bluuebunny/crossref_metadata_2025 huggingface dataset:
An optic to replace space and its application towards ultra-thin imaging systems
Authors: Reshef Orad , DelMastro Michael P. , Bearne Katherine K. M. , Alhulaymi Ali H. , Giner Lambert , Boyd Robert W. , Lundeen Jeff S.
Published: June 2021

Centuries of effort to improve imaging has focused on perfecting and combining lenses to obtain better optical performance and new functionalities. The arrival of nanotechnology has brought to this effort engineered surfaces called metalenses, which promise to make imaging devices more compact. However, unaddressed by this promise is the space between the lenses, which is crucial for image formation but takes up by far the most room in imaging systems. Here, we address this issue by presenting the concept of and experimentally demonstrating an optical ‘spaceplate’, an optic that effectively propagates light for a distance that can be considerably longer than the plate thickness. Such an optic would shrink future imaging systems, opening the possibility for ultra-thin monolithic cameras. More broadly, a spaceplate can be applied to miniaturize important devices that implicitly manipulate the spatial profile of light, for example, solar concentrators, collimators for light sources, integrated optical components, and spectrometers.
BRCA1 binds TERRA RNA and suppresses R-Loop-based telomeric DNA damage
Authors: Vohhodina Jekaterina , Goehring Liana J. , Liu Ben , Kong Qing , Botchkarev Vladimir V. , Huynh Mai , Liu Zhiqi , Abderazzaq Fieda O. , Clark Allison P. , Ficarro Scott B. , Marto Jarrod A. , Hatchi Elodie , Livingston David M.
Published: June 2021

R-loop structures act as modulators of physiological processes such as transcription termination, gene regulation, and DNA repair. However, they can cause transcription-replication conflicts and give rise to genomic instability, particularly at telomeres, which are prone to forming DNA secondary structures. Here, we demonstrate that BRCA1 binds TERRA RNA, directly and physically via its N-terminal nuclear localization sequence, as well as telomere-specific shelterin proteins in an R-loop-, and a cell cycle-dependent manner. R-loop-driven BRCA1 binding to CpG-rich TERRA promoters represses TERRA transcription, prevents TERRA R-loop-associated damage, and promotes its repair, likely in association with SETX and XRN2. BRCA1 depletion upregulates TERRA expression, leading to overly abundant TERRA R-loops, telomeric replication stress, and signs of telomeric aberrancy. Moreover, BRCA1 mutations within the TERRA-binding region lead to an excess of TERRA-associated R-loops and telomeric abnormalities. Thus, normal BRCA1/TERRA binding suppresses telomere-centered genome instability.
Algebraic graph-assisted bidirectional transformers for molecular property prediction
Authors: Chen Dong , Gao Kaifu , Nguyen Duc Duy , Chen Xin , Jiang Yi , Wei Guo-Wei , Pan Feng
Published: June 2021

The ability of molecular property prediction is of great significance to drug discovery, human health, and environmental protection. Despite considerable efforts, quantitative prediction of various molecular properties remains a challenge. Although some machine learning models, such as bidirectional encoder from transformer, can incorporate massive unlabeled molecular data into molecular representations via a self-supervised learning strategy, it neglects three-dimensional (3D) stereochemical information. Algebraic graph, specifically, element-specific multiscale weighted colored algebraic graph, embeds complementary 3D molecular information into graph invariants. We propose an algebraic graph-assisted bidirectional transformer (AGBT) framework by fusing representations generated by algebraic graph and bidirectional transformer, as well as a variety of machine learning algorithms, including decision trees, multitask learning, and deep neural networks. We validate the proposed AGBT framework on eight molecular datasets, involving quantitative toxicity, physical chemistry, and physiology datasets. Extensive numerical experiments have shown that AGBT is a state-of-the-art framework for molecular property prediction.
Wide-range lifetime-tunable and responsive ultralong organic phosphorescent multi-host/guest system
Authors: Xie Zongliang , Zhang Xiayu , Wang Hailan , Huang Cheng , Sun Haodong , Dong Mengyang , Ji Lei , An Zhongfu , Yu Tao , Huang Wei
Published: June 2021

The rational lifetime-tuning strategy of ultralong organic phosphorescence is extraordinarily important but seldom reported. Herein, a series of multi-host/guest ultralong organic phosphorescence materials with dynamic lifetime-tuning properties were reported. By doping a non-room-temperature phosphorescence emitter into various solid host matrices with continuously reduced triplet energy levels, a wide-range lifetime (from 3.9 ms gradually to 376.9 ms) phosphorescence with unchangeable afterglow colors were realized. Further studies revealed that the host matrices were employed to afford rigid environment and proper energy levels to generate and stabilize the long-live triplet excitons. Meanwhile, these multi-host/guest ultralong organic phosphorescence materials also exhibited excitation-dependent phosphorescence and temperature-controlled afterglow on/off switching properties, according to the virtue of various photophysical and thermal properties of the host matrices. This work provides a guiding strategy to realize lifetime-tuning ultralong organic phosphorescence with lifetime-order encoding characteristic towards widespread applications in time-resolved information displaying, higher-level security protection, and dynamic multi-dimensional anti-counterfeiting.
Crustal rejuvenation stabilised Earth’s first cratons
Authors: Mulder Jacob A. , Nebel Oliver , Gardiner Nicholas J. , Cawood Peter A. , Wainwright Ashlea N. , Ivanic Timothy J.
Published: June 2021

