bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of ACEs: From coping behaviors to epigenetics as explanatory frameworks for the biology of adverse childhood experiences
Authors: Müller Ruth , Kenney Martha
Published: October 2024

Adverse childhood experiences (ACEs) have become a topic of public and scientific attention. ACEs denote a range of negative experiences in early life, from sexual abuse to emotional neglect, that are thought to impact health over the life course. The term was coined in the CDC-Kaiser ACE Study, an epidemiological study that surveyed 17,421 adults about ACEs and correlated the responses with participants’ current health records. Shortly after the study was published in 1998, the US CDC deemed ACEs an important public health target; however, it is only recently that ACEs feature prominently in scientific and public discourses. We contend that this rise in popularity is linked to the adoption of epigenetic explanations for how ACEs affect health. Based on a literature analysis, we trace the evolution of explanatory frameworks for ACEs—from coping behaviors to allostatic load to epigenetics—and analyze how each of these explanations not only reconsiders the mechanisms by which ACEs affect health, but also who should be held responsible for addressing ACEs and how. Epigenetics provides distinctly different discursive possibilities than previous frameworks: firstly, it offers one distinct molecular mechanism for how ACEs work, lending “molecular credibility” to epidemiological findings; secondly, it raises the possibility of reversing the negative effects of ACEs on the biological level. This epigenetic articulation makes ACEs attractive for new actors in science and society. Particularly, it facilitates novel interdisciplinary collaborations and attracts actors in health advocacy who are interested in non-deterministic readings of ACEs that counteract stigma and support positive health interventions and healing.
Communication with Health Personnel and Human Rights: A Perspective from People with Mental Disorders
Authors: Agudelo-Hernández Felipe , Guapacha-Montoya Marcela , Rojas-Andrade Rodrigo , Acuña Mejía Paula Andrea
Published: October 2024

Mental health care has focused on participation, which, in addition to improving recovery processes, constitutes a tool to defend the human rights of people with mental disorders. For this participation, communication is a fundamental element. The objective of the present research was to analyzed the perception of the human rights and communication with healthcare personnel in care processes, from leaders of mutual aid groups or support groups in various contexts of Colombia. It is expected that the generated information can contribute to the evaluation of the quality of mental health services from a human rights and health participation perspective, in contexts similar to the one being analyzed. A qualitative approach has been used, which takes information from six leaders of support groups for mental health, in four regions of Colombia. Said information was analyzed through a thematic analysis, contrasting with the vision of the researchers and with the current theory. It is found that the subject of communication was made up of categories such as Previous ineffective treatments and Perception of a violation of dignity. Communication barriers are pointed out, such as attitudes of mental health professionals, but the influence that the health system and social and political barriers can have on the same communication is recognized. From the perception of leaders of mental health support groups, it is concluded that it is necessary to improve aspects of communication in health personnel. In addition, clinical mental health care could also be a space for the promotion of human rights.
»Haltungsfigur«
Authors: Hoffmann Torsten
Published: October 2024

Auf keinen anderen zeitgenössischen Schriftsteller beruft sich die Neue Rechte so emphatisch wie auf Botho Strauß und dessen Essay Anschwellender Bocksgesang (1993). Der Beitrag geht der Frage nach, welche Funktionsstelle Strauß in der neurechten Literaturpolitik des 21. Jahrhunderts zugewiesen wird. Zu beobachten ist, dass Strauß und sein Essay (I.) metapolitisch, (II.) zur Absicherung der eigenen Intellektualität, (III.) für interne Flügelkämpfe und (IV.) ästhetisch genutzt werden. All das kulminiert in einer Strauß zugewiesenen ›Haltungsfigur‹, die von zentraler Bedeutung für das Selbstverständnis der gegenwärtigen Neuen Rechten ist.
Computational approaches and the epistemology of scholarly editing
Authors: Cugliana Elisa , Ward Aengus , van Zundert Joris J. , Kuczera Andreas , Grüntgens Max
Published: October 2024

Digital Scholarly Editing has followed a fundamentally conservative model over the last forty years. As a result, the epistemological advantages of digital possibilities have not yet been fully explored. The current article proposes that alternative models for editions (e.g. graphs) provide new conceptual and practical opportunities, importantly moving scholarly editing from a static result-oriented practice towards a dynamic knowledge process oriented one. By means of a concrete example, which uses the glyph as its key building block, we suggest that part of the reasoning in the constitution of digital scholarly editions will shift from implicit in the scholar to explicit in forms of code and explicit analysis, calculation, reasoning and logic, and that this will necessarily have significant implications for the nature of authority, the requirement for transparency, the operationalisation of workflow and, ultimately, the very nature and conceptualising of the works that we study.
Oxidative Stress and Its Biomarkers in Cardiovascular Diseases
Authors: Valaitienė Julija , Laučytė-Cibulskienė Agnė
Published: October 2024

Background

Cardiovascular diseases (CVDs) are the most common cause of death worldwide. CVDs share heterogeneous pathophysiologic mechanisms, one of which includes increased oxidative stress.

Main Body

Surplus levels of reactive oxygen species induce damage to cellular macromolecules such as DNA, proteins, and lipids. Increased reactive oxygen species result in decreased nitric oxide availability, vasoconstriction, and the development of procoagulant and proinflammatory states in blood vessels.

