bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases
Authors: He Haibing , Bian Guangkai , Herbst-Gervasoni Corey J. , Mori Takahiro , Shinsky Stephen A. , Hou Anwei , Mu Xin , Huang Minjian , Cheng Shu , Deng Zixin , Christianson David W. , Abe Ikuro , Liu Tiangang
Published: August 2020

Catalytic versatility is an inherent property of many enzymes. In nature, terpene cyclases comprise the foundation of molecular biodiversity as they generate diverse hydrocarbon scaffolds found in thousands of terpenoid natural products. Here, we report that the catalytic activity of the terpene cyclases AaTPS and FgGS can be switched from cyclase to aromatic prenyltransferase at basic pH to generate prenylindoles. The crystal structures of AaTPS and FgGS provide insights into the catalytic mechanism of this cryptic function. Moreover, aromatic prenyltransferase activity discovered in other terpene cyclases indicates that this cryptic function is broadly conserved among the greater family of terpene cyclases. We suggest that this cryptic function is chemoprotective for the cell by regulating isoprenoid diphosphate concentrations so that they are maintained below toxic thresholds.
Synthesis and assembly of extended quintulene
Authors: Hou Hao , Zhao Xin-Jing , Tang Chun , Ju Yang-Yang , Deng Ze-Ying , Wang Xin-Rong , Feng Liu-Bin , Lin Dong-Hai , Hou Xu , Narita Akimitsu , Müllen Klaus , Tan Yuan-Zhi
Published: August 2020

Quintulene, a non-graphitic cycloarene with fivefold symmetry, has remained synthetically elusive due to its high molecular strain originating from its curved structure. Here we report the construction of extended quintulene, which was unambiguously characterized by mass and NMR spectroscopy. The extended quintulene represents a naturally curved nanocarbon based on its conical molecular geometry. It undergoes dimerization in solution via π−π stacking to form a metastable, but isolable bilayer complex. Thermodynamic and kinetic characterization reveals the dimerization process as entropy-driven and following second-order kinetics with a high activation energy. These findings provide a deeper understanding of the assembly of conical nanocarbons. Comparison of optical properties of monomer and dimer points toward a H-type interlayer coupling in the dimer.
Visualizing the enzyme mechanism of mevalonate diphosphate decarboxylase
Authors: Chen Chun-Liang , Paul Lake N. , Mermoud James C. , Steussy Calvin Nicklaus , Stauffacher Cynthia V.
Published: August 2020

Mevalonate diphosphate decarboxylases (MDDs) catalyze the ATP-dependent-Mg2+-decarboxylation of mevalonate-5-diphosphate (MVAPP) to produce isopentenyl diphosphate (IPP), which is essential in both eukaryotes and prokaryotes for polyisoprenoid synthesis. The substrates, MVAPP and ATP, have been shown to bind sequentially to MDD. Here we report crystals in which the enzyme remains active, allowing the visualization of conformational changes in Enterococcus faecalis MDD that describe sequential steps in an induced fit enzymatic reaction. Initial binding of MVAPP modulates the ATP binding pocket with a large loop movement. Upon ATP binding, a phosphate binding loop bends over the active site to recognize ATP and bring the molecules to their catalytically favored configuration. Positioned substrates then can chelate two Mg2+ ions for the two steps of the reaction. Closure of the active site entrance brings a conserved lysine to trigger dissociative phosphoryl transfer of γ-phosphate from ATP to MVAPP, followed by the production of IPP.
Reversal of pre-existing NGFR-driven tumor and immune therapy resistance
Authors: Boshuizen Julia , Vredevoogd David W. , Krijgsman Oscar , Ligtenberg Maarten A. , Blankenstein Stephanie , de Bruijn Beaunelle , Frederick Dennie T. , Kenski Juliana C. N. , Parren Mara , Brüggemann Marieke , Madu Max F. , Rozeman Elisa A. , Song Ji-Ying , Horlings Hugo M. , Blank Christian U. , van Akkooi Alexander C. J. , Flaherty Keith T. , Boland Genevieve M. , Peeper Daniel S.
Published: August 2020

Melanomas can switch to a dedifferentiated cell state upon exposure to cytotoxic T cells. However, it is unclear whether such tumor cells pre-exist in patients and whether they can be resensitized to immunotherapy. Here, we chronically expose (patient-derived) melanoma cell lines to differentiation antigen-specific cytotoxic T cells and observe strong enrichment of a pre-existing NGFRhi population. These fractions are refractory also to T cells recognizing non-differentiation antigens, as well as to BRAF + MEK inhibitors. NGFRhi cells induce the neurotrophic factor BDNF, which contributes to T cell resistance, as does NGFR. In melanoma patients, a tumor-intrinsic NGFR signature predicts anti-PD-1 therapy resistance, and NGFRhi tumor fractions are associated with immune exclusion. Lastly, pharmacologic NGFR inhibition restores tumor sensitivity to T cell attack in vitro and in melanoma xenografts. These findings demonstrate the existence of a stable and pre-existing NGFRhi multitherapy-refractory melanoma subpopulation, which ought to be eliminated to revert intrinsic resistance to immunotherapeutic intervention.
Revealing the role of crystal orientation of protective layers for stable zinc anode
Authors: Zhang Qi , Luan Jingyi , Huang Xiaobing , Wang Qi , Sun Dan , Tang Yougen , Ji Xiaobo , Wang Haiyan
Published: August 2020

