bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained elevation of MG53 in the bloodstream increases tissue regenerative capacity without compromising metabolic function
Authors: Bian Zehua , Wang Qiang , Zhou Xinyu , Tan Tao , Park Ki Ho , Kramer H. Fritz , McDougal Alan , Laping Nicholas J. , Kumar Sanjay , Adesanya T. M. Ayodele , Sermersheim Matthew , Yi Frank , Wang Xinxin , Wu Junwei , Gumpper Kristyn , Jiang Qiwei , He Duofen , Lin Pei-Hui , Li Haichang , Guan Fangxia , Zhou Jingsong , Kohr Mark J. , Zeng Chunyu , Zhu Hua , Ma Jianjie
Published: October 2019

MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body.
Contribution of retrotransposition to developmental disorders
Authors: Gardner Eugene J. , Prigmore Elena , Gallone Giuseppe , Danecek Petr , Samocha Kaitlin E. , Handsaker Juliet , Gerety Sebastian S. , Ironfield Holly , Short Patrick J. , Sifrim Alejandro , Singh Tarjinder , Chandler Kate E. , Clement Emma , Lachlan Katherine L. , Prescott Katrina , Rosser Elisabeth , FitzPatrick David R. , Firth Helen V. , Hurles Matthew E.
Published: October 2019

Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands. We ascertain 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04%), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we estimate genome-wide germline ME mutation rate and selective constraint and demonstrate that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.
In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration
Authors: Zhu Meifeng , Li Wen , Dong Xianhao , Yuan Xingyu , Midgley Adam C. , Chang Hong , Wang Yuhao , Wang Haoyu , Wang Kai , Ma Peter X. , Wang Hongjun , Kong Deling
Published: October 2019

Implanted scaffolds with inductive niches can facilitate the recruitment and differentiation of host cells, thereby enhancing endogenous tissue regeneration. Extracellular matrix (ECM) scaffolds derived from cultured cells or natural tissues exhibit superior biocompatibility and trigger favourable immune responses. However, the lack of hierarchical porous structure fails to provide cells with guidance cues for directional migration and spatial organization, and consequently limit the morpho-functional integration for oriented tissues. Here, we engineer ECM scaffolds with parallel microchannels (ECM-C) by subcutaneous implantation of sacrificial templates, followed by template removal and decellularization. The advantages of such ECM-C scaffolds are evidenced by close regulation of in vitro cell activities, and enhanced cell infiltration and vascularization upon in vivo implantation. We demonstrate the versatility and flexibility of these scaffolds by regenerating vascularized and innervated neo-muscle, vascularized neo-nerve and pulsatile neo-artery with functional integration. This strategy has potential to yield inducible biomaterials with applications across tissue engineering and regenerative medicine.
Snow depth variability in the Northern Hemisphere mountains observed from space
Authors: Lievens Hans , Demuzere Matthias , Marshall Hans-Peter , Reichle Rolf H. , Brucker Ludovic , Brangers Isis , de Rosnay Patricia , Dumont Marie , Girotto Manuela , Immerzeel Walter W. , Jonas Tobias , Kim Edward J. , Koch Inka , Marty Christoph , Saloranta Tuomo , Schöber Johannes , De Lannoy Gabrielle J. M.
Published: October 2019

Accurate snow depth observations are critical to assess water resources. More than a billion people rely on water from snow, most of which originates in the Northern Hemisphere mountain ranges. Yet, remote sensing observations of mountain snow depth are still lacking at the large scale. Here, we show the ability of Sentinel-1 to map snow depth in the Northern Hemisphere mountains at 1 km² resolution using an empirical change detection approach. An evaluation with measurements from ~4000 sites and reanalysis data demonstrates that the Sentinel-1 retrievals capture the spatial variability between and within mountain ranges, as well as their inter-annual differences. This is showcased with the contrasting snow depths between 2017 and 2018 in the US Sierra Nevada and European Alps. With Sentinel-1 continuity ensured until 2030 and likely beyond, these findings lay a foundation for quantifying the long-term vulnerability of mountain snow-water resources to climate change.
Structure and functional implications of WYL domain-containing bacterial DNA damage response regulator PafBC
Authors: Müller Andreas U. , Leibundgut Marc , Ban Nenad , Weber-Ban Eilika
Published: October 2019

In mycobacteria, transcriptional activator PafBC is responsible for upregulating the majority of genes induced by DNA damage. Understanding the mechanism of PafBC activation is impeded by a lack of structural information on this transcription factor that contains a widespread, but poorly understood WYL domain frequently encountered in bacterial transcription factors. Here, we determine the crystal structure of Arthrobacter aurescens PafBC. The protein consists of two modules, each harboring an N-terminal helix-turn-helix DNA-binding domain followed by a central WYL and a C-terminal extension (WCX) domain. The WYL domains exhibit Sm-folds, while the WCX domains adopt ferredoxin-like folds, both characteristic for RNA-binding proteins. Our results suggest a mechanism of regulation in which WYL domain-containing transcription factors may be activated by binding RNA or other nucleic acid molecules. Using an in vivo mutational screen in Mycobacterium smegmatis, we identify potential co-activator binding sites on PafBC.
Few-cycle laser driven reaction nanoscopy on aerosolized silica nanoparticles
Authors: Rupp Philipp , Burger Christian , Kling Nora G. , Kübel Matthias , Mitra Sambit , Rosenberger Philipp , Weatherby Thomas , Saito Nariyuki , Itatani Jiro , Alnaser Ali S. , Raschke Markus B. , Rühl Eckart , Schlander Annika , Gallei Markus , Seiffert Lennart , Fennel Thomas , Bergues Boris , Kling Matthias F.
Published: October 2019

