bluuebunny/crossref_metadata_2025 huggingface dataset:
Remarkable performance of the unique Pd–Fe2O3 catalyst towards EOR and ORR: non-Pt and non-carbon electrode materials for low-temperature fuel cells
Authors: Adhikary Rajib , Sarkar Dipankar , Mukherjee Manabendra , Datta Jayati
Published: December 2020

Unique catalyst Pd NPs/Fe2O3 exhibits outstanding EOR and ORR activity in alkaline environment: a Pt and carbon free approach.
Unveiling the mechanistic implications of water oxidation reactions boosted by guanidine proton relays: a chemical-electrochemical-chemical pathway and a non-concerted proton-electron transfer
Authors: Shamsipur Mojtaba , Ardeshiri Moslem , Taherpour Avat (Arman) , Pashabadi Afshin
Published: December 2020

Concerted or non-concerted are two competitive pathways involved in proton-coupled electron transfer–driven artificial water oxidation reactions (WORs).
Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor
Authors: Xu Jingwen , Yan Xiangji , Ge Xin , Zhang Mingzhen , Dang Xugang , Yang Yan , Xu Feng , Luo Yanling , Li Guoliang
Published: December 2020

The PEG-based nanaovehicles with desired drug types and content were fabricated, it has profound significance in multidrug resistant tumors sustained treatments.
Flexible temperature sensors based on carbon nanomaterials
Authors: Chen Zetong , Zhao Danna , Ma Rui , Zhang Xujing , Rao Jihong , Yin Yajiang , Wang Xiaofeng , Yi Fang
Published: December 2020

Flexible temperature sensors based on carbon nanomaterials can be attached to the surface of human skin or curved surfaces directly for continuous and stable data measurements, and have attracted extensive attention in myriad areas.
Sensitivity analysis‐based optimal PMU placement for fault observability
Authors: Mohammadi Pooria , Mehraeen Shahab , Nazaripouya Hamidreza
Published: December 2020

This paper proposes an algorithm that finds the optimal sets of phasor measurement units (PMUs) to achieve a fault observable system, while it addresses the multi‐estimation issue. The optimal PMU placement (OPP) problem here is to find a set of PMU locations with minimum number of members that enables fault observability in a system and satisfies a defined minimum sensitivity requirement in measurements. The proposed algorithm generalizes the impedance method in fault analysis and optimizes PMU utilization to maintain a required minimum sensitivity in each set of measurements, given the required fault detection accuracy. Also, the set of measurements is unique and distinctive for each fault scenario, preventing multi‐estimation. A fault is referred to as a set of affected faulty line, fault location, and fault impedance. A sensitivity analysis is performed and sensitivity indices are derived to evaluate measurements quality to detect changes in fault line, location, or resistance. The algorithm is executed on IEEE 7‐bus, 14‐bus, and 30‐bus test systems. Subsequently, artificial neural networks (ANN) are employed to build fault locators through offline training. ANN use an optimal PMU set obtained by the proposed algorithm to uniquely map between the corresponding measurements set and the faults.
Novel method for power system synthesis load identification
Authors: Sheng Siqing , Ma Yunting , Ye Huarui , Zhu Siyu , Zhao Qing
Published: December 2020

Power load parameters are one of the most important parameters for power system model. The load has the characteristics of time‐varying, diversity and non‐linearity. Therefore, obtaining the load parameters accurately is crucial to the safe and stable operation of the power system. The research in this paper is based on the synthesis load model which takes into account the impedance of distribution network. The multi‐fault curves identification method and chaos‐whale algorithm are adopted to improve the accuracy and practicability of load parameter identification. First, the algorithm proposed in this paper applies chaos algorithm to whale algorithm, and uses the randomness and ergodicity of chaos algorithm to make up for the shortcomings of the whale algorithm that the solution accuracy is not high and it is easy to fall into local optimum. Secondly, the identification method of multi‐fault curves is to select several different faults for parameter identification, and the average value of each group of results obtained is regarded as the final result. Then compared with single curve identification, the multi‐fault curves method is more superior. Finally, the accuracy of the results is verified by other faults. Simulation results show that the method is reliable to a certain extent.
Digital aspects of management of the agro-industrial complex of Russia
Authors: Shogentsukova Zalina Kh. , Shogentsukov Ali Kh.
Published: December 2020

The article is devoted to the study of digital and innovative management mechanisms of the agro-industrial complex of Russia. These mechanisms can act as a significant stimulus for the development of the industry, allowing to take into account the achievements and modern trends in technology and science, which is especially important in the context of the digitalization of the economy. The use of digital technologies and innovations in the agro-industrial complex of Russia are a competitive advantage both in the development of the production process of an agricultural enterprise and in improving the management efficiency of the agro-industrial complex. At the same time, with the help of the digital transformation of agriculture in Russia, the industry is being modified into a high-tech and competitive one not only at the national level, but also in the international capital markets. The digital transformation of the agro-industrial complex of the Russian Federation must be viewed from the position of state regulation since the digitalization of the industry also requires improving the mechanisms of state support for the introduction of digital technologies into the industry. The study of the digital aspects of agro-industrial complex management allows us to generalize the existing developments and build a mechanism for the digital transformation of agriculture. It is the use of digital and innovative mechanisms in the agro-industrial complex that makes it possible to manage the processes of the influence of climatic, natural, and other factors on agriculture. The seasonality of agricultural production is an inhibiting factor in the development of the industry. In addition, the digitalization of the agro-industrial complex makes it possible not only to increase the efficiency of management and production processes but also to create conditions for the functioning of new economic models using modern technologies.
The application efficiency of organic fungicides against soybean diseases in the central zone of the Krasnodar region of the Russian Federation
Authors: Bushnev Alexander , Babenko Sergey , Bushneva Nadezhda
Published: December 2020

