bluuebunny/crossref_metadata_2025 huggingface dataset:
First evaluation of genetic diversity among honeybee populations in Kazakhstan
Authors: Gritsenko Dilyara , Temirbayeva Kamshat , Taskuzhina Aisha , Kostyukova Valeriya , Pozharskiy Alexandr , Kolchenko Mariya , Khusnitdinova Marina , Krupskiy Oleg , Mayer Andrey , Nuralieva Ulzhan , Moldakhmetova Gaukhar
Published: December 2023

Beekeeping as a staple of agriculture in Kazakhstan is believed to have emerged when external bee colonies were introduced into the country. To date, six subspecies have been distributed across commercial apiaries (Apis mellifera sossimai, A. m. carpatica, A. m. mellifera, A. m. ligustica, A. m. caucasica, and A. m. carnica). In this study, we analyzed mitochondrial DNA from 21 geographically distinct populations with diverse subspecies composition and discovered 19 unique haplotypes belonging to C and M evolutionary lineages. Analysis of 9 microsatellite loci revealed strong polymorphism, with a range of 5 to 35 alleles at each locus. The observed heterozygosity across the populations varied from 0.2892 to 0.9099, and clustering analysis only allowed differentiation of each population based on its geographical location. High degree of admixture among subspecies was identified in every population, including a potential introgression from the endemic bee A. m. pomonella. Unregulated cross-breeding for the past 50 years has laid the foundation for the promiscuous genetic nature of honeybee populations in Kazakhstan.
Encouraging Young Women into STEM Careers: A Study Comparing Career Intention of Female STEM Students in China and Scotland
Authors: McNeill Fiona , Wei Linyi
Published: December 2023

Women are underrepresented in the science, technology, engineering, and mathematics (STEM) workforce. Whilst this is a worldwide phenomenon, there are differences in how this manifests in different countries. In order to understand this more deeply in a particular context, this study investigates the employment intentions of university STEM students in Scotland and China, analysing and comparing the intentions and the reasons behind them affecting young women in the two regions. The data represented 747 students from the University of Edinburgh, a large Scottish university, and Nankai University, a large Chinese university. The data showed that women are less likely to enter STEM careers than their male peers in both regions. In general we found that women in China had more hesitations about entering STEM careers than women in Scotland, but that Chinese women studying in Scotland had more similar responses to Chinese women studying in China than they did to other women studying in Scotland. Following an initial questionnaire, a semi-structured interview was designed to explore why the factors that affect women in different regions differed. Finally, combining the results of the quantitative and qualitative research, a number of recommendations are made that could encourage more young women into STEM careers.
Dry Fractionation of Plant-Based Proteins for Better Meat Analogue Applications
Authors: Hopf Andreas , Dehghani Fariba , Buckow Roman
Published: December 2023

Purpose of Review

With the increasing global demand for protein, there is a critical need to make nutritious and cost-effective protein from alternative sources widely accessible. Dry fractionation emerges as a promising technology for producing sustainable, protein-rich raw materials from plants such as pulses. This paper offers an overview of recent advancements in the extrusion of dry-fractionated plant proteins (DFPPs) for applications in meat analogues.

Recent Findings

Fibrous meat analogues can be produced from plant-based proteins through both high- and low-moisture extrusion processes. Dry-fractionated pulse proteins, which are products with high protein content (exceeding 70%), can be utilised either independently or blended with protein isolates or other ingredients. However, it is important to note that dry-fractionated protein can have adverse effects on the colour, sensory characteristics, and textural properties of the extruded products. Consequently, adjustments in extruder parameters are necessary to create fibrous materials incorporating DFPPs effectively.

This review article provides insights into technologies employed for protein extraction, options for enhancing their functional and sensory properties (including addressing beany tastes), and various techniques developed to achieve a fibrous and meat-like texture.
Na5YSi4O12 fast ion conductor protection layer enabled dendrite-free Zn metal anode
Authors: Xu Ningbo , Yuan Chenbo , Sun Ge , Chen Nan , Yao Shiyu , Du Fei
Published: December 2023

