bluuebunny/crossref_metadata_2025 huggingface dataset:
The mRNA of TCTP functions as a sponge to maintain homeostasis of TCTP protein levels in hepatocellular carcinoma
Authors: Liu Wei , Liu Qi , Zhang Beilei , Lin Zhibin , Li Xia , Yang Xisheng , Pu Meng , Zou Rongzhi , He Zhiying , Wang Fu , Dou Kefeng
Published: November 2020

Translationally controlled tumor protein (TCTP) is a highly conserved protein that accumulated in the tumorigenesis of various malignancies. Despite the important role of TCTP protein in tumor progression, the precise function and underlying mechanistic regulation of TCTP mRNA in hepatocellular carcinoma (HCC) remain unclear. In this study, we found that TCTP protein was overexpressed in HCC patients but TCTP mRNA expression levels were reversed. TCTP knockout HCC cells exhibited attenuated abilities of proliferation, migration, and invasion. The knockdown of TCTP by siRNA effectively reduced TCTP mRNA levels but not protein levels in HCC cells. Moreover, although the constitutive knockdown of TCTP inhibited almost 80% of TCTP protein expression levels in tumors of wildtype transgenic mice (TCTP KD/WT), partial restoration of TCTP protein expression was observed in the tumors of heterozygous TCTP mice (TCTP KD/TCTP±). The blockage of mRNA synthesis with ActD stimulated TCTP protein expression in HCC cells. In contrast, combined treatment with ActD and CHX or MG132 treatment alone did not lead to the TCTP protein accumulation in cells. Furthermore, following the introduction of exogenous TCTP in cells and orthotopic HCC tumor models, the endogenous TCTP protein did not change with the recombinational TCTP expression and kept a rather stable level. Dual-luciferase assays revealed that the coding sequence of TCTP mRNA functions as a sponge to regulate the TCTP protein expression. Collectively, our results indicated that the TCTP mRNA and protein formed a closed regulatory circuit and works as a buffering system to keep the homeostasis of TCTP protein levels in HCC.
Pharmacological antagonism of kainate receptor rescues dysfunction and loss of dopamine neurons in a mouse model of human parkin-induced toxicity
Authors: Regoni Maria , Cattaneo Stefano , Mercatelli Daniela , Novello Salvatore , Passoni Alice , Bagnati Renzo , Davoli Enrico , Croci Laura , Consalez Gian Giacomo , Albanese Federica , Zanetti Letizia , Passafaro Maria , Serratto Giulia Maia , Di Fonzo Alessio , Valtorta Flavia , Ciammola Andrea , Taverna Stefano , Morari Michele , Sassone Jenny
Published: November 2020

Mutations in the PARK2 gene encoding the protein parkin cause autosomal recessive juvenile Parkinsonism (ARJP), a neurodegenerative disease characterized by dysfunction and death of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Since a neuroprotective therapy for ARJP does not exist, research efforts aimed at discovering targets for neuroprotection are critically needed. A previous study demonstrated that loss of parkin function or expression of parkin mutants associated with ARJP causes an accumulation of glutamate kainate receptors (KARs) in human brain tissues and an increase of KAR-mediated currents in neurons in vitro. Based on the hypothesis that such KAR hyperactivation may contribute to the death of nigral DA neurons, we investigated the effect of KAR antagonism on the DA neuron dysfunction and death that occur in the parkinQ311X mouse, a model of human parkin-induced toxicity. We found that early accumulation of KARs occurs in the DA neurons of the parkinQ311X mouse, and that chronic administration of the KAR antagonist UBP310 prevents DA neuron loss. This neuroprotective effect is associated with the rescue of the abnormal firing rate of nigral DA neurons and downregulation of GluK2, the key KAR subunit. This study provides novel evidence of a causal role of glutamate KARs in the DA neuron dysfunction and loss occurring in a mouse model of human parkin-induced toxicity. Our results support KAR as a potential target in the development of neuroprotective therapy for ARJP.
The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response
Authors: Gu Zhiwen , Chen Xueying , Yang Wenyong , Qi Yu , Yu Hui , Wang Xiaomeng , Gong Yanqiu , Chen Qianqian , Zhong Bo , Dai Lunzhi , Qi Shiqian , Zhang Zhiqiang , Zhang Huiyuan , Hu Hongbo
Published: November 2020

Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications, including ubiquitination, SUMOylation, and phosphorylation; however, the underlying molecular mechanism is not fully understood. In this study, TRIM60 negatively regulated the formation and activation of the TAK1 signalosome. Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I. Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination, resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways. The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562; substitution of these lysines with arginines abolished the SUMOylation of TAB2. In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock andL. monocytogenesinfection. Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response, potentially paving the way for a new strategy to control antibacterial immune responses.
Akt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth
Authors: Sun Gongping , Ding Xun Austin , Argaw Yewubdar , Guo Xiaoran , Montell Denise J.
Published: November 2020

