bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multifunctional system for genome editing and large-scale interspecies gene transfer
Authors: Teufel Marc , Klein Carlo A. , Mager Maurice , Sobetzko Patrick 
Published: June 2022

AbstractCRISPR SWAPnDROP extends the limits of genome editing to large-scale in-vivo DNA transfer between bacterial species. Its modular platform approach facilitates species specific adaptation to confer genome editing in various species. In this study, we show the implementation of the CRISPR SWAPnDROP concept for the model organism Escherichia coli, the fast growing Vibrio natriegens and the plant pathogen Dickeya dadantii. We demonstrate the excision, transfer and integration of large chromosomal regions between E. coli, V. natriegens and D. dadantii without size-limiting intermediate DNA extraction. CRISPR SWAPnDROP also provides common genome editing approaches comprising scarless, marker-free, iterative and parallel insertions and deletions. The modular character facilitates DNA library applications, and recycling of standardized parts. Its multi-color scarless co-selection system significantly improves editing efficiency and provides visual quality controls throughout the assembly and editing process.
SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish
Authors: Liang Fang , Zhang Yu , Li Lin , Yang Yexin , Fei Ji-Feng , Liu Yanmei , Qin Wei 
Published: June 2022

AbstractPrecise genetic modifications in model organisms are essential for biomedical research. The recent development of PAM-less base editors makes it possible to assess the functional impact and pathogenicity of nucleotide mutations in animals. Here we first optimize SpG and SpRY systems in zebrafish by purifying protein combined with synthetically modified gRNA. SpG shows high editing efficiency at NGN PAM sites, whereas SpRY efficiently edit PAM-less sites in the zebrafish genome. Then, we generate the SpRY-mediated cytosine base editor SpRY-CBE4max and SpRY-mediated adenine base editor zSpRY-ABE8e. Both target relaxed PAM with up to 96% editing efficiency and high product purity. With these tools, some previously inaccessible disease-relevant genetic variants are generated in zebrafish, supporting the utility of high-resolution targeting across genome-editing applications. Our study significantly improves CRISPR-Cas targeting in the genomic landscape of zebrafish, promoting the application of this model organism in revealing gene function, physiological mechanisms, and disease pathogenesis.
Approaching intrinsic dynamics of MXenes hybrid hydrogel for 3D printed multimodal intelligent devices with ultrahigh superelasticity and temperature sensitivity
Authors: Liu Haodong , Du Chengfeng , Liao Liling , Zhang Hongjian , Zhou Haiqing , Zhou Weichang , Ren Tianning , Sun Zhicheng , Lu Yufei , Nie Zhentao , Xu Feng , Zhu Jixin , Huang Wei 
Published: June 2022

AbstractHydrogels are investigated broadly in flexible sensors which have been applied into wearable electronics. However, further application of hydrogels is restricted by the ambiguity of the sensing mechanisms, and the multi-functionalization of flexible sensing systems based on hydrogels in terms of cost, difficulty in integration, and device fabrication remains a challenge, obstructing the specific application scenarios. Herein, cost-effective, structure-specialized and scenario-applicable 3D printing of direct ink writing (DIW) technology fabricated two-dimensional (2D) transition metal carbides (MXenes) bonded hydrogel sensor with excellent strain and temperature sensing performance is developed. Gauge factor (GF) of 5.7 (0 − 191% strain) and high temperature sensitivity (−5.27% °C−1) within wide working range (0 − 80 °C) can be achieved. In particular, the corresponding mechanisms are clarified based on finite element analysis and the first use of in situ temperature-dependent Raman technology for hydrogels, and the printed sensor can realize precise temperature indication of shape memory solar array hinge.
Ursodeoxycholic acid reduces antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation
Authors: Shen Yingying , Lu Chaojie , Song Zhengbo , Qiao Chenxiao , Wang Jiaoli , Chen Jinbiao , Zhang Chengyan , Zeng Xianchang , Ma Zeyu , Chen Tao , Li Xu , Lin Aifu , Guo Jufeng , Wang Jianli , Cai Zhijian 
Published: June 2022

