bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinesin-1 activity recorded in living cells with a precipitating dye
Authors: Angerani Simona , Lindberg Eric , Klena Nikolai , Bleck Christopher K. E. , Aumeier Charlotte , Winssinger Nicolas 
Published: March 2021

AbstractKinesin-1 is a processive motor protein that uses ATP-derived energy to transport a variety of intracellular cargoes toward the cell periphery. The ability to visualize and monitor kinesin transport in live cells is critical to study the myriad of functions associated with cargo trafficking. Herein we report the discovery of a fluorogenic small molecule substrate (QPD-OTf) for kinesin-1 that yields a precipitating dye along its walking path on microtubules (MTs). QPD-OTf enables to monitor native kinesin-1 transport activity in cellulo without external modifications. In vitro assays show that kinesin-1 and MTs are sufficient to yield fluorescent crystals; in cells, kinesin-1 specific transport of cargo from the Golgi appears as trails of fluorescence over time. These findings are further supported by docking studies, which suggest the binding of the activity-based substrate in the nucleotide binding site of kinesin-1.
Point-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP
Authors: Bokelmann Lukas , Nickel Olaf , Maricic Tomislav , Pääbo Svante , Meyer Matthias , Borte Stephan , Riesenberg Stephan 
Published: March 2021

AbstractEfforts to contain the spread of SARS-CoV-2 have spurred the need for reliable, rapid, and cost-effective diagnostic methods which can be applied to large numbers of people. However, current standard protocols for the detection of viral nucleic acids while sensitive, require a high level of automation and sophisticated laboratory equipment to achieve throughputs that allow whole communities to be tested on a regular basis. Here we present Cap-iLAMP (capture and improved loop-mediated isothermal amplification) which combines a hybridization capture-based RNA extraction of gargle lavage samples with an improved colorimetric RT-LAMP assay and smartphone-based color scoring. Cap-iLAMP is compatible with point-of-care testing and enables the detection of SARS-CoV-2 positive samples in less than one hour. In contrast to direct addition of the sample to improved LAMP (iLAMP), Cap-iLAMP prevents false positives and allows single positive samples to be detected in pools of 25 negative samples, reducing the reagent cost per test to ~1 Euro per individual.
Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking
Authors: Schiweck Juliane , Murk Kai , Ledderose Julia , Münster-Wandowski Agnieszka , Ornaghi Marta , Vida Imre , Eickholt Britta J. 
Published: March 2021

AbstractThe brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. In turn, DBN loss leads to defective astrocyte scar formation and excessive neurodegeneration following brain injuries. At the cellular level, we show that DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds, facilitating the formation of RAB8-positive membrane tubules. This injury-specific RAB8 membrane compartment serves as hub for the trafficking of surface proteins involved in astrogliosis and adhesion mediators, such as β1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice.
A single inverse-designed photonic structure that performs parallel computing
Authors: Camacho Miguel , Edwards Brian , Engheta Nader 
Published: March 2021

AbstractIn the search for improved computational capabilities, conventional microelectronic computers are facing various problems arising from the miniaturization and concentration of active electronics. Therefore, researchers have explored wave systems, such as photonic or quantum devices, for solving mathematical problems at higher speeds and larger capacities. However, previous devices have not fully exploited the linearity of the wave equation, which as we show here, allows for the simultaneous parallel solution of several independent mathematical problems within the same device. Here we demonstrate that a transmissive cavity filled with a judiciously tailored dielectric distribution and embedded in a multi-frequency feedback loop can calculate the solutions of a number of mathematical problems simultaneously. We design, build, and test a computing structure at microwave frequencies that solves two independent integral equations with any two arbitrary inputs and also provide numerical results for the calculation of the inverse of four 5 x 5 matrices.
Improving gene function predictions using independent transcriptional components
Authors: Urzúa-Traslaviña Carlos G. , Leeuwenburgh Vincent C. , Bhattacharya Arkajyoti , Loipfinger Stefan , van Vugt Marcel A. T. M. , de Vries Elisabeth G. E. , Fehrmann Rudolf S. N. 
Published: March 2021