Conclusion

Improved knowledge of biomolecular processes triggered by oxidative stress has helped develop tools for assessing oxidative stress markers and applying them in clinical settings. Nevertheless, some research gaps should be filled, specifically by defining the most clinically relevant biomarkers for oxidative stress with high sensitivity and specificity for CVD.
Knowledge, Attitudes, and Practices towards Acceptance of Health Science Information among WeChat Public Account Users: A Cross-Sectional Study
Authors: Wang Yanan , Liu Peiqiang , Zhang Qiong
Published: October 2024

Objective

This study aimed to assess the knowledge, attitude, and practice (KAP) of WeChat users towards health-related public accounts.

Methods

The study included 567 participants who completed the questionnaire. Pearson correlation analysis was used to evaluate the correlation among the 3 dimensions. Multivariate analysis identified independent factors associated with KAP scores.

Results

The mean scores for knowledge, attitude, and practice were 6.12 ± 2.29 (61.2% of the total), 55.83 ± 7.33 (69.8% of the total), and 14.07 ± 3.72 (70.4% of the total), respectively. Significant positive correlations were observed between knowledge and practice (r = 0.392, P < 0.001) as well as between attitude and practice (r = 0.319, P < 0.001). Age [OR = 0.29 (0.09, 0.91), P = 0.034], marital status [OR = 2.11 (1.04, 4.29), P = 0.038], income [OR = 2.42 (1.23, 4.75), P = 0.010], and physical condition [OR = 0.45 (0.24, 0.85), P = 0.014] were independent factors associated with KAP scores.

Conclusions

WeChat users in China had relatively adequate knowledge and positive attitudes towards health-related public accounts. The findings highlight the potential of WeChat in enhancing health information dissemination in China.
The relationship between minimum wage and employment. A synthetic control method approach
Authors: Arnadillo Juan J. , Fuenmayor Amadeo , Granell Rafael
Published: October 2024

Spain increased its minimum wage (MW) by 22% in 2019. Given the intense debate in the economic literature on the impact of MW increases on the labour market, we conduct an impact assessment of this policy. The synthetic control method will be used to replicate the Spanish labour market by means of a pool of European countries that, in the absence of other reliable measures, simulates the evolution of Spanish employment. This will allow us to identify the causal effect from the increase in the MW. After applying the technique, the increase in the MW is found to have no effect on employment. The results have been subjected to robustness tests such as leave one out or segmentation by gender or age.
Linear stability analysis of oblique Couette–Poiseuille flows
Authors: Abdullah Muhammad , Park George I.
Published: October 2024

We perform a detailed numerical study of modal and non-modal stability in oblique Couette–Poiseuille profiles, which are among the simplest examples of three-dimensional boundary layers. Through a comparison with the Orr–Sommerfeld operator for the aligned case, we show how an effective wall speed succinctly characterizes modal stability. Large-scale parameter sweeps reveal that the misalignment between the pressure gradient and wall motion is, in general, destabilizing. For flows that are sufficiently oblique, the instability is found to depend exclusively on the direction of wall motion and not on its speed, a conclusion supported, in part, by the perturbation energy budget and the evolution of the critical layers. Closed forms for the critical parameters in this regime are derived using a simple analysis. From a non-modal perspective, pseudoresonance is examined through the resolvent and the

$\epsilon$

-pseudospectra. An analysis of the unforced initial value problem shows that the maximum energy gain is highly dependent on both the magnitude and direction of the wall velocity. However, the strongest amplification is always achieved for configurations that are only weakly skewed. Finally, the optimal perturbations appear to develop via a lift-up effect enhanced by an Orr-like mechanism, the latter driven by cross-flow shear.
Analysis of group evaporation characteristics of droplet clusters in an evaporating spray
Authors: Pandurangan Nandhakumar , Sahu Srikrishna
Published: October 2024

Droplet clustering in sprays refers to the dynamic evolution of highly concentrated regions due to the preferential accumulation of the polydisperse droplets in the turbulent airflow entrained by the spray. In the current study, we aim to experimentally investigate the collective vaporization of the droplets in droplet clusters in an air-assisted acetone spray characterized by the Group number,

$G$

. The magnitude of

$G$

depends on the cluster length scale and interdroplet spacing, and it indicates the vaporization mode that may vary from the isolated mode (

$G \ll 1$

) to external group mode (

$G \gg 1$

). The droplet measurements were obtained under atmospheric conditions at different axial and radial locations within the spray. Application of the Voronoi analysis to particle image velocimetry images of the spray droplets facilitated the identification and characterization of the droplet clusters, which allowed the measurement of

$G$

for each cluster. The results highlighted that multiscale clustering of the evaporating droplets leads to multimode group evaporation of the clusters (characterized by a wide range of

$G$

: 0.001–10). The trend of interdroplet spacing versus cluster area allowed the classification of the droplet clusters into small-scale clusters (which are of the order of the Kolmogorov length scale) and large-scale clusters (that scale with the large-scale turbulent eddies), that are found to exhibit distinct group evaporation behaviour. A theoretical model is invoked to correlate

