bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudo-Darwinian evolution of physical flows in complex networks
Authors: Berthelot Geoffroy , Tupikina Liubov , Kang Min-Yeong , Sapoval Bernard , Grebenkov Denis S.
Published: September 2020

The evolution of complex transport networks is investigated under three strategies of link removal: random, intentional attack and “Pseudo-Darwinian” strategy. At each evolution step and regarding the selected strategy, one removes either a randomly chosen link, or the link carrying the strongest flux, or the link with the weakest flux, respectively. We study how the network structure and the total flux between randomly chosen source and drain nodes evolve. We discover a universal power-law decrease of the total flux, followed by an abrupt transport collapse. The time of collapse is shown to be determined by the average number of links per node in the initial network, highlighting the importance of this network property for ensuring safe and robust transport against random failures, intentional attacks and maintenance cost optimizations.
Structural analysis of a new carotenoid-binding protein: the C-terminal domain homolog of the OCP
Authors: Dominguez-Martin Maria Agustina , Hammel Michal , Gupta Sayan , Lechno-Yossef Sigal , Sutter Markus , Rosenberg Daniel J. , Chen Yan , Petzold Christopher J. , Ralston Corie Y. , Polívka Tomáš , Kerfeld Cheryl A.
Published: September 2020

The Orange Carotenoid Protein (OCP) is a water-soluble protein that governs photoprotection in many cyanobacteria. The 35 kDa OCP is structurally and functionally modular, consisting of an N-terminal effector domain (NTD) and a C-terminal regulatory domain (CTD); a carotenoid spans the two domains. The CTD is a member of the ubiquitous Nuclear Transport Factor-2 (NTF2) superfamily (pfam02136). With the increasing availability of cyanobacterial genomes, bioinformatic analysis has revealed the existence of a new family of proteins, homologs to the CTD, the C-terminal domain-like carotenoid proteins (CCPs). Here we purify holo-CCP2 directly from cyanobacteria and establish that it natively binds canthaxanthin (CAN). We use small-angle X-ray scattering (SAXS) to characterize the structure of this carotenoprotein in two distinct oligomeric states. A single carotenoid molecule spans the two CCPs in the dimer. Our analysis with X-ray footprinting-mass spectrometry (XFMS) identifies critical residues for carotenoid binding that likely contribute to the extreme red shift (ca. 80 nm) of the absorption maximum of the carotenoid bound by the CCP2 dimer and a further 10 nm shift in the tetramer form. These data provide the first structural description of carotenoid binding by a protein consisting of only an NTF2 domain.
Translation elongation factor 2 depletion by siRNA in mouse liver leads to mTOR-independent translational upregulation of ribosomal protein genes
Authors: Gerashchenko Maxim V. , Nesterchuk Mikhail V. , Smekalova Elena M. , Paulo Joao A. , Kowalski Piotr S. , Akulich Kseniya A. , Bogorad Roman , Dmitriev Sergey E. , Gygi Steven , Zatsepin Timofei , Anderson Daniel G. , Gladyshev Vadim N. , Koteliansky Victor E.
Published: September 2020

Due to breakthroughs in RNAi and genome editing methods in the past decade, it is now easier than ever to study fine details of protein synthesis in animal models. However, most of our understanding of translation comes from unicellular organisms and cultured mammalian cells. In this study, we demonstrate the feasibility of perturbing protein synthesis in a mouse liver by targeting translation elongation factor 2 (eEF2) with RNAi. We were able to achieve over 90% knockdown efficacy and maintain it for 2 weeks effectively slowing down the rate of translation elongation. As the total protein yield declined, both proteomics and ribosome profiling assays showed robust translational upregulation of ribosomal proteins relative to other proteins. Although all these genes bear the TOP regulatory motif, the branch of the mTOR pathway responsible for translation regulation was not activated. Paradoxically, coordinated translational upregulation of ribosomal proteins only occurred in the liver but not in murine cell culture. Thus, the upregulation of ribosomal transcripts likely occurred via passive mTOR-independent mechanisms. Impaired elongation sequesters ribosomes on mRNA and creates a shortage of free ribosomes. This leads to preferential translation of transcripts with high initiation rates such as ribosomal proteins. Furthermore, severe eEF2 shortage reduces the negative impact of positively charged amino acids frequent in ribosomal proteins on ribosome progression.
Roles of the Tol-Pal system in the Type III secretion system and flagella-mediated virulence in enterohemorrhagic Escherichia coli
Authors: Hirakawa Hidetada , Suzue Kazutomo , Takita Ayako , Awazu Chikako , Kurushima Jun , Tomita Haruyoshi
Published: September 2020

