bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between drift kinetics, gyrokinetics and magnetohydrodynamics in the long-wavelength limit
Authors: McMillan B.F.
Published: March 2023

Gyrokinetic theories, even ‘global’ models, typically rely on a separation in scale (in perpendicular wavelength) between the fluctuations and the system scale. In such models direct simulation of system-scale dynamics like magnetohydrodynamic (MHD) motion is formally not consistent. Drift-kinetic theory, on the other hand, may be directly applied to model system-scale MHD-ordered behaviour. I review the long-wavelength limit of standard gyrokinetics and drift kinetics to present the relationships between these theories in an elementary fashion. This provides a pathway to global gyrokinetic modelling, resulting in an approach that is structurally similar to kinetic MHD, and I present dynamical equations for solving global field evolution in this framework. Departures from certain earlier global gyrokinetic theories include the appearance of magnetosonic (fast) modes, and the cross-coupling of the parallel and perpendicular currents with perpendicular and parallel magnetic field components. A periodic two-dimensional testcase is outlined as a benchmarking and implementation target, to help clarify practical aspects of these theories, with minimal complexity in terms of boundary conditions, and a proof-of-principle implementation of a field-solver is exhibited. To motivate this work, I first illustrate certain limitations of existing global gyrokinetic frameworks and directly identify how scale separation approximations lead to certain ‘missing’ system-scale field terms in global gyrokinetics, largely as a result of simplifications associated with the field representation in terms of

$A_{\|}$

and

$B_{\|}$

. As a result, the currents in the gyrokinetic Ampère's law resulting from a gyrokinetic equilibrium distribution do not match the currents implied by Ampère's law in a force-balance MHD equilibrium. I present a simple choice of equilibrium distribution function whose drift-kinetic currents are consistent with MHD currents; a specific Grad–Shafranov equilibrium is used to illustrate the size of the components of the parallel currents.
Artificial word formation in the epic tradition: θοῦρος (‘fierce’) and the formula θούριδος ἀλκῆς
Authors: van Beek Lucien
Published: March 2023

The Homeric adjectives θοῦρος and θοῦρις (gen. -ιδος) are normally glossed as ‘rushing, impetuous, furious’. While θοῦρις exclusively qualifies feminine nouns, no feminine form of θοῦρος is attested. What was the exact relationship between θοῦρος and θοῦρις? In this paper it is argued that θοῦρις is not the paradigmatic feminine of θοῦρος, but an artificial formation of epic Greek. It arose in the formula θούριδος ἀλκῆς due to the metrical constraints of epic hexameter, and subsequently ousted the original feminine of θοῦρος. In elaborating this scenario, I show that the basic meaning of θοῦρος and θοῦρις is ‘fierce’. Other instances of artificial change of inflection in the HomericKunstspracheare discussed, and it is argued that the mechanism underlying their creation is linguistic contamination.
Deconstructing the Phoenician myth: ‘Cadmus and the palm-leaf tablets’ revisited
Authors: Waal Willemijn
Published: March 2023

According to Herodotus, the expressionphoinikeia grammatameans ‘Phoenician letters’ and refers to the Phoenician origins of the Greek alphabet. This account has found general acceptance, but it is not the only interpretation possible and other theories circulated in antiquity. The adjective φοῖνιξ does not only mean ‘Phoenician’; it can also refer to a palm tree or the colour red. This article argues that the expressionphoinikeia grammatadid not originally refer to the alphabet, but to Linear B writing on palm leaves, as already suggested by Frederick Ahl. It is shown that the account of Herodotus is the result of a ‘learned reinterpretation’, triggered by the ambiguity of the word φοῖνιξ. The new understanding ofphoinikeia grammataproposeds here has some important consequences: it implies that Linear B, as has long been suspected, was primarily written on palm leaves (hence ‘palm-leaf writing’) and that in classical antiquity there was at least a limited historical awareness of the existence of pre-alphabetic writing systems in the Aegean. This paper adduces additional evidence to substantiate these claims. Lastly, a case will be made that Herodotus’ incorrect reinterpretation has led to the ‘Phoenicianization’ of Cadmus, who was originally a Greek hero.
Challenges and tension fields in classical instrumental group tuition: interviews with Swedish Art and Music School teachers
Authors: Knutsson Ida
Published: March 2023

Group teaching is rapidly spreading across the world, but little research has been conducted to investigate its impact on students’ musical abilities in comparison to inclusion in group tuition contexts. This article investigates how music teachers from the classical orchestra instrumental tradition discuss group tuition. Three focus group interviews were conducted with participants from one Art and Music School in Sweden. The results show a tension field between progression and inclusion as well as different views on the definition of these concepts. These differing views on teaching quality imply a balancing act for the different agents within the profession.
Hunter territoriality creates refuges for threatened primates
Authors: Griffiths Brian M , Bowler Mark , Gilmore Michael P
Published: March 2023

