bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated model-predictive design of synthetic promoters to control transcriptional profiles in bacteria
Authors: LaFleur Travis L. , Hossain Ayaan , Salis Howard M. 
Published: September 2022

AbstractTranscription rates are regulated by the interactions between RNA polymerase, sigma factor, and promoter DNA sequences in bacteria. However, it remains unclear how non-canonical sequence motifs collectively control transcription rates. Here, we combine massively parallel assays, biophysics, and machine learning to develop a 346-parameter model that predicts site-specific transcription initiation rates for any σ70 promoter sequence, validated across 22132 bacterial promoters with diverse sequences. We apply the model to predict genetic context effects, design σ70 promoters with desired transcription rates, and identify undesired promoters inside engineered genetic systems. The model provides a biophysical basis for understanding gene regulation in natural genetic systems and precise transcriptional control for engineering synthetic genetic systems.
Step-by-step state-selective tracking of fragmentation dynamics of water dications by momentum imaging
Authors: Severt Travis , Streeter Zachary L. , Iskandar Wael , Larsen Kirk A. , Gatton Averell , Trabert Daniel , Jochim Bethany , Griffin Brandon , Champenois Elio G. , Brister Matthew M. , Reedy Dylan , Call Demitri , Strom Richard , Landers Allen L. , Dörner Reinhard , Williams Joshua B. , Slaughter Daniel S. , Lucchese Robert R. , Weber Thorsten , McCurdy C. William , Ben-Itzhak Itzik 
Published: September 2022

AbstractThe double photoionization of a molecule by one photon ejects two electrons and typically creates an unstable dication. Observing the subsequent fragmentation products in coincidence can reveal a surprisingly detailed picture of the dynamics. Determining the time evolution and quantum mechanical states involved leads to deeper understanding of molecular dynamics. Here in a combined experimental and theoretical study, we unambiguously separate the sequential breakup via D+ + OD+ intermediates, from other processes leading to the same D+ + D+ + O final products of double ionization of water by a single photon. Moreover, we experimentally identify, separate, and follow step by step, two pathways involving the b 1Σ+ and a 1Δ electronic states of the intermediate OD+ ion. Our classical trajectory calculations on the relevant potential energy surfaces reproduce well the measured data and, combined with the experiment, enable the determination of the internal energy and angular momentum distribution of the OD+ intermediate.
Rtt105 regulates RPA function by configurationally stapling the flexible domains
Authors: Kuppa Sahiti , Deveryshetty Jaigeeth , Chadda Rahul , Mattice Jenna R. , Pokhrel Nilisha , Kaushik Vikas , Patterson Angela , Dhingra Nalini , Pangeni Sushil , Sadauskas Marisa K. , Shiekh Sajad , Balci Hamza , Ha Taekjip , Zhao Xiaolan , Bothner Brian , Antony Edwin 
Published: September 2022

AbstractReplication Protein A (RPA) is a heterotrimeric complex that binds to single-stranded DNA (ssDNA) and recruits over three dozen RPA-interacting proteins to coordinate multiple aspects of DNA metabolism including DNA replication, repair, and recombination. Rtt105 is a molecular chaperone that regulates nuclear localization of RPA. Here, we show that Rtt105 binds to multiple DNA binding and protein-interaction domains of RPA and configurationally staples the complex. In the absence of ssDNA, Rtt105 inhibits RPA binding to Rad52, thus preventing spurious binding to RPA-interacting proteins. When ssDNA is available, Rtt105 promotes formation of high-density RPA nucleoprotein filaments and dissociates during this process. Free Rtt105 further stabilizes the RPA-ssDNA filaments by inhibiting the facilitated exchange activity of RPA. Collectively, our data suggest that Rtt105 sequesters free RPA in the nucleus to prevent untimely binding to RPA-interacting proteins, while stabilizing RPA-ssDNA filaments at DNA lesion sites.
Heterogeneity and transcriptome changes of human CD8+ T cells across nine decades of life
Authors: Lu Jian , Ahmad Raheel , Nguyen Thomas , Cifello Jeffrey , Hemani Humza , Li Jiangyuan , Chen Jinguo , Li Siyi , Wang Jing , Achour Achouak , Chen Joseph , Colie Meagan , Lustig Ana , Dunn Christopher , Zukley Linda , Chia Chee W. , Burd Irina , Zhu Jun , Ferrucci Luigi , Weng Nan-ping 
Published: September 2022