Nanoparticles offer unique properties as photocatalysts with large surface areas. Under irradiation with light, the associated near-fields can induce, enhance, and control molecular adsorbate reactions on the nanoscale. So far, however, there is no simple method available to spatially resolve the near-field induced reaction yield on the surface of nanoparticles. Here we close this gap by introducing reaction nanoscopy based on three-dimensional momentum-resolved photoionization. The technique is demonstrated for the spatially selective proton generation in few-cycle laser-induced dissociative ionization of ethanol and water on SiO2 nanoparticles, resolving a pronounced variation across the particle surface. The results are modeled and reproduced qualitatively by electrostatic and quasi-classical mean-field Mie Monte-Carlo (M3C) calculations. Reaction nanoscopy is suited for a wide range of isolated nanosystems and can provide spatially resolved ultrafast reaction dynamics on nanoparticles, clusters, and droplets.
Author Correction: Emerging photoluminescence from the dark-exciton phonon replica in monolayer WSe2
Authors: Li Zhipeng , Wang Tianmeng , Jin Chenhao , Lu Zhengguang , Lian Zhen , Meng Yuze , Blei Mark , Gao Shiyuan , Taniguchi Takashi , Watanabe Kenji , Ren Tianhui , Tongay Sefaattin , Yang Li , Smirnov Dmitry , Cao Ting , Shi Su-Fei
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
Authors: Bhusal Ram Prasad , Jiao Wanting , Kwai Brooke X. C. , Reynisson Jóhannes , Collins Annabelle J. , Sperry Jonathan , Bashiri Ghader , Leung Ivanhoe K. H.
Published: October 2019

Isocitrate lyase is important for lipid utilisation byMycobacterium tuberculosisbut its ICL2 isoform is poorly understood. Here we report that binding of the lipid metabolites acetyl-CoA or propionyl-CoA to ICL2 induces a striking structural rearrangement, substantially increasing isocitrate lyase and methylisocitrate lyase activities. Thus, ICL2 plays a pivotal role regulating carbon flux between the tricarboxylic acid (TCA) cycle, glyoxylate shunt and methylcitrate cycle at high lipid concentrations, a mechanism essential for bacterial growth and virulence.
Advantages of eutectic alloys for creating catalysts in the realm of nanotechnology-enabled metallurgy
Authors: Tang Jianbo , Daiyan Rahman , Ghasemian Mohammad B. , Idrus-Saidi Shuhada A. , Zavabeti Ali , Daeneke Torben , Yang Jiong , Koshy Pramod , Cheong Soshan , Tilley Richard D. , Kaner Richard B. , Amal Rose , Kalantar-Zadeh Kourosh
Published: October 2019

The nascent field of nanotechnology-enabled metallurgy has great potential. However, the role of eutectic alloys and the nature of alloy solidification in this field are still largely unknown. To demonstrate one of the promises of liquid metals in the field, we explore a model system of catalytically active Bi-Sn nano-alloys produced using a liquid-phase ultrasonication technique and investigate their phase separation, surface oxidation, and nucleation. The Bi-Sn ratio determines the grain boundary properties and the emergence of dislocations within the nano-alloys. The eutectic system gives rise to the smallest grain dimensions among all Bi-Sn ratios along with more pronounced dislocation formation within the nano-alloys. Using electrochemical CO2 reduction and photocatalysis, we demonstrate that the structural peculiarity of the eutectic nano-alloys offers the highest catalytic activity in comparison with their non-eutectic counterparts. The fundamentals of nano-alloy formation revealed here may establish the groundwork for creating bimetallic and multimetallic nano-alloys.
Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator
Authors: Riglar David T. , Richmond David L. , Potvin-Trottier Laurent , Verdegaal Andrew A. , Naydich Alexander D. , Bakshi Somenath , Leoncini Emanuele , Lyon Lorena G. , Paulsson Johan , Silver Pamela A.
Published: October 2019

Synthetic gene oscillators have the potential to control timed functions
and periodic gene expression in engineered cells. Such oscillators have been refined
in bacteria in vitro, however, these systems have lacked the robustness and
precision necessary for applications in complex in vivo environments, such as the
mammalian gut. Here, we demonstrate the implementation of a synthetic oscillator
capable of keeping robust time in the mouse gut over periods of days. The
oscillations provide a marker of bacterial growth at a single-cell level enabling
quantification of bacterial dynamics in response to inflammation and underlying
variations in the gut microbiota. Our work directly detects increased bacterial
growth heterogeneity during disease and differences between spatial niches in the
gut, demonstrating the deployment of a precise engineered genetic oscillator in
real-life settings.
The allotetraploid origin and asymmetrical genome evolution of the common carp Cyprinus carpio
Authors: Xu Peng , Xu Jian , Liu Guangjian , Chen Lin , Zhou Zhixiong , Peng Wenzhu , Jiang Yanliang , Zhao Zixia , Jia Zhiying , Sun Yonghua , Wu Yidi , Chen Baohua , Pu Fei , Feng Jianxin , Luo Jing , Chai Jing , Zhang Hanyuan , Wang Hui , Dong Chuanju , Jiang Wenkai , Sun Xiaowen
Published: October 2019