Diseases are one of the main factors limiting the receiving of high yields of soybean. The use of biopreparations for plant protection will result in successful disease control and improve the quality of products. In 2018-2020, at V.S. Pustovoit All-Russian Research Institute of Oil Crops (Krasnodar), we studied the application effectiveness of biopreparations under the trademarks of BSka-3 with the active ingredients Trichoderma veride, Pseudomonas koreensis, Bacillus subtilis and BFTIM with the active ingredient Bacillus amyloliquefaciens against soybean diseases. We applied organic fungicides for seed treatment and on vegetative plants at the budding stage. The variants BSka-3 G + BFTIM G (62 %) and BSka-3 Zh + BFTIM Zh (50 %) showed the highest biological effectiveness against purple Cercospora blight, and the variant BSka-3 E + BFTIM E showed 66 % and 52 % of effectiveness against pustular and angular spot diseases. The biological effectiveness of Pyraclostrobin, EC against purple Cercospora blight, pustular and angular spot diseases was the lowest – 21, 12, and 10 %, respectively. We observed the best economic efficiency in case of application of BSka-3 E + BFTIM G – 2.31 t/ha.
Laser Safety and the Microscope
Authors: Barat Ken
Published: December 2020

Few scientific instruments can trace their origins back in time as far the optical microscope. In the last two decades, microscopes have seen an explosion of variation. From a laser safety perspective, I would say the laser scanning confocal microscope ushered in a new era, as the laser supplies a unique illumination and excitation tool.
Laser Audits: What Is Looked at, and Being Prepared
Authors: Barat Ken
Published: December 2020

While the emphasis of the laser user is their research activity, on occasion their workspace will receive an audit. This can be from a regulatory agency (most likely a rare event), in-house safety review by a laser safety officer or corporate review, or maybe even from funding sources. The goal of this chapter is to list and explain a number of auditable items and how to avoid noncompliance. For auditors and regulators, it is difficult to keep up with technological changes. In addition, lasers are usually a small part of an auditor's scope of work, so many times one will find their knowledge of life with lasers and user issues is limited. This is why they prefer black and white items, like whether you had training or not, rather than how creative your use of beam blocks is. That reality is not reflected in the list of audit items. Many of these items might go unnoticed by an auditor, but this section is written as if I was your auditor (sinister music).

Note: From years of experience, for anyone being audited, never offer to demonstrate how well something works, it will not.
The Industrial Laser: The 21st Century's Most Versatile Machine Tool
Authors: Ball Neil
Published: December 2020

This chapter is a short and personal introduction to the use of lasers in a wide range of commercial applications. For the laser researcher, it is a reminder of where their laser research finds a home and where their work may lead them.
Resources
Authors: Barat Ken
Published: December 2020

This chapter is titled Resources. As the name implies, it contains an eclectic collection of useful items: material such as the reflectivity of different materials, experienced proven best lab practices, and a review of Class 4 control measures. Of most interest to the reader might be images showing solutions to a number of common laser lab problems, some of which the user may not have recognized as potential safety problems. I strongly recommend the reader take a careful look over the chapter.
Minimising mortalities in capturing wildlife: refinement of helicopter darting of chital deer (
Authors: Hampton Jordan O. , Amos Matthew , Pople Anthony , Brennan Michael , Forsyth David M.
Published: December 2020

Abstract Context Helicopter darting has been used to capture wild deer, but this method has never been used for chital deer (Axis axis). Aim The aims of this study were to develop, assess and refine a helicopter darting technique for wild chital deer in northern Australia by quantifying: (1) reliable pharmacological doses for immobilisation; (2) the efficacy of the technique (including the duration of procedures); and (3) the frequency of adverse animal welfare events. Methods The study was conducted in three stages: an initial protocol (n = 25 deer captured) in July−August 2018; a refined second protocol implemented in June 2019 (n = 12 deer captured); and a further refined third protocol implemented in June 2019 (n = 12 deer captured). Parameters to estimate the duration of procedures were measured and the frequency of several adverse animal welfare events during capture were quantified: mortality (at the time of capture and within 14 days of capture), hyperthermia, hypoxaemia, dart inaccuracy and manual restraint. Finally, GPS location collars with a mortality-sensing function were used to monitor post-release mortality. Results Mortality within 14 days of capture was 40% for the first stage, 25% for the second stage and 17% for the third stage. Considerable refinement of procedures occurred between stages in consultation with an Animal Ethics Committee. One-third of all 15 mortalities occurred at the time of capture and were attributed to ballistic trauma from dart impact and acute capture myopathy. The majority (n = 10) of mortalities, however, occurred post-release and were only detected by mortality-sensing GPS location collars. These post-release mortalities were attributed to capture myopathy. Conclusions Helicopter darting of wild chital deer poses animal welfare risks, but these can be minimised through the selection of the most appropriate pharmacological agents and attempts at preventing factors such as hyperthermia and hypoxaemia that contribute to the development of capture myopathy. Further research into capture protocols is needed for helicopter-based immobilisation of chital deer. Fitting animals with GPS location collars enabled post-release mortality, which was significant, to be evaluated.
“How dare you call her a pig, I know several pigs who would be upset if they knew”*
Authors: Esposito Eleonora , Zollo Sole Alba
Published: December 2020

