bluuebunny/crossref_metadata_2025 huggingface dataset:
Very-Low-Frequency transmitters bifurcate energetic electron belt in near-earth space
Authors: Hua Man , Li Wen , Ni Binbin , Ma Qianli , Green Alex , Shen Xiaochen , Claudepierre Seth G. , Bortnik Jacob , Gu Xudong , Fu Song , Xiang Zheng , Reeves Geoffrey D.
Published: September 2020

Very-Low-Frequency (VLF) transmitters operate worldwide mostly at frequencies of 10–30 kilohertz for submarine communications. While it has been of intense scientific interest and practical importance to understand whether VLF transmitters can affect the natural environment of charged energetic particles, for decades there remained little direct observational evidence that revealed the effects of these VLF transmitters in geospace. Here we report a radially bifurcated electron belt formation at energies of tens of kiloelectron volts (keV) at altitudes of ~0.8–1.5 Earth radii on timescales over 10 days. Using Fokker-Planck diffusion simulations, we provide quantitative evidence that VLF transmitter emissions that leak from the Earth-ionosphere waveguide are primarily responsible for bifurcating the energetic electron belt, which typically exhibits a single-peak radial structure in near-Earth space. Since energetic electrons pose a potential danger to satellite operations, our findings demonstrate the feasibility of mitigation of natural particle radiation environment.
PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade
Authors: Peng Qi , Qiu Xiangyan , Zhang Zihan , Zhang Silin , Zhang Yuanyuan , Liang Yong , Guo Jingya , Peng Hua , Chen Mingyi , Fu Yang-Xin , Tang Haidong
Published: September 2020

Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.
Porous carbon nanowire array for surface-enhanced Raman spectroscopy
Authors: Chen Nan , Xiao Ting-Hui , Luo Zhenyi , Kitahama Yasutaka , Hiramatsu Kotaro , Kishimoto Naoki , Itoh Tamitake , Cheng Zhenzhou , Goda Keisuke
Published: September 2020

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool for vibrational spectroscopy as it provides several orders of magnitude higher sensitivity than inherently weak spontaneous Raman scattering by exciting localized surface plasmon resonance (LSPR) on metal substrates. However, SERS can be unreliable for biomedical use since it sacrifices reproducibility, uniformity, biocompatibility, and durability due to its strong dependence on “hot spots”, large photothermal heat generation, and easy oxidization. Here, we demonstrate the design, fabrication, and use of a metal-free (i.e., LSPR-free), topologically tailored nanostructure composed of porous carbon nanowires in an array as a SERS substrate to overcome all these problems. Specifically, it offers not only high signal enhancement (~106) due to its strong broadband charge-transfer resonance, but also extraordinarily high reproducibility due to the absence of hot spots, high durability due to no oxidization, and high compatibility to biomolecules due to its fluorescence quenching capability.
Fault valving and pore pressure evolution in simulations of earthquake sequences and aseismic slip
Authors: Zhu Weiqiang , Allison Kali L. , Dunham Eric M. , Yang Yuyun
Published: September 2020

Fault-zone fluids control effective normal stress and fault strength. While most earthquake models assume a fixed pore fluid pressure distribution, geologists have documented fault valving behavior, that is, cyclic changes in pressure and unsteady fluid migration along faults. Here we quantify fault valving through 2-D antiplane shear simulations of earthquake sequences on a strike-slip fault with rate-and-state friction, upward Darcy flow along a permeable fault zone, and permeability evolution. Fluid overpressure develops during the interseismic period, when healing/sealing reduces fault permeability, and is released after earthquakes enhance permeability. Coupling between fluid flow, permeability and pressure evolution, and slip produces fluid-driven aseismic slip near the base of the seismogenic zone and earthquake swarms within the seismogenic zone, as ascending fluids pressurize and weaken the fault. This model might explain observations of late interseismic fault unlocking, slow slip and creep transients, swarm seismicity, and rapid pressure/stress transmission in induced seismicity sequences.
Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions
Authors: Liu Meng , Apriceno Azzurra , Sipin Miguel , Scarpa Edoardo , Rodriguez-Arco Laura , Poma Alessandro , Marchello Gabriele , Battaglia Giuseppe , Angioletti-Uberti Stefano
Published: September 2020

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects. Using statistical mechanical modelling, we describe here how multivalency can be exploited to achieve what we dub range selectivity, that is, binding only to targets bearing a number of receptors within a specified range. We use our model to characterise the region in parameter space where one can expect range selective targeting to occur, and provide experimental support for this phenomenon. Overall, range selectivity represents a potential path to increase the targeting selectivity of multivalent constructs.
MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme
Authors: Li Yingzhong , Ivica Nikola A. , Dong Ting , Papageorgiou Dimitrios P. , He Yanpu , Brown Douglas R. , Kleyman Marianna , Hu Guangan , Chen Walter W. , Sullivan Lucas B. , Del Rosario Amanda , Hammond Paula T. , Vander Heiden Matthew G. , Chen Jianzhu
Published: September 2020

ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these outputs are regulated to balance the cellular requirement for energy and heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples mitochondrial respiration to switch ATP synthesis to thermogenesis in response to heme. When heme levels are low, MSFD7C promotes ATP synthesis by interacting with components of the electron transport chain (ETC) complexes III, IV, and V, and destabilizing sarcoendoplasmic reticulum Ca2+-ATPase 2b (SERCA2b). Upon heme binding to the N-terminal domain, MFSD7C dissociates from ETC components and SERCA2b, resulting in SERCA2b stabilization and thermogenesis. The heme-regulated switch between ATP synthesis and thermogenesis enables cells to match outputs of mitochondrial respiration to their metabolic state and nutrient supply, and represents a cell intrinsic mechanism to regulate mitochondrial energy metabolism.
Copper catalysis at operando conditions—bridging the gap between single nanoparticle probing and catalyst-bed-averaging
Authors: Albinsson David , Boje Astrid , Nilsson Sara , Tiburski Christopher , Hellman Anders , Ström Henrik , Langhammer Christoph
Published: September 2020

In catalysis, nanoparticles enable chemical transformations and their structural and chemical fingerprints control activity. To develop understanding of such fingerprints, methods studying catalysts at realistic conditions have proven instrumental. Normally, these methods either probe the catalyst bed with low spatial resolution, thereby averaging out single particle characteristics, or probe an extremely small fraction only, thereby effectively ignoring most of the catalyst. Here, we bridge the gap between these two extremes by introducing highly multiplexed single particle plasmonic nanoimaging of model catalyst beds comprising 1000 nanoparticles, which are integrated in a nanoreactor platform that enables online mass spectroscopy activity measurements. Using the example of CO oxidation over Cu, we reveal how highly local spatial variations in catalyst state dynamics are responsible for contradicting information about catalyst active phase found in the literature, and identify that both surface and bulk oxidation state of a Cu nanoparticle catalyst dynamically mediate its activity.
Functional genetic encoding of sulfotyrosine in mammalian cells
Authors: He Xinyuan , Chen Yan , Beltran Daisy Guiza , Kelly Maia , Ma Bin , Lawrie Justin , Wang Feng , Dodds Eric , Zhang Limei , Guo Jiantao , Niu Wei
Published: September 2020

Protein tyrosine O-sulfation (PTS) plays a crucial role in extracellular biomolecular interactions that dictate various cellular processes. It also involves in the development of many human diseases. Regardless of recent progress, our current understanding of PTS is still in its infancy. To promote and facilitate relevant studies, a generally applicable method is needed to enable efficient expression of sulfoproteins with defined sulfation sites in live mammalian cells. Here we report the engineering, in vitro biochemical characterization, structural study, and in vivo functional verification of a tyrosyl-tRNA synthetase mutant for the genetic encoding of sulfotyrosine in mammalian cells. We further apply this chemical biology tool to cell-based studies on the role of a sulfation site in the activation of chemokine receptor CXCR4 by its ligand. Our work will not only facilitate cellular studies of PTS, but also paves the way for economical production of sulfated proteins as therapeutic agents in mammalian systems.
Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer
Authors: Kocher Hemant M. , Basu Bristi , Froeling Fieke E. M. , Sarker Debashis , Slater Sarah , Carlin Dominic , deSouza Nandita M. , De Paepe Katja N. , Goulart Michelle R. , Hughes Christine , Imrali Ahmet , Roberts Rhiannon , Pawula Maria , Houghton Richard , Lawrence Cheryl , Yogeswaran Yathushan , Mousa Kelly , Coetzee Carike , Sasieni Peter , Prendergast Aaron , Propper David J.
Published: September 2020

Pre-clinical models have shown that targeting pancreatic stellate cells with all-trans-retinoic-acid (ATRA) reprograms pancreatic stroma to suppress pancreatic ductal adenocarcinoma (PDAC) growth. Here, in a phase Ib, dose escalation and expansion, trial for patients with advanced, unresectable PDAC (n = 27), ATRA is re-purposed as a stromal-targeting agent in combination with gemcitabine-nab-paclitaxel chemotherapy using a two-step adaptive continual re-assessment method trial design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D, primary outcome) is the FDA/EMEA approved dose of gemcitabine-nab-paclitaxel along-with ATRA (45 mg/m2 orally, days 1–15/cycle). Dose limiting toxicity (DLT) is grade 4 thrombocytopenia (n = 2). Secondary outcomes show no detriment to ATRA pharmacokinetics.. Median overall survival for RP2D treated evaluable population, is 11.7 months (95%CI 8.6–15.7 m, n = 15, locally advanced (2) and metastatic (13)). Exploratory pharmacodynamics studies including changes in diffusion-weighted (DW)-MRI measured apparent diffusion coefficient after one cycle, and, modulation of cycle-specific serum pentraxin 3 levels over various cycles indicate stromal modulation. Baseline stromal-specific retinoid transport protein (FABP5, CRABP2) expression may be predicitve of response. Re-purposing ATRA as a stromal-targeting agent with gemcitabine-nab-paclitaxel is safe and tolerable. This combination will be evaluated in a phase II randomized controlled trial for locally advanced PDAC. Clinical trial numbers: EudraCT: 2015-002662-23; NCT03307148. Trial acronym: STARPAC.
Fabrication of a novel magnetic topological heterostructure and temperature evolution of its massive Dirac cone
Authors: Hirahara T. , Otrokov M. M. , Sasaki T. T. , Sumida K. , Tomohiro Y. , Kusaka S. , Okuyama Y. , Ichinokura S. , Kobayashi M. , Takeda Y. , Amemiya K. , Shirasawa T. , Ideta S. , Miyamoto K. , Tanaka K. , Kuroda S. , Okuda T. , Hono K. , Eremeev S. V. , Chulkov E. V.
Published: September 2020