Common carp (Cyprinus carpio) is an allotetraploid species derived from recent whole genome duplication and provides a model to study polyploid genome evolution in vertebrates. Here, we generate three chromosome-level reference genomes of C. carpio and compare to related diploid Cyprinid genomes. We identify a Barbinae lineage as potential diploid progenitor of C. carpio and then divide the allotetraploid genome into two subgenomes marked by a distinct genome similarity to the diploid progenitor. We estimate that the two diploid progenitors diverged around 23 Mya and merged around 12.4 Mya based on the divergence rates of homoeologous genes and transposable elements in two subgenomes. No extensive gene losses are observed in either subgenome. Instead, we find gene expression bias across surveyed tissues such that subgenome B is more dominant in homoeologous expression. CG methylation in promoter regions may play an important role in altering gene expression in allotetraploid C. carpio.
A chemically fueled non-enzymatic bistable network
Authors: Maity Indrajit , Wagner Nathaniel , Mukherjee Rakesh , Dev Dharm , Peacock-Lopez Enrique , Cohen-Luria Rivka , Ashkenasy Gonen
Published: October 2019

One of the grand challenges in contemporary systems chemistry research is to mimic life-like functions using simple synthetic molecular networks. This is particularly true for systems that are out of chemical equilibrium and show complex dynamic behaviour, such as multi-stability, oscillations and chaos. We report here on thiodepsipeptide-based non-enzymatic networks propelled by reversible replication processes out of equilibrium, displaying bistability. Accordingly, we present quantitative analyses of the bistable behaviour, featuring a phase transition from the simple equilibration processes taking place in reversible dynamic chemistry into the bistable region. This behaviour is observed only when the system is continuously fueled by a reducing agent that keeps it far from equilibrium, and only when operating within a specifically defined parameter space. We propose that the development of biomimetic bistable systems will pave the way towards the study of more elaborate functions, such as information transfer and signalling.
Mapping the increased minimum mortality temperatures in the context of global climate change
Authors: Yin Qian , Wang Jinfeng , Ren Zhoupeng , Li Jie , Guo Yuming
Published: October 2019

Minimum mortality temperature (MMT) is an important indicator to assess the temperature–mortality relationship. It reflects human adaptability to local climate. The existing MMT estimates were usually based on case studies in data rich regions, and limited evidence about MMT was available at a global scale. It is still unclear what the most significant driver of MMT is and how MMT will change under global climate change. Here, by analysing MMTs in 420 locations covering six continents (Antarctica was excluded) in the world, we found that although the MMT changes geographically, it is very close to the local most frequent temperature (MFT) in the same period. The association between MFT and MMT is not changed when we adjust for latitude and study year. Based on the MFT~MMT association, we estimate and map the global distribution of MMTs in the present (2010s) and the future (2050s) for the first time.
Species abundance information improves sequence taxonomy classification accuracy
Authors: Kaehler Benjamin D. , Bokulich Nicholas A. , McDonald Daniel , Knight Rob , Caporaso J. Gregory , Huttley Gavin A.
Published: October 2019

Popular naive Bayes taxonomic classifiers for amplicon sequences assume that all species in the reference database are equally likely to be observed. We demonstrate that classification accuracy degrades linearly with the degree to which that assumption is violated, and in practice it is always violated. By incorporating environment-specific taxonomic abundance information, we demonstrate a significant increase in the species-level classification accuracy across common sample types. At the species level, overall average error rates decline from 25% to 14%, which is favourably comparable to the error rates that existing classifiers achieve at the genus level (16%). Our findings indicate that for most practical purposes, the assumption that reference species are equally likely to be observed is untenable. q2-clawback provides a straightforward alternative for samples from common environments.
Proteomic atlas of organ vasculopathies triggered by Staphylococcus aureus sepsis
Authors: Toledo Alejandro Gómez , Golden Gregory , Campos Alexandre Rosa , Cuello Hector , Sorrentino James , Lewis Nathan , Varki Nissi , Nizet Victor , Smith Jeffrey W. , Esko Jeffrey D.
Published: October 2019

Sepsis is a life-threatening condition triggered by a dysregulated host response to microbial infection resulting in vascular dysfunction, organ failure and death. Here we provide a semi-quantitative atlas of the murine vascular cell-surface proteome at the organ level, and how it changes during sepsis. Using in vivo chemical labeling and high-resolution mass spectrometry, we demonstrate the presence of a vascular proteome that is perfusable and shared across multiple organs. This proteome is enriched in membrane-anchored proteins, including multiple regulators of endothelial barrier functions and innate immunity. Further, we automated our workflows and applied them to a murine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis to unravel changes during systemic inflammatory responses. We provide an organ-specific atlas of both systemic and local changes of the vascular proteome triggered by sepsis. Collectively, the data indicates that MRSA-sepsis triggers extensive proteome remodeling of the vascular cell surfaces, in a tissue-specific manner.
Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus
Authors: Mugenzi Leon M. J. , Menze Benjamin D. , Tchouakui Magellan , Wondji Murielle J. , Irving Helen , Tchoupo Micareme , Hearn Jack , Weedall Gareth D. , Riveron Jacob M. , Wondji Charles S.
Published: October 2019

Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa. Applying this assay we demonstrate, using semi-field experimental huts, that CYP6P9b-mediated resistance associates with reduced effectiveness of LLINs. Furthermore, we establish that CYP6P9b combines with another P450, CYP6P9a, to additively exacerbate the reduced efficacy of insecticide-treated nets. Double homozygote resistant mosquitoes (RR/RR) significantly survive exposure to insecticide-treated nets and successfully blood feed more than other genotypes. This study provides tools to track and assess the impact of multi-gene driven metabolic resistance to pyrethroids, helping improve resistance management.
Breakdown of energy transfer gap laws revealed by full-dimensional quantum scattering between HF molecules
Authors: Yang Dongzheng , Huang Jing , Hu Xixi , Guo Hua , Xie Daiqian
Published: October 2019

Inelastic collisions involving molecular species are key to energy transfer in gaseous environments. They are commonly governed by an energy gap law, which dictates that transitions are dominated by those between initial and final states with roughly the same ro-vibrational energy. Transitions involving rotational inelasticity are often further constrained by the rotational angular momentum. Here, we demonstrate using full-dimensional quantum scattering on an ab initio based global potential energy surface (PES) that HF–HF inelastic collisions do not obey the energy and angular momentum gap laws. Detailed analyses attribute the failure of gap laws to the exceedingly strong intermolecular interaction. On the other hand, vibrational state-resolved rate coefficients are in good agreement with existing experimental results, validating the accuracy of the PES. These new and surprising results are expected to extend our understanding of energy transfer and provide a quantitative basis for numerical simulations of hydrogen fluoride chemical lasers.
Anthropogenic shift towards higher risk of flash drought over China
Authors: Yuan Xing , Wang Linying , Wu Peili , Ji Peng , Sheffield Justin , Zhang Miao
Published: October 2019

Flash droughts refer to a type of droughts that have rapid intensification without sufficient early warning. To date, how will the flash drought risk change in a warming future climate remains unknown due to a diversity of flash drought definition, unclear role of anthropogenic fingerprints, and uncertain socioeconomic development. Here we propose a new method for explicitly characterizing flash drought events, and find that the exposure risk over China will increase by about 23% ± 11% during the middle of this century under a socioeconomic scenario with medium challenge. Optimal fingerprinting shows that anthropogenic climate change induced by the increased greenhouse gas concentrations accounts for 77% ± 26% of the upward trend of flash drought frequency, and population increase is also an important factor for enhancing the exposure risk of flash drought over southernmost humid regions. Our results suggest that the traditional drought-prone regions would expand given the human-induced intensification of flash drought risk.
Second messenger Ap4A polymerizes target protein HINT1 to transduce signals in FcεRI-activated mast cells
Authors: Yu Jing , Liu Zaizhou , Liang Yuanyuan , Luo Feng , Zhang Jie , Tian Cuiping , Motzik Alex , Zheng Mengmeng , Kang Jingwu , Zhong Guisheng , Liu Cong , Fang Pengfei , Guo Min , Razin Ehud , Wang Jing
Published: October 2019

Signal transduction systems enable organisms to monitor their external environments and accordingly adjust the cellular processes. In mast cells, the second messenger Ap4A binds to the histidine triad nucleotide-binding protein 1 (HINT1), disrupts its interaction with the microphthalmia-associated transcription factor (MITF), and eventually activates the transcription of genes downstream of MITF in response to immunostimulation. How the HINT1 protein recognizes and is regulated by Ap4A remain unclear. Here, using eight crystal structures, biochemical experiments, negative stain electron microscopy, and cellular experiments, we report that Ap4A specifically polymerizes HINT1 in solution and in activated rat basophilic leukemia cells. The polymerization interface overlaps with the area on HINT1 for MITF interaction, suggesting a possible competitive mechanism to release MITF for transcriptional activation. The mechanism depends precisely on the length of the phosphodiester linkage of Ap4A. These results highlight a direct polymerization signaling mechanism by the second messenger.
Inflight leg cuff test does not identify the risk for orthostatic hypotension after long-duration spaceflight
Authors: Wood Katelyn N. , Murray Kevin R. , Greaves Danielle K. , Hughson Richard L.
Published: October 2019