AbstractThe interpretation of high throughput sequencing data is limited by our incomplete functional understanding of coding and non-coding transcripts. Reliably predicting the function of such transcripts can overcome this limitation. Here we report the use of a consensus independent component analysis and guilt-by-association approach to predict over 23,000 functional groups comprised of over 55,000 coding and non-coding transcripts using publicly available transcriptomic profiles. We show that, compared to using Principal Component Analysis, Independent Component Analysis-derived transcriptional components enable more confident functionality predictions, improve predictions when new members are added to the gene sets, and are less affected by gene multi-functionality. Predictions generated using human or mouse transcriptomic data are made available for exploration in a publicly available web portal.
Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription
Authors: Zuo Linyu , Zhang Guanwei , Massett Matthew , Cheng Jun , Guo Zicong , Wang Liang , Gao Yifei , Li Ru , Huang Xu , Li Pilong , Qi Zhi 
Published: March 2021

AbstractAbnormally formed FUS/EWS/TAF15 (FET) fusion oncoproteins are essential oncogenic drivers in many human cancers. Interestingly, at the molecular level, they also form biomolecular condensates at specific loci. However, how these condensates lead to gene transcription and how features encoded in the DNA element regulate condensate formation remain unclear. Here, we develop an in vitro single-molecule assay to visualize phase separation on DNA. Using this technique, we observe that FET fusion proteins undergo phase separation at target binding loci and the phase separated condensates recruit RNA polymerase II and enhance gene transcription. Furthermore, we determine a threshold number of fusion-binding DNA elements that can enhance the formation of FET fusion protein condensates. These findings suggest that FET fusion oncoprotein promotes aberrant gene transcription through loci-specific phase separation, which may contribute to their oncogenic transformation ability in relevant cancers, such as sarcomas and leukemia.
Single cell transcriptomics reveals lineage trajectory of retinal ganglion cells in wild-type and Atoh7-null retinas
Authors: Wu Fuguo , Bard Jonathan E. , Kann Julien , Yergeau Donald , Sapkota Darshan , Ge Yichen , Hu Zihua , Wang Jie , Liu Tao , Mu Xiuqian 
Published: March 2021

AbstractAtoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 and Isl1 are known to regulate RGC specification and differentiation. Here we report our further study of the roles of these transcription factors. Using bulk RNA-seq, we identify genes regulated by the three transcription factors, which expand our understanding of the scope of downstream events. Using scRNA-seq on wild-type and mutant retinal cells, we reveal a transitional cell state of retinal progenitor cells (RPCs) co-marked by Atoh7 and other genes for different lineages and shared by all early retinal lineages. We further discover the unexpected emergence of the RGC lineage in the absence of Atoh7. We conclude that competence of RPCs for different retinal fates is defined by lineage-specific genes co-expressed in the transitional state and that Atoh7 defines the RGC competence and collaborates with other factors to shepherd transitional RPCs to the RGC lineage.
Wildfire smoke impacts respiratory health more than fine particles from other sources: observational evidence from Southern California
Authors: Aguilera Rosana , Corringham Thomas , Gershunov Alexander , Benmarhnia Tarik 
Published: March 2021