$G$

with the droplet evaporation rate for individual clusters, and some interesting observations are identified, which are explained in the paper.
Melting of olive oil in immiscible surroundings: experiments and theory
Authors: Waasdorp Pim , van den Bogaard Aron , van Wijngaarden Leen , Huisman Sander G.
Published: October 2024

We report on the melting dynamics of frozen olive oil in quiescent water for Rayleigh numbers up to

$10^9$

. The density difference results in an upward buoyancy-driven flow of liquid oil forming a thin film around the frozen oil. We experimentally investigate flat, cylindrical and spherical shapes and we derive theoretical expressions for the local film thickness, velocity and the local melt rate for these three canonical geometries. Our theoretical models predict the correct order of magnitude and the correct scaling as compared with our experimental findings.
Inmigración e identidades étnicas: Discursividades y mediaciones en la formación de uniones mixtas en México
Authors: Navarrete-Suárez Johana
Published: October 2024

La conformación de uniones mixtas entre personas inmigrantes y nativas se ha considerado un elemento central en el proceso de integración social, sobre todo cuando intervienen atributos como la nacionalidad y la identidad étnica. Aunque este tema ha sido ampliamente investigado en otros contextos, ha recibido menos atención en México. Este artículo busca analizar las dimensiones relacionadas con el proyecto migratorio, los discursos sobre la diferencia en México y el efecto del mestizaje sobre la formación de uniones y dinámicas de socialización de las personas. A partir de un acercamiento cualitativo que comprende el análisis de treinta y dos relatos de vida de inmigrantes latinoamericanos residentes en México, se encontró que este tipo de arreglos sociales no se traducen de manera directa en el debilitamiento de fronteras sociales, sino que pueden constituirse, en algunos casos, en elementos de reforzamiento de las barreras que dificultan la integración en distintas esferas de reproducción social.
Evaluation of a probiotic blend on psychosocial health and biomarkers of inflammatory, immune and stress response in adults with subthreshold depression: a double-blind, randomised, placebo-controlled trial
Authors: Moschonis George , Sarapis Katerina , Resciniti Stephanie , Hall Renate , Yim Kanny , Tonkovic Matilda , Fitzgerald Clare , Anixiadis Fay , Vinh Antony , Dinh Quynh Nhu , Cronin Rachael A. , Hale Matthew W. , Wright Bradley J. , Pane Marco , Tuck Caroline J. , Biesiekierski Jessica R.
Published: October 2024

This study examined the efficacy of a probiotic in reducing depressive symptom severity in people with subthreshold depression. In a double-blind, randomised, placebo-controlled trial, a probiotic (1 × 10^9 live cells per strain: Limosilactobacillus fermentum LF16 (DSM26956), Lacticaseibacillus rhamnosus LR06 (DSM21981), Lactiplantibacillus plantarum LP01 (LMG P-21021) and Bifidobacterium longum 04 (DSM23233)) or placebo was taken daily for 12 weeks. Data were collected at baseline, 6 and 12 weeks including psychological symptom severity (Beck Depression Inventory, BDI; Patient Health Questionnaire, PHQ; Hospital Anxiety Depression Scale, HADS; and Depression Anxiety and Stress Scale, DASS). Biomarkers of glycaemia, inflammation (high-sensitivity C-reactive protein, hs-CRP), antioxidant status (total glutathione (GSH)) and stress (cortisol awakening response, CAR) were also measured. Thirty-nine participants (nineteen probiotic; twenty placebo) were enrolled. There were no significant between-group differences in the examined psychological symptom severity scores, despite certain significant within-group changes observed in both groups from baseline to 6 and/or 12 weeks of follow-up. Regarding biomarkers, the probiotic group showed reduced hs-CRP (–1520; 95 % CI –273·7, −2766·2 ng/dl) and CAR (–0·28; 95 % CI −0·05, −0·51 μg/dl) at 12 weeks, but increased total GSH (3·9; 95 % CI 0·1, 7·5 ng/dl) at 6 weeks, compared with the placebo. The current study reported favourable decreases in depressive symptoms in both groups. Although the within-group changes observed in the probiotic group were supported by favourable inflammatory, antioxidant status and stress biomarker changes compared with the placebo, further research is required to shed more light on the role of gut microbiota modulation on emotional regulation.
An exploratory study of sponges, sponge-associated, and planktonic prokaryotic communities in an artificial coral reef environment
Authors: Cleary Daniel F. R. , Stuij Tamara Maria , Janse Max , Gomes Newton C. M. , de Voogd Nicole J.
Published: October 2024