Unsustainable hunting threatens biodiversity in the tropics through the removal of key seed-dispersing frugivorous primates. Traditionally, hunting in the Amazon Basin was managed through hunter territoriality, with the threat of social sanctions for overexploitation. We examined hunter territoriality and differential prey selection as alternative hypotheses to central-place foraging. Territoriality occurred beyond common hunting grounds, which were on major rivers and immediately surrounding the community. Hunters displayed selectivity in prey choice, with 50% of hunters not hunting primates. The combination of hunter territoriality and differential prey selection means that over 22% of the hunted area of the Sucusari river basin could be considered primate refuge. Of the remaining hunted area, 16% was hunted relatively little by primate hunters. We suggest that the combination of territoriality and selection against primates creates refuges, mitigating the effects of sustained hunting pressure and contributing to the conservation of these species.
A Science of Reform and Retrenchment: Black Kinship Studies, Decolonisation and the Dutch Welfare State
Authors: Schields Chelsea
Published: March 2023

This paper charts the emergence of social scientific studies on Black kinship from its origins in the United States and colonial Caribbean to its revivification in the decolonisation-era Netherlands. Demonstrating how racial knowledge was from its inception a tool of transnational governance, the author argues that Black kinship studies also informed the development of the Dutch welfare state in the aftermath of decolonisation. Drawing upon Dutch state – and municipal – archival sources as well as the private papers and published works of key figures in Black kinship studies, she charts how publicly-funded sociologists and anthropologists tracked Dutch citizens from Suriname and the Netherlands Antilles through the metropolitan welfare state, producing a corpus of knowledge that connected kinship and welfare reliance. Though Caribbean-born Dutch citizens opposed the racist assumptions of state-funded scholarship, research on Black kinship ultimately informed the course of Dutch welfarism from the expansion of interventionist programmes in the 1970s to retrenchment in the 1990s.
“HOW CAN I LIBERATE THE SLAVES?” THE NEGLECTED TRADITION OF DEVELOPMENTAL ABOLITIONISM
Authors: Gaiya Abel B. S.
Published: March 2023

The abolition of slavery in the nineteenth and twentieth centuries was a long process. In terms of the economic views of abolitionists, there has been an excessive focus on the economic ideas of liberal abolitionists and their approach to “Civilization, Christianity, and Commerce.” However, there was a “developmental abolitionism” that has received little attention. Afro-American Martin R. Delany and Liberian James S. Payne were writers who approached abolitionism through this developmentalism. They favored more interventionist measures aimed at building the material power and national autonomy of Black nations to undercut the power of slave-using African chiefs, to provide indigenous Africans with employment, and to undermine the profitability of slave-based cotton production in the Americas. They also implicitly and indirectly approached labor scarcity with solutions ranging from promoting labor-saving technology to cultivating national prosperity that would improve emigration to Africa or increase birth rates.
UroLift implants as surrogate fiducial markers for cone-beam CT-based prostate image-guided radiotherapy
Authors: Al-Balushi Ahmed , Cain Michelle , Reynolds Phil , Bridge Pete
Published: March 2023

Introduction:

UroLift implants are a novel treatment for the obstructive lower urinary tract symptoms arising from benign prostatic hyperplasia. This case study aimed to assess their effectiveness as fiducial marker (FM) surrogates in prostate image-guided radiotherapy (IGRT).

Method:

Cone-beam CT images from a patient receiving prostate radiation therapy underwent manual alignment using UroLift implants and also prostate soft-tissue matching by five experienced therapeutic radiographers. The match values of both methods were compared using Bland–Altman analysis. All five observers were also asked to score the ease of matching using both approaches.

Results:

The 95% mean level of agreement for the UroLift matches were within a 2-mm threshold in all dimensions. Comparison of UroLift and prostate matches had 95% limit of agreement values of −0·98 to 1·78, −0·58 to 0·49 and −1·83 to 1·04 mm in the vertical, longitudinal and lateral planes, respectively. All of the UroLift matches were rated as ‘very easy’ or ‘possible with little difficulty’ by the five observers.

Conclusion:

A small difference between the CBCT UroLift and CBCT prostate match was found. It has been shown that IGRT to the prostate with the aid of the UroLift system implants and CBCT is feasible and can eliminate the need for FM implants. Wider evaluation in a large cohort is recommended.
Community Science‐Informed Local Policy: A Case Study in Pinole Creek Litter Assessment
Authors: Cowger Win , Gomez Itzel , Martinez‐Rubin Norma , Moriarty Ann , Harwell Todd , Anich Lisa
Published: March 2023

California is one of the only states actively managing trash in its rivers. Several community groups in Pinole, CA, USA collaborated on a Thriving Earth Exchange community science project. Its purpose was to assess the trash in Pinole Creek and identify policy development opportunities for the community. The key scientific questions were: how much trash was in the creek at the time of the study, what types of trash were most abundant, and where should the community be most concerned about trash in the creek? The team enlisted additional community volunteers at local events. A randomized sampling design and a community science‐adapted version of The San Francisco Estuary Institute's Trash Monitoring Playbook was used to survey the trash in the creek. The Thriving Earth Team estimated there were 37 m3 and 47,820 pieces of total trash in the creek channel with an average concentration of 2 m3 per km and 2,697 pieces per km. The community gained an understanding of the scale of the problem. Plastic and single‐use trash were most abundant, and the community members expressed high concern about plastic single‐use food packaging and tobacco‐related waste. The community identified locations in the creek where trash was abundant and prioritized follow‐up study locations. Seven new recommendations were presented to the Pinole City Council. The City Council unanimously voted to further discuss ordinance‐related recommendations. And that was when community science contributed to local policy development.
A Tiny New Device Could Help Find Extraterrestrial Life
Authors: White Mackenzie
Published: March 2023

