bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of MRN activity by a telomere protein motif
Authors: Khayat Freddy , Cannavo Elda , Alshmery Majedh , Foster William R. , Chahwan Charly , Maddalena Martino , Smith Christopher , Oliver Antony W. , Watson Adam T. , Carr Antony M. , Cejka Petr , Bianchi Alessandro 
Published: June 2021

AbstractThe MRN complex (MRX in Saccharomyces cerevisiae, made of Mre11, Rad50 and Nbs1/Xrs2) initiates double-stranded DNA break repair and activates the Tel1/ATM kinase in the DNA damage response. Telomeres counter both outcomes at chromosome ends, partly by keeping MRN-ATM in check. We show that MRX is disabled by telomeric protein Rif2 through an N-terminal motif (MIN, MRN/X-inhibitory motif). MIN executes suppression of Tel1, DNA end-resection and non-homologous end joining by binding the Rad50 N-terminal region. Our data suggest that MIN promotes a transition within MRX that is not conductive for endonuclease activity, DNA-end tethering or Tel1 kinase activation, highlighting an Achilles’ heel in MRN, which we propose is also exploited by the RIF2 paralog ORC4 (Origin Recognition Complex 4) in Kluyveromyces lactis and the Schizosaccharomyces pombe telomeric factor Taz1, which is evolutionarily unrelated to Orc4/Rif2. This raises the possibility that analogous mechanisms might be deployed in other eukaryotes as well.
Repurposing tRNAs for nonsense suppression
Authors: Albers Suki , Beckert Bertrand , Matthies Marco C. , Mandava Chandra Sekhar , Schuster Raphael , Seuring Carolin , Riedner Maria , Sanyal Suparna , Torda Andrew E. , Wilson Daniel N. , Ignatova Zoya 
Published: June 2021

AbstractThree stop codons (UAA, UAG and UGA) terminate protein synthesis and are almost exclusively recognized by release factors. Here, we design de novo transfer RNAs (tRNAs) that efficiently decode UGA stop codons in Escherichia coli. The tRNA designs harness various functionally conserved aspects of sense-codon decoding tRNAs. Optimization within the TΨC-stem to stabilize binding to the elongation factor, displays the most potent effect in enhancing suppression activity. We determine the structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon in the A site at 2.9 Å resolution. In the context of the suppressor tRNA, the conformation of the UGA codon resembles that of a sense-codon rather than when canonical translation termination release factors are bound, suggesting conformational flexibility of the stop codons dependent on the nature of the A-site ligand. The systematic analysis, combined with structural insights, provides a rationale for targeted repurposing of tRNAs to correct devastating nonsense mutations that introduce a premature stop codon.
Anomalous formation of trihydrogen cations from water on nanoparticles
Authors: Alghabra M. Said , Ali Rami , Kim Vyacheslav , Iqbal Mazhar , Rosenberger Philipp , Mitra Sambit , Dagar Ritika , Rupp Philipp , Bergues Boris , Mathur Deepak , Kling Matthias F. , Alnaser Ali S. 
Published: June 2021

AbstractRegarded as the most important ion in interstellar chemistry, the trihydrogen cation, $${{\rm{H}}}_{{{3}}}^{+}$$

H

3

+

, plays a vital role in the formation of water and many complex organic molecules believed to be responsible for life in our universe. Apart from traditional plasma discharges, recent laboratory studies have focused on forming the trihydrogen cation from large organic molecules during their interactions with intense radiation and charged particles. In contrast, we present results on forming $${{\rm{H}}}_{{{3}}}^{+}$$

H

3

+

from bimolecular reactions that involve only an inorganic molecule, namely water, without the presence of any organic molecules to facilitate its formation. This generation of $${{\rm{H}}}_{{{3}}}^{+}$$

H

3

+

is enabled by “engineering” a suitable reaction environment comprising water-covered silica nanoparticles exposed to intense, femtosecond laser pulses. Similar, naturally-occurring, environments might exist in astrophysical settings where hydrated nanometer-sized dust particles are impacted by cosmic rays of charged particles or solar wind ions. Our results are a clear manifestation of how aerosolized nanoparticles in intense femtosecond laser fields can serve as a catalysts that enable exotic molecular entities to be produced via non-traditional routes.
The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer’s disease
Authors: Park So-Hee , Lee Eun-Hye , Kim Hyung-Ji , Jo Sungyang , Lee Sunju , Seo Sang Won , Park Hyun-Hee , Koh Seong-Ho , Lee Jae-Hong 
Published: June 2021

