bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehospital Surgical Cricothyrotomy in a Ground-Based 9-1-1 EMS System: A Retrospective Review
Authors: Lulla Al , Dickson Robert , Wells Michael , Gilbert Matthew , Rogers Keene Kelly , Patrick Casey
Published: April 2024

Background:

Airway management is a cornerstone in the prehospital care of critically ill or injured patients. Surgical cricothyrotomy offers a rapid and effective solution when oxygenation and ventilation fail using less-invasive techniques. However, the exact indications, incidence, and success of prehospital surgical cricothyrotomy are unknown, with variable rates reported in the literature. This study aimed to examine prehospital indications and success rates for surgical cricothyrotomy within a large, suburban, ground-based Emergency Medical Services (EMS) system.

Methods:

This is a retrospective analysis of 31 patients who underwent paramedic performed surgical cricothyrotomy from 2012 through 2022. Key demographic parameters were analyzed, including the incidence of cardiac arrest, call type (trauma versus medical), initial airway management attempts, number of endotracheal intubation (ETI) attempts before surgical airway, and average time to the establishment of a surgical airway in relation to the number of ETI attempts. Surgical cricothyrotomy success was defined as the acquisition of four-phase end-tidal capnography reading. The primary data sources were the EMS electronic medical records, and descriptive statistics were calculated.

Results:

A total of 31 patients were included in the final analysis. Of those who received a surgical cricothyrotomy, 42% (13/31) occurred in the trauma setting, while 58% (18/31) were medical calls. In all patients who underwent surgical cricothyrotomy, the median (IQR) time to the procedure was 17 minutes (IQR = 11-24). In trauma patients, the median time to surgical cricothyrotomy was 12 minutes (IQR = 9-19) versus 19 minutes (IQR = 14-33) in medical patients. End-tidal carbon dioxide (ETCO2) detection and placement success was confirmed in 94% (29/31) of patients. Endotracheal intubation was attempted in 55% (17/31) before subsequent surgical cricothyrotomy, with 29% (9/31) receiving more than one ETI attempt. The median time to surgical cricothyrotomy when multiple prior intubation attempts occurred was 33 minutes (IQR = 23-36) compared to 14.5 minutes (IQR = 6-19) in patients without a preceding intubation attempt.

Conclusion:

Prehospital surgical airway can be performed by paramedics with a high degree of success. Identification of the need for surgical cricothyrotomy should be determined as soon as possible to allow for rapid securement of the airway and to ensure adequate oxygenation and ventilation.
Global Analysis of Surface Ocean CO2 Fugacity and Air‐Sea Fluxes With Low Latency
Authors: Chau Thi‐Tuyet‐Trang , Chevallier Frédéric , Gehlen Marion
Published: April 2024

The Surface Ocean CO2 Atlas (SOCAT) of CO2 fugacity (fCO2) observations is a key resource supporting annual assessments of CO2 uptake by the ocean and its side effects on the marine ecosystem. SOCAT data are usually released with a lag of up to 1.5 years which hampers timely quantification of recent variations of carbon fluxes between the Earth System components, not only with the ocean. This study uses a statistical ensemble approach to analyze fCO2 with a latency of one month only based on the previous SOCAT release and a series of predictors. Results indicate a modest degradation in a retrospective prediction test for 2021–2022. The generated fCO2 and fluxes for January–August 2023 show a progressive reduction in the Equatorial Pacific source following the La Niña retreat. A breaking‐record decrease in the northeastern Atlantic CO2 sink has been diagnosed on account of the marine heatwave event in June 2023.
Modeling Ion Conic Formation in Io's Auroral Footprint
Authors: Glocer A. , Garcia‐Sage K. , Sulaiman A. , Clark G. , Szalay J. R. , Sarkango Y. , Bell J.
Published: April 2024

