bluuebunny/crossref_metadata_2025 huggingface dataset:
An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation
Authors: Forte Maurizio , Bianchi Franca , Cotugno Maria , Marchitti Simona , Stanzione Rosita , Maglione Vittorio , Sciarretta Sebastiano , Valenti Valentina , Carnevale Roberto , Versaci Francesco , Frati Giacomo , Volpe Massimo , Rubattu Speranza
Published: October 2021

The mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneously hypertensive rat. Overexpression of UCP2 counteracts the negative effects of high-salt feeding in both animal models. We tested in vitro the ability of UCP2 to stimulate autophagy and mitophagy as a mechanism mediating its protective effects upon high-salt exposure in endothelial and renal tubular cells. UCP2 silencing reduced autophagy and mitophagy, whereas the opposite was true upon UCP2 overexpression. High-salt exposure increased level of reactive oxygen species (ROS), UCP2, autophagy and autophagic flux in both endothelial and renal tubular cells. In contrast, high-salt was unable to induce autophagy and autophagic flux in UCP2-silenced cells, concomitantly with excessive ROS accumulation. The addition of an autophagy inducer, Tat-Beclin 1, rescued the viability of UCP2-silenced cells even when exposed to high-salt. In summary, UCP2 mediated the interaction between high-salt-induced oxidative stress and autophagy to preserve viability of both endothelial and renal tubular cells. In the presence of excessive ROS accumulation (achieved upon UCP2 silencing and high-salt exposure of silenced cells) autophagy was turned off. In this condition, an exogenous autophagy inducer rescued the cellular damage induced by excess ROS level. Our data confirm the protective role of UCP2 toward high-salt-induced vascular and renal injury, and they underscore the role of autophagy/mitophagy as a mechanism counteracting the high-salt-induced oxidative stress damage.
OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice
Authors: Schünke Hannah , Göbel Ulrike , Dikic Ivan , Pasparakis Manolis
Published: October 2021

Linear ubiquitination regulates inflammatory and cell death signalling. Deficiency of the linear ubiquitin chain-specific deubiquitinase, OTULIN, causes OTULIN-related autoinflammatory syndrome (ORAS), a systemic inflammatory pathology affecting multiple organs including the skin. Here we show that mice with epidermis-specific OTULIN deficiency (OTULINE-KO) develop inflammatory skin lesions that are driven by TNFR1 signalling in keratinocytes and require RIPK1 kinase activity. OTULINE-KO mice lacking RIPK3 or MLKL have only very mild skin inflammation, implicating necroptosis as an important etiological mediator. Moreover, combined loss of RIPK3 and FADD fully prevents skin lesion development, showing that apoptosis also contributes to skin inflammation in a redundant function with necroptosis. Finally, MyD88 deficiency suppresses skin lesion development in OTULINE-KO mice, suggesting that toll-like receptor and/or IL-1 signalling are involved in mediating skin inflammation. Thus, OTULIN maintains homeostasis and prevents inflammation in the skin by inhibiting TNFR1-mediated, RIPK1 kinase activity-dependent keratinocyte death and primarily necroptosis.
An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma
Authors: Xu Bo , Tian Lei , Chen Jing , Wang Jing , Ma Rui , Dong Wenjuan , Li Aimin , Zhang Jianying , Antonio Chiocca E. , Kaur Balveen , Feng Mingye , Caligiuri Michael A. , Yu Jianhua
Published: October 2021

Oncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 ‘don’t eat me’ signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.
Supertoroidal light pulses as electromagnetic skyrmions propagating in free space
Authors: Shen Yijie , Hou Yaonan , Papasimakis Nikitas , Zheludev Nikolay I.
Published: October 2021

Topological complex transient electromagnetic fields give access to nontrivial light-matter interactions and provide additional degrees of freedom for information transfer. An important example of such electromagnetic excitations are space-time non-separable single-cycle pulses of toroidal topology, the exact solutions of Maxwell’s equations described by Hellwarth and Nouchi in 1996 and recently observed experimentally. Here we introduce an extended family of electromagnetic excitation, the supertoroidal electromagnetic pulses, in which the Hellwarth-Nouchi pulse is just the simplest member. The supertoroidal pulses exhibit skyrmionic structure of the electromagnetic fields, multiple singularities in the Poynting vector maps and fractal-like distributions of energy backflow. They are of interest for transient light-matter interactions, ultrafast optics, spectroscopy, and toroidal electrodynamics.
Cavity-induced quantum spin liquids
Authors: Chiocchetta Alessio , Kiese Dominik , Zelle Carl Philipp , Piazza Francesco , Diehl Sebastian
Published: October 2021

