bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer associated fibroblasts secreted exosomal miR-1290 contributes to prostate cancer cell growth and metastasis via targeting GSK3β
Authors: Wang Shuo , Du Peng , Cao Yudong , Ma Jinchao , Yang Xiao , Yu Ziyi , Yang Yong 
Published: August 2022

AbstractCancer-associated fibroblasts (CAFs) play crucial roles in mediating tumor growth and metastasis via transferring exosomes to neighboring cells, whereas the mechanisms by which CAFs regulate the tumorgenesis of prostate cancer (PC) remain largely unknown. In this study, CAFs and normal fibroblasts (NFs) were isolated from PC tissues and adjacent normal tissues, respectively. Exosomes (NFs-Exo and CAFs-Exo) were then isolated from the supernatant of NFs and CAFs. Next, the differentially expressed miRNAs (DEMs) between NFs-Exo and CAFs-Exo were identified using RNA-sequencing. Cell viability, migration and invasion were detected with CCK-8 and Transwell assays. Protein expression was measured with western blot. We found that CAFs-Exo remarkably enhanced PC cell migration, invasion, stemness, epithelial-mesenchymal transition (EMT) and metastasis. Significantly, miR-1290 level was upregulated in CAFs-Exo compared to NFs-Exo. In addition, CAFs could transfer exosomes to PC cells, resulting in a marked increase of miR-1290 level in cells. Moreover, exosomal miR-1290 could inhibit GSK3β/β-catenin signaling by binding with the downstream target GSK3β mRNA. Meanwhile, miR-1290 antagomir notably reversed the effects of CAFs-Exo on PC cells through activating GSK3β/β-catenin signaling. Collectively, exosomal miR-1290 from CAFs could promote PC cell growth and metastasis via inhibiting GSK3β/β-catenin signaling, suggesting that miR-1290 may serve as potential therapeutic target for the treatment of PC.
Parents’ understanding of genome and exome sequencing for pediatric health conditions: a systematic review
Authors: Gereis Jessica , Hetherington Kate , Ha Lauren , Robertson Eden G. , Ziegler David S. , Barlow-Stewart Kristine , Tucker Katherine M. , Marron Jonathan M. , Wakefield Claire E. 
Published: August 2022

AbstractGenome and exome sequencing (GS/ES) are increasingly being used in pediatric contexts. We summarize evidence regarding the actual and perceived understanding of GS/ES of parents of a child offered testing for diagnosis and/or management of a symptomatic health condition. We searched four databases (2008–2021) and identified 1264 unique articles, of which 16 met inclusion criteria. We synthesized data from qualitative and quantitative studies and organized results using Ayuso et al. (2013)’s framework of key elements of information for informed consent to GS/ES. Many of the parents represented had prior experience with genetic testing and accessed a form of genetic counseling. Parents’ understanding was varied across the domains evaluated. Parents demonstrated understanding of the various potential direct clinical benefits to their child undergoing GS/ES, including in relation to other genetic tests. We found parents had mixed understanding of the nature of potential secondary findings, and of issues related to data privacy, confidentiality, and usage of sequencing results beyond their child’s clinical care. Genetic counseling consultations improved understanding. Our synthesis indicates that ES/GS can be challenging for families to understand and underscores the importance of equipping healthcare professionals to explore parents’ understanding of ES/GS and the implications of testing for their child.
Integrated 3D printing of flexible electroluminescent devices and soft robots
Authors: Zhang Pei , Lei Iek Man , Chen Guangda , Lin Jingsen , Chen Xingmei , Zhang Jiajun , Cai Chengcheng , Liang Xiangyu , Liu Ji 
Published: August 2022