In the present study, we assessed the sponge fauna, sponge-associated, and planktonic prokaryotic communities residing in Burgers' Zoo Ocean aquarium, Arnhem, the Netherlands. The Ocean aquarium consisted of separate displays and life support systems, and included fish-only systems in addition to a large, 750,000 L tank containing a living, tropical coral reef ecosystem. Sponges were observed throughout the aquarium system and were identified as belonging to the genera Chalinula, Chondrilla, Chondrosia, Cinachyrella, Stylissa, Suberites and Tethya. There was a highly significant difference in composition between sponge-associated and planktonic prokaryotic communities. The tanks in which the sponges were sampled appeared to have a secondary structural effect on prokaryotic composition with sponges and water from the same tanks sharing several microorganisms. Both sponge-associated and planktonic prokaryotic communities housed prokaryotic taxa, which were highly similar to microorganisms previously recorded in sponges or coral reef environments, including taxa potentially involved in nitrification, denitrification, sulphur oxidation, and antibiotic biosynthesis. Several abundant microorganisms were only recorded in sponges and these may play a role in maintaining water quality in the aquarium system. Potential pathogens, e.g. related to Photobacterium damselae, and beneficial organisms, e.g. related to Pseudovibrio denitrificans, were also detected. The present study showed that Burgers' Zoo Ocean aquarium housed diverse free-living and host-associated prokaryotic communities. Future research should focus on identifying conditions and microbial communities conducive to a healthy aquarium environment.
Morphological differences yet genetic similarity among seasonal cohorts of Japanese anchovy during the early life stages in the Kii Channel
Authors: Yasue Naotaka , Yanagimoto Takashi , Noguchi Daiki , Takasuka Akinori
Published: October 2024

Species in the genus Engraulis show extensive intraspecific as well as interspecific morphological and genetic diversity. Since morphological differences do not necessarily correspond to genetic differences, it is necessary to clarify the relationship between morphological differences and genetic differences for a better understanding of the population structure. Fish morphology at a given standard length differs between cohorts of Japanese anchovy Engraulis japonicus during the early life stages in the Kii Channel, but it is unknown whether the differences are caused by genetic differences or not. The Kii Channel includes the boundary between the Pacific (southern side of the Kii Channel) and the Seto Inland Sea stocks (northern side), but stock separation is based primarily on demographic characteristics. In the present study, genetic analyses were conducted to examine the genetic differences among samples (month and area) based on mitochondrial DNA cytochrome b region (Cyt b), control region (CR) and microsatellite markers. AMOVA revealed that the percentage of genetic variation among samples was low at 0.11% for Cyt b, 0.30% for CR and 0.00% for microsatellite, and no significant genetic variation was observed among samples. Although two clades were identified in the unrooted neighbour-joining tree for Cyt b and CR, both Cyt b and CR sequences were similar between months and between areas. Accordingly, the morphological differences among cohorts can be attributed to phenotypic plasticity. Additionally, there were no genetic differences between samples from the southern side and the northern side of the Kii Channel, suggesting strong genetic connectivity in these areas.
Revealing further insights on extralimital records of Burmeister's porpoise (Phocoena spinipinnis, Burmeister, 1865) in the Southwestern Atlantic Ocean
Authors: Carvalho R. R. , Ikeda J. , Daoualibi Y. , Guari E. B. , Teixeira P. , Santos-Neto E. B. , Lailson-Brito J. , Barbosa L. , Ramos-Nogueira M. , Azevedo A. F.
Published: October 2024

Burmeister's porpoise (Phocoena spinipinnis) is an endemic species found in both the South Pacific and Atlantic Oceans, along the coastal regions of South America. In the Southwestern Atlantic Ocean, the species is reported from Tierra del Fuego, Argentina to Santa Catarina, Brazil, and the Falkland Islands. This study provides new insights on two stranded P. spinipinnis specimens in Southeastern Brazil, including the first occurrence in the state of Rio de Janeiro. Despite the advanced decomposition of the carcasses, which limited necropsy findings, we provide new data on the general characteristics of the specimens found in this extralimital geographical range, such as total body length, age, sex, vertebral count, and cranial measurements.
Cognitive Representations of Social Relationships and their Developmental Origins
Authors: Thomas Ashley J.
Published: October 2024

In the human mind, what is a social relationship, and what are the developmental origins of this representation? I consider findings from infant psychology and propose that our representations of social relationships are intuitive theories built on core knowledge. I propose three central components of this intuitive theory. The purpose of the first component is to recognize whether a relationship exists, the purpose of the second is to characterize the relationship by categorizing it into a model and to compute its strength (i.e., intensity, pull, or thickness), and the purpose of the third is to understand how to change relationships through explicit or implicit communication. I propose that infants possess core knowledge on which this intuitive theory is built. This paper focuses on the second component and considers evidence that infants characterize relationships. Following Relational Models Theory (A. P. Fiske, 1992, 2004) I propose that from infancy humans recognize relationships that belong to three models: communal sharing (where people are ‘one’), authority ranking (where people are ranked), and equality matching (where people are separate, but evenly balanced). I further propose that humans, and potentially infants, recognize a relationship's strength which can be thought of as a continuous representation of obligations (the extent to which certain actions are expected), and commitment (the likelihood that people will continue the relationship). These representations and the assumption that others share them allow us to form, maintain, and change social relationships throughout our lives by informing how we interpret and evaluate the actions of others and plan our own.
A “Promise to Preserve Proper Decorum”: Organized Dancers, Filipino Patrons, and the Politics of Night Work in 1920s Seattle
Authors: Pollnow Sarah
Published: October 2024

