bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib
Authors: Chen Wei , Li Zhouqi , Liu Hao , Jiang Sujing , Wang Guannan , Sun Lifeng , Li Jun , Wang Xiaochen , Yu Shaojun , Huang Jianjin , Dong Ying
Published: March 2020

Gastrointestinal stromal tumors (GISTs), the most widespread type of sarcoma, contain driver gene mutations predominantly of receptor tyrosine kinase and platelet-derived growth factor receptor alpha. However, the inevitable development of resistance to imatinib (IM) cannot be fully attributed to secondary driver gene mutations. In this study, we investigated the role of microRNA-30a in sensitization of GIST cells to IM in vivo and in vitro. Higher levels of miR-30a were detected in GIST-T1 cells, which were more sensitive to IM than GIST-882 cells. IM treatment also reduced miR-30a levels, indicating the possible role of miR-30a in GIST IM resistance. Subsequently, miR-30a was confirmed to be an IM sensitizer via a mechanism that was attributed to its involvement in the regulation of cell autophagy. The interaction of miR-30a and autophagy in IM treated GIST cells was found to be linked by beclin-1. Beclin-1 knockdown increased IM sensitivity in GIST cell lines. Finally, miR-30a was confirmed to enhance IM sensitivity of GIST cells in mouse tumor models. Our study provides evidence for the possible role of miR-30a in the emergence of secondary IM resistance in GIST patients, indicating a promising target for overcoming this chemoresistance.
IL28A protein homotetramer structure is required for autolysosomal degradation of HCV-NS5A in vitro
Authors: Ma Yuan-yuan , Li Jian-rui , Peng Zong-gen , Zhang Jing-pu
Published: March 2020

Interferon lambda-2 (IL28A) has a wide antiviral effect with fewer side-effects. Autophagy is a host mechanism to maintain intracellular homeostasis and defends invasion of pathogenic microorganisms. HCV NS5A can disable host defense systems to support HCV replication. Thus, molecular mechanism of interaction among interferon lambda, autophagy, and HCV was concerned and explored in this study. We report that HCV NS5A activated an incomplete autophagy by promoting the autophagic ubiquitylation-like enzymes ATG3, ATG5, ATG7, ATG10, and autophagosome maker LC3B, but blocked autophagy flux; IL28A bound to NS5A at NS5A-ISDR region, and degraded HCV-NS5A by promoting autolysosome formations in HepG2 cells. A software prediction of IL28A protein conformation indicated a potential structure of IL28A homotetramer; the first α-helix of IL28A locates in the interfaces among the four IL28A chains to maintain IL28A homotetrameric conformation. Co-IP and cell immunofluorescence experiments with sequential deletion mutants demonstrate that IL28A preferred a homotetramer conformation to a monomer in the cells; the IL28A homotetramer is positively correlated with autolysosomal degradation of HCV NS5A and the other HCV proteins. Summarily, the first α-helix of IL28A protein is the key domain for maintaining IL28A homotetramer which is required for promoting formation of autolysosomes and degradation of HCV proteins in vitro.
Peroxiredoxin 5 deficiency exacerbates iron overload-induced neuronal death via ER-mediated mitochondrial fission in mouse hippocampus
Authors: Lee Dong Gil , Kam Min Kyoung , Lee Sang-Rae , Lee Hong Jun , Lee Dong-Seok
Published: March 2020

Iron is an essential element for cellular functions, including those of neuronal cells. However, an imbalance of iron homeostasis, such as iron overload, has been observed in several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Iron overload causes neuronal toxicity through mitochondrial fission, dysregulation of Ca2+, ER-stress, and ROS production. Nevertheless, the precise mechanisms between iron-induced oxidative stress and iron toxicity related to mitochondria and endoplasmic reticulum (ER) in vivo are not fully understood. Here, we demonstrate the role of peroxiredoxin 5 (Prx5) in iron overload-induced neurotoxicity using Prx5-deficient mice. Iron concentrations and ROS levels in mice fed a high iron diet were significantly higher in Prx5−/− mice than wildtype (WT) mice. Prx5 deficiency also exacerbated ER-stress and ER-mediated mitochondrial fission via Ca2+/calcineurin-mediated dephosphorylation of Drp1 at Serine 637. Moreover, immunoreactive levels of cleaved caspase3 in the CA3 region of the hippocampus were higher in iron-loaded Prx5−/− mice than WT mice. Furthermore, treatment with N-acetyl-cysteine, a reactive oxygen species (ROS) scavenger, attenuated iron overload-induced hippocampal damage by inhibiting ROS production, ER-stress, and mitochondrial fission in iron-loaded Prx5−/− mice. Therefore, we suggest that iron overload-induced oxidative stress and ER-mediated mitochondrial fission may be essential for understanding iron-mediated neuronal cell death in the hippocampus and that Prx5 may be useful as a novel therapeutic target in the treatment of iron overload-mediated diseases and neurodegenerative diseases.
Context is everything: extrinsic signalling and gain-of-function p53 mutants
Authors: Amelio Ivano , Melino Gerry
Published: March 2020

