higher in the pericarp and leaves of RP longan than in ‘Shixia’ longan. Sequence alignment analysis revealed two amino acid substitutions in the R3 domain between DlMYB113rp in RP longan and DlMYB113sx in ‘Shixia’ longan. Transient expression of DlMYB113rp significantly increased anthocyanin accumulation in tobacco leaves, whereas DlMYB113sx had negligible effect. Meanwhile, DlMYB113 overexpression promotes anthocyanin accumulation in Arabidopsis and longan calli. Site-directed mutation detection revealed divergence in DlMYB113 function when the R3 repeat 197-position base T was replaced with G, and the 317- and 318-position AT bases were replaced with GA. Our findings indicate that DlMYB113 can regulate anthocyanin production in RP longan, and three mutations in its nucleic acid sequence lead to anthocyanin accumulation, thereby developing molecular markers associated with the anthocyanin accumulation trait in RP longan. This study will facilitate early screening of longan hybrids with desirable fruit color and be significant for breeding new characteristic varieties.
Applying Benford's Law for Assessing the Validity of Social Science Data
Authors: Long Michael A. , Stretesky Paul B. , Berry Kenneth J. , Johnston Janis E. , Lynch Michael J.
Published: November 2023

Benford's Law is a probability distribution for the likelihood of the leading digit in a set of numbers. This book seeks to improve and systematize the use of Benford's Law in the social sciences to assess the validity of self-reported data. The authors first introduce a new measure of conformity to the Benford distribution that is created using permutation statistical methods and employs the concept of statistical agreement. In a switch from a typical Benford application, this book moves away from using Benford's Law to test whether the data conform to the Benford distribution, to using it to draw conclusions about the validity of the data. The concept of 'Benford validity' is developed, which indicates whether a dataset is valid based on comparisons with the Benford distribution and, in relation to this, diagnostic procedure that assesses the impact of not having Benford validity on data analysis is devised.
Self-Reliance and Pig Husbandry in Los Angeles Chinatown (1880–1933): New Evidence from Dental Calculus Analysis and Historical Records
Authors: Wang Jiajing , Ng Laura Wai , Serrao-Leiva Tamara
Published: November 2023

This study explores the pig-raising practices of Chinese migrants in Los Angeles Chinatown during the Chinese Exclusion Era. Chinese butcher shops sold pork meat, and previous research indicates that they likely sold the more profitable parts outside of Chinatown for additional income while consuming cheaper cuts themselves. Using dental calculus analysis and archival research, this study further explores how Chinatown residents relied on pork to thrive in an anti-Chinese environment. Dental calculus results suggest that Chinese migrants raised their own pigs with food waste and by-products from rice fields; this pork was then sold to meat markets or consumed within the community. The analysis of immigration records indicates that Chinese butcher shops provided employment opportunities as well as housing, banking, and immigration support for Chinese migrants. Pig raising, therefore, not only supplied a source of meat for Chinese migrants but also supported a range of social and financial services for a marginalized group that faced everyday discrimination from dominant society. Overall, this study traces the labor and networks that small businesses in the late nineteenth and early twentieth centuries needed to source and distribute pork, and it highlights how a Chinese diasporic community developed a pork production system to resist racism.
Public Health Response Measures for COVID-19 in Kazakhstan
Authors: Battakova Zhamilya , Imasheva Bagdat , Slazhneva Tatyana , Imashev Marat , Beloussov Vyacheslav , Pignatelli Massimo , Tursynkhan Aigerim , Askarov Albert , Abdrakhmanova Shynar , Adayeva Assel , Akimbayeva Anara , Suleimanova Natalya
Published: November 2023

The article describes measures developed to counter the spread of coronavirus infection in the Republic of Kazakhstan. The first cases of coronavirus disease 2019 (COVID-19) in Kazakhstan were detected on March 13, 2020, among people who arrived from Germany. After declaring the state of emergency in the country, the Ministry of Healthcare of the Republic of Kazakhstan began to formulate and implement a comprehensive package of measures aimed at slowing down and stopping the transmission of infection, preventing outbreaks, ensuring optimal care for all patients, especially the seriously ill, minimizing the negative impact of the pandemic on health systems, social services, and economic activities. Developed set of restrictive measures was approved by the Country Office of Word Health Organization (WHO) in Kazakhstan, being later adapted by the European Union (EU) countries and applied in Kyrgyzstan. In addition, article identifies Kazakhstan’s experience in creating epidemiological surveillance systems, studying virus mutations, and the clinical aspects of dealing with it to combat the infection. It also indicates the impact of the epidemic on health-care workers and the development of measures to protect them, strengthening infection prevention, and control in medical organizations.
Prevalence and contributing factors of anaemia among children aged 6–24 months and 25–59 months in Mali
Authors: Gebreegziabher Tafere , Sidibe Saran
Published: November 2023