Aqueous zinc-ion batteries (AZIBs) are promising for future large-scale energy storage systems, however, suffer from inferior cycling life due to the dendrites growth and side reaction on Zn metal anode. Herein, a fast ion conductor Na5YSi4O12 (NYSO) was synthesized and fabricated as a protection layer of the Zn metal anode. By adjusting the thickness, an optimized NYSO coating of 20.3 µm was obtained and the corresponding symmetry cell demonstrates an extended life span of 1896 h at the current density of 0.5 mA cm−2. In addition, a favorable rate performance of the NYSO@Zn anode at a high current density of 10 mA cm−2 was achieved. Benefiting from the NYSO coating, uniform diffusion and deposition of Zn2+ on the Zn anode could be realized, leading to the elimination of Zn dendrites and side reactions. Therefore, the aqueous NYSO@Zn|CNT@MnO2 full cell shows superior capacity and cycling stability to that of the bare Zn full cell.
Impact of RegTech on compliance risk due to financial misconduct in the United States banking industry
Authors: Jeyasingh Benita Bommi Felicia
Published: December 2023

Financial misconduct is a growing issue in the financial sector, leading to increased regulations. The increased need to comply with these regulations preceded the need for regulatory technology. Regulatory technology (RegTech) helps the financial industry comply with regulations. This study aims to identify regulatory technology’s impact on financial misconduct within the United States banking industry. This study uses an evidence-based approach to help make informed decisions on adopting regulatory technology to control financial misconduct. The researcher used the qualitative, Rapid Evidence Assessment methodology to find ten articles (quantitative and qualitative), critically appraise, code, and synthesize them to provide findings and recommendations to the United States banking industry, regulatory agencies, and regulatory technology solution providers. Data from the Financial Industry Regulatory Authority annual reports and Financial Crime Enforcement statistics helped triangulate the findings from the evidence synthesis to increase the study's validity. The results indicated that the adoption of RegTech provided advanced risk assessment and monitoring capabilities that increased compliance with regulations, minimized financial misconduct, and improved the stability and profitability of the United States banking system though it introduced information privacy risk.
Principles, challenges, and advances in ribosome profiling: from bulk to low-input and single-cell analysis
Authors: Wang Qiuyi , Mao Yuanhui
Published: December 2023

Ribosome profiling has revolutionized our understanding of gene expression regulation by providing a snapshot of global translation in vivo. This powerful technique enables the investigation of the dynamics of translation initiation, elongation, and termination, and has provided insights into the regulation of protein synthesis under various conditions. Despite its widespread adoption, challenges persist in obtaining high-quality ribosome profiling data. In this review, we discuss the fundamental principles of ribosome profiling and related methodologies, including selective ribosome profiling and translation complex profiling. We also delve into quality control to assess the reliability of ribosome profiling datasets, and the efforts to improve data quality by modifying the standard procedures. Additionally, we highlight recent advancements in ribosome profiling that enable the transition from bulk to low-input and single-cell applications. Single-cell ribosome profiling has emerged as a crucial tool for exploring translation heterogeneity within specific cell populations. However, the challenges of capturing mRNAs efficiently and the sparse nature of footprint reads in single-cell ribosome profiling present ongoing obstacles. The need to refine ribosome profiling techniques remains, especially when used at the single-cell level.
History as capture
Authors: Hamid Sarah T.
Published: December 2023

Myth, hype and industry-captured historiographies of AI, machine learning and computing depict the current moment as a unique and unprecedented confrontation with computational power, paying particular attention to the devastating effects this has on vulnerable communities (better: communities made vulnerable). But automated decision schemes are neither new nor newly urgent; they are the inheritance of almost seventy years of computing history, a history that has never not been entangled with state repression, genocidal and ecocidal violence and racialized expropriation. Carceralilty and artificial intelligence have a shared history, and the entanglements between them remain underappreciated by history writing on computing – despite the near-universal injunction to leverage history as a means to critique and counteract the cultural hegemony of computing. This paper examines some of the tensions underlying such calls for historical critique, calling into question the efficacy of such a project. I offer a study of the complex senses of history and development at work in the 2006 International Congress of Mathematics, discuss recent historiographies of computing (and science) from guild historians, and describe the ways academic history writing reproduces the same relations of dominance and campaigns of creation and conservation that scaffold mathematics and artificial intelligence.
Institutional Logics: Motivating Action and Overcoming Resistance to Change
Authors: Haveman Heather A. , Joseph-Goteiner David , Li Danyang
Published: December 2023

