bluuebunny/crossref_metadata_2025_split huggingface dataset:
DYRK1A signalling synchronizes the mitochondrial import pathways for metabolic rewiring
Authors: Marada Adinarayana , Walter Corvin , Suhm Tamara , Shankar Sahana , Nandy Arpita , Brummer Tilman , Dhaouadi Ines , Vögtle F.-Nora , Meisinger Chris 
Published: June 2024

AbstractMitochondria require an extensive proteome to maintain a variety of metabolic reactions, and changes in cellular demand depend on rapid adaptation of the mitochondrial protein composition. The TOM complex, the organellar entry gate for mitochondrial precursors in the outer membrane, is a target for cytosolic kinases to modulate protein influx. DYRK1A phosphorylation of the carrier import receptor TOM70 at Ser91 enables its efficient docking and thus transfer of precursor proteins to the TOM complex. Here, we probe TOM70 phosphorylation in molecular detail and find that TOM70 is not a CK2 target nor import receptor for MIC19 as previously suggested. Instead, we identify TOM20 as a MIC19 import receptor and show off-target inhibition of the DYRK1A-TOM70 axis with the clinically used CK2 inhibitor CX4945 which activates TOM20-dependent import pathways. Taken together, modulation of DYRK1A signalling adapts the central mitochondrial protein entry gate via synchronization of TOM70- and TOM20-dependent import pathways for metabolic rewiring. Thus, DYRK1A emerges as a cytosolic surveillance kinase to regulate and fine-tune mitochondrial protein biogenesis.
Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice
Authors: Stefens Sanne J. M. , van Vliet Nicole , IJpma Arne , Burger Joyce , Li Yunlei , van Heijningen Paula M. , Lindeman Jan H. N. , Majoor-Krakauer Danielle , Verhagen Hence J. M. , Kanaar Roland , Essers Jeroen , van der Pluijm Ingrid 
Published: June 2024

AbstractAortic aneurysms are dilatations of the aorta that can rupture when left untreated. We used the aneurysmal Fibulin-4R/R mouse model to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4R/R aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating the involvement of senescence. Analysis of aorta histology and of vascular smooth muscle cells (VSMCs) in vitro confirmed the senescent phenotype of Fibulin-4R/R VSMCs by revealing increased SA-β-gal, p21, and p16 staining, increased IL-6 secretion, increased presence of DNA damage foci and increased nuclei size. Additionally, we found that p21 luminescence was increased in the dilated aorta of Fibulin-4R/R|p21-luciferase mice. Our studies identify a cellular aging cascade in Fibulin-4 aneurysmal disease, by revealing that Fibulin-4R/R aortic VSMCs have a pronounced SASP and a senescent phenotype that may underlie aortic wall degeneration. Additionally, we demonstrated the therapeutic effect of JAK/STAT and TGF-β pathway inhibition, as well as senolytic treatment on Fibulin-4R/R VSMCs in vitro. These findings can contribute to improved therapeutic options for aneurysmal disease aimed at reducing senescent cells.
Effects of wall materials on the physicochemical properties of spray-dried bitter gourd (Momordica charantia L.) powders
Authors: Deng Yuanyuan , Liu Guang , Zhang Huimin , Zhou Pengfei , Tang Xiaojun , Li Ping , Zhao Zhihao , Zhang Yan , Wang Zhangying , Wei Zhencheng , Zhang Mingwei 
Published: June 2024