AbstractMicroglial activation is a central player in the pathophysiology of Alzheimer’s disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.
First complete genome sequence and molecular characterization of Canine morbillivirus isolated in Central Brazil
Authors: da Costa Vivaldo Gomes , Saivish Marielena Vogel , de Oliveira Priscila Gomes , Silva-Júnior Abelardo , Moreli Marcos Lázaro , Krüger Ricardo Henrique 
Published: June 2021

AbstractThe Brazilian regions are still highly endemic areas for Canine morbillivirus [canine distemper virus (CDV)]. However, little is known regarding the genetic variability of the strain circulating in several Brazilian regions. Here, we report the first full-length genome and molecular characterization of CDV isolated from domestic dogs in the Brazilian Center-West region. Sequence alignment and phylogenetic analyses based on deduced amino acid and nucleotide sequences showed that the isolated strain is characterized as the South America-I/Europe genotype. However, it segregates into a CDV subgenotype branch. Interestingly, both H and F proteins have a gain of a potential N-glycosylation sites compared to the Onderstepoort vaccine strain. Therefore, this study provides a reference to further understand the epidemic and molecular characteristics of the CDV in Brazil.
Chemical insights into the atmospheric oxidation of thiophene by hydroperoxyl radical
Authors: Sharifi Maryam Seyed , Douroudgari Hamed , Vahedpour Morteza 
Published: June 2021

AbstractThe reaction mechanisms and kinetics of thiophene oxidation reactions initiated by hydroperoxyl radical, and decomposition of the related intermediates and complexes, have been considered herein by using high-level DFT and ab initio calculations. The main energetic parameters of all stationary points of the suggested potential energy surfaces have been computed at the BD(T) and CCSD(T) methods, based on the geometries optimized at the B3LYP/6-311 + g(d,p) level of theory. Rate constants of bimolecular reactions (high-pressure limit rate constants) at temperatures from 300 to 3000 K for the first steps of the title reaction have been obtained through the conventional transition state theory (TST), while the pressure dependent rate constants and the rate constants of the second and other steps have been calculated employing the Rice–Ramsperger–Kassel–Marcus/Master equation (RRKM/ME). The results show that the rate constants of addition to α and β carbons have positive temperature dependence and negative pressure dependence. It is found that the additions of HO2 to the α and β carbons of thiophene in the initial steps of the title reaction are the most favored pathways. Also, the addition to the sulfur atom has a minor contribution. But, all efforts for simulating hydrogen abstraction reactions have been unsuccessful. In this complex oxidation reaction, about 12 different products are obtained, including important isomers such as thiophene-epoxide, thiophene-ol, thiophene-oxide, oxathiane, and thiophenone. The calculated total rate constants for generation of all minimum stationary points show that the addition reactions to the α and β carbons are the fastest among all at temperatures below 1000 K, while the proposed multi-step parallel reactions are more competitive at temperatures above 1200 K. Furthermore, important inter-and intra-molecular interactions for some species have been investigated by two well-known quantum chemistry method, the NBO and AIM analyses. Thermochemical properties such as free energy, enthalpy, internal energy, and entropy for thiophene and hydroperoxyl radical and related species in the simulated reactions have been predicted using a combination of the B3LYP and BD(T) methods.
lncRNA FER1L4 is dysregulated in osteoarthritis and regulates IL-6 expression in human chondrocyte cells
Authors: He Jinhai , Wang Li , Ding Yajun , Liu Hongbing , Zou Guoyou 
Published: June 2021

AbstractOsteoarthritis (OA) is the most prevalent joint disease and is one of the major causes of disability in the world. There has been an increase in the incidence of OA, which is associated with an aging population, sedentary lifestyle, and reduced physical activity. Due to the complex OA pathogenesis, there are limited diagnostic tools. OA is a degenerative joint disorder with a recognized inflammatory component, usually described as abnormal expression of inflammatory factors. For instance, interleukin 6 (IL‐6) has been shown to be upregulated in serum and synovial fluid among patients with OA. Most of the inflammatory factors have been associated with the expression of long noncoding RNAs (lncRNAs). However, the role of the novel lncRNA Fer-1-like protein 4 (FER1L4) in OA is yet to be determined. Here, we interrogated the expression profile of FER1L4 in patients with OA to define its potential application as a diagnostic marker. We collected synovial fluid and blood samples from both OA cases and normal controls. Using qRT-PCR, we evaluated the expression of FER1L4 in plasma and synovial fluid. On the other hand, the expression of IL-6 in plasma and synovial fluid was assessed using ELISA. Besides, the effect of age, gender or disease stage in the expression of the FER1L4 in plasma was also estimated. Moreover, the receiver operating characteristic (ROC) curves were used to determine the impact of FER1L4 in OA cases compared with the normal controls. In addition, we analyzed the correlation between FER1L4 and IL-6 through Pearson correlation analysis. Also, IL-6 expression in overexpressed FER1L4 samples was detected in chondrocytes through western blot analysis, while FER1L4 expression following endogenous IL-6 exposure was detected by qRT-PCR. Our data showed that whereas lncRNA FER1L4 is downregulated in OA patients, IL‐6 is upregulated. The plasma FER1L4 levels among the OA cases were suppressed with disease progression and old age, and the down-regulation could efficiently discriminate OA patients from normal subjects. In addition, upregulation of FER1L4 inhibited IL‐6 expression in human chondrocyte cells, and treatment with different concentrations of exogenous IL‐6 did not affect the expression of FER1L4. Taken together, our data demonstrates that FER1L4 could efficiently identify OA cases from normal subjects, and can also modulate the expression of IL‐6 in human chondrocytes.
Unraveling the dynamic importance of county-level features in trajectory of COVID-19
Authors: Li Qingchun , Yang Yang , Wang Wanqiu , Lee Sanghyeon , Xiao Xin , Gao Xinyu , Oztekin Bora , Fan Chao , Mostafavi Ali 
Published: June 2021

