bluuebunny/crossref_metadata_2025 huggingface dataset:
Fdo1, Fkh1, Fkh2, and the Swi6–Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae
Authors: Singh Gurvir , Skibbens Robert V
Published: August 2024

Cohesins promote proper chromosome segregation, gene transcription, genomic architecture, DNA condensation, and DNA damage repair. Mutations in either cohesin subunits or regulatory genes can give rise to severe developmental abnormalities (such as Robert Syndrome and Cornelia de Lange Syndrome) and also are highly correlated with cancer. Despite this, little is known about cohesin regulation. Eco1 (ESCO2/EFO2 in humans) and Rad61 (WAPL in humans) represent two such regulators but perform opposing roles. Eco1 acetylation of cohesin during S phase, for instance, stabilizes cohesin-DNA binding to promote sister chromatid cohesion. On the other hand, Rad61 promotes the dissociation of cohesin from DNA. While Eco1 is essential, ECO1 and RAD61 co-deletion results in yeast cell viability, but only within a limited temperature range. Here, we report that eco1rad61 cell lethality is due to reduced levels of the cohesin subunit Mcd1. Results from a suppressor screen further reveals that FDO1 deletion rescues the temperature-sensitive (ts) growth defects exhibited by eco1rad61 double mutant cells by increasing Mcd1 levels. Regulation of MCD1 expression, however, appears more complex. Elevated expression of MBP1, which encodes a subunit of the MBF transcription complex, also rescues eco1rad61 cell growth defects. Elevated expression of SWI6, however, which encodes the Mbp1-binding partner of MBF, exacerbates eco1rad61 cell growth and also abrogates the Mpb1-dependent rescue. Finally, we identify two additional transcription factors, Fkh1 and Fkh2, that impact MCD1 expression. In combination, these findings provide new insights into the nuanced and multi-faceted transcriptional pathways that impact MCD1 expression.
Contribution of Involuntary Job Loss to the Burden of Depressive Symptoms Over Two Decades in a National Study of Aging Adults
Authors: Picciotto Sally , Eisen Ellen A , Rehkopf David H , Byers Amy L
Published: August 2024

Objectives

In recent decades, risk of job loss in America after age 50 has been high, potentially causing significant stress during the period preceding retirement. Yet no study has quantified the burden of clinically relevant depressive symptoms attributable to job loss in this age group over this period or identified the most vulnerable populations.

Methods

Participants aged 50+ in the Health and Retirement Study (recruited 1992–2016) who were employed and scored <5 on the Center for Epidemiologic Studies-Depression 8-item scale (CESD-8) at baseline (N = 18,571) were followed for depressive symptoms until they first had CESD-8 ≥5 or died, or through the 2018 survey. Parametric g-formula analyses examined the difference in cumulative risk of having CESD-8 ≥5 if there had been no involuntary job loss compared to the observed scenario, adjusting for sex, race/ethnicity, age, and dynamic measures of recent marriage end (divorce or widowhood), having a working spouse, assets/debt, and health changes.

Results

We estimated that risk of CESD-8 ≥5 would have been 1.1% (95% confidence interval [0.55, 1.37]) lower if no involuntary job loss had occurred; job loss accounted for 11% of the total burden among those who lost a job. Stronger associations were observed for women (1.2% [0.7, 1.8] vs men 0.5% [0.2, 1.1]), White respondents (1.0% [0.6, 1.5] vs Black respondents 0.5% [−0.1, 1.4]), and those in the lowest quartile of baseline assets (1.1% [0.4, 1.9] vs wealthiest quartile 0.5% [−0.4, 0.9]).

Discussion

Involuntary job loss is associated with high depressive symptom burden in older persons, suggesting that screening and intervention soon after job loss may help mitigate depression.
Thermal rock magnetic cycling (TRMC): a method to track thermal alteration details for palaeointensity interpretations
Authors: Miao Junxiang , Wang Huapei
Published: August 2024

Accurate absolute palaeointensity is essential for understanding dynamo processes on the Earth and other planetary bodies. Although great efforts have been made to propose techniques to obtain magnetic field strength from rock samples, such as Thellier-series methods, the amount of high-fidelity palaeointensities remains limited. One primary reason for this is the thermal alteration of samples that pervasively occurred during palaeointensity experiments. In this study, we developed a comprehensive rock magnetic experiment, termed thermal rock magnetic cycling (TRMC), that can utilize measurements of critical rock magnetic properties at elevated temperatures during multiple heating-cooling cycles to track thermal changes in bulk samples and individual magnetic components with different Curie temperatures in samples for palaeointensity interpretations. We demonstrate this method on a Galapagos lava sample, GA 84.6. The results for this specimen revealed that GA 84.6v underwent thermophysical alteration throughout the TRMC experiment, resulting in changes in its remanence carrying capacity. These findings were then used to interpret the palaeointensity results of specimen GA 84.6c, which revealed that the two-slope Arai plot yielded two linear segments with distinct palaeointensity values that were both biased by thermophysical alteration. To further test the TRMC method, we selected another historical lava sample (HS 2) from Mt Lassen, detecting slight thermal-physical changes after heating the specimen HS 2–8C to a target temperature of 400 °C. We also isolated a stable magnetic component with a Curie temperature below 400 °C using the TRMC method, which may provide a more reliable palaeointensity estimate of 51 μT. By providing a method for tracking thermal alteration independent of palaeointensity experiments, the TRMC method can explore subtle, unrecognizable thermal alteration processes in less detailed palaeointensity measurements, which can help to assess the thermal stability of the measured samples and interpret the changes in the TRM unblocking spectrum and palaeointensity estimates, facilitating the acquisition of more reliable records for constrain the formation of the inner core and the evolution of Earth's magnetic field.
The Korean infrasound catalogue (1999–2022)
Authors: Park Junghyun , Arrowsmith Stephen , Che Il-Young , Hayward Chris , Stump Brian
Published: August 2024

