bluuebunny/crossref_metadata_2025 huggingface dataset:
Congo Basin Water Balance and Terrestrial Fluxes Inferred From Satellite Observations of the Isotopic Composition of Water Vapor
Authors: Worden Sarah , Bloom A. Anthony , Worden John , Levine Paul , Shi Mingjie , Fu Rong
Published: July 2024

Large spatio‐temporal gradients in the Congo basin vegetation and rainfall are observed. However, its water‐balance (evapotranspiration minus precipitation, or ET − P) is typically measured at basin‐scales, limited primarily by river‐discharge data, spatial resolution of terrestrial water storage measurements, and poorly constrained ET. We use observations of the isotopic composition of water vapor to quantify the spatio‐temporal variability of net surface water fluxes across the Congo Basin between 2003 and 2018. These data are calibrated at basin scale using satellite gravity and total Congo river discharge measurements and then used to estimate time‐varying ET − P over four quadrants representing the Congo Basin, providing first estimates of this kind for the region. We find that the multi‐year record, seasonality, and interannual variability of ET − P from both the isotopes and the gravity/river discharge based estimates are consistent. Additionally, we use precipitation and gravity‐based estimates with our water vapor isotope‐based ET − P to calculate time and space averaged ET and net river discharge within the Congo Basin. These quadrant‐scale moisture flux estimates indicate (a) substantial recycling of moisture in the Congo Basin (temporally and spatially averaged ET/P > 70%), consistent with models and visible light‐based ET estimates, and (b) net river outflow is largest in the Western Congo where there are more rivers and higher flow rates. Our results confirm the importance of ET in modulating the Congo water cycle relative to other water sources.
Investigating the Intense Sediment Load by Dam‐Break Floods Using a Meshless Two‐Phase Mathematical Model
Authors: Guan Xiafei , Hu Kailun , Chen Xin , Gao Junliang , Shi Huabin
Published: July 2024

Extreme precipitation is increasing the risk of dam breaks and formation occurring debris dams. Accurate prediction of dam‐break wave propagation is critical to disaster emergency management. Intense bed‐load transport by dam‐break floods can result in a dramatic change of topography, which in turn may affect flood propagation. However, only a very few studies have investigated the thin intense bed‐load layer under dam‐break floods. In this paper, a meshless two‐phase mathematical model is utilized to examine the water velocity, sediment velocity and volumetric fraction, and bed‐load transport flux as well as energy dissipation in bed‐load layer. The model is applied to simulate two‐ and three‐dimensional laboratory experiments of dam‐break wave over erodible beds. For the two‐dimensional experiment, the relative root mean square errors in computed water surface are all below 3.60% and those in profiles of bed‐load layer and static bed are mostly below 13.40%. For the three‐dimensional case, the relative error in computed highest water level is lower than 5.9%. Sediment stream‐wise velocity in bed‐load layer follows a power‐law vertical distribution while sediment volumetric fraction decreases linearly upwards. Accordingly, a formulation of the vertical distribution of bed‐load transport flux, contradictory to the parabolic law in existing studies, is proposed. Most of the water mechanical energy transferred to the sediment is dissipated due to the shear stress in the intense bed‐load layer while only a limit part is kept by the sediment grains. Energy dissipation due to sediment shear stress dominates the consumption of total mechanical energy in the two‐phase system.
Graph Neural Networks for Pressure Estimation in Water Distribution Systems
Authors: Truong Huy , Tello Andrés , Lazovik Alexander , Degeler Victoria
Published: July 2024

Pressure and flow estimation in water distribution networks (WDNs) allows water management companies to optimize their control operations. For many years, mathematical simulation tools have been the most common approach to reconstructing an estimate of the WDNs hydraulics. However, pure physics‐based simulations involve several challenges, for example, partially observable data, high uncertainty, and extensive manual calibration. Thus, data‐driven approaches have gained traction to overcome such limitations. In this work, we combine physics‐based modeling and graph neural networks (GNN), a data‐driven approach, to address the pressure estimation problem. Our work has two main contributions. First, a training strategy that relies on random sensor placement making our GNN‐based estimation model robust to unexpected sensor location changes. Second, a realistic evaluation protocol that considers real temporal patterns and noise injection to mimic the uncertainties intrinsic to real‐world scenarios. As a result, a new state‐of‐the‐art model, GAT with Residual Connections, for pressure estimation is available. Our model surpasses the performance of previous studies on several WDNs benchmarks, showing a reduction of absolute error of ≈40% on average.
First Observation of Harmonics of Magnetosonic Waves in Martian Magnetosheath Region
Authors: Kakad Bharati , Kakad Amar , Omura Yoshiharu , Yoon Peter H.
Published: July 2024