AbstractThe objective of this study was to investigate the importance of multiple county-level features in the trajectory of COVID-19. We examined feature importance across 2787 counties in the United States using data-driven machine learning models. Existing mathematical models of disease spread usually focused on the case prediction with different infection rates without incorporating multiple heterogeneous features that could impact the spatial and temporal trajectory of COVID-19. Recognizing this, we trained a data-driven model using 23 features representing six key influencing factors affecting the pandemic spread: social demographics of counties, population activities, mobility within the counties, movement across counties, disease attributes, and social network structure. Also, we categorized counties into multiple groups according to their population densities, and we divided the trajectory of COVID-19 into three stages: the outbreak stage, the social distancing stage, and the reopening stage. The study aimed to answer two research questions: (1) The extent to which the importance of heterogeneous features evolved at different stages; (2) The extent to which the importance of heterogeneous features varied across counties with different characteristics. We fitted a set of random forest models to determine weekly feature importance. The results showed that: (1) Social demographic features, such as gross domestic product, population density, and minority status maintained high-importance features throughout stages of COVID-19 across 2787 studied counties; (2) Within-county mobility features had the highest importance in counties with higher population densities; (3) The feature reflecting the social network structure (Facebook, social connectedness index), had higher importance for counties with higher population densities. The results showed that the data-driven machine learning models could provide important insights to inform policymakers regarding feature importance for counties with various population densities and at different stages of a pandemic life cycle.
Saccharomyces cerevisiae strains used industrially for bioethanol production
Authors: Jacobus Ana Paula , Gross Jeferson , Evans John H. , Ceccato-Antonini Sandra Regina , Gombert Andreas Karoly 
Published: June 2021

Abstract
Fuel ethanol is produced by the yeast Saccharomyces cerevisiae mainly from corn starch in the United States and from sugarcane sucrose in Brazil, which together manufacture ∼85% of a global yearly production of 109.8 million m3 (in 2019). While in North America genetically engineered (GE) strains account for ∼80% of the ethanol produced, including strains that express amylases and are engineered to produce higher ethanol yields; in South America, mostly (&gt;90%) non-GE strains are used in ethanol production, primarily as starters in non-aseptic fermentation systems with cell recycling. In spite of intensive research exploring lignocellulosic ethanol (or second generation ethanol), this option still accounts for &lt;1% of global ethanol production. In this mini-review, we describe the main aspects of fuel ethanol production, emphasizing bioprocesses operating in North America and Brazil. We list and describe the main properties of several commercial yeast products (i.e., yeast strains) that are available worldwide to bioethanol producers, including GE strains with their respective genetic modifications. We also discuss recent studies that have started to shed light on the genes and traits that are important for the persistence and dominance of yeast strains in the non-aseptic process in Brazil. While Brazilian bioethanol yeast strains originated from a historical process of domestication for sugarcane fermentation, leading to a unique group with significant economic applications, in U.S.A., guided selection, breeding and genetic engineering approaches have driven the generation of new yeast products for the market.
The Effect of Deep Brain Stimulation of the Subthalamic Nucleus on Language Function in Parkinson's Disease: A Systematic Review
Authors: Vos Sandra H. , Kessels Roy P. C. , Vinke R. Saman , Esselink Rianne A. J. , Piai Vitória 
Published: June 2021

Purpose
This systematic review focuses on the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on language function in Parkinson's disease (PD). It fills an important gap in recent reviews by considering other language tasks in addition to verbal fluency.

Method
We critically and systematically reviewed the literature on studies that investigated the effect of bilateral STN-DBS on language function in PD. All studies included a matched PD control group who were on best medical treatment, with language testing at similar baseline and follow-up intervals as the DBS PD group.