The Tol-Pal system is a protein complex that is highly conserved in many gram-negative bacteria. We show here that the Tol-Pal system is associated with the enteric pathogenesis of enterohemorrhagic E. coli (EHEC). Deletion of tolB, which is required for the Tol-Pal system decreased motility, secretion of the Type III secretion system proteins EspA/B, and the ability of bacteria to adhere to and to form attaching and effacing (A/E) lesions in host cells, but the expression level of LEE genes, including espA/B that encode Type III secretion system proteins were not affected. The Citrobacter rodentium, tolB mutant, that is traditionally used to estimate Type III secretion system associated virulence in mice did not cause lethality in mice while it induced anti-bacterial immunity. We also found that the pal mutant, which lacks activity of the Tol-Pal system, exhibited lower motility and EspA/B secretion than the wild-type parent. These combined results indicate that the Tol-Pal system contributes to the virulence of EHEC associated with the Type III secretion system and flagellar activity for infection at enteric sites. This finding provides evidence that the Tol-Pal system may be an effective target for the treatment of infectious diseases caused by pathogenic E. coli.
Multiplex enzyme activity imaging by MALDI-IMS of substrate library conversions
Authors: Klein Oliver , Haeckel Akvile , Reimer Ulf , Nebrich Grit , Schellenberger Eyk
Published: September 2020

Enzymes are fundamental to biological processes and involved in most pathologies. Here we demonstrate the concept of simultaneously mapping multiple enzyme activities (EA) by applying enzyme substrate libraries to tissue sections and analyzing their conversion by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). To that end, we spray-applied a solution of 20 naturally derived peptides that are known substrates for proteases, kinases, and phosphatases to zinc-fixed paraffin tissue sections of mouse kidneys. After enzyme conversion for 5 to 120 min at 37 °C and matrix application, the tissue sections were imaged by MALDI-IMS. We could image incubation time-dependently 16 of the applied substrates with differing signal intensities and 12 masses of expected products. Utilizing inherent enzyme amplification, EA-IMS can become a powerful tool to locally study multiple, potentially even lowly expressed, enzyme activities, networks, and their pharmaceutical modulation. Differences in the substrate detectability highlight the need for future optimizations.
Complex genetic encoding of the hepatitis B virus on-drug persistence
Authors: Thai Hong , Lara James , Xu Xiaojun , Kitrinos Kathryn , Gaggar Anuj , Chan Henry Lik Yuen , Xia Guo-liang , Ganova-Raeva Lilia , Khudyakov Yury
Published: September 2020

Tenofovir disoproxil fumarate (TDF) is one of the nucleotide analogs capable of inhibiting the reverse transcriptase (RT) activity of HIV and hepatitis B virus (HBV). There is no known HBV resistance to TDF. However, detectable variation in duration of HBV persistence in patients on TDF therapy suggests the existence of genetic mechanisms of on-drug persistence that reduce TDF efficacy for some HBV strains without affording actual resistance. Here, the whole genome of intra-host HBV variants (N = 1,288) was sequenced from patients with rapid (RR, N = 5) and slow response (SR, N = 5) to TDF. Association of HBV genomic and protein polymorphic sites to RR and SR was assessed using phylogenetic analysis and Bayesian network methods. We show that, in difference to resistance to nucleotide analogs, which is mainly associated with few specific mutations in RT, the HBV on-TDF persistence is defined by genetic variations across the entire HBV genome. Analysis of the inferred 3D-structures indicates no difference in affinity of TDF binding by RT encoded by intra-host HBV variants that rapidly decline or persist in presence of TDF. This finding suggests that effectiveness of TDF recognition and binding does not contribute significantly to on-drug persistence. Differences in patterns of genetic associations to TDF response between HBV genotypes B and C and lack of a single pattern of mutations among intra-host variants sensitive to TDF indicate a complex genetic encoding of the trait. We hypothesize that there are many genetic mechanisms of on-drug persistence, which are differentially available to HBV strains. These pervasive mechanisms are insufficient to prevent viral inhibition completely but may contribute significantly to robustness of actual resistance. On-drug persistence may reduce the overall effectiveness of therapy and should be considered for development of more potent drugs.
Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma
Authors: Cubillos-Zapata Carolina , Martínez-García Miguel Ángel , Díaz-García Elena , Jaureguizar Ana , Campos-Rodríguez Francisco , Sánchez-de-la-Torre Manuel , Nagore Eduardo , Martorell-Calatayud Antonio , Blasco Luis Hernández , Pastor Esther , Abad-Capa Jorge , Montserrat Josep María , Cabriada-Nuño Valentín , Cano-Pumarega Irene , Corral-Peñafiel Jaime , Arias Eva , Mediano Olga , Somoza-González María , Dalmau-Arias Joan , Almendros Isaac , Farré Ramón , López-Collazo Eduardo , Gozal David , García-Río Francisco
Published: September 2020

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients.
A protein-coated micro-sucker patch inspired by octopus for adhesion in wet conditions
Authors: Meloni Gabriella , Tricinci Omar , Degl’Innocenti Andrea , Mazzolai Barbara
Published: September 2020

In medical robotics, micromanipulation becomes particularly challenging in the presence of blood and secretions. Nature offers many examples of adhesion strategies, which can be divided into two macro-categories: morphological adjustments and chemical adaptations. This paper analyzes how two successful specializations from different marine animals can converge into a single biomedical device usable in moist environments. Taking inspiration from the morphology of the octopus sucker and the chemistry of mussel secretions, we developed a protein-coated octopus-inspired micro-sucker device that retains in moist conditions about half of the adhesion it shows in dry environments. From a robotic perspective, this study emphasizes the advantages of taking inspiration from specialized natural solutions to optimize standard robotic designs.
A modified protocol of Capture-C allows affordable and flexible high-resolution promoter interactome analysis
Authors: Golov Arkadiy K. , Abashkin Dmitrii A. , Kondratyev Nikolay V. , Razin Sergey V. , Gavrilov Alexey A. , Golimbet Vera E.
Published: September 2020