Researchers developed a mini analyzer that could be a giant step forward in the search for life and habitable environments beyond Earth.
Three-dimensional single particle tracking using 4π self-interference of temporally phase-shifted fluorescence
Authors: Maurice Leanne , Bilenca Alberto
Published: March 2023

Single particle tracking in three dimensions is an indispensable tool for studying dynamic processes in various disciplines, including material sciences, physics, and biology, but often shows anisotropic three-dimensional spatial localization precision, which restricts the tracking precision, and/or a limited number of particles that can be tracked simultaneously over extended volumes. Here we developed an interferometric, three-dimensional fluorescence single particle tracking method based on conventional widefield excitation and temporal phase-shift interference of the emitted, high-aperture-angle, fluorescence wavefronts in a greatly simplified, free-running, triangle interferometer that enables tracking of multiple particles at the same time with <10-nm spatial localization precision in all three dimensions over extended volumes (~35 × 35 × 2 μm3) at video rate (25 Hz). We applied our method to characterize the microenvironment of living cells and up to ~40 μm deep in soft materials.
Deep learning-enabled virtual histological staining of biological samples
Authors: Bai Bijie , Yang Xilin , Li Yuzhu , Zhang Yijie , Pillar Nir , Ozcan Aydogan
Published: March 2023

Histological staining is the gold standard for tissue examination in clinical pathology and life-science research, which visualizes the tissue and cellular structures using chromatic dyes or fluorescence labels to aid the microscopic assessment of tissue. However, the current histological staining workflow requires tedious sample preparation steps, specialized laboratory infrastructure, and trained histotechnologists, making it expensive, time-consuming, and not accessible in resource-limited settings. Deep learning techniques created new opportunities to revolutionize staining methods by digitally generating histological stains using trained neural networks, providing rapid, cost-effective, and accurate alternatives to standard chemical staining methods. These techniques, broadly referred to as virtual staining, were extensively explored by multiple research groups and demonstrated to be successful in generating various types of histological stains from label-free microscopic images of unstained samples; similar approaches were also used for transforming images of an already stained tissue sample into another type of stain, performing virtual stain-to-stain transformations. In this Review, we provide a comprehensive overview of the recent research advances in deep learning-enabled virtual histological staining techniques. The basic concepts and the typical workflow of virtual staining are introduced, followed by a discussion of representative works and their technical innovations. We also share our perspectives on the future of this emerging field, aiming to inspire readers from diverse scientific fields to further expand the scope of deep learning-enabled virtual histological staining techniques and their applications.
Upconversion nanoscopy revealing surface heterogeneity of tumor-secreted extracellular vesicles
Authors: Pu Rui , Zhan Qiuqiang
Published: March 2023

Super-resolution microscopic imaging employing upconversion nanoparticles is applied to reveal the surface heterogeneity of tumor cell-derived small extracellular vesicles, i.e., exosome. The number of surface antigens of every extracellular vesicles can be quantified by both the high imaging resolution and stable brightness of upconversion nanoparticles. This method proves its great potential in nanoscale biological studies.
In-situ growth of low-dimensional perovskite-based insular nanocrystals for highly efficient light emitting diodes
Authors: Wang Hao , Xu Weidong , Wei Qi , Peng Si , Shang Yuequn , Jiang Xianyuan , Yu Danni , Wang Kai , Pu Ruihua , Zhao Chenxi , Zang Zihao , Li Hansheng , Zhang Yile , Pan Ting , Peng Zijian , Shen Xiaoqin , Ling Shengjie , Liu Weimin , Gao Feng , Ning Zhijun
Published: March 2023

Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices. However, judicious control of the grain growth for perovskite light emitting diodes is elusive due to its multiple requirements in terms of morphology, composition, and defect. Herein, we demonstrate a supramolecular dynamic coordination strategy to regulate perovskite crystallization. The combined use of crown ether and sodium trifluoroacetate can coordinate with A site and B site cations in ABX3perovskite, respectively. The formation of supramolecular structure retard perovskite nucleation, while the transformation of supramolecular intermediate structure enables the release of components for slow perovskite growth. This judicious control enables a segmented growth, inducing the growth of insular nanocrystal consist of low-dimensional structure. Light emitting diode based on this perovskite film eventually brings a peak external quantum efficiency up to 23.9%, ranking among the highest efficiency achieved. The homogeneous nano-island structure also enables high-efficiency large area (1 cm2) device up to 21.6%, and a record high value of 13.6% for highly semi-transparent ones.
Serine-arginine protein kinase 1 (SRPK1) promotes EGFR-TKI resistance by enhancing GSK3β Ser9 autophosphorylation independent of its kinase activity in non-small-cell lung cancer
Authors: Huang Jing-Qiang , Duan Ling-Xin , Liu Qiu-Yu , Li He-Feng , Hu Ao-Ping , Song Jun-Wei , Lin Chuxuan , Huang Bingsheng , Yao Da , Peng Bin , Sun Yehong , Wen Yuxin , Yang Lin , Xu Xingzhi , Gong Li-Yun
Published: March 2023

Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a major challenge for clinicians and patients with non-small cell lung cancer (NSCLC). Serine-arginine protein kinase 1 (SRPK1) is a key oncoprotein in the EGFR/AKT pathway that participates in tumorigenesis. We found that high SRPK1 expression was significantly associated with poor progression-free survival (PFS) in patients with advanced NSCLC undergoing gefitinib treatment. Both in vitro and in vivo assays suggested that SRPK1 reduced the ability of gefitinib to induce apoptosis in sensitive NSCLC cells independently of its kinase activity. Moreover, SRPK1 facilitated binding between LEF1, β-catenin and the EGFR promoter region to increase EGFR expression and promote the accumulation and phosphorylation of membrane EGFR. Furthermore, we verified that the SRPK1 spacer domain bound to GSK3β and enhanced its autophosphorylation at Ser9 to activate the Wnt pathway, thereby promoting the expression of Wnt target genes such as Bcl-X. The correlation between SRPK1 and EGFR expression was confirmed in patients. In brief, our research suggested that the SRPK1/GSK3β axis promotes gefitinib resistance by activating the Wnt pathway and may serve as a potential therapeutic target for overcoming gefitinib resistance in NSCLC.
USP35 promotes cell proliferation and chemotherapeutic resistance through stabilizing FUCA1 in colorectal cancer
Authors: Xiao Yi , Jiang Xiaoyu , Yin Ke , Miao Tianshu , Lu Hanlin , Wang Wenqing , Ma Lijuan , Zhao Yinghui , Liu Chunyan , Qiao Yun , Zhang Pengju
Published: March 2023

Ubiquitin-specific-processing proteases 35 (USP35) is an under-characterized deubiquitinase and its role in colorectal cancer (CRC) remains unclear. Here, we focus on delineating the impact of USP35 on CRC cell proliferation and chemo-resistance, as well as the possible regulatory mechanism. By examining the genomic database and clinical samples, we found that USP35 was overexpressed in CRC. Further functional studies showed that enhanced USP35 expression promoted CRC cell proliferation and resistance to oxaliplatin (OXA) and 5-fluorouracil (5-FU), whereas USP35 depletion impeded cell proliferation and sensitized cells to OXA and 5-FU treatments. Then, to explore the possible mechanism underlying USP35-triggered cellular responses, we performed co-immunoprecipitation (co-IP) followed by mass spectrometry (MS) analysis and identified α-L-fucosidase 1 (FUCA1) as a direct deubiquitiation target of USP35. Importantly, we demonstrated that FUCA1 was an essential mediator for USP35-induced cell proliferation and chemo-resistance in vitro and in vivo. Finally, we observed that nucleotide excision repair (NER) components (e.g., XPC, XPA, ERCC1) were up-regulated by USP35-FUCA1 axis, indicating a potential mechanism for USP35-FUCA1-mediated platinum resistance in CRC. Together, our results for the first time explored the role and important mechanism of USP35 in CRC cell proliferation and chemotherapeutic response, providing a rationale for USP35-FUCA1-targeted therapy in CRC.
Cancer-specific tissue-resident memory T-cells express ZNF683 in colorectal cancer
Authors: Kitakaze Masatoshi , Uemura Mamoru , Hara Tomoaki , Chijimatsu Ryota , Motooka Daisuke , Hirai Toshiro , Konno Masamitsu , Okuzaki Daisuke , Sekido Yuki , Hata Tsuyoshi , Ogino Takayuki , Takahashi Hidekazu , Miyoshi Norikatsu , Ofusa Ken , Mizushima Tsunekazu , Eguchi Hidetoshi , Doki Yuichiro , Ishii Hideshi
Published: March 2023

Background

Tissue-resident memory T (Trm) cells are associated with cytotoxicity not only in viral infection and autoimmune disease pathologies but also in many cancers. Tumour-infiltrating CD103+ Trm cells predominantly comprise CD8 T cells that express cytotoxic activation and immune checkpoint molecules called exhausted markers. This study aimed to investigate the role of Trm in colorectal cancer (CRC) and characterise the cancer-specific Trm.

Methods

Immunochemical staining with anti-CD8 and anti-CD103 antibodies for resected CRC tissues was used to identify the tumour-infiltrating Trm cells. The Kaplan–Meier estimator was used to evaluate the prognostic significance. Cells immune to CRC were targeted for single-cell RNA-seq analysis to characterise cancer-specific Trm cells in CRC.