The formation of stable, evolved (silica-rich) crust was essential in constructing Earth’s first cratons, the ancient nuclei of continents. Eoarchaean (4000–3600 million years ago, Ma) evolved crust occurs on most continents, yet evidence for older, Hadean evolved crust is mostly limited to rare Hadean zircons recycled into younger rocks. Resolving why the preserved volume of evolved crust increased in the Eoarchaean is key to understanding how the first cratons stabilised. Here we report new zircon uranium-lead and hafnium isotope data from the Yilgarn Craton, Australia, which provides an extensive record of Hadean–Eoarchaean evolved magmatism. These data reveal that the first stable, evolved rocks in the Yilgarn Craton formed during an influx of juvenile (recently extracted from the mantle) magmatic source material into the craton. The concurrent shift to juvenile sources and onset of crustal preservation links craton stabilisation to the accumulation of enduring rafts of buoyant, melt-depleted mantle.
Controlled self-assembly of plant proteins into high-performance multifunctional nanostructured films
Authors: Kamada Ayaka , Rodriguez-Garcia Marc , Ruggeri Francesco Simone , Shen Yi , Levin Aviad , Knowles Tuomas P. J.
Published: June 2021

The abundance of plant-derived proteins, as well as their biodegradability and low environmental impact make them attractive polymeric feedstocks for next-generation functional materials to replace current petroleum-based systems. However, efforts to generate functional materials from plant-based proteins in a scalable manner have been hampered by the lack of efficient methods to induce and control their micro and nanoscale structure, key requirements for achieving advantageous material properties and tailoring their functionality. Here, we demonstrate a scalable approach for generating mechanically robust plant-based films on a metre-scale through controlled nanometre-scale self-assembly of water-insoluble plant proteins. The films produced using this method exhibit high optical transmittance, as well as robust mechanical properties comparable to engineering plastics. Furthermore, we demonstrate the ability to impart nano- and microscale patterning into such films through templating, leading to the formation of hydrophobic surfaces as well as structural colour by controlling the size of the patterned features.
A robotic prebiotic chemist probes long term reactions of complexifying mixtures
Authors: Asche Silke , Cooper Geoffrey J. T. , Keenan Graham , Mathis Cole , Cronin Leroy
Published: June 2021

To experimentally test hypotheses about the emergence of living systems from abiotic chemistry, researchers need to be able to run intelligent, automated, and long-term experiments to explore chemical space. Here we report a robotic prebiotic chemist equipped with an automatic sensor system designed for long-term chemical experiments exploring unconstrained multicomponent reactions, which can run autonomously over long periods. The system collects mass spectrometry data from over 10 experiments, with 60 to 150 algorithmically controlled cycles per experiment, running continuously for over 4 weeks. We show that the robot can discover the production of high complexity molecules from simple precursors, as well as deal with the vast amount of data produced by a recursive and unconstrained experiment. This approach represents what we believe to be a necessary step towards the design of new types of Origin of Life experiments that allow testable hypotheses for the emergence of life from prebiotic chemistry.
Spectral signatures of the surface anomalous Hall effect in magnetic axion insulators
Authors: Gu Mingqiang , Li Jiayu , Sun Hongyi , Zhao Yufei , Liu Chang , Liu Jianpeng , Lu Haizhou , Liu Qihang
Published: June 2021

The topological surface states of magnetic topological systems, such as Weyl semimetals and axion insulators, are associated with unconventional transport properties such as nonzero or half-quantized surface anomalous Hall effect. Here we study the surface anomalous Hall effect and its spectral signatures in different magnetic topological phases using both model Hamiltonian and first-principles calculations. We demonstrate that by tailoring the magnetization and interlayer electron hopping, a rich three-dimensional topological phase diagram can be established, including three types of topologically distinct insulating phases bridged by Weyl semimetals, and can be directly mapped to realistic materials such as MnBi2Te4/(Bi2Te3)n systems. Among them, we find that the surface anomalous Hall conductivity in the axion-insulator phase is a well-localized quantity either saturated at or oscillating around e2/2h, depending on the magnetic homogeneity. We also discuss the resultant chiral hinge modes embedded inside the side surface bands as the potential experimental signatures for transport measurements. Our study is a significant step forward towards the direct realization of the long-sought axion insulators in realistic material systems.
Machine learning analyses of antibody somatic mutations predict immunoglobulin light chain toxicity
Authors: Garofalo Maura , Piccoli Luca , Romeo Margherita , Barzago Maria Monica , Ravasio Sara , Foglierini Mathilde , Matkovic Milos , Sgrignani Jacopo , De Gasparo Raoul , Prunotto Marco , Varani Luca , Diomede Luisa , Michielin Olivier , Lanzavecchia Antonio , Cavalli Andrea
Published: June 2021