Large-scale epigenomic projects have mapped hundreds of thousands of potential regulatory sites in the human genome, but only a small proportion of these elements are proximal to transcription start sites. It is believed that the majority of these sequences are remote promoter-activating genomic sites scattered within several hundreds of kilobases from their cognate promoters and referred to as enhancers. It is still unclear what principles, aside from relative closeness in the linear genome, determine which promoter(s) is controlled by a given enhancer; however, this understanding is of great fundamental and clinical relevance. In recent years, C-methods (chromosome conformation capture-based methods) have become a powerful tool for the identification of enhancer–promoter spatial contacts that, in most cases, reflect their functional link. Here, we describe a new hybridisation-based promoter Capture-C protocol that makes use of biotinylated dsDNA probes generated by PCR from a custom pool of long oligonucleotides. The described protocol allows high-resolution promoter interactome description, providing a flexible and cost-effective alternative to the existing promoter Capture-C modifications. Based on the obtained data, we propose several tips on probe design that could potentially improve the results of future experiments.
Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array
Authors: Jiman Ahmad A. , Ratze David C. , Welle Elissa J. , Patel Paras R. , Richie Julianna M. , Bottorff Elizabeth C. , Seymour John P. , Chestek Cynthia A. , Bruns Tim M.
Published: September 2020

Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8–9 µm in diameter, 150–250 µm in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1–91.7 µV and signal-to-noise ratios of 2.0–8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7–4.4 m/s) and efferent (0.7–8.8 m/s) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.
Conditional effects of gaze on automatic imitation: the role of autistic traits
Authors: Trilla Irene , Wnendt Hannah , Dziobek Isabel
Published: September 2020

Establishing direct gaze has been shown to enhance the tendency to automatically imitate the other person’s actions, an effect that seems to be reduced in autism. Most previous studies, however, used experimental tasks that may have confounded the measurement of automatic imitation with spatial compatibility effects. This calls into question whether gaze cues regulate automatic imitation, or instead affect domain-general processes of response inhibition. Using a task that disentangled imitative from spatial compatibility effects, the current study re-examined the role of autistic traits on the modulation of automatic imitation by direct and averted gaze cues. While our results do not provide evidence for an overall significant influence of gaze on neither automatic imitation nor spatial compatibility, autistic traits were predictive of a reduced inhibition of imitative behaviour following averted gaze. Nonetheless, exploratory analyses suggested that the observed modulation by autistic traits may actually be better explained by the effects of concomitant social anxiety symptoms. In addition, the ethnicity of the imitated agent was identified as another potential modulator of the gaze effects on automatic imitation. Overall, our findings highlight the contextual nature of automatic imitation, but call for a reconsideration of the role of gaze on imitative behaviour.
A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014
Authors: Nishimura Yoshito , Harada Ko , Koyama Toshihiro , Hagiya Hideharu , Otsuka Fumio
Published: September 2020

In the era of hyper-ageing, Creutzfeldt–Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005–2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4–5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7–8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.
Injectable pre-cultured tissue modules catalyze the formation of extensive functional microvasculature in vivo
Authors: Friend Nicole E. , Rioja Ana Y. , Kong Yen P. , Beamish Jeffrey A. , Hong Xiaowei , Habif Julia C. , Bezenah Jonathan R. , Deng Cheri X. , Stegemann Jan P. , Putnam Andrew J.
Published: September 2020

Revascularization of ischemic tissues is a major barrier to restoring tissue function in many pathologies. Delivery of pro-angiogenic factors has shown some benefit, but it is difficult to recapitulate the complex set of factors required to form stable vasculature. Cell-based therapies and pre-vascularized tissues have shown promise, but the former require time for vascular assembly in situ while the latter require invasive surgery to implant vascularized scaffolds. Here, we developed cell-laden fibrin microbeads that can be pre-cultured to form primitive vascular networks within the modular structures. These microbeads can be delivered in a minimally invasive manner and form functional microvasculature in vivo. Microbeads containing endothelial cells and stromal fibroblasts were pre-cultured for 3 days in vitro and then injected within a fibrin matrix into subcutaneous pockets on the dorsal flanks of SCID mice. Vessels deployed from these pre-cultured microbeads formed functional connections to host vasculature within 3 days and exhibited extensive, mature vessel coverage after 7 days in vivo. Cellular microbeads showed vascularization potential comparable to bulk cellular hydrogels in this pilot study. Furthermore, our findings highlight some potentially advantageous characteristics of pre-cultured microbeads, such as volume preservation and vascular network distribution, which may be beneficial for treating ischemic diseases.
Stability and robustness of asymptotic autocatalytic systems
Authors: Yun-Cárcamo Sohyoun , Carrasco Sebastián , Rogan José , Correa-Burrows Paulina , Valdivia Juan Alejandro
Published: September 2020