The Korean infrasound catalogue (KIC) covers 1999–2022 and characterizes a rich variety of source types as well as document the effects of the time-varying atmosphere on event detection and location across the Korean Peninsula. The KIC is produced using data from six South Korean infrasound arrays that are cooperatively operated by Southern Methodist University and Korea Institute of Geoscience and Mineral Resources. Signal detection relies on an Adaptive F-Detector that estimates arrival time and backazimuth, which draws a distinction between detection and parameter estimation. Detections and associated parameters are input into a Bayesian Infrasonic Source Location procedure. The resulting KIC contains 38 455 infrasound events and documents repeated events from several locations. The catalogue includes many anthropogenic sources such as an industrial chemical explosion, explosions at limestone open-pit mines and quarries, North Korean underground nuclear explosions and other atmospheric or underwater events of unknown origin. Most events in the KIC occur during working hours and days, suggesting a dominance of human-related signals. The expansion of infrasound arrays over the years in South Korea and the inclusion of data from the International Monitoring System infrasound stations in Russia and Japan increase the number of infrasound events and improve location accuracy because of the increase in azimuthal station coverage. A review of selected events and associated signals at multiple arrays provides a location quality assessment. We quantify infrasound events that have accompanying seismic arrivals (seismoacoustic events) to support the source type assessment. Ray tracing using the Ground-to-Space (G2S) atmospheric model generally predicts observed arrivals when strong stratospheric winds exist, although the predicted arrival times have significant discrepancies. In some cases, local atmospheric data better captures small-scale variations in the wind velocity of the shallow atmosphere and can improve arrival time predictions that are not well matched by the G2S model. The analysis of selected events also illustrates the importance of topographic effects on tropospheric infrasound propagation at local distances. The KIC is the first infrasound catalogue compiled in this region, and it can serve as a valuable data set in developing more robust infrasound source localization and characterization methods.
Integrating youth participatory action research and health communication to inform youth and young adult covid-19 vaccine communication research
Authors: Kikut-Stein Ava , Givan Kathleen , Fishman Jeffrey , Blanco-Liz Ashley , Alvarez-Sanchez David , Fletcher Janelle , Gambrell Raki , Hernandez Alondra , Richardson Ciani , Shaw Adrianna , von Oiste James Joseph
Published: August 2024

COVID-19 vaccination rates remain lower among adolescents compared with adults. Youth participatory action research (YPAR) offers opportunities to inform youth vaccine communication at the local and population level. However, few studies have integrated systematic health communication research with YPAR. In the current study, a diverse team of paid high school interns, undergraduate student mentors and communication researchers in West Philadelphia YPAR programs developed a theory-informed communication survey to measure teen COVID-19 vaccine beliefs, information sources and behavior. The survey was distributed locally and informed youth-created vaccine campaign messages. In addition, YPAR-derived survey measures complimented a qualitative online elicitation survey with US young adults. Responses were coded using inductive content analysis, informing measures for a subsequent population-level study of young adults. This research followed protocols approved by an Institutional Review Board. Applying a YPAR framework elevated youth voices in the study development process. Communication theory and methods aided the development of survey studies to advance both local YPAR program objectives and population-level research. Future implications are discussed.
Colombia as the ‘Laboratory’ for Transitional Justice: Consolidation and Innovation of Global Formulas
Authors: Jespersgaard Jakobsen Line
Published: August 2024

ABSTRACT∞

This article examines the standardization of transitional justice, using Colombia—regarded by international observers as a contemporary laboratory—as a case. It investigates the extent to which transitional justice, as a global blueprint for addressing past atrocities, is being embraced in Colombia and how Colombian experiences contribute to both innovation and advancement of transitional justice internationally. Colombia offers a unique perspective on how transitional justice experts and institutions engage in and construct national, regional and international networks experimentally, under the guidance of international lab certifiers and informal standardizers. Drawing on a study focused on the justice pillar of transitional justice, the article argues that the significant level of local agency, coupled with international recognition and involvement, has contributed to strengthening, rather than weakening, the international transitional justice standard through innovation and localization.
Leveraging Data From a Longitudinal Birth Cohort to Improve Attribution of Diarrhea Etiology Among Children in Low-Resource Settings
Authors: Garcia Quesada Maria , Platts-Mills James A , Liu Jie , Houpt Eric R , Rogawski McQuade Elizabeth T
Published: August 2024