Rechargeable aqueous zinc-ion batteries are a promising candidate for next-generation energy storage devices. However, their practical application is limited by the severe safety issue caused by uncontrollable dendrite growth on zinc anodes. Here we develop faceted titanium dioxide with relatively low zinc affinity, which can restrict dendrite formation and homogenize zinc deposition when served as the protective layer on zinc anodes. The as-prepared zinc anodes can be stripped and plated steadily for more than 460 h with low voltage hysteresis and flat voltage plateau in symmetric cells. This work reveals the key role of crystal orientation in zinc affinity and its internal mechanism is suitable for various crystal materials applied in the surface modification of other metal anodes such as lithium and sodium.
A neural circuit encoding mating states tunes defensive behavior in Drosophila
Authors: Liu Chenxi , Zhang Bei , Zhang Liwei , Yang Tingting , Zhang Zhewei , Gao Zihua , Zhang Wei
Published: August 2020

Social context can dampen or amplify the perception of touch, and touch in turn conveys nuanced social information. However, the neural mechanism behind social regulation of mechanosensation is largely elusive. Here we report that fruit flies exhibit a strong defensive response to mechanical stimuli to their wings. In contrast, virgin female flies being courted by a male show a compromised defensive response to the stimuli, but following mating the response is enhanced. This state-dependent switch is mediated by a functional reconfiguration of a neural circuit labelled with the Tmc-L gene in the ventral nerve cord. The circuit receives excitatory inputs from peripheral mechanoreceptors and coordinates the defensive response. While male cues suppress it via a doublesex (dsx) neuronal pathway, mating sensitizes it by stimulating a group of uterine neurons and consequently activating a leucokinin-dependent pathway. Such a modulation is crucial for the balance between defense against body contacts and sexual receptivity.
A nonenzymatic method for cleaving polysaccharides to yield oligosaccharides for structural analysis
Authors: Amicucci Matthew J. , Nandita Eshani , Galermo Ace G. , Castillo Juan Jose , Chen Siyu , Park Dayoung , Smilowitz Jennifer T. , German J. Bruce , Mills David A. , Lebrilla Carlito B.
Published: August 2020

Polysaccharides are the most abundant biomolecules in nature, but are the least understood in terms of their chemical structures and biological functions. Polysaccharides cannot be simply sequenced because they are often highly branched and lack a uniform structure. Furthermore, large polymeric structures cannot be directly analyzed by mass spectrometry techniques, a problem that has been solved for polynucleotides and proteins. While restriction enzymes have advanced genomic analysis, and trypsin has advanced proteomic analysis, there has been no equivalent enzyme for universal polysaccharide digestion. We describe the development and application of a chemical method for producing oligosaccharides from polysaccharides. The released oligosaccharides are characterized by advanced liquid chromatography–mass spectrometry (LC–MS) methods with high sensitivity, accuracy and throughput. The technique is first used to identify polysaccharides by oligosaccharide fingerprinting. Next, the polysaccharide compositions of food and feces are determined, further illustrating the utility of technique in food and clinical studies.
Distinct thalamocortical network dynamics are associated with the pathophysiology of chronic low back pain
Authors: Tu Yiheng , Fu Zening , Mao Cuiping , Falahpour Maryam , Gollub Randy L. , Park Joel , Wilson Georgia , Napadow Vitaly , Gerber Jessica , Chan Suk-Tak , Edwards Robert R. , Kaptchuk Ted J. , Liu Thomas , Calhoun Vince , Rosen Bruce , Kong Jian
Published: August 2020

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.
Transient dormant monomer states for supramolecular polymers with low dispersity
Authors: Jalani Krishnendu , Das Anjali Devi , Sasmal Ranjan , Agasti Sarit S. , George Subi J.
Published: August 2020

Temporally controlled cooperative and living supramolecular polymerization by the buffered release of monomers has been recently introduced as an important concept towards obtaining monodisperse and multicomponent self-assembled materials. In synthetic, dynamic supramolecular polymers, this requires efficient design strategies for the dormant, inactive states of the monomers to kinetically retard the otherwise spontaneous nucleation process. However, a generalized design principle for the dormant monomer states to expand the scope of precision supramolecular polymers has not been established yet, due to the enormous differences in the mechanism, energetic parameters of self-assembly and monomer exchange dynamics of the diverse class of supramolecular polymers. Here we report the concept of transient dormant states of monomers generated by redox reactions as a predictive general design to achieve monodisperse supramolecular polymers of electronically active, chromophoric or donor-acceptor, monomers. The concept has been demonstrated with charge-transfer supramolecular polymers with an alternating donor-acceptor sequence.
Enthalpy-entropy compensation of atomic diffusion originates from softening of low frequency phonons
Authors: Gelin Simon , Champagne-Ruel Alexandre , Mousseau Normand
Published: August 2020