Although considerable global initiatives have been undertaken to tackle anaemia, its prevalence continues to be high in sub-Saharan African nations. In Mali specifically, anaemia represents a significant and pressing public health issue. The purpose of the present study was to examine the key risk factors related to anaemia among children aged 6–24 months (younger age group) and 25–59 months (older age group). We used the Mali 2018 Demographic and Health Survey data, collected from 8861 mothers with children under five. Logistic regression was used to assess the risk factors for childhood anaemia. The results suggest that the prevalence of anaemia was 88 % in the younger and 76 % in the older age groups. The risk factors unique to the younger age group were malaria (OR 4⋅05; CI 0⋅95, 11⋅3) and place of residence (OR 0⋅55; CI 0⋅32, 0⋅94), while for the older age group, they were morbidity (OR 1⋅91; CI 1⋅12, 3⋅24), drinking from a bottle (OR 1⋅52; CI 1⋅04, 2⋅22), and micronutrient intake (OR 0⋅61; CI 0⋅40, 0⋅91). Risk factors that significantly contributed to both age groups include breastfeeding, deworming, maternal anaemia, maternal education, and wealth index. Anaemia also varied by region. The widespread prevalence of anaemia can be attributed to a multitude of factors. In addressing this issue, it is imperative to acknowledge the unique characteristics of specific regions and rural areas, where the incidence of anaemia surpasses the national average. Therefore, any intervention efforts should be tailored to the specific needs and challenges of these areas.
Changing Capitalist Structures and Settler-Colonial Land Purchases in Northern Palestine, 1897–1922
Authors: Alff Kristen
Published: November 2023

By tracing Zionist and German Templer efforts to buy arable private property in Palestine between 1897 and 1922, I show the ways in which the changing balance of Ottoman and Levantine forces over land and labor—as well as political and economic institutions and social structures—facilitated settler-colonialism in northern Palestine. In this article, I examine official records of the Ottoman state, Jewish organizations, and Levantine, Jewish, and Templer real estate papers. I argue that changing capitalist practices in northern Palestine, driven especially by interactions of Beirut-based companies with the changing global capitalist market, facilitated settler-colonialism in the region. Specifically, Ottoman state-sponsored violence during World War I increased peasant dispossessions in the fertile region of northern Palestine, already in progress since at least the mid-19th century, making settler colonies possible.
‘Circles of Women’: Feminist Movements in the Choreography of Oona Doherty
Authors: HILL SHONAGH
Published: November 2023

The focus of this article is the range of feminisms which circulate through Belfast-based Oona Doherty's choreographies for groups of women, namely the second episode of Hard to Be Soft: A Belfast Prayer (2017), which is titled ‘Sugar Army', and Lady Magma: The Birth of a Cult (2019). This analysis is motivated by the need to expand discussion of feminisms in tandem with examination of more complex identities in Northern Ireland: to look beyond a Nationalist–Unionist binary within post-conflict society and examine the intersections of gender, class and race. Tracking the movement of feminisms through Doherty's choreographies will explore how they mobilize, and fail, these women, as well as revealing the potential for, and pitfalls of, community and solidarity. Doherty's work has the potential to mobilize a dynamic intergenerational and intersectional feminism which recognizes the experiences of ‘differently positioned women’.
Global international relations and the essentialism trap
Authors: Barnett Michael , Zarakol Ayşe
Published: November 2023