Materials that possess nontrivial topology and magnetism is known to exhibit exotic quantum phenomena such as the quantum anomalous Hall effect. Here, we fabricate a novel magnetic topological heterostructure Mn4Bi2Te7/Bi2Te3 where multiple magnetic layers are inserted into the topmost quintuple layer of the original topological insulator Bi2Te3. A massive Dirac cone (DC) with a gap of 40–75 meV at 16 K is observed. By tracing the temperature evolution, this gap is shown to gradually decrease with increasing temperature and a blunt transition from a massive to a massless DC occurs around 200–250 K. Structural analysis shows that the samples also contain MnBi2Te4/Bi2Te3. Magnetic measurements show that there are two distinct Mn components in the system that corresponds to the two heterostructures; MnBi2Te4/Bi2Te3 is paramagnetic at 6 K while Mn4Bi2Te7/Bi2Te3 is ferromagnetic with a negative hysteresis (critical temperature  ~20 K). This novel heterostructure is potentially important for future device applications.
Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
Authors: Daisley Brendan A. , Chanyi Ryan M. , Abdur-Rashid Kamilah , Al Kait F. , Gibbons Shaeley , Chmiel John A. , Wilcox Hannah , Reid Gregor , Anderson Amanda , Dewar Malcolm , Nair Shiva M. , Chin Joseph , Burton Jeremy P.
Published: September 2020

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.
Machine learning identifies scale-free properties in disordered materials
Authors: Yu Sunkyu , Piao Xianji , Park Namkyoo
Published: September 2020

The vast amount of design freedom in disordered systems expands the parameter space for signal processing. However, this large degree of freedom has hindered the deterministic design of disordered systems for target functionalities. Here, we employ a machine learning approach for predicting and designing wave-matter interactions in disordered structures, thereby identifying scale-free properties for waves. To abstract and map the features of wave behaviors and disordered structures, we develop disorder-to-localization and localization-to-disorder convolutional neural networks, each of which enables the instantaneous prediction of wave localization in disordered structures and the instantaneous generation of disordered structures from given localizations. We demonstrate that the structural properties of the network architectures lead to the identification of scale-free disordered structures having heavy-tailed distributions, thus achieving multiple orders of magnitude improvement in robustness to accidental defects. Our results verify the critical role of neural network structures in determining machine-learning-generated real-space structures and their defect immunity.
Laser-induced graphitization of polydopamine leads to enhanced mechanical performance while preserving multifunctionality
Authors: Lee Kyueui , Park Minok , Malollari Katerina G. , Shin Jisoo , Winkler Sally M. , Zheng Yuting , Park Jung Hwan , Grigoropoulos Costas P. , Messersmith Phillip B.
Published: September 2020

Polydopamine (PDA) is a simple and versatile conformal coating material that has been proposed for a variety of uses; however in practice its performance is often hindered by poor mechanical properties and high roughness. Here, we show that blue-diode laser annealing dramatically improves mechanical performance and reduces roughness of PDA coatings. Laser-annealed PDA (LAPDA) was shown to be >100-fold more scratch resistant than pristine PDA and even better than hard inorganic substrates, which we attribute to partial graphitization and covalent coupling between PDA subunits during annealing. Moreover, laser annealing provides these benefits while preserving other attractive properties of PDA, as demonstrated by the superior biofouling resistance of antifouling polymer-grafted LAPDA compared to PDA modified with the same polymer. Our work suggests that laser annealing may allow the use of PDA in mechanically demanding applications previously considered inaccessible, without sacrificing the functional versatility that is so characteristic of PDA.
The social and environmental complexities of extracting energy transition metals
Authors: Lèbre Éléonore , Stringer Martin , Svobodova Kamila , Owen John R. , Kemp Deanna , Côte Claire , Arratia-Solar Andrea , Valenta Rick K.
Published: September 2020