Experimental data accumulated over more than 120 years show not only that diffusion coefficients of impurities ordinarily obey the Arrhenius law in crystalline solids, but also that diffusion pre-exponential factors measured in a same solid increase exponentially with activation energies. This so-called compensation effect has been argued to result from a universal positive linear relationship between entropic contributions and energy barriers to diffusion. However, no physical model of entropy has ever been successfully tested against experimental compensation data. Here, we solve this decades-old problem by demonstrating that atomistically computed harmonic vibrational entropic contributions account for most of compensation effects in silicon and aluminum. We then show that, on average, variations of atomic interactions along diffusion reaction paths simultaneously soften low frequency phonons and stiffen high frequency ones; because relative frequency variations are larger in the lower region of the spectrum, softening generally prevails over stiffening and entropy ubiquitously increases with energy.
Atomic-scale phase separation induced clustering of solute atoms
Authors: Zou Lianfeng , Cao Penghui , Lei Yinkai , Zakharov Dmitri , Sun Xianhu , House Stephen D. , Luo Langli , Li Jonathan , Yang Yang , Yin Qiyue , Chen Xiaobo , Li Chaoran , Qin Hailang , Stach Eric A. , Yang Judith C. , Wang Guofeng , Zhou Guangwen
Published: August 2020

Dealloying typically occurs via the chemical dissolution of an alloy component through a corrosion process. In contrast, here we report an atomic-scale nonchemical dealloying process that results in the clustering of solute atoms. We show that the disparity in the adatom–substrate exchange barriers separate Cu adatoms from a Cu–Au mixture, leaving behind a fluid phase enriched with Au adatoms that subsequently aggregate into supported clusters. Using dynamic, atomic-scale electron microscopy observations and theoretical modeling, we delineate the atomic-scale mechanisms associated with the nucleation, rotation and amorphization–crystallization oscillations of the Au clusters. We expect broader applicability of the results because the phase separation process is dictated by the inherent asymmetric adatom-substrate exchange barriers for separating dissimilar atoms in multicomponent materials.
Vernier frequency division with dual-microresonator solitons
Authors: Wang Beichen , Yang Zijiao , Zhang Xiaobao , Yi Xu
Published: August 2020

Microresonator solitons are critical to miniaturize optical frequency combs to chip scale and have the potential to revolutionize spectroscopy, metrology and timing. With the reduction of resonator diameter, high repetition rates up to 1 THz become possible, and they are advantageous to wavelength multiplexing, coherent sampling, and self-referencing. However, the detection of comb repetition rate, the precursor to all comb-based applications, becomes challenging at these repetition rates due to the limited bandwidth of photodiodes and electronics. Here, we report a dual-comb Vernier frequency division method to vastly reduce the required electrical bandwidth. Free-running 216 GHz “Vernier” solitons sample and divide the main soliton’s repetition frequency from 197 GHz to 995 MHz through electrical processing of a pair of low frequency dual-comb beat notes. Our demonstration relaxes the instrumentation requirement for microcomb repetition rate detection, and could be applied for optical clocks, optical frequency division, and microwave photonics.
Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites
Authors: Promonet Alexy , Padioleau Ismaël , Liu Yaqun , Sanz Lionel , Biernacka Anna , Schmitz Anne-Lyne , Skrzypczak Magdalena , Sarrazin Amélie , Mettling Clément , Rowicka Maga , Ginalski Krzysztof , Chedin Frédéric , Chen Chun-Long , Lin Yea-Lih , Pasero Philippe
Published: August 2020

R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops in the human genome, here, we map RNA:DNA hybrids, replication stress markers and DNA double-strand breaks (DSBs) in cells depleted for Topoisomerase I (Top1), an enzyme that relaxes DNA supercoiling and prevents R-loop formation. RNA:DNA hybrids are found at both promoters (TSS) and terminators (TTS) of highly expressed genes. In contrast, the phosphorylation of RPA by ATR is only detected at TTS, which are preferentially replicated in a head-on orientation relative to the direction of transcription. In Top1-depleted cells, DSBs also accumulate at TTS, leading to persistent checkpoint activation, spreading of γ-H2AX on chromatin and global replication fork slowdown. These data indicate that fork pausing at the TTS of highly expressed genes containing R-loops prevents head-on conflicts between replication and transcription and maintains genome integrity in a Top1-dependent manner.
Storage and retrieval of microwave pulses with molecular spin ensembles
Authors: Bonizzoni Claudio , Ghirri Alberto , Santanni Fabio , Atzori Matteo , Sorace Lorenzo , Sessoli Roberta , Affronte Marco
Published: August 2020

Hybrid architectures combining complementary quantum systems will be largely used in quantum technologies and the integration of different components is one of the key issues. Thanks to their long coherence times and the easy manipulation with microwave pulses, electron spins hold a potential for the realization of quantum memories. Here, we test diluted oxovanadium tetraphenyl porphyrin (VO(TPP)) as a prototypical molecular spin system for the Storage/Retrieval of microwave pulses when embedded into planar superconducting microwave resonators. We first investigate the efficiency of several pulse sequences in addressing the spins. The Carr-Purcell and the Uhrig Dynamical Decoupling enhance the memory time up to three times with threeπpulses. We then successfully store and retrieve trains of up to 5 small pulses by using a single recovery pulse. These results demonstrate the memory capabilities of molecular spin ensembles when embedded into quantum circuits.
Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling
Authors: Reeves P. M. , Raju Paul S. , Baeten L. , Korek S. E. , Yi Y. , Hess J. , Sobell D. , Scholzen A. , Garritsen A. , De Groot A. S. , Moise L. , Brauns T. , Bowen R. , Sluder A. E. , Poznansky M. C.
Published: August 2020