Global IR is an encompassing term for a range of work that has set out to globalize the discipline in terms of its core concepts, assumptions, and substantive areas of study. Our symposium supports Global IR's goals but also offers some friendly critiques of the project with the aim of increasing its impact and durability. In this Introduction to the symposium, we posit that Global IR is vulnerable to a dynamic that limits its capacity to upend the status quo, which we term the ‘essentialism trap’. Essentialism captures a range of commitments oriented around the notion that the world is constituted by pre-formed, fixed, internally coherent, and bounded social forms. The trap involves the overuse of essentialist categories by radical projects, a process that can result in the reinforcement of status quo categories and assumptions. With reference to previous openings in IR that have succumbed to this trap, we identify the dynamics that lead to this trap and suggest ways in which Global IR can avoid it by leaning more into relationalism and global history, and, thereby, fulfil the promise contained in the range of movements it speaks with and for.
It Is Time to Develop Sustainable Management of Agricultural Sulfur
Authors: Gerson Jacqueline R. , Hinckley Eve‐Lyn S.
Published: November 2023

Globally, sulfur (S) applications to croplands result in S inputs that often exceed historical atmospheric deposition. Sulfur is applied to crops as a fertilizer, fungicide, soil conditioner, pH regulator, and carrier for other elements. However, excess S in soils and aquatic ecosystems can have detrimental ecological and biogeochemical consequences, including soil base cation depletion, surface water acidification, hydrogen sulfide toxicity, and increased production of methyl mercury. The dichotomy between S benefits to crops and environmental consequences parallels that of nitrogen and phosphorus; however, there has not yet been a focus on developing sustainable S management plans in agriculture. We review the current literature on S cycling in agricultural systems and propose solutions that reduce S inputs, losses, and ecological consequences, including field applications of organic matter, adaptation of precision agriculture, and implementation of total maximum daily loads. We suggest opportunities for technological innovation, including analysis of remote sensing imagery to identify location and timing of S deficiencies and stresses, crop genetic modification to reduce S requirements, inoculation of plants with arbuscular mycorrhizal fungi to enhance plant S acquisition, and remediation of wetlands and other anoxic environments with high S loads. We conclude with areas for continued research on S biogeochemistry.
Impact of Urban Representation on Simulation of Hurricane Rainfall
Authors: Patel Pratiman , Ankur Kumar , Jamshidi Sajad , Tiwari Alka , Nadimpalli Raghu , Busireddy N. K. R. , Safaee Samira , Osuri Krishna K. , Karmakar Subhankar , Ghosh Subimal , Aliaga Daniel , Smith James , Marks Frank , Yang Zong‐Liang , Niyogi Dev
Published: November 2023

Taking the examples of Hurricane Florence (2018) over the Carolinas and Hurricane Harvey (2017) over the Texas Gulf Coast, the study attempts to understand the performance of slab, single‐layer Urban Canopy Model (UCM), and Building Environment Parameterization (BEP) in simulating hurricane rainfall using the Weather Research and Forecasting (WRF) model. The WRF model simulations showed that for an intense, large‐scale event such as a hurricane, the model quantitative precipitation forecast over the urban domain was sensitive to the model urban physics. The spatial and temporal verification using the modified Kling‐Gupta efficiency and Method for Object based Diagnostic and Evaluation in Time Domain suggests that UCM performance is superior to the BEP scheme. Additionally, using the BEP urban physics scheme over UCM for landfalling hurricane rainfall simulations has helped simulate heavy rainfall hotspots.
A Reappraisal of Subtropical Subsurface Water Ice Stability on Mars
Authors: Lange L. , Forget F. , Vincendon M. , Spiga A. , Vos E. , Aharonson O. , Millour E. , Bierjon A. , Vandemeulebrouck R.
Published: November 2023

Massive reservoirs of subsurface water ice in equilibrium with atmospheric water vapor are found poleward of 45° latitude on Mars. The absence of CO2 frost on steep pole‐facing slopes and simulations of atmospheric‐soil water exchanges suggested that water ice could be stable underneath these slopes down to 25° latitude. We revisit these arguments with a new slope microclimate model. Our model shows that below 30° latitude, slopes are warmer than previously estimated as the air above is heated by warm surrounding plains. This additional heat prevents the formation of surface CO2 frost and subsurface water ice for most slopes. Our model suggests the presence of subsurface water ice beneath pole‐facing slopes down to 30° latitude, and possibly 25° latitude on sparse steep dusty slopes. While unstable ice deposits might be present, our results suggest that water ice is rarer than previously thought in the ±30° latitude range considered for human exploration.
Divergent mechanisms of reduced growth performance in Betula ermanii saplings from high-altitude and low-latitude range edges
Authors: Aihara Takaki , Araki Kyoko , Onuma Yunosuke , Cai Yihan , Paing Aye Myat Myat , Goto Susumu , Hisamoto Yoko , Tomaru Nobuhiro , Homma Kosuke , Takagi Masahiro , Yoshida Toshiya , Iio Atsuhiro , Nagamatsu Dai , Kobayashi Hajime , Hirota Mitsuru , Uchiyama Kentaro , Tsumura Yoshihiko
Published: November 2023