Environmental, social and governance pressures should feature in future scenario planning about the transition to a low carbon future. As low-carbon energy technologies advance, markets are driving demand for energy transition metals. Increased extraction rates will augment the stress placed on people and the environment in extractive locations. To quantify this stress, we develop a set of global composite environmental, social and governance indicators, and examine mining projects across 20 metal commodities to identify the co-occurrence of environmental, social and governance risk factors. Our findings show that 84% of platinum resources and 70% of cobalt resources are located in high-risk contexts. Reflecting heightened demand, major metals like iron and copper are set to disturb more land. Jurisdictions extracting energy transition metals in low-risk contexts are positioned to develop and maintain safeguards against mining-related social and environmental risk factors.
Constructing phase boundary in AgNbO3 antiferroelectrics: pathway simultaneously achieving high energy density and efficiency
Authors: Luo Nengneng , Han Kai , Cabral Matthew J. , Liao Xiaozhou , Zhang Shujun , Liao Changzhong , Zhang Guangzu , Chen Xiyong , Feng Qin , Li Jing-Feng , Wei Yuezhou
Published: September 2020

Dielectric capacitors with high energy storage density (Wrec) and efficiency (η) are in great demand for high/pulsed power electronic systems, but the state-of-the-art lead-free dielectric materials are facing the challenge of increasing one parameter at the cost of the other. Herein, we report that high Wrec of 6.3 J cm-3 with η of 90% can be simultaneously achieved by constructing a room temperature M2–M3 phase boundary in (1-x)AgNbO3-xAgTaO3 solid solution system. The designed material exhibits high energy storage stability over a wide temperature range of 20–150 °C and excellent cycling reliability up to 106 cycles. All these merits achieved in the studied solid solution are attributed to the unique relaxor antiferroelectric features relevant to the local structure heterogeneity and antiferroelectric ordering, being confirmed by scanning transmission electron microscopy and synchrotron X-ray diffraction. This work provides a good paradigm for developing new lead-free dielectrics for high-power energy storage applications.
Optoribogenetic control of regulatory RNA molecules
Authors: Pilsl Sebastian , Morgan Charles , Choukeife Moujab , Möglich Andreas , Mayer Günter
Published: September 2020

Short regulatory RNA molecules underpin gene expression and govern cellular state and physiology. To establish an alternative layer of control over these processes, we generated chimeric regulatory RNAs that interact reversibly and light-dependently with the light-oxygen-voltage photoreceptor PAL. By harnessing this interaction, the function of micro RNAs (miRs) and short hairpin (sh) RNAs in mammalian cells can be regulated in a spatiotemporally precise manner. The underlying strategy is generic and can be adapted to near-arbitrary target sequences. Owing to full genetic encodability, it establishes optoribogenetic control of cell state and physiology. The method stands to facilitate the non-invasive, reversible and spatiotemporally resolved study of regulatory RNAs and protein function in cellular and organismal environments.
Publisher Correction: Reconciling qualitative, abstract, and scalable modeling of biological networks
Authors: Paulevé Loïc , Kolčák Juri , Chatain Thomas , Haar Stefan
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: The protonation state of an evolutionarily conserved histidine modulates domain swapping stability of FoxP1
Authors: Medina Exequiel , Villalobos Pablo , Coñuecar Ricardo , Ramírez-Sarmiento César A. , Babul Jorge
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Purified Sika deer antler protein attenuates GM-induced nephrotoxicity by activating Nrf2 pathway and inhibiting NF-κB pathway
Authors: Wang Zhenyi , Wang Lulu , Wang Jing , Luo Jiacheng , Ruan Haonan , Zhang Jing
Published: September 2020

Although gentamicin is widely used as an antibiotic in clinical practice, it also has some side-effects, such as acute kidney injury, which is a common condition caused by the abuse of gentamicin. Sika deer antler protein (SDAPR) can antagonize drug-induced AKI. Since SDAPR is recognized as an effective part of velvet antler, its components were further separated. Two components named SDAP1 and SDAP2 were obtained. The protective effects of SDAPR, SDAP1 and SDAP2 on GM-induced cytotoxicity to HEK293 and its potential mechanisms were studied. MTT and xCELLigence Real-Time cell analysis showed that SDAPR, SDAP1 and SDAP2 could protect HEK293 cells from GM toxicity. Similarly, SDAPR, SDAP1 and SDAP2 can reduce ROS level, reduce oxidative stress and improve inflammation Further studies have shown that SDAPR, SDAP1 and SDAP2 upregulate the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1, and down-regulate the NF-κB pathway by reducing the protein expression of NF-κB. Annexin V/PI flow cytometry and Hoechst 33258 staining showed that SDAPR, SDAP1 and SDAP2 inhibited GM-induced apoptosis in HEK293 cells. Western blot analysis showed SDAPR, SDAP1 and SDAP2 decreased expression level of Bax and Cleaved-caspase-3, and increased the expression level of Bcl-2. In addition, we examined the feasibility of SDAP1 and SDAP1 to avoid kidney injury in a GM mouse model. In conclusion, SDAPR, SDAP1 and SDAP2 can be used to prevent GM-induced HEK293 cytotoxicity, probably because they have strong anti-oxidative stress, anti-inflammatory and anti-apoptotic effects. And SDAP1 and SDAP2 can inhibit GM-induced acute kidney injury in mice.
Design principles of gene evolution for niche adaptation through changes in protein–protein interaction networks
Authors: Carmi Gon , Tagore Somnath , Gorohovski Alessandro , Sivan Aviad , Raviv-Shay Dorith , Frenkel-Morgenstern Milana
Published: September 2020