AbstractFlexible and stretchable light emitting devices are driving innovation in myriad applications, such as wearable and functional electronics, displays and soft robotics. However, the development of flexible electroluminescent devices via conventional techniques remains laborious and cost-prohibitive. Here, we report a facile and easily-accessible route for fabricating a class of flexible electroluminescent devices and soft robotics via direct ink writing-based 3D printing. 3D printable ion conducting, electroluminescent and insulating dielectric inks were developed, enabling facile and on-demand creation of flexible and stretchable electroluminescent devices with good fidelity. Robust interfacial adhesion with the multilayer electroluminescent devices endowed the 3D printed devices with attractive electroluminescent performance. Integrated our 3D printed electroluminescent devices with a soft quadrupedal robot and sensing units, an artificial camouflage that can instantly self-adapt to the environment by displaying matching color was fabricated, laying an efficient framework for the next generation soft camouflages.
Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals
Authors: Abe Yasuko O. , Yoshitane Hikari , Kim Dae Wook , Kawakami Satoshi , Koebis Michinori , Nakao Kazuki , Aiba Atsu , Kim Jae Kyoung , Fukada Yoshitaka 
Published: August 2022

AbstractIn mammals, the circadian clock consists of transcriptional and translational feedback loops through DNA cis-elements such as E-box and RRE. The E-box-mediated core feedback loop is interlocked with the RRE-mediated feedback loop, but biological significance of the RRE-mediated loop has been elusive. In this study, we established mutant cells and mice deficient for rhythmic transcription of Bmal1 gene by deleting its upstream RRE elements and hence disrupted the RRE-mediated feedback loop. We observed apparently normal circadian rhythms in the mutant cells and mice, but a combination of mathematical modeling and experiments revealed that the circadian period and amplitude of the mutants were more susceptible to disturbance of CRY1 protein rhythm. Our findings demonstrate that the RRE-mediated feedback regulation of Bmal1 underpins the E-box-mediated rhythm in cooperation with CRY1-dependent posttranslational regulation of BMAL1 protein, thereby conferring the perturbation-resistant oscillation and chronologically-organized output of the circadian clock.
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes
Authors: Akbari Parsa , Sosina Olukayode A. , Bovijn Jonas , Landheer Karl , Nielsen Jonas B. , Kim Minhee , Aykul Senem , De Tanima , Haas Mary E. , Hindy George , Lin Nan , Dinsmore Ian R. , Luo Jonathan Z. , Hectors Stefanie , Geraghty Benjamin , Germino Mary , Panagis Lampros , Parasoglou Prodromos , Walls Johnathon R. , Halasz Gabor , Atwal Gurinder S. ,   Regeneron Genetics Center, Della Gatta Giusy ,   DiscovEHR Collaboration, Jones Marcus , LeBlanc Michelle G. , Still Christopher D. , Carey David J. , Giontella Alice , Orho-Melander Marju , Berumen Jaime , Kuri-Morales Pablo , Alegre-Díaz Jesus , Torres Jason M. , Emberson Jonathan R. , Collins Rory , Rader Daniel J. , Zambrowicz Brian , Murphy Andrew J. , Balasubramanian Suganthi , Overton John D. , Reid Jeffrey G. , Shuldiner Alan R. , Cantor Michael , Abecasis Goncalo R. , Ferreira Manuel A. R. , Sleeman Mark W. , Gusarova Viktoria , Altarejos Judith , Harris Charles , Economides Aris N. , Idone Vincent , Karalis Katia , Della Gatta Giusy , Mirshahi Tooraj , Yancopoulos George D. , Melander Olle , Marchini Jonathan , Tapia-Conyer Roberto , Locke Adam E. , Baras Aris , Verweij Niek , Lotta Luca A. 
Published: August 2022

AbstractBody fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10−09), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease.
Sub-10-fs observation of bound exciton formation in organic optoelectronic devices
Authors: Maimaris Marios , Pettipher Allan J. , Azzouzi Mohammed , Walke Daniel J. , Zheng Xijia , Gorodetsky Andrei , Dong Yifan , Tuladhar Pabitra Shakya , Crespo Helder , Nelson Jenny , Tisch John W. G. , Bakulin Artem A. 
Published: August 2022