In 1920s Seattle, dance halls charging ten cents per dance became the focus of debate. Tracing the dance workers’ self-representations and labor organizing in a city increasingly hostile to interracial social spaces, this paper evaluates how gender, race, labor organizing, and politics intersected in unprecedented ways in Seattle’s nightlife. In a decade of tepid labor organizing and in a sexual labor sector where unions were extremely rare, female dancers in Seattle unionized. Moreover, they did so in what became under Mayor Betha Knight Landes (1926–1928) the first major American city to have a female mayor. The Women Dancing Entertainers’ Union’s (WDEU) tactics of emphasizing the respectability of their profession enjoyed initial successes, yet faltered when dance hall critics increasingly constructed the presence of interracial couples as a sign of immorality. The closure in 1929 of numerous ten-cent halls south of Yesler Way reflects how Anti-Asian prejudice entered into regulation of the city’s nightlife, adversely impacting dance hall workers, women in politics, and minoritized men. The WDEU’s insistence that they were upstanding workers and economic providers nonetheless provides a powerful corrective to contemporaries’ and, until recently, historians’ tendency to overlook sexual sector night labor.
Unravelling military aggression: Ontological insecurity, great power narcissism, and Japan’s international relations, 1868–1971
Authors: Hagström Linus
Published: October 2024

This article examines the extent to which or how self-identified great powers resort to military aggression following events that challenge their sense of greatness. It problematises the prevalent notion that great powers and events exist and have effects independently of the narratives that constitute them. The article does this by engaging with Ontological Security Studies, Great Power Narcissism, and the psychology of vulnerable and grandiose narcissism, as well as by analysing Japanese identity narratives in two periods seemingly marked by equally challenging events – the Meiji era (1868–1912) and the post-war period (1950–71). It finds that Japan’s military aggression against China in 1894–5 was enabled by vulnerable narratives of shame and insult, while the decision to wage war with Russia a decade later was facilitated more by grandiose narratives. Despite Japan’s overwhelming defeat in the Second World War and the persistent desire among conservative elites for great power status and identity, however, overall post-war narratives did not feature similarly negative emotions and calls for revenge. Japanese great power aspirations were arguably curtailed in this period through intense narrative contestation, notably progressive counter-narratives featuring more self-reflective expressions of guilt and remorse, and even the self-reflexive desire for a non-great power identity.
The impact of propagule type and burial depth on knotroot foxtail (Setaria parviflora) emergence and plant development, compared to other Setaria species
Authors: Dyer Logan M. , Henry Gerald M. , McCullough Patrick E. , Belcher Jason , Zaccaro-Gruener Maria Leticia , Basinger Nicholas T.
Published: October 2024

Knotroot foxtail [Setaria parviflora (Poir.) Kerguélen], a perennial Setaria species, is becoming more problematic in forage and grazing systems across the southeastern United States. Setaria parviflora reproduces through the production of rhizomes and seeds, further complicating management strategies. Significant knowledge gaps exist regarding the biology and control of this species. This research aimed to understand the influence of burial depth on S. parviflora propagules and the physiological differences between it and other Setaria spp. Experiments were conducted between October 2019 and February 2021 in Clarke County, GA, to investigate the influence of burial depth (1, 2, 4, 8, and 16 cm) on the emergence and growth of S. parviflora rhizomes and seeds. Zero emergence was estimated at 8.7, 10.8, and 11.2 cm for small rhizomes, large rhizomes, and seeds, respectively. Therefore, producers could implement tillage events to a depth of 11.2 cm or greater to control S. parviflora. A separate study compared S. parviflora, yellow foxtail [Setaria pumila (Poir.) Roem. & Schult.], green foxtail [Setaria viridis (L.) P. Beauv.], and giant foxtail (Setaria faberi Herrm.) plant morphology. Despite similar aboveground appearances, S. pumila and S. parviflora had different total and belowground biomass 2 to 5 mo after emergence, which suggests differences in root formation and perennialization of S. parviflora. The present research determined that burying propagules using tillage could be included in management recommendations concerning S. parviflora; however, it should be complemented with herbicide applications during the growing season to assist in controlling S. parviflora plants produced by seeds.
A Deep Learning Approach for Automatic Ionogram Parameters Recognition With Convolutional Neural Networks
Authors: Sherstyukov Ruslan , Moges Samson , Kozlovsky Alexander , Ulich Thomas
Published: October 2024

Typical ionosondes operate with >5 min time intervals, which is enough to obtain regular parameters of the ionosphere, but insufficient to observe short‐term processes in the Earth's ionosphere. The key point for this study is to increase the ionosondes data time resolution by automatization of ionogram scaling routine. In this study we show the results of implementation of deep learning approach for ionogram parameters scaling. We trained the model on 13 years ionogram data set of Sodankyla ionosonde at high latitude region (67°N). We tested our autoscaling program tool on 2021 years data set and evaluate errors between operator and automatic parameters scaling. The root mean square errors for critical frequencies foF2, foF1, foE, foEs, fmin, fbEs and virtual heights h′F, h′E, h′Es are estimated as 0.12 MHz (2 pixels), 0.07 MHz (1.16 pixels), 0.15 MHz (2.5 pixels), 0.33 MHz (5.5 pixels), 0.15 MHz (2.5 pixels), 0.17 MHz (2.83 pixels), 7.7 km (1.34 pixels), 7.0 km (1.22 pixels), 7.1 km (1.24 pixels), respectively.
Shear Instability and Turbulent Mixing by Kuroshio Intrusion Into the Changjiang River Plume
Authors: Tu Junbiao , Wu Jiaxue , Fan Daidu , Liu Zhiyu , Zhang Qianjiang , Smyth William
Published: October 2024

