bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbonaceous Fractions Contents and Carbon Stable Isotope Compositions of Aerosols Collected in the Atmosphere of Montreal (Canada): Seasonality, Sources, and Implications
Authors: Morera-Gómez Yasser , Cong Zhiyuan , Widory David
Published: March 2021

With the objective of better understanding the sources and dynamics of carbonaceous fractions of the aerosols present in the atmosphere of Montreal, we implemented here an online wet oxidation/isotope ratio mass spectrometry (IRMS) method to simultaneously measure both water-soluble organic carbon (WSOC) content and the corresponding δ13C of aerosol samples collected at four monitoring stations over a 1-year period representing distinct types of environmental conditions (i.e., background, road traffic, industrial, and downtown). We coupled these data with the corresponding concentrations of other carbon fractions: total carbon (TC), elemental carbon plus organic carbon (EC + OC), and carbonates. Results show that TC (6.64 ± 2.88 μg m–3), EC + OC (4.98 ± 2.23 μg m–3), and carbonates (1.71 ± 1.09 μg m–3) were characterized by lower concentrations in winter and higher ones between spring and early autumn, with all fractions expectedly showing significantly lower concentrations for aerosols collected at the background station. We observed a seasonal dependence of the δ13CEC+OC (−25.31 ± 0.94‰) with the EC + OC/total suspended particles (TSP) ratio: (i) an increase of the ratio during late spring, summer and early autumn associated to road traffic emissions characterized by a δ13C of ∼−25‰ and (ii) lower ratios during the winter months indicating the influence of two distinct emission sources, a first one with a δ13C ∼−27‰, suggesting the local influence of combined biomass burning from residential heating and of fossil fuel combustion, and a second one with a δ13C ∼−21‰, likely related to more regional emissions. WSOC (1.14 ± 0.67 μg m–3) presented a similar seasonal pattern for all monitoring stations, with low concentrations in winter, early spring and late autumn that rapidly increased until summer. Our results indicate that this seasonality is controlled by higher anthropogenic contributions from southern Canada and northeastern United States regions and probably from biogenic emissions during the warm months. Moreover, δ13CWSOC (−25.08 ± 1.47‰) showed a 13C-depletion in summer, indicating higher fossil fuel and biogenic contributions, whereas the higher isotope compositions observed in winter may result from the photochemical aging of regional aerosols. Ultimately, we identified the influence of local industrial emissions late in 2013 as well as the impact of aerosol emissions associated to the Lac-Mégantic rail disaster that occurred on July 6, ∼200 km east of Montreal.
Hypothesis and Theory: Fungal Spores in Stemflow and Potential Bark Sources
Authors: Magyar Donát , Van Stan John T. , Sridhar Kandikere R.
Published: March 2021

The study of stemflow fungi began over 50 years ago. Past work has been performed in different climatic regions of the world, with different sampling methods, by mycologists focusing on different taxonomical groups. Therefore, we aim to synthesize this work to delineate major conclusions and emerging hypothesis. Here, we present: (1) a systematic compilation of observations on stemflow conidial concentration, flux, and species composition; (2) an evaluation of the methods underlying these observations; (3) a testable theory to understand spatiotemporal dynamics in stemflow (including honeydews) conidial assemblages, with a focus on their relationship to bark structure and microhabitats; and (4) a discussion of major hypotheses based on past observations and new data. This represents a knowledge gap in our understanding of fungal dispersal mechanisms in forests, in a spatially-concentrated hydrologic flux that interacts with habitats throughout the forest microbiome. The literature synthesis and new data represent observations for 228 fungal species’ conidia in stemflow collected from 58 tree species, 6 palm species, and 1 bamboo species. Hypothetical relationships were identified regarding stemflow production and conidial concentration, flux, and species composition. These relationships appear to be driven by bark physico-chemical properties, tree canopy setting, the diversity of in-canopy microenvironments (e.g., tree holes, bark fissures, and epiphytes), and several possible conidia exchange processes (teleomorph aerosols, epi-faunal exchanges, fungal colonization of canopy microhabitats, and droplet impacts, etc.). The review reveals a more complex function of stemflow fungi, having a role in self-cleaning tree surfaces (which play air quality-related ecoservices themselves), and, on the other hand, these fungi may have a role in the protection of the host plant.
Evaluating the Impact of REDD+ Interventions on Household Forest Revenue in Peru
Authors: Solis David , Cronkleton Peter , Sills Erin O. , Rodriguez-Ward Dawn , Duchelle Amy E.
Published: March 2021

REDD+ was conceived as a system of incentives for reducing emissions from deforestation and degradation. While this could include many different types of interventions to reduce deforestation and degradation, a consensus has emerged that they should safeguard and “do no harm” to the forest-based livelihoods of local people. Many REDD+ projects have been designed to incentivize forest conservation and support local livelihoods by promoting sustainable use of the forest, hence increasing the revenues earned by local households from forest products. We examine two such projects in the Peruvian Amazon, using panel survey data from over 400 households gathered in 2011 and 2014. In the 3 years between surveys, we observed a severe decline in forest revenue. However, by using a BACI study design and matching, we show that this decrease was not caused by the REDD+ interventions. Thus, REDD+ “did no harm” to local people, at least in terms of forest revenues in the early phases of these two projects in the Peruvian Amazon.
A Novel Biomarker Identification Approach for Gastric Cancer Using Gene Expression and DNA Methylation Dataset
Authors: Zhang Ge , Xue Zijing , Yan Chaokun , Wang Jianlin , Luo Huimin
Published: March 2021