AbstractFundamental mechanisms underlying exciton formation in organic semiconductors are complex and elusive as it occurs on ultrashort sub-100-fs timescales. Some fundamental aspects of this process, such as the evolution of exciton binding energy, have not been resolved in time experimentally. Here, we apply a combination of sub-10-fs Pump-Push-Photocurrent, Pump-Push-Photoluminescence, and Pump-Probe spectroscopies to polyfluorene devices to track the ultrafast formation of excitons. While Pump-Probe is sensitive to the total concentration of excited states, Pump-Push-Photocurrent and Pump-Push-Photoluminescence are sensitive to bound states only, providing access to exciton binding dynamics. We find that excitons created by near-absorption-edge photons are intrinsically bound states, or become such within 10 fs after excitation. Meanwhile, excitons with a modest >0.3 eV excess energy can dissociate spontaneously within 50 fs before acquiring bound character. These conclusions are supported by excited-state molecular dynamics simulations and a global kinetic model which quantitatively reproduce experimental data.
Rainfall and sea level drove the expansion of seasonally flooded habitats and associated bird populations across Amazonia
Authors: Sawakuchi A. O. , Schultz E. D. , Pupim F. N. , Bertassoli D. J. , Souza D. F. , Cunha D. F. , Mazoca C. E. , Ferreira M. P. , Grohmann C. H. , Wahnfried I. D. , Chiessi C. M. , Cruz F. W. , Almeida R. P. , Ribas C. C. 
Published: August 2022

AbstractSpatial arrangement of distinct Amazonian environments through time and its effect on specialized biota remain poorly known, fueling long-lasting debates about drivers of biotic diversification. We address the late Quaternary sediment deposition that assembled the world's largest seasonally flooded ecosystems. Genome sequencing was used to reconstruct the demographic history of bird species specialized in either early successional vegetation or mature floodplain forests. Sediment deposition that built seasonally flooded habitats accelerated throughout the Holocene (last 11,700 years) under sea level highstand and intensification of the South American Monsoon, at the same time as global increases in atmospheric methane concentration. Bird populations adapted to seasonally flooded habitats expanded due to enlargement of Amazonian river floodplains and archipelagos. Our findings suggest that the diversification of the biota specialized in seasonally flooded habitats is coupled to sedimentary budget changes of large rivers, which rely on combined effects of sea level and rainfall variations.
De novo protein design of photochemical reaction centers
Authors: Ennist Nathan M. , Zhao Zhenyu , Stayrook Steven E. , Discher Bohdana M. , Dutton P. Leslie , Moser Christopher C. 
Published: August 2022

AbstractNatural photosynthetic protein complexes capture sunlight to power the energetic catalysis that supports life on Earth. Yet these natural protein structures carry an evolutionary legacy of complexity and fragility that encumbers protein reengineering efforts and obfuscates the underlying design rules for light-driven charge separation. De novo development of a simplified photosynthetic reaction center protein can clarify practical engineering principles needed to build new enzymes for efficient solar-to-fuel energy conversion. Here, we report the rational design, X-ray crystal structure, and electron transfer activity of a multi-cofactor protein that incorporates essential elements of photosynthetic reaction centers. This highly stable, modular artificial protein framework can be reconstituted in vitro with interchangeable redox centers for nanometer-scale photochemical charge separation. Transient absorption spectroscopy demonstrates Photosystem II-like tyrosine and metal cluster oxidation, and we measure charge separation lifetimes exceeding 100 ms, ideal for light-activated catalysis. This de novo-designed reaction center builds upon engineering guidelines established for charge separation in earlier synthetic photochemical triads and modified natural proteins, and it shows how synthetic biology may lead to a new generation of genetically encoded, light-powered catalysts for solar fuel production.
Duplicated ribosomal protein paralogs promote alternative translation and drug resistance
Authors: Malik Ghulam Mustafa , Catala Mathieu , Reulet Gaspard , Scott Michelle S. , Abou Elela Sherif 
Published: August 2022