Results

The number of CD103+/CD8+ tumour-infiltrating lymphocytes (TILs) was a favourable prognostic and predictive factor of the overall survival and recurrence-free survival in patients with CRC. Single-cell RNA-seq analysis of 17,257 CRC-infiltrating immune cells revealed a more increased zinc finger protein 683 (ZNF683) expression in cancer Trm cells than in noncancer Trm cells and in high-infiltrating Trm cells than low-infiltrating Trm in cancer, with an upregulated T-cell receptor (TCR)- and interferon-γ (IFN-γ) signalling-related gene expression in ZNF683+ Trm cells.

Conclusions

The number of CD103+/CD8+ TILs is a prognostic predictive factor in CRC. In addition, we identified the ZNF683 expression as one of the candidate markers of cancer-specific Trm cells. IFN-γ and TCR signalling and ZNF683 expression are involved in Trm cell activation in tumours and are promising targets for cancer immunity regulation.
RNA splicing analysis using heterogeneous and large RNA-seq datasets
Authors: Vaquero-Garcia Jorge , Aicher Joseph K. , Jewell San , Gazzara Matthew R. , Radens Caleb M. , Jha Anupama , Norton Scott S. , Lahens Nicholas F. , Grant Gregory R. , Barash Yoseph
Published: March 2023

The ubiquity of RNA-seq has led to many methods that use RNA-seq data to analyze variations in RNA splicing. However, available methods are not well suited for handling heterogeneous and large datasets. Such datasets scale to thousands of samples across dozens of experimental conditions, exhibit increased variability compared to biological replicates, and involve thousands of unannotated splice variants resulting in increased transcriptome complexity. We describe here a suite of algorithms and tools implemented in the MAJIQ v2 package to address challenges in detection, quantification, and visualization of splicing variations from such datasets. Using both large scale synthetic data and GTEx v8 as benchmark datasets, we assess the advantages of MAJIQ v2 compared to existing methods. We then apply MAJIQ v2 package to analyze differential splicing across 2,335 samples from 13 brain subregions, demonstrating its ability to offer insights into brain subregion-specific splicing regulation.
Fibroblastic reticular cells in lymph node potentiate white adipose tissue beiging through neuro-immune crosstalk in male mice
Authors: Cheong Lai Yee , Wang Baile , Wang Qin , Jin Leigang , Kwok Kelvin H. M. , Wu Xiaoping , Shu Lingling , Lin Huige , Chung Sookja Kim , Cheng Kenneth K. Y. , Hoo Ruby L. C. , Xu Aimin
Published: March 2023

Lymph nodes (LNs) are always embedded in the metabolically-active white adipose tissue (WAT), whereas their functional relationship remains obscure. Here, we identify fibroblastic reticular cells (FRCs) in inguinal LNs (iLNs) as a major source of IL-33 in mediating cold-induced beiging and thermogenesis of subcutaneous WAT (scWAT). Depletion of iLNs in male mice results in defective cold-induced beiging of scWAT. Mechanistically, cold-enhanced sympathetic outflow to iLNs activates β1- and β2-adrenergic receptor (AR) signaling in FRCs to facilitate IL-33 release into iLN-surrounding scWAT, where IL-33 activates type 2 immune response to potentiate biogenesis of beige adipocytes. Cold-induced beiging of scWAT is abrogated by selective ablation of IL-33 or β1- and β2-AR in FRCs, or sympathetic denervation of iLNs, whereas replenishment of IL-33 reverses the impaired cold-induced beiging in iLN-deficient mice. Taken together, our study uncovers an unexpected role of FRCs in iLNs in mediating neuro-immune interaction to maintain energy homeostasis.
Site-specific anisotropic assembly of amorphous mesoporous subunits on crystalline metal–organic framework
Authors: Liu Minchao , Shang Cheng , Zhao Tiancong , Yu Hongyue , Kou Yufang , Lv Zirui , Hou Mengmeng , Zhang Fan , Li Qiaowei , Zhao Dongyuan , Li Xiaomin
Published: March 2023

As an important branch of anisotropic nanohybrids (ANHs) with multiple surfaces and functions, the porous ANHs (p-ANHs) have attracted extensive attentions because of the unique characteristics of high surface area, tunable pore structures and controllable framework compositions, etc. However, due to the large surface-chemistry and lattice mismatches between the crystalline and amorphous porous nanomaterials, the site-specific anisotropic assembly of amorphous subunits on crystalline host is challenging. Here, we report a selective occupation strategy to achieve site-specific anisotropic growth of amorphous mesoporous subunits on crystalline metal–organic framework (MOF). The amorphous polydopamine (mPDA) building blocks can be controllably grown on the {100} (type 1) or {110} (type 2) facets of crystalline ZIF-8 to form the binary super-structured p-ANHs. Based on the secondary epitaxial growth of tertiary MOF building blocks on type 1 and 2 nanostructures, the ternary p-ANHs with controllable compositions and architectures are also rationally synthesized (type 3 and 4). These intricate and unprecedented superstructures provide a good platform for the construction of nanocomposites with multiple functionalities and understanding of the structure-property-function relationships.
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors
Authors: Mainwaring Oliver J. , Weishaupt Holger , Zhao Miao , Rosén Gabriela , Borgenvik Anna , Breinschmid Laura , Verbaan Annemieke D. , Richardson Stacey , Thompson Dean , Clifford Steven C. , Hill Rebecca M. , Annusver Karl , Sundström Anders , Holmberg Karl O. , Kasper Maria , Hutter Sonja , Swartling Fredrik J.
Published: March 2023

Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.
Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase
Authors: Schindler Natalie , Tonn Matthias , Kellner Vanessa , Fung Jia Jun , Lockhart Arianna , Vydzhak Olga , Juretschke Thomas , Möckel Stefanie , Beli Petra , Khmelinskii Anton , Luke Brian
Published: March 2023

Single ribonucleoside monophosphates (rNMPs) are transiently present in eukaryotic genomes. The RNase H2-dependent ribonucleotide excision repair (RER) pathway ensures error-free rNMP removal. In some pathological conditions, rNMP removal is impaired. If these rNMPs hydrolyze during, or prior to, S phase, toxic single-ended double-strand breaks (seDSBs) can occur upon an encounter with replication forks. How such rNMP-derived seDSB lesions are repaired is unclear. We expressed a cell cycle phase restricted allele of RNase H2 to nick at rNMPs in S phase and study their repair. Although Top1 is dispensable, the RAD52 epistasis group and Rtt101Mms1-Mms22 dependent ubiquitylation of histone H3 become essential for rNMP-derived lesion tolerance. Consistently, loss of Rtt101Mms1-Mms22 combined with RNase H2 dysfunction leads to compromised cellular fitness. We refer to this repair pathway as nick lesion repair (NLR). The NLR genetic network may have important implications in the context of human pathologies.
An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping
Authors: Wang Zhao , Liang Qian , Qian Xinyi , Hu Bolang , Zheng Zhanye , Wang Jianhua , Hu Yuelin , Bao Zhengkai , Zhao Ke , Zhou Yao , Feng Xiangling , Yi Xianfu , Li Jin , Shi Jiandang , Liu Zhe , Hao Jihui , Chen Kexin , Yu Ying , Sham Pak Chung , Lu Wange , Wang Xiaoyan , Song Weihong , Li Mulin Jun
Published: March 2023

Genetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of autoimmune disease pleiotropic loci, we found most of these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize causal pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal. Mechanistically, the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific loop to promote IRF5-short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.
Return of the Tbx5; lineage-tracing reveals ventricular cardiomyocyte-like precursors in the injured adult mammalian heart
Authors: Siatra Panagiota , Vatsellas Giannis , Chatzianastasiou Athanasia , Balafas Evangelos , Manolakou Theodora , Papapetropoulos Andreas , Agapaki Anna , Mouchtouri Eleni-Taxiarchia , Ruchaya Prashant J. , Korovesi Artemis G. , Mavroidis Manolis , Thanos Dimitrios , Beis Dimitris , Kokkinopoulos Ioannis
Published: March 2023

The single curative measure for heart failure patients is a heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult mammalian cardiac muscle, often leads to a heart attack through the irreversible loss of a large number of cardiomyocytes, due to an idle regenerative capability. Recent reports in zebrafish indicate that Tbx5a is a vital transcription factor for cardiomyocyte regeneration. Preclinical data underscore the cardioprotective role of Tbx5 upon heart failure. Data from our earlier murine developmental studies have identified a prominent unipotent Tbx5-expressing embryonic cardiac precursor cell population able to form cardiomyocytes, in vivo, in vitro and ex vivo. Using a developmental approach to an adult heart injury model and by employing a lineage-tracing mouse model as well as the use of single-cell RNA-seq technology, we identify a Tbx5-expressing ventricular cardiomyocyte-like precursor population, in the injured adult mammalian heart. The transcriptional profile of that precursor cell population is closer to that of neonatal than embryonic cardiomyocyte precursors. Tbx5, a cardinal cardiac development transcription factor, lies in the center of a ventricular adult precursor cell population, which seems to be affected by neurohormonal spatiotemporal cues. The identification of a Tbx5-specific cardiomyocyte precursor-like cell population, which is capable of dedifferentiating and potentially deploying a cardiomyocyte regenerative program, provides a clear target cell population for translationally-relevant heart interventional studies.
Human exposure to per- and polyfluoroalkyl substances and other emerging contaminants in drinking water
Authors: Cserbik Dora , Redondo-Hasselerharm Paula E. , Farré Maria J. , Sanchís Josep , Bartolomé Arantxa , Paraian Alexandra , Herrera Eva María , Caixach Josep , Villanueva Cristina M. , Flores Cintia
Published: March 2023