Attributing infectious causes of diarrhea is critical to inform treatment and burden estimates. The attributable fraction (AF) approach based on the association between pathogen quantity and diarrhea has been frequently used but may underestimate incidence. We leveraged data from the multisite birth-cohort Malnutrition and Enteric Disease (MAL-ED) Study, where diarrheal and nondiarrheal stools were collected from 1715 children aged 0–2 years. We compared attribution using a longitudinal AF method that considers the temporal association between pathogen quantity and diarrhea symptoms to previously published AF estimates. For rotavirus and Shigella, attribution did not meaningfully change. For others like adenovirus 40 and 41, astrovirus, norovirus GII, sapovirus, Campylobacter jejuni or Campylobacter coli, heat-stable toxin enterotoxigenic Escherichia coli, typical enteropathogenic E. coli, and Cryptosporidium attribution increased, demonstrating longitudinal data may be informative for pathogens with weak associations between quantity and diarrhea. We further derived accuracy-based, pathogen-specific quantity cutoffs that may improve attribution in the absence of longitudinal data.
Temperature-dependent trophic associations modulate soil bacterial communities along latitudinal gradients
Authors: Huang Xing , Wang Jianjun , Dumack Kenneth , Anantharaman Karthik , Ma Bin , He Yan , Liu Weiping , Di Hongjie , Li Yong , Xu Jianming
Published: August 2024

Understanding the environmental and biological mechanisms shaping latitudinal patterns in microbial diversity is challenging in the field of ecology. Although multiple hypotheses have been proposed to explain these patterns, a consensus has rarely been reached. Here, we conducted a large-scale field survey and microcosm experiments to investigate how environmental heterogeneity and putative trophic interactions (exerted by protist–bacteria associations and T4-like virus–bacteria associations) affect soil bacterial communities along a latitudinal gradient. We found that the microbial latitudinal diversity was kingdom dependent, showing decreasing, clumped, and increasing trends in bacteria, protists, and T4-like viruses, respectively. Climatic and edaphic drivers played predominant roles in structuring the bacterial communities; the intensity of the climatic effect increased sharply from 30°N to 32°N, whereas the intensity of the edaphic effect remained stable. Biotic associations were also essential in shaping the bacterial communities, with protist–bacteria associations showing a quadratic distribution, whereas virus–bacteria associations were significant only at high latitudes. The microcosm experiments further revealed that the temperature component, which is affiliated with climate conditions, is the primary regulator of trophic associations along the latitudinal gradient. Overall, our study highlights a previously underestimated mechanism of how the putative biotic interactions influence bacterial communities and their response to environmental gradients.
Towards cross-application model-agnostic federated cohort discovery
Authors: Dobbins Nicholas J , Morris Michele , Sadhu Eugene , MacFadden Douglas , Nazaire Marc-Danie , Simons William , Weber Griffin , Murphy Shawn , Visweswaran Shyam
Published: August 2024

Objectives

To demonstrate that 2 popular cohort discovery tools, Leaf and the Shared Health Research Information Network (SHRINE), are readily interoperable. Specifically, we adapted Leaf to interoperate and function as a node in a federated data network that uses SHRINE and dynamically generate queries for heterogeneous data models.

Materials and Methods

SHRINE queries are designed to run on the Informatics for Integrating Biology & the Bedside (i2b2) data model. We created functionality in Leaf to interoperate with a SHRINE data network and dynamically translate SHRINE queries to other data models. We randomly selected 500 past queries from the SHRINE-based national Evolve to Next-Gen Accrual to Clinical Trials (ENACT) network for evaluation, and an additional 100 queries to refine and debug Leaf’s translation functionality. We created a script for Leaf to convert the terms in the SHRINE queries into equivalent structured query language (SQL) concepts, which were then executed on 2 other data models.

Results and Discussion

91.1% of the generated queries for non-i2b2 models returned counts within 5% (or ±5 patients for counts under 100) of i2b2, with 91.3% recall. Of the 8.9% of queries that exceeded the 5% margin, 77 of 89 (86.5%) were due to errors introduced by the Python script or the extract-transform-load process, which are easily fixed in a production deployment. The remaining errors were due to Leaf’s translation function, which was later fixed.