AbstractRibosomes are often seen as monolithic machines produced from uniformly regulated genes. However, in yeast most ribosomal proteins come from duplicated genes. Here, we demonstrate that gene duplication may serve as a stress-adaptation mechanism modulating the global proteome through the differential expression of ribosomal protein paralogs. Our data indicate that the yeast paralog pair of the ribosomal protein L7/uL30 produces two differentially acetylated proteins. Under normal conditions most ribosomes incorporate the hypo-acetylated major form favoring the translation of genes with short open reading frames. Exposure to drugs, on the other hand, increases the production of ribosomes carrying the hyper-acetylated minor paralog that increases translation of long open reading frames. Many of these paralog-dependent genes encode cell wall proteins that could promote tolerance to drugs as their translation increases after exposure to drugs. Together our data suggest a mechanism of translation control that functions through a differential use of near-identical ribosomal protein isoforms.
ERα-LBD, an isoform of estrogen receptor alpha, promotes breast cancer proliferation and endocrine resistance
Authors: Strillacci Antonio , Sansone Pasquale , Rajasekhar Vinagolu K. , Turkekul Mesruh , Boyko Vitaly , Meng Fanli , Houck-Loomis Brian , Brown David , Berger Michael F. , Hendrickson Ronald C. , Chang Qing , de Stanchina Elisa , Pareja Fresia , Reis-Filho Jorge S. , Rajappachetty Ramya Segu , Del Priore Isabella , Liu Bo , Cai Yanyan , Penson Alex , Mastroleo Chiara , Berishaj Marjan , Borsetti Francesca , Spisni Enzo , Lyden David , Chandarlapaty Sarat , Bromberg Jacqueline 
Published: August 2022

AbstractEstrogen receptor alpha (ERα) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs. We now identify the induction of an ERα isoform, ERα-LBD, that is encoded by an alternative ESR1 transcript and lacks the activation function and DNA binding domains. Despite lacking the transcriptional activity, ERα-LBD is found to promote breast cancer growth and resistance to the ERα antagonist fulvestrant. ERα-LBD is predominantly localized to the cytoplasm and mitochondria of BC cells and leads to enhanced glycolysis, respiration and stem-like features. Intriguingly, ERα-LBD expression and function does not appear to be restricted to cancers that express full length ERα but also promotes growth of triple-negative breast cancers and ERα-LBD transcript (ESR1-LBD) is also present in BC samples from both ERα(+) and ERα(−) human tumors. These findings point to ERα-LBD as a potential mediator of breast cancer progression and therapy resistance.
Equivariant graph neural networks for fast electron density estimation of molecules, liquids, and solids
Authors: Jørgensen Peter Bjørn , Bhowmik Arghya 
Published: August 2022

AbstractElectron density $$\rho (\overrightarrow{{{{\bf{r}}}}})$$

ρ

(

r

→

)

is the fundamental variable in the calculation of ground state energy with density functional theory (DFT). Beyond total energy, features and changes in $$\rho (\overrightarrow{{{{\bf{r}}}}})$$

ρ

(

r

→

)

distributions are often used to capture critical physicochemical phenomena in functional materials. We present a machine learning framework for the prediction of $$\rho (\overrightarrow{{{{\bf{r}}}}})$$

ρ

(

r

→

)

. The model is based on equivariant graph neural networks and the electron density is predicted at special query point vertices that are part of the message-passing graph, but only receive messages. The model is tested across multiple datasets of molecules (QM9), liquid ethylene carbonate electrolyte (EC) and LixNiyMnzCo(1-y-z)O2 lithium ion battery cathodes (NMC). For QM9 molecules, the accuracy of the proposed model exceeds typical variability in $$\rho (\overrightarrow{{{{\bf{r}}}}})$$

ρ

(

r

→

)

obtained from DFT done with different exchange-correlation functionals. The accuracy on all three datasets is beyond state of the art and the computation time is orders of magnitude faster than DFT.
Superior printed parts using history and augmented machine learning
Authors: Jiang Meng , Mukherjee Tuhin , Du Yang , DebRoy Tarasankar 
Published: August 2022

AbstractMachine learning algorithms are a natural fit for printing fully dense superior metallic parts since 3D printing embodies digital technology like no other manufacturing process. Since traditional machine learning needs a large volume of reliable historical data to optimize many printing variables, the algorithm is augmented with human intelligence derived from the rich knowledge base of metallurgy and physics-based models. The augmentation improves the computational efficiency and makes the problem tractable by enabling the algorithm to use a small set of data. We provide a verifiable quantitative index for achieving fully dense superior parts, facilitate material selection, uncover the hierarchy of important variables that affect the density, and present easy-to-use visual process maps. These findings can improve the quality consistency of 3D printed parts that now limit their greater industrial adaptation. The approach used here can be applied to solve other problems of 3D printing and beyond.
Light-dominated selection shaping filamentous cyanobacterial assemblages drives odor problem in a drinking water reservoir
Authors: Su Ming , Zhu Yiping , Andersen Tom , Wang Xianyun , Yu Zhiyong , Lu Jinping , Song Yichao , Cao Tengxin , Yu Jianwei , Zhang Yu , Yang Min 
Published: August 2022