On the occasion of the 2017 UK election campaign, Amnesty International conducted a large-scale, sentiment-based analysis of online hate speech against women MPs on Twitter (Dhrodia 2018), identifying the “Top 5” most attacked women MPs as Diane Abbott, Joanna Cherry, Emily Thornberry, Jess Phillips and Anna Soubry.

Taking Amnesty International’s results as a starting point, this paper investigates online misogyny against the “Top 5” women MPs, with a specific focus on the video-sharing platform YouΤube, whose loosely censored cyberspace is known as a breeding ground for antagonism, impunity and disinhibition (Pihlaja 2014), and, therefore, merits investigation.

By collecting and analysing a corpus of YouTube multimodal data we explore, critique and contextualize online misogyny as a techno-social phenomenon applying a Social Media Critical Discourse Studies (SM-CDS) approach (KhosraviNik and Esposito 2018). Mapping a vast array of discursive strategies, this study offers an in-depth analysis on how technology-facilitated gender-based violence contributes to discursively constructing the political arena as a fundamentally male-oriented space, and reinforces stereotypical and sexist representation of women in politics and beyond.
Distinct advantages of using sonochemical over laser ablation methods for a rapid-high quality gold nanoparticles production
Authors: Ali Dheyab Mohammed , Abdul Aziz Azlan , Moradi Khaniabadi Pegah , Jameel Mahmood S , Ahmed Naser Mahmoud , Taha Ali Abdullah
Published: December 2020

Gold nanoparticles (AuNPs) have numerous usage in various applications, primarily in chemical and biological sensing. There are also various methods of producing AuNPs. However, in some of those methods, removing excess reagents, including ions or residual surfactants, can be difficult and time-consuming, while the functionalization of AuNPs with other types of molecules can only be achieved at lower efficacy. In this report, the AuNPs were produced using a rapid and solvent-free sonochemical and laser ablation methods. Morphology, structure and the colloidal stability of AuNPs produced by the two methods were analyzed and compared. Results have shown that the purity, homogeneity and crystallinity of AuNPs produced using the sonochemical technique showed better characteristics than those acquired by the laser ablation method. AuNPs also demonstrated smaller particle sizes (22 nm), smooth surfaces with higher colloidal stability (50.7 mV). The findings indicate that ultrasound irradiation power improves the crystalline properties of AuNPs and inhibits their agglomeration. The sonochemical approach can, therefore, be used to produce AuNPs with better physicochemical characteristics compared to laser ablation methods.
Fabrication of chlorine nitrogen co-doped carbon nanomaterials by an injection catalytic vapor deposition method
Authors: Maboya Winny K , Coville Neil J , Mhlanga Sabelo D
Published: December 2020

The synthesis of both covalently bonded chlorine and nitrogen-doped carbon materials (Cl-N-CNMs) has been little studied. In this paper we report on the investigation of the synthesis of Cl-N-CNMs using a feedstock containing a mixture of dichlorobenzene (DCB), acetylene and acetonitrile over a Fe-Co/CaCO3 catalyst using an injection CVD method at 800 °C. By varying the acetonitrile:DCB concentration ratio (66.7:33.3; 33.3:66.7 and 20:80), the morphology and physicochemical properties of the CNMs was varied. The products contained varying amounts of Cl (0.5%–1.2%) and N (0.88%–1.47%) and the total amount of Cl and N increased with the Cl content in the feed, as determined by XPS. A graphitic N environment dominated in feeds containing 33.3 and 66.7 vol.% DCB, whilst pyrrolic N dominated in feeds containing pure acetonitrile and 80 vol.% DCB. The chlorine in the feed promoted the formation of CNMs with various shapes namely horn-shaped, spaghetti-like, and pencil-like shapes, some with open-ends and others with closed-ends as determined by TEM and SEM studies. Although no direct correlation with the amounts of the reactants used and the morphology of the products was established, trends in the product shapes were noted with highly defected products produced from 66.7 vol.% DCB, and feeds containing 33.3 and 80 vol.% had tubes with similar open-ended horn-shaped morphology and less defects.
Investigations of interfacial heat transfer efficiency in HFQ® process of high strength aluminum alloy
Authors: Jiang Y F , Ding H
Published: December 2020