The present study provides an evidence for the generation of harmonics of magnetosonic waves in the Martian magnetosheath region. The wave signatures are manifested in the magnetic field measurements recorded by the fluxgate magnetometer instrument onboard the Mars Atmosphere and Volatile Evolution missioN (MAVEN) spacecraft in the dawn sector around 5–10 LT at an altitude of 4,000–6,000 kms. The wave that is observed continuously from 19.1 to 20.7 UT below the proton cyclotron frequency (fci ≈ 46 mHz) is identified as fundamental mode of the magnetosonic wave. Whereas harmonics of the magnetosonic wave are observed during 19.7–20.3 UT at frequencies that are multiple of fci. The ambient solar wind proton density and plasma flow velocity are found to vary with a fundamental mode frequency of 46 mHz. It is noticed that the fundamental mode is mainly associated with the left‐hand (LH), and higher frequency harmonics are associated with the right‐hand (RH) circular polarizations. A clear difference in the polarization and ellipticity is noticed during the time of occurrence of harmonics. The magnetosonic wave harmonics are found to propagate in the quasi‐perpendicular directions to the ambient magnetic field. The results of linear theory and Particle‐In‐Cell simulation performed here are in agreement with the observations. The present study provides a conclusive evidence for the occurrence of harmonics of magnetosonic wave in the close vicinity of the magnetosheath region of the unmagnetized planet Mars.
Berkeley‐RWAWC: A New CYGNSS‐Based Watermask Unveils Unique Observations of Seasonal Dynamics in the Tropics
Authors: Pu Tianjiao , Gerlein‐Safdi Cynthia , Xiong Ying , Li Mengze , Kort Eric A. , Bloom A. Anthony
Published: July 2024

The UC Berkeley Random Walk Algorithm WaterMask from CYGNSS (Berkeley‐RWAWC) is a new data product designed to address the challenges of monitoring inundation in regions hindered by dense vegetation and cloud cover as is the case in most of the Tropics. The Cyclone Global Navigation Satellite System (CYGNSS) constellation provides data with a higher temporal repeat frequency compared to single‐satellite systems, offering the potential for generating moderate spatial resolution inundation maps with improved temporal resolution while having the capability to penetrate clouds and vegetation. This paper details the development of a computer vision algorithm for inundation mapping over the entire CYGNSS domain (37.4°N–37.4°S). The sole reliance on CYGNSS data sets our method apart in the field, highlighting CYGNSS's indication of water existence. Berkeley‐RWAWC provides monthly, low‐latency inundation maps starting in August 2018 and across the CYGNSS latitude range, with a spatial resolution of 0.01° × 0.01°. Here we present our workflow and parameterization strategy, alongside a comparative analysis with established surface water data sets (SWAMPS, WAD2M) in four regions: the Amazon Basin, the Pantanal, the Sudd, and the Indo‐Gangetic Plain. The comparisons reveal Berkeley‐RWAWC's enhanced capability to detect seasonal variations, demonstrating its usefulness in studying tropical wetland hydrology. We also discuss potential sources of uncertainty and reasons for variations in inundation retrievals. Berkeley‐RWAWC represents a valuable addition to environmental science, offering new insights into tropical wetland dynamics.
Myofibroblasts derived type V collagen promoting tissue mechanical stress and facilitating metastasis and therapy resistance of lung adenocarcinoma cells
Authors: Zhu Guangsheng , Wang Yanan , Wang Yingjie , Huang Hua , Li Boshi , Chen Peijie , Chen Chen , Zhang Hongbing , Li Yongwen , Liu Hongyu , Chen Jun
Published: July 2024

Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.
LINC01133 promotes pancreatic ductal adenocarcinoma epithelial–mesenchymal transition mediated by SPP1 through binding to Arp3
Authors: Yang Yefan , Gong Yuxi , Ding Ying , Sun Shuning , Bai Rumeng , Zhuo Shuaishuai , Zhang Zhihong
Published: July 2024