Here, we address the consequences of the extension in the space of a simple model of a system that is closed to efficient causation: the (M,R)-system model. To do so, we use a diffusion term to describe the collective motion of the nutrients’ concentration across the compartmentalized space that defines the organism. We show that the non-trivial stable steady state remains despite such generalization, as long as the system is small enough to deal with the transport of the precursors to feed the entire protocell and dispose of a sufficient concentration of it in its surroundings. Such consideration explains the emergence of a bifurcation with two parameters that we characterize. Finally, we show that the robustness of the system under catastrophic losses of catalysts also remains, preserving the original’s model character.
Higher visit-to-visit total cholesterol variability is associated with lower cognitive function among middle-aged and elderly Chinese men
Authors: Hua Jianian , Qiao Yanan , Ke Chaofu , Shen Yueping
Published: September 2020

To examine the prospective associations between total cholesterol (TC) variability and cognitive function in a large sample of Chinese participants aged 45 years and above. A total of 6,377 people who participated in the China Health and Retirement Longitudinal Study (CHARLS) were included. TC variability was defined as the intra-individual standard deviation over two blood tests in CHARLS 2011 and 2015 (Wave 1 and Wave 3). Cognitive function was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status (TICS). Multivariate linear regression models (MRLMs) and generalized estimating equation (GEE) were used to investigate associations between TC variability and cognitive scores. After adjusting for potential confounders, male participants with higher visit-to-visit TC variability showed lower global cognition scores (β = − 0.71, P < 0.001). After further adjustment for baseline cognition, the association remained statistically significant (β = − 0.68, P < 0.001). The domains with declines were focused on episodic memory (β = − 0.22, P = 0.026) and TICS (β = − 0.44, P = 0.004). However, these associations were not found in women (β = − 0.10, P = 0.623). For men, the rates of decline in global cognition increased by 0.14 (β = − 0.14, P = 0.009) units per year while TC variability increased by 1 mmol/L. For males, higher visit-to-visit TC variability correlated with lower cognitive function and an increased rate of decreases in memory. More attention should be paid to cognitive decline in males with high TC variability, and particularly, on decreases in memory, calculation, attention and orientation.
Osmolytes dynamically regulate mutant Huntingtin aggregation and CREB function in Huntington’s disease cell models
Authors: Aravindan Shreyaas , Chen Samantha , Choudhry Hannaan , Molfetta Celine , Chen Kuang Yu , Liu Alice Y. C.
Published: September 2020

Osmolytes are organic solutes that change the protein folding landscape shifting the equilibrium towards the folded state. Herein, we use osmolytes to probe the structuring and aggregation of the intrinsically disordered mutant Huntingtin (mHtt) vis-a-vis the pathogenicity of mHtt on transcription factor function and cell survival. Using an inducible PC12 cell model of Huntington’s disease (HD), we show that stabilizing polyol osmolytes drive the aggregation of Htt103QExon1-EGFP from a diffuse ensemble into inclusion bodies (IBs), whereas the destabilizing osmolyte urea does not. This effect of stabilizing osmolytes is innate, generic, countered by urea, and unaffected by HSP70 and HSC70 knockdown. A qualitatively similar result of osmolyte-induced mHtt IB formation is observed in a conditionally immortalized striatal neuron model of HD, and IB formation correlates with improved survival under stress. Increased expression of diffuse mHtt sequesters the CREB transcription factor to repress CREB-reporter gene activity. This repression is mitigated either by stabilizing osmolytes, which deplete diffuse mHtt or by urea, which negates protein–protein interaction. Our results show that stabilizing polyol osmolytes promote mHtt aggregation, alleviate CREB dysfunction, and promote survival under stress to support the hypothesis that lower molecular weight entities of disease protein are relevant pathogenic species in neurodegeneration.
The S-nitrosylation of parkin attenuated the ubiquitination of divalent metal transporter 1 in MPP+-treated SH-SY5Y cells
Authors: Zhong Yanmin , Li Xin , Du Xixun , Bi Mingxia , Ma Fengtong , Xie Junxia , Jiang Hong
Published: September 2020

Abnormal iron accumulation caused by elevated levels of divalent metal transporter 1 (DMT1) contributes to progressive neurodegeneration in Parkinson's disease (PD). Parkin is a E3 ubiquitin ligase for the ubiquitination of DMT1. S-nitrosylated parkin (SNO-parkin) is commonly observed in PD. However, the effects of S-nitrosylation on the E3 ubiquitin ligase activity of parkin for the ubiquitination of DMT1 in PD are largely unknown. To elucidate the role of S-nitrosylated parkin and DMT1 in PD, SH-SY5Y cells were transfected with parkin, being treated with S-nitrosoglutathione (GSNO) and 1-methyl-4-phenylpyridinium (MPP+). The results showed increased levels of oxidized nitric oxide (NO) and S-nitrosylated parkin after the treatment of GSNO and MPP+ in parkin-transfected cells. Consistently, increased levels of DMT1, iron uptake and cell viability were observed. Interestingly, inhibition of S-nitrosylated parkin reduced the level of DMT1. Further, S-nitrosylation of parkin significantly inhibited the ubiquitination of DMT1. When HEK293T cells were transfected with plasmid of parkin with single site mutation (Cys241A, Cys260A, Cys323A), ubiquitination of DMT1 was also inhibited. However, the cells cotransfected with plasmids containing all three mutations, GSNO treatment did not affect the ubiquitination of DMT1. The expression of SNO-parkin and DMT1 protein in substantia nigra increased significantly gradually after 2 h, 4 h and 24 h with MPTP injection. These results indicate that the S-nitrosylation of parkin inhibits its E3 ubiquitin ligase activity for the ubiquitination of DMT1, which contributes to iron accumulation and degenerative process in PD. Targeted S-nitrosylation could provide a potential therapeutic strategy against PD.
Optokinetic stimulation induces vertical vergence, possibly through a non-visual pathway
Authors: Wibble Tobias , Pansell Tony
Published: September 2020