Institutional logics are interrelated sets of cultural elements (norms, values, beliefs, and symbols) that help people and organizations make sense of their everyday activities and order those activities in time and space. In this paper, we describe the rise of a robust literature on institutional logics, which mostly focuses on Western societies. We then describe changes in Chinese society and economy over the past four decades, as it shifted from state-controlled planning and redistribution to market-mediated exchange. We detail how the institutional logics that guide Chinese firms have been transformed in the wake of the economic transition. The state logic, which developed in the Maoist era, valorizes equality, national community, and political stability. Although it is still in evidence, it has been partly supplanted by a market logic that encourages efficiency, competition, and property rights. But this market logic differs from the one that prevails in Western capitalist economies. The Chinese version of the market logic valorizes the central role that the state and the Communist Party continue to play in economic life. Therefore, in the Chinese version of the market logic, efficiency, competition, and property rights are tempered by a continued concern for political stability. We review and summarize the existing literature on institutional logics and Chinese firms, and then identify fruitful lines that future research could take.
HOW TO EXTEND CLOSURE AND INTERIOR OPERATIONS TO MORE MODULES
Authors: EPSTEIN NEIL , R. G. REBECCA , VASSILEV JANET
Published: December 2023

There are several ways to convert a closure or interior operation to a different operation that has particular desirable properties. In this paper, we axiomatize three ways to do so, drawing on disparate examples from the literature, including tight closure, basically full closure, and various versions of integral closure. In doing so, we explore several such desirable properties, including hereditary, residual, and cofunctorial, and see how they interact with other properties such as the finitistic property.
Evolutionary Transitions in Individuality and Life Cycle Closure
Authors: Doulcier Guilhem , Takacs Peter , Bourrat Pierrick
Published: December 2023

We propose a novel account of evolutionary transitions in individuality as life cycle closure: that is, the emergence of a new embedding life cycle. To characterize this process, we show how the life trajectory of lower-level entities (e.g., cells) can be coarse-grained into classes of a higher-level entity. We argue that only higher-level entities displaying two necessary conditions for the existence of a life cycle (e.g., multicellular organisms) have achieved life cycle closure. Throughout, we illustrate our point with stage-structured demographic models that yield a rigorous characterization of the conditions for life cycle closure.
Minority Reports: Registering Dissent in Science
Authors: Dang Haixin
Published: December 2023

Consensus reporting is valuable for presenting unified scientific evidence to the public. When a consensus does not exist, I argue that scientists ought not to default to majority reporting in its place. Majority reporting has several epistemic drawbacks because it can obscure underlying justifications and lines of evidence, which may be in conflict or contested. I argue that minority reporting, in conjunction with majority reporting, is an epistemically superior mechanism for scientists to report on the full range of reasons and evidence available within a group. This article addresses several objections, including worries over group cohesion, fringe reporting, and elite capture.
Limitations of precipitation reconstructions using equilibrium-line altitudes exemplified for former glaciers in the Southern Black Forest, Central Europe
Authors: Hofmann Felix Martin , Steiner Martin , Hergarten Stefan ,   ASTER Team, Preusser Frank
Published: December 2023

To further elucidate the Late Pleistocene glacial history of mid-elevation mountainous regions in Central Europe, 10Be cosmic-ray exposure (CRE) dating was applied to moraines in the Zastler Tal Valley in the Southern Black Forest. Periods of glacier recession from moraines in this valley began no later than 16 ka, 15 ka, and 13 ka. CRE ages of moraines in this and other parts of the Southern Black Forest cluster around 17–16 ka and 15–14 ka, thus suggesting a common forcing of glacier recession. Equilibrium-line altitudes (ELAs) during moraine formation were calculated for precipitation reconstruction. Observed spatial discrepancies in ELAs at ca. 15–14 ka are explained best by the size of snow-contributing areas. The reconstructed annual precipitation at the ELA for ca. 16 ka and ca. 15 ka is affected by large uncertainties, representing a wide range from ~50% to ~150% of present-day values. Due to various factors, such as drifting snow, the lower bounds of the estimates appear most realistic, thus concurring with the common hypothesis of less precipitation during the last glacial termination than today in Central Europe. Further research is needed before ELAs of small ice masses can be employed for precise precipitation estimates.
Why are international standards not set? Explaining “weak” cases in shadow banking regulation
Authors: James Scott , Quaglia Lucia
Published: December 2023

Why are international regulatory standards not set? While most of the literature focuses on explaining positive cases of standard-setting where international rules are agreed upon, weak or negative cases remain prevalent and yet surprisingly under-explored. To explain these cases in the area of financial services, we integrate an inter-state explanation, which focuses on competition between major jurisdictions, with a transgovernmental explanation, which relates to conflict between different regulatory bodies at the international level. We also consider how these dimensions interact with financial industry lobbying. This allows us to construct a typology differentiating between distinct types of cases concerning international standard-setting: (1) absent standards, (2) non-agreed standards, (3) symbolic standards, and (4) agreed standards. The explanatory leverage of our approach is illustrated through a systematic structured focused comparison of four post-crisis cases related to “shadow banking.” The article generates novel insights into regulatory conflicts and the scope conditions for international agreement.
The relevance of electrocardiogram filtering in the differential diagnosis of Brugada syndrome: An illustrative case report
Authors: Baena-Palomino Carlos , Castellano-Martínez Ana , Rodríguez-González Moisés
Published: December 2023