Landing day symptoms from orthostatic hypotension after prolonged spaceflight can be debilitating, but severity of these symptoms can be unpredictable and highly individual. We tested the hypothesis that an impaired baroreflex response to an inflight leg cuff test could predict orthostatic intolerance on return to Earth. Eight male astronauts (44 ± 7 years of age (mean ± SD); mean mission length: 167 ± 12 days) participated in a standardized supine-to-sit-to-stand test (5 min–30s–3 min) pre- and postflight, and a 3 min thigh cuff occlusion test pre- and inflight with continuous monitoring of heart rate and arterial blood pressure. The arterial baroreflex was not changed inflight as shown by similar reductions in mean arterial pressure (MAP) response to leg cuff deflation (preflight −19 ± 2 mmHg vs. inflight −18 ± 5 mmHg). With the sit/stand test, the nadir of MAP was lower postflight (−17 ± 9 mmHg) than preflight (−11 ± 6 mmHg, p < 0.05). A greater increase in heart rate (25 ± 7; 16 ± 3 bpm) and decrease in stroke volume (−24 ± 11; −6 ± 4 mL) occurred with sit/stand postflight than leg cuffs inflight (p < 0.001). Inflight testing was influenced by elevated cardiac output resulting in a smaller drop in total peripheral resistance. Two of eight subjects exhibited orthostatic hypotension during the postflight stand test; their responses were not predicted by the inflight leg cuff deflation test. These results suggest that the baroreflex response examined by inflight leg cuff deflation was not a reliable indicator of postflight stand responses.
Quantitative Histopathology of Stained Tissues using Color Spatial Light Interference Microscopy (cSLIM)
Authors: Majeed Hassaan , Keikhosravi Adib , Kandel Mikhail E. , Nguyen Tan H. , Liu Yuming , Kajdacsy-Balla Andre , Tangella Krishnarao , Eliceiri Kevin W. , Popescu Gabriel
Published: October 2019

Tissue biopsy evaluation in the clinic is in need of quantitative disease markers for diagnosis and, most importantly, prognosis. Among the new technologies, quantitative phase imaging (QPI) has demonstrated promise for histopathology because it reveals intrinsic tissue nanoarchitecture through the refractive index. However, a vast majority of past QPI investigations have relied on imaging unstained tissues, which disrupts the established specimen processing. Here we present color spatial light interference microscopy (cSLIM) as a new whole-slide imaging modality that performs interferometric imaging on stained tissue, with a color detector array. As a result, cSLIM yields in a single scan both the intrinsic tissue phase map and the standard color bright-field image, familiar to the pathologist. Our results on 196 breast cancer patients indicate that cSLIM can provide stain-independent prognostic information from the alignment of collagen fibers in the tumor microenvironment. The effects of staining on the tissue phase maps were corrected by a mathematical normalization. These characteristics are likely to reduce barriers to clinical translation for the new cSLIM technology.
Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
Authors: Rawi Reda , Mall Raghvendra , Shen Chen-Hsiang , Farney S. Katie , Shiakolas Andrea , Zhou Jing , Bensmail Halima , Chun Tae-Wook , Doria-Rose Nicole A. , Lynch Rebecca M. , Mascola John R. , Kwong Peter D. , Chuang Gwo-Yu
Published: October 2019

Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have promising utility in prevention and treatment of HIV-1 infection, and several are currently undergoing clinical trials. Due to the high sequence diversity and mutation rate of HIV-1, viral isolates are often resistant to specific bNAbs. Currently, resistant isolates are commonly identified by time-consuming and expensive in vitro neutralization assays. Here, we report machine learning classifiers that accurately predict resistance of HIV-1 isolates to 33 bNAbs. Notably, our classifiers achieved an overall prediction accuracy of 96% for 212 clinical isolates from patients enrolled in four different clinical trials. Moreover, use of gradient boosting machine – a tree-based machine learning method – enabled us to identify critical features, which had high accordance with epitope residues that distinguished between antibody resistance and sensitivity. The availability of an in silico antibody resistance predictor should facilitate informed decisions of antibody usage and sequence-based monitoring of viral escape in clinical settings.
Identification of Genes/Proteins Related to Submergence Tolerance by Transcriptome and Proteome Analyses in Soybean
Authors: Lin Yanhui , Li Wei , Zhang Yanwei , Xia Changjian , Liu Yun , Wang Caijie , Xu Ran , Zhang Lifeng
Published: October 2019

Flooding can lead to yield reduction of soybean. Therefore, identification of flooding tolerance genes has great significance in production practice. In this study, Qihuang 34, a highly-resistant variety to flooding stress, was selected for submergence treatments. Transcriptome and proteome analyses were conducted, by which twenty-two up-regulated differentially expressed genes (DEGs)/differentially expressed proteins (DEPs) associated with five KEGG pathways were isolated. The number of the DEGs/DEPs enriched in glycolysis/gluconeogenesis was the highest. Four of these genes were confirmed by RT-qPCR, suggesting that glycolysis/gluconeogenesis may be activated to generate energy for plant survival under anaerobic conditions. Thirty-eight down-regulated DEGs/DEPs associated with six KEGG pathways were identified under submergence stress. Eight DEGs/DEPs enriched in phenylpropanoid biosynthesis were assigned to peroxidase, which catalyzes the conversion of coumaryl alcohol to hydroxy-phenyl lignin in the final step of lignin biosynthesis. Three of these genes were confirmed by RT-qPCR. The decreased expression of these genes led to the inhibition of lignin biosynthesis, which may be the cause of plant softening under submergence stress for a long period of time. This study revealed a number of up-/down-regulated pathways and the corresponding DEGs/DEPs, by which, a better understanding of the mechanisms of submergence tolerance in soybean may be achieved.
Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals
Authors: Young Jamie L. , Yan Xiaofang , Xu Jianxiang , Yin Xinmin , Zhang Xiang , Arteel Gavin E. , Barnes Gregory N. , States J. Christopher , Watson Walter H. , Kong Maiying , Cai Lu , Freedman Jonathan H.
Published: October 2019