AbstractThe decline of CD8+ T cell functions contributes to deteriorating health with aging, but the mechanisms that underlie this phenomenon are not well understood. We use single-cell RNA sequencing with both cross-sectional and longitudinal samples to assess how human CD8+ T cell heterogeneity and transcriptomes change over nine decades of life. Eleven subpopulations of CD8+ T cells and their dynamic changes with age are identified. Age-related changes in gene expression result from changes in the percentage of cells expressing a given transcript, quantitative changes in the transcript level, or a combination of these two. We develop a machine learning model capable of predicting the age of individual cells based on their transcriptomic features, which are closely associated with their differentiation and mutation burden. Finally, we validate this model in two separate contexts of CD8+ T cell aging: HIV infection and CAR T cell expansion in vivo.
Optical-Tweezers-integrating-Differential-Dynamic-Microscopy maps the spatiotemporal propagation of nonlinear strains in polymer blends and composites
Authors: Peddireddy Karthik R. , Clairmont Ryan , Neill Philip , McGorty Ryan , Robertson-Anderson Rae M. 
Published: September 2022

AbstractHow local stresses propagate through polymeric fluids, and, more generally, how macromolecular dynamics give rise to viscoelasticity are open questions vital to wide-ranging scientific and industrial fields. Here, to unambiguously connect polymer dynamics to force response, and map the deformation fields that arise in macromolecular materials, we present Optical-Tweezers-integrating-Differential -Dynamic-Microscopy (OpTiDMM) that simultaneously imposes local strains, measures resistive forces, and analyzes the motion of the surrounding polymers. Our measurements with blends of ring and linear polymers (DNA) and their composites with stiff polymers (microtubules) uncover an unexpected resonant response, in which strain alignment, superdiffusivity, and elasticity are maximized when the strain rate is comparable to the entanglement rate. Microtubules suppress this resonance, while substantially increasing elastic storage, due to varying degrees to which the polymers buildup, stretch and flow along the strain path, and configurationally relax induced stress. More broadly, the rich multi-scale coupling of mechanics and dynamics afforded by OpTiDDM, empowers its interdisciplinary use to elucidate non-trivial phenomena that sculpt stress propagation dynamics–critical to commercial applications and cell mechanics alike.
A gene cluster in Ginkgo biloba encodes unique multifunctional cytochrome P450s that initiate ginkgolide biosynthesis
Authors: Forman Victor , Luo Dan , Geu-Flores Fernando , Lemcke René , Nelson David R. , Kampranis Sotirios C. , Staerk Dan , Møller Birger Lindberg , Pateraki Irini 
Published: September 2022

AbstractThe ginkgo tree (Ginkgo biloba) is considered a living fossil due to its 200 million year’s history under morphological stasis. Its resilience is partly attributed to its unique set of specialized metabolites, in particular, ginkgolides and bilobalide, which are chemically complex terpene trilactones. Here, we use a gene cluster-guided mining approach in combination with co-expression analysis to reveal the primary steps in ginkgolide biosynthesis. We show that five multifunctional cytochrome P450s with atypical catalytic activities generate the tert-butyl group and one of the lactone rings, characteristic of all G. biloba trilactone terpenoids. The reactions include scarless C–C bond cleavage as well as carbon skeleton rearrangement (NIH shift) occurring on a previously unsuspected intermediate. The cytochrome P450s belong to CYP families that diversifies in pre-seed plants and gymnosperms, but are not preserved in angiosperms. Our work uncovers the early ginkgolide pathway and offers a glance into the biosynthesis of terpenoids of the Mesozoic Era.
Fast, efficient, and accurate neuro-imaging denoising via supervised deep learning
Authors: Chaudhary Shivesh , Moon Sihoon , Lu Hang 
Published: September 2022