Q-fever is a flu-like illness caused byCoxiella burnetii(Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune protection toCbinfection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control ofCbinfection. Using a vaccine-challenge model in HLA-DR transgenic mice, we demonstrated significant alterations in circulating T-cell and innate immune populations that distinguished vaccinated from naïve mice within 10 days, and persisted until at least 35 days post-vaccination. Following challenge, vaccinated mice exhibited reduced bacterial burden and splenomegaly, along with distinct effector T-cell and monocyte profiles. Correlation of HDI data to serological and pathological measurements was performed. Our data indicate a Th1-biased response toCb, consistent with previous reports, and identify Ly6C, CD73, and T-bet expression in T-cell, NK-cell, and monocytic populations as distinguishing features between vaccinated and naïve mice. This study refines the understanding of the integrated immune response toCbvaccine and challenge, which can inform the assessment of candidate vaccines forCb.
Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment
Authors: Cho Hanna , Kim Young-Eun , Chae Wonjeong , Kim Ko Woon , Kim Jong-Won , Kim Hee Jin , Na Duk L. , Ki Chang-Seok , Seo Sang Won
Published: August 2020

The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer’s disease (AD). We sought to investigate the distribution of APOE genotypes across the full clinical AD spectrum including AD, late-stage amnestic mild cognitive impairment (L-aMCI), early-stage aMCI (E-aMCI), subjective memory impairment (SMI), and controls. We prospectively recruited 713 AD patients, 735 aMCI patients, 575 SMI patients, and 8,260 individuals as controls. The frequency of the APOE e4 allele revealed an ordered fashion in the AD (30.8%), L-aMCI (24.0%), E-aMCI (15.1%), SMI (11.7%), and control (9.1%) groups. APOE e3/e4 and e4/e4 genotype frequencies also appeared in an ordered fashion in the AD group (39.1% of e3/e4 and 10.9% of e4/e4), as well as the L-aMCI (28.3% and 9.4%), E-aMCI (22.3% and 3.7%), SMI (18.3% and 1.9%), and control (15.1% and 0.8%) groups. In the comparisons of APOE e3/e3 vs. e3/e4 genotypes, all patient groups had a higher frequency of APOE e3/e4 relative to the control group. Relative to the SMI and E-aMCI groups, the AD and L-aMCI groups had higher frequency of the APOE e3/e4 genotype, and the AD group had a higher frequency relative to the L-aMCI group. However, there was no significant difference between the E-aMCI and SMI groups. In our longitudinal data, APOE e4 carrier showed a steeper incline slope in a clinical dementia rating sum of boxes (CDR-SB) score than APOE e4 non-carrier in SMI (B = 0.0066, p = 0.0104), E-aMCI (B = 0.0313, p < 0.0001), and L-aMCI (B = 0.0178, p = 0.0007). APOE e4 carrier showed a steeper decline slope in the CDR-SB than APOE e4 non-carrier in AD (B = − 0.0309, p = 0.0003). These findings suggest that E-aMCI and SMI are associated with a similarly increased frequency of the APOE e4 allele compared to controls, suggesting a greater genetic risk for AD and the importance of monitoring the allele more closely.
The Multiplex Efficiency Index: unveiling the Brazilian air transportation multiplex network—BATMN
Authors: Oliveira Izabela M. , Carpi Laura C. , Atman A. P. F.
Published: August 2020

Modern society is increasingly massively connected, reflecting an omnipresent tendency to organize social, economic, and technological structures in complex networks. Recently, with the advent of the so-called multiplex networks, new concepts and tools were necessary to better understand the characteristics of this type of system, as well as to analyze and quantify its performance and efficiency. The concept of diversity in multiplex networks is a striking example of this intrinsically interdisciplinary effort to better understand the nature of complex networks. In this work, we introduce the Multiplex Efficiency Index, which allows quantifying the temporal evolution of connectivity diversity, particularly when the number of layers of the multiplex network varies over time. Using data related to air passenger transportation in Brazil we investigate, through the new index, how the Brazilian air transportation network has being changing over the years due to the privatization processes of airports and mergers of airlines in Brazil. Besides that, we show how the Multiplex Efficiency Index is able to quantify fluctuations in network efficiency in a non-biased way, limiting its values between 0 and 1, taking into account the number of layers in the multiplex structure. We believe that the proposed index is of great value for the evaluation of the performance of any multiplex network, and to analyze, in a quantitative way, its temporal evolution independently of the variation in the number of layers.
Gold nanoparticles disrupt actin organization and pulmonary endothelial barriers
Authors: Sinclair Whitney E. , Chang Huei-Huei , Dan Arkaprava , Kenis Paul J. A. , Murphy Catherine J. , Leckband Deborah E.
Published: August 2020

This study explored the impact of gold nanoparticles on the metabolic activity and morphology of human pulmonary endothelial cell monolayers. We developed a gold nanoparticle library of three different sizes and two surface chemistries that include anionic citrate and the cationic polyelectrolyte poly(allylamine hydrochloride). The nanoparticles were characterized in cell culture medium to assess how their physical properties are altered after exposure to biological fluids. A bovine serum albumin pretreatment protocol was developed to stabilize the nanoparticles in cell culture medium. Results of this study show that an 18 h exposure of human pulmonary artery endothelial cells to the different nanoparticles modestly affects cellular metabolic activity. However, nanoparticle exposure perturbs the cortical actin networks and induces the formation of intercellular gaps. In particular, exposure to the poly(allylamine hydrochloride)-coated particles reduces the area of cell–cell junctions—a change that correlates with increased leakiness of endothelial barriers. The presence of excess polyelectrolyte capping agents in the supernatant of poly(allylamine hydrochloride)-coated nanoparticles significantly impacts endothelial morphology. Pretreatment of the particle supernatant with bovine serum albumin mitigates the negative effects of free or bound polyelectrolytes on endothelial cell monolayers.
Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development
Authors: Ohlebusch Barbara , Borst Angela , Frankenbach Tina , Klopocki Eva , Jakob Franz , Liedtke Daniel , Graser Stephanie
Published: August 2020

Hypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We show that expression of alpl is present during embryonic stages and in adult neuronal tissues. Analyses of enzyme function reveal zones of pronounced Tnap-activity within the telencephalon and the mesencephalon. Treatment of zebrafish embryos with chemical Tnap inhibitors followed by axonal and cartilage/mineralized tissue staining imply functional consequences of Tnap deficiency on neuronal and skeletal development. Based on the results from neuronal and skeletal tissue analyses, which demonstrate an evolutionary conserved role of this enzyme, we consider zebrafish as a promising species for modeling HPP in order to discover new potential therapy strategies in the long-term.
A tailored polylactic acid/polycaprolactone biodegradable and bioactive 3D porous scaffold containing gelatin nanofibers and Taurine for bone regeneration
Authors: Samadian Hadi , Farzamfar Saeed , Vaez Ahmad , Ehterami Arian , Bit Arindam , Alam Mostafa , Goodarzi Arash , Darya Gholamhossein , Salehi Majid
Published: August 2020

The focus of the current study was to develop a functional and bioactive scaffold through the combination of 3D polylactic acid (PLA)/polycaprolactone (PCL) with gelatin nanofibers (GNFs) and Taurine (Tau) for bone defect regeneration. GNFs were fabricated via electrospinning dispersed in PLA/PCL polymer solution, Tau with different concentrations was added, and the polymer solution converted into a 3D and porous scaffold via the thermally-induced phase separation technique. The characterization results showed that the scaffolds have interconnected pores with the porosity of up to 90%. Moreover, Tau increased the wettability and weight loss rate, while compromised the compressive strengths. The scaffolds were hemo- and cytocompatible and supported cell viability and proliferation. The in vivo studies showed that the defects treated with scaffolds filled with new bone. The computed tomography (CT) imaging and histopathological observation revealed that the PLA/PCL/Gel/Tau 10% provided the highest new bone formation, angiogenesis, and woven bone among the treatment groups. Our finding illustrated that the fabricated scaffold was able to regenerate bone within the defect and can be considered as the effective scaffold for bone tissue engineering application.
Glycosylhydrolase genes control respiratory tubes sizes and airway stability
Authors: Behr Matthias , Riedel Dietmar
Published: August 2020

Tight barriers are crucial for animals. Insect respiratory cells establish barriers through their extracellular matrices. These chitinous-matrices must be soft and flexible to provide ventilation, but also tight enough to allow oxygen flow and protection against dehydration, infections, and environmental stresses. However, genes that control soft, flexible chitin-matrices are poorly known. We investigated the genes of the chitinolytic glycosylhydrolase-family 18 in the tracheal system of Drosophila melanogaster. Our findings show that five chitinases and three chitinase-like genes organize the tracheal chitin-cuticles. Most of the chitinases degrade chitin from airway lumina to enable oxygen delivery. They further improve chitin-cuticles to enhance tube stability and integrity against stresses. Unexpectedly, some chitinases also support chitin assembly to expand the tube lumen properly. Moreover, Chitinase2 plays a decisive role in the chitin-cuticle formation that establishes taenidial folds to support tube stability. Chitinase2 is apically enriched on the surface of tracheal cells, where it controls the chitin-matrix architecture independently of other known cuticular proteins or chitinases. We suppose that the principle mechanisms of chitin-cuticle assembly and degradation require a set of critical glycosylhydrolases for flexible and not-flexible cuticles. The same glycosylhydrolases support thick laminar cuticle formation and are evolutionarily conserved among arthropods.
Impact of isolation methods on the biophysical heterogeneity of single extracellular vesicles
Authors: Sharma Shivani , LeClaire Michael , Wohlschlegel James , Gimzewski James
Published: August 2020

Extracellular vesicles (EVs) have raised high expectations as a novel class of diagnostics and therapeutics. However, variabilities in EV isolation methods and the unresolved structural complexity of these biological-nanoparticles (sub-100 nm) necessitate rigorous biophysical characterization of single EVs. Here, using atomic force microscopy (AFM) in conjunction with direct stochastic optical reconstruction microscopy (dSTORM), micro-fluidic resistive pore sizing (MRPS), and multi-angle light scattering (MALS) techniques, we compared the size, structure and unique surface properties of breast cancer cell-derived small EVs (sEV) obtained using four different isolation methods. AFM and dSTORM particle size distributions showed coherent unimodal and bimodal particle size populations isolated via centrifugation and immune-affinity methods respectively. More importantly, AFM imaging revealed striking differences in sEV nanoscale morphology, surface nano-roughness, and relative abundance of non-vesicles among different isolation methods. Precipitation-based isolation method exhibited the highest particle counts, yet nanoscale imaging revealed the additional presence of aggregates and polymeric residues. Together, our findings demonstrate the significance of orthogonal label-free surface characteristics of single sEVs, not discernable via conventional particle sizing and counts alone. Quantifying key nanoscale structural characteristics of sEVs, collectively termed ‘EV-nano-metrics’ enhances the understanding of the complexity and heterogeneity of sEV isolates, with broad implications for EV-analyte based research and clinical use.
An enriched sugarcane diversity panel for utilization in genetic improvement of sugarcane
Authors: Fickett Nathanael D. , Ebrahimi Leila , Parco Arnold P. , Gutierrez Andres V. , Hale Anna L. , Pontif Michael J. , Todd James , Kimbeng Collins A. , Hoy Jeffrey W. , Ayala-Silva Tomas , Gravois Kenneth A. , Baisakh Niranjan
Published: August 2020