Energetic ions outflowing from Jupiter's atmosphere was observed during Juno's 12th perijove crossing (PJ12) in the vicinity of Io's auroral footprint and reported by prior studies. It was hypothesized that Wave‐Particle Interactions (WPI) with ion cyclotron waves observed coincident with the ion outflow may be responsible for the heating and subsequent outflow. This study uses numerical simulation and data model comparison to test whether ion cyclotron resonant heating is indeed a plausible mechanism to explain the intense ion outflow observed. Our simulations assume that the wave heating is of limited duration due to Io's footprint motion. The simulations are moreover compared to the previously published Jupiter Energetic Particle Detector Instruments (JEDI) observations at high energies, and the lower energy Jovian Auroral Distributions Experiment (JADE) observations that were not previously reported. We find that the ion cyclotron resonant heating mechanism can indeed lead to ion conic formation and strong vertical transport under certain assumptions about the distribution of wave power with altitude. We also find that the ion outflow is energized quickly with very rapid formation of the ion conic distribution. The implications of the intense ion outflow are also examined and it is found that such strong wave heating can lead to a depletion of the topside ionosphere.
Foundations in Hazards and Disasters for Undergraduate Students
Authors: Hinga Bethany
Published: April 2024

A new textbook for undergraduates explores different types of natural hazards and disasters through foundational scientific knowledge, engaging case studies, and mitigation strategies.
Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration
Authors: Wu Jiayi , Li Feifei , Yu Peng , Yu Changhao , Han Chuyi , Wang Yitian , Yu Fanyuan , Ye Ling
Published: April 2024

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.
Nicotinamide Mononucleotide improves oocyte maturation of mice with type 1 diabetes
Authors: Guo Fucheng , Wang Luyao , Chen Yurong , Zhu Haibo , Dai Xiangpeng , Zhang Xiaoling
Published: April 2024

Background

The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN’s effect.

Methods

Streptozotocin (STZ) was used to establish the mouse models with type 1 diabetes. The successful establishment of the models was confirmed by the results of body weight test, fasting blood glucose test and haematoxylin and eosin (H&E) staining. The in vitro maturation (IVM) rate of oocytes from diabetic mice was examined. Immunofluorescence staining (IF) was performed to examine the reactive oxygen species (ROS) level, spindle/chromosome structure, mitochondrial function, actin dynamics, DNA damage and histone modification of oocytes, which are potential factors affecting the oocyte quality. The quantitative reverse transcription PCR (RT-qPCR) was used to detect the mRNA levels of Sod1, Opa1, Mfn2, Drp1, Sirt1 and Sirt3 in oocytes.

Results

The NMN supplementation increased the oocyte maturation rate of the mice with diabetes. Furthermore, NMN supplementation improved the oocyte quality by rescuing the actin dynamics, reversing meiotic defects, improving the mitochondrial function, reducing ROS level, suppressing DNA damage and restoring changes in histone modifications of oocytes collected from the mice with diabetes.

Conclusion

NMN could improve the maturation rate and quality of oocytes in STZ-induced diabetic mice, which provides a significant clue for the treatment of infertility of the patients with diabetes.
GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation
Authors: Yang Yuxi , Song Shuangshuang , Li Shujing , Kang Jie , Li Yulin , Zhao Nannan , Ye Dongman , Qin Fengying , Du Yixin , Sun Jing , Yu Tao , Wu Huijian
Published: April 2024

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65’s transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.
Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling
Authors: Wang Kun , Liu Yin , Li Huimin , Liang Xiaoqing , Hao Mengdi , Yuan Dajin , Ding Lei
Published: April 2024

Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.
CMYC-initiated HNF1A-AS1 overexpression maintains the stemness of gastric cancer cells
Authors: Zhao Ruinan , Guo Xiangyu , Zhang Guohao , Liu Sen , Ma Ranran , Wang Mengqi , Chen Shiming , Zhu Wenjie , Liu Yuan , Gao Peng , Liu Haiting
Published: April 2024