AbstractVolumetric functional imaging is widely used for recording neuron activities in vivo, but there exist tradeoffs between the quality of the extracted calcium traces, imaging speed, and laser power. While deep-learning methods have recently been applied to denoise images, their applications to downstream analyses, such as recovering high-SNR calcium traces, have been limited. Further, these methods require temporally-sequential pre-registered data acquired at ultrafast rates. Here, we demonstrate a supervised deep-denoising method to circumvent these tradeoffs for several applications, including whole-brain imaging, large-field-of-view imaging in freely moving animals, and recovering complex neurite structures inC. elegans. Our framework has 30× smaller memory footprint, and is fast in training and inference (50–70 ms); it is highly accurate and generalizable, and further, trained with only small, non-temporally-sequential, independently-acquired training datasets (∼500 pairs of images). We envision that the framework will enable faster and long-term imaging experiments necessary to study neuronal mechanisms of many behaviors.
Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core
Authors: Park Sangbin , Kang Gyumin , Kim Chansu , Kim Dongwook , Han Sunkyu 
Published: September 2022

AbstractSecurinega alkaloids have fascinated the synthetic chemical community for over six decades. Historically, major research foci in securinega alkaloid synthesis have been on the efficient construction of the fused tetracyclic framework that bears a butenolide moiety and tertiary amine-based heterocycles. These “basic” securinega alkaloids have evolved to undergo biosynthetic oxidative diversifications, especially on the piperidine core. However, a general synthetic solution to access these high-oxidation state securinega alkaloids is lacking. In this study, we have completed the total synthesis of various C4-oxygenated securinine-type alkaloids including securingines A, C, D, securitinine, secu’amamine D, phyllanthine, and 4-epi-phyllanthine. Our synthetic strategy features stereocontrolled oxidation, rearrangement, and epimerization at N1 and C2–C4 positions of the piperidine core within (neo)securinane scaffolds. Our discoveries provide a fundamental synthetic solution to all known securinine-type natural products with various oxidative and stereochemical variations around the central piperidine ring.
Identification of a cross-neutralizing antibody that targets the receptor binding site of H1N1 and H5N1 influenza viruses
Authors: Li Tingting , Chen Junyu , Zheng Qingbing , Xue Wenhui , Zhang Limin , Rong Rui , Zhang Sibo , Wang Qian , Hong Minqing , Zhang Yuyun , Cui Lingyan , He Maozhou , Lu Zhen , Zhang Zhenyong , Chi Xin , Li Jinjin , Huang Yang , Wang Hong , Tang Jixian , Ying Dong , Zhou Lizhi , Wang Yingbin , Yu Hai , Zhang Jun , Gu Ying , Chen Yixin , Li Shaowei , Xia Ningshao 
Published: September 2022

AbstractInfluenza A viruses pose a significant threat globally each year, underscoring the need for a vaccine- or antiviral-based broad-protection strategy. Here, we describe a chimeric monoclonal antibody, C12H5, that offers neutralization against seasonal and pandemic H1N1 viruses, and cross-protection against some H5N1 viruses. Notably, C12H5 mAb offers broad neutralizing activity against H1N1 and H5N1 viruses by controlling virus entry and egress, and offers protection against H1N1 and H5N1 viral challenge in vivo. Through structural analyses, we show that C12H5 engages hemagglutinin (HA), the major surface glycoprotein on influenza, at a distinct epitope overlapping the receptor binding site and covering the 140-loop. We identified eight highly conserved (~90%) residues that are essential for broad H1N1 recognition, with evidence of tolerance for Asp or Glu at position 190; this site is a molecular determinant for human or avian host-specific recognition and this tolerance endows C12H5 with cross-neutralization potential. Our results could benefit the development of antiviral drugs and the design of broad-protection influenza vaccines.
Widespread irreversible changes in surface temperature and precipitation in response to CO2 forcing
Authors: Kim Soong-Ki , Shin Jongsoo , An Soon-Il , Kim Hyo-Jeong , Im Nari , Xie Shang-Ping , Kug Jong-Seong , Yeh Sang-Wook 
Published: September 2022