The reduced growth performance of individuals from range edges is a common phenomenon in various taxa, and considered to be an evolutionary factor that limits the species’ range. However, most studies did not distinguish between two mechanisms that can lead to this reduction: genetic load and adaptive selection to harsh conditions. To address this lack of understanding, we investigated the climatic and genetic factors underlying the growth performance of Betula ermanii saplings transplanted from 11 populations including high-altitude edge and low-latitude edge population. We estimated the climatic position of the populations within the overall B. ermanii’s distribution, and the genetic composition and diversity using restriction-site associated DNA sequencing, and measured survival, growth rates and individual size of the saplings. The high-altitude edge population (APW) was located below the 95% significance interval for the mean annual temperature range, but did not show any distinctive genetic characteristics. In contrast, the low-latitude edge population (SHK) exhibited a high level of linkage disequilibrium, low genetic diversity, a distinct genetic composition from the other populations, and a high relatedness coefficient. Both APW and SHK saplings displayed lower survival rates, heights and diameters, while SHK saplings also exhibited lower growth rates than the other populations’ saplings. The low heights and diameters of APW saplings was likely the result of adaptive selection to harsh conditions, while the low survival and growth rates of SHK saplings was likely the result of genetic load. Our findings shed light on the mechanisms underlying the reduced growth performance of range-edge populations.
NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing
Authors: Feng Wei , Beer Joanne C. , Hao Qinyu , Ariyapala Ishara S. , Sahajan Aparna , Komarov Andrei , Cha Katie , Moua Mason , Qiu Xiaolei , Xu Xiaomei , Iyengar Shweta , Yoshimura Thu , Nagaraj Rajini , Wang Li , Yu Ming , Engel Kate , Zhen Lucas , Xue Wen , Lee Chen-jung , Park Chan Ho , Peng Cheng , Zhang Kaiyuan , Grzybowski Adrian , Hahm Johnnie , Schmidt Susanne V. , Odainic Alexandru , Spitzer Jasper , Buddika Kasun , Kuo Dwight , Fang Lei , Zhang Bingqing , Chen Steve , Latz Eicke , Yin Yiyuan , Luo Yuling , Ma Xiao-Jun
Published: November 2023

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.
A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process
Authors: Liao Ruiqi , Babatunde Abiola , Qiu Stephanie , Harikumar Hamsini , Coon Joshua J. , Overmyer Katherine A. , Hannun Yusuf A. , Luberto Chiara , Bresnick Emery H.
Published: November 2023

Transcriptional mechanisms controlling developmental processes establish and maintain proteomic networks, which can govern the levels of intracellular small molecules. Although dynamic changes in bioactive small molecules can link transcription factor and genome activity with cell state transitions, many mechanistic questions are unresolved. Using quantitative lipidomics and multiomics, we discover that the hematopoietic transcription factor GATA1 establishes ceramide homeostasis during erythroid differentiation by regulating genes encoding sphingolipid metabolic enzymes. Inhibiting a GATA1-induced sphingolipid biosynthetic enzyme, delta(4)-desaturase, or disrupting ceramide homeostasis with cell-permeable dihydroceramide or ceramide is detrimental to erythroid, but not myeloid, progenitor activity. Coupled with genetic editing-based rewiring of the regulatory circuitry, we demonstrate that ceramide homeostasis commissions vital stem cell factor and erythropoietin signaling by opposing an inhibitory protein phosphatase 2A-dependent, dual-component mechanism. Integrating bioactive lipids as essential components of GATA factor mechanisms to control cell state transitions has implications for diverse cell and tissue types.
EASTR: Identifying and eliminating systematic alignment errors in multi-exon genes
Authors: Shinder Ida , Hu Richard , Ji Hyun Joo , Chao Kuan-Hao , Pertea Mihaela
Published: November 2023

