bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and regulation of full-length human leucine-rich repeat kinase 1
Authors: Metcalfe Riley D. , Martinez Fiesco Juliana A. , Bonet-Ponce Luis , Kluss Jillian H. , Cookson Mark R. , Zhang Ping 
Published: August 2023

AbstractThe human leucine-rich repeat kinases (LRRKs), LRRK1 and LRRK2 are large and unusually complex multi-domain kinases, which regulate fundamental cellular processes and have been implicated in human disease. Structures of LRRK2 have recently been determined, but the structure and molecular mechanisms regulating the activity of the LRRK1 as well as differences in the regulation of LRRK1 and LRRK2 remain unclear. Here, we report a cryo-EM structure of the LRRK1 monomer and a lower-resolution cryo-EM map of the LRRK1 dimer. The monomer structure, in which the kinase is in an inactive conformation, reveals key interdomain interfaces that control kinase activity as we validate experimentally. Both the LRRK1 monomer and dimer are structurally distinct compared to LRRK2. Overall, our results provide structural insights into the activation of the human LRRKs, which advance our understanding of their physiological and pathological roles.
High-performance thermomagnetic generator controlled by a magnetocaloric switch
Authors: Liu Xianliang , Chen Haodong , Huang Jianyi , Qiao Kaiming , Yu Ziyuan , Xie Longlong , Ramanujan Raju V. , Hu Fengxia , Chu Ke , Long Yi , Zhang Hu 
Published: August 2023

AbstractLow grade waste heat accounts for ~65% of total waste heat, but conventional waste heat recovery technology exhibits low conversion efficiency for low grade waste heat recovery. Hence, we designed a thermomagnetic generator for such applications. Unlike its usual role as the coil core or big magnetic yoke in previous works, here the magnetocaloric material acts as a switch that controls the magnetic circuit. This makes it not only have the advantage of flux reversal of the pretzel-like topology, but also present a simpler design, lower magnetic stray field, and higher performance by using less magnetocaloric material than preceding devices. The effects of key structural and system parameters were studied through a combination of experiments and finite element simulations. The optimized max power density PDmax produced by our device is significantly higher than those of other existing active thermomagnetic, thermo, and pyroelectric generators. Such high performance shows the effectiveness of our topology design of magnetic circuit with magnetocaloric switch.
TRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6
Authors: Zhao Yiqi , Lu Yongxu , Richardson Samuel , Sreekumar Meghna , Albarnaz Jonas D. , Smith Geoffrey L. 
Published: August 2023

AbstractHuman tripartite motif protein 5α (TRIM5α) is a well-characterized restriction factor for some RNA viruses, including HIV1–5; however, reports are limited for DNA viruses6,7. Here we demonstrate that TRIM5α also restricts orthopoxviruses and, via its SPRY domain, binds to the orthopoxvirus capsid protein L3 to diminish virus replication and activate innate immunity. In response, several orthopoxviruses, including vaccinia, rabbitpox, cowpox, monkeypox, camelpox and variola viruses, deploy countermeasures. First, the protein C6 binds to TRIM5 via the RING domain to induce its proteasome-dependent degradation. Second, cyclophilin A (CypA) is recruited via interaction with the capsid protein L3 to virus factories and virions to antagonize TRIM5α; this interaction is prevented by cyclosporine A (CsA) and the non-immunosuppressive derivatives alisporivir and NIM811. Both the proviral effect of CypA and the antiviral effect of CsA are dependent on TRIM5α. CsA, alisporivir and NIM811 have antiviral activity against orthopoxviruses, and because these drugs target a cellular protein, CypA, the emergence of viral drug resistance is difficult. These results warrant testing of CsA derivatives against orthopoxviruses, including monkeypox and variola.
Tail engagement of arrestin at the glucagon receptor
Authors: Chen Kun , Zhang Chenhui , Lin Shuling , Yan Xinyu , Cai Heng , Yi Cuiying , Ma Limin , Chu Xiaojing , Liu Yuchen , Zhu Ya , Han Shuo , Zhao Qiang , Wu Beili 
Published: August 2023

AbstractArrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing G protein activation and mediating receptor internalization1,2. It has been proposed that the arrestin binds to the receptor in two different conformations, ‘tail’ and ‘core’, which were suggested to govern distinct processes of receptor signalling and trafficking3,4. However, little structural information is available for the tail engagement of the arrestins. Here we report two structures of the glucagon receptor (GCGR) bound to β-arrestin 1 (βarr1) in glucagon-bound and ligand-free states. These structures reveal a receptor tail-engaged binding mode of βarr1 with many unique features, to our knowledge, not previously observed. Helix VIII, instead of the receptor core, has a major role in accommodating βarr1 by forming extensive interactions with the central crest of βarr1. The tail-binding pose is further defined by a close proximity between the βarr1 C-edge and the receptor helical bundle, and stabilized by a phosphoinositide derivative that bridges βarr1 with helices I and VIII of GCGR. Lacking any contact with the arrestin, the receptor core is in an inactive state and loosely binds to glucagon. Further functional studies suggest that the tail conformation of GCGR–βarr governs βarr recruitment at the plasma membrane and endocytosis of GCGR, and provides a molecular basis for the receptor forming a super-complex simultaneously with G protein and βarr to promote sustained signalling within endosomes. These findings extend our knowledge about the arrestin-mediated modulation of GPCR functionalities.
Mitochondrial integrated stress response controls lung epithelial cell fate
Authors: Han SeungHye , Lee Minho , Shin Youngjin , Giovanni Regina , Chakrabarty Ram P. , Herrerias Mariana M. , Dada Laura A. , Flozak Annette S. , Reyfman Paul A. , Khuder Basil , Reczek Colleen R. , Gao Lin , Lopéz-Barneo José , Gottardi Cara J. , Budinger G. R. Scott , Chandel Navdeep S. 
Published: August 2023

AbstractAlveolar epithelial type 1 (AT1) cells are necessary to transfer oxygen and carbon dioxide between the blood and air. Alveolar epithelial type 2 (AT2) cells serve as a partially committed stem cell population, producing AT1 cells during postnatal alveolar development and repair after influenza A and SARS-CoV-2 pneumonia1–6. Little is known about the metabolic regulation of the fate of lung epithelial cells. Here we report that deleting the mitochondrial electron transport chain complex I subunit Ndufs2 in lung epithelial cells during mouse gestation led to death during postnatal alveolar development. Affected mice displayed hypertrophic cells with AT2 and AT1 cell features, known as transitional cells. Mammalian mitochondrial complex I, comprising 45 subunits, regenerates NAD+ and pumps protons. Conditional expression of yeast NADH dehydrogenase (NDI1) protein that regenerates NAD+ without proton pumping7,8 was sufficient to correct abnormal alveolar development and avert lethality. Single-cell RNA sequencing revealed enrichment of integrated stress response (ISR) genes in transitional cells. Administering an ISR inhibitor9,10 or NAD+ precursor reduced ISR gene signatures in epithelial cells and partially rescued lethality in the absence of mitochondrial complex I function. Notably, lung epithelial-specific loss of mitochondrial electron transport chain complex II subunit Sdhd, which maintains NAD+ regeneration, did not trigger high ISR activation or lethality. These findings highlight an unanticipated requirement for mitochondrial complex I-dependent NAD+ regeneration in directing cell fate during postnatal alveolar development by preventing pathological ISR induction.
Red-tailed hawk algorithm for numerical optimization and real-world problems
Authors: Ferahtia Seydali , Houari Azeddine , Rezk Hegazy , Djerioui Ali , Machmoum Mohamed , Motahhir Saad , Ait-Ahmed Mourad 
Published: August 2023