We present a clinical case of a teenager in whom a Brugada syndrome electrical pattern was found which was finally diagnosed as a Brugada phenocopy due to a wrong setup of the high-pass filter on the electrocardiogram
The Impact of Professional Training in Public and Policy Engagement
Authors: Tama Jordan , Rublee Maria Rost , Urban Kathryn
Published: December 2023

Engaging with audiences and communities beyond academia is now a common practice for political scientists. Yet, political scientists rarely are trained in how to conduct public or policy engagement, and we know little about the impact that training programs have on their preparedness to communicate with the public and policy makers. In this study, we evaluate whether professional training equips scholars with the skills needed to perform public and policy outreach. We find that a four-day training program generates remarkably large increases in the number of participants reporting that they possess high levels of knowledge, preparation, and confidence for public and policy engagement. This finding suggests that investments in public-engagement training by universities and the discipline of political science have the potential to significantly boost public outreach by faculty members.
Performing the Post-Anthropocene
Authors: van Heerden Imke , Duman Çağdaş , Bas Anil
Published: December 2023

Promoted as the first theatrical play written by artificial intelligence, AI: When a Robot Writes a Play (2021) anticipates the post-Anthropocene in both content and form. The machine-generated script problematizes the necessity of human (including dramatic) activities and invites exploration of theatre’s role in the post-anthropocentric condition. AI renders the stage as a transitional site—a potential gateway to other realities.
Cost and affordability of healthy diets in Vietnam
Authors: Van Duong TT , Herforth Anna W , Trinh Huong T , Dao Binh TT , Do Ha TP , Talsma Elise F , Feskens Edith JM
Published: December 2023

Objectives:

To estimate the cost and affordability of healthy diets recommended by the 2016–2020 Vietnamese food-based dietary guidelines (FBDG).

Design:

Cross-sectional analysis. The Cost of a Healthy Diet (CoHD) indicator was used to estimate the lowest cost of healthy diets and compare the cost differences by food group, region and seasonality. The affordability of healthy diets was measured by further comparing the CoHD to food expenditures and incomes.

Setting:

Food prices of 176 food items from January 2016 to December 2020 were derived using data from monthly Consumer Price Index databases nationally and regionally.

Participants:

Food expenditures and incomes of participants from three latest Vietnam Household Living Standard Surveys were used.

Results:

The average CoHD between 2016 and 2020 in Vietnam was 3·08 international dollars using 2017 Purchasing Power Parity (24 070 Vietnamese Dongs). The nutrient-rich food groups, including protein-rich foods, vegetables, fruits and dairy, comprised approximately 80 % of the total CoHD in all regions, with dairy accounting for the largest proportion. Between 2016 and 2020, the cheapest form of a healthy diet was affordable for all high-income and upper-middle-income households but unaffordable for approximately 70 % of low-income households, where adherence to the Vietnamese FBDG can cost up to 70 % of their income.

Conclusions:

Interventions in local food systems must be implemented to reduce the cost of nutrient-rich foods to support the attainment of healthier diets in the Vietnamese population, especially for low-income households.
Untangling the Uncertainties in Plant Water Source Partitioning With Isotopes
Authors: Gai Haoqi , Shi Peijun , Li Zhi
Published: December 2023

Plant water source partitioning suffers from multiple uncertainty sources including tracers, depleted xylem water deuterium, and mixing models, but the uncertainties have rarely been systematically evaluated. Taking apple trees of different ages as example, we combined four tracers of different characteristics (2H, 3H, 17O, and 18O), two xylem water deuterium bias correction methods (soil water excess and stem relative water content), and four mixing models (IsoSource, SIAR, MixSIR, and MixSIAR) to quantify the total uncertainty and the uncertainty of each component. For the total uncertainty, the contributions of the mixing models were the largest (37%), followed by those of tracers (28%) and interaction of tracers and models (27%), while the contributions of other sources were the smallest (8%). In particular, the xylem water deuterium bias correction methods had an uncertainty of 2%, implying its minor role in deviating plant water source partitioning. After evaluating the performance of the three components with four target functions, we recommend tracer combination of 2H18O with MixSIAR as the best framework for water source partitioning of apple trees on the Loess Plateau. The decomposed uncertainties and recommended methods provide technical support and promote understanding of variable results in plant water source partitioning.
A Tectonic Manifesto
Authors: Stern Robert , Gerya Taras , Tackley Paul
Published: December 2023