In contrast to fossorial and above-ground organisms, subterranean species have adapted to the extreme stresses of living underground. We analyzed the predicted protein–protein interactions (PPIs) of all gene products, including those of stress-response genes, among nine subterranean, ten fossorial, and 13 aboveground species. We considered 10,314 unique orthologous protein families and constructed 5,879,879 PPIs in all organisms using ChiPPI. We found strong association between PPI network modulation and adaptation to specific habitats, noting that mutations in genes and changes in protein sequences were not linked directly with niche adaptation in the organisms sampled. Thus, orthologous hypoxia, heat-shock, and circadian clock proteins were found to cluster according to habitat, based on PPIs rather than on sequence similarities. Curiously, "ordered" domains were preserved in aboveground species, while "disordered" domains were conserved in subterranean organisms, and confirmed for proteins in DistProt database. Furthermore, proteins with disordered regions were found to adopt significantly less optimal codon usage in subterranean species than in fossorial and above-ground species. These findings reveal design principles of protein networks by means of alterations in protein domains, thus providing insight into deep mechanisms of evolutionary adaptation, generally, and particularly of species to underground living and other confined habitats.
The importance of socioeconomic position in smoking, cessation and environmental tobacco smoke exposure during pregnancy
Authors: Madureira Joana , Camelo Alexandra , Silva Ana Inês , Reis Ana Teresa , Esteves Filipa , Ribeiro Ana Isabel , Teixeira João Paulo , Costa Carla
Published: September 2020

Tobacco is still a leading cause of premature death and morbidity. Particular attention has been given to pregnant women due to the scientific evidence on the importance of early life exposures for disease onset later in life. The purpose of this study was to assess smoking prevalence, smoking cessation rate and environmental tobacco smoke (ETS) exposure, and the role of socioeconomic position (SEP) on these behaviors among pregnant women. Cross-sectional data of 619 pregnant women, aged between 18 and 46 years, from Porto Metropolitan Area, Portugal, on current smoking, ETS exposure and SEP indicators was collected, face-to-face, using a questionnaire filled in during a personal interview at the postpartum hospital stay. The smoking prevalence, and ETS exposure among non-smokers before pregnancy was 27.6% and 57.4%, respectively. 4.1% of the participants reported to have stopped smoking before pregnancy, whereas about 41% quitted along pregnancy, resulting in a smoking prevalence at birth of 14.6%. Exposure to ETS also decreased throughout pregnancy to 49.8% at birth. Lower educational level was significantly associated with both higher smoking prevalence and exposure to ETS and lower smoking cessation. This study demonstrates that smoking and ETS exposure during pregnancy remains high, and that there are still significant socioeconomic inequalities in smoking; thus tobacco-focused preventive interventions need to be reinforced.
Nanomechanics of graphene oxide-bacteriophage based self-assembled porous composites
Authors: Sun Yiwei , Passaretti Paolo , Hernandez Ignacio , Gonzalez Jesus , Liu Wei , Rodriguez Fernando , Dunstan David J. , Goldberg Oppenheimer Pola , Humphreys Colin J.
Published: September 2020

Graphene oxide, integrated with the filamentous bacteriophage M13, forms a 3D large-scale multifunctional porous structure by self-assembly, with considerable potential for applications. We performed Raman spectroscopy under pressure on this porous composite to understand its fundamental mechanics. The results show that at low applied pressure, the$$sp^2$$sp2bonds of graphene oxide stiffen very little with increasing pressure, suggesting a complicated behaviour of water intercalated between the graphene layers. The key message of this paper is that water in a confined space can have a significant impact on the nanostructure that hosts it. We introduced carbon nanotubes during the self-assembly of graphene oxide and M13, and a similar porous macro-structure was observed. However, in the presence of carbon nanotubes, pressure is transmitted to the$$sp^2$$sp2bonds of graphene oxide straightforwardly as in graphite. The electrical conductivity of the composite containing carbon nanotubes is improved by about 30 times at a bias voltage of 10 V. This observation suggests that the porous structure has potential in applications where good electrical conductivity is desired, such as sensors and batteries.
Parasite intensity drives fetal development and sex allocation in a wild ungulate
Authors: Aleuy O. Alejandro , Serrano Emmanuel , Ruckstuhl Kathreen E. , Hoberg Eric P. , Kutz Susan
Published: September 2020