Apoptosis is an ancient and evolutionarily conserved cell suicide program. During apoptosis, executioner caspase enzyme activation has been considered a point of no return. However, emerging evidence suggests that some cells can survive caspase activation following exposure to apoptosis-inducing stresses, raising questions as to the physiological significance and underlying molecular mechanisms of this unexpected phenomenon. Here, we show that, following severe tissue injury, Drosophila wing disc cells that survive executioner caspase activation contribute to tissue regeneration. Through RNAi screening, we identify akt1 and a previously uncharacterized Drosophila gene CG8108, which is homologous to the human gene CIZ1, as essential for survival from the executioner caspase activation. We also show that cells expressing activated oncogenes experience apoptotic caspase activation, and that Akt1 and dCIZ1 are required for their survival and overgrowth. Thus, survival following executioner caspase activation is a normal tissue repair mechanism usurped to promote oncogene-driven overgrowth.
Brightness modulations of our nearest terrestrial planet Venus reveal atmospheric super-rotation rather than surface features
Authors: Lee Y. J. , García Muñoz A. , Imamura T. , Yamada M. , Satoh T. , Yamazaki A. , Watanabe S.
Published: November 2020

Terrestrial exoplanets orbiting within or near their host stars’ habitable zone are potentially apt for life. It has been proposed that time-series measurements of reflected starlight from such planets will reveal their rotational period, main surface features and some atmospheric information. From imagery obtained with the Akatsuki spacecraft, here we show that Venus’ brightness at 283, 365, and 2020 nm is modulated by one or both of two periods of 3.7 and 4.6 days, and typical amplitudes  <10% but occasional events of 20–40%. The modulations are unrelated to the solid-body rotation; they are caused by planetary-scale waves superimposed on the super-rotating winds. Here we propose that two modulation periods whose ratio of large-to-small values is not an integer number imply the existence of an atmosphere if detected at an exoplanet, but it remains ambiguous whether the atmosphere is optically thin or thick, as for Earth or Venus respectively. Multi-wavelength and long temporal baseline observations may be required to decide between these scenarios. Ultimately, Venus represents a false positive for interpretations of brightness modulations of terrestrial exoplanets in terms of surface features.
Developmental divergence of sensory stimulus representation in cortical interneurons
Authors: Kastli Rahel , Vighagen Rasmus , van der Bourg Alexander , Argunsah Ali Özgür , Iqbal Asim , Voigt Fabian F. , Kirschenbaum Daniel , Aguzzi Adriano , Helmchen Fritjof , Karayannis Theofanis
Published: November 2020

Vasocative-intestinal-peptide (VIP+) and somatostatin (SST+) interneurons are involved in modulating barrel cortex activity and perception during active whisking. Here we identify a developmental transition point of structural and functional rearrangements onto these interneurons around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Additionally, we find that Ca2+ signaling dynamics increase in precision as the cells and network mature. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ neurons at both time points. In addition, whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.
Collider bias undermines our understanding of COVID-19 disease risk and severity
Authors: Griffith Gareth J. , Morris Tim T. , Tudball Matthew J. , Herbert Annie , Mancano Giulia , Pike Lindsey , Sharp Gemma C. , Sterne Jonathan , Palmer Tom M. , Davey Smith George , Tilling Kate , Zuccolo Luisa , Davies Neil M. , Hemani Gibran
Published: November 2020

Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight the challenge of interpreting observational evidence from such non-representative samples. Collider bias can induce associations between two or more variables which affect the likelihood of an individual being sampled, distorting associations between these variables in the sample. Analysing UK Biobank data, compared to the wider cohort the participants tested for COVID-19 were highly selected for a range of genetic, behavioural, cardiovascular, demographic, and anthropometric traits. We discuss the mechanisms inducing these problems, and approaches that could help mitigate them. While collider bias should be explored in existing studies, the optimal way to mitigate the problem is to use appropriate sampling strategies at the study design stage.
Artificially innervated self-healing foams as synthetic piezo-impedance sensor skins
Authors: Guo Hongchen , Tan Yu Jun , Chen Ge , Wang Zifeng , Susanto Glenys Jocelin , See Hian Hian , Yang Zijie , Lim Zi Wei , Yang Le , Tee Benjamin C. K.
Published: November 2020

Human skin is a self-healing mechanosensory system that detects various mechanical contact forces efficiently through three-dimensional innervations. Here, we propose a biomimetic artificially innervated foam by embedding three-dimensional electrodes within a new low-modulus self-healing foam material. The foam material is synthesized from a one-step self-foaming process. By tuning the concentration of conductive metal particles in the foam at near-percolation, we demonstrate that it can operate as a piezo-impedance sensor in both piezoresistive and piezocapacitive sensing modes without the need for an encapsulation layer. The sensor is sensitive to an object’s contact force directions as well as to human proximity. Moreover, the foam material self-heals autonomously with immediate function restoration despite mechanical damage. It further recovers from mechanical bifurcations with gentle heating (70 °C). We anticipate that this material will be useful as damage robust human-machine interfaces.
The sino-nasal warzone: transcriptomic and genomic studies on sino-nasal aspergillosis in dogs
Authors: Valdes I. D. , Hart de Ruijter A. B. P. , Torres C. J. , Breuker J. C. A. , Wösten H. A. B. , de Cock H.
Published: November 2020