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment methods. Long non-coding RNAs (lncRNAs) have been found involved in tumorigenic and progression. The present study revealed that LINC01133, a fewly reported lncRNA, was one of 16 hub genes that could predict PDAC patients’ prognosis. LINC01133 was over-expressed in PDAC tumors compared to adjacent pancreas and could promote PDAC proliferation and metastasis in vitro and in vivo, as well as inhibit PDAC apoptosis. LINC01133 expression positively correlated to secreted phosphoprotein 1 (SPP1) expression, leading to an enhanced epithelial-mesenchymal transition (EMT) process. LINC01133 bound with actin-related protein 3 (Arp3), the complex reduced SPP1 mRNA degradation which increased SPP1 mRNA level, ultimately leading to PDAC proliferation. This research revealed a novel mechanism of PDAC development and provided a potential prognosis indicator that may benefit PDAC patients.
SETD8 inhibits apoptosis and ferroptosis of Ewing’s sarcoma through YBX1/RAC3 axis
Authors: Chen Huimou , Hu Jing , Xiong Xilin , Chen Hongling , Liao Qiaofang , Lin Biaojun , Chen Yusong , Peng Yanting , Li Yang , Cheng Di , Li Zhihua
Published: July 2024

Ewing’s sarcoma (ES) represents a rare yet exceedingly aggressive neoplasm that poses a significant health risk to the pediatric and adolescent population. The clinical outcomes for individuals with relapsed or refractory ES are notably adverse, primarily attributed to the constrained therapeutic alternatives available. Despite significant advancements in the field, molecular pathology-driven therapeutic strategies have yet to achieve a definitive reduction in the mortality rates associated with ES. Consequently, there exists an imperative need to discover innovative therapeutic targets to effectively combat ES. To reveal the mechanism of the SETD8 (also known as lysine methyltransferase 5A) inhibitor UNC0379, cell death manners were analyzed with different inhibitors. The contributions of SETD8 to the processes of apoptosis and ferroptosis in ES cells were evaluated employing the histone methyltransferase inhibitor UNC0379 in conjunction with RNA interference techniques. The molecular regulatory mechanisms of SETD8 in ES were examined through the application of RNA sequencing (RNA-seq) and mass spectrometry-based proteomic analysis. Moreover, nude mouse xenograft models were established to explore the role of SETD8 in ES in vivo. SETD8, a sole nucleosome-specific methyltransferase that catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), was found to be upregulated in ES, and its overexpression was associated with dismal outcomes of patients. SETD8 knockdown dramatically induced the apoptosis and ferroptosis of ES cells in vitro and suppressed tumorigenesis in vivo. Mechanistic investigations revealed that SETD8 facilitated the nuclear translocation of YBX1 through post-transcriptional regulatory mechanisms, which subsequently culminated in the transcriptional upregulation of RAC3. In summary, SETD8 inhibits the apoptosis and ferroptosis of ES cells through the YBX1/RAC3 axis, which provides new insights into the mechanism of tumorigenesis of ES. SETD8 may be a potential target for clinical intervention in ES patients.
Effects of polygenic risk score and sodium and potassium intake on hypertension in Asians: A nationwide prospective cohort study
Authors: Bae Eunjin , Ji Yunmi , Jo Jinyeon , Kim Yaerim , Lee Jung Pyo , Won Sungho , Lee Jeonghwan
Published: July 2024

Genetic factors, lifestyle, and diet have been shown to play important roles in the development of hypertension. Increased salt intake is an important risk factor for hypertension. However, research on the involvement of genetic factors in the relationship between salt intake and hypertension in Asians is lacking. We aimed to investigate the risk of hypertension in relation to sodium and potassium intake and the effects of genetic factors on their interactions. We used Korean Genome and Epidemiology Study data and calculated the polygenic risk score (PRS) for the effect of systolic and diastolic blood pressure (SBP and DBP). We also conducted multivariable logistic modeling to evaluate associations among incident hypertension, PRSSBP, PRSDBP, and sodium and potassium intake. In total, 41,351 subjects were included in the test set. The top 10% PRSSBP group was the youngest of the three groups (bottom 10%, middle, top 10%), had the highest proportion of women, and had the highest body mass index, baseline BP, red meat intake, and alcohol consumption. The multivariable logistic regression model revealed the risk of hypertension was significantly associated with higher PRSSBP, higher sodium intake, and lower potassium intake. There was significant interaction between sodium intake and PRSSBP for incident hypertension especially in sodium intake ≥2.0 g/day and PRSSBP top 10% group (OR 1.27 (1.07–1.51), P = 0.007). Among patients at a high risk of incident hypertension due to sodium intake, lifestyle modifications and sodium restriction were especially important to prevent hypertension.
Immuno-oncologic profiling of pediatric brain tumors reveals major clinical significance of the tumor immune microenvironment
Authors: Levine Adrian B. , Nobre Liana , Das Anirban , Milos Scott , Bianchi Vanessa , Johnson Monique , Fernandez Nicholas R. , Stengs Lucie , Ryall Scott , Ku Michelle , Rana Mansuba , Laxer Benjamin , Sheth Javal , Sbergio Stefanie-Grace , Fedoráková Ivana , Ramaswamy Vijay , Bennett Julie , Siddaway Robert , Tabori Uri , Hawkins Cynthia
Published: July 2024