Quantum spin liquids provide paradigmatic examples of highly entangled quantum states of matter. Frustration is the key mechanism to favor spin liquids over more conventional magnetically ordered states. Here we propose to engineer frustration by exploiting the coupling of quantum magnets to the quantized light of an optical cavity. The interplay between the quantum fluctuations of the electro-magnetic field and the strongly correlated electrons results in a tunable long-range interaction between localized spins. This cavity-induced frustration robustly stabilizes spin liquid states, which occupy an extensive region in the phase diagram spanned by the range and strength of the tailored interaction. This occurs even in originally unfrustrated systems, as we showcase for the Heisenberg model on the square lattice.
Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response
Authors: Gajewska K. A. , Lescesen H. , Ramialison M. , Wagstaff K. M. , Jans D. A.
Published: October 2021

The importin superfamily member Importin-13 is a bidirectional nuclear transporter. To delineate its functional roles, we performed transcriptomic analysis on wild-type and Importin-13-knockout mouse embryonic stem cells, revealing enrichment of differentially expressed genes involved in stress responses and apoptosis regulation. De novo promoter motif analysis on 277 Importin-13-dependent genes responsive to oxidative stress revealed an enrichment of motifs aligned to consensus sites for the transcription factors specificity protein 1, SP1, or Kruppel like factor 4, KLF4. Analysis of embryonic stem cells subjected to oxidative stress revealed that Importin-13-knockout cells were more resistant, with knockdown of SP1 or KLF4 helping protect wild-type embryonic stem cells against stress-induced death. Importin-13 was revealed to bind to SP1 and KLF4 in a cellular context, with a key role in oxidative stress-dependent nuclear export of both transcription factors. The results are integral to understanding stress biology, highlighting the importance of Importin-13 in the stress response.
CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression
Authors: Schneider Enja , Winzer Riekje , Rissiek Anne , Ricklefs Isabell , Meyer-Schwesinger Catherine , Ricklefs Franz L. , Bauche Andreas , Behrends Jochen , Reimer Rudolph , Brenna Santra , Wasielewski Hauke , Lauten Melchior , Rissiek Björn , Puig Berta , Cortesi Filippo , Magnus Tim , Fliegert Ralf , Müller Christa E. , Gagliani Nicola , Tolosa Eva
Published: October 2021

Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.
Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease
Authors: Scortecci Jessica Fernandes , Molday Laurie L. , Curtis Susan B. , Garces Fabian A. , Panwar Pankaj , Van Petegem Filip , Molday Robert S.
Published: October 2021

ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor membranes. Loss-of-function mutations cause Stargardt disease (STGD1), a macular dystrophy associated with severe vision loss. To define the mechanisms underlying substrate binding and STGD1, we determine the cryo-EM structure of ABCA4 in its substrate-free and bound states. The two structures are similar and delineate an elongated protein with the two transmembrane domains (TMD) forming an outward facing conformation, extended and twisted exocytoplasmic domains (ECD), and closely opposed nucleotide binding domains. N-Ret-PE is wedged between the two TMDs and a loop from ECD1 within the lumen leaflet consistent with a lateral access mechanism and is stabilized through hydrophobic and ionic interactions with residues from the TMDs and ECDs. Our studies provide a framework for further elucidating the molecular mechanism associated with lipid transport and disease and developing promising disease interventions.
Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex
Authors: Klug Yoel A. , Deme Justin C. , Corey Robin A. , Renne Mike F. , Stansfeld Phillip J. , Lea Susan M. , Carvalho Pedro
Published: October 2021

Lipid droplets (LDs) are universal lipid storage organelles with a core of neutral lipids, such as triacylglycerols, surrounded by a phospholipid monolayer. This unique architecture is generated during LD biogenesis at endoplasmic reticulum (ER) sites marked by Seipin, a conserved membrane protein mutated in lipodystrophy. Here structural, biochemical and molecular dynamics simulation approaches reveal the mechanism of LD formation by the yeast Seipin Sei1 and its membrane partner Ldb16. We show that Sei1 luminal domain assembles a homooligomeric ring, which, in contrast to other Seipins, is unable to concentrate triacylglycerol. Instead, Sei1 positions Ldb16, which concentrates triacylglycerol within the Sei1 ring through critical hydroxyl residues. Triacylglycerol recruitment to the complex is further promoted by Sei1 transmembrane segments, which also control Ldb16 stability. Thus, we propose that LD assembly by the Sei1/Ldb16 complex, and likely other Seipins, requires sequential triacylglycerol-concentrating steps via distinct elements in the ER membrane and lumen.
A frequency-amplitude coordinator and its optimal energy consumption for biological oscillators
Authors: Qin Bo-Wei , Zhao Lei , Lin Wei
Published: October 2021