AbstractSome climate variables do not show the same response to declining atmospheric CO2 concentrations as before the preceding increase. A comprehensive understanding of this hysteresis effect and its regional patterns is, however, lacking. Here we use an Earth system model with an idealized CO2 removal scenario to show that surface temperature and precipitation exhibit globally widespread irreversible changes over a timespan of centuries. To explore the climate hysteresis and reversibility on a regional scale, we develop a quantification method that visualizes their spatial patterns. Our experiments project that 89% and 58% of the global area experiences irreversible changes in surface temperature and precipitation, respectively. Strong irreversible response of surface temperature is found in the Southern Ocean, Arctic and North Atlantic Ocean and of precipitation in the tropical Pacific, global monsoon regions and the Himalayas. These global hotspots of irreversible changes can indicate elevated risks of negative impacts on developing countries.
Weakening of the Atlantic Niño variability under global warming
Authors: Crespo Lander R. , Prigent Arthur , Keenlyside Noel , Koseki Shunya , Svendsen Lea , Richter Ingo , Sánchez-Gómez Emilia 
Published: September 2022

AbstractThe Atlantic Niño is one of the most important patterns of interannual tropical climate variability, but how climate change will influence this pattern is not well known due to large climate model biases. Here we show that state-of-the-art climate models robustly predict a weakening of Atlantic Niños in response to global warming, mainly due to a decoupling of subsurface and surface temperature variations as the upper equatorial Atlantic Ocean warms. This weakening is predicted by most (>80%) models in the Coupled Model Intercomparison Project Phases 5 and 6 under the highest emission scenarios. Our results indicate a reduction in variability by the end of the century by 14%, and as much as 24–48% when accounting for model errors using a simple emergent constraint analysis. Such a weakening of Atlantic Niño variability will potentially impact climate conditions and the skill of seasonal predictions in many regions.
TILES-2019: A longitudinal physiologic and behavioral data set of medical residents in an intensive care unit
Authors: Yau Joanna C. , Girault Benjamin , Feng Tiantian , Mundnich Karel , Nadarajan Amrutha , Booth Brandon M. , Ferrara Emilio , Lerman Kristina , Hsieh Eric , Narayanan Shrikanth 
Published: September 2022

AbstractThe TILES-2019 data set consists of behavioral and physiological data gathered from 57 medical residents (i.e., trainees) working in an intensive care unit (ICU) in the United States. The data set allows for the exploration of longitudinal changes in well-being, teamwork, and job performance in a demanding environment, as residents worked in the ICU for three weeks. Residents wore a Fitbit, a Bluetooth-based proximity sensor, and an audio-feature recorder. They completed daily surveys and interviews at the beginning and end of their rotation. In addition, we collected data from environmental sensors (i.e., Internet-of-Things Bluetooth data hubs) and obtained hospital records (e.g., patient census) and residents’ job evaluations. This data set may be may be of interest to researchers interested in workplace stress, group dynamics, social support, the physical and psychological effects of witnessing patient deaths, predicting survey data from sensors, and privacy-aware and privacy-preserving machine learning. Notably, a small subset of the data was collected during the first wave of the COVID-19 pandemic.
A chromosome-level genome assembly of the redfin culter (Chanodichthys erythropterus)
Authors: Zhao Shihu , Yang Xiufeng , Pang Bo , Zhang Lei , Wang Qi , He Shangbin , Dou Huashan , Zhang Honghai 
Published: September 2022