Hot form quench (HFQ®) is a novel hot stamping process to deform complex-shaped parts applied in automobile industry, and interfacial heat transfer coefficient (IHTC) play an important role in HFQ® process. In this research, the average IHTC values were compared under different forming conditions during die quenching based on the calculation and finite element (FE) simulation results. Beside, transmission electron microscope (TEM), differential scanning calorimeter (DSC) and tensile tests were performed to investigate the relationship among IHTC, microstuructures and mechanical properties. The results show that the experimental results agree well with those achieved by FE simulation. The value of IHTC for AA7075 increased with the increased contact pressure during HFQ® process. In contrast, the increasing temperature of forming die has a negative impact on IHTC. The critical quenching rate (Qc), inducing the formation of a large number of equilibrium phases η, is between 14.3 °C s−1–18.5 °C s−1, and the corresponding IHTC range is 2468 W·m2 k–2656 W·m2 k. With regard to the condition with cooling rate lower than Qc, the formation of a large amount of η is recognized as the reason for the strength decrease.
The U.S. Must Embrace Partner-led Global Health Engagement
Authors: Callahan Robert P
Published: December 2020

Direct-care Medical Readiness Training Exercises (MEDRETEs) are a popular method for conducting global health engagement. Unfortunately, direct-care MEDRETEs build partnerships without building partner nation capacity. This article proposes that global health engagement should instead focus on partner-led health engagements to accomplish both of these goals.
Quantifying the contributions technicians make to research
Authors: McLaren Clare , Dent Alan
Published: December 2020

Technicians play a highly significant, but often invisible, role in research. Despite growing recognition of the importance of technicians, through initiatives such as the Technician’s Commitment, their contribution is inconsistently recognized across research groups, between disciplines, and within institutions. This article presents a simple framework, based on existing standards that can be easily integrated into common research workflows to capture technician contributions. By utilizing ORCID identifiers, Digital Object Identifiers, and the CRediT contributor role taxonomy, technician contribution can be quantified, recognized, and valuable additional data can be created for the planning and management of future research. Presented in the context of the Australasian higher education system, the framework is illustrated with a Science, Technology, Engineering and Mathematics focus but is applicable across all disciplines.
Carriers of haemophilia: pregnancy, childbirth and postpartum
Authors: Falcón Rodríguez María
Published: December 2020

Management of haemophilia carrier women during labour and postpartum is yet to be standardized. Pregnancy was accompanied by a marked rise in factor VIII levels compared with only a small rise in factor IX levels. After delivery, a carrier's factor level drops down to prepregnancy levels, which increases the chance of postpartum haemorrhage. Availability of management guideline and care provided in a multidisciplinary approach can help to minimize bleeding complications in carriers of haemophilia and their newborns.
Fibroblast Activation Protein Inhibitor PET/CT
Authors: Sharma Punit , Singh Shashank Shekhar , Gayana Shankaramurthy
Published: December 2020

Purpose

Fibroblast activation protein (FAP) is a cell membrane–bound serine peptidase, overexpressed in cancer-associated fibroblasts and activated fibroblasts at wound healing/inflammatory sites. Recently, molecular PET/CT imaging with radiolabeled FAP inhibitor (FAPI) has been evaluated in different diseases. We aimed to assess its potential role based on the available literature.

Patients and Methods

We conducted a comprehensive review of the available preclinical and clinical data on FAPI PET/CT in an attempt to summarize its current status and potential future role. Based on that, we have discussed the pathophysiology behind FAP-based imaging, followed by a discussion of FAPI radiopharmaceuticals including their synthesis, biodistribution, and dosimetry. Next, we have discussed studies evaluating FAPI PET/CT in different oncological and nononcological pathologies. The potential of FAPI PET/CT in theranostics has also been addressed.

Results

Based on the early scientific evidence available, including preclinical and clinical studies, FAPI PET/CT seems to be a promising molecular imaging tool, especially in oncology. It can be used for imaging different types of cancers and outperforms 18F-FDG PET/CT in some of these. Its potential as a theranostic tool warrants special attention.

Conclusions

Fibroblast activation protein inhibitor PET/CT has the potential to emerge as a powerful molecular imaging tool in the future. However, as of yet, the available evidence is limited, warranting further research and trials in this field.
Antimalarial andPlasmodium falciparumserpentine receptor 12 targeting effect of a purinergic receptor antagonist FDA approved drug
Authors: Gupta Sonal , Joshi Nishant , Saini Monika , Singh Shailja
Published: December 2020