Shear instability is a dominant mechanism for mixing in the stratified oceans and coastal seas. For the first time, we present fine‐scale, direct measurements of shear instabilities in the bottom front generated by the Kuroshio intrusion into the Changjiang (Yangtze) river plume. Shear instabilities were identified using a shipboard echo‐sounder and the resulting turbulent mixing was quantified using a turbulence microstructure profiler. The shear instabilities generate vigorous turbulent mixing with dissipation rate and vertical diffusivity up to O (10−4 m2 s−3) and O (10−1 m2 s−1), respectively, comparable to values associated with shear instabilities observed in river plumes and western boundary currents but several orders of magnitude larger than typical values in the open ocean. The enhanced turbulence may contribute significantly to mixing between the Kuroshio water and coastal water and thereby alter the coastal biogeochemistry cycles.
MRI and CT compatible asymmetric bilayer hydrogel electrodes for EEG-based brain activity monitoring
Authors: Ren Guoqiang , Zhang Mingxuan , Zhuang Liping , Li Lianhui , Zhao Shunying , Guo Jinxiu , Zhao Yinchao , Peng Zhaoxiang , Lian Jiangfan , Liu Botao , Ma Jingyun , Hu Xiaodong , Zhang Zhewei , Zhang Ting , Lu Qifeng , Hao Mingming
Published: October 2024

The exploration of multi-dimensional brain activity with high temporal and spatial resolution is of great significance in the diagnosis of neurological disease and the study of brain science. Although the integration of electroencephalogram (EEG) with magnetic resonance imaging (MRI) and computed tomography (CT) provides a potential solution to achieve a brain-functional image with high spatiotemporal resolution, the critical issues of interface stability and magnetic compatibility remain challenging. Therefore, in this research, we proposed a conductive hydrogel EEG electrode with an asymmetrical bilayer structure, which shows the potential to overcome the challenges. Benefiting from the bilayer structure with different moduli, the hydrogel electrode exhibits high biological and mechanical compatibility with the heterogeneous brain-electrode interface. As a result, the impedance can be reduced compared with conventional metal electrodes. In addition, the hydrogel-based ionic conductive electrodes, which are free from metal conductors, are compatible with MRI and CT. Therefore, they can obtain high spatiotemporal resolution multi-dimensional brain information in clinical settings. The research outcome provides a new approach for establishing a platform for early diagnosis of brain diseases and the study of brain science.
Integrity of the circadian clock determines regularity of high-frequency and diurnal LFP rhythms within and between brain areas
Authors: Volkmann Paul , Geiger Annika E. I. , Hühne-Landgraf Anisja , Miljanovic Nina , Bly Jessica , Engl Tobias , Potschka Heidrun , Rossner Moritz J. , Landgraf Dominic
Published: October 2024

Circadian clocks control most physiological processes of many species. We specifically wanted to investigate the influence of environmental and endogenous rhythms and their interplay on electrophysiological dynamics of neuronal populations. Therefore, we measured local field potential (LFP) time series in wild-type and Cryptochrome 1 and 2 deficient (Cry1/2−/−) mice in the suprachiasmatic nucleus and the nucleus accumbens under regular light conditions and constant darkness. Using refined descriptive and statistical analyses, we systematically profiled LFP time series activity. We show that both environmental and endogenous rhythms strongly influence the rhythmicity of LFP signals and their frequency components, but also shape neuronal patterns on much smaller time scales, as neuronal activity in Cry1/2−/− mice is significantly less regular but at each time more synchronous within and between brain areas than in wild-type mice. These results show that functional circadian rhythms are integral for both circadian and non-circadian coordination of neuronal ensemble dynamics.
Ror2 signaling regulated by differential Wnt proteins determines pathological fate of muscle mesenchymal progenitors
Authors: Kamizaki Koki , Katsukawa Mitsuko , Yamamoto Ayano , Fukada So-ichiro , Uezumi Akiyoshi , Endo Mitsuharu , Minami Yasuhiro
Published: October 2024

Skeletal muscle mesenchymal progenitors (MPs) play a critical role in supporting muscle regeneration. However, under pathological conditions, they contribute to intramuscular adipose tissue accumulation, involved in muscle diseases, including muscular dystrophy and sarcopenia, age-related muscular atrophy. How MP fate is determined in these different contexts remains unelucidated. Here, we report that Ror2, a non-canonical Wnt signaling receptor, is selectively expressed in MPs and regulates their pathological features in a differential ligand-dependent manner. We identified Wnt11 and Wnt5b as ligands of Ror2. In vitro, Wnt11 inhibited MP senescence, which is required for normal muscle regeneration, and Wnt5b promoted MP proliferation. We further found that both Wnts are abundant in degenerating muscle and synergistically stimulate Ror2, leading to unwanted MP proliferation and eventually intramuscular adipose tissue accumulation. These findings provide evidence that Ror2-mediated signaling elicited by differential Wnts plays a critical role in determining the pathological fate of MPs.
Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway
Authors: Feng Chen , Mao Wei , Yuan Chenyang , Dong Pin , Liu Yuying
Published: October 2024