Tectonics is the scientific discipline that studies the relationship between planetary convection and surface deformation and magmatism. In recent years global tectonic regimes and planetary evolution have become foci of astronomical and planetological research dealing in particular with potential habitability of planets orbiting other stars in our galaxy (exoplanets). This broadens the scientific impact of “tectonics” and makes it useful to outline a few guiding principles. For many, the term “tectonics” is synonymous with Plate Tectonics on Earth, but it should not be limited to only the planet we know best. Specifically, the concept should be generalized to encompass other rocky planets and moons in our Solar System and exoplanets. This article summarizes 15 general concepts about how such bodies are expected to behave.
Revealing the Key Drivers Conducive to the “Once‐In‐A‐Century” 2021 Peninsular Malaysia Flood
Authors: Dong Luojie , Wang Jingyu , Zhi Xiefei , Park Edward , Wang Xianfeng , Yim Steve Hung‐Lam , Zhang Hugh , Lee Joshua , Tran Dung Duc
Published: December 2023

In December 2021, Super Typhoon Rai caused significant devastation to the South Philippines and East Malaysia. In the meantime, an unprecedented flood event occurred in Peninsular Malaysia at 2,000 km west of the typhoon's path, causing comparable socioeconomic impacts as Rai. Record‐breaking 3‐day precipitation was received by Peninsular Malaysia during 16–18 December. Based on the storm tracking results, this study identified two mesoscale convective systems (MCSs) that were directly responsible for the flooding. The two MCSs were directly initiated by a tropical depression and sustained by an elongated easterly water vapor corridor originating from the Super Typhoon Rai. The return period and joint frequency analysis of key drivers indicate that the 3‐day downpour was more severe than a “once‐in‐a‐century” event. Historical records suggest such anomalous moisture channel has become more frequent in Southeast Asia, which alarms heightened attention in forecasting winter flood.
Local Time Variations of Ionospheric F Layer Radial Current in Response to Enhanced Solar Wind Input
Authors: Zhong Yunfang , Wang Hui , Lühr Hermann , Zhang Kedeng , Xia Hao , Qian Chengyu , Wang Chengzhi , Sun Yu
Published: December 2023

Using Challenging Minisatellite Payload and the Republic of China Satellite‐1 observations, the response of ionospheric radial current (IRC) in the F region to the enhancement of merging electric field (Em) at different magnetic local times (MLT) is investigated. Possible physical mechanisms are discussed in terms of neutral wind, conductivity, and prompt penetration electric field (PPEF). The disturbance IRC (ΔIRC) increases in the upward (downward) direction in the daytime (nighttime) within 3 hr after Em enhancement. However, disturbance zonal winds increase westward (eastward) at 12–18 MLT (00–06 MLT). The reduced F region electron density may help weaken IRC at 06–12 MLT and 18–24 MLT. This work indicates that the daytime eastward (nighttime westward) PPEF drives equatorward (poleward) Hall current (JH) at low latitudes, resulting in both upward (downward) ΔIRC and eastward (westward) plasma drift at the F region magnetic equator.
Microbial underdogs: exploring the significance of low-abundance commensals in host-microbe interactions
Authors: Han Geongoo , Vaishnava Shipra
Published: December 2023

Our understanding of host-microbe interactions has broadened through numerous studies over the past decades. However, most investigations primarily focus on the dominant members within ecosystems while neglecting low-abundance microorganisms. Moreover, laboratory animals usually do not have microorganisms beyond bacteria. The phenotypes observed in laboratory animals, including the immune system, have displayed notable discrepancies when compared to real-world observations due to the diverse microbial community in natural environments. Interestingly, recent studies have unveiled the beneficial roles played by low-abundance microorganisms. Despite their rarity, these keystone taxa play a pivotal role in shaping the microbial composition and fulfilling specific functions in the host. Consequently, understanding low-abundance microorganisms has become imperative to unravel true commensalism. In this review, we provide a comprehensive overview of important findings on how low-abundance commensal microorganisms, including low-abundance bacteria, fungi, archaea, and protozoa, interact with the host and contribute to host phenotypes, with emphasis on the immune system. Indeed, low-abundance microorganisms play vital roles in the development of the host’s immune system, influence disease status, and play a key role in shaping microbial communities in specific niches. Understanding the roles of low-abundance microbes is important and will lead to a better understanding of the true host-microbe relationships.
Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss
Authors: Tran Thanh-Tam , Lee Gyuseok , Huh Yun Hyun , Chung Ki-Ho , Lee Sun Young , Park Ka Hyon , Kwon Seung Hee , Kook Min-Suk , Chun Jang-Soo , Koh Jeong-Tae , Ryu Je-Hwang
Published: December 2023