The TP53 genomic locus is a target of mutational events in at least half of cancers. Despite several decades of study, a full consensus on the relevance of the acquisition of p53 gain-of-function missense mutants has not been reached. Depending on cancer type, type of mutations and other unidentified factors, the relevance for tumour development and progression of the oncogenic signalling directed by p53 mutants might significantly vary, leading to inconsistent observations that have fuelled a long and fierce debate in the field. Here, we discuss how interaction with the microenvironment and stressors might dictate the gain-of-function effects exerted by individual mutants. We report evidence from the most recent literature in support of the context dependency of p53 mutant biology. This perspective article aims to raise a discussion in the field on the relevance that context might have on p53 gain-of-function mutants, assessing whether this should generally be considered a cell non-autonomous process.
Developing a highly efficient hydroxytyrosol whole-cell catalyst by de-bottlenecking rate-limiting steps
Authors: Yao Jun , He Yang , Su Nannan , Bharath Sakshibeedu R. , Tao Yong , Jin Jian-Ming , Chen Wei , Song Haiwei , Tang Shuang-Yan
Published: March 2020

Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, we design an efficient whole-cell catalyst of hydroxytyrosol inEscherichia coliby de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC ofE. colithrough structure-guided modeling and directed evolution. Next, we elucidate the structure of theCorynebacterium glutamicumVanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.
Publisher Correction: Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
Authors: Cuomo Anna S. E. , Seaton Daniel D. , McCarthy Davis J. , Martinez Iker , Bonder Marc Jan , Garcia-Bernardo Jose , Amatya Shradha , Madrigal Pedro , Isaacson Abigail , Buettner Florian , Knights Andrew , Natarajan Kedar Nath ,   HipSci Consortium, Agu Chukwuma A. , Alderton Alex , Danecek Petr , Denton Rachel , Durbin Richard , Gaffney Daniel J. , Goncalves Angela , Halai Reena , Harper Sarah , Kirton Christopher M. , Kolb-Kokocinski Anja , Leha Andreas , McCarthy Shane A. , Memari Yasin , Patel Minal , Birney Ewan , Casale Francesco Paolo , Clarke Laura , Harrison Peter W. , Kilpinen Helena , Streeter Ian , Denovi Davide , Meleckyte Ruta , Moens Natalie , Watt Fiona M. , Ouwehand Willem H. , Lamond Angus I. , Bensaddek Dalila , Beales Philip , Vallier Ludovic , Marioni John C. , Chhatriwala Mariya , Stegle Oliver
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation
Authors: Zhong Yichen , Paudel Bishnu P. , Ryan Daniel P. , Low Jason K. K. , Franck Charlotte , Patel Karishma , Bedward Max J. , Torrado Mario , Payne Richard J. , van Oijen Antoine M. , Mackay Joel P.
Published: March 2020

Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and it is unclear if it is conserved among the four remodeller families. Here we use single-molecule assays to examine the mechanism of action of CHD4, which is part of the least well understood family. We demonstrate that the binding energy for CHD4-nucleosome complex formation—even in the absence of nucleotide—triggers significant conformational changes in DNA at the entry side, effectively priming the system for remodelling. During remodelling, flanking DNA enters the nucleosome in a continuous, gradual manner but exits in concerted 4–6 base-pair steps. This decoupling of entry- and exit-side translocation suggests that ATP-driven movement of entry-side DNA builds up strain inside the nucleosome that is subsequently released at the exit side by DNA expulsion. Based on our work and previous studies, we propose a mechanism for nucleosome sliding.
Size-selective molecular recognition based on a confined DNA molecular sieve using cavity-tunable framework nucleic acids
Authors: Fu Xiaoyi , Ke Guoliang , Peng Fangqi , Hu Xue , Li Jiaqi , Shi Yuyan , Kong Gezhi , Zhang Xiao-Bing , Tan Weihong
Published: March 2020

Size selectivity is an important mechanism for molecular recognition based on the size difference between targets and non-targets. However, rational design of an artificial size-selective molecular recognition system for biological targets in living cells remains challenging. Herein, we construct a DNA molecular sieve for size-selective molecular recognition to improve the biosensing selectivity in living cells. The system consists of functional nucleic acid probes (e.g., DNAzymes, aptamers and molecular beacons) encapsulated into the inner cavity of framework nucleic acid. Thus, small target molecules are able to enter the cavity for efficient molecular recognition, while large molecules are prohibited. The system not only effectively protect probes from nuclease degradation and nonspecific proteins binding, but also successfully realize size-selective discrimination between mature microRNA and precursor microRNA in living cells. Therefore, the DNA molecular sieve provides a simple, general, efficient and controllable approach for size-selective molecular recognition in biomedical studies and clinical diagnoses.
Regulating vesicle bilayer permeability and selectivity via stimuli-triggered polymersome-to-PICsome transition
Authors: Wang Xiaorui , Yao Chenzhi , Zhang Guoying , Liu Shiyong
Published: March 2020