Vertical vergence is generally associated with one of three mechanisms: vestibular activation during a head tilt, induced by vertical visual disparity, or as a by-product of ocular torsion. However, vertical vergence can also be induced by seemingly unrelated visual conditions, such as optokinetic rotations. This study aims to investigate the effect of vision on this latter form of vertical vergence. Eight subjects (4m/4f) viewed a visual scene in head erect position in two different viewing conditions (monocular and binocular). The scene, containing white lines angled at 45° against a black background, was projected at an eye-screen distance of 2 m, and rotated 28° at an acceleration of 56°/s2. Eye movements were recorded using a Chronos Eye-Tracker, and eye occlusions were carried out by placing an infrared-translucent cover in front of the left eye during monocular viewing. Results revealed vergence amplitudes during binocular viewing to be significantly lower than those seen for monocular conditions (p = 0.003), while torsion remained unaffected. This indicates that vertical vergence to optokinetic stimulation, though visually induced, is visually suppressed during binocular viewing. Considering that vertical vergence is generally viewed as a vestibular signal, the findings may reflect a visually induced activation of a vestibular pathway.
Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy
Authors: Yamashita Satoshi , Hattori Naoko , Fujii Satoshi , Yamaguchi Takeshi , Takahashi Masato , Hozumi Yasuo , Kogawa Takahiro , El-Omar Omar , Liu Yu-Yu , Arai Nobuaki , Mori Akiko , Higashimoto Hiroko , Ushijima Toshikazu , Mukai Hirofumi
Published: September 2020

HER2-positive breast cancers that achieve pathological complete response (pCR) after HER2-directed therapy consistently have good survival. We previously identified HSD17B4 methylation as a marker for pCR by methylation screening. Here, we aimed to identify a new marker by conducting a multi-omics analysis of materials prepared by laser capture microdissection, and adding 71 new samples. In the screening set (n = 36), mutations, methylation, and expression were analyzed by targeted sequencing, Infinium 450 K, and expression microarray, respectively, and 15 genes were identified as differentially expressed and eight genomic regions as differentially methylated between cancer samples with and without pCR. In a validation set (n = 47), one gene showed differential expression, and one region had differential methylation. Further, in the re-validation set (n = 55), all new samples, only HSD17B4 methylation was significantly different. The HSD17B4 methylation was at the transcriptional start site of its major variant, and was associated with its silencing. HSD17B4 was highly expressed in the vast majority of human cancers, and its methylation was present only in breast cancers and one lymphoblastic leukemia cell line. A combination of estrogen receptor-negative status and HSD17B4 methylation showed a positive predictive value of 80.0%. During HER2-directed neoadjuvant therapy, HSD17B4 methylation was the most reliable marker to monitor response to the therapy. These results showed that HSD17B4 methylation is a candidate predictive and response marker of HER2-positive breast cancer to HER2-directed therapy.
Relationship between domains of physical activity and cardiac autonomic modulation in adults: a cross-sectional study
Authors: Tebar William R. , Ritti-Dias Raphael M. , Mota Jorge , Farah Breno Q. , Saraiva Bruna T. C. , Damato Tatiana M. M. , Delfino Leandro D. , Aguilar Beatriz A. S. , dos Santos Amanda B. , Silva Stefany C. B. , Vanderlei Luiz Carlos M. , Christofaro Diego G. D.
Published: September 2020

This study aimed to analyze the relationship of physical activity in different domains with cardiac autonomic modulation in adults. A sample of 252 adults was randomly selected, with mean age of 42.1 (± 16.5) years, being 58% of women. Cardiac autonomic modulation was assessed through indexes of heart rate variability in time (SDNN, RMSSD) and frequency (LF, HF) domains for linear method, and by Poincaré plot for non-linear method (SD1, SD2 components). Domains of PA (occupation, sport, leisure time/commuting, and total) were assessed by Baecke’s questionnaire. Variables of age, gender, socioeconomic status (questionnaire) and body mass index (objectively measures) were covariates. Occupational PA was positively related to LF (β = 2.39, 95% CI 0.24; 4.54), sports PA was positively related to SDNN (β = 3.26, 95% CI 0.18; 7.05), RMSSD (β = 4.07, 95% CI 0.31; 7.85), and SD1 (β = 2.85, 95% CI 0.11; 5.81), and leisure time/commuting PA was positively related to SDNN (β = 3.36, 95% CI 0.28; 6.70) and RMSSD (β = 3.53, 95% CI 0.46; 7.52) indexes. Total PA was related to RMSSD (β = 1.70, 95% CI 0.04; 3.72). Sports, leisure time/commuting, and total PA were related to higher parasympathetic modulation, while occupational PA was related to higher sympathetic modulation to the heart in adults.
CMOS-compatible synaptic transistor gated by chitosan electrolyte-Ta2O5 hybrid electric double layer
Authors: Min Shin-Yi , Cho Won-Ju
Published: September 2020