Oral diseases exhibit a significant association with metabolic syndrome, including dyslipidemia. However, direct evidence supporting this relationship is lacking, and the involvement of cholesterol metabolism in the pathogenesis of periodontitis (PD) has yet to be determined. In this study, we showed that high cholesterol caused periodontal inflammation in mice. Cholesterol homeostasis in human gingival fibroblasts was disrupted by enhanced uptake through C-X-C motif chemokine ligand 16 (CXCL16), upregulation of cholesterol hydroxylase (CH25H), and the production of 25-hydroxycholesterol (an oxysterol metabolite of CH25H). Retinoid-related orphan receptor α (RORα) mediated the transcriptional upregulation of inflammatory mediators; consequently, PD pathogenesis mechanisms, including alveolar bone loss, were stimulated. Our collective data provided direct evidence that hyperlipidemia is a risk factor for PD and supported that inhibition of the CXCL16-CH25H-RORα axis is a potential treatment mechanism for PD as a systemic disorder manifestation.
Spatiotemporal characterization of glial cell activation in an Alzheimer’s disease model by spatially resolved transcriptomics
Authors: Choi Hongyoon , Lee Eun Ji , Shin Jin Seop , Kim Hyun , Bae Sungwoo , Choi Yoori , Lee Dong Soo
Published: December 2023

The molecular changes that occur with the progression of Alzheimer’s disease (AD) are well known, but an understanding of the spatiotemporal heterogeneity of changes in the brain is lacking. Here, we investigated the spatially resolved transcriptome in a 5XFAD AD model at different ages to understand regional changes at the molecular level. Spatially resolved transcriptomic data were obtained from 5XFAD AD models and age-matched control mice. Differentially expressed genes were identified using spots clustered by anatomical structures. Gene signatures of activation of microglia and astrocytes were calculated and mapped on the spatially resolved transcriptomic data. We identified early alterations in the white matter (WM) of the AD model before the definite accumulation of amyloid plaques in the gray matter (GM). Changes in the early stage of the disease involved primarily glial cell activation in the WM, whereas the changes in the later stage of pathology were prominent in the GM. We confirmed that disease-associated microglia (DAM) and astrocyte (DAA) signatures also showed initial changes in WM and that activation spreads to GM. Trajectory inference using microglial gene sets revealed the subdivision of DAMs with different spatial patterns. Taken together, these results help to understand the spatiotemporal changes associated with reactive glial cells as a major pathophysiological characteristic of AD. The heterogeneous spatial molecular changes apply to identifying diagnostic and therapeutic targets caused by amyloid accumulation in AD.
Precise base editing without unintended indels in human cells and mouse primary myoblasts
Authors: Yoon Da Eun , Kim Na-Rae , Park Soo-Ji , Jeong Tae Yeong , Eun Bokkee , Cho Yongcheol , Lim Soo-Yeon , Lee Hyunji , Seong Je Kyoung , Kim Kyoungmi
Published: December 2023

Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications.
Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota–HIF1a/PTBP1 pathway
Authors: Xuan Lihui , Xu Zheng , Luo Jinhua , Wang Yin , Yan Yuhui , Qu Can , Xie Zuozhong , Skonieczna Magdalena , Zhou Ping-Kun , Huang Ruixue
Published: December 2023

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut–lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50–100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial–mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.
Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function
Authors: Li Xiaoyan , Jiang Yiyang , Liu Xu , Fu Jingfei , Du Juan , Luo Zhenhua , Xu Junji , Bhawal Ujjal Kumar , Liu Yi , Guo Lijia
Published: December 2023

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.
AURKAIP1 actuates tumor progression through stabilizing DDX5 in triple negative breast cancer
Authors: Tian Wenwen , Tang Yuhui , Luo Yongzhou , Xie Jindong , Zheng Shaoquan , Zou Yutian , Huang Xiaojia , Wu Linyu , Zhang Junsheng , Sun Yuying , Tang Hailin , Du Wei , Li Xing , Xie Xiaoming
Published: December 2023