Results
Thirteen identified studies included a form of a verbal fluency task, seven studies included picture naming, and only two studies included more language-oriented tasks. We found that verbal fluency was negatively affected after DBS, whereas picture naming was unaffected. Studies investigating individual change patterns using reliable change indices showed that individual variability is larger for picture naming than for verbal fluency.

Conclusions
Verbal fluency is the most frequently investigated aspect of language function. Our analysis showed a pattern of decline in verbal fluency across multiple studies after STN-DBS, whereas picture naming was unaffected. Data on more language-oriented tests in a large DBS sample and best medical treatment control group are sparse. The investigation of language function in PD after DBS requires sensitive language tests (with and without time pressure) and experimental designs as used in the studies reviewed here. Reliable change index statistics are a promising tool for investigating individual differences in performance after DBS.

Supplemental Material

https://doi.org/10.23641/asha.14794458
An improved natural frequency based transmission line fault location method with full utilization of frequency spectrum information
Authors: Nie Yuan , Liu Yu , Lu Dayou , Wang Binglin 
Published: June 2021

AbstractAn improved natural frequency based method is proposed to accurately locate faults in transmission lines. The method only requires three phase instantaneous current measurements at the local terminal of the line and is compatible with protective relays using high‐speed tripping techniques. First, the theoretical peak frequencies along the entire frequency spectrum of the measured currents are derived, for different fault types, locations and resistances. Next, the fault location is determined by finding the minimum average distance between the theoretical and the measured peak frequencies. Compared to the existing natural frequency based fault location methods, the proposed method solves the mode mixing problem during single phase to ground faults and systematically considers the effect of fault resistances. In addition, the proposed method fully utilizes the frequency spectrum information instead of only the dominant frequency, and therefore overcomes the difficulty to extract the dominant frequency. Numerical experiments have shown that, compared to the existing method, the proposed method presents much higher fault location accuracy during single phase to ground faults, and slightly higher (comparable) fault location accuracy for other types of faults, regardless of fault locations and fault resistances.
Passive‐compensation clamp‐on two‐stage current transformer for online calibration
Authors: Hu Haoliang , Xu Yan , Wu Xiong , Lin Fuchang , Xiao Xia , Lei Min 
Published: June 2021

AbstractDigital measurement equipment such as electronic transformers enable real‐time functional control and monitoring systems to be built in power grids to accommodate the large‐scale access of distributed renewable energy to the grid. However, the current offline calibration of electronic transformers is difficult to implement; therefore, an online calibration method for electronic transformers must be developed to ensure their accuracy. The design of a clamp‐on two‐stage current transformer (CTS‐CT) with a passive compensation loop is presented herein. The compensation loop is utilised to reduce both the amplitude and phase errors, thereby achieving high accuracy. The formulas for calculating the resistance and capacitance of the passive compensation loop are presented. The expanded uncertainties (95% confidence level) of the proposed CTS‐CT are estimated to be lower 0.03% for the amplitude error and 1′ for the phase error. Experimental results indicate that the proposed CTS‐CT prototype is not affected by the external magnetic field nor the opening and closing times, thereby enabling good‐quality online calibration for field applications. Moreover, the proposed CTS‐CT adopts neither an active compensatory circuit nor software compensation; therefore, the manufacturing of the CTS‐CT is steady and simple, and the calibration procedures are simplified.
New ex-OH maser detections in the northern celestial hemisphere
Authors: Patoka O. , Antyufeyev O. , Shmeld I. , Bezrukovs V. , Bleiders M. , Orbidans A. , Aberfelds A. , Shulga V. 
Published: June 2021

Aims.Molecular masers, including methanol and hydroxyl masers, and in particular the ones in excited rotational states (ex-OH masers), are one of the most informative tools for studying star-forming regions. So, the discovery, of new maser sources in these regions is of great importance. Many studies and surveys of ex-OH maser sources have been carried out in the southern celestial hemisphere, but only a few have been done in the northern hemisphere. The specific aim of this work is to close this gap.Methods.The star-forming regions in the northern hemisphere with known active methanol masers were observed to search for new ex-OH maser sources with the 32 m and 16 m radio telescopes of the Ventspils International Radio Astronomy Centre (VIRAC).Results.Three OH maser lines in the excited state at the 6035 MHz in three northern hemisphere star-forming regions are detected. The maser 189.030+0.783 was previously known, but we suggest this maser is a possible variable. We confirm recent detections of the ex-OH masers 85.41+0.00 and 90.92+1.49 by other authors. The magnetic field strength in the masering regions is estimated by using right circular polarization and left circular polarization pair splitting. The high-velocity resolution provides us with an estimation of a comparatively small magnetic field strength for the 189.030+0.783 and 90.92+1.49 star-forming regions.