Compared to liposomes, polymersomes of block copolymers (BCPs) possess enhanced stability, along with compromised bilayer permeability. Though polyion complex vesicles (PICsomes) from oppositely charged block polyelectrolytes possess semipermeable bilayers, they are unstable towards physiologically relevant ionic strength and temperature; moreover, permselectivity tuning of PICsomes has remained a challenge. Starting from a single component diblock or triblock precursor, we solve this dilemma by stimuli-triggered chemical reactions within pre-organized BCP vesicles, actuating in situ polymersome-to-PICsome transition and achieving molecular size-selective cargo release at tunable rates. UV light and reductive milieu were utilized to trigger carboxyl decaging and generate ion pairs within hydrophobic polymersome bilayers containing tertiary amines. Contrary to conventional PICsomes, in situ generated ones are highly stable towards extreme pH range (pH 2-12), ionic strength (~3 M NaCl), and elevated temperature (70 °C) due to multivalent ion-pair interactions at high local concentration and cooperative hydrogen bonding interactions of pre-organized carbamate linkages.
Rapid expansion of Treg cells protects from collateral colitis following a viral trigger
Authors: Schorer Michelle , Lambert Katharina , Rakebrandt Nikolas , Rost Felix , Kao Kung-Chi , Yermanos Alexander , Spörri Roman , Oderbolz Josua , Raeber Miro E. , Keller Christian W. , Lünemann Jan D. , Rogler Gerhard , Boyman Onur , Oxenius Annette , Joller Nicole
Published: March 2020

Foxp3+ regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose for autoimmunity, additional environmental triggers, such as viral infections, are usually required to initiate the onset of disease. Here, we show that viral infection with LCMV results in type I IFN-dependent Treg cell loss that is rapidly compensated by the conversion and expansion of Vβ5+ conventional T cells into iTreg cells. Using Vβ5-deficient mice, we show that these Vβ5+ iTreg cells are dispensable for limiting anti-viral immunity. Rather, the delayed replenishment of Treg cells in Vβ5-deficient mice compromises suppression of microbiota-dependent activation of CD8+ T cells, resulting in colitis. Importantly, recovery from clinical symptoms in IBD patients is marked by expansion of the corresponding Vβ2+ Treg population in humans. Collectively, we provide a link between a viral trigger and an impaired Treg cell compartment resulting in the initiation of immune pathology.
A 12-Lead ECG database to identify origins of idiopathic ventricular arrhythmia containing 334 patients
Authors: Zheng Jianwei , Fu Guohua , Anderson Kyle , Chu Huimin , Rakovski Cyril
Published: March 2020

Cardiac catheter ablation has shown the effectiveness of treating the idiopathic premature ventricular complex and ventricular tachycardia. As the most important prerequisite for successful therapy, criteria based on analysis of 12-lead ECGs are employed to reliably speculate the locations of idiopathic ventricular arrhythmia before a subsequent catheter ablation procedure. Among these possible locations, right ventricular outflow tract and left outflow tract are the major ones. We created a new 12-lead ECG database under the auspices of Chapman University and Ningbo First Hospital of Zhejiang University that aims to provide high quality data enabling detection of the distinctions between idiopathic ventricular arrhythmia from right ventricular outflow tract to left ventricular outflow tract. The dataset contains 334 subjects who successfully underwent a catheter ablation procedure that validated the accurate origins of idiopathic ventricular arrhythmia.
Blast resistance gene Pi54 over-expressed in rice to understand its cellular and sub-cellular localization and response to different pathogens
Authors: Singh Jyoti , Gupta Santosh Kumar , Devanna B. N. , Singh Sunil , Upadhyay Avinash , Sharma Tilak R.
Published: March 2020

Rice blast resistance gene, Pi54 provides broad-spectrum resistance against different strains of Magnaporthe oryzae. Understanding the cellular localization of Pi54 protein is an essential step towards deciphering its place of interaction with the cognate Avr-gene. In this study, we investigated the sub-cellular localization of Pi54 with Green Fluorescent Protein (GFP) as a molecular tag through transient and stable expression in onion epidermal cells (Allium cepa) and susceptible japonica cultivar rice Taipei 309 (TP309), respectively. Confocal microscopy based observations of the onion epidermal cells revealed nucleus and cytoplasm specific GFP signals. In the stable transformed rice plants, GFP signal was recorded in the stomata, upper epidermal cells, mesophyll cells, vascular bundle, and walls of bundle sheath and bulliform cells of leaf tissues. These observations were further confirmed by Immunocytochemical studies. Using GFP specific antibodies, it was found that there was sufficient aggregation of GFP::Pi54protein in the cytoplasm of the leaf mesophyll cells and periphery of the epidermal cells. Interestingly, the transgenic lines developed in this study could show a moderate level of resistance to Xanthomonas oryzae and Rhizoctonia solani, the causal agents of the rice bacterial blight and sheath blight diseases, respectively. This study is a first detailed report, which emphasizes the cellular and subcellular distribution of the broad spectrum blast resistance gene Pi54 in rice and the impact of its constitutive expression towards resistance against other fungal and bacterial pathogens of rice.
Contribution of cortical lesions to cognitive impairment in Japanese patients with multiple sclerosis
Authors: Shinoda Koji , Matsushita Takuya , Nakamura Yuri , Masaki Katsuhisa , Sakai Shiori , Nomiyama Haruka , Togao Osamu , Hiwatashi Akio , Niino Masaaki , Isobe Noriko , Kira Jun-ichi
Published: March 2020