An understanding of the mechanisms influencing prenatal characteristics is fundamental to comprehend the role of ecological and evolutionary processes behind survival and reproductive success in animals. Although the negative influence of parasites on host fitness is undisputable, we know very little about how parasitic infection in reproductive females might influence prenatal factors such as fetal development and sex allocation. Using an archival collection of Dall’s sheep (Ovis dalli dalli), a capital breeder that depends on its body reserves to overcome the arctic winter, we investigated the direct and indirect impacts of the parasite community on fetal development and sex allocation. Using partial least squares modelling, we observed a negative effect of parasite community on fetal development, driven primarily by the nematodeMarshallagia marshalli. Principal component analysis demonstrated that mothers with low parasite burden and in good body condition were more likely to have female versus male fetuses. This association was primarily driven by the indirect effect ofM. marshallion ewe body condition. Refining our knowledge of the direct and indirect impact that parasite communities can have on reproduction in mammals is critical for understanding the effects of infectious diseases on wildlife populations. This can be particularly relevant for species living in ecosystems sensitive to the effects of global climate change.
Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets
Authors: Velázquez Diego , Albacar Marcel , Zhang Chunyi , Calafí Carlos , López-Malo María , Torres-Torronteras Javier , Martí Ramón , Kovalchuk Sergey I. , Pinson Benoit , Jensen Ole N. , Daignan-Fornier Bertrand , Casamayor Antonio , Ariño Joaquín
Published: September 2020

Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in Saccharomyces cerevisiae. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of HOG1 attenuates the growth defect of Ppz1-overexpressing cells, while that of SKO1 aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle.
Exoskeleton home and community use in people with complete spinal cord injury
Authors: van Dijsseldonk Rosanne B. , van Nes Ilse J. W. , Geurts Alexander C. H. , Keijsers Noël L. W.
Published: September 2020

A consequence of a complete spinal cord injury (SCI) is the loss of gait capacity. Wearable exoskeletons for the lower extremity enable household and community ambulation in people with SCI. This study assessed the amount, purpose, and location of exoskeleton use in the home and community environment, without any restrictions. The number of steps taken was read from the exoskeleton software. Participants kept a daily logbook, and completed two user experience questionnaires (Quebec User Evaluation of Satisfaction with assistive Technology (D-QUEST) and System Usability Scale (SUS)). Fourteen people with a complete SCI used the ReWalk exoskeleton a median of 9 (range [1–15]) out of 16 ([12–21]) days, in which participants took a median of 3,226 ([330–28,882]) steps. The exoskeleton was mostly used for exercise purposes (74%) and social interaction (20%). The main location of use was outdoors (48%). Overall, participants were satisfied with the exoskeleton (D-QUEST 3.7 ± 0.4) and its usability (SUS 72.5 [52.5–95.0]). Participants with complete SCI report satisfaction with the exoskeleton for exercise and social interaction in the home and community, but report limitations as an assistive device during daily life.
Cyclic AMP efflux through MRP4 regulates actin dynamics signalling pathway and sperm motility in bovines
Authors: Chiarante Nicolás , Alonso Carlos A. I. , Plaza Jessica , Lottero-Leconte Raquel , Arroyo-Salvo Camila , Yaneff Agustín , Osycka-Salut Claudia E. , Davio Carlos , Miragaya Marcelo , Perez-Martinez Silvina
Published: September 2020

Previously we demonstrated that multidrug resistance-associated protein 4 transporter (MRP4) mediates cAMP efflux in bovine spermatozoa and that extracellular cAMP (ecAMP) triggers events associated to capacitation. Here, we deepen the study of the role of MRP4 in bovine sperm function by using MK571, an MRP4 inhibitor. The incubation of spermatozoa with MK571 during 45 min inhibited capacitation-associated events. MRP4 was localized in post-acrosomal region and mid-piece at 15 min capacitation, while at 45 min it was mainly located in the acrosome. After 15 min, MK571 decreased total sperm motility (TM), progressive motility (PM) and several kinematic parameters. The addition of ecAMP rescued MK571 effect and ecAMP alone increased the percentage of motile sperm and kinematics parameters. Since actin cytoskeleton plays essential roles in the regulation of sperm motility, we investigated if MRP4 activity might affect actin polymerization. After 15 min capacitation, an increase in F-actin was observed, which was inhibited by MK571. This effect was reverted by the addition of ecAMP. Furthermore, ecAMP alone increased F-actin levels while no F-actin was detected with ecAMP in the presence of PKA inhibitors. Our results support the importance of cAMP efflux through MRP4 in sperm capacitation and suggest its involvement in the regulation of actin polymerization and motility.
Aldosterone up-regulates voltage-gated potassium currents and NKCC1 protein membrane fractions
Authors: Bazard Parveen , Ding Bo , Chittam Harish K. , Zhu Xiaoxia , Parks Thomas A. , Taylor-Clark Thomas E. , Bhethanabotla Venkat R. , Frisina Robert D. , Walton Joseph P.
Published: September 2020