Exposure to the environmental toxicant cadmium (Cd) contributes to the development of obesity-associated diseases. Obesity is a risk factor for a spectrum of unhealthy conditions including systemic metabolic dyshomeostasis. In the present study, the effects of whole-life exposure to environmentally-relevant concentrations of Cd on systemic essential metal distribution in adult mice fed a high-fat diet (HFD) were examined. For these studies, male and female mice were exposed to Cd-containing drinking water for >2 weeks before breeding. Pregnant mice and dams with offspring were exposed to Cd-containing drinking water. After weaning, offspring were continuously exposed to the same Cd concentration as their parents, and divided into HFD and normal (low) fat diet (LFD) groups. At 10 and 24 weeks, mice were sacrificed and blood, liver, kidney and heart harvested for metal analyses. There were significant concentration dependent increases in Cd levels in offspring with kidney > liver > heart. Sex significantly affected Cd levels in kidney and liver, with female animals accumulating more metal than males. Mice fed the HFD showed > 2-fold increase in Cd levels in the three organs compared to similarly treated LFD mice. Cadmium significantly affected essential metals levels in blood, kidney and liver. Additionally, HFD affected essential metal levels in these three organs. These findings suggest that Cd interacts with HFD to affect essential metal homeostasis, a phenomenon that may contribute to the underlying mechanism responsible for the development of obesity-associated pathologies.
Carbon and Water Use Efficiencies: A Comparative Analysis of Ten Terrestrial Ecosystem Models under Changing Climate
Authors: El Masri Bassil , Schwalm Christopher , Huntzinger Deborah N. , Mao Jiafu , Shi Xiaoying , Peng Changhui , Fisher Joshua B. , Jain Atul K. , Tian Hanqin , Poulter Benjamin , Michalak Anna M.
Published: October 2019

Terrestrial ecosystems carbon and water cycles are tightly coupled through photosynthesis and evapotranspiration processes. The ratios of carbon stored to carbon uptake and water loss to carbon gain are key ecophysiological indicators essential to assess the magnitude and response of the terrestrial plant to the changing climate. Here, we use estimates from 10 terrestrial ecosystem models to quantify the impacts of climate, atmospheric CO2 concentration, and nitrogen (N) deposition on water use efficiency (WUE), and carbon use efficiency (CUE). We find that across models, WUE increases over the 20th Century particularly due to CO2 fertilization and N deposition and compares favorably to experimental studies. Also, the results show a decrease in WUE with climate for the last 3 decades, in contrasts with up-scaled flux observations that demonstrate a constant WUE. Modeled WUE responds minimally to climate with modeled CUE exhibiting no clear trend across space and time. The divergence between simulated and observationally-constrained WUE and CUE is driven by modeled NPP and autotrophic respiration, nitrogen cycle, carbon allocation, and soil moisture dynamics in current ecosystem models. We suggest that carbon-modeling community needs to reexamine stomatal conductance schemes and the soil-vegetation interactions for more robust modeling of carbon and water cycles.
Forensic microbiology reveals that Neisseria animaloris infections in harbour porpoises follow traumatic injuries by grey seals
Authors: Foster Geoffrey , Whatmore Adrian M. , Dagleish Mark P. , Malnick Henry , Gilbert Maarten J. , Begeman Lineke , Macgregor Shaheed K. , Davison Nicholas J. , Roest Hendrik Jan , Jepson Paul , Howie Fiona , Muchowski Jakub , Brownlow Andrew C. , Wagenaar Jaap A. , Kik Marja J. L. , Deaville Rob , Doeschate Mariel T. I. ten , Barley Jason , Hunter Laura , IJsseldijk Lonneke L.
Published: October 2019

Neisseria animaloris is considered to be a commensal of the canine and feline oral cavities. It is able to cause systemic infections in animals as well as humans, usually after a biting trauma has occurred. We recovered N. animaloris from chronically inflamed bite wounds on pectoral fins and tailstocks, from lungs and other internal organs of eight harbour porpoises. Gross and histopathological evidence suggest that fatal disseminated N. animaloris infections had occurred due to traumatic injury from grey seals. We therefore conclude that these porpoises survived a grey seal predatory attack, with the bite lesions representing the subsequent portal of entry for bacteria to infect the animals causing abscesses in multiple tissues, and eventually death. We demonstrate that forensic microbiology provides a useful tool for linking a perpetrator to its victim. Moreover, N. animaloris should be added to the list of potential zoonotic bacteria following interactions with seals, as the finding of systemic transfer to the lungs and other tissues of the harbour porpoises may suggest a potential to do likewise in humans.
Brain lateralization probed by water diffusion at the atomic to micrometric scale
Authors: Natali F. , Dolce C. , Peters J. , Stelletta C. , Demé B. , Ollivier J. , Leduc G. , Cupane A. , Barbier E. L.
Published: October 2019

Combined neutron scattering and diffusion nuclear magnetic resonance experiments have been used to reveal significant interregional asymmetries (lateralization) in bovine brain hemispheres in terms of myelin arrangement and water dynamics at micron to atomic scales. Thicker myelin sheaths were found in the left hemisphere using neutron diffraction. 4.7 T dMRI and quasi-elastic neutron experiments highlighted significant differences in the properties of water dynamics in the two hemispheres. The results were interpreted in terms of hemisphere-dependent cellular composition (number of neurons, cell distribution, etc.) as well as specificity of neurological functions (such as preferential networking).
In vitro nephrotoxicity and anticancer potency of newly synthesized cadmium complexes
Authors: Abyar Selda , Khandar Ali Akbar , Salehi Roya , Abolfazl Hosseini-Yazdi Seyed , Alizadeh Effat , Mahkam Mehrdad , Jamalpoor Amer , White Jonathan M. , Shojaei Motahhareh , Aizpurua-Olaizola O. , Masereeuw Rosalinde , Janssen Manoe J.
Published: October 2019