Sugarcane crop is important for both sugar and biofuels. A world collection of sugarcane and related grasses (WCSRG) maintained at Miami, FL contains > 1,200 non-redundant clones of different species and genera within the Saccharum complex. However, linkage of undesirable alleles with useful genes in wild species has hindered its efficient utilization in sugarcane breeding. A core collection developed previously with smaller number of clones representing WCSRG did not take into account > 120 wild/exotic clones maintained at the USDA-ARS Sugarcane Research Unit in Houma, Louisiana. Moreover, the genome complexity and sub-tropical to temperate growing climate of Louisiana warrant a region-specific core collection that can be used for base-broadening breeding aimed at efficient introgression of desirable alleles. Genetic diversity of 1,485 clones within WCSRG and Louisiana (commercials, wild/exotic) using 423 SSR alleles showed an average gene diversity (h) at 0.208 among all species groups where Erianthus-like Saccharum species (ELSS), Miscanthus spp., and S. spontaneum each formed a distinct cluster, Saccharum robustum, S. officinarum, hybrid cultivars, and S. edule grouped together in a major cluster, and Saccharum sinense and S. barberi formed distinct grouping. A 309-clone diversity panel (SDP1) was developed that captured the genetic diversity based on the combination of maximum length subtree and manual selection to maximize representation of Louisiana clones and minimize import of clones from Miami. SDP1 shared 324 alleles out of the 423 alleles in the entire population of 1,485 clones and captured the genetic diversity of the entire collection with an average gene diversity (h) at 0.163. The variation within (11–17%) and among (83–89%) the populations in SDP1 were comparable with the entire population of 1,485 clones (9–15% and 85–91%, respectively). The breadth of the genetic variation of SDP1 was exemplified by the intra- and inter-specific diversity of a 190-clone mini-core collection with markers derived from known cold-responsive genes. SDP1 will facilitate genome-wide association studies for identification of trait-specific markers for use in marker-assisted breeding in Louisiana and elsewhere.
Spray dried VSV-vectored vaccine is thermally stable and immunologically active in vivo
Authors: Toniolo Steven P. , Afkhami Sam , D’Agostino Michael R. , Lichty Brian D. , Cranston Emily D. , Xing Zhou , Thompson Michael R.
Published: August 2020

Effective vaccine delivery and coverage to rural and resource-poor countries is hindered by the dependence on cold chain storage. As such, developments of cold chain-free technologies are highly sought. Although spray dried adenoviral vectors have shown long term stability at ambient temperatures and relatively low humidity, it remains to be determined whether similar excipient formulations are applicable to other viral vectors. To address this, we have spray dried vesicular stomatitis virus (VSV)-vectors with a panel of well-characterized sugar excipients to determine the optimal formulation for vector stabilization. Upon reconstitution, we show that trehalose conferred superior stability of VSV both in vitro and in vivo. Importantly, following cold chain-free storage at elevated temperatures at 37 °C for 15 days, we show that a VSV-vectored vaccine retains its in vivo immunogenicity, whereas a liquid control completely lost its immune-stimulating ability. Our results provide foundational evidence that spray drying with properly tested excipients can stabilize viral vectors such as VSV, allowing them to be stored long-term at elevated temperatures without dependency on cold chain conditions.
Rock inhibition promotes NaV1.5 sodium channel-dependent SW620 colon cancer cell invasiveness
Authors: Poisson Lucile , Lopez-Charcas Osbaldo , Chadet Stéphanie , Bon Emeline , Lemoine Roxane , Brisson Lucie , Ouaissi Mehdi , Baron Christophe , Besson Pierre , Roger Sébastien , Moussata Driffa
Published: August 2020

The acquisition of invasive capacities by carcinoma cells, i.e. their ability to migrate through and to remodel extracellular matrices, is a determinant process leading to their dissemination and to the development of metastases. these cancer cell properties have often been associated with an increased Rho-ROCK signalling, and ROCK inhibitors have been proposed for anticancer therapies. In this study we used the selective ROCK inhibitor, Y-27632, to address the participation of the Rho-ROCK signalling pathway in the invasive properties of SW620 human colon cancer cells. Contrarily to initial assumptions, Y-27632 induced the acquisition of a pro-migratory cell phenotype and increased cancer cell invasiveness in both 3- and 2-dimensions assays. This effect was also obtained using the other ROCK inhibitor Fasudil as well as with knocking down the expression of ROCK-1 or ROCK-2, but was prevented by the inhibition of NaV1.5 voltage-gated sodium channel activity. Indeed, ROCK inhibition enhanced the activity of the pro-invasive NaV1.5 channel through a pathway that was independent of gene expression regulation. In conclusions, our evidence identifies voltage-gated sodium channels as new targets of the ROCK signalling pathway, as well as responsible for possible deleterious effects of the use of ROCK inhibitors in the treatment of cancers.
Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation
Authors: Hong Jungwan , Yoon Dongyeong , Nam Youngpyo , Seo Donggun , Kim Jong-Heon , Kim Min Sung , Lee Tae Yong , Kim Kyung Suk , Ko Pan-Woo , Lee Ho-Won , Suk Kyoungho , Kim Sang Ryong
Published: August 2020