Accurate alignment of transcribed RNA to reference genomes is a critical step in the analysis of gene expression, which in turn has broad applications in biomedical research and in the basic sciences. We reveal that widely used splice-aware aligners, such as STAR and HISAT2, can introduce erroneous spliced alignments between repeated sequences, leading to the inclusion of falsely spliced transcripts in RNA-seq experiments. In some cases, the ‘phantom’ introns resulting from these errors make their way into widely-used genome annotation databases. To address this issue, we present EASTR (Emending Alignments of Spliced Transcript Reads), a software tool that detects and removes falsely spliced alignments or transcripts from alignment and annotation files. EASTR improves the accuracy of spliced alignments across diverse species, including human, maize, and Arabidopsis thaliana, by detecting sequence similarity between intron-flanking regions. We demonstrate that applying EASTR before transcript assembly substantially reduces false positive introns, exons, and transcripts, improving the overall accuracy of assembled transcripts. Additionally, we show that EASTR’s application to reference annotation databases can detect and correct likely cases of mis-annotated transcripts.
Reconciling Southern Ocean fronts equatorward migration with minor Antarctic ice volume change during Miocene cooling
Authors: Hou Suning , Stap Lennert B. , Paul Ryan , Nelissen Mei , Hoem Frida S. , Ziegler Martin , Sluijs Appy , Sangiorgi Francesca , Bijl Peter K.
Published: November 2023

Gradual climate cooling and CO2 decline in the Miocene were recently shown not to be associated with major ice volume expansion, challenging a fundamental paradigm in the functioning of the Antarctic cryosphere. Here, we explore Miocene ice-ocean-climate interactions by presenting a multi-proxy reconstruction of subtropical front migration, bottom water temperature and global ice volume change, using dinoflagellate cyst biogeography, benthic foraminiferal clumped isotopes from offshore Tasmania. We report an equatorward frontal migration and strengthening, concurrent with surface and deep ocean cooling but absence of ice volume change in the mid–late-Miocene. To reconcile these counterintuitive findings, we argue based on new ice sheet modelling that the Antarctic ice sheet progressively lowered in height while expanding seawards, to maintain a stable volume. This can be achieved with rigorous intervention in model precipitation regimes on Antarctica and ice-induced ocean cooling and requires rethinking the interactions between ice, ocean and climate.
Stepwise taming of triplet excitons via multiple confinements in intrinsic polymers for long-lived room-temperature phosphorescence
Authors: Gao Liang , Huang Jiayue , Qu Lunjun , Chen Xiaohong , Zhu Ying , Li Chen , Tian Quanchi , Zhao Yanli , Yang Chaolong
Published: November 2023

Polymeric materials exhibiting room temperature phosphorescence (RTP) show a promising application potential. However, the conventional ways of preparing such materials are mainly focused on doping, which may suffer from phase separation, poor compatibility, and lack of effective methods to promote intersystem crossing and suppress the nonradiative deactivation rates. Herein, we present an intrinsically polymeric RTP system producing long-lived phosphorescence, high quantum yields and multiple colors by stepwise structural confinement to tame triplet excitons. In this strategy, the performance of the materials is improved in two aspects simultaneously: the phosphorescence lifetime of one polymer (9VA-B) increased more than 4 orders of magnitude, and the maximum phosphorescence quantum yield reached 16.04% in halogen-free polymers. Moreover, crack detection is realized by penetrating steam through the materials exposed to humid surroundings as a special quenching effect, and the information storage is carried out by employing the Morse code and the variations in lifetimes. This study provides a different strategy for constructing intrinsically polymeric RTP materials toward targeted applications.
Co-option of a non-retroviral endogenous viral element in planthoppers
Authors: Huang Hai-Jian , Li Yi-Yuan , Ye Zhuang-Xin , Li Li-Li , Hu Qing-Ling , He Yu-Juan , Qi Yu-Hua , Zhang Yan , Li Ting , Lu Gang , Mao Qian-Zhuo , Zhuo Ji-Chong , Lu Jia-Bao , Xu Zhong-Tian , Sun Zong-Tao , Yan Fei , Chen Jian-Ping , Zhang Chuan-Xi , Li Jun-Min
Published: November 2023

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.
MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis
Authors: Llorente Alicia , Blasco María Teresa , Espuny Irene , Guiu Marc , Ballaré Cecilia , Blanco Enrique , Caballé Adrià , Bellmunt Anna , Salvador Fernando , Morales Andrea , Nuñez Marc , Loren Guillem , Imbastari Francesca , Fidalgo Marta , Figueras-Puig Cristina , Gibler Patrizia , Graupera Mariona , Monteiro Freddy , Riera Antoni , Holen Ingunn , Avgustinova Alexandra , Di Croce Luciano , Gomis Roger R.
Published: November 2023