AbstractThis study suggests a new nature-inspired metaheuristic optimization algorithm called the red-tailed hawk algorithm (RTH). As a predator, the red-tailed hawk has a hunting strategy from detecting the prey until the swoop stage. There are three stages during the hunting process. In the high soaring stage, the red-tailed hawk explores the search space and determines the area with the prey location. In the low soaring stage, the red-tailed moves inside the selected area around the prey to choose the best position for the hunt. Then, the red-tailed swings and hits its target in the stooping and swooping stages. The proposed algorithm mimics the prey-hunting method of the red-tailed hawk for solving real-world optimization problems. The performance of the proposed RTH algorithm has been evaluated on three classes of problems. The first class includes three specific kinds of optimization problems: 22 standard benchmark functions, including unimodal, multimodal, and fixed-dimensional multimodal functions, IEEE Congress on Evolutionary Computation 2020 (CEC2020), and IEEE CEC2022. The proposed algorithm is compared with eight recent algorithms to confirm its contribution to solving these problems. The considered algorithms are Farmland Fertility Optimizer (FO), African Vultures Optimization Algorithm (AVOA), Mountain Gazelle Optimizer (MGO), Gorilla Troops Optimizer (GTO), COOT algorithm, Hunger Games Search (HGS), Aquila Optimizer (AO), and Harris Hawks optimization (HHO). The results are compared regarding the accuracy, robustness, and convergence speed. The second class includes seven real-world engineering problems that will be considered to investigate the RTH performance compared to other published results profoundly. Finally, the proton exchange membrane fuel cell (PEMFC) extraction parameters will be performed to evaluate the algorithm with a complex problem. The proposed algorithm will be compared with several published papers to approve its performance. The ultimate results for each class confirm the ability of the proposed RTH algorithm to provide higher performance for most cases. For the first class, the RTH mostly got the optimal solutions for most functions with faster convergence speed. The RTH provided better performance for the second and third classes when resolving the real word engineering problems or extracting the PEMFC parameters.
Monitoring and analysis of surface deformation in alpine valley areas based on multidimensional InSAR technology
Authors: Yang Fan , An Yan , Ren Chuang , Xu Jia , Li Jinbo , Li Dongliang , Peng Zhiwei 
Published: August 2023

AbstractJoshimath has received much attention for its massive ground subsidence at the beginning of the year. Rapid urbanization and its unique geographical location may have been one of the factors contributing to the occurrence of this geological disaster. In high mountain valley areas, the complex occurrence mechanism and diverse disaster patterns of geological hazards highlight the inadequacy of manual monitoring. To address this problem, the inversion of deformation of the Joshimath surface in multiple directions can be achieved by multidimensional InSAR techniques. Therefore, in this paper, the multidimensional SBAS-InSAR technique was used to process the lift-track Sentinel-1 data from 2020 to 2023 to obtain the two-dimensional vertical and horizontal deformation rates and time series characteristics of the Joshimath ground surface. To discover the causes of deformation and its correlation with anthropogenic activities and natural disasters by analyzing the spatial and temporal evolution of surface deformation. The results show that the area with the largest cumulative deformation is located in the northeastern part of the town, with a maximum cumulative subsidence of 271.2 mm and a cumulative horizontal movement of 336.5 mm. The spatial distribution of surface deformation is based on the lower part of the hill and develops towards the upper part of the hill, showing a trend of expansion from the bottom to the top. The temporal evolution is divided into two phases: gentle to rapid, and it is tentatively concluded that the decisive factor that caused the significant change in the rate of surface deformation and the early onset of the geological subsidence hazard was triggered by the 4.7 magnitude earthquake that struck near the town on 11 September 2021.
Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid
Authors: Lennartz Maximilian , Csomós Henrietta , Chirico Viktoria , Weidemann Sören , Gorbokon Natalia , Menz Anne , Büscheck Franziska , Hube-Magg Claudia , Höflmayer Doris , Bernreuther Christian , Blessin Niclas C. , Lebok Patrick , Sauter Guido , Steurer Stefan , Burandt Eike , Dum David , Krech Till , Simon Ronald , Minner Sarah , Jacobsen Frank , Clauditz Till S. , Luebke Andreas M. , Siraj Abdul Khalid , Al-Dayel Fouad , Al-Kuraya Khawla S. , Hinsch Andrea 
Published: August 2023

AbstractCadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16–56%), various subtyped of carcinomas of the uterus (18–40%), as well as in various subtypes of neuroendocrine neoplasms (4–26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker—as a part of a panel—for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.
A method for constructing word sense embeddings based on word sense induction
Authors: Sun Yujia , Platoš Jan 
Published: August 2023

AbstractPolysemy is an inherent characteristic of natural language. In order to make it easier to distinguish between different senses of polysemous words, we propose a method for encoding multiple different senses of polysemous words using a single vector. The method first uses a two-layer bidirectional long short-term memory neural network and a self-attention mechanism to extract the contextual information of polysemous words. Then, a K-means algorithm, which is improved by optimizing the density peaks clustering algorithm based on cosine similarity, is applied to perform word sense induction on the contextual information of polysemous words. Finally, the method constructs the corresponding word sense embedded representations of the polysemous words. The results of the experiments demonstrate that the proposed method produces better word sense induction than Euclidean distance, Pearson correlation, and KL-divergence and more accurate word sense embeddings than mean shift, DBSCAN, spectral clustering, and agglomerative clustering.
A smart and sustainable pathway for abatement of single and binary mixtures of dyes through magnetically retrievable Ca4Fe9O17 anchored on Biochar matrix
Authors: Yadav Gaurav , Mishra Soumya Ranjan , Gadore Vishal , Yadav Nidhi , Ahmaruzzaman Md. 
Published: August 2023

AbstractIn this work, the author developed Ca4Fe9O17/biochar (CFB) via a green method through a facile co-precipitation procedure involving egg shells as calcium precursor and investigating its performance in single as well as binary solution of methylene blue (MB) and rhodamine B (RhB). The CFB nanocomposite was characterized by XRD, SEM, TEM, XPS, Raman, FTIR, BET, and VSM. ESR studies show the presence of hydroxyl (·OH) and superoxide (O2·¯) radicals, which are primary radical species for pollutant degradation. The average crystalline size of CFB nanocomposites was found to be 32.992 nm using XRD, whereas TEM analysis indicates a particle diameter of 35–36 nm. The degradation efficacy of MB and RhB dyes was achieved at 99.2% and 98.6%, respectively, in a single solution, whereas 99.4% and 99.2%, respectively, in a binary solution within 36 min. Additionally, an iron cluster was formed during the degradation process of MB dye. The degradation of organic contaminants and generation of iron clusters from the degraded dye products were both expedited by the remarkable extension effect of the Ca4Fe9O17 in the CFB nanocomposites. The three processes were achieved using CFB nanocomposite: (1) the advanced oxidation process; (2) degradation of MB and RhB dye in single as well as binary solution with enhanced efficiency, (3) the production of the iron cluster from degraded products. Thus, these three steps constitute a smart and sustainable way that leads to an effective effluent water treatment system and the generation of iron clusters preventing secondary pollution.
High maternal mortality rate associated with advanced maternal age in Japan
Authors: Tanaka Hiroaki , Hasegawa Junichi , Katsuragi Shinji , Tanaka Kayo , Arakaki Tatsuya , Nakamura Masamitsu , Hayata Eijiro , Nakata Masahiko , Murakoshi Takeshi , Sekizawa Akihiko , Ishiwata Isamu , Ikeda Tomoaki 
Published: August 2023

AbstractThis study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3–4.7) for < 20 years, 2.6 (95% CI 1.7–3.8) for 20–24 years, 2.9 (95% CI 2.3–3.6) for 25–29 years, 3.9 (95% CI 3.3–4.5) for 30–34 years, 6.8 (95% CI 5.9–7.9) for 35–39 years, and 11.2 (95% CI 8.8–14.3) for ≥ 40 years of age. Patients who were ≥ 40 years of age had a significantly higher mortality rate compared to that in other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54%]) was the most common cause of hemorrhagic stroke. Maternal mortality is significantly higher in older than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women > 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.
Prospective validation of VEGF and eNOS polymorphisms as predictors of first-line bevacizumab efficacy in patients with metastatic colorectal cancer
Authors: Marisi Giorgia , Azzali Irene , Passardi Alessandro , Rebuzzi Francesca , Bartolini Giulia , Urbini Milena , Canale Matteo , Molinari Chiara , Matteucci Laura , Sullo Francesco Giulio , Debonis Silvia Angela , Gallio Chiara , Gallo Graziana , Frassineti Giovanni Luca , Ulivi Paola 
Published: August 2023