Cortical lesions (CLs) have a low prevalence and are associated with physical disabilities in Japanese patients with multiple sclerosis (MS). However, the contribution of CLs to cognitive impairment remains unclear in Asian MS. Sixty-one prospectively enrolled MS patients underwent three-dimensional double inversion recovery MR imaging, the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Apathy Scale (AS), the Fatigue Questionnaire (FQ), and the Hospital Anxiety and Depression Scale (HADS) within a 1-week period. The cognitive impairment index (CII) score was calculated to measure patients’ overall cognitive impairment. MS patients with CLs had poorer scores than those without CLs in most BRB-N tests, but scored comparably in the FQ, AS, and HADS. The number of CLs correlated negatively with all BRB-N test scores and positively with total CII scores. Leukocortical lesions were more extensively associated with cognitive dysfunction in various domains than intracortical lesions. Stepwise multiple regression analysis revealed that potential confounding factors for the highest quartile of CII score were the number of CLs (odds ratio 2.38, p = 0.0070) and the Expanded Disability Severity Scale score (odds ratio 2.13, p = 0.0003). Our results demonstrate that the presence and number of CLs are robustly associated with cognitive dysfunction in Asian MS patients.
Effects of predation risk on egg steroid profiles across multiple populations of threespine stickleback
Authors: McGhee Katie E. , Paitz Ryan T. , Baker John A. , Foster Susan A. , Bell Alison M.
Published: March 2020

Predation often has consistent effects on prey behavior and morphology, but whether the physiological mechanisms underlying these effects show similarly consistent patterns across different populations remains an open question. In vertebrates, predation risk activates the hypothalamic-pituitary-adrenal (HPA) axis, and there is growing evidence that activation of the maternal HPA axis can have intergenerational consequences via, for example, maternally-derived steroids in eggs. Here, we investigated how predation risk affects a suite of maternally-derived steroids in threespine stickleback eggs across nine Alaskan lakes that vary in whether predatory trout are absent, native, or have been stocked within the last 25 years. Using liquid chromatography coupled with mass spectroscopy (LC-MS/MS), we detected 20 steroids within unfertilized eggs. Factor analysis suggests that steroids covary within and across steroid classes (i.e. glucocorticoids, progestogens, sex steroids), emphasizing the modularity and interconnectedness of the endocrine response. Surprisingly, egg steroid profiles were not significantly associated with predator regime, although they were more variable when predators were absent compared to when predators were present, with either native or stocked trout. Despite being the most abundant steroid, cortisol was not consistently associated with predation regime. Thus, while predators can affect steroids in adults, including mothers, the link between maternal stress and embryonic development is more complex than a simple one-to-one relationship between the population-level predation risk experienced by mothers and the steroids mothers transfer to their eggs.
Systematic alteration of ATAC-seq for profiling open chromatin in cryopreserved nuclei preparations from livestock tissues
Authors: Halstead M. M. , Kern C. , Saelao P. , Chanthavixay G. , Wang Y. , Delany M. E. , Zhou H. , Ross P. J.
Published: March 2020

The use of Assay for Transposase-Accessible Chromatin (ATAC-seq) to profile chromatin accessibility has surged over the past years, but its applicability to tissues has been very limited. With the intent of preserving nuclear architecture during long-term storage, cryopreserved nuclei preparations from chicken lung were used to optimize ATAC-seq. Sequencing data were compared with existing DNase-seq, ChIP-seq, and RNA-seq data to evaluate library quality, ultimately resulting in a modified ATAC-seq method capable of generating high quality chromatin accessibility data from cryopreserved nuclei preparations. Using this method, nucleosome-free regions (NFR) identified in chicken lung overlapped half of DNase-I hypersensitive sites, coincided with active histone modifications, and specifically marked actively expressed genes. Notably, sequencing only the subnucleosomal fraction dramatically improved signal, while separation of subnucleosomal reads post-sequencing did not improve signal or peak calling. The broader applicability of this modified ATAC-seq technique was tested using cryopreserved nuclei preparations from pig tissues, resulting in NFR that were highly consistent among biological replicates. Furthermore, tissue-specific NFR were enriched for binding motifs of transcription factors related to tissue-specific functions, and marked genes functionally enriched for tissue-specific processes. Overall, these results provide insights into the optimization of ATAC-seq and a platform for profiling open chromatin in animal tissues.
Surface passivation of zero-mode waveguide nanostructures: benchmarking protocols and fluorescent labels
Authors: Patra Satyajit , Baibakov Mikhail , Claude Jean-Benoît , Wenger Jérôme
Published: March 2020

Zero mode waveguide (ZMW) nanoapertures efficiently confine the light down to the nanometer scale and overcome the diffraction limit in single molecule fluorescence analysis. However, unwanted adhesion of the fluorescent molecules on the ZMW surface can severely hamper the experiments. Therefore a proper surface passivation is required for ZMWs, but information is currently lacking on both the nature of the adhesion phenomenon and the optimization of the different passivation protocols. Here we monitor the influence of the fluorescent dye (Alexa Fluor 546 and 647, Atto 550 and 647N) on the non-specific adhesion of double stranded DNA molecule. We show that the nonspecific adhesion of DNA double strands onto the ZMW surface is directly mediated by the organic fluorescent dye being used, as Atto 550 and Atto 647N show a pronounced tendency to adhere to the ZMW while the Alexa Fluor 546 and 647 are remarkably free of this effect. Despite the small size of the fluorescent label, the surface charge and hydrophobicity of the dye appear to play a key role in promoting the DNA affinity for the ZMW surface. Next, different surface passivation methods (bovine serum albumin BSA, polyethylene glycol PEG, polyvinylphosphonic acid PVPA) are quantitatively benchmarked by fluorescence correlation spectroscopy to determine the most efficient approaches to prevent the adsorption of Atto 647N labeled DNA. Protocols using PVPA and PEG-silane of 1000 Da molar mass are found to drastically avoid the non-specific adsorption into ZMWs. Optimizing both the choice of the fluorescent dye and the surface passivation protocol are highly significant to expand the use of ZMWs for single molecule fluorescence applications.
Identification of Anoplophora glabripennis (Moschulsky) by its emitted specific volatile organic compounds
Authors: Makarow Ramona , Schäfer Sara , Kaul Peter
Published: March 2020