This study proposes a hybrid electric double layer (EDL) with complementary metal-oxide semiconductor (CMOS) process compatibility by stacking a chitosan electrolyte and a Ta2O5 high-k dielectric thin film. Bio-inspired synaptic transistors with excellent electrical stability were fabricated using the proposed hybrid EDL for the gate dielectric layer. The Ta2O5 high-k dielectric layer with high chemical resistance, thermal stability, and mechanical strength enables CMOS-compatible patterning processes on biocompatible organic polymer chitosan electrolytes. This technique achieved ion-conduction from the chitosan electrolyte to the In-Ga-Zn oxide (IGZO) channel layer. The on/off current ratio, subthreshold voltage swing, and the field-effect mobility of the fabricated IGZO EDL transistors (EDLTs) exhibited excellent electrical properties of 1.80 × 107, 96 mV/dec, and 3.73 cm2/V·s, respectively. A resistor-loaded inverter was constructed by connecting an IGZO EDLT with a load resistor (400 MΩ) in series. This demonstrated good inverter action and responded to the square-wave input signals. Synaptic behaviours such as the hysteresis window and excitatory post-synaptic current (EPSC) variations were evaluated for different DC gate voltage sweep ranges and different AC gate spike stimuli, respectively. Therefore, the proposed organic–inorganic hybrid EDL is expected to be useful for implementing an extremely compact neural architecture system.
Synchronicities that shape the perception of joint action
Authors: McEllin Luke , Knoblich Günther , Sebanz Natalie
Published: September 2020

In joint performances spanning from jazz improvisation to soccer, expert performers synchronize their movements in ways that novices cannot. Particularly, experts can align the velocity profiles of their movements in order to achieve synchrony on a fine-grained time scale, compared to novices who can only synchronize the duration of their movement intervals. This study investigated how experts’ ability to engage in velocity-based synchrony affects observers’ perception of coordination and their aesthetic experience of joint performances. Participants observed two moving dots on a screen and were told that these reflect the hand movements of two performers engaging in joint improvisation. The dots were animated to reflect the velocity-based synchrony characteristic of expert performance (in terms of jitter of the velocity profile: Experiment 1, or through aligning sharpness of the velocity profile: Experiment 2) or contained only interval-based synchrony. Performances containing velocity-based synchrony were judged as more coordinated with performers rated as liking each other more, and were rated as more beautiful, providing observers with a stronger aesthetic experience. These findings demonstrate that subtle timing cues fundamentally shape the experience of watching joint actions, directly influencing how beautiful and enjoyable we find these interactions, as well as our perception of the relationship between co-actors.
Polyol and sugar osmolytes can shorten protein hydrogen bonds to modulate function
Authors: Li Jingwen , Chen Jingfei , An Liaoyuan , Yuan Xiaoxiang , Yao Lishan
Published: September 2020

Polyol and sugar osmolytes are commonly used in therapeutic protein formulations. How they may affect protein structure and function is an important question. In this work, through NMR measurements, we show that glycerol and sorbitol (polyols), as well as glucose (sugar), can shorten protein backbone hydrogen bonds. The hydrogen bond shortening is also captured by molecular dynamics simulations, which suggest a hydrogen bond competition mechanism. Specifically, osmolytes weaken hydrogen bonds between the protein and solvent to strengthen those within the protein. Although the hydrogen bond change is small, with the average experimental cross hydrogen bond3hJNC′coupling of two proteins GB3 and TTHA increased by ~ 0.01 Hz by the three osmolytes (160 g/L), its effect on protein function should not be overlooked. This is exemplified by the PDZ3−peptide binding where several intermolecular hydrogen bonds are formed and osmolytes shift the equilibrium towards the bound state.
Latest Pliocene Northern Hemisphere glaciation amplified by intensified Atlantic meridional overturning circulation
Authors: Hayashi Tatsuya , Yamanaka Toshiro , Hikasa Yuki , Sato Masahiko , Kuwahara Yoshihiro , Ohno Masao
Published: September 2020

The global climate has been dominated by glacial–interglacial variations since the intensification of Northern Hemisphere glaciation 2.7 million years ago. Although the Atlantic meridional overturning circulation has exerted strong influence on recent climatic changes, there is controversy over its influence on Northern Hemisphere glaciation because its deep limb, North Atlantic Deep Water, was thought to have weakened. Here we show that Northern Hemisphere glaciation was amplified by the intensified Atlantic meridional overturning circulation, based on multi-proxy records from the subpolar North Atlantic. We found that the Iceland–Scotland Overflow Water, contributing North Atlantic Deep Water, significantly increased after 2.7 million years ago and was actively maintained even in early stages of individual glacials, in contrast with late stages when it drastically decreased because of iceberg melting. Probably, the active Nordic Seas overturning during the early stages of glacials facilitated the efficient growth of ice sheets and amplified glacial oscillations.
Cigarette smoke-induced changes in the murine vocal folds: a Raman spectroscopic observation
Authors: Erickson-DiRenzo Elizabeth , Singh S. P. , Martinez Joshua D. , Sanchez Santiago E. , Easwaran Meena , Valdez Tulio A.
Published: September 2020