Biorhythm including neuron firing and protein-mRNA interaction are fundamental activities with diffusive effect. Their well-balanced spatiotemporal dynamics are beneficial for healthy sustainability. Therefore, calibrating both anomalous frequency and amplitude of biorhythm prevents physiological dysfunctions or diseases. However, many works were devoted to modulate frequency exclusively whereas amplitude is usually ignored, although both quantities are equally significant for coordinating biological functions and outputs. Especially, a feasible method coordinating the two quantities concurrently and precisely is still lacking. Here, for the first time, we propose a universal approach to design a frequency-amplitude coordinator rigorously via dynamical systems tools. We consider both spatial and temporal information. With a single well-designed coordinator, they can be calibrated to desired levels simultaneously and precisely. The practical usefulness and efficacy of our method are demonstrated in representative neuronal and gene regulatory models. We further reveal its fundamental mechanism and optimal energy consumption providing inspiration for biorhythm regulation in future.
Circa-SCOPE: high-throughput live single-cell imaging method for analysis of circadian clock resetting
Authors: Manella Gal , Aizik Dan , Aviram Rona , Golik Marina , Asher Gad
Published: October 2021

Circadian clocks are self-sustained and cell-autonomous oscillators. They respond to various extracellular cues depending on the time-of-day and the signal intensity. Phase Transition Curves (PTCs) are instrumental in uncovering the full repertoire of responses to a given signal. However, the current methodologies for reconstructing PTCs are low-throughput, laborious, and resource- and time-consuming. We report here the development of an efficient and high throughput assay, dubbed Circadian Single-Cell Oscillators PTC Extraction (Circa-SCOPE) for generating high-resolution PTCs. This methodology relies on continuous monitoring of single-cell oscillations to reconstruct a full PTC from a single culture, upon a one-time intervention. Using Circa-SCOPE, we characterize the effects of various pharmacological and blood-borne resetting cues, at high temporal resolution and a wide concentration range. Thus, Circa-SCOPE is a powerful tool for comprehensive analysis and screening for circadian clocks’ resetting cues, and can be valuable for basic as well as translational research.
Human cell based directed evolution of adenine base editors with improved efficiency
Authors: Fu Junhao , Li Qing , Liu Xiaoyu , Tu Tianxiang , Lv Xiujuan , Yin Xidi , Lv Jineng , Song Zongming , Qu Jia , Zhang Jinwei , Li Jinsong , Gu Feng
Published: October 2021

Adenine base editors (ABE) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. However, the low activity of ABE at certain sites remains a major bottleneck that precludes efficacious applications. Here, to address it, we develop a directional screening system in human cells to evolve the deaminase component of the ABE, and identify three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we create a consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibit superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also find that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve user-specified traits in base editors that extend beyond augmented editing activity.
Addressing MRSA infection and antibacterial resistance with peptoid polymers
Authors: Xie Jiayang , Zhou Min , Qian Yuxin , Cong Zihao , Chen Sheng , Zhang Wenjing , Jiang Weinan , Dai Chengzhi , Shao Ning , Ji Zhemin , Zou Jingcheng , Xiao Ximian , Liu Longqiang , Chen Minzhang , Li Jin , Liu Runhui
Published: October 2021

Methicillin-Resistant Staphylococcus aureus (MRSA) induced infection calls for antibacterial agents that are not prone to antimicrobial resistance. We prepare protease-resistant peptoid polymers with variable C-terminal functional groups using a ring-opening polymerization of N-substituted N-carboxyanhydrides (NNCA), which can provide peptoid polymers easily from the one-pot synthesis. We study the optimal polymer that displays effective activity against MRSA planktonic and persister cells, effective eradication of highly antibiotic-resistant MRSA biofilms, and potent anti-infectious performance in vivo using the wound infection model, the mouse keratitis model, and the mouse peritonitis model. Peptoid polymers show insusceptibility to antimicrobial resistance, which is a prominent merit of these antimicrobial agents. The low cost, convenient synthesis and structure diversity of peptoid polymers, the superior antimicrobial performance and therapeutic potential in treating MRSA infection altogether imply great potential of peptoid polymers as promising antibacterial agents in treating MRSA infection and alleviating antibiotic resistance.
High-spatial and colourimetric imaging of histone modifications in single senescent cells using plasmonic nanoprobes
Authors: An Hyun Ji , Kim Yun , Chang Soojeong , Kim Hakchun , Song Jihwan , Park Hyunsung , Choi Inhee
Published: October 2021