Aurora-A kinase interacting protein 1 (AURKAIP1) has been proved to take an intermediary role in cancer by functioning as a negative regulator of Aurora-A kinase. However, it remains unclear whether and how AURKAIP1 itself would directly engage in regulating malignancies. The expression levels of AURKAIP1 were detected in triple negative breast cancer (TNBC) by immunohistochemistry and western blots. The CCK8, colony formation assays and nude mouse model were conducted to determine cell proliferation whereas transwell and wound healing assays were performed to observe cell migration. The interaction of AURKAIP1 and DEAD-box helicase 5 (DDX5) were verified through co-immunoprecipitation and successively western blots. From the results, we found that AURKAIP1 was explicitly upregulated in TNBC, which was positively associated with tumor size, lymph node metastases, pathological stage and unfavorable prognosis. AURKAIP1 silencing markedly inhibited TNBC cell proliferation and migration in vitro and in vivo. AURKAIP1 directly interacted with and stabilized DDX5 protein by preventing ubiquitination and degradation, and DDX5 overexpression successfully reversed proliferation inhibition induced by knockdown of AURKAIP1. Consequently, AURKAIP1 silencing suppressed the activity of Wnt/β-catenin signaling in a DDX5-dependent manner. Our study may primarily disclose the molecular mechanism by which AURKAIP1/DDX5/β-catenin axis modulated TNBC progression, indicating that AURKAIP1 might serve as a therapeutic target as well as a TNBC-specific biomarker for prognosis.
Neutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children
Authors: Bellusci Lorenza , Grubbs Gabrielle , Sait Shaimaa , Yonker Lael M. , Randolph Adrienne G. , Novak Tanya , Kobayashi Takuma ,   Overcoming COVID−19 Investigators, Khurana Surender
Published: December 2023

Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5–11, 12–21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children.
Haplotype-based inference of recent effective population size in modern and ancient DNA samples
Authors: Fournier Romain , Tsangalidou Zoi , Reich David , Palamara Pier Francesco
Published: December 2023

Individuals sharing recent ancestors are likely to co-inherit large identical-by-descent (IBD) genomic regions. The distribution of these IBD segments in a population may be used to reconstruct past demographic events such as effective population size variation, but accurate IBD detection is difficult in ancient DNA data and in underrepresented populations with limited reference data. In this work, we introduce an accurate method for inferring effective population size variation during the past ~2000 years in both modern and ancient DNA data, called HapNe. HapNe infers recent population size fluctuations using either IBD sharing (HapNe-IBD) or linkage disequilibrium (HapNe-LD), which does not require phasing and can be computed in low coverage data, including data sets with heterogeneous sampling times. HapNe shows improved accuracy in a range of simulated demographic scenarios compared to currently available methods for IBD-based and LD-based inference of recent effective population size, while requiring fewer computational resources. We apply HapNe to several modern populations from the 1,000 Genomes Project, the UK Biobank, the Allen Ancient DNA Resource, and recently published samples from Iron Age Britain, detecting multiple instances of recent effective population size variation across these groups.
Spatial transcriptomics deconvolution at single-cell resolution using Redeconve
Authors: Zhou Zixiang , Zhong Yunshan , Zhang Zemin , Ren Xianwen
Published: December 2023

Computational deconvolution with single-cell RNA sequencing data as reference is pivotal to interpreting spatial transcriptomics data, but the current methods are limited to cell-type resolution. Here we present Redeconve, an algorithm to deconvolute spatial transcriptomics data at single-cell resolution, enabling interpretation of spatial transcriptomics data with thousands of nuanced cell states. We benchmark Redeconve with the state-of-the-art algorithms on diverse spatial transcriptomics platforms and datasets and demonstrate the superiority of Redeconve in terms of accuracy, resolution, robustness, and speed. Application to a human pancreatic cancer dataset reveals cancer-clone-specific T cell infiltration, and application to lymph node samples identifies differential cytotoxic T cells between IgA+ and IgG+ spots, providing novel insights into tumor immunology and the regulatory mechanisms underlying antibody class switch.
Two-dimensional heavy fermion in a monoatomic-layer Kondo lattice YbCu2
Authors: Nakamura Takuto , Sugihara Hiroki , Chen Yitong , Yukawa Ryu , Ohtsubo Yoshiyuki , Tanaka Kiyohisa , Kitamura Miho , Kumigashira Hiroshi , Kimura Shin-ichi
Published: December 2023