We previously showed that each dog with chronic non-invasive sino-nasal aspergillosis (SNA) was infected with a single genotype of Aspergillus fumigatus. Here, we studied the transcriptome of this fungal pathogen and the canine host within the biofilm resulting from the infection. We describe here transcriptomes resulting from natural infections in animal species with A. fumigatus. The host transcriptome showed high expression of IL-8 and alarmins, uncontrolled inflammatory reaction and dysregulation of the Th17 response. The fungal transcriptome showed in particular expression of genes involved in secondary metabolites and nutrient acquisition. Single-nucleotide polymorphism analysis of fungal isolates from the biofilms showed large genetic variability and changes related with adaptation to host environmental factors. This was accompanied with large phenotypic variability in in vitro stress assays, even between isolates from the same canine patient. Our analysis provides insights in genetic and phenotypic variability of Aspergillus fumigatus in biofilms of naturally infected dogs reflecting in-host adaptation. Absence of a Th17 response and dampening of the Th1 response contributes to the formation of a chronic sino-nasal warzone.
The joint automated repository for various integrated simulations (JARVIS) for data-driven materials design
Authors: Choudhary Kamal , Garrity Kevin F. , Reid Andrew C. E. , DeCost Brian , Biacchi Adam J. , Hight Walker Angela R. , Trautt Zachary , Hattrick-Simpers Jason , Kusne A. Gilad , Centrone Andrea , Davydov Albert , Jiang Jie , Pachter Ruth , Cheon Gowoon , Reed Evan , Agrawal Ankit , Qian Xiaofeng , Sharma Vinit , Zhuang Houlong , Kalinin Sergei V. , Sumpter Bobby G. , Pilania Ghanshyam , Acar Pinar , Mandal Subhasish , Haule Kristjan , Vanderbilt David , Rabe Karin , Tavazza Francesca
Published: November 2020

The Joint Automated Repository for Various Integrated Simulations (JARVIS) is an integrated infrastructure to accelerate materials discovery and design using density functional theory (DFT), classical force-fields (FF), and machine learning (ML) techniques. JARVIS is motivated by the Materials Genome Initiative (MGI) principles of developing open-access databases and tools to reduce the cost and development time of materials discovery, optimization, and deployment. The major features of JARVIS are: JARVIS-DFT, JARVIS-FF, JARVIS-ML, and JARVIS-tools. To date, JARVIS consists of ≈40,000 materials and ≈1 million calculated properties in JARVIS-DFT, ≈500 materials and ≈110 force-fields in JARVIS-FF, and ≈25 ML models for material-property predictions in JARVIS-ML, all of which are continuously expanding. JARVIS-tools provides scripts and workflows for running and analyzing various simulations. We compare our computational data to experiments or high-fidelity computational methods wherever applicable to evaluate error/uncertainty in predictions. In addition to the existing workflows, the infrastructure can support a wide variety of other technologically important applications as part of the data-driven materials design paradigm. The JARVIS datasets and tools are publicly available at the website: https://jarvis.nist.gov.
Potential-pH diagrams considering complex oxide solution phases for understanding aqueous corrosion of multi-principal element alloys
Authors: Wang Kang , Han Junsoo , Gerard Angela Yu , Scully John R. , Zhou Bi-Cheng
Published: November 2020

The potential-pH diagram, a graphical representation of the thermodynamically predominant reaction products in aqueous corrosion, is originally proposed for the corrosion of pure metals. The original approach only leads to stoichiometric oxides and hydroxides as the oxidation products. However, numerous experiments show that non-stoichiometric oxide scales are prevalent in the aqueous corrosion of alloys. In the present study, a room temperature potential-pH diagram considering oxide solid solutions, as a generalization of the traditional potential-pH diagram with stoichiometric oxides, is constructed for an FCC single-phase multi-principal element alloy (MPEA) based on the CALculation of PHAse Diagram method. The predominant reaction products, the ions in aqueous solution, and the cation distribution in oxides are predicted. The oxide solid solution is stabilized by the mixing free energy (or mixing entropy) and the stabilizing effect becomes more significant as the temperature increases. Consequently, solid solution oxides are stable in large regions of the potential-pH diagram and the mixing free energy mostly affects the equilibrium composition of the stable oxides, while the shape of stable regions for oxides is mostly determined by the structure of the stable oxides. Agreements are found for Ni2+, Fe2+, and Mn2+ between the atomic emission spectroelectrochemistry measurements and thermodynamic calculations, while deviations exist for Cr3+ and Co2+ possibly due to surface complexation with species such as Cl− and the oxide dissolution. By incorporating the solution models of oxides, the current work presents a general and more accurate way to analyze the reaction products during aqueous corrosion of MPEAs.
A nanoparticle vaccine that targets neoantigen peptides to lymphoid tissues elicits robust antitumor T cell responses
Authors: Arbelaez Carlos A. , Estrada Juan , Gessner Melissa A. , Glaus Charles , Morales Agnieszka B. , Mohn Deanna , Phee Hyewon , Lipford J. Russell , Johnston James A.
Published: November 2020