With the success of immunotherapy in cancer, understanding the tumor immune microenvironment (TIME) has become increasingly important; however in pediatric brain tumors this remains poorly characterized. Accordingly, we developed a clinical immune-oncology gene expression assay and used it to profile a diverse range of 1382 samples with detailed clinical and molecular annotation. In low-grade gliomas we identify distinct patterns of immune activation with prognostic significance in BRAF V600E-mutant tumors. In high-grade gliomas, we observe immune activation and T-cell infiltrates in tumors that have historically been considered immune cold, as well as genomic correlates of inflammation levels. In mismatch repair deficient high-grade gliomas, we find that high tumor inflammation signature is a significant predictor of response to immune checkpoint inhibition, and demonstrate the potential for multimodal biomarkers to improve treatment stratification. Importantly, while overall patterns of immune activation are observed for histologically and genetically defined tumor types, there is significant variability within each entity, indicating that the TIME must be evaluated as an independent feature from diagnosis. In sum, in addition to the histology and molecular profile, this work underscores the importance of reporting on the TIME as an essential axis of cancer diagnosis in the era of personalized medicine.
Active species in chloroaluminate ionic liquids catalyzing low-temperature polyolefin deconstruction
Authors: Zhang Wei , Khare Rachit , Kim Sungmin , Hale Lillian , Hu Wenda , Yuan Chunlin , Sheng Yaoci , Zhang Peiran , Wahl Lennart , Mai Jiande , Yang Boda , Gutiérrez Oliver Y. , Ray Debmalya , Fulton John , Camaioni Donald M. , Hu Jianzhi , Wang Huamin , Lee Mal-Soon , Lercher Johannes A.
Published: July 2024

Chloroaluminate ionic liquids selectively transform (waste) polyolefins into gasoline-range alkanes through tandem cracking-alkylation at temperatures below 100 °C. Further improvement of this process necessitates a deep understanding of the nature of the catalytically active species and the correlated performance in the catalyzing critical reactions for the tandem polyolefin deconstruction with isoalkanes at low temperatures. Here, we address this requirement by determining the nuclearity of the chloroaluminate ions and their interactions with reaction intermediates, combining in situ 27Al magic-angle spinning nuclear magnetic resonance spectroscopy, in situ Raman spectroscopy, Al K-edge X-ray absorption near edge structure spectroscopy, and catalytic activity measurement. Cracking and alkylation are facilitated by carbenium ions initiated by AlCl3-tert-butyl chloride (TBC) adducts, which are formed by the dissociation of Al2Cl7− in the presence of TBC. The carbenium ions activate the alkane polymer strands and advance the alkylation cycle through multiple hydride transfer reactions. In situ 1H NMR and operando infrared spectroscopy demonstrate that the cracking and alkylation processes occur synchronously; alkenes formed during cracking are rapidly incorporated into the carbenium ion-mediated alkylation cycle. The conclusions are further supported by ab initio molecular dynamics simulations coupled with an enhanced sampling method, and model experiments using n-hexadecane as a feed.
Histamine H1 receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice
Authors: Cheng Li , Xiao Ling , Lin Wenkai , Li Minzhu , Liu Jiaying , Qiu Xiaoyun , Li Menghan , Zheng Yanrong , Xu Cenglin , Wang Yi , Chen Zhong
Published: July 2024

Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.
Stretchable glove for accurate and robust hand pose reconstruction based on comprehensive motion data
Authors: Park Myungsun , Park Taejun , Park Soah , Yoon Sohee John , Koo Sumin Helen , Park Yong-Lae
Published: July 2024

We propose a compact wearable glove capable of estimating both the finger bone lengths and the joint angles of the wearer with a simple stretch-based sensing mechanism. The soft sensing glove is designed to easily stretch and to be one-size-fits-all, both measuring the size of the hand and estimating the finger joint motions of the thumb, index, and middle fingers. The system was calibrated and evaluated using comprehensive hand motion data that reflect the extensive range of natural human hand motions and various anatomical structures. The data were collected with a custom motion-capture setup and transformed into the joint angles through our post-processing method. The glove system is capable of reconstructing arbitrary and even unconventional hand poses with accuracy and robustness, confirmed by evaluations on the estimation of bone lengths (mean error: 2.1 mm), joint angles (mean error: 4.16°), and fingertip positions (mean 3D error: 4.02 mm), and on overall hand pose reconstructions in various applications. The proposed glove allows us to take advantage of the dexterity of the human hand with potential applications, including but not limited to teleoperation of anthropomorphic robot hands or surgical robots, virtual and augmented reality, and collection of human motion data.
β-amyloid monomer scavenging by an anticalin protein prevents neuronal hyperactivity in mouse models of Alzheimer’s Disease
Authors: Zott Benedikt , Nästle Lea , Grienberger Christine , Unger Felix , Knauer Manuel M. , Wolf Christian , Keskin-Dargin Aylin , Feuerbach Anna , Busche Marc Aurel , Skerra Arne , Konnerth Arthur
Published: July 2024