AbstractFilamentous cyanobacteria have substantial niche overlap, and the causal mechanism behind their succession remains unclear. This has practical significance since several filamentous genera are the main producers of the musty odorant 2-methylisoborneol (MIB), which lead to odor problems in drinking water. This study investigates the relationships between two filamentous cyanobacteria, the MIB-producing genus Planktothrix and the non-MIB-producing genus Pseudanabaena, in a drinking water reservoir. We firstly identified their niche characteristics based on a monitoring dataset, combined this information with culture experiments and developed a niche-based model to clarify these processes. The results reveal that the optimal light requirements of Pseudanabaena (1.56 mol m−2 d−1) are lower than those of Planktothrix (3.67 mol m−2 d−1); their light niche differentiation led to a fundamental replacement of Planktothrix (2013) by Pseudanabaena (2015) along with MIB decreases in this reservoir during 2013 and 2015. This study suggests that light is a major driving force responsible for the succession between filamentous cyanobacteria, and that subtle niche differentiation may play an important role in shaping the filamentous cyanobacterial assemblages that drives the MIB odor problems in drinking water reservoirs.
Comparison of CEAC, BEAM and IEAC conditioning regimens followed by autologous stem cell transplantation in peripheral T-cell lymphoma patients
Authors: Xiong Yi-Ying , Wang Jing , Wang Li , Chen Jian-Bin , Liu Lin , Tang Xiao-Qiong , Wang Xin , Zhang Hong-Bin 
Published: August 2022

AbstractAutologous stem cell transplantation (ASCT) is an important treatment for peripheral T-cell lymphoma (PTCL) patients both during front and salvage therapy. In order to explore the appropriate conditioning regiments and seek ways to improve the efficacy and safety of PTCL, we retrospectively compared the outcomes of 52 PTCL patients treated with CEAC (lomustine, etoposide, cytarabine and cyclophosphamide; n = 28), BEAM (carmustine, etoposide, cytarabine and melphalan; n = 14) and IEAC (idarubicin, etoposide, cytarabine and cyclophosphamide; n = 10) regimens followed by ASCT at our center between 2012 and 2021. Although the time of neutrophil engraftment in CEAC group was earlier than that in IEAC group (P = 0.042) and platelet infusion in BEAM group was significantly more than CEAC group (P = 0.042), there were no significant difference in platelet engraftment, hematopoietic engraftment and red blood cells infusion among the 3 groups. The transplantation related mortality rate (TRM) and the early overall response rate (ORR) was 3.8% and 85.7% respectively. The 5-year OS and PFS was 62.8% (95% CI: 54.8–70.8%) and 61.0% (95% CI: 53.1–68.9%) respectively. There was no significant difference in TRM, ORR and survival among the 3 groups. Univariate and multivariate analysis showed that high PIT score (the T cell lymphoma prognostic index, > 1) and failure to reach complete response (non-CR) at 3 months after ASCT were common risk factors for OS (P = 0.036 and 0.007) and PFS (P = 0.021 and 0.012). In conclusion, CEAC and IEAC regimen can be used as alternative conditioning regiments for ASCT in PTCL patients, and their efficacy and safety are comparable to BEAM regiment. Patients with high PIT score and non-CR early after ASCT had worse outcomes.
Zinc stannate microcubes with an integrated microheater for low-temperature NO2 detection
Authors: Joshi Nirav , Long Hu , Naik Pranav , Kumar Arvind , Mastelaro Valmor R. , Oliveira Osvaldo N. , Zettl Alex , Lin Liwei 
Published: August 2022

Low temperature, microcube-shaped zinc stannate (ZnSnO3) nanostructures using a low-power microheater sensor platform to detect NO2 gas with high sensitivity and selectivity.