AbstractBevacizumab (Bev) plus chemotherapy is a standard first-line treatment in metastatic colorectal cancer (mCRC), however to date no predictive factors of response have been identified. Results of our previous analysis on patients enrolled in a randomized prospective phase III multicenter study (ITACa study) showed a predictive value of Vascular Endothelial Growth Factor (VEGF) polymorphism (VEGF + 936), a 27-nucleotide variable number tandem repeat (VNTR) of the endothelial nitric oxide synthase (eNOS) gene and eNOS + 894 polymorphism. mCRC patients, treated with Bev plus chemotherapy, were included in this prospective validation trial. eNOS + 894G > T was analyzed by Real time PCR, while the eNOS VNTR and VEGF + 936C > T were determined by standard PCR and direct sequencing analysis. These polymorphisms were assessed in relation to progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). These three polymorphisms were not predictive of PFS (p 0.91, 0.59 and 0.09, respectively), and OS (p 0.95, 0.32 and 0.46, respectively). Moreover, the haplotype analyses did not confirm what was found in our previous study; patients bearing a specific haplotype of eNOS had not significantly improved outcomes. This prospective study failed to validate the predictive impact of eNOS and VEGF polymorphisms for response to Bev plus first-line chemotherapy in mCRC patients.
Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe
Authors: Mattila Tiina M. , Svensson Emma M. , Juras Anna , Günther Torsten , Kashuba Natalija , Ala-Hulkko Terhi , Chyleński Maciej , McKenna James , Pospieszny Łukasz , Constantinescu Mihai , Rotea Mihai , Palincaș Nona , Wilk Stanisław , Czerniak Lech , Kruk Janusz , Łapo Jerzy , Makarowicz Przemysław , Potekhina Inna , Soficaru Andrei , Szmyt Marzena , Szostek Krzysztof , Götherström Anders , Storå Jan , Netea Mihai G. , Nikitin Alexey G. , Persson Per , Malmström Helena , Jakobsson Mattias 
Published: August 2023

AbstractThe genomic landscape of Stone Age Europe was shaped by multiple migratory waves and population replacements, but different regions do not all show similar patterns. To refine our understanding of the population dynamics before and after the dawn of the Neolithic, we generated and analyzed genomic sequence data from human remains of 56 individuals from the Mesolithic, Neolithic, and Eneolithic across Central and Eastern Europe. We found that Mesolithic European populations formed a geographically widespread isolation-by-distance zone ranging from Central Europe to Siberia, which was already established 10,000 years ago. We found contrasting patterns of population continuity during the Neolithic transition: people around the lower Dnipro Valley region, Ukraine, showed continuity over 4000 years, from the Mesolithic to the end of the Neolithic, in contrast to almost all other parts of Europe where population turnover drove this cultural change, including vast areas of Central Europe and around the Danube River.
Multi-stage spontaneous symmetry breaking of light in Kerr ring resonators
Authors: Hill Lewis , Oppo Gian-Luca , Del’Haye Pascal 
Published: August 2023

AbstractSymmetry breaking of light states is of interest for the understanding of nonlinear optics, photonic circuits, telecom applications and optical pulse generation. Here we demonstrate multi-stage symmetry breaking of the resonances of ring resonators with Kerr nonlinearity. This multi-stage symmetry breaking naturally occurs in a resonator with bidirectionally propagating light with orthogonal polarization components. The derived model used to theoretically describe the system shows that the four circulating field components can display full symmetry, full asymmetry, and multiple versions of partial symmetry, and are later shown to result in complex oscillatory dynamics - such as four-field self-switching, and unusual pulsing with extended delays between subsequent peaks. To highlight a few examples, our work has application in the development of photonic devices like isolators and circulators, logic gates, and random numbers generators, and could also be used for optical-sensors, e.g. by further enhancing the Sagnac effect.