Conclusion

Our results support that cohort discovery applications such as Leaf and SHRINE can interoperate in federated data networks with heterogeneous data models.
Ciliary length variations impact cilia-mediated signaling and biological responses
Authors: Kobayashi Yuki , Hamamoto Akie , Saito Yumiko
Published: August 2024

Primary cilia are thin hair-like organelles that protrude from the surface of most mammalian cells. They act as specialized cell antennas that can vary widely in response to specific stimuli. However, the effect of changes in cilia length on cellular signaling and behavior remains unclear. Therefore, we aimed to characterize the elongated primary cilia induced by different chemical agents, lithium chloride (LiCl), cobalt chloride (CoCl2) and rotenone, using human retinal pigmented epithelial 1 (hRPE1) cells expressing ciliary G protein-coupled receptor (GPCR), melanin-concentrating hormone (MCH) receptor 1 (MCHR1). MCH induces cilia shortening mainly via MCHR1-mediated Akt phosphorylation. Therefore, we verified the proper functioning of the MCH-MCHR1 axis in elongated cilia. Although MCH shortened cilia that were elongated by LiCl and rotenone, it did not shorten CoCl2-induced elongated cilia, which exhibited lesser Akt phosphorylation. Furthermore, serum readdition was found to delay cilia shortening in CoCl2-induced elongated cilia. In contrast, rotenone-induced elongated cilia rapidly shortened via a chopping mechanism at the tip of the cilia. Conclusively, we found that each chemical exerted different effects on ciliary GPCR signaling and serum-mediated ciliary structure dynamics in cells with elongated cilia. These results provide a basis for understanding the functional consequences of changes in ciliary length.
Effects of female-specific selection for reproductive investment on male fertility traits
Authors: Mason Chloe , Tschirren Barbara , Hemmings Nicola
Published: August 2024

Despite sharing an autosomal genome, the often divergent reproductive strategies of males and females cause the selection to act in a sex-specific manner. Selection acting on one sex can have negative, positive, or neutral fitness consequences on the opposite sex. Here, we test how female-limited selection on reproductive investment in Japanese quail (Coturnix japonica) affects male fertility-related traits. Despite there being no difference in the size of males’ testes from lines selected for high female reproductive investment (H-line) or low female reproductive investment (L-line), in both lines, the left testis had a greater volume of sperm-producing tissue. Since H-line females have a larger left-side restricted oviduct, this suggests a positive genetic correlation between male and female gonad function and that internal testis structure is a target of sexual selection. However, despite H-line males having previously been found to have greater fertilization success in a competitive scenario, we found little evidence of a difference between the lines in sperm number, motility, velocity, length, or the number of sperm that reached the ova. Precopulatory cues and/or the role of seminal fluid in sperm motility may thus be more likely to contribute to the H-line male fertilization advantage in this species.
Efficacy of plant-based products and nonconventional pesticides for the management of tropical bed bug
Authors: Meisyara Dita , Guswenrivo Ikhsan , Veera Singham G
Published: August 2024

Insecticide resistance is widespread in global bed bug populations. Both common bed bugs and tropical bed bugs are pyrethroid-resistant among most field populations. Plant-based products and nonconventional pesticides offer minimal-risk strategies for managing bed bug resistance, but this strategy has yet to be formally evaluated in Cimex hemipterus (F.) (Hemiptera: Cimicidae). Here, several commercial plant-based formulations (Cedarcide, EcoRaider (also known as EcoVenger), EcoSMART, and Bio-D), a novel product, Provecta, and a pyrethroid insecticide, Pesguard FG161 were tested against pyrethroid-susceptible and resistant strains of C. hemipterus using direct spray, residual exposure, and egg dipping assays. Direct spray treatments outperform residual applications against all tested bed bug strains. Cedarcide exhibits the highest consistency in eliminating bed bugs, followed by EcoRaider, EcoSMART, and Provecta that outperform Bio-D and Pesguard FG161. In comparison to Pesguard FG161, all plant-based insecticide products and Provecta showed higher efficacy against pyrethroid-resistant strains. Although effective, product efficacy varies in terms of speed. Cedarcide kills all bed bugs within 1 min after spraying; however, other products can take up to 9 days to achieve 100% mortality. The efficacy of all products was reduced when evaluated on fabric surface (42%–65% mortality). Cedarcide and EcoRaider reduced egg hatchability by 37%–73% and 47%–70%, respectively. This study suggests that certain plant-based insecticides and an unconventional insecticide can serve as alternative direct spray treatments for managing tropical bed bugs, though their residual effects are limited.
STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3
Authors: Chen Cheng , Cai Xin , Liu Zhihui , Zhang Weiguang , Yang Jiacai , Tang Yuanyang , Chen Yunxia , Huang Yong , Hu Wengang , Zhang Xiaorong , Zhou Junyi , Wu Yanjun , Yin Wenjing , Shang Ruoyu , Lu Qudong , Sheng Hao , Ju Zhenyu , Luo Gaoxing , He Weifeng
Published: August 2024

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING–STAT3–chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts.
Women hold up the shattering sky? Performance feedback on multiple conflicting goals and women’s representation in top management teams in the public sector
Authors: Huang Ting
Published: August 2024