Histones are closely related to the state of chromatin, and epigenetic modification of their tail results in regulation in cells. Therefore, developing various analytical tools to map the changes in position and distribution of histone modifications is helpful in studying underlying mechanisms. Herein, we propose a high-spatial and colourimetric imaging method using plasmonic nanoparticles as probes to visualize heterochromatin histone markers in a single nucleus. We visualized the reorganization between repressive histone markers, H3K9me3 and H3K27me3, caused by oncogene-induced senescence based on the scattering colours and spectral shift of plasmonic nanoprobes to longer wavelengths using their distance-dependent coupling effect. The measured scattering profiles were correlated with the computation results simulating the scattering spectra according to the arrangements and distances among the plasmonic nanoprobes. The plasmonic nanoprobe-based high-spatial hyperspectral imaging provides an advanced way to study the dynamics of histone modifications for predicting the progression of diseases or senescence.
Symmetry-aware recursive image similarity exploration for materials microscopy
Authors: Nguyen Tri N. M. , Guo Yichen , Qin Shuyu , Frew Kylie S. , Xu Ruijuan , Agar Joshua C.
Published: October 2021

In pursuit of scientific discovery, vast collections of unstructured structural and functional images are acquired; however, only an infinitesimally small fraction of this data is rigorously analyzed, with an even smaller fraction ever being published. One method to accelerate scientific discovery is to extract more insight from costly scientific experiments already conducted. Unfortunately, data from scientific experiments tend only to be accessible by the originator who knows the experiments and directives. Moreover, there are no robust methods to search unstructured databases of images to deduce correlations and insight. Here, we develop a machine learning approach to create image similarity projections to search unstructured image databases. To improve these projections, we develop and train a model to include symmetry-aware features. As an exemplar, we use a set of 25,133 piezoresponse force microscopy images collected on diverse materials systems over five years. We demonstrate how this tool can be used for interactive recursive image searching and exploration, highlighting structural similarities at various length scales. This tool justifies continued investment in federated scientific databases with standardized metadata schemas where the combination of filtering and recursive interactive searching can uncover synthesis-structure-property relations. We provide a customizable open-source package (https://github.com/m3-learning/Recursive_Symmetry_Aware_Materials_Microstructure_Explorer) of this interactive tool for researchers to use with their data.
Power-optimal, stabilized entangling gate between trapped-ion qubits
Authors: Blümel Reinhold , Grzesiak Nikodem , Pisenti Neal , Wright Kenneth , Nam Yunseong
Published: October 2021

To achieve scalable quantum computing, improving entangling-gate fidelity and its implementation efficiency are of utmost importance. We present here a linear method to construct provably power-optimal entangling gates on an arbitrary pair of qubits on a trapped-ion quantum computer. This method leverages simultaneous modulation of amplitude, frequency, and phase of the beams that illuminate the ions and, unlike the state of the art, does not require any search in the parameter space. The linear method is extensible, enabling stabilization against external parameter fluctuations to an arbitrary order at a cost linear in the order. We implement and demonstrate the power-optimal, stabilized gate on a trapped-ion quantum computer.
Ferromagnetism out of charge fluctuation of strongly correlated electrons in κ-(BEDT-TTF)2Hg(SCN)2Br
Authors: Yamashita Minoru , Sugiura Shiori , Ueda Akira , Dekura Shun , Terashima Taichi , Uji Shinya , Sunairi Yoshiya , Mori Hatsumi , Zhilyaeva Elena I. , Torunova Svetlana A. , Lyubovskaya Rimma N. , Drichko Natalia , Hotta Chisa
Published: October 2021

We perform magnetic susceptibility and magnetic torque measurements on the organic κ-(BEDT-TTF)2Hg(SCN)2Br, which is recently suggested to host an exotic quantum dipole-liquid in its low-temperature insulating phase. Below the metal-insulator (MI) transition temperature, the magnetic susceptibility follows a Curie–Weiss law with a positive Curie–Weiss temperature, and a particular $$M\propto \sqrt{H}$$

M
∝

H

curve is observed. The emergent ferromagnetically interacting spins amount to about 1/6 of the full spin moment of localized charges. Taking account of the possible inhomogeneous quasi-charge-order that forms a dipole-liquid, we construct a model of antiferromagnetically interacting spin chains in two adjacent charge-ordered domains, which are coupled via fluctuating charges on a Mott-dimer at the boundary. We find that the charge fluctuations can draw a weak ferromagnetic moment out of the spin singlet domains.
Metformin accelerates zebrafish heart regeneration by inducing autophagy
Authors: Xie Fangjing , Xu Shisan , Lu Yingying , Wong Kin Fung , Sun Lei , Hasan Kazi Md Mahmudul , Ma Alvin C. H. , Tse Gary , Manno Sinai H. C. , Tian Li , Yue Jianbo , Cheng Shuk Han
Published: October 2021

Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans, and demonstrated that autophagy was significantly induced in the injured area. Through a systematic evaluation of the multiple cell types related to cardiac regeneration, we found that metformin enhanced the autophagic flux and improved epicardial, endocardial and vascular endothelial regeneration, accelerated transient collagen deposition and resolution, and induced cardiomyocyte proliferation. Whereas, when the autophagic flux was blocked, then all these processes were delayed. We also showed that metformin transiently enhanced the systolic function of the heart. Taken together, our results indicate that autophagy is positively involved in the metformin-induced acceleration of heart regeneration in zebrafish and suggest that this well-known diabetic drug has clinical value for the prevention and amelioration of myocardial infarction.
Step detection and energy expenditure at different speeds by three accelerometers in a controlled environment
Authors: Stenbäck Ville , Leppäluoto Juhani , Leskelä Nelli , Viitala Linda , Vihriälä Erkki , Gagnon Dominique , Tulppo Mikko , Herzig Karl-Heinz
Published: October 2021

Physical activity (PA) is one of the most efficient ways to prevent obesity and its associated diseases worldwide. In the USA, less than 10% of the adult population were able to meet the PA recommendations when accelerometers were used to assess PA habituation. Accelerometers significantly differ from each other in step recognition and do not reveal raw data. The aim of our study was to compare a novel accelerometer, Sartorio Xelometer, which enables to gather raw data, with existing accelerometers ActiGraph GT3X+ and activPAL in terms of step detection and energy expenditure estimation accuracy. 53 healthy subjects were divided into 2 cohorts (cohort 1 optimization; cohort 2 validation) and wore 3 accelerometers and performed an exercise routine consisting of the following speeds: 1.5, 3, 4.5, 9 and 10.5 km/h (6 km/h for 2nd cohort included). Data from optimization cohort was used to optimize Sartorio step detection algorithm. Actual taken steps were recorded with a video camera and energy expenditure (EE) was measured. To observe the similarity between video and accelerometer step counts, paired samples t test and intraclass correlation were used separately for step counts in different speeds and for total counts as well as EE estimations. In speeds of 1.5, 3, 4.5, 6, 9 and 10.5 km/h mean absolute percentage error (MAPE) % were 8.1, 3.5, 4.3, 4.2, 3.1 and 7.8 for the Xelometer, respectively (after optimization). For ActiGraph GT3X+ the MAPE-% were 96.93 (87.4), 34.69 (23.1), 2.13 (2.3), 1.96 (2.6) and 2.99 (3.8), respectively and for activPAL 6.55 (5.6), 1.59 (0.6), 0.81 (1.1), 10.60 (10.3) and 15.76 (13.8), respectively. Significant intraclass correlations were observed with Xelometer estimates and actual steps in all speeds. Xelometer estimated the EE with a MAPE-% of 30.3, activPAL and ActiGraph GT3X+ with MAPE percentages of 20.5 and 24.3, respectively. The Xelometer is a valid device for assessing step counts at different gait speeds. MAPE is different at different speeds, which is of importance when assessing the PA in obese subjects and elderly. EE estimates of all three devices were found to be inaccurate when compared with indirect calorimetry.
A topology-preserving dimensionality reduction method for single-cell RNA-seq data using graph autoencoder
Authors: Luo Zixiang , Xu Chenyu , Zhang Zhen , Jin Wenfei
Published: October 2021

Dimensionality reduction is crucial for the visualization and interpretation of the high-dimensional single-cell RNA sequencing (scRNA-seq) data. However, preserving topological structure among cells to low dimensional space remains a challenge. Here, we present the single-cell graph autoencoder (scGAE), a dimensionality reduction method that preserves topological structure in scRNA-seq data. scGAE builds a cell graph and uses a multitask-oriented graph autoencoder to preserve topological structure information and feature information in scRNA-seq data simultaneously. We further extended scGAE for scRNA-seq data visualization, clustering, and trajectory inference. Analyses of simulated data showed that scGAE accurately reconstructs developmental trajectory and separates discrete cell clusters under different scenarios, outperforming recently developed deep learning methods. Furthermore, implementation of scGAE on empirical data showed scGAE provided novel insights into cell developmental lineages and preserved inter-cluster distances.
Sexual dimorphism in size and shape of the head in the sea snake Emydocephalus annulatus (Hydrophiinae, Elapidae)
Authors: Shine Richard , Goiran Claire
Published: October 2021