In systemic light chain amyloidosis (AL), pathogenic monoclonal immunoglobulin light chains (LC) form toxic aggregates and amyloid fibrils in target organs. Prompt diagnosis is crucial to avoid permanent organ damage, but delayed diagnosis is common because symptoms usually appear only after strong organ involvement. Here we present LICTOR, a machine learning approach predicting LC toxicity in AL, based on the distribution of somatic mutations acquired during clonal selection. LICTOR achieves a specificity and a sensitivity of 0.82 and 0.76, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.87. Tested on an independent set of 12 LCs sequences with known clinical phenotypes, LICTOR achieves a prediction accuracy of 83%. Furthermore, we are able to abolish the toxic phenotype of an LC by in silico reverting two germline-specific somatic mutations identified by LICTOR, and by experimentally assessing the loss of in vivo toxicity in a Caenorhabditis elegans model. Therefore, LICTOR represents a promising strategy for AL diagnosis and reducing high mortality rates in AL.
Hybrid AI-assistive diagnostic model permits rapid TBS classification of cervical liquid-based thin-layer cell smears
Authors: Zhu Xiaohui , Li Xiaoming , Ong Kokhaur , Zhang Wenli , Li Wencai , Li Longjie , Young David , Su Yongjian , Shang Bin , Peng Linggan , Xiong Wei , Liu Yunke , Liao Wenting , Xu Jingjing , Wang Feifei , Liao Qing , Li Shengnan , Liao Minmin , Li Yu , Rao Linshang , Lin Jinquan , Shi Jianyuan , You Zejun , Zhong Wenlong , Liang Xinrong , Han Hao , Zhang Yan , Tang Na , Hu Aixia , Gao Hongyi , Cheng Zhiqiang , Liang Li , Yu Weimiao , Ding Yanqing
Published: June 2021

Technical advancements significantly improve earlier diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various factors. We develop an artificial intelligence assistive diagnostic solution, AIATBS, to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria. We train AIATBS with >81,000 retrospective samples. It integrates YOLOv3 for target detection, Xception and Patch-based models to boost target classification, and U-net for nucleus segmentation. We integrate XGBoost and a logical decision tree with these models to optimize the parameters given by the learning process, and we develop a complete cervical liquid-based cytology smear TBS diagnostic system which also includes a quality control solution. We validate the optimized system with >34,000 multicenter prospective samples and achieve better sensitivity compared to senior cytologists, yet retain high specificity while achieving a speed of <180s/slide. Our system is adaptive to sample preparation using different standards, staining protocols and scanners.
Unusual competition of superconductivity and charge-density-wave state in a compressed topological kagome metal
Authors: Yu F. H. , Ma D. H. , Zhuo W. Z. , Liu S. Q. , Wen X. K. , Lei B. , Ying J. J. , Chen X. H.
Published: June 2021

Understanding the competition between superconductivity and other ordered states (such as antiferromagnetic or charge-density-wave (CDW) state) is a central issue in condensed matter physics. The recently discovered layered kagome metal AV3Sb5 (A = K, Rb, and Cs) provides us a new playground to study the interplay of superconductivity and CDW state by involving nontrivial topology of band structures. Here, we conduct high-pressure electrical transport and magnetic susceptibility measurements to study CsV3Sb5 with the highest Tc of 2.7 K in AV3Sb5 family. While the CDW transition is monotonically suppressed by pressure, superconductivity is enhanced with increasing pressure up to P1 ≈ 0.7 GPa, then an unexpected suppression on superconductivity happens until pressure around 1.1 GPa, after that, Tc is enhanced with increasing pressure again. The CDW is completely suppressed at a critical pressure P2 ≈ 2 GPa together with a maximum Tc of about 8 K. In contrast to a common dome-like behavior, the pressure-dependent Tc shows an unexpected double-peak behavior. The unusual suppression of Tc at P1 is concomitant with the rapidly damping of quantum oscillations, sudden enhancement of the residual resistivity and rapid decrease of magnetoresistance. Our discoveries indicate an unusual competition between superconductivity and CDW state in pressurized kagome lattice.
A randomised controlled trial on effectiveness and feasibility of sport climbing in Parkinson’s disease
Authors: Langer Agnes , Hasenauer Sebastian , Flotz Anna , Gassner Lucia , Pokan Rochus , Dabnichki Peter , Wizany Laurenz , Gruber Jakob , Roth Dominik , Zimmel Sarah , Treven Marco , Schmoeger Michaela , Willinger Ulrike , Maetzler Walter , Zach Heidemarie
Published: June 2021

Physical activity is of prime importance in non-pharmacological Parkinson’s disease (PD) treatment. The current study examines the effectiveness and feasibility of sport climbing in PD patients in a single-centre, randomised controlled, semi-blind trial. A total of 48 PD patients without experience in climbing (average age 64 ± 8 years, Hoehn & Yahr stage 2–3) were assigned either to participate in a 12-week sport climbing course (SC) or to attend an unsupervised physical training group (UT). The primary outcome was the improvement of symptoms on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III). Sport climbing was associated with a significant reduction of the MDS-UPDRS-III (−12.9 points; 95% CI −15.9 to −9.8), while no significant improvement was to be found in the UT (−3.0 points; 95% CI −6.0 to 0.1). Bradykinesia, rigidity and tremor subscales significantly improved in SC, but not in the unsupervised control group. In terms of feasibility, the study showed a 99% adherence of participants to climbing sessions and a drop-out rate of only 8%. No adverse events occurred. This trial provides class III evidence that sport climbing is highly effective and feasible in mildly to moderately affected PD patients.
Age-dependent transition from islet insulin hypersecretion to hyposecretion in mice with the long QT-syndrome loss-of-function mutation Kcnq1-A340V
Authors: Lubberding Anniek F. , Zhang Jinyi , Lundh Morten , Nielsen Thomas Svava , Søndergaard Mathilde S. , Villadsen Maria , Skovhøj Emil Z. , Boer Geke A. , Hansen Jakob B. , Thomsen Morten B. , Treebak Jonas T. , Holst Jens J. , Kanters Jørgen K. , Mandrup-Poulsen Thomas , Jespersen Thomas , Emanuelli Brice , Torekov Signe S.
Published: June 2021