MAF amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER+) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
Most large structural variants in cancer genomes can be detected without long reads
Authors: Choo Zi-Ning , Behr Julie M. , Deshpande Aditya , Hadi Kevin , Yao Xiaotong , Tian Huasong , Takai Kaori , Zakusilo George , Rosiene Joel , Da Cruz Paula Arnaud , Weigelt Britta , Setton Jeremy , Riaz Nadeem , Powell Simon N. , Busam Klaus , Shoushtari Alexander N. , Ariyan Charlotte , Reis-Filho Jorge , de Lange Titia , Imieliński Marcin
Published: November 2023

Short-read sequencing is the workhorse of cancer genomics yet is thought to miss many structural variants (SVs), particularly large chromosomal alterations. To characterize missing SVs in short-read whole genomes, we analyzed ‘loose ends’—local violations of mass balance between adjacent DNA segments. In the landscape of loose ends across 1,330 high-purity cancer whole genomes, most large (>10-kb) clonal SVs were fully resolved by short reads in the 87% of the human genome where copy number could be reliably measured. Some loose ends represent neotelomeres, which we propose as a hallmark of the alternative lengthening of telomeres phenotype. These pan-cancer findings were confirmed by long-molecule profiles of 38 breast cancer and melanoma cases. Our results indicate that aberrant homologous recombination is unlikely to drive the majority of large cancer SVs. Furthermore, analysis of mass balance in short-read whole genome data provides a surprisingly complete picture of cancer chromosomal structure.
Topological analysis of sharp-wave ripple waveforms reveals input mechanisms behind feature variations
Authors: Sebastian Enrique R. , Quintanilla Juan P. , Sánchez-Aguilera Alberto , Esparza Julio , Cid Elena , de la Prida Liset M.
Published: November 2023

The reactivation of experience-based neural activity patterns in the hippocampus is crucial for learning and memory. These reactivation patterns and their associated sharp-wave ripples (SWRs) are highly variable. However, this variability is missed by commonly used spectral methods. Here, we use topological and dimensionality reduction techniques to analyze the waveform of ripples recorded at the pyramidal layer of CA1. We show that SWR waveforms distribute along a continuum in a low-dimensional space, which conveys information about the underlying layer-specific synaptic inputs. A decoder trained in this space successfully links individual ripples with their expected sinks and sources, demonstrating how physiological mechanisms shape SWR variability. Furthermore, we found that SWR waveforms segregated differently during wakefulness and sleep before and after a series of cognitive tasks, with striking effects of novelty and learning. Our results thus highlight how the topological analysis of ripple waveforms enables a deeper physiological understanding of SWRs.
Transcriptionally defined amygdala subpopulations play distinct roles in innate social behaviors
Authors: Lischinsky Julieta E. , Yin Luping , Shi Chenxi , Prakash Nandkishore , Burke Jared , Shekaran Govind , Grba Maria , Corbin Joshua G. , Lin Dayu
Published: November 2023

Social behaviors are innate and supported by dedicated neural circuits, but the molecular identities of these circuits and how they are established developmentally and shaped by experience remain unclear. Here we show that medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages have distinct response patterns and functions in social behavior in male mice. MeA cells expressing the transcription factor Foxp2 (MeAFoxp2) are specialized for processing male conspecific cues and are essential for adult inter-male aggression. By contrast, MeA cells derived from the Dbx1 lineage (MeADbx1) respond broadly to social cues, respond strongly during ejaculation and are not essential for male aggression. Furthermore, MeAFoxp2 and MeADbx1 cells show differential anatomical and functional connectivity. Altogether, our results suggest a developmentally hardwired aggression circuit at the MeA level and a lineage-based circuit organization by which a cell’s embryonic transcription factor profile determines its social information representation and behavioral relevance during adulthood.
Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor
Authors: Noddings Chari M. , Johnson Jill L. , Agard David A.
Published: November 2023

Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of ‘client’ proteins, including the glucocorticoid receptor (GR). Previously, we revealed that Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding, aided by co-chaperones. In vivo, the co-chaperones FKBP51 and FKBP52 antagonistically regulate GR activity, but a molecular understanding is lacking. Here we present a 3.01 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP52 complex, revealing how FKBP52 integrates into the GR chaperone cycle and directly binds to the active client, potentiating GR activity in vitro and in vivo. We also present a 3.23 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP51 complex, revealing how FKBP51 competes with FKBP52 for GR:Hsp90 binding and demonstrating how FKBP51 can act as a potent antagonist to FKBP52. Altogether, we demonstrate how FKBP51 and FKBP52 integrate into the GR chaperone cycle to advance GR to the next stage of maturation.
ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma
Authors: Ran Longyan , Mou Xiao , Peng Zhenglin , Li Xiaochen , Li Meirong , Xu Duo , Yang Zixi , Sun Xingwang , Yin Tao
Published: November 2023

The third most often diagnosed disease globally and the second most prevalent cause of cancer-related death is colorectal cancer (CRC). Numerous human malignancies have been identified to have high expression of ADORA2A. However, it is still ambiguous about its function in CRC. RNA-seq with stable transfected SETDB1 knockdown cells was used to identify differentially expressed genes. Further, knockdown of ADORA2A in CRC cell lines SW620 and HCT116 was performed with siRNA and over expression of ADORA2A in SW480 cells was conducted with plasmids. CCK8, colony formation, wound healing, and transwell assay were used to detect the effects of cell proliferation, migration, and invasion after knockdown and over expression of ADORA2A. Also, apoptosis was analyzed by flow cytometry, apoptosis-related proteins and key PI3K/AKT pathway proteins were detected using Western blotting. ADORA2A was identified after RNA-seq analysis and played an important role in CRC prognosis. ADORA2A was relatively high in SW620 and HCT116 cell lines compared to SW480 cell lines. ADORA2A knockdown in SW620 and HCT116 inhibited cell proliferation, migration, and invasion, while ADORA2A overexpression had the opposite effect. In addition, ADORA2A also impacted the expression of apoptosis-related proteins, including Bcl-2, Bax, Cleaved caspase-3 and Cleaved caspase-9, and reduced apoptosis. Furthermore, this process may include the PI3K/AKT signaling pathway. ADORA2A promotes CRC progression and inhibits apoptosis by the PI3K/AKT signaling pathway. It may contribute to the management and treatment of CRC.
Antiproliferative effects of D-allose associated with reduced cell division frequency in glioblastoma
Authors: Suzuki Kenta , Ogawa Daisuke , Kanda Takahiro , Fujimori Takeshi , Shibayama Yuki , Rahman Asadur , Ye Juanjuan , Ohsaki Hiroyuki , Akimitsu Kazuya , Izumori Ken , Tamiya Takashi , Nishiyama Akira , Miyake Keisuke
Published: November 2023

Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3–50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.
Identification of a bile acid and bile salt metabolism-related lncRNA signature for predicting prognosis and treatment response in hepatocellular carcinoma
Authors: Cui Hao , Lian Jia , Xu Baiguo , Yu Zhenjun , Xiang Huiling , Shi Jingxiang , Gao Yingtang , Han Tao
Published: November 2023

Bile acids and salts have been shown to play a role in liver carcinogenesis through DNA damage, inflammation, and tumor proliferation. However, the correlation between bile acid metabolism and hepatocellular carcinoma (HCC) prognosis remains unclear. This study aimed to identify a predictive signature of bile acid and bile salt metabolism-related long non-coding RNAs (lncRNAs) for HCC prognosis and treatment response. The study used HCC RNA-sequencing data and corresponding clinical and prognostic data from The Cancer Genome Atlas. A prognostic model consisting of five bile acid and bile salt metabolism-related lncRNAs was developed and evaluated in a training set, a validation set and an external set. The model demonstrated good performance in predicting HCC prognosis and was shown to be an independent biomarker for prognosis. Additionally, our study revealed a significant association between the signature and immune cell infiltration, as well as its predictive value for therapeutic responses to both immunotherapy and chemotherapy. Furthermore, three LncRNAs (LUCAT1, AL031985.3 and AC015908.3) expression levels in our signature were validated through qRT-PCR in a cohort of 50 pairs of HCC patient tumor samples and corresponding adjacent non-tumor samples, along with 10 samples of normal liver tissue adjacent to benign lesions. These findings suggest that this novel bile acid and bile salt metabolism-related lncRNA signature can independently predict the prognosis of patients with HCC and may be utilized as a potential predictor of response to treatment in this setting.