In snakes, divergence in head size between the sexes has been interpreted as an adaptation to intersexual niche divergence. By overcoming gape-limitation, a larger head enables snakes of one sex to ingest larger prey items. Under this hypothesis, we do not expect a species that consumes only tiny prey items to exhibit sex differences in relative head size, or to show empirical links between relative head size and fitness-relevant traits such as growth and fecundity. Our field studies on the sea snake Emydocephalus annulatus falsify these predictions. Although these snakes feed exclusively on fish eggs, the heads of female snakes are longer and wider than those of males at the same body length. Individuals with wider heads grew more rapidly, reproduced more often, and produced larger litters. Thus, head shape can affect fitness and can diverge between the sexes even without gape-limitation. Head size and shape may facilitate other aspects of feeding (such as the ability to scrape eggs off coral) and locomotion (hydrodynamics); and a smaller head may advantage the sex that is more mobile, and that obtains its prey in narrow crevices rather than in more exposed situations (i.e., males).
Comsolic solution of an elliptic cylindrical compressible fluid flow
Authors: Hussain Azad , Hassan Ali , Mdallal Qasem Al , Ahmad Hijaz , Sherif El-Sayed M. , Rehman Aysha , Arshad Mubashar
Published: October 2021

In this article, the primary focus is to investigate the heat transfer effects with viscous compressible laminar flow in the permeable elliptic cylinder. The Reynolds number is kept 100 for flow to be laminar. The physics of heat transfer is selected to be coupled with the laminar flow. The results for particular step-size time for Velocity distribution, pressure profile, temperature profile, isothermal temperature contours, and drag coefficient have been analyzed. Mesh has been generated through COMSOL, mesh entities have been elaborated statistically. The maximum and minimum velocity profile is observed at the elliptical cylinder’s walls and upper, lower boundary respectively. The maximum velocity observed is 2.22 m/s. Pressure profile around elliptic corners is found maximum, distinct patterns are observed even under the influence of applied heat. Temperature is observed maximum at walls but it gradually increases as moving from the upper boundary towards the lower boundary. The isothermal contour patterns are observed maximum near the walls, drag coefficient of gradual decrease is observed. COMSOL multi-physics is utilized for mathematical modeling of problems and the Backward-Differentiation-Formula has been exploited to handle problems numerically. The results will help greatly to understand the characterizations of viscous fluids and in industries like air furnaces and automobile cooling systems.
Simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N′-nitrosonornicotine, and cotinine by liquid chromatography-tandem mass-spectrometry
Authors: Nikam Sampada S. , Gurjar Murari , Singhavi Hitesh , Patil Anand , Singh Arjun , Villalta Peter , Chaturvedi Pankaj , Khariwala Samir S. , Gota Vikram , Stepanov Irina
Published: October 2021

Biomarkers of exposure to harmful tobacco constituents are key tools for identifying individuals at risk and developing interventions and tobacco control measures. However, tobacco biomarker studies are scarce in many parts of the world with high prevalence of tobacco use. Our goal was to establish a robust method for simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N′-nitrosonornicotine (NNN), and cotinine at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) in Mumbai, India. These biomarkers are validated measures of exposure to the carcinogenic tobacco nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and NNN and the addictive alkaloid nicotine, respectively. The established method is characterized by excellent accuracy, linearity, and precision, and was successfully applied to the analysis of 15 smokeless tobacco (SLT) users and 15 non-users of tobacco recruited in Mumbai. This is the first report of establishment of such procedure in a laboratory in India, which offers the first in-country capacity for research on tobacco carcinogenesis in Indian SLT users.
Social media and deep learning capture the aesthetic quality of the landscape
Authors: Havinga Ilan , Marcos Diego , Bogaart Patrick W. , Hein Lars , Tuia Devis
Published: October 2021

Peoples’ recreation and well-being are closely related to their aesthetic enjoyment of the landscape. Ecosystem service (ES) assessments record the aesthetic contributions of landscapes to peoples’ well-being in support of sustainable policy goals. However, the survey methods available to measure these contributions restrict modelling at large scales. As a result, most studies rely on environmental indicator models but these do not incorporate peoples’ actual use of the landscape. Now, social media has emerged as a rich new source of information to understand human-nature interactions while advances in deep learning have enabled large-scale analysis of the imagery uploaded to these platforms. In this study, we test the accuracy of Flickr and deep learning-based models of landscape quality using a crowdsourced survey in Great Britain. We find that this novel modelling approach generates a strong and comparable level of accuracy versus an indicator model and, in combination, captures additional aesthetic information. At the same time, social media provides a direct measure of individuals’ aesthetic enjoyment, a point of view inaccessible to indicator models, as well as a greater independence of the scale of measurement and insights into how peoples’ appreciation of the landscape changes over time. Our results show how social media and deep learning can support significant advances in modelling the aesthetic contributions of ecosystems for ES assessments.
Design of a system for controlling a levitating sphere in superfluid 3He at extremely low temperatures
Authors: Arrayás Manuel , Trueba José L. , Uriarte Carlos , Zmeev Dmitry E.
Published: October 2021