Na+–K+–2Cl− Cotransporter (NKCC1) is a protein that aids in the active transport of sodium, potassium, and chloride ions across cell membranes. It has been shown that long-term systemic treatment with aldosterone (ALD) can enhance NKCC1 protein expression and activity in the aging cochlea resulting in improved hearing. In the present work, we used a cell line with confirmed NKCC1 expression to demonstrate that in vitro application of ALD increased outward voltage-gated potassium currents significantly, and simultaneously upregulated whole lysate and membrane portion NKCC1 protein expression. These ALD-induced changes were blocked by applying the mineralocorticoid receptor antagonist eplerenone. However, application of the NKCC1 inhibitor bumetanide or the potassium channel antagonist Tetraethyl ammonium had no effect. In addition, NKKC1 mRNA levels remained stable, indicating that ALD modulates NKCC1 protein expression via the activation of mineralocorticoid receptors and post-transcriptional modifications. Further, in vitro electrophysiology experiments, with ALD in the presence of NKCC1, K+ channel and mineralocorticoid receptor inhibitors, revealed interactions between NKCC1 and outward K+ channels, mediated by a mineralocorticoid receptor-ALD complex. These results provide evidence of the therapeutic potential of ALD for the prevention/treatment of inner ear disorders such as age-related hearing loss.
Valence band electronic structure of the van der Waals ferromagnetic insulators: VI$$_3$$ and CrI$$_3$$
Authors: Kundu Asish K. , Liu Yu , Petrovic C. , Valla T.
Published: September 2020

Ferromagnetic van der Waals (vdW) insulators are of great scientific interest for their promising applications in spintronics. It has been indicated that in the two materials within this class, CrI$$_3$$

3

and VI$$_3$$

3

, the magnetic ground state, the band gap, and the Fermi level could be manipulated by varying the layer thickness, strain or doping. To understand how these factors impact the properties, a detailed understanding of the electronic structure would be required. However, the experimental studies of the electronic structure of these materials are still very sparse. Here, we present the detailed electronic structure of CrI$$_3$$

3

and VI$$_3$$

3

measured by angle-resolved photoemission spectroscopy (ARPES). Our results show a band-gap of the order of 1 eV, sharply contrasting some theoretical predictions such as Dirac half-metallicity and metallic phases, indicating that the intra-atomic interaction parameter (U) and spin-orbit coupling (SOC) were not properly accounted for in the calculations. We also find significant differences in the electronic properties of these two materials, in spite of similarities in their crystal structure. In CrI$$_3$$

3

, the valence band maximum is dominated by the I 5p, whereas in VI$$_3$$

3

it is dominated by the V 3d derived states. Our results represent valuable input for further improvements in the theoretical modeling of these systems.
Establishment of a stable transfection method in Babesia microti and identification of a novel bidirectional promoter of Babesia microti
Authors: Jaijyan Dabbu Kumar , Govindasamy Kavitha , Singh Jyoti , Bhattacharya Shreya , Singh Agam Prasad
Published: September 2020

Babesia microti, an emerging human pathogen, is primarily transmitted through a bite of an infected tick and blood transfusions in human. Stable transfection technique has been reported in many protozoan parasites over the past few years. However, in vivo transient and stable transfection method has not been established for Babesia microti. Here, for the first time, we present a method of transient as well as stable transfection of the Babesia microti (B. microti) in the in vivo conditions. We have identified a novel promoter of B. microti. We also demonstrated that Plasmodium berghei DHFR promoter is recognized and functional in B. microti. We show that BM-CTQ41297 promoter control the expression of two genes, which are present on either side and thus represents a bi-functional promoter in B. microti. The predicted promoter activity values using Promoter 2.0 program is higher for BM- CTQ41297 promoter than strong promoters such as β-actin, ef-1β, and many other promoters. Furthermore, we discovered a non-essential locus for the genetic manipulation of the parasite, allowing us to stably integrate foreign genes; GFP, mCherry, into the B. microti. The transfection using an electroporation method and genetic manipulation of B. microti is now achievable and it is possible to obtain transfected viable parasites under in vivo growing conditions. The growth curve analysis of transfected and WT B. microti are similar indicating no defects in the transgenic parasites. This study will enable other researchers in understanding the B. microti biology, host modulation and diverse parasite developmental stages using reverse genetics and holds great potential to identify novel drug targets and vaccine development.
Native bacteria isolated from roots and rhizosphere of Solanum lycopersicum L. increase tomato seedling growth under a reduced fertilization regime
Authors: Pérez-Rodriguez María Micaela , Piccoli Patricia , Anzuay María Soledad , Baraldi Rita , Neri Luisa , Taurian Tania , Lobato Ureche Miguel Andrés , Segura Diana María , Cohen Ana Carmen
Published: September 2020