Previous research on the glass cliff phenomenon has primarily explored the impact of performance decline on women in leadership based on single objectives, overlooking the complexity of managing performance in the public sector. This study adopts a multigoal perspective to explore how performance feedback in a dual-goal scenario affects gender composition in top management teams (TMTs) in Chinese local governments. Drawing on behavioral theory, it differentiates between unambiguous and ambiguous feedback as two distinct types of organizational performance feedback, to test their influence on women’s proportion in TMTs. A unique data set covering 276 Chinese municipal governments from 2010 to 2018 was used to investigate how performance feedback on two conflicting objectives, economic growth and environmental protection pursued by Chinese local governments, affects women’s proportion in mayoral teams. Results from fractional logit regression suggest that unambiguous failure is positively associated with the proportion of women in TMTs. However, ambiguous performance feedback is negatively related to the proportion of women in TMTs. Implications for research on gender composition in the upper echelons and performance feedback on multiple objectives are discussed.
Obligatory Implicatures and the Relevance of Contradictions
Authors: Bar-Lev Moshe E
Published: August 2024

Magri (2009a,b) proposed a generalization according to which a sentence is infelicitous whenever exhaustification over the full set of formal alternatives of the sentence leads to contextual contradiction. While Magri proposes an account of obligatory implicatures which explains some cases where this generalization expects infelicity, he does not provide a general account of this generalization. In this paper I argue for a perspective on the ‘pruning’ of alternatives which predicts this generalization, building on the counter-intuitive idea that contradictions are relevant in every context (Lewis 1988). I further argue, using disjunction in the scope of a universal quantifier as a test case, that an extension of this view to obligatory ignorance inferences provides a new perspective on the Logical Integrity Generalization put forward by Anvari (2018b), while avoiding some empirical problems for this generalization.
External jugular venous aneurysm—a case report
Authors: Sogandji Nihal , La Torre Guglielmo , Hildebrand Diane
Published: August 2024

Aneurysms of the external jugular vein (EJV) are uncommon vascular malformations. Due to their rarity, it is currently unclear what the risk of complications are and whether surgical management should be offered. The risks associated with the surgery need to be balanced with the risk of complications from the malformation. We present the case of a young woman who presented with a painful erythematous neck swelling who was found to have an aneurysm of the EJV with thrombophlebitis. This was successfully treated with surgical excision. We discuss current evidence for treatment of neck vein aneurysms and pitfalls.
The Cosmopolitans: Cocktail Culture, Gender, and Social Status in Interwar Singapore
Authors: Lowrie Claire , Samuelsson Lauren
Published: August 2024

This article explores the emergence of cocktail culture in interwar Singapore. Mixed alcoholic drinks were consumed by British men in Singapore from at least the 1910s, including the famous “Singapore Sling.” However, it was not until the 1920s that cocktails became the drink of choice for elite men and women from Singapore’s Chinese, British, and Eurasian communities. The consumption of American popular culture and exchange with American colonists in the Philippines helped the cocktail to become a symbol of tropical modernity. At the same time, the possibilities of home entertaining were transformed by the increasing availability of American-made domestic refrigerators in Singapore from the mid-1920s. Multiethnic elites, accustomed to frequenting bars and cafés to enjoy cocktails, began to host their own cocktail parties with the help of their Chinese servants. The interwar cocktail party offered the wealthy a means to display conspicuous consumption and cosmopolitan modernity. They did so in a way that unsettled but did not overturn colonial hierarchies based on gender, race, and class.
The concerted function of a novel class of transcription factors, ZBFs, in light, jasmonate, and abscisic acid signaling pathways
Authors: Dutta Siddhartha , Chattopadhyay Sudip , Maurya Jay Prakash
Published: August 2024

Several classes of transcription factors have been investigated in light signaling pathways that bind to the light-responsive elements (LREs) present in the promoters of light regulatory genes for transcriptional regulation. Some of these transcription factors have been shown to bind to numerous promoters through genome-wide ChIP-on-chip (ChIP-chip) studies. Furthermore, through the integration of ChIP-seq and RNA-seq techniques, it has been demonstrated that a transcription factor modifies the expression of numerous genes with which it interacts. However, the mode of action of these transcription factors and their dependency on other regulators in the pathway has just started to be unraveled. In this review, we focus on a particular class of transcription factors, ZBFs (Z-box-binding factors), and their associated partners within the same or other classes of transcription factors and regulatory proteins during photomorphogenesis. Moreover, we have further made an attempt to summarize the crosstalk of these transcription factors with jasmonic acid-, abscisic acid-, and salicylic acid-mediated defense signaling pathways. This review offers an in-depth insight into the manner in which ZBFs and their interactors reshape cellular functions and plant behavior. The underlying principles not only contribute to a comprehensive understanding but also establish a framework for analyzing the interplay between early developmental events and hormone signaling, a regulation orchestrated by the ZBF family.
Shedding light on iron nutrition: exploring intersections of transcription factor cascades in light and iron deficiency signaling
Authors: Trofimov Ksenia , Mankotia Samriti , Ngigi Mary , Baby Dibin , Satbhai Santosh B , Bauer Petra
Published: August 2024