We present a new mechanical probe to study the properties of superfluid 3He at microkelvin temperatures down to 100 μK. The setup consists of a set of coils for levitating a superconducting sphere and controlling its motion in a wide variety of regimes. In particular, the realisation of motion of a levitating body at a uniform velocity presents both an experimental challenge and a promising direction into the study of the edge states in topological superfluid 3He-B. We include the theoretical study of the device stability and simulations to illustrate the capabilities of the control system.
GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients
Authors: Mahmoud Rania H. , Hefzy Enas Mamdouh , Shaker Olfat G. , Ahmed Tarek I. , Abdelghaffar Noha K. , Hassan Essam A. , Ibrahim Amal A. , Ali Doaa Y. , Mohamed Mohamed M. , Abdelaleem Omayma O.
Published: October 2021

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.
Concordance analysis of microsatellite instability status between polymerase chain reaction based testing and next generation sequencing for solid tumors
Authors: Shimozaki Keitaro , Hayashi Hideyuki , Tanishima Shigeki , Horie Sara , Chida Akihiko , Tsugaru Kai , Togasaki Kazuhiro , Kawasaki Kenta , Aimono Eriko , Hirata Kenro , Nishihara Hiroshi , Kanai Takanori , Hamamoto Yasuo
Published: October 2021

Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, a polymerase chain reaction (PCR)-based method, was the first tumor-agnostic companion diagnostic to detect MSI status in MSI-H solid tumors. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available; however, its real-world concordance with PCR-based testing of MSI-H/dMMR remains to be investigated. The co-primary end points included the positive and negative predictive values of MSI-H/dMMR. A retrospective analysis of 80 patients who had undergone both MSI testing and NGS between July 2015 and March 2021 was conducted. Five patients were confirmed to have MSI-H in both examinations. Among the 75 patients diagnosed as microsatellite stable (MSS) by PCR-based testing, one with pancreatic cancer was diagnosed as having MSI-H after NGS. One patient with pancreatic cancer was diagnosed as having MSS in both tests was found to have a mutation in MLH1 by NGS, which was confirmed as dMMR by IHC staining. NGS had positive and negative predictive values of 100% (5/5) and 98.7% (74/75), respectively, for MSI-H. The concordance between NGS and PCR-based testing was 98.8% (79/80). Thus, NGS can be useful for evaluating MSI/MMR status in clinical practice and can be an important alternative method for detecting MSI-H/dMMR in the future.
Resonant scanning design and control for fast spatial sampling
Authors: Sun Zhanghao , Quan Ronald , Solgaard Olav
Published: October 2021

Two-dimensional, resonant scanners have been utilized in a large variety of imaging modules due to their compact form, low power consumption, large angular range, and high speed. However, resonant scanners have problems with non-optimal and inflexible scanning patterns and inherent phase uncertainty, which limit practical applications. Here we propose methods for optimized design and control of the scanning trajectory of two-dimensional resonant scanners under various physical constraints, including high frame-rate and limited actuation amplitude. First, we propose an analytical design rule for uniform spatial sampling. We demonstrate theoretically and experimentally that by expanding the design space, the proposed designs outperform previous designs in terms of scanning range and fill factor. Second, we show that we can create flexible scanning patterns that allow focusing on user-defined Regions-of-Interest (RoI) by modulation of the scanning parameters. The scanning parameters are found by an optimization algorithm. In simulations, we demonstrate the benefits of these designs with standard metrics and higher-level computer vision tasks (LiDAR odometry and 3D object detection). Finally, we experimentally implement and verify both unmodulated and modulated scanning modes using a two-dimensional, resonant MEMS scanner. Central to the implementations is high bandwidth monitoring of the phase of the angular scans in both dimensions. This task is carried out with a position-sensitive photodetector combined with high-bandwidth electronics, enabling fast spatial sampling at $$\sim 100$$

∼
100

Hz frame-rate.
Diattenuation and retardance signature of plasmonic gold nanorods in turbid media revealed by Mueller matrix polarimetry
Authors: Ray Subir Kumar , Ghosh Nirmalya , Vitkin Alex
Published: October 2021