Explorative experiments were done to figure out differences in the emission of volatile organic compounds (VOCs) of not infested trees and trees infested by Anoplophora glabripennis (Asian longhorn beetle, ALB), a quarantine pest. Therefore, VOCs from some native insect species, Anoplophora glabripennis infested Acer, stressed Acer, healthy Acer, Populus and Salix were obtained by enrichment on adsorbents. Qualitative analysis was done by thermal desorption gas chromatography coupled with a mass selective detector (TD-GC/MS). Altogether 169 substances were identified. 11 substances occur from ALB infested or mechanically damaged trees i.e. stressed trees, but not from healthy trees. (+)-Cyclosativene, (+)-α-longipinene, copaene and caryophyllene are detectable only from ALB-infested Acer not from mechanically damaged or healthy Acer. However, these substances are also emitted by healthy Salix. 2,4-Dimethyl-1-heptene is among all tree samples exclusively present in the ambience of ALB-infested trees. It´s rarely detectable from native insect species’ samples.
Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina
Authors: Höfling Larissa , Oesterle Jonathan , Berens Philipp , Zeck Günther
Published: March 2020

Retinal implants are used to replace lost photoreceptors in blind patients suffering from retinopathies such as retinitis pigmentosa. Patients wearing implants regain some rudimentary visual function. However, it is severely limited compared to normal vision because non-physiological stimulation strategies fail to selectively activate different retinal pathways at sufficient spatial and temporal resolution. The development of improved stimulation strategies is rendered difficult by the large space of potential stimuli. Here we systematically explore a subspace of potential stimuli by electrically stimulating healthy and blind mouse retina in epiretinal configuration using smooth Gaussian white noise delivered by a high-density CMOS-based microelectrode array. We identify linear filters of retinal ganglion cells (RGCs) by fitting a linear-nonlinear-Poisson (LNP) model. Our stimulus evokes spatially and temporally confined spiking responses in RGC which are accurately predicted by the LNP model. Furthermore, we find diverse shapes of linear filters in the linear stage of the model, suggesting diverse preferred electrical stimuli of RGCs. The linear filter base identified by our approach could provide a starting point of a model-guided search for improved stimuli for retinal prosthetics.
Physical assessments of termites (Termitidae) under 2.45 GHz microwave irradiation
Authors: Yanagawa Aya , Kajiwara Atsushi , Nakajima Hiroki , Desmond-Le Quéméner Elie , Steyer Jean-Philippe , Lewis Vernard , Mitani Tomohiko
Published: March 2020

Demands for chemical-free treatments for controlling insect pests are increasing worldwide. One such treatment is microwave heating; however, two critical issues arise when using microwaves as a heat source: intensive labor and excessive energy-consumption. Optimization is thus required to reduce energy consumption while effectively killing insects. Currently, the lethal effect of microwaves on insects is considered to be due to the temperature of the irradiated materials. This study examines how the conditions of irradiation, such as resonance or traveling mode, changed the conversion of electromagnetic energy into heat when 2.45 GHz microwaves penetrated the body of the termite,C. formosanus. Our results indicated that it is possible to heat and kill termites with microwaves under resonance condition. Termites were however found to be very tolerant to microwave irradiation as the permittivity of the insect was low compared with other reported insects and plants. Electron spin resonance revealed that termites contained several paramagnetic substances in their bodies, such as Fe3+, Cu2+, Mn2+, and organic radicals. Interestingly, irradiation with traveling microwaves hardly produced heat, but increased the organic radicals in termite bodies indicating non-thermal effects of microwaves.
Remarkably preserved cysts of the extinct synurophyte, Mallomonas ampla, uncovered from a 48 Ma freshwater Eocene lake
Authors: Siver Peter A.
Published: March 2020

Chrysophyte algae produce a siliceous stage in their life cycle, through either asexual or sexual reproduction, known as a cyst. Cysts form in response to shifts in environmental conditions, population density, or predation pressure, and upon germination provide a seed source for future populations. Cysts are morphologically distinct for each species, and since their remains become part of the sediment or fossil record cysts are valuable tools in ecological and paleolimnological investigations. However, their value as biological indicators is limited because the vast majority of cyst morphotypes have not been linked to specific vegetative species. In the current work, an exquisitely preserved and morphologically complex cyst type is described from a 48 million year old early Eocene fossil site. This finding is remarkable since many of the cysts were still associated with components of the living vegetative cells that produced them, enabling the morphotype to be immediately linked to the synurophyte, Mallomonas ampla. Fusion of identifiable components of the living cell post cyst formation is unknown in modern investigations. The identification of the cyst structure for M. ampla could be valuable in determining cyst morphotypes for other species in the lineage.
Unravelling the mechanism of pressure induced polyamorphic transition in an inorganic molecular glass
Authors: Kalkan Bora , Okay Gokce , Aitken Bruce G. , Clark Simon M. , Sen Sabyasachi
Published: March 2020