In the dynamic environment of plants, the interplay between light-dependent growth and iron nutrition is a recurring challenge. Plants respond to low iron levels by adjusting growth and physiology through enhanced iron acquisition from the rhizosphere and internal iron pool reallocation. Iron deficiency response assays and gene co-expression networks aid in documenting physiological reactions and unraveling gene-regulatory cascades, offering insight into the interplay between hormonal and external signaling pathways. However, research directly exploring the significance of light in iron nutrition remains limited. This review provides an overview on iron deficiency regulation and its cross-connection with distinct light signals, focusing on transcription factor cascades and long-distance signaling. The circadian clock and retrograde signaling influence iron uptake and allocation. The light-activated shoot-to-root mobile transcription factor ELONGATED HYPOCOTYL5 (HY5) affects iron homeostasis responses in roots. Blue light triggers the formation of biomolecular condensates containing iron deficiency-induced protein complexes. The potential of exploiting the connection between light and iron signaling remains underutilized. With climate change and soil alkalinity on the rise, there is a need to develop crops with improved nutrient use efficiency and modified light dependencies. More research is needed to understand and leverage the interplay between light signaling and iron nutrition.
Local signal from Trichoderma afroharzianum T22 induces host transcriptome and endophytic microbiome leading to growth promotion in sorghum
Authors: Kabir Ahmad H , Thapa Asha , Hasan Md Rokibul , Parvej Md Rasel
Published: August 2024

Trichoderma, a highly abundant soil fungus, may benefit plants, yet it remains understudied in sorghum (Sorghum bicolor). In this study, sorghum plants were grown for 5 weeks in pots of soil with or without inoculation of T. afroharzianum T22. Inoculation with T. afroharzianum T22 significantly increased growth parameters and nutrient levels, demonstrating its beneficial role in sorghum. A split-root assay demonstrated that T. afroharzianum T22 is essential in both compartments of the pot for promoting plant growth, suggesting that local signals from this fungus drive symbiotic benefits in sorghum. RNA-seq analysis revealed that inoculation with T. afroharzianum T22 induced genes responsible for mineral transport (such as nitrate and aquaporin transporters), auxin response, sugar assimilation (hexokinase), and disease resistance (thaumatin) in sorghum roots. Microbial community analysis further unveiled the positive role of T. afroharzianum T22 in enriching Penicillium and Streptomyces while reducing disease-causing Fusarium in the roots. The microbial consortium, consisting of enriched microbiomes from bacterial and fungal communities, showed disrupted morphological features in plants inoculated with T. afroharzianum T22 in the absence of Streptomyces griseus. However, this disruption was not observed in the absence of Penicillium chrysogenum. These results indicate that S. griseus acts as a helper microbe in close association with T. afroharzianum T22 in the sorghum endosphere. This study provides the first comprehensive explanation of how T. afroharzianum T22 modulates host molecular determinants and endophytic helper microbes, thereby collectively promoting sorghum growth. These findings may facilitate the formulation of synthetic microbial inoculants dominated by T. afroharzianum T22 to enhance growth and stress resilience in sorghum and similar crops.
Dysphagia and chest pain in a 7-year-old girl
Authors: Chen Charles B , Cherupalla Balaji
Published: August 2024

Dysphagia is a common gastrointestinal complaint in the pediatric population and should raise concern for oropharyngeal as well as esophageal disorders. We describe a 7-year old patient who was admitted to the hospital for sudden onset dysphagia, abdominal pain, and decreased oral intake. Extensive evaluations including endoscopy eventually revealed herpes simplex esophagitis as well as eosinophilic esophagitis. Herpes simplex esophagitis is a rare condition in the immunocompetent population and is typically self-resolving. Eosinophilic esophagitis is a chronic, inflammatory condition characterized by esophageal eosinophilia and signs of esophageal dysfunction. The concurrent presentation of both conditions in the pediatric population has rarely been described.
Nature, Meaning, and Function of General Principles of Law in International Law
Authors: Dumberry Patrick
Published: August 2024

This chapter discusses the nature, meaning, and function of the general principles of law (GPL) in international law. While the matter has been contested by some authors in the past, it is now settled that GPL are a formal source of international law. Just like treaties and custom, GPL are a means for the creation of the law. GPL are therefore an authoritative and, most importantly, an autonomous source of law which can be used by international judges and arbitrators in the context of a dispute involving questions of international law. The chapter then considers the three different conceptions of GPL under general public international law as well as in the specific context of investment arbitration. Meanwhile, GPL serve a gap-filling function. It has been noted by some authors that international law is more susceptible to needing GPL to fill gaps than other legal orders. In addition, GPL are a source of interpretation for uncertain and ambiguous treaty and custom norms.
The production of “evidence” for migrant integration policy in the European Union
Authors: Dodevska Iva
Published: August 2024