AbstractWildfires are becoming more frequent and destructive in a changing climate. Fine particulate matter, PM2.5, in wildfire smoke adversely impacts human health. Recent toxicological studies suggest that wildfire particulate matter may be more toxic than equal doses of ambient PM2.5. Air quality regulations however assume that the toxicity of PM2.5 does not vary across different sources of emission. Assessing whether PM2.5 from wildfires is more or less harmful than PM2.5 from other sources is a pressing public health concern. Here, we isolate the wildfire-specific PM2.5 using a series of statistical approaches and exposure definitions. We found increases in respiratory hospitalizations ranging from 1.3 to up to 10% with a 10 μg m−3 increase in wildfire-specific PM2.5, compared to 0.67 to 1.3% associated with non-wildfire PM2.5. Our conclusions point to the need for air quality policies to consider the variability in PM2.5 impacts on human health according to the sources of emission.
Single-cell measurement of plasmid copy number and promoter activity
Authors: Shao Bin , Rammohan Jayan , Anderson Daniel A. , Alperovich Nina , Ross David , Voigt Christopher A. 
Published: March 2021

AbstractAccurate measurements of promoter activities are crucial for predictably building genetic systems. Here we report a method to simultaneously count plasmid DNA, RNA transcripts, and protein expression in single living bacteria. From these data, the activity of a promoter in units of RNAP/s can be inferred. This work facilitates the reporting of promoters in absolute units, the variability in their activity across a population, and their quantitative toll on cellular resources, all of which provide critical insights for cellular engineering.
Hyocholic acid species as novel biomarkers for metabolic disorders
Authors: Zheng Xiaojiao , Chen Tianlu , Zhao Aihua , Ning Zhangchi , Kuang Junliang , Wang Shouli , You Yijun , Bao Yuqian , Ma Xiaojing , Yu Haoyong , Zhou Jian , Jiang Miao , Li Mengci , Wang Jieyi , Ma Xiaohui , Zhou Shuiping , Li Yitao , Ge Kun , Rajani Cynthia , Xie Guoxiang , Hu Cheng , Guo Yike , Lu Aiping , Jia Weiping , Jia Wei 
Published: March 2021

AbstractHyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.
psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation
Authors: Strittmatter Lisa M. , Capitanchik Charlotte , Newman Andrew J. , Hallegger Martina , Norman Christine M. , Fica Sebastian M. , Oubridge Chris , Luscombe Nicholas M. , Ule Jernej , Nagai Kiyoshi 
Published: March 2021

AbstractRNA helicases remodel the spliceosome to enable pre-mRNA splicing, but their binding and mechanism of action remain poorly understood. To define helicase-RNA contacts in specific spliceosomal states, we develop purified spliceosome iCLIP (psiCLIP), which reveals dynamic helicase-RNA contacts during splicing catalysis. The helicase Prp16 binds along the entire available single-stranded RNA region between the branchpoint and 3′-splice site, while Prp22 binds diffusely downstream of the branchpoint before exon ligation, but then switches to more narrow binding in the downstream exon after exon ligation, arguing against a mechanism of processive translocation. Depletion of the exon-ligation factor Prp18 destabilizes Prp22 binding to the pre-mRNA, suggesting that proofreading by Prp22 may sense the stability of the spliceosome during exon ligation. Thus, psiCLIP complements structural studies by providing key insights into the binding and proofreading activity of spliceosomal RNA helicases.
The stability of subducted glaucophane with the Earth’s secular cooling
Authors: Bang Yoonah , Hwang Huijeong , Kim Taehyun , Cynn Hyunchae , Park Yong , Jung Haemyeong , Park Changyong , Popov Dmitry , Prakapenka Vitali B. , Wang Lin , Liermann Hanns-Peter , Irifune Tetsuo , Mao Ho-Kwang , Lee Yongjae 
Published: March 2021