Most cerebellar ataxias (CAs) are incurable neurological disorders, resulting in a lack of voluntary control by inflamed or damaged cerebellum. Although CA can be either directly or indirectly related to cerebellar inflammation, there is no suitable animal model of CA with neuroinflammation. In this study, we evaluated the utility of an intracerebellar injection of lipopolysaccharide (LPS) to generate an animal model of inflammatory CA. We observed that LPS administration induced the expression of pro-inflammatory molecules following activation of glial cells. In addition, the administration of LPS resulted in apoptotic Purkinje cell death and induced abnormal locomotor activities, such as impaired motor coordination and abnormal hindlimb clasping posture. Our results suggest that intracerebellar LPS administration in experimental animals may be useful for studying the inflammatory component of CA.
Neutron activation of gadolinium for ion therapy: a Monte Carlo study of charged particle beams
Authors: Van Delinder Kurt W. , Khan Rao , Gräfe James L.
Published: August 2020

This study investigates the photon production from thermal neutron capture in a gadolinium (Gd) infused tumor as a result of secondary neutrons from particle therapy. Gadolinium contrast agents used in MRI are distributed within the tumor volume and can act as neutron capture agents. As a result of particle therapy, secondary neutrons are produced and absorbed by Gd in the tumor providing potential enhanced localized dose in addition to a signature photon spectrum that can be used to produce an image of the Gd enriched tumor. To investigate this imaging application, Monte Carlo (MC) simulations were performed for 10 different particles using a 5–10 cm spread out-Bragg peak (SOBP) centered on an 8 cm3, 3 mg/g Gd infused tumor. For a proton beam, 1.9 × 106 neutron captures per RBE weighted Gray Equivalent dose (GyE) occurred within the Gd tumor region. Antiprotons ($$\bar{P}$$

P

¯

), negative pions (− π), and helium (He) ion beams resulted in 10, 17 and 1.3 times larger Gd neutron captures per GyE than protons, respectively. Therefore, the characteristic photon based spectroscopic imaging and secondary Gd dose enhancement could be viable and likely beneficial for these three particles.
Psychological predictors of quality of life after anterior cervical discectomy and fusion for degenerative cervical spine disease
Authors: Wagner Arthur , Shiban Youssef , Zeller Leonie , Aftahy Kaywan , Lange Nicole , Motov Stefan , Joerger Ann-Kathrin , Meyer Bernhard , Shiban Ehab
Published: August 2020

We aimed to identify independent psychological predictors of quality of life (QOL) and functional outcome after anterior cervical discectomy and fusion (ACDF) for degenerative cervical spine disease. We prospectively included patients undergoing ACDF for degenerative cervical disc herniation and stenosis. Patients completed a structured psychological assessment including the Center for Epidemiological Studies Depression Scale (ADS-K), Post-Traumatic Stress Scale-10 (PTSS-10), State Trait Anxiety Inventory-State Anxiety and - Trait Anxiety (STAI-S and STAI-T) and Anxiety Sensitivity Index-3 (ASI-3) before surgery, after 3 and 12 months. Outcome measures included EuroQol-5D (EQ), Short Form-36 (SF-36) and Oswestry Disability Index (ODI) scores. Of 104 included patients who underwent ACDF between March 2013 and November 2017, 92 completed follow-up after 3 and 12 months. The mean Visual Analogue Scale (VAS) scores for neck pain (− 1.4; p < .001) and arm pain (− 1.8; p = .031) significantly decreased by 12 months. QOL scores significantly increased by 3 months (EQ: + 0.2; p < .001; SF-36 PCS: + 6.2; p < .001; SF-36 MCS: + 2.5; p = .044), a benefit which was retained at 12 months. Linear regression analyses identified statistically significant predictors in preoperative ASI-3, SF-36 MCS and STAI-S for postoperative QOL and ODI scores. There is a benefit for patients in terms of quality of life and function after undergoing surgery for degenerative cervical spine disease. With the ASI-3, SF-36 MCS and STAI-S there exist some predictors for postoperative QOL and ODI scores.
Artificial eyespots on cattle reduce predation by large carnivores
Authors: Radford Cameron , McNutt John Weldon , Rogers Tracey , Maslen Ben , Jordan Neil
Published: August 2020

Eyespots evolved independently in many taxa as anti-predator signals. There remains debate regarding whether eyespots function as diversion targets, predator mimics, conspicuous startling signals, deceptive detection, or a combination. Although eye patterns and gaze modify human behaviour, anti-predator eyespots do not occur naturally in contemporary mammals. Here we show that eyespots painted on cattle rumps were associated with reduced attacks by ambush carnivores (lions and leopards). Cattle painted with eyespots were significantly more likely to survive than were cross-marked and unmarked cattle, despite all treatment groups being similarly exposed to predation risk. While higher survival of eyespot-painted cattle supports the detection hypothesis, increased survival of cross-marked cattle suggests an effect of novel and conspicuous marks more generally. To our knowledge, this is the first time eyespots have been shown to deter large mammalian predators. Applying artificial marks to high-value livestock may therefore represent a cost-effective tool to reduce livestock predation.
Ab initio modeling of 2D and quasi-2D lead organohalide perovskites with divalent organic cations and a tunable band gap
Authors: Fraccarollo Alberto , Zoccante Alberto , Marchese Leonardo , Cossi Maurizio
Published: August 2020