The atomic structure of a germanium doped phosphorous selenide glass of composition Ge2.8P57.7Se39.5 is determined as a function of pressure from ambient to 24 GPa using Monte-Carlo simulations constrained by high energy x-ray scattering data. The ambient pressure structure consists primarily of P4Se3 molecules and planar edge shared phosphorus rings, reminiscent of those found in red phosphorous as well as a small fraction of locally clustered corner-sharing GeSe4 tetrahedra. This low-density amorphous phase transforms into a high-density amorphous phase at ~6.3 GPa. The high-pressure phase is characterized by an extended network structure. The polyamorphic transformation between these two phases involves opening of the P3 ring at the base of the P4Se3 molecules and subsequent reaction with red phosphorus type moieties to produce a cross linked structure. The compression mechanism of the low-density phase involves increased molecular packing, whereas that of the high pressure phase involves an increase in the nearest-neighbor coordination number while the bond angle distributions broaden and shift to smaller angles. The entropy and volume changes associated with this polyamorphic transformation are positive and negative, respectively, and consequently the corresponding Clapeyron slope for this transition would be negative. This result has far reaching implications in our current understanding of the thermodynamics of polyamorphic transitions in glasses and glass-forming liquids.
An In-situ and Direct Confirmation of Super-Planckian Thermal Radiation Emitted From a Metallic Photonic-Crystal at Optical Wavelengths
Authors: Lin Shawn-Yu , Hsieh Mei-Li , John Sajeev , Frey B. , Bur James A. , Luk Ting-Shan , Wang Xuanjie , Narayanan Shankar
Published: March 2020

Planck’s law predicts the distribution of radiation energy, color and intensity, emitted from a hot object at thermal equilibrium. The Law also sets the upper limit of radiation intensity, the blackbody limit. Recent experiments reveal that micro-structured tungsten can exhibit significant deviation from the blackbody spectrum. However, whether thermal radiation with weak non-equilibrium pumping can exceed the blackbody limit in the far field remains un-answered experimentally. Here, we compare thermal radiation from a micro-cavity/tungsten photonic crystal (W-PC) and a blackbody, which are both measured from the same sample and alsoin-situ. We show that thermal radiation can exceed the blackbody limit by >8 times at λ = 1.7 μm resonant wavelength in the far-field. Our observation is consistent with a recent calculation by Wang and John performed for a 2D W-PC filament. This finding is attributed to non-equilibrium excitation of localized surface plasmon resonances coupled to nonlinear oscillators and the propagation of the electromagnetic waves through non-linear Bloch waves of the W-PC structure. This discovery could help create super-intense narrow band thermal light sources and even an infrared emitter with a laser-like input-output characteristic.
Impaired experience-dependent maternal care in presynaptic active zone protein CAST-deficient dams
Authors: Hagiwara Akari , Sugiyama Naoko , Ohtsuka Toshihisa
Published: March 2020

Although sociological studies affirm the importance of parental care in the survival of offspring, maltreatment—including child neglect—remains prevalent in many countries. While child neglect is well known to affect child development, the causes of maternal neglect are poorly understood. Here, we found that female mice with a deletion mutation of CAST (a presynaptic release-machinery protein) showed significantly reduced weaning rate when primiparous and a recovered rate when multiparous. Indeed, when nurturing, primiparous and nulliparous CAST knock out (KO) mice exhibited less crouching time than control mice and moved greater distances. Contrary to expectations, plasma oxytocin (OXT) was not significantly reduced in CAST KO mice even though terminals of magnocellular neurons in the posterior pituitary expressed CAST. We further found that compared with control mice, CAST KO mice drank significantly less water when nurturing and had a greater preference for sucrose during pregnancy. We suggest that deficiency in presynaptic release-machinery protein impairs the facilitation of some maternal behaviours, which can be compensated for by experience and learning.
Combined transcriptomic and metabolomic analyses uncover rearranged gene expression and metabolite metabolism in tobacco during cold acclimation
Authors: Xu Jiayang , Chen Zheng , Wang Fazhan , Jia Wei , Xu Zicheng
Published: March 2020

Cold temperatures often severely restrict the growth, distribution and productivity of plants. The freezing tolerance of plants from temperate climates can be improved by undergoing periods of cold acclimation (CA). Tobacco is an important economic plant and is sensitive to cold stress. However, the dynamic changes and regulatory mechanisms of gene expression and metabolic processes during CA remain largely unknown. In this study, we performed RNA sequencing and metabolomic profiling analyses to identify the genes and metabolites specifically expressed during CA. Our transcriptomic data revealed 6905 differentially expressed genes (DEGs) during CA. Functional annotation and enrichment analyses revealed that the DEGs were involved mainly in signal transduction, carbohydrate metabolism and phenylpropanoid biosynthesis. Moreover, a total of 35 significantly changed metabolites were identified during CA via an LC-MS platform. Many protective metabolites, such as amino acids, carbohydrates, tricarboxylic acid (TCA) cycle intermediates and phenylpropanoid-related substances, were identified during CA. The gene-metabolite network extensively outlined the biological processes associated with the utilization of sugars, activation of amino acid metabolism, TCA cycle and phenylpropanoid biosynthesis in tobacco under CA. The results of our present study provide a comprehensive view of signal transduction and regulation, gene expression and dynamic changes in metabolites during CA.
The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers
Authors: Hao Wenjun , Yu Meng , Lin Jiaxing , Liu Bitian , Xing Haotian , Yang Jieping , Sun Dan , Chen Feilong , Jiang Mingzhe , Tang Chaozhi , Zhang Xizhe , Zhao Yongkang , Zhu Yuyan
Published: March 2020

Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. However, the functions of the many variants of these proteins in cancer remain incompletely understood. In this work, we used the most comprehensive database available, including more than 10000 samples across more than 30 tumor types, to analyze the six members of the netrin family. We performed comprehensive analysis of genetic change and expression of the netrin genes and analyzed epigenetic and pathway relationships, as well as the correlation of expression of these proteins with drug sensitivity. Although the mutation rate of the netrin family is low in pan-cancer, among the tumor patients with netrin mutations, the highest number are Uterine Corpus Endometrial Carcinoma patients, accounting for 13.6% of cases (54 of 397). Interestingly, the highest mutation rate of a netrin family member is 38% for NTNG1 (152 of 397). Netrin proteins may participate in the development of endocrine-related tumors and sex hormone-targeting organ tumors. Additionally, the participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets. This analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer.
Low-dose 17α-ethinyl estradiol (EE) exposure exacerbates lupus renal disease and modulates immune responses to TLR7/9 agonists in genetically autoimmune-prone mice
Authors: Edwards Michael R. , Dai Rujuan , Heid Bettina , Cowan Catharine , Werre Stephen R. , Cecere Thomas , Ahmed S. Ansar
Published: March 2020

Estrogens have been shown to regulate the immune system and modulate multiple autoimmune diseases. 17α-ethinyl estradiol (EE), a synthetic analog of 17β-estradiol, is prescribed commonly and found in oral contraceptives and hormone replacement therapies. Surprisingly, few studies have investigated the immunoregulatory effects of exposure to EE, especially in autoimmunity. In this study, we exposed autoimmune-prone female MRL/lpr mice to a human-relevant dose of EE through the oral route of exposure. Since lupus patients are prone to infections, groups of mice were injected with viral (Imiquimod, a TLR7 agonist) or bacterial (ODN 2395, a TLR9 agonist) surrogates. We then evaluated autoimmune disease parameters, kidney disease, and response to in vivo TLR7/9 pathogenic signals. EE-exposed mice had increased proteinuria as early as 7 weeks of age. Proteinuria, blood urea nitrogen, and glomerular immune complex deposition were also exacerbated when compared to controls. Production of cytokines by splenic leukocytes were altered in EE-exposed mice. Our study shows that oral exposure to EE, even at a very low dose, can exacerbate azotemia, increase clinical markers of renal disease, enhance glomerular immune complex deposition, and modulate TLR7/9 cytokine production in female MRL/lpr mice. This study may have implications for EE-exposure risk for genetically lupus-prone individuals.
Study of cardiovascular disease prediction model based on random forest in eastern China
Authors: Yang Li , Wu Haibin , Jin Xiaoqing , Zheng Pinpin , Hu Shiyun , Xu Xiaoling , Yu Wei , Yan Jing
Published: March 2020

Cardiovascular disease (CVD) is the leading cause of death worldwide and a major public health concern. CVD prediction is one of the most effective measures for CVD control. In this study, 29930 subjects with high-risk of CVD were selected from 101056 people in 2014, regular follow-up was conducted using electronic health record system. Logistic regression analysis showed that nearly 30 indicators were related to CVD, including male, old age, family income, smoking, drinking, obesity, excessive waist circumference, abnormal cholesterol, abnormal low-density lipoprotein, abnormal fasting blood glucose and else. Several methods were used to build prediction model including multivariate regression model, classification and regression tree (CART), Naïve Bayes, Bagged trees, Ada Boost and Random Forest. We used the multivariate regression model as a benchmark for performance evaluation (Area under the curve, AUC = 0.7143). The results showed that the Random Forest was superior to other methods with an AUC of 0.787 and achieved a significant improvement over the benchmark. We provided a CVD prediction model for 3-year risk assessment of CVD. It was based on a large population with high risk of CVD in eastern China using Random Forest algorithm, which would provide reference for the work of CVD prediction and treatment in China.
Genome sequencing of Rigidoporus microporus provides insights on genes important for wood decay, latex tolerance and interspecific fungal interactions
Authors: Oghenekaro Abbot O. , Kovalchuk Andriy , Raffaello Tommaso , Camarero Susana , Gressler Markus , Henrissat Bernard , Lee Juna , Liu Mengxia , Martínez Angel T. , Miettinen Otto , Mihaltcheva Sirma , Pangilinan Jasmyn , Ren Fei , Riley Robert , Ruiz-Dueñas Francisco Javier , Serrano Ana , Thon Michael R. , Wen Zilan , Zeng Zhen , Barry Kerrie , Grigoriev Igor V. , Martin Francis , Asiegbu Fred O.
Published: March 2020

Fungal plant pathogens remain a serious threat to the sustainable agriculture and forestry, despite the extensive efforts undertaken to control their spread. White root rot disease is threatening rubber tree (Hevea brasiliensis) plantations throughout South and Southeast Asia and Western Africa, causing tree mortality and severe yield losses. Here, we report the complete genome sequence of the basidiomycete fungus Rigidoporus microporus, a causative agent of the disease. Our phylogenetic analysis confirmed the position of R. microporus among the members of Hymenochaetales, an understudied group of basidiomycetes. Our analysis further identified pathogen’s genes with a predicted role in the decay of plant cell wall polymers, in the utilization of latex components and in interspecific interactions between the pathogen and other fungi. We also detected putative horizontal gene transfer events in the genome of R. microporus. The reported first genome sequence of a tropical rubber tree pathogen R. microporus should contribute to the better understanding of how the fungus is able to facilitate wood decay and nutrient cycling as well as tolerate latex and utilize resinous extractives.
Comparison between a wireless dry electrode EEG system with a conventional wired wet electrode EEG system for clinical applications
Authors: Hinrichs Hermann , Scholz Michael , Baum Anne Katrin , Kam Julia W. Y. , Knight Robert T. , Heinze Hans-Jochen
Published: March 2020