Raman spectroscopic methods are being projected as novel tools to study the early invisible molecular level changes in the vocal folds in a label-free manner.
Photon-upconversion barcode for monitoring an enzymatic reaction with a fluorescence reporter in droplet microfluidics
Authors: Hlaváček Antonín , Křivánková Jana , Pizúrová Naděžda , Václavek Tomáš , Foret František
Published: September 2020

Photon-upconversion barcodes are compatible with simultaneous fluorescence detection.
Small molecule induced toxic human-IAPP species characterized by NMR
Authors: Cox Sarah J. , Rodriguez Camargo Diana C. , Lee Young-Ho , Dubini Romeo C. A. , Rovó Petra , Ivanova Magdalena I. , Padmini Vediappen , Reif Bernd , Ramamoorthy Ayyalusamy
Published: September 2020

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed.
Construction of a C@MoS2@C sandwiched heterostructure for accelerating the pH-universal hydrogen evolution reaction
Authors: Mei Yan , Li Ting-Ting , Qian Jinjie , Li Hongwei , Wu Miao , Zheng Yue-Qing
Published: September 2020

The sandwich structured PCN@MoS2@C composite shows remarkable electrocatalytic performance towards the hydrogen evolution reaction over a wide pH range.
Dual-template assembled hierarchical Cu-SSZ-13: morphology evolution, crystal growth and stable high-temperature selective catalytic reduction performance
Authors: Liu Li , Chen Zhiqiang , Qu Hongxia , Yuan Jiaxi , Yu Mahong , Xie Huifang , Zhong Qin
Published: September 2020

Assembled hierarchical Cu-SSZ-13 zeolites maintained excellent high-temperature activity due to mesoporous inhibition of ammonia oxidation.
A hydrogen-bonding structure in self-formed nanodroplets of water adsorbed on amorphous silica revealed via surface-selective vibrational spectroscopy
Authors: Urashima Shu-hei , Uchida Taku , Yui Hiroharu
Published: September 2020

Water adsorption onto a material surface is known to change macroscopic surface properties such as wettability and friction coefficient.
Exploring the candidates for a new protein folding – cross-α amyloid – in available protein databases
Authors: Das Mitradip , Bhargava B. L.
Published: September 2020

Prediction of the formation of cross-α amyloid, a new type of protein folding, from the primary structure of the protein using a novel algorithm.
Thermochemical unification of molecular descriptors to predict radical hydrogen abstraction with low computational cost
Authors: Nolte Tom M. , Nauser Thomas , Gubler Lorenz , Hendriks A. Jan , Peijnenburg Willie J. G. M.
Published: September 2020

Parametrization of transition-state effects via cheap quantum-chemical descriptors allows fast and accurate prediction of hydrogen abstraction rate constants.
To probe the binding pathway of a selective compound (D089-0563) to c-MYC Pu24 G-quadruplex using free ligand binding simulations and Markov state model analysis
Authors: Chen Brian , Fountain Griffin , Sullivan Holli-Joi , Paradis Nicholas , Wu Chun
Published: September 2020

D089-0563 is a highly promising anti-cancer compound that selectively binds the transcription-silencing G-quadruplex element (Pu27) at the promoter region of the human c-MYC oncogene; however, its binding mechanism remains elusive.
UV-photoelectron spectroscopy of stable radicals: the electronic structure of planar Blatter radicals as materials for organic electronics
Authors: Hande Aniket A. , Darrigan Clovis , Bartos Paulina , Baylère Patrick , Pietrzak Anna , Kaszyński Piotr , Chrostowska Anna
Published: September 2020

The electronic structure of a series of C(10)-substituted planar Blatter radical derivatives containing H, F, Cl, Br, CN, CF3 and OMe groups was investigated by gas phase UV-PES and results were correlated with solution electrochemical data.
The grain boundary effect on mechanical and electronic transport properties of a striped borophene
Authors: Sun Jie , Leng Jiancai , Zhang Guangping
Published: September 2020

The presence of GBs suppress the transport current.
Correction: Optical and electrical effects of plasmonic nanoparticles in high-efficiency hybrid solar cells
Authors: Fu Wei-Fei , Chen Xiaoqiang , Yang Xi , Wang Ling , Shi Ye , Shi Minmin , Li Han-Ying , Jen Alex K.-Y. , Chen Jun-Wu , Cao Yong , Chen Hong-Zheng
Published: September 2020

Correction for ‘Optical and electrical effects of plasmonic nanoparticles in high-efficiency hybrid solar cells’ by Wei-Fei Fu et al., Phys. Chem. Chem. Phys., 2013, 15, 17105–17111, DOI: 10.1039/C3CP52723A.
Yolk–shell (Cu,Zn)Fe2O4 ferrite nano-microspheres with highly selective triethylamine gas-sensing properties
Authors: Yang Jing , Li Xianliang , Wu Junbiao , Han Yide , Wang Zhuopeng , Zhang Xia , Xu Yan
Published: September 2020