Cancer vaccines using synthetic long peptides (SLP) targeting tumor antigens have been tested in the clinic but the outcomes have been unimpressive, perhaps because these peptides elicit predominantly CD4+ T cell responses. We hypothesized that enhanced delivery of peptide antigens to, and uptake in, secondary lymphoid tissues should elicit more robust CD8+ and CD4+ T cell responses and improved anti-tumor responses. Here, we have designed SLP-containing cationic lipoplexes (SLP–Lpx) that improve delivery of peptides to myeloid cells in the spleen and lymphatics. Using the G12D KRAS mutations as neoantigens, we found that vaccination of mice with naked synthetic peptides harboring the G12D mutation with CpG adjuvant stimulated mainly CD4+ T cell responses with limited tumor growth inhibition. On the other hand, immunization with SLP–Lpx stimulated both CD4+ and CD8+ T cells and suppressed tumor growth in a CD8+ T cell-dependent manner. Combination of the SLP–Lpx vaccines with a checkpoint inhibitor led to profound growth suppression of established tumors. These studies suggest that preferential targeting of peptides derived from neoantigens to the spleen via lipoplexes elicits potent CD4+ and CD8+ T cell responses that inhibit tumor growth.
Mucosal delivery of a multistage subunit vaccine promotes development of lung-resident memory T cells and affords interleukin-17-dependent protection against pulmonary tuberculosis
Authors: Counoupas Claudio , Ferrell Kia C. , Ashhurst Anneliese , Bhattacharyya Nayan D. , Nagalingam Gayathri , Stewart Erica L. , Feng Carl G. , Petrovsky Nikolai , Britton Warwick J. , Triccas James A.
Published: November 2020

The development of effective vaccines against bacterial lung infections requires the induction of protective, pathogen-specific immune responses without deleterious inflammation within the pulmonary environment. Here, we made use of a polysaccharide-adjuvanted vaccine approach to elicit resident pulmonary T cells to protect against aerosol Mycobacterium tuberculosis infection. Intratracheal administration of the multistage fusion protein CysVac2 and the delta-inulin adjuvant Advax™ (formulated with a TLR9 agonist) provided superior protection against aerosol M. tuberculosis infection in mice, compared to parenteral delivery. Surprisingly, removal of the TLR9 agonist did not impact vaccine protection despite a reduction in cytokine-secreting T cell subsets, particularly CD4+IFN-γ+IL-2+TNF+ multifunctional T cells. CysVac2/Advax-mediated protection was associated with the induction of lung-resident, antigen-specific memory CD4+ T cells that expressed IL-17 and RORγT, the master transcriptional regulator of Th17 differentiation. IL-17 was identified as a key mediator of vaccine efficacy, with blocking of IL-17 during M. tuberculosis challenge reducing phagocyte influx, suppressing priming of pathogen-specific CD4+ T cells in local lymph nodes and ablating vaccine-induced protection. These findings suggest that tuberculosis vaccines such as CysVac2/Advax that are capable of eliciting Th17 lung-resident memory T cells are promising candidates for progression to human trials.
A comprehensive spectral assay library to quantify the Escherichia coli proteome by DIA/SWATH-MS
Authors: Midha Mukul K. , Kusebauch Ulrike , Shteynberg David , Kapil Charu , Bader Samuel L. , Reddy Panga Jaipal , Campbell David S. , Baliga Nitin S. , Moritz Robert L.
Published: November 2020

Data-Independent Acquisition (DIA) is a method to improve consistent identification and precise quantitation of peptides and proteins by mass spectrometry (MS). The targeted data analysis strategy in DIA relies on spectral assay libraries that are generally derived from a priori measurements of peptides for each species. Although Escherichia coli (E. coli) is among the best studied model organisms, so far there is no spectral assay library for the bacterium publicly available. Here, we generated a spectral assay library for 4,014 of the 4,389 annotated E. coli proteins using one- and two-dimensional fractionated samples, and ion mobility separation enabling deep proteome coverage. We demonstrate the utility of this high-quality library with robustness in quantitation of the E. coli proteome and with rapid-chromatography to enhance throughput by targeted DIA-MS. The spectral assay library supports the detection and quantification of 91.5% of all E. coli proteins at high-confidence with 56,182 proteotypic peptides, making it a valuable resource for the scientific community. Data and spectral libraries are available via ProteomeXchange (PXD020761, PXD020785) and SWATHAtlas (SAL00222-28).
Engineering bioactive surfaces on nanoparticles and their biological interactions
Authors: Matur Meghana , Madhyastha Harishkumar , Shruthi T. S. , Madhyastha Radha , Srinivas S. P. , Navya P. N. , Daima Hemant Kumar
Published: November 2020

The successful integration of nanoparticles into biomedical applications requires modulation of their surface properties so that the interaction with biological systems is regulated to minimize toxicity for biological function. In the present work, we have engineered bioactive surfaces on gold (Au) and silver (Ag) nanoparticles and subsequently evaluated their interaction with mouse skin fibroblasts and macrophages. The Au and Ag nanoparticles were synthesized using tyrosine, tryptophan, isonicotinylhydrazide, epigallocatechin gallate, and curcumin as reducing and stabilizing agents. The nanoparticles thus prepared showed surface corona and exhibited free radical scavenging and enzyme activities with limited cytotoxicity and genotoxicity. We have thus developed avenues for engineering the surface of nanoparticles for biological applications.
Formation of α-tocopherol hydroperoxide and α-tocopheroxyl radical: relevance for photooxidative stress in Arabidopsis
Authors: Kumar Aditya , Prasad Ankush , Pospíšil Pavel
Published: November 2020