The Kondo effect between localized f-electrons and conductive carriers leads to exotic physical phenomena. Among them, heavy-fermion (HF) systems, in which massive effective carriers appear due to the Kondo effect, have fascinated many researchers. Dimensionality is also an important characteristic of the HF system, especially because it is strongly related to quantum criticality. However, the realization of the perfect two-dimensional (2D) HF materials is still a challenging topic. Here, we report the surface electronic structure of the monoatomic-layer Kondo lattice YbCu2 on a Cu(111) surface observed by synchrotron-based angle-resolved photoemission spectroscopy. The 2D conducting band and the Yb 4f state, located very close to the Fermi level, are observed. These bands are hybridized at low-temperature, forming the 2D HF state, with an evaluated coherence temperature of about 30 K. The effective mass of the 2D state is enhanced by a factor of 100 by the development of the HF state. Furthermore, clear evidence of the hybridization gap formation in the temperature dependence of the Kondo-resonance peak has been observed below the coherence temperature. Our study provides a new candidate as an ideal 2D HF material for understanding the Kondo effect at low dimensions.
Early warning signals have limited applicability to empirical lake data
Authors: O’Brien Duncan A. , Deb Smita , Gal Gideon , Thackeray Stephen J. , Dutta Partha S. , Matsuzaki Shin-ichiro S. , May Linda , Clements Christopher F.
Published: December 2023

Research aimed at identifying indicators of persistent abrupt shifts in ecological communities, a.k.a regime shifts, has led to the development of a suite of early warning signals (EWSs). As these often perform inaccurately when applied to real-world observational data, it remains unclear whether critical transitions are the dominant mechanism of regime shifts and, if so, which EWS methods can predict them. Here, using multi-trophic planktonic data on multiple lakes from around the world, we classify both lake dynamics and the reliability of classic and second generation EWSs methods to predict whole-ecosystem change. We find few instances of critical transitions, with different trophic levels often expressing different forms of abrupt change. The ability to predict this change is highly processing dependant, with most indicators not performing better than chance, multivariate EWSs being weakly superior to univariate, and a recent machine learning model performing poorly. Our results suggest that predictive ecology should start to move away from the concept of critical transitions, developing methods suitable for predicting resilience loss not limited to the strict bounds of bifurcation theory.
Charge-4e superconductivity and chiral metal in 45°-twisted bilayer cuprates and related bilayers
Authors: Liu Yu-Bo , Zhou Jing , Wu Congjun , Yang Fan
Published: December 2023

The material realization of charge-4e/6e superconductivity (SC) is a big challenge. Here, we propose to realize charge-4e SC in maximally-twisted homobilayers, such as 45∘-twisted bilayer cuprates and 30∘-twisted bilayer graphene, referred to as twist-bilayer quasicrystals (TB-QC). When each monolayer hosts a pairing state with the largest pairing angular momentum, previous studies have found that the second-order interlayer Josephson coupling would drive chiral topological SC (TSC) in the TB-QC. Here we propose that, above the Tc of the chiral TSC, either charge-4e SC or chiral metal can arise as vestigial phases, depending on the ordering of the total- and relative-pairing-phase fields of the two layers. Based on a thorough symmetry analysis to get the low-energy effective Hamiltonian, we conduct a combined renormalization-group and Monte-Carlo study and obtain the phase diagram, which includes the charge-4e SC and chiral metal phases.
Vertical tearing of subducting plates controlled by geometry and rheology of oceanic plates
Authors: Chen Yaguang , Chen Hanlin , Liu Mingqi , Gerya Taras
Published: December 2023

Lateral non-uniform subduction is impacted by continuous plate segmentation owing to vertical tearing of the subducting plate. However, the dynamics and physical controls of vertical tearing remain controversial. Here, we employed 3D numerical models to investigate the effects of trench geometry (offset by a transform boundary) and plate rheology (plate age and the magnitude of brittle/plastic strain weakening) on the evolution of shear stress-controlled vertical tearing within a homogenous subducting oceanic plate. Numerical results suggest that the trench offset geometry could result in self-sustained vertical tearing as a narrow shear zone within the intact subducting oceanic plate, and that this process of tearing could operate throughout the entire subduction process. Further, the critical trench offset length for the maturation of vertical tearing is impacted by plate rheology. Comparison between numerical modelling results and natural observations suggests that vertical tearing attributed to trench offset geometry is broadly developed in modern subduction and collision systems worldwide.