AbstractThe blueschist to eclogite transition is one of the major geochemical–metamorphic processes typifying the subduction zone, which releases fluids triggering earthquakes and arc volcanism. Although glaucophane is an index hydrous mineral for the blueschist facies, its stability at mantle depths in diverse subduction regimes of contemporary and early Earth has not been experimentally determined. Here, we show that the maximum depth of glaucophane stability increases with decreasing thermal gradients of the subduction system. Along cold subduction geotherm, glaucophane remains stable down ca. 240 km depth, whereas it dehydrates and breaks down at as shallow as ca. 40 km depth under warm subduction geotherm or the Proterozoic tectonic setting. Our results imply that secular cooling of the Earth has extended the stability of glaucophane and consequently enabled the transportation of water into deeper interior of the Earth, suppressing arc magmatism, volcanism, and seismic activities along subduction zones.
Contrasting long-term temperature trends reveal minor changes in projected potential evapotranspiration in the US Midwest
Authors: Basso Bruno , Martinez-Feria Rafael A. , Rill Lydia , Ritchie Joe T. 
Published: March 2021

AbstractWarming generally leads to increased evaporative demand, altering the amount of water needed for growing crops. For the Midwest, some studies have suggested that reaching yield targets by 2050 will not be possible without additional precipitation or large expansion of irrigation. Here, we show that this claim is not supported by the historical summer climate trends, which indicate that the warming of daily average temperatures is largely driven by increases in minimum temperatures, while maximum temperatures have decreased. This has translated into a net decrease in vapor pressure deficit (VPD) and potential evapotranspiration (PET). With the increasing rainfall, this suggests that crop water deficits have likely become less frequent in the region despite the warming climate. By projecting these trends into 2050 and ancillary use of a crop model, we estimate minor changes in PET that would have minimal effects on corn yields (<6%) under persistence of these trends.
Inherently confinable split-drive systems in Drosophila
Authors: Terradas Gerard , Buchman Anna B. , Bennett Jared B. , Shriner Isaiah , Marshall John M. , Akbari Omar S. , Bier Ethan 
Published: March 2021

AbstractCRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleavage, can interrupt the spread of gene-drive elements. We hypothesized that drives targeting genes essential for viability or reproduction also carrying recoded sequences that restore endogenous gene functionality should benefit from dominantly-acting maternal clearance of NHEJ alleles combined with recessive Mendelian culling processes. Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that are inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). In single generation crosses, sGDs copy with variable efficiencies and display sex-biased transmission. In multigenerational cage trials, sGDs follow distinct drive trajectories reflecting their differential tendencies to induce target chromosome damage and/or lethal/sterile mosaic Cas9-dependent phenotypes, leading to inherently confinable drive outcomes.
Prediction of crossing nodal-lines and large intrinsic spin Hall conductivity in topological Dirac semimetal Ta3As family
Authors: Hou Wenjie , Liu Jian , Zuo Xi , Xu Jian , Zhang Xueying , Liu Desheng , Zhao Mingwen , Zhu Zhen-Gang , Luo Hong-Gang , Zhao Weisheng 
Published: March 2021

AbstractTopological insulators (TIs) are considered as ideal platforms for generating large spin Hall conductivity (SHC), however, the bulk carrier problem, which is unavoidable in TIs, hinders their practical applications. Recently, topological semimetals (TSMs) have been proposed to achieve large SHC to replace TIs. However, the ideal TSM candidates with large SHC are still lacking. In terms of first-principles calculations, we predict that Ta3As family compounds exhibit complex crossing nodal-lines (CNL) properties in absence of the spin-orbit coupling (SOC). However, they transfer to Dirac TSMs under the influence of strong SOC, and present large SHC around Fermi level in particular. Remarkably, the SHC value of Ta3Y (Y = As, Sb, Bi) is around 1500–1700 $$(\hbar /e)({\mathrm{{\Omega}}} \cdot {\mathrm{cm}})^{ - 1}$$

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, which is comparable to noble metal Pt and much larger than TIs, Weyl TSMs, and 4d/5d transition metals. Our work not only suggests a kind of TSM family with interesting Dirac CNL around Fermi level, but also paves the way for searching large intrinsic SHC materials in complex CNL TSM systems.
The Prostate Health Index aids multi-parametric MRI in diagnosing significant prostate cancer
Authors: Fan Yu-Hua , Pan Po-Hsun , Cheng Wei-Ming , Wang Hsin-Kai , Shen Shu-Huei , Liu Hsian-Tzu , Cheng Hao-Min , Chen Wei-Ren , Huang Tzu-Hao , Wei Tzu-Chun , Huang I-Shen , Lin Chih-Chieh , Huang Eric Y. H. , Chung Hsiao-Jen , Huang William J. S. , Lin Tzu-Ping 
Published: March 2021