We describe theoretically the structure and properties of layered lead organohalide perovskites, considering purely bi-dimensional (2D) PbI4 layers, and quasi-2D systems where the inorganic layers are formed by more than one lead iodide sheet.
Confocal controlled LIBS microscopy with high spatial resolution and stability
Authors: Huang Weihua , He Chunjing , Wang Yun , Zhao Weiqian , Qiu Lirong
Published: August 2020

A confocal controlled LIBS microscope for the analysis of natural ore samples with a lateral resolution of 10 μm.
A turn-on fluorescence strategy for cellular glutathione determination based on the aggregation-induced emission enhancement of self-assembled copper nanoclusters
Authors: Wang Hai-Bo , Mao An-Li , Gan Tian , Liu Yan-Ming
Published: August 2020

A turn-on fluorescence method has been designed for the determination of cellular GSH levels based on the controlled aggregation-induced emission enhancement of self-assembled CuNCs.
Poly(ethylene glycol)-mediated mineralization of metal–organic frameworks
Authors: Yu Qun , Tian Yuan , Li Meng , Jiang Yuan , Sun Haifeng , Zhang Guiqiang , Gao Zhiliang , Zhang Wei , Hao Jingcheng , Hu Ming , Cui Jiwei
Published: August 2020

Scalable mineralization of zeolitic imidazolate framework-8 nanoparticles with versatility of cargo encapsulation and excellent colloidal dispersibility and stability is engineered using poly(ethylene glycol) as the mineralizer for therapeutic delivery.
Heteropoly acid-driven assembly of glutathione into redox-responsive underwater adhesive
Authors: Liu Xiaohuan , Xu Jing , Xie Xiaoming , Ma Zhiyuan , Zheng Tingting , Wu Lixin , Li Bao , Li Wen
Published: August 2020

A glutathione-based underwater adhesive with dynamic attachment/detachment behaviour was achieved via the reversible formation and breakage of disulfide bonds of glutathione.
Tailoring a hybrid three-component photoinitiating system for 3D printing
Authors: Ley C. , IShak A. , Metral B. , Brendlé J. , Allonas X.
Published: August 2020

Hybrid photoinitiating system for additive manufacturing.
The impact of biofilm thickness-restraint and carrier type on attached growth system performance, solids characteristics and settleability
Authors: Arabgol Raheleh , Vanrolleghem Peter A. , Piculell Maria , Delatolla Robert
Published: August 2020

MBBR carrier type and physical properties have a significant effect on the solids production, detachment and subsequently the solids distribution size and settleability.
Defatted flaxseed flour improves weight loss and lipid profile in overweight and obese adults: a randomized controlled trial
Authors: Kuang Xiaotong , Kong Yan , Hu Xiaojie , Li Kelei , Guo Xiaofei , Liu Chunxiao , Han Lei , Li Duo
Published: August 2020

A randomized control trial to investigate the effect of flaxseed meal (FM) supplemented biscuits in overweight and obese participants found that it has beneficial effects on body weight, body composition, and blood lipids.
Peptidomic analysis of pilose antler and its inhibitory effect on triple-negative breast cancer at multiple sites
Authors: Zheng Kexin , Li Qilong , Lin Dongdong , Zong Xiaoyan , Luo Xue , Yang Mei , Yue Xiqing , Ma Shiliang
Published: August 2020

Pilose antler (PA) is a traditional Chinese functional food and 22 tumor-suppressing polypeptides was detected in its water extract. They inhibit the progression and metastasis of triple-negative 4T1 breast cancer at multiple key sites.
A one-step tannic acid coating to improve cell adhesion and proliferation on polydimethylsiloxane
Authors: Lv Xiaohui , Wang Linxiang , Fu Jingjing , Li Yuan , Yu Ling
Published: August 2020

A green and straightforward tannic acid functionalization can enhance cell adhesion and proliferation on PDMS, and thus, can be potentially used for microfluidic cell assay devices for cellular physiological study or drug screening.
Novel formation of Au/Ag bimetallic nanoparticles from a mixture of monometallic nanoparticles and their application for the rapid detection of lead in onion samples
Authors: Sahu Sushama , Sharma Srishti , Ghosh Kallol K.
Published: August 2020

Characterization of gold, silver and gold/silver bimetallic nanoparticles for colorimetric detection of lead in onion samples.
Ironvs.ruthenium: syntheses, structures and IR spectroelectrochemical characterisation of half-sandwich Group 8 acetylide complexes
Authors: Harrison Daniel P. , Kumar Varshini J. , Noppers Johanna N. , Gluyas Josef B. G. , Sobolev Alexandre N. , Moggach Stephen A. , Low Paul J.
Published: August 2020

A synthetic ‘trick’ affording complexes [M(CCR)(dppe)Cp′] (M = Fe, Ru) in high purity directly from the reaction vessel is described.
First-principles exploration of superconductivity in MXenes
Authors: Bekaert Jonas , Sevik Cem , Milošević Milorad V.
Published: August 2020

New superconducting MXenes are presented, discovered through extensive first-principles exploration, furthermore hosting interplay with other quantum phases, such as charge density waves.