Intraerythrocytic stages ofPlasmodium falciparumresponsible for all clinical manifestations of malaria are regulated by array of signaling cascades and effector molecules that represents attractive targets for antimalarial therapy. G-protein coupled receptors (GPCRs) are druggable targets in treatment of various pathological conditions however there is limited understanding about the role of GPCRs in malaria pathogenesis. InPlasmodium,serpentine receptors (PfSR1, PfSR10, PfSR12 and PfSR25) with GPCR like membrane topology have been reported with the finite knowledge about their potential as antimalarial targets. Herein we evaluated the druggability of PfSR12 using FDA approved P2Y type of purinergic signaling antagonist, Prasugrel. Blocking of purinergic receptor signaling resulted in inhibition of growth and development ofP. falciparum. Progression studies indicated the inhibitory effect of purinergic signalling inhibitor begins in late erythrocyte stages predominantly in the schizonts. Furthermore, purinoreceptor inhibitor blockedin vivogrowth of malaria parasite in mouse experimental model. The localization of PfSR1, PfSR10, PfSR12 and PfSR25 was analyzed by immunofluorescence assays. The putative purinergic receptor PfSR12 is found to be expressed in late intraerythrocytic stages. Prasugrel, a generic purinoreceptor inhibitor and agonist ATP showed specific binding to recombinant PfSR12 confirming it as purinergic receptor. This study indicates the presence of P2Y type of purinergic signaling in growth and development of malaria parasite and suggests PfSR12 as putative purinergic receptor.
Random forest model for feature-based Alzheimer’s disease conversion prediction from early mild cognitive impairment subjects
Authors: Velazquez Matthew , Lee Yugyung ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

Alzheimer’s Disease (AD) conversion prediction from the mild cognitive impairment (MCI) stage has been a difficult challenge. This study focuses on providing an individualized MCI to AD conversion prediction using a balanced random forest model that leverages clinical data. In order to do this, 383 Early Mild Cognitive Impairment (EMCI) patients were gathered from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Of these patients, 49 would eventually convert to AD (EMCI_C), whereas the remaining 335 did not convert (EMCI_NC). All of these patients were split into training and testing data sets with 95 patients reserved for testing. Nine clinical features were selected, comprised of a mix of demographic, brain volume, and cognitive testing variables. Oversampling was then performed in order to balance the initially imbalanced classes. Our results showed that a random forest model was effective (93.6% accuracy) at predicting the conversion of EMCI patients to AD based on these clinical features. Additionally, we assessed the importance of each clinical feature at both the individual and model level for interpretation of the prediction itself. Our model could impact the clinical environment as a tool to predict the conversion to AD from a prodromal stage or to identify ideal candidates for clinical trials.
Messenger RNA cap methylation by PCIF1 attenuates the interferon-β induced antiviral state
Authors: Tartell Michael A. , Boulias Konstantinos , Hoffmann Gabriela Brunsting , Greer Eric Lieberman , Whelan Sean P. J.
Published: December 2020

Interferons induce cell intrinsic responses associated with resistance to viral infection. To overcome the suppressive action of interferons and their downstream effectors viruses have evolved diverse mechanisms. Working with vesicular stomatitis virus (VSV) we report a role for the host cell N6-adenosine mRNA cap-methylase, phosphorylated C-terminal domain interacting factor 1 (PCIF1), in attenuating the antiviral activity of interferon-β. Using cell based andin vitrobiochemical assays we demonstrate that PCIF1 efficiently modifies VSV mRNA cap structures to m7Gpppm6Am, and we identify thecis-acting elements required for this modification. Under basal conditions, N6-methylation of VSV mRNA cap structures is functionally inert with regard to mRNA stability, translation and viral infectivity. Induction of an antiviral state by treatment of cells with interferon-β prior to infection uncovered a functional role for PCIF1 in attenuation of the antiviral response. Cells lacking PCIF1 or expressing a catalytically inactive PCIF1, exhibit an augmented effect of interferon-β in the inhibition of viral replication and gene expression. This work identifies a function of PCIF1 and cap-proximal m6Amin attenuation of the host response to VSV infection that likely extends to other viruses.

Significance

The cap structure present at the 5’ end of eukaryotic mRNAs regulates RNA stability, translation, and marks mRNA as self, thereby impeding recognition by the innate immune system. Cellular transcripts beginning with adenosine are additionally modified at the N6 position of the 2’-O methylated cap-proximal residue by the methyltransferase PCIF1 to m7Gpppm6Am. We define a function for this N6-adenosine methylation in attenuating the interferon-β mediated suppression of viral infection. Cells lacking PCIF1, or defective in its enzymatic activity, augment the cell intrinsic suppressive effect of interferon-β treatment on vesicular stomatitis virus gene expression. VSV mRNAs are efficiently methylated by PCIF1, suggesting this contributes to viral evasion of innate immune suppression.
HUMAN ADENOVIRUS TYPE 4 COMPRISES TWO MAJOR PHYLOGROUPS WITH DISTINCT REPLICATIVE FITNESS AND VIRULENCE PHENOTYPES
Authors: Bair Camden R. , Zhang Wei , Gonzalez Gabriel , Kamali Arash , Stylos Daniel , Blanco Jorge C. G. , Kajon Adriana E.
Published: December 2020