Tocopherols, lipid-soluble antioxidants play a crucial role in the antioxidant defense system in higher plants. The antioxidant function of α-tocopherol has been widely studied; however, experimental data on the formation of its oxidation products is missing. In this study, we attempt to provide spectroscopic evidence on the detection of oxidation products of α-tocopherol formed by its interaction with singlet oxygen and lipid peroxyl radical. Singlet oxygen was formed using photosensitizer rose bengal and thylakoid membranes isolated from Arabidopsis thaliana. Singlet oxygen reacts with polyunsaturated fatty acid forming lipid hydroperoxide which is oxidized by ferric iron to lipid peroxyl radical. The addition of singlet oxygen to double bond carbon on the chromanol head of α-tocopherol forms α-tocopherol hydroperoxide detected using fluorescent probe swallow-tailed perylene derivative. The decomposition of α-tocopherol hydroperoxide forms α-tocopherol quinone. The hydrogen abstraction from α-tocopherol by lipid peroxyl radical forms α-tocopheroxyl radical detected by electron paramagnetic resonance. Quantification of lipid and protein hydroperoxide from the wild type and tocopherol deficient (vte1) mutant Arabidopsis leaves using a colorimetric ferrous oxidation-xylenol orange assay reveals that α-tocopherol prevents formation of both lipid and protein hydroperoxides at high light. Identification of oxidation products of α-tocopherol might contribute to a better understanding of the protective role of α-tocopherol in the prevention of oxidative damage in higher plants at high light.
Investigation of the response of tear-film neutrophils to interleukin 8 and their sensitivity to centrifugation, fixation, and incubation
Authors: Jin Yutong , Jones Lyndon , Gorbet Maud
Published: November 2020

During eye closure, a large number of neutrophils (polymorphonuclear neutrophils, PMNs) invade the ocular surface and are often referred to as tear-film PMNs. While immunophenotyping experiments have been performed on tear-film PMNs, the impact of commonly used experimental procedures on their phenotype as well as their response to interleukin-8 (IL-8), a physiological inflammatory mediator, have not yet been investigated. A gentle eye wash method was used to collect cells at home. In the morning upon awaking, participants washed their eyes with sterile phosphate buffer saline (PBS) and collected the runoff into a sterile polypropylene tube. The cell collection was then delivered to the lab within two hours. The effects of centrifugation, incubation and fixation with paraformaldehyde (PFA) before (pre-fixed staining) or after (post-fixed staining) incubation with antibodies were characterized. Tear-film PMNs as well as blood PMNs (used for comparison) were also stimulated with IL-8. To assess the reproducibility of cell collection and variability in receptor expression over time, participants were also asked to collect cells three times over a period of a month. The change in expression of surface receptors, CD11b, CD16, CD55, CD66b, important inflammatory and activation markers, and CD45 (PAN leukocyte marker) was assessed by flow cytometry. Fixing tear-film PMNs prior to the staining with antibodies resulted in a significant (fivefold or more) reduction in the expression of CD11b, CD16 and CD45 when compared to unfixed samples, while CD16 was the only receptor to undergo significant downregulation upon post-staining fixation. Furthermore, additional centrifugation step prior to antibody incubation as well as long (4 h) incubation at 37 °C resulted in significant reductions in expression of CD11b, CD16 and CD55 when compared to control samples. As opposed to blood PMNs, stimulating tear-film PMNs with IL-8 did not induce any significant changes in expression of CD11b, CD16, CD55 and CD66b. When working with collected tear-film PMNs, our results suggest that any additional centrifugation and incubation step should be avoided, or at least limited, and post fixation staining is recommended in order to preserve cell phenotype and cell integrity of tear film PMNs. Our study also adds further information on the reproducibility of the gentle eye wash as well as the inability of tear-film PMNs to modulate their surface receptors upon stimulation with IL-8. The latter may be due to prior exposure to IL-8, activation in the closed-eye environment, or a reduced ability to respond to inflammatory stimulus. Further mechanistic studies will be needed to gain a better understanding of the tear-film neutrophil phenotype.
Estimating possible bumblebee range shifts in response to climate and land cover changes
Authors: Suzuki-Ohno Yukari , Yokoyama Jun , Nakashizuka Tohru , Kawata Masakado
Published: November 2020

Wild bee decline has been reported worldwide. Some bumblebee species (Bombusspp.) have declined in Europe and North America, and their ranges have shrunk due to climate and land cover changes. In countries with limited historical and current occurrence data, it is often difficult to investigate bumblebee range shifts. Here we estimated the past/present distributions of six major bumblebee species in Japan with species distribution modeling using current occurrence data and past/present climate and land cover data. The differences identified between estimated past and present distributions indicate possible range shifts. The estimated ranges ofB. diversus,B. hypocrita,B. ignitus,B. honshuensis, andB. beaticolashrank over the past 26 years, but that ofB. ardensexpanded. The lower altitudinal limits of the estimated ranges became higher as temperature increased. When focusing on the effects of land cover change, the estimated range ofB. diversusslightly shrank due to an increase in forest area. Such increase in forest area may result from the abandonment of agricultural lands and the extension of the rotation time of planted coniferous forests and secondary forests. Managing old planted coniferous forests and secondary forests will be key to bumblebee conservation for adaptation to climate change.
Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome
Authors: Matsuki Yasuko , Matsuo Yoshitaka , Nakano Yu , Iwasaki Shintaro , Yoko Hideyuki , Udagawa Tsuyoshi , Li Sihan , Saeki Yasushi , Yoshihisa Tohru , Tanaka Keiji , Ingolia Nicholas T. , Inada Toshifumi
Published: November 2020