In semiarid regions is important to use native strains best adapted to these environments to optimize plant-PGPR interaction. We aimed to isolate and characterize PGPR from roots and rhizosphere of a tomato crop, as well as studying the effect of its inoculation on tomato seedlings growth. We selected four strains considering their effectiveness of fixing nitrogen, solubilizing phosphate, producing siderophores and indole acetic acid. They belong to the genera Enterobacter, Pseudomonas, Cellulosimicrobium, and Ochrobactrum. In addition, we also analyzed the ability to solubilize Ca3(PO4)2, FePO4 and AlPO4 and the presence of one of the genes encoding the cofactor PQQ in their genome. Enterobacter 64S1 and Pseudomonas 42P4 showed the highest phosphorus solubilizing activity and presence of pqqE gene. Furthermore, in a tomato-based bioassay in speed-bed demonstrated that a sole inoculation at seedling stage with the strains increased dry weight of roots (49–88%) and shoots (39–55%), stem height (8–13%) and diameter (5–8%) and leaf area (22–31%) and were equal or even higher than fertilization treatment. Leaf nitrogen and chlorophyll levels were also increased (50–80% and 26–33%) compared to control. These results suggest that Enterobacter 64S1 and Pseudomonas 42P4 can be used as bio-inoculant in order to realize a nutrient integrated management.
Burn resuscitation strategy influences the gut microbiota-liver axis in swine
Authors: Muraoka Wayne T. , Granados Jose C. , Gomez Belinda I. , Nicholson Susannah E. , Chung Kevin K. , Shupp Jeffrey W. , Bynum James A. , Dubick Michael A. , Burmeister David M.
Published: September 2020

Fluid resuscitation improves clinical outcomes of burn patients; however, its execution in resource-poor environments may have to be amended with limited-volume strategies. Liver dysfunction is common in burn patients and gut dysbiosis is an understudied aspect of burn sequelae. Here, the swine gut microbiota and liver transcripts were investigated to determine the impact of standard-of-care modified Brooke (MB), limited-volume colloid (LV-Co), and limited-volume crystalloid (LV-Cr) resuscitation on the gut microbiota, and to evaluate its' potential relationship with liver dysfunction. Independent of resuscitation strategy, bacterial diversity was reduced 24 h post-injury, and remained perturbed at 48 h. Changes in community structure were most pronounced with LV-Co, and correlated with biomarkers of hepatocellular damage. Hierarchical clustering revealed a group of samples that was suggestive of dysbiosis, and LV-Co increased the risk of association with this group. Compared with MB, LV-Co and LV-Cr significantly altered cellular stress and ATP pathways, and gene expression of these perturbed pathways was correlated with major dysbiosis-associated bacteria. Taken together, LV-Co resuscitation exacerbated the loss of bacterial diversity and increased the risk of dysbiosis. Moreover, we present evidence of a linkage between liver (dys)function and the gut microbiota in the acute setting of burn injury.
Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design
Authors: Kames Jacob , Holcomb David D. , Kimchi Ofer , DiCuccio Michael , Hamasaki-Katagiri Nobuko , Wang Tony , Komar Anton A. , Alexaki Aikaterini , Kimchi-Sarfaty Chava
Published: September 2020

As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses, for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.
MicroRNA molecules as predictive biomarkers of adaptive responses to strength training and physical inactivity in haemodialysis patients
Authors: Spakova Ivana , Zelko Aurel , Rabajdova Miroslava , Kolarcik Peter , Rosenberger Jaroslav , Zavacka Martina , Marekova Maria , Madarasova Geckova Andrea , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: September 2020

The miRNA-206 and miRNA-23a play an important role in muscle tissue hypertrophy, regeneration and atrophy. Both of these miRNAs have been highlighted as promising adaptation predictors; however, the available evidence on associations is inconclusive. Therefore, our aim was to assess the expression levels of these two miRNAs as predictors of change in muscle function during strength training and physical inactivity among dialysed patients. For this purpose, 46 haemodialysis patients were monitored for 12-weeks of either intradialytic strength training (EXG, n = 20) or physical inactivity during dialysis (CON, n = 26). In both groups of patients, we assessed the baseline expression levels of miRNA-23a and miRNA-206 and the isometric force generated during hip flexion (HF) contraction before and after the 12-week period. Among the EXG group, the expression of miRNA-206 predicted the change in HF (R2 = 0.63, p = 0.0005) much more strongly than the expression of miRNA-23a (R2 = 0.21, p = 0.027). Interestingly, baseline miRNA-23a (R2 = 0.30, p = 0.006) predicted the change in HF much more than miRNA-206 (p = ns) among the CON group. Our study indicates that the baseline expression of miRNA-206 could predict the response to strength training, while miRNA-23a could serve as a potential predictive marker of functional changes during physical inactivity in dialysis patients.