The European Union (EU) is at the forefront of advancing a science-for-policy paradigm, developing resources and infrastructures where “evidence” in various forms can be produced, collected, and applied into policy. This article investigates the production of “useful” knowledge in the policy area of migrant integration, in a system of research–policy configurations mediated by EU institutions. The article asks: What kind of structures are set in place to support migrant integration governance with “evidence,” what counts as “evidence,” whose expertise is sought out, and what are the implications for wider debates on mobility and diversity? First, I map and classify the key channels for research–policy collaboration at inter- and supranational levels, where researchers, policymakers, and practitioners interact to produce, exchange, and disseminate various forms of knowledge on migrants and their integration. I then explore the nature of said knowledge, analyzing the various data, statistics, and indicators that are the result on such research–policy collaboration. This article finds that the EU-level ecosystem of evidence production both makes social scientific knowledge indispensable for migrant integration governance and produces ‘integration’ simultaneously as a measurable and manageable (objective) social issue, and a common European problem. I discuss possible implications of this “policy-relevant” knowledge production and propose a research agenda for an in-depth exploration of its effects on the governance of migranticized and racialized populations.
Proof of principle X-ray reflection mass measurement of the black hole in H1743−322
Authors: Nathan Edward , Ingram Adam , Steiner James F , König Ole , Dauser Thomas , Lucchini Matteo , Mastroserio Guglielmo , van der Klis Michiel , García Javier A , Connors Riley , Kara Erin , Wang Jingyi
Published: August 2024

The black hole X-ray binary H1743−322 lies in a region of the Galaxy with high extinction, and therefore it has not been possible to make a dynamical mass measurement. In this paper, we make use of a recent model which uses the X-ray reflection spectrum to constrain the ratio of the black hole mass to the source distance. By folding in a reported distance measurement, we are able to estimate the mass of the black hole to be $12\pm 2~\text{M}_\odot {}$ ($1\sigma$ credible interval). We are then able to revise a previous disc continuum fitting estimate of black hole spin $a_*$ (previously relying on a population mass distribution) using our new mass constraint, finding $a_*=0.47\pm 0.10$. This work is a proof of principle demonstration of the method, showing it can be used to find the mass of black holes in X-ray binaries.
Forecasting galaxy cluster H i mass recovery with CHIME at redshifts z = 1 and 2 via the IllustrisTNG simulations
Authors: Polzin Ava , Newburgh Laura , Natarajan Priyamvada , Chen Hsiao-Wen
Published: August 2024

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) is a drift-scan interferometer designed to map the entire northern sky every 24 h. The all-sky coverage and sensitivity to neutral hydrogen flux at intermediate redshifts makes the instrument a resource for other exciting science in addition to cosmology for which it was originally designed. Here, we demonstrate its utility for the study of the H i content of galaxy populations across environments and redshifts. We use simulated data from the IllustrisTNG project to generate mock CHIME-like intensity maps, which we cross-correlate with various tracers – including galaxies and galaxy clusters – to recover aggregate H i signals from stacking analyses. We find that there is more flux in stacks on galaxy clusters or cluster member galaxies compared to those on a general galaxy catalogue due to the enhanced number of H i-rich sources included in the CHIME primary beam. We report that it is possible to infer an average $M_\mathrm{HI}$ for clusters as a function of redshift and selection criteria from the signal in their averaged stacks despite the instrument’s low spatial resolution. This proof-of-concept result opens up a promising, and timely, new avenue to measure the evolution of the neutral hydrogen content in intermediate-to-high redshift galaxy clusters via cross-correlation of galaxy cluster catalogues with 21-cm intensity maps.
Assembly history and internal structure of cluster cold dark matter haloes
Authors: Chen Qingxiang , Liao Shihong , Wang Jie , Gao Liang
Published: August 2024

We use the Phoenix simulations to study the mass assembly history and internal structures of cluster dark matter haloes ($M_{200} \gtrsim 5\times 10^{14} h^{-1}{\rm M}_\odot$). We confirm that cluster haloes grow inside-out, similar to galactic haloes. Major merger events dominate the growth of the internal region and minor mergers/diffuse accretion shape the outskirts. However, compared to galactic haloes, cluster haloes tend to have a younger and more actively evolving inner region. On average, the majority of mass ($\gtrsim 80$ per cent) in the inner region ($R\lt 0.1 r_{200}$) of Phoenix haloes is accreted after $z = 3$, while for galactic haloes, most mass in the central region has already been accreted before $z=6$. The density profiles of cluster haloes are less stable than those of galactic haloes over different radii. The enclosed mass within 50 or 150 kpc of all Phoenix haloes evolves substantially in the past ${\sim } 7$ Gyr, while galactic haloes remained stable during the same period. We suggest that the relatively younger and more active state explains the various observations of cluster haloes, especially in central regions.
Osimertinib-induced DNA resistance mutations in cerebrospinal fluid of epidermal growth factor receptor-mutated non-small-cell lung carcinoma patients developing leptomeningeal metastases: Osimertinib Resistance Analysis-leptomeningeal metastases study
Authors: van der Wel J W Tijmen , Boelens Mirjam C , Jebbink Merel , Smulders Sietske A , Maas Klaartje W , Luitse Merel J A , Compter Annette , Boltjes Robin P B , Sol Nik , Monkhorst Kim , van den Broek Daan , Smit Egbert F , de Langen Adrianus J , Brandsma Dieta
Published: August 2024

Background

Diagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation-positive (EGFRm +) non-small-cell lung carcinoma (NSCLC) is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma.