AbstractTo evaluate the performance of the Prostate Health Index (PHI) in magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion prostate biopsy for the detection of clinically significant prostate cancer (csPCa). We prospectively enrolled 164 patients with at least one Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) ≥ 3 lesions who underwent MRI-TRUS fusion prostate biopsy. Of the PSA-derived biomarkers, the PHI had the best performance in predicting csPCa (AUC 0.792, CI 0.707–0.877) in patients with PI-RADS 4/5 lesions. Furthermore, the predictive power of PHI was even higher in the patients with PI-RADS 3 lesions (AUC 0.884, CI 0.792–0.976). To minimize missing csPCa, we used a PHI cutoff of 27 and 7.4% of patients with PI-RADS 4/5 lesions could have avoided a biopsy. At this level, 2.0% of cases with csPCa would have been missed, with sensitivity and NPV rates of 98.0% and 87.5%, respectively. However, the subgroup of PI-RADS 3 was too small to define the optimal PHI cutoff. PHI was the best PSA-derived biomarker to predict csPCa in MRI-TRUS fusion prostate biopsies in men with PI-RADS ≥ 3 lesions, especially for the patients with PI-RADS 3 lesions who gained the most value.
RETRACTED ARTICLE: Stay-at-home policy is a case of exception fallacy: an internet-based ecological study
Authors: Savaris R. F. , Pumi G. , Dalzochio J. , Kunst R. 
Published: March 2021

AbstractA recent mathematical model has suggested that staying at home did not play a dominant role in reducing COVID-19 transmission. The second wave of cases in Europe, in regions that were considered as COVID-19 controlled, may raise some concerns. Our objective was to assess the association between staying at home (%) and the reduction/increase in the number of deaths due to COVID-19 in several regions in the world. In this ecological study, data fromwww.google.com/covid19/mobility/, ourworldindata.org and covid.saude.gov.br were combined. Countries with > 100 deaths and with a Healthcare Access and Quality Index of ≥ 67 were included. Data were preprocessed and analyzed using the difference between number of deaths/million between 2 regions and the difference between the percentage of staying at home. The analysis was performed using linear regression with special attention to residual analysis. After preprocessing the data, 87 regions around the world were included, yielding 3741 pairwise comparisons for linear regression analysis. Only 63 (1.6%) comparisons were significant. With our results, we were not able to explain if COVID-19 mortality is reduced by staying at home in ~ 98% of the comparisons after epidemiological weeks 9 to 34.
Competence-based social status and implicit preference modulate the ability to coordinate during a joint grasping task
Authors: Boukarras Sarah , Era Vanessa , Aglioti Salvatore Maria , Candidi Matteo 
Published: March 2021

AbstractStudies indicate that social status influences people’s social perceptions. Less information is available about whether induced social status influences dyadic coordination during motor interactions. To explore this issue, we designed a study in which two confederates obtained high or low competence-based status by playing a game together with the participant, while the participant always occupied the middle position of the hierarchy. Following this status-inducing phase, participants were engaged in a joint grasping task with the high- and low-status confederates in different sessions while behavioural (i.e., interpersonal asynchrony and movement start time) indexes were measured. Participants’ performance in the task (i.e., level of interpersonal asynchrony) when interacting with the low-status partner was modulated by their preference for him. The lower participants’ preference for a low- relative to a high-status confederate, the worse participants’ performance when interacting with the low-status confederate. Our results show that participants’ performance during motor interactions changes according to the social status of the interaction partner.