Cancer stem cells (CSCs) are believed to be responsible for cancer metastasis and recurrence due to their self-renewal ability and resistance to treatment. However, the mechanisms that regulate the stemness of CSCs remain poorly understood. Recently, evidence has emerged suggesting that long non-coding RNAs (lncRNAs) play a crucial role in regulating cancer cell function in different types of malignancies, including gastric cancer (GC). However, the specific means by which lncRNAs regulate the function of gastric cancer stem cells (GCSCs) are yet to be fully understood. In this study, we investigated a lncRNA known as HNF1A-AS1, which is highly expressed in GCSC s and serves as a critical regulator of GCSC stemness and tumorigenesis. Our experiments, both in vitro and in vivo, demonstrated that HNF1A-AS1 maintained the stemness of GC cells. Further analysis revealed that HNF1A-AS1, transcriptionally activated by CMYC, functioned as a competing endogenous RNA by binding to miR-150-5p to upregulate β-catenin expression. This in turn facilitated the entry of β-catenin into the nucleus to activate the Wnt/β-catenin pathway and promote CMYC expression, thereby forming a positive feedback loop that sustained the stemness of GCSCs. We also found that blocking the Wnt/β-catenin pathway effectively inhibited the function of HNF1A-AS1, ultimately resulting in the inhibition of GCSC stemness. Taken together, our results demonstrated that HNF1A-AS1 is a regulator of the stemness of GCSCs and could serve as a potential marker for targeted GC therapy.
Lineage specific transcription factor waves reprogram neuroblastoma from self-renewal to differentiation
Authors: Banerjee Deblina , Bagchi Sukriti , Liu Zhihui , Chou Hsien-Chao , Xu Man , Sun Ming , Aloisi Sara , Vaksman Zalman , Diskin Sharon J. , Zimmerman Mark , Khan Javed , Gryder Berkley , Thiele Carol J.
Published: April 2024

Temporal regulation of super-enhancer (SE) driven transcription factors (TFs) underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify SEs driving TF regulators, we use all-trans retinoic acid (ATRA) to induce NB growth arrest and differentiation. Time-course H3K27ac ChIP-seq and RNA-seq reveal ATRA coordinated SE waves. SEs that decrease with ATRA link to stem cell development (MYCN, GATA3, SOX11). CRISPR-Cas9 and siRNA verify SOX11 dependency, in vitro and in vivo. Silencing the SOX11 SE using dCAS9-KRAB decreases SOX11 mRNA and inhibits cell growth. Other TFs activate in sequential waves at 2, 4 and 8 days of ATRA treatment that regulate neural development (GATA2 and SOX4). Silencing the gained SOX4 SE using dCAS9-KRAB decreases SOX4 expression and attenuates ATRA-induced differentiation genes. Our study identifies oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.
A genomic basis of vocal rhythm in birds
Authors: Sebastianelli Matteo , Lukhele Sifiso M. , Secomandi Simona , de Souza Stacey G. , Haase Bettina , Moysi Michaella , Nikiforou Christos , Hutfluss Alexander , Mountcastle Jacquelyn , Balacco Jennifer , Pelan Sarah , Chow William , Fedrigo Olivier , Downs Colleen T. , Monadjem Ara , Dingemanse Niels J. , Jarvis Erich D. , Brelsford Alan , vonHoldt Bridgett M. , Kirschel Alexander N. G.
Published: April 2024

Vocal rhythm plays a fundamental role in sexual selection and species recognition in birds, but little is known of its genetic basis due to the confounding effect of vocal learning in model systems. Uncovering its genetic basis could facilitate identifying genes potentially important in speciation. Here we investigate the genomic underpinnings of rhythm in vocal non-learningPogoniulustinkerbirds using 135 individual whole genomes distributed across a southern African hybrid zone. We find rhythm speed is associated with two genes that are also known to affect human speech, Neurexin-1 and Coenzyme Q8A. Models leveraging ancestry reveal these candidate loci also impact rhythmic stability, a trait linked with motor performance which is an indicator of quality. Character displacement in rhythmic stability suggests possible reinforcement against hybridization, supported by evidence of asymmetric assortative mating in the species producing faster, more stable rhythms. Because rhythm is omnipresent in animal communication, candidate genes identified here may shape vocal rhythm across birds and other vertebrates.
Measuring statistics-induced entanglement entropy with a Hong–Ou–Mandel interferometer
Authors: Zhang Gu , Hong Changki , Alkalay Tomer , Umansky Vladimir , Heiblum Moty , Gornyi Igor , Gefen Yuval
Published: April 2024