Loss-of-function (LoF) mutations in KCNQ1, encoding the voltage-gated K+ channel Kv7.1, lead to long QT syndrome 1 (LQT1). LQT1 patients also present with post-prandial hyperinsulinemia and hypoglycaemia. In contrast, KCNQ1 polymorphisms are associated with diabetes, and LQTS patients have a higher prevalence of diabetes. We developed a mouse model with a LoF Kcnq1 mutation using CRISPR-Cas9 and hypothesized that this mouse model would display QT prolongation, increased glucose-stimulated insulin secretion and allow for interrogation of Kv7.1 function in islets. Mice were characterized by electrocardiography and oral glucose tolerance tests. Ex vivo, islet glucose-induced insulin release was measured, and beta-cell area quantified by immunohistochemistry. Homozygous mice had QT prolongation. Ex vivo, glucose-stimulated insulin release was increased in islets from homozygous mice at 12–14 weeks, while beta-cell area was reduced. Non-fasting blood glucose levels were decreased at this age. In follow-up studies 8–10 weeks later, beta-cell area was similar in all groups, while glucose-stimulated insulin secretion was now reduced in islets from hetero- and homozygous mice. Non-fasting blood glucose levels had normalized. These data suggest that Kv7.1 dysfunction is involved in a transition from hyper- to hyposecretion of insulin, potentially explaining the association with both hypoglycemia and hyperglycemia in LQT1 patients.
Visual mapping of body image disturbance in anorexia nervosa reveals objective markers of illness severity
Authors: Ralph-Nearman Christina , Arevian Armen C. , Moseman Scott , Sinik Megan , Chappelle Sheridan , Feusner Jamie D. , Khalsa Sahib S.
Published: June 2021

Body image disturbance (BID) is a core feature of eating disorders, for which there are few objective markers. We examined the feasibility of a novel digital tool, “Somatomap”, to index BID related to anorexia nervosa (AN) severity. Fifty-five AN inpatients and 55 healthy comparisons (HC) outlined their body concerns on a 2-Dimensional avatar. Next, they indicated sizes/shapes of body parts for their current and ideal body using sliders on a 3-Dimensional avatar. Physical measurements of corresponding body parts, in cm, were collected for reference. We evaluated regional differences in BID using proportional z-scores to generate statistical body maps, and multivariate analysis of covariance to assess perceptual discrepancies for current body, ideal body, and body dissatisfaction. The AN group demonstrated greater regional perceptual inaccuracy for their current body than HC, greater discrepancies between their current and ideal body, and higher body dissatisfaction than HCs. AN body concerns localized disproportionately to the chest and lower abdomen. The number of body concerns and perceptual inaccuracy for individual body parts was strongly associated with Eating Disorder Examination Questionnaire (Global EDE-Q) scores across both groups. Somatomap demonstrated feasibility to capture multidimensional aspects of BID. Several implicit measures were significantly associated with illness severity, suggesting potential utility for identifying objective BID markers.
Clinical and microbiological factors predicting outcomes of nonfermenting gram-negative bacilli peritonitis in peritoneal dialysis
Authors: dos Santos Ana Claudia Moro Lima , Hernandes Rodrigo Tavanelli , Montelli Augusto Cezar , Monteiro Aydir Cecília Marinho , Barbosa Thais Alves , Camargo Carlos Henrique , Ferreira Adriano Martison , Mondelli Alessandro Lia , de Lourdes Ribeiro de Souza da Cunh Maria , Barretti Pasqual
Published: June 2021

Peritonitis due to gram-negative bacilli (GNB), particularly nonfermenting GNB (NF-GNB), is a serious complication of peritoneal dialysis with a low resolution rate. Beyond the patient’s condition, microbiological properties such as antimicrobial resistance, biofilm production and other virulence factors can explain the poor outcomes. This study aimed to evaluate the influence of patient condition, microbiological characteristics, including biofilm production, and treatment on peritonitis outcome. We reviewed the records of 62 index episodes caused by NF-GNB that occurred between 1997 and 2015 in our center. The etiologies were species of Pseudomonas (51.6%), Acinetobacter (32.2%), and other NF-GNB (16.1%). There was a high (72.9%) proportion of biofilm producer lineages. The in vitro susceptibility rate of Pseudomonas spp. to amikacin, ciprofloxacin, and ceftazidime was significantly greater than that of Acinetobacter spp. and other species; however, there was a similar low resolution rate (< 45%) among the episodes attributable to them. Preexisting exit-site infection was independently associated with nonresolution. No other factor, including biofilm production, was associated with the outcome. The higher in vitro susceptibility of Pseudomonas compared to other NF-GNB that presented a similar resolution rate suggests that bacterial virulence factors such as biofilms can act in concert, thereby worsening the outcome.
The effects of mechanical noise bandwidth on balance across flat and compliant surfaces
Authors: Khor Jeshaiah Zhen Syuen , Gopalai Alpha Agape , Lan Boon Leong , Gouwanda Darwin , Ahmad Siti Anom
Published: June 2021