Yolk-shell (Cu,Zn)Fe2O4 nano-microspheres synthesized by a two-step strategy possess high response to triethylamine with excellent selectivity.
An evaluation of source apportionment of fine OC and PM2.5by multiple methods: APHH-Beijing campaigns as a case study
Authors: Xu Jingsha , Srivastava Deepchandra , Wu Xuefang , Hou Siqi , Vu Tuan V. , Liu Di , Sun Yele , Vlachou Athanasia , Moschos Vaios , Salazar Gary , Szidat Sönke , Prévôt André S. H. , Fu Pingqing , Harrison Roy M. , Shi Zongbo
Published: September 2020

This paper reports an evaluation of multiple source apportionment methods for OC and PM2.5.
Biaryl and atropisomeric biaryl aldehyde synthesis by one-step, metal-free benzannulation of aryl enals and propiolates
Authors: Hu Deqing , Yang Lu , Wan Jie-Ping
Published: September 2020

The metal-free benzannulation reactions of alkyl propiolates and aryl enals have been developed for biaryl and atropisomeric biaryl aldehyde synthesis.
Mass spectrometric characteristics and preliminary figures of merit for polyaromatic hydrocarbons via the liquid sampling-atmospheric pressure glow discharge microplasma
Authors: Williams Tyler J. , Bills Jacob R. , Marcus R. Kenneth
Published: September 2020

The versatility of the LS-APGD microplasma is extended beyond elemental and polar molecular species to non-polar, low molecular weight polyaromatic hydrocarbons. Insights into ionization mechanisms are gained, with preliminary LODs determined.
Determining available potassium in soil by laser-induced breakdown spectroscopy combined with cation exchange membrane adsorption
Authors: Fu Xinglan , Zhao Chunjiang , Ma Shixiang , Tian Hongwu , Dong Daming , Li GuangLin
Published: September 2020

Potassium in soil is an essential nutrient for plants.
Selective cell encapsulation, lysis, pico-injection and size-controlled droplet generation using traveling surface acoustic waves in a microfluidic device
Authors: Mutafopulos Kirk , Lu Peter J. , Garry Ryan , Spink Pascal , Weitz David A.
Published: September 2020

We generate traveling surface acoustic waves with an interdigital transducer to create droplets on-demand; encapsulate single cells; lyse cells and immediately encapsulate their contents; and pico-inject new materials into existing droplets.
Folding dynamics of Aβ42 monomer at pH 4.0–7.5 with and without physiological salt conditions – does the β1 or β2 region fold first?
Authors: Xing Xiaofeng , Liu Chengqiang , Yang Huijuan , Nouman Muhammad Fahad , Ai Hongqi
Published: September 2020

The seeding region of Aβ42 monomer is jointly affected by the solution acidity, ionic distribution of the salt, and charged residues.
A facile size tunable one-pot synthesis of dipicolinate@nZVI core–shell nanoparticles: material properties for trace cadmium ion removal
Authors: Rončević Sanda , Nemet Ivan , Zagorec Viktor , Selmani Atiđa
Published: September 2020

Dipicolinic acid capped iron nanoparticles were obtained by a facile one-pot chemical synthesis and the ellipsoidal forms of PDCA@nZVI nanoparticles showed enhanced adsorption of cadmium ions at trace levels.
Enantiomeric separation and molecular docking study of seven imidazole antifungal drugs on a cellulose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase
Authors: Liu Yanru , Cai Liangzhao , Lun Jia , Zhao Min , Guo Xingjie
Published: September 2020

Chiral separation and molecular docking study of seven imidazole antifungal drugs were performed on a cellulose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase (Chiralcel OD-RH).
Bifuran-bridged bisboranes: highly luminescent B-doped oligohetarenes
Authors: Riensch Nicolas Alexander , Fest Maximilian , Fritze Lars , Helbig Andreas , Krummenacher Ivo , Braunschweig Holger , Helten Holger
Published: September 2020

Boron-doping of oligohetarenes – via classical metathesis or silicon/boron exchange routes – led to strongly luminescent and twofold reversibly reducible oligomers.
Structural colouration in the Himalayan monal, hydrophobicity and refractive index modulated sensing
Authors: Rashid Ijaz , Hassan Muhammad Umair , Nazim Muhammad , Elsherif Mohamed , Dou Qian , Hu Debo , Kamran Muhammad , Dai Qing , Butt Haider
Published: September 2020

The Himalayan monal is a bird in the pheasant family, and it is the national bird of Nepal.
Hierarchically self-assembled NiCo2O4 nanopins as a high-performance supercapacitor cathodic material: a morphology controlled study
Authors: Hassanpoor Shahed , Aghely Farzaneh
Published: September 2020

In this study, 3D hierarchically self-assembled NiCo2O4 nanopins were synthesized by a morphology controlled hydrothermal method.
Regiocontrol in the oxidative Heck reaction of indole by ligand-enabled switch of the regioselectivity-determining step
Authors: Wang Yu-Jie , Yuan Chen-Hui , Chu De-Zhao , Jiao Lei
Published: September 2020

Ligand-enabled switch of the regioselectivity-determining step allowed for efficient regiocontrol in the aerobic oxidative Heck reaction of indole.