Despite its ubiquity in quantum computation and quantum information, a universally applicable definition of quantum entanglement remains elusive. The challenge is further accentuated when entanglement is associated with other key themes, e.g., quantum interference and quantum statistics. Here, we introduce two novel motifs that characterize the interplay of entanglement and quantum statistics: an ‘entanglement pointer’ and a ‘statistics-induced entanglement entropy’. The two provide a quantitative description of the statistics-induced entanglement: (i) they are finite only in the presence of quantum entanglement underlined by quantum statistics and (ii) their explicit form depends on the quantum statistics of the particles (e.g., fermions, bosons, and anyons). We have experimentally implemented these ideas by employing an electronic Hong–Ou–Mandel interferometer fed by two highly diluted electron beams in an integer quantum Hall platform. Performing measurements of auto-correlation and cross-correlation of current fluctuations of the scattered beams (following ‘collisions’), we quantify the statistics-induced entanglement by experimentally accessing the entanglement pointer and the statistics-induced entanglement entropy. Our theoretical and experimental approaches pave the way to study entanglement in various correlated platforms, e.g., those involving anyonic Abelian and non-Abelian states.
Ocean cavity regime shift reversed West Antarctic grounding line retreat in the late Holocene
Authors: Lowry Daniel P. , Han Holly K. , Golledge Nicholas R. , Gomez Natalya , Johnson Katelyn M. , McKay Robert M.
Published: April 2024

Recent geologic and modeled evidence suggests that the grounding line of the Siple Coast of the West Antarctic Ice Sheet (WAIS) retreated hundreds of kilometers beyond its present position in the middle to late Holocene and readvanced within the past 1.7 ka. This grounding line reversal has been attributed to both changing rates of isostatic rebound and regional climate change. Here, we test these two hypotheses using a proxy-informed ensemble of ice sheet model simulations with varying ocean thermal forcing, global glacioisostatic adjustment (GIA) model simulations, and coupled ice sheet-GIA simulations that consider the interactions between these processes. Our results indicate that a warm to cold ocean cavity regime shift is the most likely cause of this grounding line reversal, but that GIA influences the rate of ice sheet response to oceanic changes. This implies that the grounding line here is sensitive to future changes in sub-ice shelf ocean circulation.
Boosting thermoelectric performance of single-walled carbon nanotubes-based films through rational triple treatments
Authors: Liu Yuan-Meng , Shi Xiao-Lei , Wu Ting , Wu Hao , Mao Yuanqing , Cao Tianyi , Wang De-Zhuang , Liu Wei-Di , Li Meng , Liu Qingfeng , Chen Zhi-Gang
Published: April 2024

Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational “triple treatments” to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm−1 K−2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 μW cm−2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.
Structural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans
Authors: Hao Meng-Shu , Mazurkewich Scott , Li He , Kvammen Alma , Saha Srijani , Koskela Salla , Inman Annie R. , Nakajima Masahiro , Tanaka Nobukiyo , Nakai Hiroyuki , Brändén Gisela , Bulone Vincent , Larsbrink Johan , McKee Lauren S.
Published: April 2024

Carbohydrate-binding modules (CBMs) are non-catalytic proteins found appended to carbohydrate-active enzymes. Soil and marine bacteria secrete such enzymes to scavenge nutrition, and they often use CBMs to improve reaction rates and retention of released sugars. Here we present a structural and functional analysis of the recently established CBM family 92. All proteins analysed bind preferentially to β−1,6-glucans. This contrasts with the diversity of predicted substrates among the enzymes attached to CBM92 domains. We present crystal structures for two proteins, and confirm by mutagenesis that tryptophan residues permit ligand binding at three distinct functional binding sites on each protein. Multivalent CBM families are uncommon, so the establishment and structural characterisation of CBM92 enriches the classification database and will facilitate functional prediction in future projects. We propose that CBM92 proteins may cross-link polysaccharides in nature, and might have use in novel strategies for enzyme immobilisation.
Atomic-scale observation of localized phonons at FeSe/SrTiO3 interface
Authors: Shi Ruochen , Li Qize , Xu Xiaofeng , Han Bo , Zhu Ruixue , Liu Fachen , Qi Ruishi , Zhang Xiaowen , Du Jinlong , Chen Ji , Yu Dapeng , Zhu Xuetao , Guo Jiandong , Gao Peng
Published: April 2024