eIF2α phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, translational control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated translational controls during UPR. Tunicamycin-induced ER stress enhanced the levels of ubiquitination of the ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination of eS7A was required for resistance to tunicamycin, whereas E3 ligase Hel2-mediated ubiquitination of uS10 was not. Ribosome profiling showed that the monoubiquitination of eS7A was crucial for translational regulation, including the upregulation of the spliced form of HAC1 (HAC1i) mRNA and the downregulation of Histidine triad NucleoTide-binding 1 (HNT1) mRNA. Downregulation of the deubiquitinating enzyme complex Upb3-Bre5 increased the levels of ubiquitinated eS7A during UPR in an Ire1-independent manner. These findings suggest that the monoubiquitination of ribosomal protein eS7A plays a crucial role in translational controls during the ER stress response in yeast.
Selection of sponge-associated bacteria with high potential for the production of antibacterial compounds
Authors: Riyanti  , Balansa Walter , Liu Yang , Sharma Abha , Mihajlovic Sanja , Hartwig Christoph , Leis Benedikt , Rieuwpassa Frets Jonas , Ijong Frans Gruber , Wägele Heike , König Gabriele M. , Schäberle Till F.
Published: November 2020

The potential of sponge-associated bacteria for the biosynthesis of natural products with antibacterial activity was evaluated. In a preliminary screening 108 of 835 axenic isolates showed antibacterial activity. Active isolates were identified by 16S rRNA gene sequencing and selection of the most promising strains was done in a championship like approach, which can be done in every lab and field station without expensive equipment. In a competition assay, strains that inhibited most of the other strains were selected. In a second round, the strongest competitors from each host sponge competed against each other. To rule out that the best competitors selected in that way represent similar strains with the same metabolic profile, BOX PCR experiments were performed, and extracts of these strains were analysed using metabolic fingerprinting. This proved that the strains are different and have various metabolic profiles, even though belonging to the same genus,i.e. Bacillus. Furthermore, it was shown that co-culture experiments triggered the production of compounds with antibiotic activity,i.e.surfactins and macrolactin A. Since many members of the genusBacilluspossess the genetic equipment for the biosynthesis of these compounds, a potential synergism was analysed, showing synergistic effects between C14-surfactin and macrolactin A against methicillin-resistantStaphylococcus aureus(MRSA).
Investigation of slow release of urea from biodegradable single- and double-layered hollow nanofibre yarns
Authors: Javazmi Leila , Low Tobias , Ash Gavin , Young Anthony
Published: November 2020

Urea is the most common form of nitrogenous fertiliser. Recently, research has focused on the development of delivery systems to prolong fertiliser release and prevent fertiliser loss through leaching and volatilization. This study investigates and compares single- and double-layered hollow nanofibrous yarns as novel delivery systems to encapsulate and release urea. Single-layered hollow polyl-lactic acid (PLLA) nanofibre yarns loaded with urea fertiliser were fabricated using a customized electrospinning. Double-layered hollow nanofibre yarns were produced by electrospinning polyhydroxybutyrate (PHB) nanofibres as an outer layer, with urea-impregnated PLLA nanofibres as the inner layer. Scanning electron microscopy (SEM) with an energy-dispersive spectroscopy (EDS) was used to characterize the morphology of hollow electrospun nanofibre yarns. A total nitrogen instrument (TNM-1) was used to study the urea release from single- and double-layered hollow nanofibres yarn in water. A Carbon:Nitrogen (CN) elemental analyser determined encapsulated nitrogen in PLLA nanofibres samples. Results indicated that urea-impregnated double-layered hollow nanofibre yarns significantly started nitrogen releasing at much lower amount during first 12 h compared to single-layered hollow nanofibre yarns (P value = 0.000). In conclusion, double-layered hollow nanofibre yarn has potential as an effective alternative to current methods for the slow release of fertilisers and other plant-required chemicals.
Flexible and monolithically integrated multicolor light emitting diodes using morphology-controlled GaN microstructures grown on graphene films
Authors: Lee Keundong , Yoo Dongha , Oh Hongseok , Yi Gyu-Chul
Published: November 2020

We report flexible and monolithically integrated multicolor light-emitting diode (LED) arrays using morphology-controlled growth of GaN microstructures on chemical-vapor-deposited (CVD) graphene films. As the morphology-controlled growth template of GaN microstructures, we used position-controlled ZnO nanostructure arrays with different spacings grown on graphene substrates. In particular, we investigated the effect of the growth parameters, including micropattern spacings and growth time and temperature, on the morphology of the GaN microstructures when they were coated on ZnO nanostructures on graphene substrates. By optimizing the growth parameters, both GaN microrods and micropyramids formed simultaneously on the graphene substrates. Subsequent depositions of InGaN/GaN quantum well and p-GaN layers and n- and p-type metallization yielded monolithic integration of microstructural LED arrays on the same substrate, which enabled multicolor emission depending on the shape of the microstructures. Furthermore, the CVD graphene substrates beneath the microstructure LEDs facilitated transfer of the LED arrays onto any foreign substrate. In this study, Cu foil was used for flexible LEDs. The flexible devices exhibited stable electroluminescence, even under severe bending conditions. Cyclic bending tests demonstrated the excellent mechanical stability and reliability of the devices.
Mid-gestation low-dose LPS administration results in female-specific excessive weight gain upon a western style diet in mouse offspring
Authors: Dijkstra Dorieke J. , Verkaik-Schakel Rikst Nynke , Eskandar Sharon , Limonciel Alice , Stojanovska Violeta , Scherjon Sicco A. , Plösch Torsten
Published: November 2020

Gestational complications, including preeclampsia and gestational diabetes, have long-term adverse consequences for offspring’s metabolic and cardiovascular health. A low-grade systemic inflammatory response is likely mediating this. Here, we examine the consequences of LPS-induced gestational inflammation on offspring’s health in adulthood. LPS was administered to pregnant C57Bl/6J mice on gestational day 10.5. Maternal plasma metabolomics showed oxidative stress, remaining for at least 5 days after LPS administration, likely mediating the consequences for the offspring. From weaning on, all offspring was fed a control diet; from 12 to 24 weeks of age, half of the offspring received a western-style diet (WSD). The combination of LPS-exposure and WSD resulted in hyperphagia and increased body weight and body fat mass in the female offspring. This was accompanied by changes in glucose tolerance, leptin and insulin levels and gene expression in liver and adipose tissue. In the hypothalamus, expression of genes involved in food intake regulation was slightly changed. We speculate that altered food intake behaviour is a result of dysregulation of hypothalamic signalling. Our results add to understanding of how maternal inflammation can mediate long-term health consequences for the offspring. This is relevant to many gestational complications with a pro-inflammatory reaction in place.
Shifts in the developmental rate of spadefoot toad larvae cause decreased complexity of post-metamorphic pigmentation patterns
Authors: Hyeun-Ji Lee , Rendón Miguel Ángel , Liedtke Hans Christoph , Gomez-Mestre Ivan
Published: November 2020

Amphibian larvae are plastic organisms that can adjust their growth and developmental rates to local environmental conditions. The consequences of such developmental alterations have been studied in detail, both at the phenotypic and physiological levels. While largely unknown, it is of great importance to assess how developmental alterations affect the pigmentation pattern of the resulting metamorphs, because pigmentation is relevant for communication, mate choice, and camouflage and hence influences the overall fitness of the toads. Here we quantify the variation in several aspects of the pigmentation pattern of juvenile spadefoot toads experimentally induced to accelerate their larval development in response to decreased water level. It is known that induced developmental acceleration comes at the cost of reduced size at metamorphosis, higher metabolic rate, and increased oxidative stress. In this study, we show that spadefoot toads undergoing developmental acceleration metamorphosed with a less complex, more homogeneous, darker dorsal pattern consisting of continuous blotches, compared to the more contrasted pattern with segregated blotches and higher fractal dimension in normally developing individuals, and at a smaller size. We also observed a marked effect of population of origin in the complexity of the pigmentation pattern. Complexity of the post-metamorphic dorsal pigmentation could therefore be linked to pre-metamorphic larval growth and development.
Differences of liver CT perfusion of blunt trauma treated with therapeutic embolization and observation management
Authors: Wong Yon-Cheong , Wang Li-Jen , Wu Cheng-Hsien , Chen Huan-Wu , Yuan Kuo-Ching , Hsu Yu-Pao , Lin Being-Chuan , Kang Shih-Ching
Published: November 2020

Massive hepatic necrosis after therapeutic embolization has been reported. We employed a 320-detector CT scanner to compare liver perfusion differences between blunt liver trauma patients treated with embolization and observation. This prospective study with informed consent was approved by institution review board. From January 2013 to December 2016, we enrolled 16 major liver trauma patients (6 women, 10 men; mean age 34.9 ± 12.8 years) who fulfilled inclusion criteria. Liver CT perfusion parameters were calculated by a two-input maximum slope model. Of 16 patients, 9 received embolization and 7 received observation. Among 9 patients of embolization group, their arterial perfusion (78.1 ± 69.3 versus 163.1 ± 134.3 mL/min/100 mL, p = 0.011) and portal venous perfusion (74.4 ± 53.0 versus 160.9 ± 140.8 mL/min/100 mL, p = 0.008) were significantly lower at traumatic parenchyma than at non-traumatic parenchyma. Among 7 patients of observation group, only portal venous perfusion was significantly lower at traumatic parenchyma than non-traumatic parenchyma (132.1 ± 127.1 vs. 231.1 ± 174.4 mL/min/100 mL, p = 0.018). The perfusion index between groups did not differ. None had massive hepatic necrosis. They were not different in age, injury severity score and injury grades. Therefore, reduction of both arterial and portal venous perfusion can occur when therapeutic embolization was performed in preexisting major liver trauma, but hepatic perfusion index may not be compromised.
Anomalous electrical conduction and negative temperature coefficient of resistance in nanostructured gold resistive switching films
Authors: Mirigliano M. , Radice S. , Falqui A. , Casu A. , Cavaliere F. , Milani P.
Published: November 2020

We report the observation of non-metallic electrical conduction, resistive switching, and a negative temperature coefficient of resistance in nanostructured gold films above the electrical percolation and in strong-coupling regime, from room down to cryogenic temperatures (24 K). Nanostructured continuous gold films are assembled by supersonic cluster beam deposition of Au aggregates formed in the gas phase. The structure of the cluster-assembled films is characterized by an extremely high density of randomly oriented crystalline nanodomains, separated by grain boundaries and with a large number of lattice defects. Our data indicates that space charge limited conduction and Coulomb blockade are at the origin of the anomalous electrical behavior. The high density of extended defects and grain boundaries causes the localization of conduction electrons over the entire investigated temperature range.
Handicap theory is applied to females but not males in relation to mate choice in the stalk-eyed fly Sphyracephala detrahens
Authors: Takeda Koji , Furuta Tomoki , Hamada Masaki , Sato Yo , Taniguchi Kiichiro , Tanizawa Akihiro , Yagi Tomomasa , Adachi-Yamada Takashi
Published: November 2020

Handicap theory explains that exaggeratedly developed sexual traits become handicaps but serve as honest signals of quality. Because very weak signals are less likely to provide benefits than to simply incur costs, it is interesting to elucidate how sexual traits are generated and developed during evolution. Many stalk-eyed fly species belonging to tribe Diopsini exhibit marked sexual dimorphism in their eye spans, and males with larger eye spans have larger bodies and reproductive capacities, which are more advantageous in terms of contests between males and acceptance for mating by females. In this study, we investigated the role of eye span in a more primitive species,Sphyracephala detrahens,in tribe Sphyracephalini with less pronounced sexual dimorphism. Male-male, female-female, and male–female pairs showed similar contests influenced by eye span, which was correlated with nutrition and reproductive ability in both sexes. During mating, males did not distinguish between sexes and chose individuals with larger eye spans, whereas females did not choose males. However, males with larger eye spans copulated repeatedly. These results indicate that, in this species, eye span with a small sexual difference does not function in sex recognition but affects contest and reproductive outcomes, suggesting the primitive state of sexual dimorphism.
Impacts of zinc oxide nano and bulk particles on redox-enzymes of the Punica granatum callus
Authors: Farghaly Fatma A. , Radi Abeer A. , Al-Kahtany Fatma A. , Hamada Afaf M.
Published: November 2020

The structure and function of cellular membranes were sustained by redox-enzymes. We studied the interaction between the oxidative stress caused by excessive accumulation of ZnO-nanoparticles (ZnO-NPs) in plants and the role of redox-enzymes that can alleviate this stress. The crude callus extract from pomegranate, which was treated with 0, 10, and 150 µg mL−1ZnO-NPs or bulk particles (ZnO-BPs), was applied to study the activity and kinetics of redox-enzymes. The elevated ZnO-NPs, enhanced the lipoxygenase and polyphenol oxidase activity, while the ZnO-BPs did not modify them. The activities of superoxide dismutase, catalase, and phenylalanine ammonia-lyase were induced under ZnO-NPs or BPs treatments, whilst the opposite trend of peroxidase was observed. Ascorbate peroxidase activity increased under ZnO-NPs treatments but decreased under ZnO-BPs. The kinetics activity of enzymes showed changes under different levels of NPs and BPs. Additionally, NPs or BPs treatments reduced the uptake of copper, iron, magnesium, but increased zinc accumulation in callus tissues. Meanwhile, these treatments enhanced the accumulation of manganese ions but did not affect the accumulation of potassium and phosphorous in ZnO-NPs or BPs-stressed calli. Collectively, these results gave a quantitative evaluation of the competition of zinc and other minerals on the carriers, and in addition, they provided a basis for how to control ZnO-NPs or BPs toxicity via redox-enzymes.
Enhanced bioelectrochemical treatment of petroleum refinery wastewater with Labaneh whey as co-substrate
Authors: Mohanakrishna Gunda , Abu-Reesh Ibrahim M. , Pant Deepak
Published: November 2020

Petroleum refinery wastewater (PRW) that contains recalcitrant components as the major portion of constituents is difficult to treat by conventional biological processes. Microbial fuel cells (MFCs) which also produce renewable energy were found to be promising for the treatment of PRW. However, due to the high total dissolved solids and low organic matter content, the efficiency of the process is limited. Labaneh whey (LW) wastewater, having higher biodegradability and high organic matter was evaluated as co-substrate along with PRW in standard dual chambered MFC to achieve improved power generation and treatment efficiency. Among several concentrations of LW as co-substrate in the range of 5–30% (v/v) with PRW, 85:15 (PRW:LW) showed to have the highest power generation (power density (PD), 832 mW/m2), which is two times higher than the control with PRW as sole substrate (PD, 420 mW/m2). On the contrary, a maximum substrate degradation rate of 0.420 kg COD/m3-day (ξCOD, 63.10%), was registered with 80:20 feed. Higher LW ratios in PRW lead to the production of VFA which in turn gradually decreased the anolyte pH to below 4.5 (70:30 feed). This resulted in a drop in the performance of MFC with respect to power generation (274 mW/m2, 70:30 feed) and substrate degradation (ξCOD, 17.84%).