Complexes based on heavy metals have great potential for the treatment of a wide variety of cancers but their use is often limited due to toxic side effects. Here we describe the synthesis of two new cadmium complexes using N(4)-phenyl-2-formylpyridine thiosemicarbazone (L1) and 5-aminotetrazole (L2) as organic ligands and the evaluation of their anti-cancer and nephrotoxic potential in vitro. The complexes were characterized by Single-crystal X-ray data diffraction, 1HNMR, FT-IR, LC/MS spectrometry and CHN elemental analysis. Next, cytotoxicity of these cadmium complexes was evaluated in several cancer cell lines, including MCF-7 (breast), Caco-2 (colorectal) and cisplatin-resistant A549 (lung) cancer cell lines, as well as in conditionally-immortalized renal proximal tubule epithelial cell lines for evaluating nephrotoxicity compared to cisplatin. We found that both compounds were toxic to the cancer cell lines in a cell-cycle dependent manner and induced caspase-mediated apoptosis and caspase-independent cell death. Nephrotoxicity of these compounds was compared to cisplatin, a known nephrotoxic drug, in vitro. Our results demonstrate that compound {2}, but not compound {1}, exerts increased cytotoxicity in MCF-7 and A549 cell lines, combined with reduced nephrotoxic potential compared to cisplatin. Together these data make compound {2} a likely candidate for further development in cancer treatment.
Quantification of Contractile Dynamic Complexities Exhibited by Human Stem Cell-Derived Cardiomyocytes Using Nonlinear Dimensional Analysis
Authors: Hoang Plansky , Jacquir Sabir , Lemus Stephanie , Ma Zhen
Published: October 2019

Understanding the complexity of biological signals has been gaining widespread attention due to increasing knowledge on the nonlinearity that exists in these systems. Cardiac signals are known to exhibit highly complex dynamics, consisting of high degrees of interdependency that regulate the cardiac contractile functions. These regulatory mechanisms are important to understand for the development of novel in vitro cardiac systems, especially with the exponential growth in deriving cardiac tissue directly from human induced pluripotent stem cells (hiPSCs). This work describes a unique analytical approach that integrates linear amplitude and frequency analysis of physical cardiac contraction, with nonlinear analysis of the contraction signals to measure the signals’ complexity. We generated contraction motion waveforms reflecting the physical contraction of hiPSC-derived cardiomyocytes (hiPSC-CMs) and implemented these signals to nonlinear analysis to compute the capacity and correlation dimensions. These parameters allowed us to characterize the dynamics of the cardiac signals when reconstructed into a phase space and provided a measure of signal complexity to supplement contractile physiology data. Thus, we applied this approach to evaluate drug response and observed that relationships between contractile physiology and dynamic complexity were unique to each tested drug. This illustrated the applicability of this approach in not only characterization of cardiac signals, but also monitoring and diagnostics of cardiac health in response to external stress.
Single-tube, dual channel pentaplexing for the identification of Candida strains associated with human infection
Authors: Jainlabdin Mohd Hanif , Batra Ambalika , Sánchez Paredes Edith , Hernández Hernández Francisca , Fu Guoliang , Tovar-Torres Jorge
Published: October 2019

Invasive candidiasis is one of the most common nosocomial fungal infections worldwide. Delayed implementation of effective antifungal treatment caused by inefficient Candida diagnosis contributes to its notoriously high mortality rates. The availability of better Candida diagnostic tools would positively impact patient outcomes. Here, we report on the development of a single-tube, dual channel pentaplex molecular diagnostic assay based on Multiplex Probe Amplification (MPA) technology. It allows simultaneous identification of C. auris, C. glabrata and C. krusei, at species-level as well as of six additional albicans and non-albicans pathogenic Candida at genus level. The assay overcomes the one-channel one-biomarker limitation of qPCR-based assays. Assay specificities are conferred by unique biomarker probe pairs with characteristic melting temperatures; post-amplification melting curve analysis allows simple identification of the infectious agent. Alerting for the presence of C. auris, the well-characterised multi-drug resistant outbreak strain, will facilitate informed therapy decisions and aid antifungal stewardship. The MPA-Candida assay can also be coupled to a pan-Fungal assay when differentiation between fungal and bacterial infections might be desirable. Its multiplexing capacity, detection range, specificity and sensitivity suggest the potential use of this novel MPA-Candida assay in clinical diagnosis and in the control and management of hospital outbreaks.
Spatial connectivity pattern of expanding gilthead seabream populations and its interactions with aquaculture sites: a combined population genetic and physical modelling approach
Authors: Žužul Iva , Šegvić-Bubić Tanja , Talijančić Igor , Džoić Tomislav , Lepen Pleić Ivana , Beg Paklar Gordana , Ivatek-Šahdan Stjepan , Katavić Ivan , Grubišić Leon
Published: October 2019