A wide range of chemicals was measured in different types of drinking water and urine samples through target and non-target screening (NTS) to estimate human exposure. Tap water samples collected from 42 locations in Barcelona (August–October/2020, May/2021), tap water filtered with domestic activated carbon filters (AC, N = 6) and reverse osmosis (RO, N = 5), commercial bottled water (N = 10), and urine (N = 39) samples were included. 35 per- and polyfluoroalkyl substances (PFAS), bisphenol A, and nonylphenol were analyzed using LC–MS/MS and GC–MS/MS, and NTS using LC–HRMS. 9 PFAS were detected in unfiltered tap water of first sampling (79% samples, median = 30 ng/L), 6 in the second (69%, median = 9.8 ng/L), and 5 in 13% urine samples. NTS tentatively identified pharmaceuticals and other industrial chemicals in drinking water. PFAS were removed by RO and not by AC filters. Findings provide valuable information for exposure science and water quality monitoring of emerging drinking water contaminants.
Sand fly population dynamics in areas of American cutaneous leishmaniasis, Municipality of Paraty, Rio de Janeiro, Brazil
Authors: Vieira Vanessa Rendeiro , de Aguiar Gustavo Marins , de Azevedo Alfredo Carlos Rodrigues , Rangel Elizabeth Ferreira , Guimarães Anthony Érico
Published: March 2023

The present study is the second and last part of the study that investigated the fauna and behavior of sand flies in areas prone to cutaneous leishmaniasis outbreaks, in the State of Rio de Janeiro, in the municipality of Paraty. To collect the sand flies, CDC and Shannon light traps were used, installed in the peridomiciliary and forest areas, and manual suction tubes on the walls of the home and in the animal shelters. A total of 102,937 sand flies, belonging to nine genera and 23 species were captured from October 2009 to September 2012. Regarding the monthly frequency of sand flies, the period of highest density was from November to March, with a maximum peak in January. The lowest density was observed in June and July. In the studied area, the species of epidemiological importance, Nyssomyia intermedia, Pintomyia fischeri, Migonemyia migonei and Nyssomyia whitmani, were found in all months of the year, a period in which residents may be in contact with these vectors of the etiological agent of cutaneous leishmaniasis.
Full C-band wavelength-tunable, 250 MHz repetition rate mode-locked polarization-maintaining fiber laser
Authors: Jang Yoon-Soo , Park Jungjae , Jin Jonghan
Published: March 2023

We demonstrate a full C-band wavelength-tunable mode-locked fiber laser with a repetition rate of 250 MHz, representing the highest repetition rate for C-band tunable mode-locked lasers thus far to the best of our knowledge. The polarization-maintaining fiber-based Fabry–Perot cavity enables a fundamental repetition rate of 250 MHz with a semiconductor saturable absorber mirror as a mode-locker. We observed a stable and single soliton mode-locking state with wide tunability of the center wavelength from 1505 to 1561 nm by adjusting the incident angle of a bandpass filter inside the cavity. The wavelength-tunable high-repetition-rate mode-locked laser covering the full C-band is expected to be a compelling source for many frequency-comb-based applications, including high-precision optical metrology, broadband absorption spectroscopy, and broadband optical frequency synthesizers.
Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer
Authors: Ricordel Charles , Chaillot L. , Vlachavas E. I. , Logotheti M. , Jouannic A. , Desvallees T. , Lecuyer G. , Aubry M. , Kontogianni G. , Mastrokalou C. , Jouan F. , Jarry U. , Corre R. , Le Guen Y. , Guillaudeux T. , Lena H. , Chatziioannou A. , Pedeux Rémy
Published: March 2023

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.
Observational evidence of salt finger in the diurnal thermocline
Authors: Ashin K. , Girishkumar M. S. , D’Asaro Eric , Jofia J. , Sherin V. R. , Sureshkumar N. , Rao E. Pattabhi Ram
Published: March 2023

Due to strong turbulent mixing, the ocean surface boundary layer region is generally not conducive to double diffusion. However, vertical microstructure profiles observations in the northeastern Arabian Sea during May 2019 imply the formation of salt fingers in the diurnal thermocline (DT) region during the daytime. In the DT layer, conditions are favorable for salt fingering: Turner angle values are between 50 and 55° with both temperature and salinity decreasing with depth; shear-driven mixing is weak with a turbulent Reynolds number of about 30. The presence of salt fingering in the DT is confirmed by the presence of staircase-like structures with step sizes larger than the Ozmidov length and by the dissipation ratio that is larger than the mixing coefficient. The unusual daytime salinity maximum in the mixed layer that supports salt fingering is primarily due to a daytime reduction in vertical entrainment of fresh water along with minor contributions from evaporation and horizontal advection and a significant contribution from detrainment processes.
Microbiomes of a disease-resistant genotype of Acropora cervicornis are resistant to acute, but not chronic, nutrient enrichment
Authors: Klinges J. Grace , Patel Shalvi H. , Duke William C. , Muller Erinn M. , Vega Thurber Rebecca L.
Published: March 2023