Human adenovirus type 4 (HAdV-E4) is the only type (and serotype) classified within speciesHuman mastadenovirus Ethat has been isolated from a human host to the present. Recent phylogenetic analysis of whole genome sequences of strains representing the spectrum of intratypic genetic diversity described to date identified two major evolutionary lineages designated phylogroups (PG) I, and II, and validated the early clustering of HAdV-E4 genomic variants into two major groups by low resolution restriction fragment length polymorphism analysis. In this study we expanded our original analysis of intra- and inter-PG genetic variability, and used a panel of viruses representative of the spectrum of genetic diversity described for HAdV-E4 to examine the magnitude of inter- and intra-PG phenotypic diversity using an array of cell-based assays and a cotton rat model of HAdV respiratory infection. Our proteotyping of HAdV-E strains using concatenated protein sequences in selected coding regions including E1A, E1B-19K and −55K, DNA polymerase, L4-100K, various E3 proteins, and E4-34K confirmed that the two clades encode distinct variants/proteotypes at most of these loci. Ourin vitroandin vivostudies demonstrated that PG I and PG II differ in their growth, spread, and cell killing phenotypes in cell culture and in their pulmonary pathogenic phenotypes. Surprisingly, the differences in replicative fitness documentedin vitrobetween PGs did not correlate with the differences in virulence observed in the cotton rat model. This body of work is the first reporting phenotypic correlates of naturally occurring intratypic genetic variability for HAdV-E4.

IMPORTANCE

Human adenovirus type 4 (HAdV-E4) is a prevalent causative agent of acute respiratory illness of variable severity and of conjunctivitis and comprises two major phylogroups that carry distinct coding variations in proteins involved in viral replication and modulation of host responses to infection. Our data show that PG I and PG II are intrinsically different regarding their ability to grow and spread in culture and to cause pulmonary disease in cotton rats.

This is the first report of phenotypic divergence among naturally occurring known genetic variants of a HAdV type of medical importance. This research reveals readily detectable phenotypic differences between strains representing phylogroups I and II, and it introduces a unique experimental system for the elucidation of the genetic basis of adenovirus fitness and virulence and thus for increasing our understanding of the implications of intratypic genetic diversity in the presentation and course of HAdV-E4-associated disease.
PySCNet: A tool for reconstructing and analyzing gene regulatory network from single-cell RNA-Seq data
Authors: Wu Ming , Kacprowski Tim , Zehn Dietmar
Published: December 2020

The Advanced capacities of high throughput single cell technologies have facilitated a great understanding of complex biological systems, ranging from cell heterogeneity to molecular expression kinetics. Several pipelines have been introduced to standardize the scRNA-seq analysis workflow. These include cell population identification, cell marker detection and cell trajectory reconstruction. Yet, establishing a systematized pipeline to capture regulatory relationships among transcription factors (TFs) and genes at the cellular level still remains challenging. Here we present PySCNet, a python toolkit that enables reconstructing and analyzing gene regulatory networks (GRNs) from single cell transcriptomic data. PySCNet integrates competitive gene regulatory construction methodologies for cell specific or trajectory specific GRNs and allows for gene co-expression module detection and gene importance evaluation. Moreover, PySCNet offers a user-friendly dashboard website, where GRNs can be customized in an intuitive way.

Availability

Source code and documentation are available:https://github.com/MingBit/PySCNet

Contact

ming.wu@tum.de
Structural and biophysical characterization of the tandem substrate-binding domains of the ABC importer GlnPQ
Authors: Ploetz Evelyn , Schuurman-Wolters Gea K. , Zijlstra Niels , Jager Amarins W. , Griffith Douglas A. , Guskov Albert , Gouridis Giorgos , Poolman Bert , Cordes Thorben
Published: December 2020

The ATP-binding cassette transporter GlnPQ is an essential uptake system that transports glutamine, glutamic acid, and asparagine in Gram-positive bacteria. It features two extracytoplasmic substrate-binding domains (SBDs) that are linked in tandem to the transmembrane domain of the transporter. The two SBDs differ in their ligand specificities, binding affinities and their distance to the transmembrane domain. Here, we elucidate the effects of the tandem arrangement of the domains on the biochemical, biophysical and structural properties of the protein. For this, we determined the crystal structure of the ligand-free tandem SBD1-2 protein fromL. lactisin the absence of the transporter and compared the tandem to the isolated SBDs. We also used isothermal titration calorimetry to determine the ligand-binding affinity of the SBDs and single-molecule Förster-resonance energy transfer (smFRET) to relate ligand binding to conformational changes in each of the domains of the tandem. We show that substrate binding and conformational changes are not notably affected by the presence of the adjoining domain in the wild-type protein, and changes only occur when the linker between the domains is shortened. In a proof-of-concept experiment, we combine smFRET with protein-induced fluorescence enhancement and show that a decrease in SBD linker length is observed as a linear increase in donor-brightness for SBD2 while we can still monitor the conformational states (open/closed) of SBD1. These results demonstrate the feasibility of PIFE-FRET to monitor protein-protein interactions and conformational states simultaneously.