Plasmonic gold nanorods (GNRs) are finding increasing use in biomedicine due to their unique electromagnetic properties, optical contrast enhancement and biocompatibility; they also show promise as polarization contrast agents. However, quantification of their polarization-enhancing properties within heterogeneous turbid media remains challenging. We report on polarization response in controlled tissue phantoms consisting of dielectric microsphere scatterers with varying admixtures of GRNs. Experimental Mueller matrix measurements and polarization sensitive Monte-Carlo simulations show excellent agreement. Despite the GNRs’ 3D random orientation and distribution in the strong multiply scattering background, significant linear diattenuation and retardance were observed. These exclusive measurable characteristics of GNRs suggest their potential uses as contrast enhancers for polarimetric assessment of turbid biological tissue.
Interpretation of the adsorption of metals on quartz crystal based-macromolecule via advanced modeling of equilibrium isotherms
Authors: Aouaini Fatma , Ben Yahia Mohamed , I. Alrebdi Haifa , A. Alothman Miysoon
Published: October 2021

In this article, new insights about the metals-porphyrin complexes are proved by analyzing the zinc, nickel and chromium adsorption process over the well-known porphyrin macromolecule. The use of the quartz crystal microbalance (QCM) apparatus allows the control of the complexation systems’ experimental adsorption data operating at four temperatures. The experimental results and the physical models reveal that the zinc and nickel complexation processes are to be examined using the mono layer adsorption model. While, the double layer model describes the interaction between the chromium compound and the porphyrin. Actually, the three metals are shown to be adsorbed by a multi-docking process in the physicochemical description. The endothermic character of the investigated processes is shown through the appropriate data of the principal parameter adsorbent sites’ density. Hence, several porphyrin sites are exclusively stimulated at high temperature. The parameters of van del Waals, depicting the influences of the lateral interactions, explain the nickel isotherms down trend. The chemical bonds are shown to be carried out between the zinc and the porphyrin through the calculated adsorption energies. Considering the thermodynamic study, and referring to the configurational entropy and the free enthalpy, it is to be noted that the disorder peak of the three mechanisms is reached when the equilibrium concentration is equal to the energetic parameters’ values for each system. The nickel enthalpy revealed for high concentration that the adsorbates’ lateral interactions disapproved the nickel chloride adsorption. The free enthalpy trends, that observed two stability states of the chromium compound, confirmed the chromium double layer mechanism.
Expansion and application of dye tracers for measuring solid food intake and food preference in Drosophila
Authors: Shell Brandon C. , Luo Yuan , Pletcher Scott , Grotewiel Mike
Published: October 2021

The Drosophila model is used to investigate the effects of diet on physiology as well as the effects of genetic pathways, neural systems and environment on feeding behavior. We previously showed that Blue 1 works well as a dye tracer to track consumption of agar-based media in Drosophila in a method called Con-Ex. Here, we describe Orange 4 as a novel dye for use in Con-Ex studies that expands the utility of this method. Con-Ex experiments using Orange 4 detect the predicted effects of starvation, mating status, strain, and sex on feeding behavior in flies. Orange 4 is consumed and excreted into vials linearly with time in Con-Ex experiments, the number of replicates required to detect differences between groups when using Orange 4 is comparable to that for Blue 1, and excretion of the dye reflects the volume of consumed dye. In food preference studies using Orange 4 and Blue 1 as a dye pair, flies decreased their intake of food laced with the aversive tastants caffeine and NaCl as determined using Con-Ex or a more recently described modification called EX-Q. Our results indicate that Orange 4 is suitable for Con-Ex experiments, has comparable utility to Blue 1 in Con-Ex studies, and can be paired with Blue 1 to assess food preference via both Con-Ex and EX-Q.
Predicting cognitive impairment in outpatients with epilepsy using machine learning techniques
Authors: Lin Feng , Han Jiarui , Xue Teng , Lin Jilan , Chen Shenggen , Zhu Chaofeng , Lin Han , Chen Xianyang , Lin Wanhui , Huang Huapin
Published: October 2021

Many studies report predictions for cognitive function but there are few predictions in epileptic patients; therefore, we established a workflow to efficiently predict outcomes of both the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in outpatients with epilepsy. Data from 441 outpatients with epilepsy were included; of these, 433 patients met the 12 clinical characteristic criteria and were divided into training (n = 304) and experimental (n = 129) groups. After descriptive statistics were analyzed, cross-validation was used to select the optimal model. The random forest (RF) algorithm was combined with the redundancy analysis (RDA) algorithm; then, optimal feature selection and resampling were carried out after removing linear redundancy information. The features that contributed more to multiple outcomes were selected. Finally, the external traceability of the model was evaluated using the follow-up data. The RF algorithm was the best prediction model for both MMSE and MoCA outcomes. Finally, seven markers were screened by overlapping the top ten important features for MMSE ranked by RF modeling, those ranked for MoCA ranked by RF modeling, and those for both assessments ranked by RDA. The optimal combination of features were namely, sex, age, age of onset, seizure frequency, brain MRI abnormalities, epileptiform discharge in EEG and usage of drugs. which was the most efficient in predicting outcomes of MMSE, MoCA, and both assessments.