The mucosal epithelium of the head and neck region (including the oral cavity, nasal cavity, pharynx, nasopharynx, and larynx) is the primary site exposed to tobacco smoke, and its presence of nicotinic acetylcholine receptors (nAChRs) has been observed in the mucosal epithelial cells of this area. It remains unclear whether HNSC cells can migrate and invade through nAChR signaling. A model of HNSC cells exposed to nicotine is established. Cell proliferation following nicotine exposure is assessed using the CCK-8 assay, while migration and invasion are evaluated through wound healing and Transwell assays. The effects of CHRNA5 knockdown and overexpression are also investigated. Immunofluorescence staining is used to analyze CHRNA5 expression and localization, and clonogenic assays are performed to measure colony proliferation after CHRNA5 knockdown and overexpression. The interaction between CHRNA5 and CES1 is examined using molecular docking, co-immunoprecipitation, and immunofluorescence. Differentially expressed genes are subjected to pathway enrichment analysis, and MEK/ERK protein expression and phosphorylation are validated via western blot. Tumor formation assays are performed in nude mice using sh-CHRNA5 Cal27 cells, followed by western blot and immunohistochemical staining. Additionally, laryngeal and hypopharyngeal cancer tissues are analyzed through immunohistochemistry. Nicotine significantly enhanced the proliferation, migration, and invasion capabilities of head and neck tumor cells, including Cal27, Fadu, HN6, and Tu686 cells, through the expression of CHRNA5. Knockdown of CHRNA5 can reduce cell migration, invasion, and proliferation, whereas nicotine exposure can reverse this trend. Additionally, the mRNA and protein expression of CES1 decreases with the knockdown of CHRNA5, indicating a regulatory relationship between the two. Transcriptomics revealed that the knockdown of CHRNA5 is associated with the MEK/ERK signaling pathway. Further cellular- and tissue-level evidence confirmed that the levels of p-MEK/MEK, p-ERK/ERK, and CES1 decreased following knockdown of CHRNA5, a trend that nicotine can reverse. Nicotine promotes the proliferation, migration, and invasion of HNSC by upregulating CHRNA5 expression. Knockdown of CHRNA5 reduces these effects, which can be reversed by nicotine. Nicotine exposure activates CHRNA5, regulating CES1 expression via the MEK/ERK pathway, contributing to the recurrence and metastasis of head and neck squamous carcinoma.
Nr1d1 inhibition mitigates intermittent hypoxia-induced pulmonary hypertension via Dusp1-mediated Erk1/2 deactivation and mitochondrial fission attenuation
Authors: Pan Zhou , Yao Yan , Liu Xu , Wang Yixuan , Zhang Xinyue , Zha Shiqian , Hu Ke
Published: October 2024

Intermittent hypoxia (IH) precipitates pulmonary vasoconstriction, culminating in the onset of pulmonary hypertension (PH) among individuals afflicted with sleep apnea. While Nuclear receptor subfamily 1 group D member 1 (Nr1d1) is progressively recognized as pivotal regulator of cellular physiology, the role in the pathogenesis of IH-induced PH remains largely uncharted. The expression of Nr1d1 was examined in IH-induced rodent PH and in IH-treated PASMCs. To elucidate the contribution of Nr1d1 to the development of IH-induced PH, we employed siRNA to modulate Nr1d1 expression in vitro and employed serotype 1 adeno-associated virus (AAV1) in vivo. Nr1d1 levels were elevated in IH-induced rodents PH lung tissues and IH-treated PASMCs. Knocking down Nr1d1 by AAV1 effectively inhibited PH progression in chronic IH-induced PH models. Mechanistic investigations identified dual specificity phosphatase 1 (Dusp1), as a direct target that Nr1d1 trans-repressed, mediating Nr1d1’s regulatory influence on Erk1/2/Drp1 signaling. Nr1d1 deficiency ameliorates mitochondrial dysfunction and fission by restoring Dusp1 dysregulation and Drp1 phosphorylation. Activation of Erk1/2 with PMA reversed the Dusp1-mediated regulation of Drp1 phosphorylation, indicating the involvement of the Erk1/2 pathway in Drp1 phosphorylation controlled by Dusp1. Meanwhile, intermittent hypoxia induced more severe PH in Dusp1 knockout mice compared with wild-type mice. Our data unveil a novel role for Nr1d1 in IH-induced PH pathogenesis and an undisclosed Nr1d1-Dusp1 axis in PASMCs mitochondrial fission regulation.
Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer
Authors: Saito Yohei , Xiao Yi , Yao Jun , Li Yunhai , Liu Wendao , Yuzhalin Arseniy E. , Shyu Yueh-Ming , Li Hongzhong , Yuan Xiangliang , Li Ping , Zhang Qingling , Li Ziyi , Wei Yongkun , Yin Xuedong , Zhao Jun , Kariminia Seyed M. , Wu Yao-Chung , Wang Jinyang , Yang Jun , Xia Weiya , Sun Yutong , Jho Eek-hoon , Chiao Paul J. , Hwang Rosa F. , Ying Haoqiang , Wang Huamin , Zhao Zhongming , Maitra Anirban , Hung Mien-Chie , DePinho Ronald A. , Yu Dihua
Published: October 2024