AbstractBitter gourd has numerous health-promoting effects on the human body. However, its use has been greatly limited due to its poor acceptance by consumers, resulting from its strong bitterness. This study investigated the effects of five wall materials, namely, soybean protein isolate, gum arabic, maltodextrin, resistant starch, and a soybean lecithin calcium caseinate mixture, on the physicochemical properties of spray-dried bitter gourd powders. The results showed that all five wall materials reduced the moisture content, water activity, browning degree, agglomeration, and bitterness of the spray-dried bitter gourd powder. Maltodextrin was found to be the most effective at reducing water activity, while soybean protein isolate was best at protecting the colour, and the soybean lecithin calcium caseinate mixture was best at reducing hygroscopicity and masking bitterness. Additionally, all five wall materials improved the preservation of flavonoids, saponins, and vitamin C, with soybean protein isolate being the most effective in improving the total flavonoid retention ratio and the soybean lecithin calcium caseinate mixture being the best in improving the retention ratios of total saponins and vitamin C. The spray-dried bitter gourd powder prepared with soybean protein isolate had the highest antioxidant activity and α-glucosidase inhibitory activity. These results are significant for understanding the relationship between wall materials and the physicochemical properties of spray-dried powder. Additionally, these materials provide bitter gourd product manufacturers with useful guidance for producing high-quality products. Furthermore, the results could provide useful insights for processing fruits with similar product characteristics, thus contributing to the enrichment of food processing knowledge.
The maintenance of oocytes in the mammalian ovary involves extreme protein longevity
Authors: Harasimov Katarina , Gorry Rebecca L. , Welp Luisa M. , Penir Sarah Mae , Horokhovskyi Yehor , Cheng Shiya , Takaoka Katsuyoshi , Stützer Alexandra , Frombach Ann-Sophie , Taylor Tavares Ana Lisa , Raabe Monika , Haag Sara , Saha Debojit , Grewe Katharina , Schipper Vera , Rizzoli Silvio O. , Urlaub Henning , Liepe Juliane , Schuh Melina 
Published: June 2024

AbstractWomen are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman’s reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline.
Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation
Authors: Verhagen Mathijs P. , Joosten Rosalie , Schmitt Mark , Välimäki Niko , Sacchetti Andrea , Rajamäki Kristiina , Choi Jiahn , Procopio Paola , Silva Sara , van der Steen Berdine , van den Bosch Thierry P. P. , Seinstra Danielle , de Vries Annemarie C. , Doukas Michail , Augenlicht Leonard H. , Aaltonen Lauri A. , Fodde Riccardo 
Published: June 2024

AbstractAccording to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice. Upon inflammation, Paneth cell-specificApcmutations led to intestinal tumors reminiscent not only of those arising in patients with inflammatory bowel disease, but also of a larger fraction of human sporadic colon cancers. The latter is possibly because of the inflammatory consequences of western-style dietary habits, a major colon cancer risk factor. Machine learning methods designed to predict the cell-of-origin of cancer from patient-derived tumor samples confirmed that, in a substantial fraction of sporadic cases, the origins of colon cancer reside in secretory lineages and not in stem cells.
Cu-nanoparticles enhance the sustainable growth and yield of drought-subjected wheat through physiological progress
Authors: Raza Muhammad Aown Sammar , Amin Jawad , Valipour Mohammad , Iqbal Rashid , Aslam Muhammad Usman , Zulfiqar Bilal , Muhammad Faqeer , Ibrahim Muhammad Arif , Al-Ghamdi Abdullah Ahmed , Elshikh Mohamed S. , Iqbal Javed , Toleikienė Monika , Elsalahy Heba H. 
Published: June 2024

AbstractDrought stress (DS) is a significant abiotic stress that limits agricultural productivity worldwide. In semi-arid climates, one potential solution to alleviate the deleterious effects of drought is the use of soil amendments such as nanoparticles. The current research was conducted out to probe the sway of drought at critical growth stages (CGS) of wheat crop (D0: Control, D1: Drought at tillering stage, and D2: Drought at anthesis stage) and the application of Cu-nanoparticles (T0: 0 mg L−1, T1: 300 mg L−1, T2: 700 mg L−1, and T3: 950 mg L−1) in order to improve drought resilience. Results of the study revealed that DS considerably decreased the wheat growth and yield during CGS. However, Cu-nanoparticles application alleviated the detrimental backlash of DS and led to improvements in various aspects of wheat growth and yield, including plant height, spike length, 1000 grain weight, stomatal conductance, leaf chlorophyll content, water use efficiency, leaf turgor potential, relative water content, and ultimately the grain yield. The use of principal component analysis allowed us to integrate and interpret the diverse findings of our study, elucidating the impact of Cu-nanoparticle treatment on wheat growth and yield under drought. Overall, the study concluded that DS during the anthesis stage had the most significant negative impact on crop yield. However, applying Cu-nanoparticles at the rate of 300 mg L−1 proved to be an effective strategy for improving crop productivity by reducing the harmful effects of drought.
An improved gray wolf optimization algorithm solving to functional optimization and engineering design problems
Authors: Qiu Yihui , Yang Xiaoxiao , Chen Shuixuan 
Published: June 2024