Methods

EGFRm + patients with new or progressive LM during osimertinib were enrolled. NGS Ampliseq was performed on DNA isolated from CSF. Patients were prescribed osimertinib dose escalation (DE, 160 mg QD) following lumbar puncture. Clinical and radiological response was evaluated 4 weeks after osimertinib DE.

Results

Twenty-eight patients were included. The driver mutation was identified in 93% of CSF samples (n = 26). Seven (27%) harbored ≥1 RM. Twenty-five patients (89%) were prescribed osimertinib DE. Four weeks afterwards, symptoms improved in 5 patients, stabilized in 9 and worsened in 11 patients. Twenty-one (84%) patients underwent MR imaging. Four showed radiological improvement, 14 stabilization, and 3 worsening.

Conclusions

In 27% of patients, an RM was found in CSF ctDNA, none of which are targetable at the time of writing, and the clinical efficacy of osimertinib DE seems limited. There is much to gain in diagnostic as well as therapeutic strategies in EGFRm + NSCLC LM.
Interferon regulatory factor 8-driven reprogramming of the immune microenvironment enhances antitumor adaptive immunity and reduces immunosuppression in murine glioblastoma
Authors: Montoya Megan , Collins Sara A , Chuntova Pavlina , Patel Trishna S , Nejo Takahide , Yamamichi Akane , Kasahara Noriyuki , Okada Hideho
Published: August 2024

Background

Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell (cDC1) development, in a syngeneic murine GBM model. We hypothesized that RRV-mediated delivery of IRF8 could “reprogram” intratumoral MDSCs into antigen-presenting cells and thereby restore T-cell responses.

Methods

Effects of RRV-IRF8 on survival and tumor growth kinetics were examined in the SB28 murine GBM model. The immunophenotype was analyzed by flow cytometry and gene expression assays. We assayed functional immunosuppression and antigen presentation by ex vivo T-cell-myeloid co-culture.

Results

Intratumoral injection of RRV-IRF8 in mice bearing intracerebral SB28 glioma significantly suppressed tumor growth and prolonged survival. RRV-IRF8 treated tumors exhibited significant enrichment of cDC1s and CD8+ T-cells. Additionally, myeloid cells derived from RRV-IRF8 tumors showed decreased expression of the immunosuppressive markers Arg1 and IDO1 and demonstrated reduced suppression of naïve T-cell proliferation in ex vivo co-culture, compared to controls. Furthermore, DCs from RRV-IRF8 tumors showed increased antigen presentation compared to those from control tumors. In vivo treatment with azidothymidine (AZT), a viral replication inhibitor, showed that IRF8 transduction in both tumor and non-tumor cells is necessary for survival benefit, associated with a reprogrammed, cDC1- and CD8 T-cell-enriched TIME.

Conclusions

Our results indicate that reprogramming of glioma-infiltrating myeloid cells by in vivo expression of IRF8 may reduce immunosuppression and enhance antigen presentation, achieving improved tumor control.
Effect of bevacizumab on refractory meningiomas: 3D volumetric growth rate versus response assessment in neuro-oncology criteria
Authors: Faye Borenstein Sara , Eliahou Ruth , Amiel Alexandra , Talianski Alisa , Ofer Jonathan , Even-Haim Shaked , Kanner Andrew , Laviv Yosef , Limon Dror , Siegal Tali , Yust-Katz Shlomit
Published: August 2024

Background

Meningiomas are the most common primary tumor in the central nervous system. About 15%–20% are aggressive and tend to recur and progress despite conventional treatment. Bevacizumab has been found to be effective in the treatment of refractory meningiomas in retrospective studies. The Response Assessment in Neuro-Oncology (RANO) criteria are widely used to assess the effect of treatment. Recent studies suggest that the 3D volumetric growth rate (3DVGR) may be more accurate for irregularly shaped tumors. The aim of this study was to compare these approaches.

Methods

Twenty patients with refractory meningiomas were treated with bevacizumab. Tumors were measured using the RANO criteria and 3DVGR before and after initiation of treatment by 2 radiologists using PACS and BRAIN LAB iPLAN software, respectively, findings were compared.

Results

A total of 46 lesions were included in the final analysis. Bevacizumab was shown to be effective by both assessment methods. According to RANO criteria, the rate of progression-free survival at 6 months was 47%. According to 3DVGR, all lesions were characterized by either a decrease in volume or stable growth after treatment initiation. A decrease in 3DVGR of 50% or more was found in 90% of lesions. In several patients, there were discordances between RANO criteria and 3DVGR.

Conclusions

Although RANO criteria are widely accepted for evaluation of response to treatment of meningiomas, 3DVGR seems to generate more precise measurements of irregularly shaped tumors. The results of this study offer important evidence that bevacizumab may be beneficial in treating refractory meningiomas.