AbstractTGF-β is essential for inducing systemic tumor immunosuppression; thus, blocking TGF-β can greatly enhance antitumor immunity. However, there are still no effective TGF-β inhibitors in clinical use. Here, we show that the clinically approved compound ursodeoxycholic acid (UDCA), by degrading TGF-β, enhances antitumor immunity through restraining Treg cell differentiation and activation in tumor-bearing mice. Furthermore, UDCA synergizes with anti-PD-1 to enhance antitumor immunity and tumor-specific immune memory in tumor-bearing mice. UDCA phosphorylates TGF-β at T282 site via TGR5-cAMP-PKA axis, causing increased binding of TGF-β to carboxyl terminus of Hsc70-interacting protein (CHIP). Then, CHIP ubiquitinates TGF-β at the K315 site, initiating p62-dependent autophagic sorting and subsequent degradation of TGF-β. Notably, results of retrospective analysis shows that combination therapy with anti-PD-1 or anti-PD-L1 and UDCA has better efficacy in tumor patients than anti-PD-1 or anti-PD-L1 alone. Thus, our results show a mechanism for TGF-β regulation and implicate UDCA as a potential TGF-β inhibitor to enhance antitumor immunity.
Prognostic significance of RNA-based TP53 pathway function among estrogen receptor positive and negative breast cancer cases
Authors: Hurson Amber N. , Abubakar Mustapha , Hamilton Alina M. , Conway Kathleen , Hoadley Katherine A. , Love Michael I. , Olshan Andrew F. , Perou Charles M. , Garcia-Closas Montserrat , Troester Melissa A. 
Published: June 2022

AbstractTP53 and estrogen receptor (ER) are essential in breast cancer development and progression, but TP53 status (by DNA sequencing or protein expression) has been inconsistently associated with survival. We evaluated whether RNA-based TP53 classifiers are related to survival. Participants included 3213 women in the Carolina Breast Cancer Study (CBCS) with invasive breast cancer (stages I–III). Tumors were classified for TP53 status (mutant-like/wildtype-like) using an RNA signature. We used Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific survival (BCSS) among ER- and TP53-defined subtypes. RNA-based results were compared to DNA- and IHC-based TP53 classification, as well as Basal-like versus non-Basal-like subtype. Findings from the diverse (50% Black), population-based CBCS were compared to those from the largely white METABRIC study. RNA-based TP53 mutant-like was associated with BCSS among both ER-negatives and ER-positives (HR (95% CI) = 5.38 (1.84–15.78) and 4.66 (1.79–12.15), respectively). Associations were attenuated when using DNA- or IHC-based TP53 classification. In METABRIC, few ER-negative tumors were TP53-wildtype-like, but TP53 status was a strong predictor of BCSS among ER-positives. In both populations, the effect of TP53 mutant-like status was similar to that for Basal-like subtype. RNA-based measures of TP53 status are strongly associated with BCSS and may have value among ER-negative cancers where few prognostic markers have been robustly validated. Given the role of TP53 in chemotherapeutic response, RNA-based TP53 as a prognostic biomarker could address an unmet need in breast cancer.
Large-scale programmable assembly of functional micro-components for advanced electronics via light-regulated adhesion and polymer growth
Authors: Guo Chan , Pan Zhangxu , Li Changhao , Zou Shenghan , Pang Chao , Wang Jiantai , Hu Jinhua , Gong Zheng 
Published: June 2022

AbstractLarge-area, programmable assembly of diverse micro-objects onto arbitrary substrates is a fundamental yet challenging task. Herein a simple wafer-level micro-assembly technique based on the light-triggered change in both surface topography and interfacial adhesion of a soft photo-sensitive polymer is proposed. In particular, the light-regulated polymer growth creates locally indented and elevated zones on the stamp surface. The light-mediated adhesion reduction, on the other hand, facilitates the inks to be released from the polymer. The interplay of these two effects makes it feasible for the programmable assembly of ultra-small components onto various substrates coated with supplementary adhesive layers. The fidelity of this technique is validated by assembling diverse materials and functional devices, with the printing size up to 4-inch. This work provides a rational strategy for large-scale and programmable assembly of diverse delicate micro-objects, bypassing the common issues of some existing techniques such as poor transfer uniformity, small printing area, and high cost.
Metabolic profilings of rat INS-1 β-cells under changing levels of essential amino acids
Authors: Xu Lianbin , Lin Xueyan , Li Xiuli , Hu Zhiyong , Hou Qiuling , Wang Yun , Wang Zhonghua 
Published: June 2022