Although the application of sub-sensory mechanical noise to the soles of the feet has been shown to enhance balance, there has been no study on how the bandwidth of the noise affects balance. Here, we report a single-blind randomized controlled study on the effects of a narrow and wide bandwidth mechanical noise on healthy young subjects’ sway during quiet standing on firm and compliant surfaces. For the firm surface, there was no improvement in balance for both bandwidths—this may be because the young subjects could already balance near-optimally or optimally on the surface by themselves. For the compliant surface, balance improved with the introduction of wide but not narrow bandwidth noise, and balance is improved for wide compared to narrow bandwidth noise. This could be explained using a simple model, which suggests that adding noise to a sub-threshold pressure stimulus results in markedly different frequency of nerve impulse transmitted to the brain for the narrow and wide bandwidth noise—the frequency is negligible for the former but significantly higher for the latter. Our results suggest that if a person’s standing balance is not optimal (for example, due to aging), it could be improved by applying a wide bandwidth noise to the feet.
Serum free culture for the expansion and study of type 2 innate lymphoid cells
Authors: de Lucía Finkel Pablo , Sherwood Christopher , Saranchova Iryna , Xia Wenjing , Munro Lonna , Pfeifer Cheryl G. , Piret James M. , Jefferies Wilfred A.
Published: June 2021

Type 2 innate lymphoid cells (ILC2s) were discovered approximately ten years ago and their clinical relevance is gaining greater importance. However, their successful isolation from mammalian tissues and in vitro culture and expansion continues to pose challenges. This is partly due to their scarcity compared to other leukocyte populations, but also because our current knowledge of ILC2 biology is incomplete. This study is focused on ST2+ IL-25Rlo lung resident ILC2s and demonstrate for the first time a methodology allowing mouse type 2 innate lymphoid cells to be cultured, and their numbers expanded in serum-free medium supplemented with Interleukins IL-33, IL-2, IL-7 and TSLP. The procedures described methods to isolate ILC2s and support their growth for up to a week while maintaining their phenotype. During this time, they significantly expand from low to high cell concentrations. Furthermore, for the first time, sub-cultures of primary ILC2 purifications in larger 24- and 6-well plates were undertaken in order to compare their growth in other media. In culture, ILC2s had doubling times of 21 h, a growth rate of 0.032 h−1 and could be sub-cultured in early or late phases of exponential growth. These studies form the basis for expanding ILC2 populations that will facilitate the study and potential applications of these rare cells under defined, serum-free conditions.
Leisure-time, occupational, and commuting physical activity and the risk of chronic kidney disease in a working population
Authors: Yamamoto Shohei , Inoue Yosuke , Kuwahara Keisuke , Miki Takako , Nakagawa Tohru , Honda Toru , Yamamoto Shuichiro , Hayashi Takeshi , Mizoue Tetsuya
Published: June 2021

Physical activity has been linked to a lower risk of chronic kidney disease (CKD); however, evidence on the relationship between domain-specific physical activity and CKD is scarce. This study aimed to examine the risk of CKD in relation to leisure-time, occupational, and commuting physical activities in a large occupational cohort in Japan. Participants were 17,331 workers (20–65 years old) without CKD and were followed-up for a maximum period of 13 years. Incident CKD was defined as an estimated glomerular filtration rate of < 60 mL/min/1.73 m2 and/or proteinuria determined using the dipstick test. The Cox proportional hazards models were used to examine the associations. During 147,752 person-years of follow-up, 4013 participants developed CKD. Workers who were standing or walking at work and those who were fairly active at work had adjusted hazard ratios of 0.88 (95% confidence interval 0.86–0.96) and 0.89 (95% confidence interval 0.78–1.02), respectively, for developing CKD than sedentary workers. Leisure-time physical activity and walking for commute were not associated with CKD risk. Our findings suggest that occupational, but not leisure-time and commuting physical activities, is associated with a lower CKD risk.
The Komagataeibacter europaeus GqqA is the prototype of a novel bifunctional N-Acyl-homoserine lactone acylase with prephenate dehydratase activity
Authors: Werner Nadine , Petersen Katrin , Vollstedt Christel , Garcia Pablo Perez , Chow Jennifer , Ferrer Manuel , Fernandez-Lopez Laura , Falke Sven , Perbandt Markus , Hinrichs Winfried , Betzel Christian , Streit Wolfgang R.
Published: June 2021

Previously, we reported the isolation of a quorum quenching protein (QQ), designated GqqA, from Komagataeibacter europaeus CECT 8546 that is highly homologous to prephenate dehydratases (PDT) (Valera et al. in Microb Cell Fact 15, 88. https://doi.org/10.1186/s12934-016-0482-y, 2016). GqqA strongly interfered with N-acyl-homoserine lactone (AHL) quorum sensing signals from Gram-negative bacteria and affected biofilm formation in its native host strain Komagataeibacter europaeus. Here we present and discuss data identifying GqqA as a novel acylase. ESI–MS–MS data showed unambiguously that GqqA hydrolyzes the amide bond of the acyl side-chain of AHL molecules, but not the lactone ring. Consistent with this observation the protein sequence does not carry a conserved Zn2+ binding motif, known to be essential for metal-dependent lactonases, but in fact harboring the typical periplasmatic binding protein domain (PBP domain), acting as catalytic domain. We report structural details for the native structure at 2.5 Å resolution and for a truncated GqqA structure at 1.7 Å. The structures obtained highlight that GqqA acts as a dimer and complementary docking studies indicate that the lactone ring of the substrate binds within a cleft of the PBP domain and interacts with polar residues Y16, S17 and T174. The biochemical and phylogenetic analyses imply that GqqA represents the first member of a novel type of QQ family enzymes.
Prediction of caregiver quality of life in amyotrophic lateral sclerosis using explainable machine learning
Authors: Antoniadi Anna Markella , Galvin Miriam , Heverin Mark , Hardiman Orla , Mooney Catherine
Published: June 2021