Abstract
As a newly proposed optimization algorithm based on the social hierarchy and hunting behavior of gray wolves, grey wolf algorithm (GWO) has gradually become a popular method for solving the optimization problems in various engineering fields. In order to further improve the convergence speed, solution accuracy, and local minima escaping ability of the traditional GWO algorithm, this work proposes a multi-strategy fusion improved gray wolf optimization (IGWO) algorithm. First, the initial population is optimized using the lens imaging reverse learning algorithm for laying the foundation for global search. Second, a nonlinear control parameter convergence strategy based on cosine variation is proposed to coordinate the global exploration and local exploitation ability of the algorithm. Finally, inspired by the tunicate swarm algorithm (TSA) and the particle swarm algorithm (PSO), a nonlinear tuning strategy for the parameters, and a correction based on the individual historical optimal positions and the global optimal positions are added in the position update equations to speed up the convergence of the algorithm. The proposed algorithm is assessed using 23 benchmark test problems, 15 CEC2014 test problems, and 2 well-known constraint engineering problems. The results show that the proposed IGWO has a balanced E&P capability in coping with global optimization as analyzed by the Wilcoxon rank sum and Friedman tests, and has a clear advantage over other state-of-the-art algorithms.
Enhancing the electrical readout of the spin-dependent recombination current in SiC JFETs for EDMR based magnetometry using a tandem (de-)modulation technique
Authors: Gottscholl Andreas , Kraus Hannes , Aichinger Thomas , Cochrane Corey J. 
Published: June 2024

AbstractElectrically detected magnetic resonance (EDMR) is a promising method to readout spins in miniaturized devices utilized as quantum magnetometers. However, the sensitivity has remained challenging. In this study, we present a tandem (de-)modulation technique based on a combination of magnetic field and radio frequency modulation. By enabling higher demodulation frequencies to avoid 1/f-noise, enhancing self-calibration capabilities, and eliminating background signals by 3 orders of magnitude, this technique represents a significant advancement in the field of EDMR-based sensors. This novel approach paves the way for EDMR being the ideal candidate for ultra-sensitive magnetometry at ambient conditions without any optical components, which brings it one step closer to a chip-based quantum sensor for future applications.
The impact of cognitive distraction on gustatory perception in volunteers with obesity
Authors: Ruda Iryna , Chellapandian Deepak Charles , Freiherr Jessica 
Published: June 2024

AbstractObesity, a global health challenge, is influenced by biological, behavioral, socioeconomical, and environmental factors. In our technology-driven world, distracted eating is prevalent, yet neurocognitive mechanisms behind it remain poorly understood. This study targets individuals with overweight and obesity, exploring taste perception under distraction comprehensively. Participants formed two distinct groups based on their Body Mass Index (BMI), lean and overweight/obese. During the experiment participants received gustatory stimuli while playing a Tetris game of various difficulty levels. Participants rated taste intensity and pleasantness, with linear mixed models analyzing distraction effects. Results confirmed that high distraction levels reduced perception of taste intensity (p = 0.017) and taste pleasantness (p = 0.022), with variations influenced by gender and weight status. Individuals in the overweight/obese group exhibited most profound intensity changes during distraction (p = 0.01). Taste sensitivity ratings positively correlated with BMI interacting with gender (male r = 0.227, p < 0.001; female r = 0.101, p < 0.001). Overall across both groups, female participants demonstrated higher taste sensitivity compared to male participants (p < 0.001). This study highlights the impact of cognitive distraction during consumption on taste perception, particularly in relation to weight status and gender, underscoring their significant roles in this interplay.
Machine learning for the prediction of in-hospital mortality in patients with spontaneous intracerebral hemorrhage in intensive care unit
Authors: Mao Baojie , Ling Lichao , Pan Yuhang , Zhang Rui , Zheng Wanning , Shen Yanfei , Lu Wei , Lu Yuning , Xu Shanhu , Wu Jiong , Wang Ming , Wan Shu 
Published: June 2024