In single unit-cell FeSe grown on SrTiO3, the superconductivity transition temperature features a significant enhancement. Local phonon modes at the interface associated with electron-phonon coupling may play an important role in the interface-induced enhancement. However, such phonon modes have eluded direct experimental observations. The complicated atomic structure of the interface brings challenges to obtain the accurate structure-phonon relation knowledge. Here, we achieve direct characterizations of atomic structure and phonon modes at the FeSe/SrTiO3 interface with atomically resolved imaging and electron energy loss spectroscopy in an electron microscope. We find several phonon modes highly localized (~1.3 nm) at the unique double layer Ti-O terminated interface, one of which (~ 83 meV) engages in strong interactions with the electrons in FeSe based on ab initio calculations. This finding of the localized interfacial phonon associated with strong electron-phonon coupling provides new insights into understanding the origin of superconductivity enhancement at the FeSe/SrTiO3 interface.
Autonomous self-healing supramolecular polymer transistors for skin electronics
Authors: Vo Ngoc Thanh Phuong , Nam Tae Uk , Jeong Min Woo , Kim Jun Su , Jung Kyu Ho , Lee Yeongjun , Ma Guorong , Gu Xiaodan , Tok Jeffrey B.-H. , Lee Tae Il , Bao Zhenan , Oh Jin Young
Published: April 2024

Skin-like field-effect transistors are key elements of bio-integrated devices for future user-interactive electronic-skin applications. Despite recent rapid developments in skin-like stretchable transistors, imparting self-healing ability while maintaining necessary electrical performance to these transistors remains a challenge. Herein, we describe a stretchable polymer transistor capable of autonomous self-healing. The active material consists of a blend of an electrically insulating supramolecular polymer with either semiconducting polymers or vapor-deposited metal nanoclusters. A key feature is to employ the same supramolecular self-healing polymer matrix for all active layers, i.e., conductor/semiconductor/dielectric layers, in the skin-like transistor. This provides adhesion and intimate contact between layers, which facilitates effective charge injection and transport under strain after self-healing. Finally, we fabricate skin-like self-healing circuits, including NAND and NOR gates and inverters, both of which are critical components of arithmetic logic units. This work greatly advances practical self-healing skin electronics.
Phytoalexin sakuranetin attenuates endocytosis and enhances resistance to rice blast
Authors: Jiang Lihui , Zhang Xiaoyan , Zhao Yiting , Zhu Haiyan , Fu Qijing , Lu Xinqi , Huang Wuying , Yang Xinyue , Zhou Xuan , Wu Lixia , Yang Ao , He Xie , Dong Man , Peng Ziai , Yang Jing , Guo Liwei , Wen Jiancheng , Huang Huichuan , Xie Yong , Zhu Shusheng , Li Chengyun , He Xiahong , Zhu Youyong , Friml Jiří , Du Yunlong
Published: April 2024

Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.
Freshwater genome-reduced bacteria exhibit pervasive episodes of adaptive stasis
Authors: Serra Moncadas Lucas , Hofer Cyrill , Bulzu Paul-Adrian , Pernthaler Jakob , Andrei Adrian-Stefan
Published: April 2024

The emergence of bacterial species is rooted in their inherent potential for continuous evolution and adaptation to an ever-changing ecological landscape. The adaptive capacity of most species frequently resides within the repertoire of genes encoding the secreted proteome (SP), as it serves as a primary interface used to regulate survival/reproduction strategies. Here, by applying evolutionary genomics approaches to metagenomics data, we show that abundant freshwater bacteria exhibit biphasic adaptation states linked to the eco-evolutionary processes governing their genome sizes. While species with average to large genomes adhere to the dominant paradigm of evolution through niche adaptation by reducing the evolutionary pressure on their SPs (via the augmentation of functionally redundant genes that buffer mutational fitness loss) and increasing the phylogenetic distance of recombination events, most of the genome-reduced species exhibit a nonconforming state. In contrast, their SPs reflect a combination of low functional redundancy and high selection pressure, resulting in significantly higher levels of conservation and invariance. Our findings indicate that although niche adaptation is the principal mechanism driving speciation, freshwater genome-reduced bacteria often experience extended periods of adaptive stasis. Understanding the adaptive state of microbial species will lead to a better comprehension of their spatiotemporal dynamics, biogeography, and resilience to global change.
Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma
Authors: Pucci Perla , Lee Liam C. , Han Miaojun , Matthews Jamie D. , Jahangiri Leila , Schlederer Michaela , Manners Eleanor , Sorby-Adams Annabel , Kaggie Joshua , Trigg Ricky M. , Steel Christopher , Hare Lucy , James Emily R. , Prokoph Nina , Ducray Stephen P. , Merkel Olaf , Rifatbegovic Firkret , Luo Ji , Taschner-Mandl Sabine , Kenner Lukas , Burke G. A. Amos , Turner Suzanne D.
Published: April 2024

Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis. It follows that the farnesyltransferase inhibitor (FTI) lonafarnib in addition to ALK TKIs act synergistically in neuroblastoma, inducing apoptosis in vitro. In particular, on combined treatment of neuroblastoma patient derived xenografts with an FTI and an ALK TKI complete regression of tumour growth is observed although tumours rapidly regrow on cessation of therapy. Overall, our data suggests that combined use of ALK TKIs and FTIs, constitutes a therapeutic approach to treat high risk neuroblastoma although prolonged therapy is likely required to prevent relapse.
Room-temperature stabilizing strongly competing ferrielectric and antiferroelectric phases in PbZrO3 by strain-mediated phase separation
Authors: Yu Ziyi , Fan Ningbo , Fu Zhengqian , He Biao , Yan Shiguang , Cai Henghui , Chen Xuefeng , Zhang Linlin , Zhang Yuanyuan , Xu Bin , Wang Genshui , Xu Fangfang
Published: April 2024

PbZrO3 has been broadly considered as a prototypical antiferroelectric material for high-power energy storage. A recent theoretical study suggests that the ground state of PbZrO3 is threefold-modulated ferrielectric, which challenges the generally accepted antiferroelectric configuration. However, such a novel ferrielectric phase was predicted only to be accessible at low temperatures. Here, we successfully achieve the room-temperature construction of the strongly competing ferrielectric and antiferroelectric state by strain-mediated phase separation in PbZrO3/SrTiO3 thin film. We demonstrate that the phase separation occurs spontaneously in quasi-periodic stripe-like patterns under a compressive misfit strain and can be tailored by varying the film thickness. The ferrielectric phase strikingly exhibitsa threefold modulation period with a nearly up-up-down configuration, which could be stabilized and manipulated by the formation and evolution of interfacial defects under applied strain. The present results construct a fertile ground for further exploring the physical properties and applications based on the novel ferrielectric phase.
Temporal coordination of the transcription factor response to H2O2 stress
Authors: Jose Elizabeth , March-Steinman Woody , Wilson Bryce A. , Shanks Lisa , Parkinson Chance , Alvarado-Cruz Isabel , Sweasy Joann B. , Paek Andrew L.
Published: April 2024

Oxidative stress from excess H2O2 activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by H2O2, it is unclear whether they are activated at the same H2O2 concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death. Here, we show that transcription factor activation is both dose-dependent and coordinated over time. Low levels of H2O2 activate p53, NRF2 and JUN. Yet under high H2O2, these transcription factors are repressed, and FOXO1, NF-κB, and NFAT1 are activated. Time-lapse imaging revealed that the order in which these two groups of transcription factors are activated depends on whether H2O2 is administered acutely by bolus addition, or continuously through the glucose oxidase enzyme. Finally, we provide evidence that 2-Cys peroxiredoxins control which group of transcription factors are activated.
Designer peptide–DNA cytoskeletons regulate the function of synthetic cells
Authors: Daly Margaret L. , Nishi Kengo , Klawa Stephen J. , Hinton Kameryn Y. , Gao Yuan , Freeman Ronit
Published: April 2024