HIGHLIGHTS

Resolved crystal structure of tandem SBD1-2 of GlnPQ fromLactococcus lactis

Conformational states and ligand binding affinities of individual domains SBD1 and SBD2 are similar to tandem SBD1-2

No cooperative effects are seen for different ligands for SBDs in the tandem

Proof of concept experiments show that PIFE-FRET can monitor SBD conformations and protein-protein interaction simultaneously
Disentangling the aging network of a termite queen
Authors: Monroy Kuhn Jose Manuel , Meusemann Karen , Korb Judith
Published: December 2020

Background: Most insects are relatively short-lived, with a maximum lifespan of a few weeks, like the aging model organism, the fruit-fly Drosophila melanogaster. By contrast, the queens of social insects (termites, ants, some bees and wasps) can live for more than a decade. This makes social insects promising new models in aging research providing insights into how a long reproductive life can be achieved. Yet, aging studies on social insect reproductives are hampered by a lack of quantitative data on age-dependent survival and time series analyses that cover the whole lifespan of such long-lived individuals. We studied aging in queens of the drywood termite Cryptotermes secundus by determining survival probabilities over more than 15 years and performed transcriptome analyses for queens of known age that covered their whole lifespan. Results: The maximum lifespan of C. secundus queens was 13 years with a median maximum longevity of 11.0 years. Time course and co-expression network analyses of gene expression patterns over time indicated a non-gradual aging pattern. It was characterized by networks of genes that became differentially expressed only late in life, namely after an age of 10 years, which associates well with the median maximum lifespan for queens. These old-age gene networks reflect processes of physiological upheaval. We detected strong signs of stress, decline, defence and repair at the transcriptional level of epigenetic control as well as at the post-transcriptional level with changes in transposable element activity and the proteostasis network. The latter depicts an upregulation of protein degradation, together with protein synthesis and protein folding, processes which are often down-regulated in old animals. The simultaneous upregulation of protein synthesis and autophagy is indicative for a stress-response mediated by the transcription factor cnc, a homolog of human nrf genes. Conclusion: Our results show non-linear senescence with a rather sudden physiological upheaval at old-age. Most importantly, they point to a re-wiring in the proteostatis network as central for explaining the long life of social insect queens.
Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates and Recently Emerged Variants from Humans and Minks Suggests Minimal Pre-Existing Resistance to Remdesivir
Authors: Martin Ross , Li Jiani , Parvangada Aiyippa , Perry Jason , Cihlar Tomas , Mo Hongmei , Porter Danielle , Svarovskaia Evguenia
Published: December 2020

Remdesivir (RDV) exhibits potent antiviral activity against SARS-CoV-2 and is currently the only drug approved for the treatment of COVID-19. However, little is currently known about the potential for pre-existing resistance to RDV and the possibility of SARS-CoV-2 genetic diversification that might impact RDV efficacy as the virus continue to spread globally. In this study, >90,000 SARS-CoV-2 sequences from globally circulating clinical isolates, including sequences from recently emerged United Kingdom and South Africa variants, and >300 from mink isolates were analyzed for genetic diversity in the RNA replication complex (nsp7, nsp8, nsp10, nsp12, nsp13, and nsp14) with a focus on the RNA-dependent RNA polymerase (nsp12), the molecular target of RDV. Overall, low genetic variation was observed with only 12 amino acid substitutions present in the entire RNA replication complex in ≥0.5% of analyzed sequences with the highest overall frequency (82.2%) observed for nsp12 P323L that consistently increased over time. Low sequence variation in the RNA replication complex was also observed among the mink isolates. Importantly, the coronavirus Nsp12 mutations previously selected in vitro in the presence of RDV were identified in only 2 isolates (0.002%) within all the analyzed sequences. In addition, among the sequence variants observed in ≥0.5% clinical isolates, including P323L, none were located near the established polymerase active site or sites critical for the RDV mechanism of inhibition. In summary, the low diversity and high genetic stability of the RNA replication complex observed over time and in the recently emerged SARS-CoV-2 variants suggests a minimal global risk of pre-existing SARS-CoV-2 resistance to RDV.
Downtown Diet: a global meta-analysis of urbanization on consumption patterns of vertebrate predators
Authors: Gámez Siria , Potts Abigail , Mills Kirby L. , Allen Aurelia A. , Holman Allyson , Randon Peggy , Linson Olivia , Harris Nyeema C.
Published: December 2020

Predation is a fundamental ecological process that shapes communities and drives long-term evolutionary dynamics. As the world rapidly urbanizes, it is critical to understand how the built environment and other human perturbations alter predation across taxa. We conducted a meta-analysis to quantify the effects of urban environments on three components of trophic ecology in predators: dietary species richness (DSR), dietary evenness (DEV), and stable isotopic ratios (δ13C and δ15N IR). We then evaluated whether intensity of anthropogenic pressure, using the human footprint index (HFI), explained variation in the effect sizes of dietary attributes using a meta-regression. We calculated Hedges’ g effect sizes from 44 studies including 11,986 samples across 40 predatory species in 39 cities globally. The direction and magnitude of effect sizes varied between predator taxonomic groups with reptile diets exhibiting the most sensitivity to urbanization. Effect sizes revealed that predators in cities had comparable DSR, DEV, and nitrogen ratios, though carbon consumption was significantly higher. We found that HFI did not explain variation in effect sizes, a result consistent between the 1993 and 2009 editions of this metric. Our study provides the first assessment of how urbanization has perturbed predator-prey interactions for multiple taxa at a global scale, revealing that the functional role of predators is conserved in cities and urbanization does not inherently relax predation.
XlinkCyNET: a Cytoscape application for visualization of protein interaction networks based on cross-linking mass-spectrometry identifications
Authors: Lima Diogo Borges , Zhu Ying , Liu Fan
Published: December 2020