Hyperactivity mediated by synaptotoxic β-amyloid (Aβ) oligomers is one of the earliest forms of neuronal dysfunction in Alzheimer’s disease. In the search for a preventive treatment strategy, we tested the effect of scavenging Aβ peptides before Aβ plaque formation. Using in vivo two-photon calcium imaging and SF-iGluSnFR-based glutamate imaging in hippocampal slices, we demonstrate that an Aβ binding anticalin protein (Aβ-anticalin) can suppress early neuronal hyperactivity and synaptic glutamate accumulation in the APP23xPS45 mouse model of β-amyloidosis. Our results suggest that the sole targeting of Aβ monomers is sufficient for the hyperactivity-suppressing effect of the Aβ-anticalin at early disease stages. Biochemical and neurophysiological analyses indicate that the Aβ-anticalin-dependent depletion of naturally secreted Aβ monomers interrupts their aggregation to neurotoxic oligomers and, thereby, reverses early neuronal and synaptic dysfunctions. Thus, our results suggest that Aβ monomer scavenging plays a key role in the repair of neuronal function at early stages of AD.
High-density vertical sidewall MoS2 transistors through T-shape vertical lamination
Authors: Tao Quanyang , Wu Ruixia , Zou Xuming , Chen Yang , Li Wanying , Lu Zheyi , Ma Likuan , Kong Lingan , Lu Donglin , Yang Xiaokun , Song Wenjing , Li Wei , Liu Liting , Ding Shuimei , Liu Xiao , Duan Xidong , Liao Lei , Liu Yuan
Published: July 2024

Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2transistors within a small vertical footprint, corresponding to a device density over 108 cm−2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.
Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes
Authors: Yamada Kazuhiro , St. Croix Claudette , Stolz Donna B. , Tyurina Yulia Y. , Tyurin Vladimir A. , Bradley Laura R. , Kapralov Alexander A. , Deng Yanhan , Zhou Xiuxia , Wei Qi , Liao Bo , Fukuda Nobuhiko , Sullivan Mara , Trudeau John , Ray Anuradha , Kagan Valerian E. , Zhao Jinming , Wenzel Sally E.
Published: July 2024

A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)−1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.
Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity
Authors: Su Yujuan , Xu Jinhao , Zhu Ziai , Chin Jisun , Xu Le , Yu Haoze , Nudell Victoria , Dash Barsha , Moya Esteban A. , Ye Li , Nimmerjahn Axel , Sun Xin
Published: July 2024

Exaggerated airway constriction triggered by repeated exposure to allergen, also called hyperreactivity, is a hallmark of asthma. Whereas vagal sensory neurons are known to function in allergen-induced hyperreactivity1–3, the identity of downstream nodes remains poorly understood. Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA sequencing, followed by RNAscope assay at baseline and allergen challenges, showed that a Dbh+ nTS population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+ nTS neurons project to the nucleus ambiguus (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.
The quantum transition of the two-dimensional Ising spin glass
Authors: Bernaschi Massimo , González-Adalid Pemartín Isidoro , Martín-Mayor Víctor , Parisi Giorgio
Published: July 2024

Quantum annealers are commercial devices that aim to solve very hard computational problems1, typically those involving spin glasses2,3. Just as in metallurgic annealing, in which a ferrous metal is slowly cooled4, quantum annealers seek good solutions by slowly removing the transverse magnetic field at the lowest possible temperature. Removing the field diminishes the quantum fluctuations but forces the system to traverse the critical point that separates the disordered phase (at large fields) from the spin-glass phase (at small fields). A full understanding of this phase transition is still missing. A debated, crucial question regards the closing of the energy gap separating the ground state from the first excited state. All hopes of achieving an exponential speed-up, compared to classical computers, rest on the assumption that the gap will close algebraically with the number of spins5–9. However, renormalization group calculations predict instead that there is an infinite-randomness fixed point10. Here we solve this debate through extreme-scale numerical simulations, finding that both parties have grasped parts of the truth. Although the closing of the gap at the critical point is indeed super-algebraic, it remains algebraic if one restricts the symmetry of possible excitations. As this symmetry restriction is experimentally achievable (at least nominally), there is still hope for the quantum annealing paradigm11–13.
Prognostic value of Maspin protein level in patients with triple negative breast cancer
Authors: do Nascimento Renan Gomes , da Conceição Mércia Patrícia Ferreira , de Bastos Daniel Rodrigues , de Toledo Osorio Cynthia Aparecida Bueno , López Rossana Verónica Mendoza , Reis Eduardo Moraes , Cerqueira Otto Luiz Dutra
Published: July 2024

The search for prognostic markers in breast cancer has bumped into a typical feature of these tumors, intra and intertumoral heterogeneity. Changes in the expression profile, localization of these proteins or shedding to the surrounding stroma can be useful in the search for new markers. In this context, classification by molecular subtypes can bring perspectives for both diagnosis and screening for appropriate treatments. However, the Triple Negative (TN) subtype, which is already the one with the worst prognosis, lacks appropriate and consistent molecular markers. In this work, we analyzed 346 human breast cancer samples in tissue microarrays (TMA) from cases diagnosed with invasive breast carcinoma to assess the expression and localization pattern of Maspin and their correlation with clinical parameters. To complement our findings, we also used TCGA data to analyze the mRNA levels of these respective genes. Our data suggests that the TN subtype demonstrates a higher level of cytoplasmic Maspin compared to the other subtypes. Maspin transcript levels follow the same trend. However, TN patients with lower Maspin expression tend to have worse overall survival and free-survival metastasis rates. Finally, we used Maspin expression data to verify possible relationships with the clinicopathological information of our cohort. Our univariate analyses indicate that Maspin is related to the expression of estrogen receptor (ER) and progesterone receptor (PR). Furthermore, Maspin expression levels also showed correlation with Scarff-Bloom-Richardson (SBR) parameter, and stromal Maspin showed a relationship with lymph node involvement. Our data is not consistently robust enough to categorize Maspin as a prognostic marker. However, it does indicate a change in the expression profile within the TN subtype.
Estimation of the UV susceptibility of aerosolized SARS-CoV-2 to 254 nm irradiation using CFD-based room disinfection simulations
Authors: van der Schans Marc , Yu Joan , de Vries Adrie , Martin Genevieve
Published: July 2024

The recent COVID-19 pandemic has raised interest in efficient air disinfection solutions. The application of germicidal ultraviolet (GUV) irradiation is an excellent contender to prevent airborne transmission of COVID-19, as well as other existing and future infectious airborne diseases. While GUV has already been proven effective in inactivating SARS-CoV-2, quantitative data on UV susceptibility and dose requirements, needed to predict and optimize the performance of GUV solutions, is still limited. In this study, the UV susceptibility of aerosolized SARS-CoV-2 to 254 nm ultraviolet (UV) irradiation is investigated. This is done by employing 3D computational fluid dynamics based simulations of SARS-CoV-2 inactivation in a test chamber equipped with an upper-room UV-C luminaire and comparing the results to previously published measurements performed in the same test chamber. The UV susceptibility found in this study is (0.6 ± 0.2) m2/J, which is equivalent to a D90 dose between 3 and 6 J/m2. These values are in the same range as previous estimations based on other corona viruses and inactivation data reported in literature.
Quantifiable and reproducible phenotypic assessment of a constitutive knockout mouse model for congenital nephrotic syndrome of the Finnish type
Authors: Lemberg Katharina , Mertens Nils D. , Yousef Kirollos , Schneider Ronen , Merz Lea M. , Mansour Bshara , Salmanullah Daanya , Kolvenbach Caroline M. , Saida Ken , Yu Seyoung , Hölzel Selina , Steinsapir Andrew , Goncalves Kevin A. , Nicolas Frank Camille , Franken Gijs A. C. , Shril Shirlee , Buerger Florian , Hildebrandt Friedhelm
Published: July 2024

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of childhood chronic kidney disease. Congenital nephrotic syndrome of the Finnish type (CNF) (MIM# 256300) is caused by biallelic variants in the gene NPHS1, encoding nephrin, an integral component of the kidney filtration barrier. No causal treatments exist, and children inevitably require kidney replacement therapy. In preparation for gene replacement therapy (GRT) in CNF, we established a quantifiable and reproducible phenotypic assessment of the nephrin-deficient CNF mouse model: 129/Sv-Nphs1tm1Rkl/J. We assessed the phenotypic spectrum of homozygous mice (Nphs1tm1Rkl/Nphs1tm1Rkl) compared to heterozygous controls (Nphs1tm1Rkl/Nphs1WT) by the following parameters: 1. cohort survival, 2. podocyte foot process (FP) density per glomerular basement membrane (GBM) using transmission electron microscopy, 3. tubular microcysts in brightfield microscopy, and 4. urinary albumin/creatinine ratios. Nphs1tm1Rkl/Nphs1tm1Rkl mice exhibited: 1. perinatal lethality with median survival of 1 day, 2. FP effacement with median FP density of 1.00 FP/µm GBM (2.12 FP/µm in controls), 3. tubular dilation with 65 microcysts per section (6.5 in controls), and 4. increased albumin/creatinine ratio of 238 g/g (4.1 g/g in controls). We here established four quantifiable phenotyping features of a CNF mouse model to facilitate future GRT studies by enabling sensitive detection of phenotypic improvements.
Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties
Authors: Inuzuka Naoki , Shobayashi Yasuhiro , Tateshima Satoshi , Sato Yuya , Ohba Yoshio , Ekdahl Kristina N. , Nilsson Bo , Teramura Yuji
Published: July 2024

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin–antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.
A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in a pancreatic cancer cell line
Authors: Mondal Priya , Alyateem George , Mitchell Allison V. , Gottesman Michael M.
Published: July 2024

Pancreatic adenocarcinoma is one of the most aggressive and lethal forms of cancer. Chemotherapy is the primary treatment for pancreatic cancer, but resistance to the drugs used remains a major challenge. A genome-wide CRISPR interference and knockout screen in the PANC-1 cell line with the drug nab-paclitaxel has identified a group of spindle assembly checkpoint (SAC) genes that enhance survival in nab-paclitaxel. Knockdown of these SAC genes (BUB1B, BUB3, and TTK) attenuates paclitaxel-induced cell death. Cells treated with the small molecule inhibitors BAY 1217389 or MPI 0479605, targeting the threonine tyrosine kinase (TTK), also enhance survival in paclitaxel. Overexpression of these SAC genes does not affect sensitivity to paclitaxel. These discoveries have helped to elucidate the mechanisms behind paclitaxel cytotoxicity. The outcomes of this investigation may pave the way for a deeper comprehension of the diverse responses of pancreatic cancer to therapies including paclitaxel. Additionally, they could facilitate the formulation of novel treatment approaches for pancreatic cancer.
Initiating-clone analysis in patients with acute myeloid leukemia secondary to essential thrombocythemia
Authors: Ushijima Yoko , Naruse Seara , Ishikawa Yuichi , Kawashima Naomi , Sanada Masashi , Nakashima Marie , Kim Jeong Hui , Terakura Seitaro , Kihara Rika , Watamoto Koichi , Nishiyama Takahiro , Kitamura Kunio , Matsushita Tadashi , Kiyoi Hitoshi
Published: July 2024

Most of essential thrombocythemia (ET) patients have the clone harboring a mutation in one of the JAK2, CALR, or MPL gene, and these clones generally acquire additional mutations at transformation to acute myeloid leukemia (AML). However, the proliferation of triple-negative clones has sometimes been observed at AML transformation. To clarify the clonal evolution of ET to AML, we analyzed paired samples at ET and AML transformation in eight patients. We identified that JAK2-unmutated AML clones proliferated at AML transformation in three patients in whom the JAK2-mutated clone was dominant at ET. In two patients, TET2-mutated, but not JAK2-mutated, clones might be common initiating clones for ET and transformed AML. In a patient with JAK2-mutated ET, SMARCC2, UBR4, and ZNF143, but not JAK2, -mutated clones proliferated at AML transformation. Precise analysis using single-cell sorted CD34+/CD38- fractions suggested that ET clone with JAK2-mutated and AML clone with TP53 mutation was derived from the common clone with these mutations. Although further study is required to clarify the biological significance of SMARCC2, UBR4, and ZNF143 mutations during disease progression of ET and AML transformation, the present results demonstrate the possibility of a common initial clone involved in both ET and transformed AML.
Combination of error-prone PCR (epPCR) and Circular Polymerase Extension Cloning (CPEC) for improving the coverage of random mutagenesis libraries
Authors: Ossa-Hernández Natalia , Marins Luis Fernando , Almeida Daniela Volcan
Published: July 2024