AbstractApplication of mass spectrometry enables the detection of metabolic differences between organisms with different nutritional settings. Divergence in the metabolic fingerprints of rat pancreatic INS-1 β-cells were systematically captured with regard to ten individual essential amino acid (EAA) availability. A high-resolution tandem mass spectrometry system coupled to liquid chromatography produced a horizontal comparison of metabolic profilings of β-cells with individual EAA elevated to 10 mmol/L by turn or removal individual EAA from the medium one by one. Quality control samples were injected at regular intervals throughout the analytical run to monitor and evaluate the stability of the system. The raw data of samples and reference compounds including study protocols have been deposited in the open metabolomics database MetaboLights to enable efficient reuse of the datasets, such as investigating the difference in metabolic process between diverse EAAs as well as screening and verifying potential metabolites affecting insulin secretion and β-cell function.
Preparation and application of chikungunya pseudovirus containing double reporter genes
Authors: Su Chunyan , Ding Kaiyun , Xu Jingwen , Wu Jianchao , Liu Jiansheng , Shen Jiayuan , Zhou Hongning , Liu Hongqi 
Published: June 2022

AbstractChikungunya virus (CHIKV), a highly infectious and rapidly spread viral pathogen, is classified as a pathogenic agent at the biosafety level 3. Operation of live authentic CHIKV needs a specific laboratory with the P3 or above containment, which greatly confines the CHIKV-associated studies. To establish an evaluation system of CHIKV that can be utilized in a BSL2 laboratory, we constructed a pseudovirus (PsV) system of CHIKV containing double reporter genes (ZsGreen1 and luciferase). The fluorescent ZsGreen1 is a convenient and cheap reporter for monitoring the efficiency of transfection and titration of PsV. The enzyme luciferase is a sensitive reporter for the application of PsV to neutralization assay or drug screening. The CHIKV PsV produced in this study, with a titer of up to 3.16 × 106 TU/ml, was confirmed by Western blotting and transmission electronic microscopy (TEM). Finally, we developed a microneutralization assay with the CHIKV PsV produced in this study, which was successfully applied to evaluate neutralizing activities of convalescent sera from CHIKV-infected patients. In summary, we have established a convenient and sensitive double-reporter CHIKV pseudovirus system, which provides a safe and effective platform for screening anti-CHIKV drugs and evaluating vaccines against CHIKV.
The human “contaminome”: bacterial, viral, and computational contamination in whole genome sequences from 1000 families
Authors: Chrisman Brianna , He Chloe , Jung Jae-Yoon , Stockham Nate , Paskov Kelley , Washington Peter , Wall Dennis P. 
Published: June 2022

AbstractThe unmapped readspace of whole genome sequencing data tends to be large but is often ignored. We posit that it contains valuable signals of both human infection and contamination. Using unmapped and poorly aligned reads from whole genome sequences (WGS) of over 1000 families and nearly 5000 individuals, we present insights into common viral, bacterial, and computational contamination that plague whole genome sequencing studies. We present several notable results: (1) In addition to known contaminants such as Epstein-Barr virus and phiX, sequences from whole blood and lymphocyte cell lines contain many other contaminants, likely originating from storage, prep, and sequencing pipelines. (2) Sequencing plate and biological sample source of a sample strongly influence contamination profile. And, (3) Y-chromosome fragments not on the human reference genome commonly mismap to bacterial reference genomes. Both experiment-derived and computational contamination is prominent in next-generation sequencing data. Such contamination can compromise results from WGS as well as metagenomics studies, and standard protocols for identifying and removing contamination should be developed to ensure the fidelity of sequencing-based studies.
A prime-masked ERP investigation on phonology in visual word processing among bilingual speakers of alphasyllabic and alphabetic orthographies
Authors: Shetty Adhvika , Hebbar Sanjana P. , Shenoy Rajath , Peter Varghese , Krishnan Gopee 
Published: June 2022