Chronically high levels of inorganic nutrients have been documented in Florida’s coral reefs and are linked to increased prevalence and severity of coral bleaching and disease. Naturally disease-resistant genotypes of the staghorn coral Acropora cervicornis are rare, and it is unknown whether prolonged exposure to acute or chronic high nutrient levels will reduce the disease tolerance of these genotypes. Recently, the relative abundance of the bacterial genus Aquarickettsia was identified as a significant indicator of disease susceptibility in A. cervicornis, and the abundance of this bacterial species was previously found to increase under chronic and acute nutrient enrichment. We therefore examined the impact of common constituents of nutrient pollution (phosphate, nitrate, and ammonium) on microbial community structure in a disease-resistant genotype with naturally low abundances of Aquarickettsia. We found that although this putative parasite responded positively to nutrient enrichment in a disease-resistant host, relative abundances remained low (< 0.5%). Further, while microbial diversity was not altered significantly after 3 weeks of nutrient enrichment, 6 weeks of enrichment was sufficient to shift microbiome diversity and composition. Coral growth rates were also reduced by 6 weeks of nitrate treatment compared to untreated conditions. Together these data suggest that the microbiomes of disease-resistant A. cervicornis may be initially resistant to shifts in microbial community structure, but succumb to compositional and diversity alterations after more sustained environmental pressure. As the maintenance of disease-resistant genotypes is critical for coral population management and restoration, a complete understanding of how these genotypes respond to environmental stressors is necessary to predict their longevity.
Effect of bacterial resistant zwitterionic derivative incorporation on the physical properties of resin-modified glass ionomer luting cement
Authors: Wu Chengzan , Kim Min-Ji , Mangal Utkarsh , Seo Ji-Young , Kim Ji-Yeong , Kim Junho , Park Ju-Young , Kwon Jae-Sung , Choi Sung-Hwan
Published: March 2023

Biofilms induce microbial-mediated surface roughening and deterioration of cement. In this study, zwitterionic derivatives (ZD) of sulfobetaine methacrylate (SBMA) and 2-methacryloyloxyethyl phosphorylcholine, were added in concentrations of 0, 1, and 3% to three different types of commercially available resin-modified glass ionomer cement (RMGIC) (RMC-I: RelyX Luting 2, RMC-II: Nexus RMGI, and RMC-III: GC FujiCEM 2). The unmodified RMGICs served as the control group for comparison. The resistance of Streptococcus mutans to ZD-modified RMGIC was evaluated with a monoculture biofilm assay. The following physical properties of the ZD-modified RMGIC were assessed: wettability, film thickness, flexural strength, elastic modulus, shear bond strength, and failure mode. The ZD-modified RMGIC significantly inhibited biofilm formation, with at least a 30% reduction compared to the control group. The addition of ZD improved the wettability of RMGIC; however, only 3% of the SBMA group was statistically different (P < 0.05). The film thickness increased in proportion to the increasing ZD concentrations; there was no statistical difference within the RMC-I (P > 0.05). The experimental groups' flexural strength, elastic modulus, and shear bond strength showed an insignificant decrease from the control group; there was no statistical difference within the RMC-I (P > 0.05). The mode of failure differed slightly in each group, but all groups showed dominance in the adhesive and mixed failure. Thus, the addition of 1 wt.% ZD in RMGIC favorably enhanced the resistance to Streptococcus mutans without any tangible loss in flexural and shear bond strength.
The temporal cost of deploying attention limits accurate target identification in rapid serial visual presentation
Authors: Kimata Anna R. , Zheng Bryan , Watanabe Takeo , Asaad Wael F.
Published: March 2023

Lag-1 sparing is a common exception to the attentional blink, where a target presented directly after T1 can be identified and reported accurately. Prior work has proposed potential mechanisms for lag 1 sparing, including the boost and bounce model and the attentional gating model. Here, we apply a rapid serial visual presentation task to investigate the temporal limitations of lag 1 sparing by testing three distinct hypotheses. We found that endogenous engagement of attention to T2 requires between 50 and 100 ms. Critically, faster presentation rates yielded lower T2 performance, whereas decreased image duration did not impair T2 detection and report. These observations were reinforced by subsequent experiments controlling for short-term learning and capacity-dependent visual processing effects. Thus, lag-1 sparing was limited by the intrinsic dynamics of attentional boost engagement rather than by earlier perceptual bottlenecks such as insufficient exposure to images in the stimulus stream or visual processing capacity limitations. Taken together, these findings support the boost and bounce theory over earlier models that focus only on attentional gating or visual short-term memory storage, informing our understanding of how the human visual system deploys attention under challenging temporal constraints.
Adaptive mechanism in Quercus brantii Lindl. leaves under climatic differentiation: morphological and anatomical traits
Authors: Soheili Forough , Heydari Mehdi , Woodward Stephen , Naji Hamid Reza
Published: March 2023

Leaf traits, which vary across different climatic conditions, can reveal evolutionary changes within a species made to adapt to the environment. Leaf traits play major roles in a plant functions under varying climatic conditions. To examine adaptive modes and mechanisms applied by plants in different climates, we analyzed leaf morphology and anatomical structures in Quercus brantii in the Zagros forests, Western Iran. The plants adapted to the environmental differences with increased dry matter content in a Mediterranean climate, and increasing leaf length, specific leaf area, stomata length (SL), stomata width, stomatal density (SD), stomatal pore index (SPI), trichome length, and width in a sub-humid climate; trichome density was increased in a semi-arid climate. There were strong, positive correlations between SPI with SL and SD. Correlations for other leaf traits were weakly significant. Such morphological and anatomical plasticity probably leads to lower transpiration rates, control of internal temperature and water status, and improved photosynthetic capability under stressing conditions. These findings provide new insights into the adaptive strategies of plants to environmental changes at the morphological and anatomical levels.