In gilthead seabream the number of domesticated individuals increased annually, and escape events occur regularly in the Adriatic Sea. Still there is a lack of population genetic characteristics and evidence of the extent and geographic scale of interbreeding resulting from fish-farm escapees. We screened 1586 individuals using a panel of 21 neutral microsatellite loci in several consecutive years and here report on the medium-scale detection of hybrid and farmed seabream in the natural environment. Wild adults showed a lack of genetic structure within basin and sampling years and reduced connectivity with wild offspring collection, suggesting their temporal residency within the Adriatic. On the contrary, by linking the results of multiannual genetic analyses with the results of coupled hydrodynamic and individual based models (IBM-Ichthyop), we observed a strong connection of wild seabream associated with tuna-aquaculture sites and offspring from the nursery grounds, indicating that the surroundings of tuna sea-cage farms can function as a spawning grounds. The study results present the genetic baseline of wild and farmed strains from the eastern Adriatic Sea, as a first step toward development of a mitigation strategy for fish escapees aimed at controlling further erosion of genetic integrity.
Prediction of various freshness indicators in fish fillets by one multispectral imaging system
Authors: Khoshnoudi-Nia Sara , Moosavi-Nasab Marzieh
Published: October 2019

In current study, a simple multispectral imaging (430–1010 nm) system along with linear and non-linear regressions were used to assess the various fish spoilage indicators during 12 days storage at 4 ± 2 °C. The indicators included Total-Volatile Basic Nitrogen (TVB-N) and Psychrotrophic Plate Count (PPC) and sensory score in fish fillets. immediately, after hyperspectral imaging, the reference values (TVB-N, PPC and sensory score) of samples were obtained by traditional method. To simplify the calibration models, nine optimal wavelengths were selected by genetic algorithm. The prediction performance of various chemometric models including partial least-squares regression (PLSR), multiple-linear regression (MLR), least-squares support vector machine (LS-SVM) and back-propagation artificial neural network (BP-ANN) were compared. All models showed acceptable performance for simultaneous predicting of PPC, TVB-N and sensory score (R2P ≥ 0.853 and RPD ≥ 2.603). Non-linear models were considered better quantitative model to predict all of three freshness indicators in fish fillets. Among the three spoilage indices, the best predictive power was obtained for PPC value and the weakest one was acquired for TVB-N content prediction. The best model for prediction TVB-N (R2p = 0.862; RMSEP = 3.542 and RPD = 2.678) and sensory score (R2p = 0.912; RMSEP = 1.802 and RPD = 3.33) belonged to GA-LS-SVM and for prediction of PPC value was BP-ANN (R2p = 0.921; RMSEP = 0.504 and RPD = 3.64). Therefore, developing multispectral imaging system based on LS-SVM model seems to be suitable for simultaneous prediction of all three indicators (R2P > 0.862 and RPD > 2.678). Further studies needed to improve the accuracy and applicability of HSI system for predicting freshness of rainbow-trout fish.
Low value for the static background dielectric constant in epitaxial PZT thin films
Authors: Boni Georgia Andra , Chirila Cristina Florentina , Hrib Luminita , Negrea Raluca , Filip Lucian Dragos , Pintilie Ioana , Pintilie Lucian
Published: October 2019

Ferroelectrics are intensively studied materials due to their unique properties with high potential for applications. Despite all efforts devoted to obtain the values of ferroelectric material constants, the problem of the magnitude of static dielectric constant remains unsolved. In this article it is shown that the value of the static dielectric constant at zero electric field and with negligible contribution from the ferroelectric polarization (also called static background dielectric constant, or just background dielectric constant) can be very low (between 10 and 15), possibly converging towards the value in the optical domain. It is also found that the natural state of an ideal, mono-domain, epitaxial ferroelectric is that of full depletion with constant capacitance at voltages outside the switching domain. The findings are based on experimental results obtained from a new custom method designed to measure the capacitance-voltage characteristic in static conditions, as well from Rayleigh analysis. These results have important implications in future analysis of conduction mechanisms in ferroelectrics and theoretical modeling of ferroelectric-based devices.
Target-engineered photo-responsive DNA strands: a novel signal-on photoelectrochemical biosensing platform for ochratoxin A
Authors: Tang Juan , Cheng Yu , Zheng Jianhong , Li Jingjing , Sun Yuanfang , Peng Siwen , Zhu Zhiqiang
Published: October 2019

In this study, we report a novel and efficient method for the conversion of the photo-response of DNA strands and the validation of their feasibility for use as a versatile signal-amplified system for constructing a photoelectrochemical DNA sensor.
The control effects of different scaffolds in chiral phosphoric acids: a case study of enantioselective asymmetric arylation
Authors: Zhu Lihan , Mohamed Hend , Yuan Haiyan , Zhang Jingping
Published: October 2019

DFT calculations disclosed that the sign of enantioselectivity in chiral-phosphoric-acid catalyzed reactions can be tuned by BINOL- or SPINOL-derived backbones.
Versatile and scalable synthesis of cyclic organic carbonates under organocatalytic continuous flow conditions
Authors: Gérardy Romaric , Estager Julien , Luis Patricia , Debecker Damien P. , Monbaliu Jean-Christophe M.
Published: October 2019

A scalable intensified flow process for the preparation of cyclic organic carbonates relying on a cheap ammonium organocatalyst.