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC.
Characterization of anti-AAV2 neutralizing antibody levels in sheep prior to and following intravitreal AAV2.7m8 injection
Authors: Ross Maya , Sade Kareen , Obolensky Alexey , Averbukh Edward , Desrosiers Melissa , Rosov Alexander , Dvir Hay , Gootwine Elisha , Banin Eyal , Dalkara Deniz , Ofri Ron
Published: October 2024

Gene augmentation therapy is a promising treatment for incurable, blinding inherited retinal diseases, and intravitreal delivery is being studied as a safe alternative to subretinal injections. Adeno-Associated Viruses (AAV) are commonly-used vectors for ocular gene augmentation therapy. Naturally occurring pre-operative exposure and infection with AAV could result in presence of neutralizing antibodies (NAB’s) in patients’ serum, and may affect the safety and efficacy of treatment. Our aim was to characterize the humoral response against AAV pre- and post-intravitreal delivery of AAV2.7m8 vectors in a naturally-occurring sheep model of CNGA3 achromatopsia. Serial serum neutralization assays were performed to screen sheep for pre-exiting anti-AAV2 NAB’s, and to assess the effect of intravitreal AAV2.7m8 injection on post-operative NAB titers and intraocular inflammation in sheep. The effect of viral dose and transgene type were also assessed. Serological screening revealed pre-operative seropositivity in 21.4% of animals, with age being a risk factor for the presence of anti-AAV2 NAB’s. NAB titers increased following intravitreal AAV administration in the majority of sheep. There was no significant difference in the degree of post-operative serum neutralization between pre-operatively seronegative sheep and those with pre-existing antibodies. However, only sheep with pre-existing antibodies presented with signs of post-operative inflammation. We conclude that pre-existing anti-AAV2 NAB’s do not affect the level of post-operative NAB titers; however, they increase the risk of post-operative ocular inflammation. Our results could have implications for the management of AAV-mediated ocular gene therapies, a technology being increasingly studied and used in patients.
Structural variation of types IV-A1- and IV-A3-mediated CRISPR interference
Authors: Čepaitė R. , Klein N. , Mikšys A. , Camara-Wilpert S. , Ragožius V. , Benz F. , Skorupskaitė A. , Becker H. , Žvejytė G. , Steube N. , Hochberg G.K.A , Randau L. , Pinilla-Redondo R. , Malinauskaitė L. , Pausch P.
Published: October 2024

CRISPR-Cas mediated DNA-interference typically relies on sequence-specific binding and nucleolytic degradation of foreign genetic material. Type IV-A CRISPR-Cas systems diverge from this general mechanism, using a nuclease-independent interference pathway to suppress gene expression for gene regulation and plasmid competition. To understand how the type IV-A system associated effector complex achieves this interference, we determine cryo-EM structures of two evolutionarily distinct type IV-A complexes (types IV-A1 and IV-A3) bound to cognate DNA-targets in the presence and absence of the type IV-A signature DinG effector helicase. The structures reveal how the effector complexes recognize the protospacer adjacent motif and target-strand DNA to form an R-loop structure. Additionally, we reveal differences between types IV-A1 and IV-A3 in DNA interactions and structural motifs that allow for in trans recruitment of DinG. Our study provides a detailed view of type IV-A mediated DNA-interference and presents a structural foundation for engineering type IV-A-based genome editing tools.
From emergence to endemicity of highly pathogenic H5 avian influenza viruses in Taiwan
Authors: Li Yao-Tsun , Ko Hui-Ying , Hughes Joseph , Liu Ming-Tsan , Lin Yi-Ling , Hampson Katie , Brunker Kirstyn
Published: October 2024

A/goose/Guangdong/1/96-like (GsGd) highly pathogenic avian influenza (HPAI) H5 viruses cause severe outbreaks in poultry when introduced. Since emergence in 1996, control measures in most countries have suppressed local GsGd transmission following introductions, making persistent transmission in domestic birds rare. However, geographical expansion of clade 2.3.4.4 sublineages has raised concern about establishment of endemic circulation, while mechanistic drivers leading to endemicity remain unknown. We reconstructed the evolutionary history of GsGd sublineage, clade 2.3.4.4c, in Taiwan using a time-heterogeneous rate phylogeographic model. During Taiwan’s initial epidemic wave (January 2015 - August 2016), we inferred that localised outbreaks had multiple origins from rapid spread between counties/cities nationwide. Subsequently, outbreaks predominantly originated from a single county, Yunlin, where persistent transmission harbours the trunk viruses of the sublineage. Endemic hotspots determined by phylogeographic reconstruction largely predicted the locations of re-emerging outbreaks in Yunlin. The transition to endemicity involved a shift to chicken-dominant circulation, following the initial bidirectional spread between chicken and domestic waterfowl. Our results suggest that following their emergence in Taiwan, source-sink dynamics from a single county have maintained GsGd endemicity up until 2023, pointing to where control efforts should be targeted to eliminate the disease.