AbstractThis study aimed to develop a machine learning (ML)-based tool for early and accurate prediction of in-hospital mortality risk in patients with spontaneous intracerebral hemorrhage (sICH) in the intensive care unit (ICU). We did a retrospective study in our study and identified cases of sICH from the MIMIC IV (n = 1486) and Zhejiang Hospital databases (n = 110). The model was constructed using features selected through LASSO regression. Among five well-known models, the selection of the best model was based on the area under the curve (AUC) in the validation cohort. We further analyzed calibration and decision curves to assess prediction results and visualized the impact of each variable on the model through SHapley Additive exPlanations. To facilitate accessibility, we also created a visual online calculation page for the model. The XGBoost exhibited high accuracy in both internal validation (AUC = 0.907) and external validation (AUC = 0.787) sets. Calibration curve and decision curve analyses showed that the model had no significant bias as well as being useful for supporting clinical decisions. XGBoost is an effective algorithm for predicting in-hospital mortality in patients with sICH, indicating its potential significance in the development of early warning systems.
Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest
Authors: Jinton Helen , Sopasakis Victoria Rotter , Sjölin Linnéa , Oldfors Anders , Jeppsson Anders , Oras Jonatan , Wernbom Mathias , Vukusic Kristina 
Published: June 2024

AbstractGlobal ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.
Stronger Arctic amplification from anthropogenic aerosols than from greenhouse gases
Authors: Wu You-Ting , Liang Yu-Chiao , Previdi Michael , Polvani Lorenzo M. , England Mark R. , Sigmond Michael , Lo Min-Hui 
Published: June 2024

AbstractArctic amplification (AA), the greater Arctic surface warming compared to the global average, has been widely attributed to increasing concentrations of greenhouse gases (GHG). However, less is known about the impacts of other forcings - notably, anthropogenic aerosols (AER) - and how they may compare to the impacts of GHG. Here we analyze sets of climate model simulations, specifically designed to isolate the AER and GHG effects on global climate. Surprisingly, we find stronger AA produced by AER than by GHG during the 1955–1984 period, when the strongest global AER increase. This stronger AER-induced AA is due to a greater sensitivity of Arctic sea ice, and associated changes in ocean-to-atmosphere heat exchange, to AER forcing. Our findings highlight the asymmetric Arctic climate response to GHG and AER forcings, and show that clean air policies which have reduced aerosol emissions may have exacerbated the Arctic warming over the past few decades.
Development and validation of a smartphone-based deep-learning-enabled system to detect middle-ear conditions in otoscopic images
Authors: Dubois Constance , Eigen David , Simon François , Couloigner Vincent , Gormish Michael , Chalumeau Martin , Schmoll Laurent , Cohen Jérémie F. 
Published: June 2024