AbstractIn this study, we experimentally manipulated the phonology of the cross-script prime-target dyads in an ERP-coupled masked priming paradigm to explore the role phonology plays in visual word processing. The written characters of certain bilingual dyads seldom show any visual/orthographic similarity, yet have the same phonological representation. While the Bilingual Interactive Activation (BIA) model relies on the orthographic similarity between the languages in a bilingual dyad, its revised version (BIA + model) additionally banks on the phonological (and semantic) similarity between the words in such dyads. Thus, there exists the need to investigate the role of phonological (and semantic) similarity between the words of a bilingual dyad, especially in the absence of orthographic similarity. Borrowed words from one language to another provide a suitable avenue to explore this question. Cross-orthographic (or cross-script) bilingual participants of this study performed the semantic judgment of visually presented words in a masked priming paradigm in each of their languages while we simultaneously collected the event-related potentials (ERPs). The primes were either translations (different phonology & orthography: P–O–; phonologically incongruent) or transliterations (same phonology & different orthography: P + O–; phonologically congruent) of the target. Overall, the results showed no difference between the two prime conditions. We discuss our findings in light of the BIA and BIA + models of bilingual visual word processing and discuss the relevance of the former model in orthographically distinct bilingual language dyads.
Simulation platform for pattern recognition based on reservoir computing with memristor networks
Authors: Tanaka Gouhei , Nakane Ryosho 
Published: June 2022

AbstractMemristive systems and devices are potentially available for implementing reservoir computing (RC) systems applied to pattern recognition. However, the computational ability of memristive RC systems depends on intertwined factors such as system architectures and physical properties of memristive elements, which complicates identifying the key factor for system performance. Here we develop a simulation platform for RC with memristor device networks, which enables testing different system designs for performance improvement. Numerical simulations show that the memristor-network-based RC systems can yield high computational performance comparable to that of state-of-the-art methods in three time series classification tasks. We demonstrate that the excellent and robust computation under device-to-device variability can be achieved by appropriately setting network structures, nonlinearity of memristors, and pre/post-processing, which increases the potential for reliable computation with unreliable component devices. Our results contribute to an establishment of a design guide for memristive reservoirs toward the realization of energy-efficient machine learning hardware.
Disruption of spatiotemporal clustering in dengue cases by wMel Wolbachia in Yogyakarta, Indonesia
Authors: Dufault Suzanne M. , Tanamas Stephanie K. , Indriani Citra , Utarini Adi , Ahmad Riris Andono , Jewell Nicholas P. , Simmons Cameron P. , Anders Katherine L. 
Published: June 2022

AbstractDengue exhibits focal clustering in households and neighborhoods, driven by local mosquito population dynamics, human population immunity, and fine scale human and mosquito movement. We tested the hypothesis that spatiotemporal clustering of homotypic dengue cases is disrupted by introduction of the arbovirus-blocking bacteriumWolbachia(wMel-strain) into theAedes aegyptimosquito population. We analysed 318 serotyped and geolocated dengue cases (and 5921 test-negative controls) from a randomized controlled trial in Yogyakarta, Indonesia ofwMel deployments. We find evidence of spatial clustering up to 300 m among the 265 dengue cases (3083 controls) in the untreated trial arm. Participant pairs enrolled within 30 days and 50 m had a 4.7-fold increase (compared to 95% CI on permutation-based null distribution: 0.1, 1.2) in the odds of being homotypic (i.e. potentially transmission-related) as compared to pairs occurring at any distance. In contrast, we find no evidence of spatiotemporal clustering among the 53 dengue cases (2838 controls) resident in thewMel-treated arm. Introgression ofwMelWolbachiaintoAedes aegyptimosquito populations interrupts focal dengue virus transmission leading to reduced case incidence; the true intervention effect may be greater than the 77% efficacy measured in the primary analysis of the Yogyakarta trial.
Change detection based on unsupervised sparse representation for fundus image pair
Authors: Fu Yinghua , Zhao Xing , Liang Yong , Zhao Tiejun , Wang Chaoli , Zhang Dawei 
Published: June 2022