Software tools that allow visualization and analysis of protein interaction networks are essential for studies in systems biology. One of the most popular network visualization tools in biology is Cytoscape, which offers a large selection of plugins for interpretation of protein interaction data. Chemical cross-linking coupled to mass spectrometry (XL-MS) is an increasingly important source for such interaction data, but there are currently no Cytoscape tools to analyze XL-MS results. In light of the suitability of Cytoscape platform but also to expand its toolbox, here we introduceXlinkCyNET, an open-source Cytoscape Java plugin for exploring large-scale XL-MS-based protein interaction networks. XlinkCyNET offers rapid and easy visualization of intra and intermolecular cross-links and the locations of protein domains in a rectangular bar style, allowing subdomain-level interrogation of the interaction network. XlinkCyNET is freely available from the Cytoscape app store:http://apps.cytoscape.org/apps/xlinkcynetand athttps://www.theliulab.com/software/xlinkcynet.
PhylUp: phylogenetic alignment building with custom taxon sampling
Authors: Kandziora Martha
Published: December 2020

In recent years it has become easier to reconstruct large-scale phylogenies with more or less automated workflows. However, they do not permit to adapt the taxon sampling strategy for the clade of interest. While most tools permit a single representative per taxon, PhylUp – the workflow presented here - enables to use different sampling strategies for different taxonomic ranks, as often needed for molecular dating analyses or for a large outgroup sampling. While PhylUp focuses on user-defined sampling strategies, it also facilitates the updating of alignments with new sequences from local and online sequence databases and their incorporation into existing alignments. To start a PhylUp run at least one sequence per locus has to be provided, PhylUp then adds new sequences to the existing one by internally using BLAST to find similar sequences and filters them according to user settings. Taxonomic sampling is increased compared to available tools and the custom taxonomic sampling allows to use automated workflows for new research fields. The workflow is presented in detail and I demonstrate the usability.
easyMF: A Web Platform for Matrix Factorization-based Biological Discovery from Large-scale Transcriptome Data
Authors: Ma Wenlong , Chen Siyuan , Zhai Jingjing , Qi Yuhong , Xie Shang , Song Minggui , Ma Chuang
Published: December 2020

With the development of high-throughput experimental technologies, large-scale RNA sequencing (RNA-Seq) data have been and continue to be produced, but have led to challenges in extracting relevant biological knowledge hidden in the produced high-dimensional gene expression matrices. Here, we present easyMF, a user-friendly web platform that aims to facilitate biological discovery from large-scale transcriptome data through matrix factorization (MF). The easyMF platform enables users with little bioinformatics experience to streamline transcriptome analysis from raw reads to gene expression and to decompose expression matrix from thousands of genes to a handful of metagenes. easyMF also offers a series of functional modules for metagene-based exploratory analysis with an emphasis on functional gene discovery. As a modular, containerized and open-source platform, easyMF can be customized to satisfy users’ specific demands and deployed as a web server for broad applications. easyMF is freely available athttps://github.com/cma2015/easyMF. We demonstrated the application of easyMF with four case studies using 940 RNA sequencing datasets from maize (Zea maysL.).
Evaluation of a polymeric composite bone filler scaffold for local antibiotic delivery to preventStaphylococcus aureusinfection in a contaminated bone defect
Authors: Beenken Karen E. , Campbell Mara J. , Ramirez Aura M. , Alghazali Karrar , Walker Christopher M. , Jackson Bailey , Griffin Christopher , King William , Bourdo Shawn E. , Rifkin Rebecca , Hecht Silke , Meeker Daniel G. , Anderson David E. , Biris Alexandru S. , Smeltzer Mark S.
Published: December 2020

We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane (dPU), nano-sized hydroxyapatite (nHA), and decellularized bovine bone particles (DBP). In this report we describe the results of studies aimed at evaluating the use of this scaffold as a means of local antibiotic delivery for the prevention of infection in a segmental bone defect contaminated withStaphylococcus aureus. We evaluated two different scaffold formulations that contained the same components in the same ratios but differed from each other with respect to overall porosity and therefore surface area. Studies done with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity was correlated with increased uptake and prolonged release of all three antibiotics. Vancomycin could be passively loaded into either scaffold formulation in an amount sufficient to prevent infection, as evidenced by the complete eradication of viable bacteria from the surgical site of most animals in a rabbit model of a contaminated mid-radial segmental bone defect. Even in those few cases in which complete eradication was not achieved, the number of viable bacteria present in the bone was significantly reduced comparison to untreated controls. There was also no radiographic evidence of osteomyelitis in any rabbit treated with vancomycin-loaded scaffold. Microcomputed tomography (μCT) of bone defects up to 84 days of exposure to scaffolds with and without vancomycin also demonstrated that the addition of vancomycin even in the highest concentration did not significantly diminish the osteogenic properties of either scaffold formulation. Together, these results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery.