bluuebunny/crossref_metadata_2025 huggingface dataset:
Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27
Authors: Wang Xiuye , Hennig Thomas , Whisnant Adam W. , Erhard Florian , Prusty Bhupesh K. , Friedel Caroline C. , Forouzmand Elmira , Hu William , Erber Luke , Chen Yue , Sandri-Goldin Rozanne M. , Dölken Lars , Shi Yongsheng
Published: January 2020

Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 3’ processing factor CPSF. It thereby induces the assembly of a dead-end 3’ processing complex, blocking mRNA 3’ cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3’ processing for viral and a subset of host transcripts. Our results unravel a bimodal activity of ICP27 that plays a key role in HSV-1-induced host shutoff and identify CPSF as an important factor that mediates regulation of transcription termination. These findings have broad implications for understanding the regulation of transcription termination by other viruses, cellular stress and cancer.
Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains
Authors: Lam Norris , Trinklein Nathan D. , Buelow Benjamin , Patterson George H. , Ojha Namrata , Kochenderfer James N.
Published: January 2020

Chimeric antigen receptor (CAR)-expressing T cells targeting B-cell maturation antigen (BCMA) have activity against multiple myeloma, but improvements in anti-BCMA CARs are needed. We demonstrated recipient anti-CAR T-cell responses against a murine single-chain variable fragment (scFv) used clinically in anti-BCMA CARs. To bypass potential anti-CAR immunogenicity and to reduce CAR binding domain size, here we designed CARs with antigen-recognition domains consisting of only a fully human heavy-chain variable domain without a light-chain domain. A CAR designated FHVH33-CD8BBZ contains a fully human heavy-chain variable domain (FHVH) plus 4-1BB and CD3ζ domains. T cells expressing FHVH33-CD8BBZ exhibit similar cytokine release, degranulation, and mouse tumor eradication as a CAR that is identical except for substitution of a scFv for FHVH33. Inclusion of 4-1BB is critical for reducing activation-induced cell death and promoting survival of T cells expressing FHVH33-containing CARs. Our results indicate that heavy-chain-only anti-BCMA CARs are suitable for evaluation in a clinical trial.
Tree species traits affect which natural enemies drive the Janzen-Connell effect in a temperate forest
Authors: Jia Shihong , Wang Xugao , Yuan Zuoqiang , Lin Fei , Ye Ji , Lin Guigang , Hao Zhanqing , Bagchi Robert
Published: January 2020

A prominent tree species coexistence mechanism suggests host-specific natural enemies inhibit seedling recruitment at high conspecific density (negative conspecific density dependence). Natural-enemy-mediated conspecific density dependence affects numerous tree populations, but its strength varies substantially among species. Understanding how conspecific density dependence varies with species’ traits and influences the dynamics of whole communities remains a challenge. Using a three-year manipulative community-scale experiment in a temperate forest, we show that plant-associated fungi, and to a lesser extent insect herbivores, reduce seedling recruitment and survival at high adult conspecific density. Plant-associated fungi are primarily responsible for reducing seedling recruitment near conspecific adults in ectomycorrhizal and shade-tolerant species. Insects, in contrast, primarily inhibit seedling recruitment of shade-intolerant species near conspecific adults. Our results suggest that natural enemies drive conspecific density dependence in this temperate forest and that which natural enemies are responsible depends on the mycorrhizal association and shade tolerance of tree species.
Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk
Authors: Wang Lijun , You Xiuling , Lotinun Sutada , Zhang Lingli , Wu Nan , Zou Weiguo
Published: January 2020

Wolff’s law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1-deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblast-osteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis.
Strategy to control magnetic coercivity by elucidating crystallization pathway-dependent microstructural evolution of magnetite mesocrystals
Authors: Park Bum Chul , Cho Jiung , Kim Myeong Soo , Ko Min Jun , Pan Lijun , Na Jin Yeong , Kim Young Keun
Published: January 2020

Mesocrystals are assemblies of smaller crystallites and have attracted attention because of their nonclassical crystallization pathway and emerging collective functionalities. Understanding the mesocrystal crystallization mechanism in chemical routes is essential for precise control of size and microstructure, which influence the function of mesocrystals. However, microstructure evolution from the nucleus stage through various crystallization pathways remains unclear. We propose a unified model on the basis of the observation of two crystallization pathways, with different ferric (oxyhydr)oxide polymorphs appearing as intermediates, producing microstructures of magnetite mesocrystal via different mechanisms. An understanding of the crystallization mechanism enables independent chemical control of the mesocrystal diameter and crystallite size, as manifested by a series of magnetic coercivity measurements. We successfully implement an experimental model system that exhibits a universal crystallite size effect on the magnetic coercivity of mesocrystals. These findings provide a general approach to controlling the microstructure through crystallization pathway selection, thus providing a strategy for controlling magnetic coercivity in magnetite systems.
Nanoelectrode design from microminiaturized honeycomb monolith with ultrathin and stiff nanoscaffold for high-energy micro-supercapacitors
Authors: Lei Zhendong , Liu Long , Zhao Huaping , Liang Feng , Chang Shilei , Li Lei , Zhang Yong , Lin Zhan , Kröger Jörg , Lei Yong
Published: January 2020

Downsizing the cell size of honeycomb monoliths to nanoscale would offer high freedom of nanostructure design beyond their capability for broad applications in different fields. However, the microminiaturization of honeycomb monoliths remains a challenge. Here, we report the fabrication of microminiaturized honeycomb monoliths—honeycomb alumina nanoscaffold—and thus as a robust nanostructuring platform to assemble active materials for micro-supercapacitors. The representative honeycomb alumina nanoscaffold with hexagonal cell arrangement and 400 nm inter-cell spacing has an ultrathin but stiff nanoscaffold with only 16 ± 2 nm cell-wall-thickness, resulting in a cell density of 4.65 × 109 cells per square inch, a surface area enhancement factor of 240, and a relative density of 0.0784. These features allow nanoelectrodes based on honeycomb alumina nanoscaffold synergizing both effective ion migration and ample electroactive surface area within limited footprint. A micro-supercapacitor is finally constructed and exhibits record high performance, suggesting the feasibility of the current design for energy storage devices.
Reference tool kinematics-kinetics and tissue surface strain data during fundamental surgical acts
Authors: Schimmoeller Tyler , Neumann Erica E. , Nagle Tara F. , Erdemir Ahmet
Published: January 2020

Haptic based surgical simulations are popular training aids in medicine. Previously, surgical tool loads and motion were measured during cutting and needle insertion on non-human tissue and several haptic based simulations were developed to enhance surgical training. However, there was a lack of realistic foundational data regarding the mechanical responses of human tissue and tools during fundamental acts of surgery, i.e., cutting, suturing, retracting, pinching and indenting. This study used four recently developed surgical tools in a variety of procedures on a diverse set of cadaver leg specimens from human donors. The kinematics and kinetics of surgical tools were recorded along with topical three-dimensional strain during commonly performed surgical procedures. Full motion and load signatures of foundational surgical acts can also be used beyond the development of authentic visual and haptic simulations of surgery, i.e., they provide mechanical specifications for the development of autonomous surgical systems.
Brian2GeNN: accelerating spiking neural network simulations with graphics hardware
Authors: Stimberg Marcel , Goodman Dan F. M. , Nowotny Thomas
Published: January 2020

“Brian” is a popular Python-based simulator for spiking neural networks, commonly used in computational neuroscience. GeNN is a C++-based meta-compiler for accelerating spiking neural network simulations using consumer or high performance grade graphics processing units (GPUs). Here we introduce a new software package, Brian2GeNN, that connects the two systems so that users can make use of GeNN GPU acceleration when developing their models in Brian, without requiring any technical knowledge about GPUs, C++ or GeNN. The new Brian2GeNN software uses a pipeline of code generation to translate Brian scripts into C++ code that can be used as input to GeNN, and subsequently can be run on suitable NVIDIA GPU accelerators. From the user’s perspective, the entire pipeline is invoked by adding two simple lines to their Brian scripts. We have shown that using Brian2GeNN, two non-trivial models from the literature can run tens to hundreds of times faster than on CPU.
Relativistic Surface Wave Oscillator in Y-Band with Large Oversized Structures Modulated by Dual Reflectors
Authors: Li Shuang , Wang Jianguo , Wang Dongyang
Published: January 2020

To increase the generation efficiency of the terahertz wave in the Y band, the idea of dual-reflector is introduced in the relativistic surface wave oscillator (SWO) with large oversized structures. The dual-reflector and the slow-wave structure (SWS) construct a resonator where the field strength of TM01 mode inside is intensively enhanced and then the efficiency is increased. The pre-modulation on electron beam caused by the reflector is also helpful in improving the output power. Meanwhile, the reflector can reduce the loss of negatively going electrons. Through the particle-in-cell (PIC) simulations, the optimized structure is tested to be stable and little power is transmitting back to the diode area. The output power reaches 138 MW in the perfectly electrical conductivity condition and the frequency is 337.7 GHz with a pure spectrum. The device’s efficiency is increased from 10.7% to 16.2%, compared with the device without any reflectors. The performance of device with lossy material is also focused on. In the situation of copper device, the output power is about 41 MW under the same input conditions and the corresponding efficiency is about 4.8%.
Hexagonal GaN nanorod-based photonic crystal slab as simultaneous yellow broadband reflector and blue emitter for phosphor-conversion white light emitting devices
Authors: Ko Suk-Min , Hur Joonseok , Lee Chulwon , Isnaeni  , Gong Su-Hyun , Kim MinKwan , Cho Yong-Hoon
Published: January 2020

We report a hexagonal GaN nanorod-based two-dimensional photonic crystal (PhC) slab for phosphor-conversion white light emitting devices analyzed by three-dimensional finite-difference time-domain simulation; this slab has a broad reflection band at yellow wavelength with low Fabry-Pérot background at normal incidence. For practical use as a wavelength-selective reflector, a buffer layer under the PhC slab is employed to sustain the nanorods in the PhC slab. However, we observed that the buffer layer placed below the slab destroys the broad reflection band due to evanescent coupling of electromagnetic field in the slab and the buffer layer. By introducing small-sized base pillars between the slab and the buffer layer, we could decouple the interaction between the slab and the buffer layer and maintain the broad reflection band without any unexpected dips. Since this GaN nanorod-based PhC slab is designed for practical light emitting devices by considering dielectric and transparent conducting layers, this structure is directly applicable for developing hybrid white light emitting devices having both an (active) blue-color-emitting nanorod emitters and a (passive) normal reflector of phosphor emission.
Removal of ammonium ion from aqueous solutions by using unmodified and H2O2-modified zeolitic waste
Authors: Vaičiukynienė Danutė , Mikelionienė Agnė , Baltušnikas Arūnas , Kantautas Aras , Radzevičius Algirdas
Published: January 2020

In the petroleum industry during a catalytic cracking process, the used zeolitic catalyst becomes waste. This article investigated the sorption capacities of ammonium ions from aqueous solutions onto the previously mentioned zeolitic waste by batch experiments. Three types of zeolitic waste were used: unmodified zeolitic waste with two different particle size distributions and H2O2-modified zeolitic waste. Several techniques, including X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET) multilayer adsorption theory measurements, and X-ray fluorescence analysis (XRF) were used to demonstrate experimentally that the zeolitic waste could be used as a sorbent for the water decontamination of NH4+ ions. The morphology of zeolitic waste investigated by scanning electron microscopy (SEM) revealed particles with a spherical shape. The nitrogen adsorption–desorption isotherms showed an isotherm mixture of types I (pure microporous) and IV (mesoporous). This suggested that the investigated zeolitic materials were mesoporous (4.84 nm) and microporous (0.852 nm), as well as containing slit/cylindric pores, according to a quench solid density functional theory (QSDFT) adsorption branch model. Zeolitic waste from the oil industry showed good NH4+ sorption properties (removal efficiency of 72%), thus becoming a potential adsorbent to be used in the treatment of contaminated aqueous effluents polluted with ammonium ions. Simultaneous waste and water decontamination can be achieved, providing a new tool and enhanced capabilities for environmental remediation.
Current-induced shuttlecock-like movement of non-axisymmetric chiral skyrmions
Authors: Murooka Remi , Leonov Andrey O. , Inoue Katsuya , Ohe Jun-ichiro
Published: January 2020

Current-induced motion of non-axisymmetric skyrmions within tilted ferromagnetic phases of polar helimagnets with the easy plane anisotropy is studied by micromagnetic simulations. Such non-axisymmetric skyrmions consist of a circular core and a crescent-shaped domain-wall region formed with respect to the tilted surrounding state. Current-driven motion of non-axisymmetric skyrmions exhibits two distinct time regimes: initially the skyrmions rotate towards the current flow direction and subsequently move along the current with the skyrmionic crescent first. According to the Thiele equation, the asymmetric distribution of the topological charge and the dissipative force tensor play an important role for giving the different velocities for the circular and the crescent-shaped constituent parts of the skyrmion what underlies such a shuttlecock-like movement. Moreover, the current-velocity relation depends on the angle of the tilted ferromagnetic phase what makes in particular the transverse velocity of skyrmions sensitive to their field-driven configurational transformation. We also argue the possibility of magnetic racetrack waveguides based on complex interplay of robust asymmetric skyrmions with multiple twisted edge states.
Role of non-linear data processing on speech recognition task in the framework of reservoir computing
Authors: Abreu Araujo Flavio , Riou Mathieu , Torrejon Jacob , Tsunegi Sumito , Querlioz Damien , Yakushiji Kay , Fukushima Akio , Kubota Hitoshi , Yuasa Shinji , Stiles Mark D. , Grollier Julie
Published: January 2020

The reservoir computing neural network architecture is widely used to test hardware systems for neuromorphic computing. One of the preferred tasks for bench-marking such devices is automatic speech recognition. This task requires acoustic transformations from sound waveforms with varying amplitudes to frequency domain maps that can be seen as feature extraction techniques. Depending on the conversion method, these transformations sometimes obscure the contribution of the neuromorphic hardware to the overall speech recognition performance. Here, we quantify and separate the contributions of the acoustic transformations and the neuromorphic hardware to the speech recognition success rate. We show that the non-linearity in the acoustic transformation plays a critical role in feature extraction. We compute the gain in word success rate provided by a reservoir computing device compared to the acoustic transformation only, and show that it is an appropriate bench-mark for comparing different hardware. Finally, we experimentally and numerically quantify the impact of the different acoustic transformations for neuromorphic hardware based on magnetic nano-oscillators.
Immediate early gene fingerprints of multi-component behaviour
Authors: Rook Noemi , Letzner Sara , Packheiser Julian , Güntürkün Onur , Beste Christian
Published: January 2020

The ability to execute different responses in an expedient temporal order is central for efficient goal-directed actions and often referred to as multi-component behaviour. However, the underlying neural mechanisms on a cellular level remain unclear. Here we establish a link between neural activity at the cellular level within functional neuroanatomical structures to this form of goal-directed behaviour by analyzing immediate early gene (IEG) expression in an animal model, the pigeon (Columba livia). We focus on the group of zif268 IEGs and ZENK in particular. We show that when birds have to cascade separate task goals, ZENK expression is increased in the avian equivalent of the mammalian prefrontal cortex, i.e. the nidopallium caudolaterale (NCL) as well as in the homologous striatum. The results provide the first link between cellular IEG expression and behavioural outcome in multitasking situations. Moreover, the data suggest that the function of the fronto-striatal circuitry is comparable across species indicating that there is limited flexibility in the implementation of complex cognition such as multi-component behaviour within functional neuroanatomical structures.
Carotenoids are used as regulators for membrane fluidity by Staphylococcus xylosus
Authors: Seel Waldemar , Baust Denise , Sons Dominik , Albers Maren , Etzbach Lara , Fuss Janina , Lipski André
Published: January 2020

Carotenoids are associated with several important biological functions as antenna pigments in photosynthesis or protectives against oxidative stress. Occasionally they were also discussed as part of the cold adaptation mechanism of bacteria. For two Staphylococcus xylosus strains we demonstrated an increased content of staphyloxanthin and other carotenoids after growth at 10 °C but no detectable carotenoids after grow at 30 °C. By in vivo measurements of generalized polarization and anisotropy with two different probes Laurdan and TMA-DPH we detected a strong increase in membrane order with a simultaneous increase in membrane fluidity at low temperatures accompanied by a broadening of the phase transition. Increased carotenoid concentration was also correlated with an increased resistance of the cells against freeze-thaw stress. In addition, the fatty acid profile showed a moderate adaptation to low temperature by increasing the portion of anteiso-branched fatty acids. The suppression of carotenoid synthesis abolished the effects observed and thus confirmed the causative function of the carotenoids in the modulation of membrane parameters. A differential transcriptome analysis demonstrated the upregulation of genes involved in carotenoid syntheses under low temperature growth conditions. The presented data suggests that upregulated synthesis of carotenoids is a constitutive component in the cold adaptation strategy of Staphylococcus xylosus and combined with modifications of the fatty acid profile constitute the adaptation to grow under low temperature conditions.
Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells
Authors: Lobos-González Lorena , Bustos Rocío , Campos América , Silva Valeria , Silva Verónica , Jeldes Emanuel , Salomon Carlos , Varas-Godoy Manuel , Cáceres-Verschae Albano , Duran Eduardo , Vera Tamara , Ezquer Fernando , Ezquer Marcelo , Burzio Verónica A. , Villegas Jaime
Published: January 2020

During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.
Ocean Sensitivity to Periodic and Constant Volcanism
Authors: Dogar Muhammad Mubashar , Sato Tomonori , Liu Fei
Published: January 2020

It is strongly believed that the explosive eruptions produce negative radiative forcing that causes long-term perturbations in the ocean. Moreover, it is anticipated that a sporadic strong cooling should initiate more vigorous vertical mixing of the upper ocean, and therefore cools the ocean more effectively than a uniform radiative forcing. However, the long-term simulations show that on average the ocean heat content responses to periodic and constant forcings are comparable. To better understand this controversy and to better quantify the post-eruption oceanic response, we conducted two sets of parallel simulations, the first with a uniform/constant volcanic forcing and the second one with a periodic volcanic forcing of magnitude 1×, 5×, 10× and 30× of Pinatubo size eruption using Geophysical Fluid Dynamics Laboratory’s coupled model, CM2.1. We systematically compared the effect of periodic volcanic forcing with an equivalent time-average volcanic cooling. Our results reveal that on average, volcanic-induced perturbations in Ocean Heat Content (OHC), and sea-level rise (SLR) following uniform and periodic eruptions are almost identical. It further emphasizes that the strength of ocean heat uptake at different ocean depths is mainly driven by the strength of the Atlantic Meridional Overturning Circulation (AMOC). These findings are important for ocean initialization in long-term climate studies, and geoengineering applications. It would help to unfold uncertainties related to ocean relaxation process, heat storage, and redistribution.
The absence of intact polar lipid-derived GDGTs in marine waters dominated by Marine Group II: Implications for lipid biosynthesis in Archaea
Authors: Besseling Marc A. , Hopmans Ellen C. , Bale Nicole J. , Schouten Stefan , Damsté Jaap S. Sinninghe , Villanueva Laura
Published: January 2020

The marine pelagic archaeal community is dominated by three major groups, the marine group I (MGI) Thaumarchaeota, and the marine groups II and III (MGII and MGIII) Euryarchaeota. Studies of both MGI cultures and the environment have shown that the MGI core membrane lipids are predominantly composed of glycerol dibiphytanyl glycerol tetraether (GDGT) lipids and the diether lipid archaeol. However, there are no cultured representatives of MGII and III archaea and, therefore, both their membrane lipid composition and potential contribution to the marine archaeal lipid pool remain unknown. Here, we show that GDGTs present in suspended particulate matter of the (sub)surface waters of the North Atlantic Ocean and the coastal North Sea are derived from MGI archaea, and that MGII archaea do not significantly contribute to the pool of GDGTs and archaeol. This implies, in contrast to previous suggestions, that their lipids do not affect the widely used sea surface temperature proxy TEX86. These findings also indicate that MGII archaea are not able to produce any known archaeal lipids, implying that our understanding of the evolution of membrane lipid biosynthesis in Archaea is far from complete.
Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population
Authors: Li Lixian , Zheng Xiaodong , Zhou Qi , Villanueva Nathaniel , Nian Weiqi , Liu Xingming , Huan Tao
Published: January 2020

Triple negative breast cancer (TNBC) is a devastating cancer disease characterized by its poor prognosis, distinct metastatic patterns, and aggressive biological behavior. Research indicates that the prevalence and presentation of TNBC varies among races, with Asian TNBC patients more commonly presenting with large invasive tumors, high node positivity, and high histologic grade. In this work, we applied ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomics to discover metabolic signatures in Asian female TNBC patients. Serum samples from 31 TNBC patients and 31 healthy controls (CN) were involved in this study. A total of 2860 metabolic features were detected in the serum samples. Among them, 77 metabolites, whose levels were significantly different between TNBC with CN, were confirmed. Using multivariate statistical analysis, literature mining, metabolic network and pathway analysis, we performed an in-depth study of the metabolic alterations in the Asian TNBC population. In addition, we discovered a panel of metabolic signatures that are highly correlated with the 5-year survival rate of the TNBC patients. This metabolomic study provides a better understanding of the metabolic details of TNBC in the Asian population.
Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain
Authors: Raldúa Demetrio , Casado Marta , Prats Eva , Faria Melissa , Puig-Castellví Francesc , Pérez Yolanda , Alfonso Ignacio , Hsu Chuan-Yu , Arick II Mark A. , Garcia-Reyero Natàlia , Ziv Tamar , Ben-Lulu Shani , Admon Arie , Piña Benjamin
Published: January 2020

Exposure to acrylamide may lead to different neurotoxic effects in humans and in experimental animals. To gain insights into this poorly understood type of neurotoxicological damage, we used a multi-omic approach to characterize the molecular changes occurring in the zebrafish brain exposed to acrylamide at metabolite, transcript and protein levels. We detected the formation of acrylamide adducts with thiol groups from both metabolites and protein residues, leading to a quasi-complete depletion of glutathione and to the inactivation of different components of the thioredoxin system. We propose that the combined loss-of-function of both redox metabolism-related systems configure a perfect storm that explains many acrylamide neurotoxic effects, like the dysregulation of genes related to microtubules, presynaptic vesicle alteration, and behavioral alterations. We consider that our mechanistical approach may help developing new treatments against the neurotoxic effects of acrylamide and of other neurotoxicants that may share its toxic mode of action.
Impact of contouring variability on oncological PET radiomics features in the lung
Authors: Yang F. , Simpson G. , Young L. , Ford J. , Dogan N. , Wang L.
Published: January 2020

Radiomics features extracted from oncological PET images are currently under intense scrutiny within the context of risk stratification for a variety of cancers. However, the lack of robustness assessment poses problems for their application across institutions and for broader patient populations. The objective of the current study was to examine the extent to which radiomics parameters from oncological PET vary in response to manual contouring variability in lung cancer. Imaging data employed in the study consisted of 26 PET scans with lesions in the lung being created through the use of an anthropomorphic phantom in conjunction with Monte Carlo simulations. From each of the simulated lesions, 25 radiomics features related to the gray-level co-occurrence matrices (GLCOM), gray-level size zone matrices (GLSZM), and gray-level neighborhood difference matrices (GLNDM) were extracted from ground truth contour and from manual contours provided by 10 raters in regard to four intensity discretization schemes with number of gray levels of 32, 64, 128, and 256, respectively. The impact of interrater variability in tumor delineation upon the agreement between raters on radiomics features was examined via interclass correlation and leave-p-out assessment. Only weak and moderate correlations were found between segmentation accuracy as measured by the Dice coefficient and percent feature error from ground truth for the vast majority of the features being examined. GLNDM-based texture parameters emerged as the top performing category of radiomcs features in terms of robustness against contouring variability for discretization schemes engaging number of gray levels of 32, 64, and 128 while GLCOM-based parameters stood out for discretization scheme engaging 256 gray levels. How and to what extent interrater reliability of radiomics features vary in response to the number of raters were largely feature-dependent. It was concluded that impact of contouring variability on PET-based radiomics features is present to varying degrees and could be experienced as a barrier to convey PET-based radiomics research to clinical relevance.
Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis
Authors: Vegi Naidu M. , Chakrabortty Sabyasachi , Zegota Maksymilian M. , Kuan Seah Ling , Stumper Anne , Rawat Vijay P. S. , Sieste Stefanie , Buske Christian , Rau Sven , Weil Tanja , Feuring-Buske Michaela
Published: January 2020

Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34+ CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells.
Long-lead Prediction of ENSO Modoki Index using Machine Learning algorithms
Authors: Pal Manali , Maity Rajib , Ratnam J. V. , Nonaka Masami , Behera Swadhin K.
Published: January 2020

The focus of this study is to evaluate the efficacy of Machine Learning (ML) algorithms in the long-lead prediction of El Niño (La Niña) Modoki (ENSO Modoki) index (EMI). We evaluated two widely used non-linear ML algorithms namely Support Vector Regression (SVR) and Random Forest (RF) to forecast the EMI at various lead times, viz. 6, 12, 18 and 24 months. The predictors for the EMI are identified using Kendall’s tau correlation coefficient between the monthly EMI index and the monthly anomalies of the slowly varying climate variables such as sea surface temperature (SST), sea surface height (SSH) and soil moisture content (SMC). The importance of each of the predictors is evaluated using the Supervised Principal Component Analysis (SPCA). The results indicate both SVR and RF to be capable of forecasting the phase of the EMI realistically at both 6-months and 12-months lead times though the amplitude of the EMI is underestimated for the strong events. The analysis also indicates the SVR to perform better than the RF method in forecasting the EMI.
Moderate Nrf2 Activation by Genetic Disruption of Keap1 Has Sex-Specific Effects on Bone Mass in Mice
Authors: Yin Yukun , Corry Kylie A. , Loughran John P. , Li Jiliang
Published: January 2020

Keap1 is a negative controller of the transcription factor Nrf2 for its activity. The Keap1/Nrf2 signaling pathway has been considered as a master regulator of cytoprotective genes, and exists in many cell types including osteoblasts and osteoclasts. Our previous study shows Nrf2 deletion decreases bone formation. Recent studies show hyperactivation of Nrf2 causes osteopenia in Keap1−/− mice, and Keap1−/− osteoblasts have significantly less proliferative potential than Keap1+/− osteoblasts. We aimed to examine if moderate Nrf2 activation by disruption of Keap1 impacts bone metabolism. We examined bone phenotype of Keap1 heterozygotic mice (Ht) in comparison with Keap1 wild type (WT) mice. Deletion or knockdown of Keap1 enhanced the gene expression of Nrf2, ALP and wnt5a in cultured primary osteoblasts compared to WT control. In male mice, compared with their age-matched littermate WT controls, Keap1 Ht mice showed significant increase in bone formation rate (+30.7%, P = 0.0029), but did not change the ultimate force (P < 0.01). The osteoclast cell numbers (−32.45%, P = 0.01) and surface (−32.58%, P = 0.03) were significantly reduced by Keap1 deficiency in male mice. Compared to male WT mice, serum bone resorption marker in male Keap1 Ht mice was significantly decreased. Our data suggest that moderate Nrf2 activation by disruption of Keap1 improved bone mass by regulating bone remodeling in male mice.
Predicting success in the worldwide start-up network
Authors: Bonaventura Moreno , Ciotti Valerio , Panzarasa Pietro , Liverani Silvia , Lacasa Lucas , Latora Vito
Published: January 2020

By drawing on large-scale online data we are able to construct and analyze the time-varying worldwide network of professional relationships among start-ups. The nodes of this network represent companies, while the links model the flow of employees and the associated transfer of know-how across companies. We use network centrality measures to assess, at an early stage, the likelihood of the long-term positive economic performance of a start-up. We find that the start-up network has predictive power and that by using network centrality we can provide valuable recommendations, sometimes doubling the current state of the art performance of venture capital funds. Our network-based approach supports the theory that the position of a start-up within its ecosystem is relevant for its future success, while at the same time it offers an effective complement to the labour-intensive screening processes of venture capital firms. Our results can also enable policy-makers and entrepreneurs to conduct a more objective assessment of the long-term potentials of innovation ecosystems, and to target their interventions accordingly.
Assessment of the heavy metal bioremediation efficiency of the novel marine lactic acid bacterium, Lactobacillus plantarum MF042018
Authors: Ameen Fatma A. , Hamdan Amira M. , El-Naggar Moustafa Y.
Published: January 2020

Heavy metal pollution is one of the most serious environmental and human health risk problem associated with industrial progress. The present study was conducted with the goal of isolation and characterization of metal-resistant lactic acid bacteria (LAB) from the Alexandrian Mediterranean Seacoast, Egypt, with their possible exploitation in metal remediation. Lactobacillus plantarum MF042018 exhibited high degree of resistance, up to 500 and 100 ppm, to both nickel and chromium, respectively, with multiple antibiotic resistance (MAR) index above 0.5. In an attempt to improve chromium removal by L. plantarum MF042018, Plackett-Burman followed by Box-Behnken statistical designs were applied. An initial Cr2+ concentration of 100 ppm and inoculum size of 3% presented the best conditions for the accumulation of chromium by L. plantarum MF042018. The study was also navigated to assess the biosorption capacity of L. plantarum MF042018, the maximum uptake capacity (q) of both Cd2+ and Pb2+ was recorded at pH 2.0 and a temperature of 22 °C after 1 hr. The biosorption process of Cd2+ and Pb2+ was well explained by the Langmuir isotherm model better than the Freundlich isotherm. Furthermore, the results revealed that the use of L. plantarum MF042018 is an effective tool for the treatment of hazardous metal-polluted battery-manufacturing effluent. Therefore, the present study implies that L. plantarum MF042018 can be applied as a promising biosorbent for the removal of heavy metals from industrial wasterwaters.
Synthesis of Au/SnO2 nanostructures allowing process variable control
Authors: Choi Myung Sik , Na Han Gil , Kim Sangwoo , Bang Jae Hoon , Oum Wansik , Choi Sun-Woo , Kim Sang Sub , Lee Kyu Hyoung , Kim Hyoun Woo , Jin Changhyun
Published: January 2020

Theoretical advances in science are inherently time-consuming to realise in engineering, since their practical application is hindered by the inability to follow the theoretical essence. Herein, we propose a new method to freely control the time, cost, and process variables in the fabrication of a hybrid featuring Au nanoparticles on a pre-formed SnO2 nanostructure. The above advantages, which were divided into six categories, are proven to be superior to those achieved elsewhere, and the obtained results are found to be applicable to the synthesis and functionalisation of other nanostructures. Furthermore, the reduction of the time-gap between science and engineering is expected to promote the practical applications of numerous scientific theories.
Defect states and kinetic parameter analysis of ZnAl2O4 nanocrystals by X-ray photoelectron spectroscopy and thermoluminescence
Authors: Jain Megha , Manju  , Kumar Ravi , Won Sung Ok , Chae Keun Hwa , Vij Ankush , Thakur Anup
Published: January 2020

Defect states in ZnAl2O4 have a significant role in its applicability as a luminescent material. To understand the nature and distribution of defects in its crystal lattice, thermoluminescence (TL) study has been carried out. Excellent TL response is observed from γ- and ultraviolet-irradiated samples at different doses and exposure durations, respectively. Different type of fuels employed in combustion synthesis show a remarkable effect on the trap distribution and hence luminescence properties. Shallow and deep traps are observed in crystals attributed to O− vacancies and F+ centers. The mechanism of trapping, retrapping and recombination have been depicted through schematic band model diagram. X-ray photoelectron spectroscopy indicated the presence of various types of defects specifically AlZn antisite defect, oxygen and zinc vacancies which are further upheld by photoluminescence and Raman spectroscopy. All results when summed up, predict ZnAl2O4 to be a quality material for dosimetry.
Retrospective analysis of clinical phenotype and prognosis of hypertrophic cardiomyopathy complicated with hypertension
Authors: Luo Qin , Chen Jin , Zhang Tianhua , Tang Xiaoyu , Yu Bilian
Published: January 2020

We here studied the clinical features, cardiac structure, and functional changes and prognosis of hypertrophic cardiomyopathy (HCM) patients with hypertension (HTN). A total of 90 HCM patients with HTN and 172 patients without HTN were divided into a hypertensive group and non-hypertensive group. The clinical characteristics, cardiac structure and function, and prognosis of the two groups were compared. Our study found that HCM patients with HTN had fewer syncope events in their medical histories (8% vs. 22%, P < 0.01) and sudden deaths in the family (3% vs. 10%, P < 0.05). The prevalence of apical hypertrophy (18% vs. 7%, P < 0.01) and midventricular obstruction (26% vs. 15%, P < 0.05) was higher in the HTN group. Besides, simple HCM patients had more pathogenic gene mutations, while those with HTN were more likely to have mutations of uncertain clinical significance (64% vs. 24%, P < 0.05). Evaluation of 5-year survival rate showed a trend for a worse prognosis in HCM patients with HTN, but the results were not statistically insignificant (P = 0.065). In conclusion, we found that the clinical phenotypes of HCM patients with HTN differed from those of patients with HCM alone, suggesting that HTN may play a pathogenic role in the pathogenesis of hypertensive hypertrophic cardiomyopathy patients.
Degeneracy in the emergence of spike-triggered average of hippocampal pyramidal neurons
Authors: Jain Abha , Narayanan Rishikesh
Published: January 2020

Hippocampal pyramidal neurons are endowed with signature excitability characteristics, exhibit theta-frequency selectivity — manifesting as impedance resonance and as a band-pass structure in the spike-triggered average (STA) — and coincidence detection tuned for gamma-frequency inputs. Are there specific constraints on molecular-scale (ion channel) properties in the concomitant emergence of cellular-scale encoding (feature detection and selectivity) and excitability characteristics? Here, we employed a biophysically-constrained unbiased stochastic search strategy involving thousands of conductance-based models, spanning 11 active ion channels, to assess the concomitant emergence of 14 different electrophysiological measurements. Despite the strong biophysical and physiological constraints, we found models that were similar in terms of their spectral selectivity, operating mode along the integrator-coincidence detection continuum and intrinsic excitability characteristics. The parametric combinations that resulted in these functionally similar models were non-unique with weak pair-wise correlations. Employing virtual knockout of individual ion channels in these functionally similar models, we found a many-to-many relationship between channels and physiological characteristics to mediate this degeneracy, and predicted a dominant role for HCN and transient potassium channels in regulating hippocampal neuronal STA. Our analyses reveals the expression of degeneracy, that results from synergistic interactions among disparate channel components, in the concomitant emergence of neuronal excitability and encoding characteristics.
In silico study of the effects of anti-arrhythmic drug treatment on sinoatrial node function for patients with atrial fibrillation
Authors: Bai Jieyun , Lu Yaosheng , Zhang Henggui
Published: January 2020

Sinus node dysfunction (SND) is often associated with atrial fibrillation (AF). Amiodarone is the most frequently used agent for maintaining sinus rhythm in patients with AF, but it impairs the sinoatrial node (SAN) function in one-third of AF patients. This study aims to gain mechanistic insights into the effects of the antiarrhythmic agents in the setting of AF-induced SND. We have adapted a human SAN model to characterize the SND conditions by incorporating experimental data on AF-induced electrical remodelling, and then integrated actions of drugs into the modified model to assess their efficacy. Reductions in pacing rate upon the implementation of AF-induced electrical remodelling associated with SND agreed with the clinical observations. And the simulated results showed the reduced funny current (If) in these remodelled targets mainly contributed to the heart rate reduction. Computational drug treatment simulations predicted a further reduction in heart rate during amiodarone administration, indicating that the reduction was the result of actions of amiodarone on INa, IKur, ICaL, ICaT, If and beta-adrenergic receptors. However, the heart rate was increased in the presence of disopyramide. We concluded that disopyramide may be a desirable choice in reversing the AF-induced SND phenotype.
Postprandial Metabolism is Impaired in Overweight Normoglycemic Young Adults without Family History of Diabetes
Authors: Kumar A. Aneesh , Satheesh Gopika , Vijayakumar Gadadharan , Chandran Mahesh , Prabhu Priya R. , Simon Leena , Kutty Vellappillil Raman , Kartha Chandrasekharan C. , Jaleel Abdul
Published: January 2020

While the risk factors for Type 2 diabetes (T2DM) are known, early predictive markers of transition from normal to a prediabetes state are unidentified. We studied the basal metabolism and metabolic response to a mixed-meal challenge in 110 healthy subjects in the age group of 18 to 40 years (Male:Female = 1:1); grouped into first degree relatives of patients with T2DM (n = 30), those with a body mass index >23 kg/m2 but <30 kg/m2 (n = 30), those with prediabetes (n = 20) and normal controls (n = 30). We performed an untargeted metabolomics analysis of plasma and related that with clinical and biochemical parameters, markers of inflammation, and insulin sensitivity. Similar to prediabetes subjects, overweight subjects had insulin resistance and significantly elevated levels of C-peptide, adiponectin and glucagon and lower level of ghrelin. Metabolites such as MG(22:2(13Z, 16Z)/0:0/0:0) and LysoPC (15:0) were reduced in overweight and prediabetes subjects. Insulin sensitivity was significantly lower in men. Fasting levels of uric acid, xanthine, and glycochenodeoxycholic-3-glucuronide were elevated in men. However, both lysophospholipids and antioxidant defense metabolites were higher in women. Impaired postprandial metabolism and insulin sensitivity in overweight normoglycemic young adults indicates a risk of developing hyperglycemia. Our results also indicate a higher risk of diabetes in young men.