AbstractDetecting changes is an important issue for ophthalmology to compare longitudinal fundus images at different stages and obtain change regions. Illumination variations bring distractions on the change regions by the pixel-by-pixel comparison. In this paper, a new unsupervised change detection method based on sparse representation classification (SRC) is proposed for the fundus image pair. First, the local neighborhood patches are extracted from the reference image to build a dictionary of the local background. Then the current image patch is represented sparsely and its background is reconstructed by the obtained dictionary. Finally, change regions are given through background subtracting. The SRC method can correct automatically illumination variations through the representation coefficients and filter local contrast and global intensity effectively. In experiments of this paper, the AUC and mAP values of SRC method are 0.9858 and 0.8647 respectively for the image pair with small lesions; the AUC and mAP values of the fusion method of IRHSF and SRC are 0.9892 and 0.9692 separately for the image pair with the big change region. Experiments show that the proposed method in this paper is more robust than RPCA for the illumination variations and can detect change regions more effectively than pixel-wised image differencing.
Population structure of blackfin tuna (Thunnus atlanticus) in the western Atlantic Ocean inferred from microsatellite loci
Authors: Saillant Eric A. , Luque Patricia L. , Short Emily , Antoni Luca , Reynal Lionel , Pau Cedric , Arocha Freddy , Roque Pollyana , Hazin Fabio 
Published: June 2022

AbstractThe blackfin tuna,Thunnus atlanticus, is a small tropical tuna exploited by recreational and commercial fisheries in various parts of its range. Information on stock structure is needed to develop management plans for this species but is currently lacking. In this work, 470 blackfin tuna from nine geographic populations were assayed at 13 homologous microsatellite markers to provide a first assessment of stock structure across the species range. The overall divergence among locality samples was very low (overall FST = 0.0004) indicating high connectivity of blackfin tuna across their range. No clear grouping of localities in differentiated units was inferred but structuring followed a weak isolation by distance pattern (r = 0.16, P = 0.032). Pairwise exact tests and spatial analysis of molecular variance suggested divergence of the sample collected offshore Baía Formosa (Brazil) possibly reflecting reproductive isolation of Brazilian populations from those in the Caribbean region and further north. Further study of the status of Brazilian populations and the transition between this region and the Caribbean is warranted. Cryptic subdivision within the Northern Hemisphere part of the range is possible and should be evaluated using increased marker density and a more comprehensive geographic coverage.
Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries
Authors: Khanam Riffat , Sengupta Arunima , Mukhopadhyay Dipankar , Chakraborty Santanu 
Published: June 2022

AbstractPathological cardiac remodeling as an aftermath of a severe cardiac injury can lead to ventricular dysfunction and subsequent heart failure. Adamts4, a metalloproteinase, and disintegrin with thrombospondin-like motif, involved in the turnover of certain extracellular matrix molecules and pathogenesis of osteoarthritis, also plays a role in cardiac remodeling although little is presently known about its expression and function in the heart. Here, we have investigated the dynamic expression pattern of Adamts4 during cardiogenesis and also in the adult heart. To our surprise, adult cardiac injury reactivated Adamts4 expression concomitant with fibrosis induction. To better understand the mechanism, cultured H9c2 cardiomyocyte cells were subjected to ROS injury and Hypoxia. Moreover, through combinatorial treatment with SB431542 (an inhibitor of Tgf-β1), and Adamts4 siRNA mediated gene knockdown, we were able to decipher a regulatory hierarchy to the signal cascade being at the heart of Tgf-β regulation. Besides the hallmark expression of Adamts4 and Tgf-β1, expression of other fibrosis-related markers like Collagen-III, alpha-SMA and Periostin were also assessed. Finally, increased levels of Adamts4 and alpha-SMA proteins in cardiac patients also resonated well with our animal and cell culture studies. Overall, in this study, we highlight, Adamts4 as a novel biomarker of adult cardiac injury.