AbstractMiddle-ear conditions are common causes of primary care visits, hearing impairment, and inappropriate antibiotic use. Deep learning (DL) may assist clinicians in interpreting otoscopic images. This study included patients over 5 years old from an ambulatory ENT practice in Strasbourg, France, between 2013 and 2020. Digital otoscopic images were obtained using a smartphone-attached otoscope (Smart Scope, Karl Storz, Germany) and labeled by a senior ENT specialist across 11 diagnostic classes (reference standard). An Inception-v2 DL model was trained using 41,664 otoscopic images, and its diagnostic accuracy was evaluated by calculating class-specific estimates of sensitivity and specificity. The model was then incorporated into a smartphone app called i-Nside. The DL model was evaluated on a validation set of 3,962 images and a held-out test set comprising 326 images. On the validation set, all class-specific estimates of sensitivity and specificity exceeded 98%. On the test set, the DL model achieved a sensitivity of 99.0% (95% confidence interval: 94.5–100) and a specificity of 95.2% (91.5–97.6) for the binary classification of normal vs. abnormal images; wax plugs were detected with a sensitivity of 100% (94.6–100) and specificity of 97.7% (95.0–99.1); other class-specific estimates of sensitivity and specificity ranged from 33.3% to 92.3% and 96.0% to 100%, respectively. We present an end-to-end DL-enabled system able to achieve expert-level diagnostic accuracy for identifying normal tympanic aspects and wax plugs within digital otoscopic images. However, the system’s performance varied for other middle-ear conditions. Further prospective validation is necessary before wider clinical deployment.
Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity
Authors: Kitamura Akira , Fujimoto Ai , Kawashima Rei , Lyu Yidan , Sasaki Kotetsu , Hamada Yuta , Moriya Kanami , Kurata Ayumi , Takahashi Kazuho , Brielmann Reneé , Bott Laura C. , Morimoto Richard I. , Kinjo Masataka 
Published: June 2024

AbstractCarboxy terminal fragments (CTFs) of TDP-43 contain an intrinsically disordered region (IDR) and form cytoplasmic condensates containing amyloid fibrils. Such condensates are toxic and associated with pathogenicity in amyotrophic lateral sclerosis. However, the molecular details of how the domain of TDP-43 CTFs leads to condensation and cytotoxicity remain elusive. Here, we show that truncated RNA/DNA-recognition motif (RRM) at the N-terminus of TDP-43 CTFs leads to the structural transition of the IDR, whereas the IDR itself of TDP-43 CTFs is difficult to assemble even if they are proximate intermolecularly. Hetero-oligomers of TDP-43 CTFs that have recruited other proteins are more toxic than homo-oligomers, implicating loss-of-function of the endogenous proteins by such oligomers is associated with cytotoxicity. Furthermore, such toxicity of TDP-43 CTFs was cell-nonautonomously affected in the nematodes. Therefore, misfolding and oligomeric characteristics of the truncated RRM at the N-terminus of TDP-43 CTFs define their condensation properties and toxicity.
Dorsomorphin inhibits AMPK, upregulates Wnt and Foxo genes and promotes the activation of dormant follicles
Authors: Madsen Julie Feld , Ernst Emil Hagen , Amoushahi Mahboobeh , Dueholm Margit , Ernst Erik , Lykke-Hartmann Karin 
Published: June 2024

AbstractAMPK is a well-known energy sensor regulating cellular metabolism. Metabolic disorders such as obesity and diabetes are considered detrimental factors that reduce fecundity. Here, we show that pharmacologically induced in vitro activation (by metformin) or inhibition (by dorsomorphin) of the AMPK pathway inhibits or promotes activation of ovarian primordial follicles in cultured murine ovaries and human ovarian cortical chips. In mice, activation of primordial follicles in dorsomorphin in vitro-treated ovaries reduces AMPK activation and upregulates Wnt and FOXO genes, which, interestingly, is associated with decreased phosphorylation of β-catenin. The dorsomorphin-treated ovaries remain of high quality, with no detectable difference in reactive oxygen species production, apoptosis or mitochondrial cytochrome c oxidase activity, suggesting safe activation. Subsequent maturation of in vitro-treated follicles, using a 3D alginate cell culture system, results in mature metaphase eggs with protruding polar bodies. These findings demonstrate that the AMPK pathway can safely regulate primordial follicles by modulating Wnt and FOXO genes, and reduce β-catenin phosphorylation.