AbstractChanodichthys erythropterus is a fierce carnivorous fish widely found in East Asian waters. It is not only a popular food fish in China, it is also a representative victim of overfishing. Genetic breeding programs launched to meet market demands urgently require high-quality genomes to facilitate genomic selection and genetic research. In this study, we constructed a chromosome-level reference genome of C. erythropterus by taking advantage of long-read single-molecule sequencing and de novo assembly by Oxford Nanopore Technology (ONT) and Hi-C. The 1.085 Gb C. erythropterus genome was assembled from 132 Gb of Nanopore sequence. The assembled genome represents 98.5% completeness (BUSCO) with a contig N50 length of 23.29 Mb. The contigs were clustered and ordered onto 24 chromosomes covering roughly 99.49% of the genome assembly with Hi-C data. Additionally, 33,041 (98.0%) genes were functionally annotated from a total of 33,706 predicted protein-coding sequences by combining transcriptome data from seven tissues. This high-quality assembled genome will be a precious resource for future molecular breeding and functional genomics research of C. erythropterus.
An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment
Authors: Shen Qian , Li JunChen , Pan Xue , Zhang ChuanLong , Jiang XiaoChen , Li Yi , Chen Yan , Pang Bo 
Published: September 2022

AbstractTo establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA–mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis.
Importance of frequency and intensity of strength training for work ability among physical therapists
Authors: Calatayud Joaquín , Morera Álvaro , Ezzatvar Yasmín , López-Bueno Rubén , Andersen Lars L. , Cuenca-Martínez Ferran , Suso-Martí Luis , Sanchís-Sánchez Enrique , López-Bueno Laura , Casaña José 
Published: September 2022

AbstractThe aim of the study was to evaluate the association between frequency and intensity of strength training participation and work ability among physical therapists (PTs). The Work Ability Index questionnaire (WAI) and a questionnaire about participation in strength training during leisure time were administered to a sample of Spanish PTs. In addition, participants provided information on gender, age, body mass index, education, substance use, working experience and working hours per week. The odds for having excellent WAI (score 44–49) as a function of intensity or frequency of strength training participation were determined using binary logistic regression controlled for various confounders. Data from 981 PTs were analysed. High-intensity strength training (> 80% 1 RM) showed strong associations with excellent WAI (odds ratio = 9.7; 95% confidence interval, 2.9–31.6). In addition, performing strength training more than 3 times per week was associated with excellent WAI (odds ratio = 1.79; 95% confidence interval, 1.24–2.59), however, no significant associations were found with lower levels of frequency and intensities. High-intensity strength training 3 times per week is associated with excellent WAI among PTs. Training programs meeting these features may importantly contribute to maintain or improve WAI.
Self-initialized active contours for microscopic cell image segmentation
Authors: Niaz Asim , Iqbal Ehtesham , Akram Farhan , Kim Jin , Choi Kwang Nam 
Published: September 2022

AbstractLevel set models are suitable for processing topological changes in different regions of images while performing segmentation. Active contour models require an empirical setting for initial parameters, which is tedious for the end-user. This study proposes an incremental level set model with the automatic initialization of contours based on local and global fitting energies that enable it to capture image regions containing intensity corruption or other light artifacts. The region-based area and the region-based length terms use signed pressure force (SPF) to strengthen the balloon force. SPF helps to achieve a smooth version of the gradient descent flow in terms of energy minimization. The proposed model is tested on multiple synthetic and real images. Our model has four advantages: first, there is no need for the end user to initialize the parameters; instead, the model is self-initialized. Second, it is more accurate than other methods. Third, it shows lower computational complexity. Fourth, it does not depend on the starting position of the contour. Finally, we evaluated the performance of our model on microscopic cell images (Coelho et al., in: 2009 IEEE international symposium on biomedical imaging: from nano to macro, IEEE, 2009) to confirm that its performance is superior to that of other state-of-the-art models.