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative, fatal and currently incurable disease. People with ALS need support from informal caregivers due to the motor and cognitive decline caused by the disease. This study aims to identify caregivers whose quality of life (QoL) may be impacted as a result of caring for a person with ALS. In this study, we worked towards the identification of the predictors of a caregiver’s QoL in addition to the development of a model for clinical use to alert clinicians when a caregiver is at risk of experiencing low QoL. The data were collected through the Irish ALS Registry and via interviews on several topics with 90 patient and caregiver pairs at three time-points. The McGill QoL questionnaire was used to assess caregiver QoL—the MQoL Single Item Score measures the overall QoL and was selected as the outcome of interest in this work. The caregiver’s existential QoL and burden, as well as the patient’s depression and employment before the onset of symptoms were the features that had the highest impact in predicting caregiver quality of life. A small subset of features that could be easy to collect was used to develop a second model to use it in a clinical setting. The most predictive features for that model were the weekly caregiving duties, age and health of the caregiver, as well as the patient’s physical functioning and age of onset.
Colloidal density control with Bessel–Gauss beams
Authors: Acevedo Cristian Hernando , Wu Ruitao , Miller J. Keith , Johnson Eric G. , Dogariu Aristide
Published: June 2021

Optical manipulation of colloidal systems is of high interest for both fundamental studies and practical applications. It has been shown that optically induced thermophoresis and nonlinear interactions can significantly affect the properties of dense colloidal media. However, macroscopic scale phenomena can also be generated at thermal equilibrium. Here, we demonstrate that steady-state variations of particle density can be created over large, three-dimensional regions by appropriately structured external optical fields. We prove analytically and experimentally that an optical vortex beam can dynamically control the spatial density of microscopic particles along the direction of its propagation. We show that these artificial steady-states can be generated at will and can be maintained indefinitely, which can be beneficial for applications such as path clearing and mass transportation.
Author Correction: Low vector competence in sylvatic mosquitoes limits Zika virus to initiate an enzootic cycle in South America
Authors: Fernandes Rosilainy S. , Bersot Maria I. , Castro Marcia G. , Telleria Erich Loza , Ferreira-de-Brito Anielly , Raphael Lidiane M. , Bonaldo Myrna C. , Lourenço-de-Oliveira Ricardo
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Large scale self-assembly of plasmonic nanoparticles on deformed graphene templates
Authors: Gole Matthew T. , Yin Zhewen , Wang Michael Cai , Lin Wayne , Zhou Ziran , Leem Juyoung , Takekuma Satoshi , Murphy Catherine J. , Nam SungWoo
Published: June 2021

Hierarchical heterostructures of two-dimensional (2D) nanomaterials are versatile platforms for nanoscale optoelectronics. Further coupling of these 2D materials with plasmonic nanostructures, especially in non-close-packed morphologies, imparts new metastructural properties such as increased photosensitivity as well as spectral selectivity and range. However, the integration of plasmonic nanoparticles with 2D materials has largely been limited to lithographic patterning and/or undefined deposition of metallic structures. Here we show that colloidally synthesized zero-dimensional (0D) gold nanoparticles of various sizes can be deterministically self-assembled in highly-ordered, anisotropic, non-close-packed, multi-scale morphologies with templates designed from instability-driven, deformed 2D nanomaterials. The anisotropic plasmonic coupling of the particle arrays exhibits emergent polarization-dependent absorbance in the visible to near-IR regions. Additionally, controllable metasurface arrays of nanoparticles by functionalization with varying polymer brushes modulate the plasmonic coupling between polarization dependent and independent assemblies. This self-assembly method shows potential for bottom-up nanomanufacturing of diverse optoelectronic components and can potentially be adapted to a wide array of nanoscale 0D, 1D, and 2D materials.
Assessing the impact of multiple ultraviolet disinfection cycles on N95 filtering facepiece respirator integrity
Authors: Ontiveros C. Carolina , Sweeney Crystal L. , Smith Christopher , MacIsaac Sean , Bennett Jessica L. , Munoz Sebastian , Stoddart Amina K. , Gagnon Graham A.
Published: June 2021

During the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs) were recommended to protect healthcare workers when providing care to infected patients. Despite their single-use disposable nature, the need to disinfect and repurpose FFRs is paramount during this global emergency. The objectives of this study were to (1) determine if UV treatment has an observable impact on respirator integrity; (2) test the impact of UV treatment on N95 FFR user fit; and (3) test the impact of UV treatment on FFR integrity. Ultraviolet (UV) disinfection was assessed in maintaining N95 FFR integrity. Two models of FFRs were exposed to UV fluences ranging from 0 to 10,000 mJ cm−2 per side and subsequently tested for fit, respirator integrity, and airflow. Inspection of N95 FFRs before and after UV treatment via microscopy methods showed no observable or tactile abnormalities in the integrity of respirator material or straps. Tensile loading tests on UV-treated and untreated respirator straps also demonstrated no impact on breaking strength. Standardized fit test methods showed no compromise in user fit following UV treatment. Evaluation of particle penetration and airflow through N95 FFRs showed no impact on integrity, and average filtration efficiency did not fall below 95% for any of the respirator types or fluence levels. This work provides evidence that UV disinfection does not compromise N95 FFR integrity at UV fluences up to 10,000 mJ cm−2. UV disinfection is a viable treatment option to support healthcare professionals in their strategy against the spread of COVID-19.
Transfer RNA-derived fragments in aging Caenorhabditis elegans originate from abundant homologous gene copies
Authors: Shin GiWon , Koo Hee Jung , Seo Mihwa , Lee Seung-Jae V. , Nam Hong Gil , Jung Gyoo Yeol
Published: June 2021

Small RNAs that originate from transfer RNA (tRNA) species, tRNA-derived fragments (tRFs), play diverse biological functions but little is known for their association with aging. Moreover, biochemical aspects of tRNAs limit discovery of functional tRFs by high throughput sequencing. In particular, genes encoding tRNAs exist as multiple copies throughout genome, and mature tRNAs have various modified bases, contributing to ambiguities for RNA sequencing-based analysis of tRFs. Here, we report age-dependent changes of tRFs in Caenorhabditis elegans. We first analyzed published RNA sequencing data by using a new strategy for tRNA-associated sequencing reads. Our current method used unique mature tRNAs as a reference for the sequence alignment, and properly filtered out false positive enrichment for tRFs. Our analysis successfully distinguished de novo mutation sites from differences among homologous copies, and identified potential RNA modification sites. Overall, the majority of tRFs were upregulated during aging and originated from 5′-ends, which we validated by using Northern blot analysis. Importantly, we revealed that the major source of tRFs upregulated during aging was the tRNAs with abundant gene copy numbers. Our analysis suggests that tRFs are useful biomarkers of aging particularly when they originate from abundant homologous gene copies.
Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
Authors: Brent Mikkel Bo , Thomsen Jesper Skovhus , Brüel Annemarie
Published: June 2021

Glucocorticoids (GCs), such as prednisolone, are widely used to treat inflammatory diseases. Continuously long-term or high dose treatment with GCs is one of the most common causes of secondary osteoporosis and is associated with sarcopenia and increased risk of debilitating osteoporotic fragility fractures. Abaloparatide (ABL) is a potent parathyroid hormone-related peptide analog, which can increase bone mineral density (aBMD), improve trabecular microarchitecture, and increase bone strength. The present study aimed to investigate whether GC excess blunts the osteoanabolic effect of ABL. Sixty 12–13-week-old female RjOrl:SWISS mice were allocated to the following groups: Baseline, Control, ABL, GC, and GC + ABL. ABL was administered as subcutaneous injections (100 μg/kg), while GC was delivered by subcutaneous implantation of a 60-days slow-release prednisolone-pellet (10 mg). The study lasted four weeks. GC induced a substantial reduction in muscle mass, trabecular mineral apposition rate (MAR) and bone formation rate (BFR/BS), and endocortical MAR compared with Control, but did not alter the trabecular microarchitecture or bone strength. In mice not receiving GC, ABL increased aBMD, bone mineral content (BMC), cortical and trabecular microarchitecture, mineralizing surface (MS/BS), MAR, BFR/BS, and bone strength compared with Control. However, when administered concomitantly with GC, the osteoanabolic effect of ABL on BMC, cortical morphology, and cortical bone strength was blunted. In conclusion, at cortical bone sites, the osteoanabolic effect of ABL is generally blunted by short-term GC excess.
The role of anthropogenic disturbance and invasion of yellow crazy ant in a recent decline of land crab population
Authors: Lee Ching-Chen , Chiu Ming-Chung , Shih Chun-Han , Yang Chin-Cheng Scotty , Liu Hung-Chang , Lin Chung-Chi
Published: June 2021

The yellow crazy ant,Anoplolepis gracilipeswas first reported in Kenting National Park, Taiwan, in the 2000s, raising the concern of this invasive ant’s potential effects on the native land crab populations. We investigated the distribution and abundance ofA.gracilipesand its adverse effect on the land crab populations at four land crab hotspots within the park. Our survey results indicated thatA.gracilipeswas widespread and abundant at three of the study sites (Hsiangchiaowan, Shadao, and Natural Spring), while the distribution was much more confined at the fourth site (Houwan). Land crab populations experienced a notable decline at all the study sites except Houwan, indicating an inverse relationship between the population of land crabs and distribution/abundance ofA.gracilipes. Combining the results of visual observations, the decline of land crab populations can be attributed, at least partially, to direct attacks byA.gracilipeson land crabs in their natural habitat and during the breeding migration season. Generalized additive model showed that worker abundance of this ant is associated with human disturbance levels, suggesting that anthropogenic disturbance may have contributed to the decline in land crab populations via promoting the abundance ofA.gracilipes.
Deciphering the constrained total energy expenditure model in humans by associating accelerometer-measured physical activity from wrist and hip
Authors: Fernández-Verdejo Rodrigo , Alcantara Juan M. A. , Galgani Jose E. , Acosta Francisco M. , Migueles Jairo H. , Amaro-Gahete Francisco J. , Labayen Idoia , Ortega Francisco B. , Ruiz Jonatan R.
Published: June 2021

The constrained total energy expenditure (TEE) model posits that progressive increases in physical activity (PA) lead to increases in TEE; but after certain PA threshold, TEE plateaus. Then, a compensatory reduction in the expenditure of non-essential activities constrains the TEE. We hypothesized that high PA levels as locomotion associate with a compensatory attenuation in arm movements. We included 209 adults (64% females, mean [SD] age 32.1 [15.0] years) and 105 children (40% females, age 10.0 [1.1] years). Subjects wore, simultaneously, one accelerometer in the non-dominant wrist and another in the hip for ≥ 4 days. We analyzed the association between wrist-measured (arm movements plus locomotion) and hip-measured PA (locomotion). We also analyzed how the capacity to dissociate arm movements from locomotion influences total PA. In adults, the association between wrist-measured and hip-measured PA was better described by a quadratic than a linear model (Quadratic-R2 = 0.54 vs. Linear-R2 = 0.52; P = 0.003). Above the 80th percentile of hip-measured PA, wrist-measured PA plateaued. In children, there was no evidence that a quadratic model fitted the association between wrist-measured and hip-measured PA better than a linear model (R2 = 0.58 in both models, P = 0.25). In adults and children, those with the highest capacity to dissociate arm movements from locomotion—i.e. higher arm movements for a given locomotion—reached the highest total PA. We conclude that, in adults, elevated locomotion associates with a compensatory reduction in arm movements (probably non-essential fidgeting) that partially explains the constrained TEE model. Subjects with the lowest arm compensation reach the highest total PA.
Deep learning-based estimation of Flory–Huggins parameter of A–B block copolymers from cross-sectional images of phase-separated structures
Authors: Hagita Katsumi , Aoyagi Takeshi , Abe Yuto , Genda Shinya , Honda Takashi
Published: June 2021

In this study, deep learning (DL)-based estimation of the Flory–Huggins χ parameter of A-B diblock copolymers from two-dimensional cross-sectional images of three-dimensional (3D) phase-separated structures were investigated. 3D structures with random networks of phase-separated domains were generated from real-space self-consistent field simulations in the 25–40 χN range for chain lengths (N) of 20 and 40. To confirm that the prepared data can be discriminated using DL, image classification was performed using the VGG-16 network. We comprehensively investigated the performances of the learned networks in the regression problem. The generalization ability was evaluated from independent images with the unlearned χN. We found that, except for large χN values, the standard deviation values were approximately 0.1 and 0.5 for A-component fractions of 0.2 and 0.35, respectively. The images for larger χN values were more difficult to distinguish. In addition, the learning performances for the 4-class problem were comparable to those for the 8-class problem, except when the χN values were large. This information is useful for the analysis of real experimental image data, where the variation of samples is limited.
Structural and functional insights into the mechanism of action of plant borate transporters
Authors: Saouros Savvas , Mohan Thotegowdanapalya C. , Cecchetti Cristina , Lehmann Silke , Barrit Joseph D. , Scull Nicola J. , Simpson Paul , Alguel Yilmaz , Cameron Alexander D. , Jones Alexandra M. E. , Byrne Bernadette
Published: June 2021

Boron has essential roles in plant growth and development. BOR proteins are key in the active uptake and distribution of boron, and regulation of intracellular boron concentrations. However, their mechanism of action remains poorly studied. BOR proteins are homologues of the human SLC4 family of transporters, which includes well studied mammalian transporters such as the human Anion Exchanger 1 (hAE1). Here we generated Arabidopsis thaliana BOR1 (AtBOR1) variants based (i) on known disease causing mutations of hAE1 (S466R, A500R) and (ii) a loss of function mutation (D311A) identified in the yeast BOR protein, ScBOR1p. The AtBOR1 variants express in yeast and localise to the plasma membrane, although both S466R and A500R exhibit lower expression than the WT AtBOR1 and D311A. The D311A, S466R and A500R mutations result in a loss of borate efflux activity in a yeast bor1p knockout strain. A. thaliana plants containing these three individual mutations exhibit substantially decreased growth phenotypes in soil under conditions of low boron. These data confirm an important role for D311 in the function of the protein and show that mutations equivalent to disease-causing mutations in hAE1 have major effects in AtBOR1. We also obtained a low resolution cryo-EM structure of a BOR protein from Oryza sativa, OsBOR3, lacking the 30 C-terminal amino acid residues. This structure confirms the gate and core domain organisation previously observed for related proteins, and is strongly suggestive of an inward facing conformation.
Deletion of the clock gene Period2 (Per2) in glial cells alters mood-related behavior in mice
Authors: Martini Tomaz , Ripperger Jürgen A. , Stalin Jimmy , Kores Andrej , Stumpe Michael , Albrecht Urs
Published: June 2021

The circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, affects not only circadian activity rhythms, but can also modulate feeding and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors, without affecting circadian activity parameters. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 2 (Gat2/Slc6a13) and Dopamine receptor D3 (Drd3) mRNA, and a reduction of glutamate levels in the nucleus accumbens (NAc). Interestingly, neuronal Per2 knock-out also reduces despair, but does not influence anxiety. The change in mood-related behavior is not a result of a defective molecular clock, as glial Bmal1 deletion has no effect on neither despair nor anxiety. Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.