Random mutagenesis, such as error-prone PCR (epPCR), is a technique capable of generating a wide variety of a single gene. However, epPCR can produce a large number of mutated gene variants, posing a challenge in ligating these mutated PCR products into plasmid vectors. Typically, the primers for mutagenic PCRs incorporate artificial restriction enzyme sites compatible with chosen plasmids. Products are cleaved and ligated to linearized plasmids, then recircularized by DNA ligase. However, this cut-and-paste method known as ligation-dependent process cloning (LDCP), has limited efficiency, as the loss of potential mutants is inevitable leading to a significant reduction in the library’s breadth. An alternative to LDCP is the circular polymerase extension cloning (CPEC) method. This technique involves a reaction where a high-fidelity DNA polymerase extends the overlapping regions between the insert and vector, forming a circular molecule. In this study, our objective was to compare the traditional cut-and-paste enzymatic method with CPEC in producing a variant library from the gene encoding the red fluorescent protein (DsRed2) obtained by epPCR. Our findings suggest that CPEC can accelerate the cloning process in gene library generation, enabling the acquisition of a greater number of gene variants compared to methods reliant on restriction enzymes.
Nano fuzzy alarming system for blood transfusion requirement detection in cancer using deep learning
Authors: Rady Raz Nasibeh , Anoushirvani Ali Arash , Rahimian Neda , Ghoerishi Maryam , Alibeik Nazanin , Sajadi Rad Masoumeh
Published: July 2024

Periodic blood transfusion is a need in cancer patients in which the disease process as well as the chemotherapy can disrupt the natural production of blood cells. However, there are concerns about blood transfusion side effects, the cost, and the availability of donated blood. Therefore, predicting the timely requirement for blood transfusion considering patient variability is a need, and here for the first-time deal with this issue in blood cancer using in vivo data. First, a data set of 98 samples of blood cancer patients including 61 features of demographic, clinical, and laboratory data are collected. After performing multivariate analysis and the approval of an expert, effective parameters are derived. Then using a deep recurrent neural network, a system is presented to predict a need for packed red blood cell transfusion. Here, we use a Long Short-Term Memory (LSTM) neural network for modeling and the cross-validation technique with 5 layers for validation of the model along with comparing the result with networking and non-networking machine learning algorithms including bidirectional LSTM, AdaBoost, bagging decision tree based, bagging KNeighbors, and Multi-Layer Perceptron (MLP). Results show the LSTM outperforms the other methods. Then, using the swarm of fuzzy bioinspired nanomachines and the most effective parameters of Hgb, PaO2, and pH, we propose a feasibility study on nano fuzzy alarming system (NFABT) for blood transfusion requirements. Alarming decisions using the Internet of Things (IoT) gateway are delivered to the physician for performing medical actions. Also, NFABT is considered a real-time non-invasive AI-based hemoglobin monitoring and alarming method. Results show the merits of the proposed method.
Assessing land-use changes and carbon storage: a case study of the Jialing River Basin, China
Authors: Yang Shuai , Li Liqin , Zhu Renhuan , Luo Chao , Lu Xiong , Sun Mili , Xu Benchuan
Published: July 2024

Land-use change is the main driver of carbon storage change in terrestrial ecosystems. Currently, domestic and international studies mainly focus on the impact of carbon storage changes on climate, while studies on the impact of land-use changes on carbon storage in complex terrestrial ecosystems are few. The Jialing River Basin (JRB), with a total area of ~ 160,000 km2, diverse topography, and elevation differences exceeding 5 km, is an ideal case for understanding the complex interactions between land-use change and carbon storage dynamics. Taking the JRB as our study area, we analyzed land-use changes from 2000 to 2020. Subsequently, we simulated land-use patterns for business-as-usual (BAU), cropland protection (CP), and ecological priority (EP) scenarios in 2035 using the PLUS model. Additionally, we assessed carbon storage using the InVEST model. This approach helps us to accurately understand the carbon change processes in regional complex terrestrial ecosystems and to formulate scientifically informed land-use policies. The results revealed the following: (1) Cropland was the most dominant land-use type (LUT) in the region, and it was the only LUT experiencing net reduction, with 92.22% of newly designated construction land originating from cropland. (2) In the JRB, total carbon storage steadily decreased after 2005, with significant spatial heterogeneity. This pattern was marked by higher carbon storage levels in the north and lower levels in the south, with a distinct demarcation line. The conversion of cropland to construction land is the main factor driving the reduction in carbon storage. (3) Compared with the BAU and EP scenarios, the CP scenario demonstrated a smaller reduction in cropland area, a smaller addition to construction land area, and a lower depletion in the JRB total carbon storage from 2020 to 2035. This study demonstrates the effectiveness of the PLUS and InVEST models in analyzing complex ecosystems and offers data support for quantitatively assessing regional ecosystem services. Strict adherence to the cropland replenishment task mandated by the Chinese government is crucial to increase cropland areas in the JRB and consequently enhance the carbon sequestration capacity of its ecosystem. Such efforts are vital for ensuring the food and ecological security of the JRB, particularly in the pursuit of the “dual-carbon” objective.