The bottom-up engineering of artificial cells requires a reconfigurable cytoskeleton that can organize at distinct locations and dynamically modulate its structural and mechanical properties. Here, inspired by the vast array of actin-binding proteins and their ability to reversibly crosslink or bundle filaments, we have designed a library of peptide–DNA crosslinkers varying in length, valency and geometry. Peptide filaments conjoint through DNA hybridization give rise to tactoid-shaped bundles with tunable aspect ratios and mechanics. When confined in cell-sized water-in-oil droplets, the DNA crosslinker design guides the localization of cytoskeletal structures at the cortex or within the lumen of the synthetic cells. The tunable spatial arrangement regulates the passive diffusion of payloads within the droplets and complementary DNA handles allow for the reversible recruitment and release of payloads on and off the cytoskeleton. Heat-induced reconfiguration of peptide–DNA architectures triggers shape deformations of droplets, regulated by DNA melting temperatures. Altogether, the modular design of peptide–DNA architectures is a powerful strategy towards the bottom-up assembly of synthetic cells.
Measurements of dune erosion processes during the RealDune/REFLEX experiments
Authors: van Wiechen Paul , Rutten Jantien , de Vries Sierd , Tissier Marion , Mieras Ryan , Anarde Katherine , Baker Christine , Reniers Ad , Mol Jan-Willem
Published: April 2024

Nearshore hydro- and morphodynamic data were collected during a field experiment under calm conditions, moderate conditions, and storm conditions with dune erosion in the collision regime. The experiment was conducted on the Sand Engine near Kijkduin, the Netherlands, from October 18, 2021, to January 7, 2022. Two artificial unvegetated dunes were constructed just above the high water line to measure storm erosion and dune impacts from higher water levels and waves. During the experiment, three storms occurred that resulted in significant erosion of both dunes. The collected hydrodynamic data include pressure sensor and velocimeter data along two cross-shore transects. The collected morphodynamic data include bathymetry and topography surveys, optical backscatter sensor data in the inner surf zone, and a continuous cross-shore line-scanning lidar data set of the dune face. This comprehensive data set can be used to (1) study relevant nearshore hydrodynamic and morphodynamic processes that occur during calm conditions, moderate conditions, and storm conditions with dune erosion in the collision regime, and (2) validate existing dune erosion models.
RASMI: Global ranges of building material intensities differentiated by region, structure, and function
Authors: Fishman Tomer , Mastrucci Alessio , Peled Yoav , Saxe Shoshanna , van Ruijven Bas
Published: April 2024

The construction materials used in buildings have large and growing implications for global material flows and emissions. Material Intensity (MI) is a metric that measures the mass of construction materials per unit of a building’s floor area. MIs are used to model buildings’ materials and assess their resource use and environmental performance, critical to global climate commitments. However, MI data availability and quality are inconsistent, incomparable, and limited, especially for regions in the Global South. To address these challenges, we present the Regional Assessment of buildings’ Material Intensities (RASMI), a new dataset and accompanying method of comprehensive and consistent representative MI value ranges that embody the variability inherent in buildings. RASMI consists of 3072 MI ranges for 8 construction materials in 12 building structure and function types across 32 regions covering the entire world. The dataset is reproducible, traceable, and updatable, using synthetic data when required. It can be used for estimating historical and future material flows and emissions, assessing demolition waste and at-risk stocks, and evaluating urban mining potentials.
Large-scale annotated dataset for cochlear hair cell detection and classification
Authors: Buswinka Christopher J. , Rosenberg David B. , Simikyan Rubina G. , Osgood Richard T. , Fernandez Katharine , Nitta Hidetomi , Hayashi Yushi , Liberman Leslie W. , Nguyen Emily , Yildiz Erdem , Kim Jinkyung , Jarysta Amandine , Renauld Justine , Wesson Ella , Wang Haobing , Thapa Punam , Bordiga Pierrick , McMurtry Noah , Llamas Juan , Kitcher Siân R. , López-Porras Ana I. , Cui Runjia , Behnammanesh Ghazaleh , Bird Jonathan E. , Ballesteros Angela , Vélez-Ortega A. Catalina , Edge Albert S. B. , Deans Michael R. , Gnedeva Ksenia , Shrestha Brikha R. , Manor Uri , Zhao Bo , Ricci Anthony J. , Tarchini Basile , Basch Martín L. , Stepanyan Ruben , Landegger Lukas D. , Rutherford Mark A. , Liberman M. Charles , Walters Bradley J. , Kros Corné J. , Richardson Guy P. , Cunningham Lisa L. , Indzhykulian Artur A.
Published: April 2024

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5–15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.
Chromosome-level genome assembly of the predatory stink bug Arma custos
Authors: Wang Yuqin , Luo Yunfei , Ge Yunkang , Liu Sha , Liang Wenkai , Wu Chaoyan , Wei Shujun , Zhu Jiaying
Published: April 2024

The stink bug Arma custos (Hemiptera: Pentatomidae) is a predatory enemy successfully used for biocontrol of lepidopteran and coleopteran pests in notorious invasive species. In this study, a high-quality chromosome-scale genome assembly of A. custos was achieved through a combination of Illumina sequencing, PacBio HiFi sequencing, and Hi-C scaffolding techniques. The final assembled genome was 969.02 Mb in size, with 935.94 Mb anchored to seven chromosomes, and a scaffold N50 length of 135.75 Mb. This genome comprised 52.78% repetitive elements. The detected complete BUSCO score was 99.34%, indicating its completeness. A total of 13,708 protein-coding genes were predicted in the genome, and 13219 of them were annotated. This genome provides an invaluable resource for further research on various aspects of predatory bugs, such as biology, genetics, and functional genomics.
Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma
Authors: Kwiatkowski Maciej , Krajewski Adrian , Durślewicz Justyna , Buchholz Karolina , Grzanka Dariusz , Gagat Maciej , Zabrzyński Jan , Klimaszewska-Wiśniewska Anna
Published: April 2024

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.
Exposure to environmental pharmaceuticals affects the macromolecular composition of mussels digestive glands
Authors: Mezzelani Marica , Notarstefano Valentina , Panni Michela , Giorgini Elisabetta , Gorbi Stefania , Regoli Francesco
Published: April 2024

Human pharmaceuticals represent a major challenge in natural environment. A better knowledge on their mechanisms of action and adverse effects on cellular pathways is fundamental to predict long-term consequences for marine wildlife. The FTIRI Imaging (FTIRI) spectroscopy represents a vibrational technique allowing to map specific areas of non-homogeneous biological samples, providing a unique biochemical and ultrastructural fingerprint of the tissue. In this study, FTIRI technique has been applied, for the first time, to characterize (i) the chemical building blocks of digestive glands of Mytilus galloprovincialis, (ii) alterations and (iii) resilience of macromolecular composition, after a 14-days exposure to 0.5 µg/L of carbamazepine (CBZ), valsartan (VAL) and their mixture, followed by a 14-days recovery period. Spectral features of mussels digestive glands provided insights on composition and topographical distribution of main groups of biological macromolecules, such as proteins, lipids, and glycosylated compounds. Pharmaceuticals caused an increase in the total amount of protein and a significant decrease of lipids levels. Changes in macromolecular features reflected the modulation of specific molecular and biochemical pathways thus supporting our knowledge on mechanisms of action of such emerging pollutants. Overall, the applied approach could represent an added value within integrated strategies for the effects-based evaluation of environmental contaminants.
Cross-sectional associations between multisensory impairment and brain volumes in older adults: Baltimore Longitudinal Study of Aging
Authors: Tian Chenxin , Schrack Jennifer A. , Agrawal Yuri , An Yang , Cai Yurun , Wang Hang , Gross Alden L. , Tian Qu , Simonsick Eleanor M. , Ferrucci Luigi , Resnick Susan M. , Wanigatunga Amal A.
Published: April 2024

Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments (MSI across vision, proprioception, vestibular function, olfactory, and hearing) are associated with brain morphometry remain unexplored. Data were from 208 cognitively unimpaired participants (mean age 72 ± 10 years; 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Multiple linear regression models were used to estimate cross-sectional associations between MSI and regional brain imaging volumes. For each additional sensory impairment, there were associated lower orbitofrontal gyrus and entorhinal cortex volumes but higher caudate and putamen volumes. Participants with MSI had lower mean volumes in the superior frontal gyrus, orbitofrontal gyrus, superior parietal lobe, and precuneus compared to participants with < 2 impairments. While MSI was largely associated with lower brain volumes, our results suggest the possibility that MSI was associated with higher basal ganglia volumes. Longitudinal analyses are needed to evaluate the temporality and directionality of these associations.