Dry electrode electroencephalogram (EEG) recording combined with wireless data transmission offers an alternative tool to conventional wet electrode EEG systems. However, the question remains whether the signal quality of dry electrode recordings is comparable to wet electrode recordings in the clinical context. We recorded the resting state EEG (rsEEG), the visual evoked potentials (VEP) and the visual P300 (P3) from 16 healthy subjects (age range: 26–79 years) and 16 neurological patients who reported subjective memory impairment (age range: 50–83 years). Each subject took part in two recordings on different days, one with 19 dry electrodes and another with 19 wet electrodes. They reported their preferred EEG system. Comparisons of the rsEEG recordings were conducted qualitatively by independent visual evaluation by two neurologists blinded to the EEG system used and quantitatively by spectral analysis of the rsEEG. The P100 visual evoked potential (VEP) and P3 event-related potential (ERP) were compared in terms of latency, amplitude and pre-stimulus noise. The majority of subjects preferred the dry electrode headset. Both neurologists reported that all rsEEG traces were comparable between the wet and dry electrode headsets. Absolute Alpha and Beta power during rest did not statistically differ between the two EEG systems (p > 0.05 in all cases). However, Theta and Delta power was slightly higher with the dry electrodes (p = 0.0004 for Theta and p < 0.0001 for Delta). For ERPs, the mean latencies and amplitudes of the P100 VEP and P3 ERP showed comparable values (p > 0.10 in all cases) with a similar spatial distribution for both wet and dry electrode systems. These results suggest that the signal quality, ease of set-up and portability of the dry electrode EEG headset used in our study comply with the needs of clinical applications.
Deviations from normal bedtimes are associated with short-term increases in resting heart rate
Authors: Faust Louis , Feldman Keith , Mattingly Stephen M. , Hachen David , V. Chawla Nitesh
Published: March 2020

Despite proper sleep hygiene being critical to our health, guidelines for improving sleep habits often focus on only a single component, namely, sleep duration. Recent works, however, have brought to light the importance of another aspect of sleep: bedtime regularity, given its ties to cognitive and metabolic health outcomes. To further our understanding of this often-neglected component of sleep, the objective of this work was to investigate the association between bedtime regularity and resting heart rate (RHR): an important biomarker for cardiovascular health. Utilizing Fitbit Charge HRs to measure bedtimes, sleep and RHR, 255,736 nights of data were collected from a cohort of 557 college students. We observed that going to bed even 30 minutes later than one’s normal bedtime was associated with a significantly higher RHR throughout sleep (Coeff +0.18; 95% CI: +0.11, +0.26 bpm), persisting into the following day and converging with one’s normal RHR in the early evening. Bedtimes of at least 1 hour earlier were also associated with significantly higher RHRs throughout sleep; however, they converged with one’s normal rate by the end of the sleep session, not extending into the following day. These observations stress the importance of maintaining proper sleep habits, beyond sleep duration, as high variability in bedtimes may be detrimental to one’s cardiovascular health.
Toxicogenomics in a soil sentinel exposure to Zn nanoparticles and ions reveals the comparative role of toxicokinetic and toxicodynamic mechanisms
Authors: Novo Marta , Lahive Elma , Díez Ortiz María , Spurgeon David J. , Kille Peter
Published: March 2020

Exposures to Zn in ion or NPs form results in stimulation of the same cellular pathways (conserved toxicodynamics), whilst exposure to NPs enhances the amplitude of the response by influencing the mechanism of uptake (altered toxicokinetics).
Whole-wheat flour particle size influences dough properties, bread structure and in vitro starch digestibility
Authors: Lin Suyun , Gao Jing , Jin Xiaoxuan , Wang Yong , Dong Zhizhong , Ying Jian , Zhou Weibiao
Published: March 2020

Whole-wheat flour (WWF) particle size is critical to dough properties, bread quality, and in vitro starch digestibility of bread.
Anisotropic properties of pipe-GaN distributed Bragg reflectors
Authors: Wu Chia-Jung , Chen Yi-Yun , Wang Cheng-Jie , Shiu Guo-Yi , Huang Chin-Han , Liu Heng-Jui , Chen Hsiang , Lin Yung-Sen , Lin Chia-Feng , Han Jung
Published: March 2020

Polarization-dependent reflectance spectra of the pipe-GaN reflector show that it can be used as a polarized light source.
A nanopatterned dual reactive surface driven by block copolymer self-assembly
Authors: Mawélé Loudy Coste , Allouche Joachim , Bousquet Antoine , Martinez Hervé , Billon Laurent
Published: March 2020

Herein, we report the selective surface functionalization of nano-domains obtained by the self-assembly of a polystyrene-block-poly(vinyl benzyl azide). Click chemistry was used to bind functional gold nanoparticles and poly(N-isopropylacrylamide).