As one type of complex disease, gastric cancer has high mortality rate, and there are few effective treatments for patients in advanced stage. With the development of biological technology, a large amount of multiple-omics data of gastric cancer are generated, which enables computational method to discover potential biomarkers of gastric cancer. That will be very important to detect gastric cancer at earlier stages and thus assist in providing timely treatment. However, most of biological data have the characteristics of high dimension and low sample size. It is hard to process directly without feature selection. Besides, only using some omic data, such as gene expression data, provides limited evidence to investigate gastric cancer associated biomarkers. In this research, gene expression data and DNA methylation data are integrated to analyze gastric cancer, and a feature selection approach is proposed to identify the possible biomarkers of gastric cancer. After the original data are pre-processed, the mutual information (MI) is applied to select some top genes. Then, fold change (FC) and T-test are adopted to identify differentially expressed genes (DEG). In particular, false discover rate (FDR) is introduced to revise p_value to further screen genes. For chosen genes, a deep neural network (DNN) model is utilized as the classifier to measure the quality of classification. The experimental results show that the approach can achieve superior performance in terms of accuracy and other metrics. Biological analysis for chosen genes further validates the effectiveness of the approach.
Neutrophils in COVID-19
Authors: Reusch Nico , De Domenico Elena , Bonaguro Lorenzo , Schulte-Schrepping Jonas , Baßler Kevin , Schultze Joachim L. , Aschenbrenner Anna C.
Published: March 2021

Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathophysiology, particularly in those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention to neutrophils has uncovered their fascinating transcriptional and functional diversity as well as their developmental trajectories. These new findings are important to better understand the many facets of neutrophil involvement not only in COVID-19 but also many other acute or chronic inflammatory diseases, both communicable and non-communicable. Here, we highlight the observed immune deviation of neutrophils in COVID-19 and summarize several promising therapeutic attempts to precisely target neutrophils and their reactivity in patients with COVID-19.
First Application of IFCB High-Frequency Imaging-in-Flow Cytometry to Investigate Bloom-Forming Filamentous Cyanobacteria in the Baltic Sea
Authors: Kraft Kaisa , Seppälä Jukka , Hällfors Heidi , Suikkanen Sanna , Ylöstalo Pasi , Anglès Sílvia , Kielosto Sami , Kuosa Harri , Laakso Lauri , Honkanen Martti , Lehtinen Sirpa , Oja Johanna , Tamminen Timo
Published: March 2021

Cyanobacteria are an important part of phytoplankton communities, however, they are also known for forming massive blooms with potentially deleterious effects on recreational use, human and animal health, and ecosystem functioning. Emerging high-frequency imaging flow cytometry applications, such as Imaging FlowCytobot (IFCB), are crucial in furthering our understanding of the factors driving bloom dynamics, since these applications provide community composition information at frequencies impossible to attain using conventional monitoring methods. However, the proof of applicability of automated imaging applications for studying dynamics of filamentous cyanobacteria is still scarce. In this study we present the first results of IFCB applied to a Baltic Sea cyanobacterial bloom community using a continuous flow-through setup. Our main aim was to demonstrate the pros and cons of the IFCB in identifying filamentous cyanobacterial taxa and in estimating their biomass. Selected environmental parameters (water temperature, wind speed and salinity) were included, in order to demonstrate the dynamics of the system the cyanobacteria occur in and the possibilities for analyzing high-frequency phytoplankton observations against changes in the environment. In order to compare the IFCB results with conventional monitoring methods, filamentous cyanobacteria were enumerated from water samples using light microscopical analysis. Two common bloom forming filamentous cyanobacteria in the Baltic Sea, Aphanizomenon flosaquae and Dolichospermum spp. dominated the bloom, followed by an increase in Oscillatoriales abundance. The IFCB results compared well with the results of the light microscopical analysis, especially in the case of Dolichospermum. Aphanizomenon biomass varied slightly between the methods and the Oscillatoriales results deviated the most. Bloom formation was initiated as water temperature increased to over 15°C and terminated as the wind speed increased, dispersing the bloom. Community shifts were closely related to movements of the water mass. We demonstrate how using a high-frequency imaging flow cytometry application can help understand the development of cyanobacteria summer blooms.
Response and Effect Traits of Coral Reef Fish
Authors: Hadj-Hammou Jeneen , Mouillot David , Graham Nicholas A. J.
Published: March 2021

The response-and-effect framework is a trait-based approach that seeks to break down the mechanistic links between ecosystem disturbances, species' traits, and ecosystem processes. We apply this framework to a review of the literature on coral reef fish traits, in order to illustrate the research landscape and structure a path forward for the field. Traits were categorized into five broad groupings: behavioral, life history, morphological, diet, and physiological. Overall, there are fewer studies linking effect traits to ecosystem processes (number of papers on herbivory, n = 14; predation, n = 12; bioerosion, n = 2; nutrient cycling, n = 0) than there are linking response traits to disturbances (climate change, n = 26; fishing, n = 20; pollution, n = 4). Through a network analysis, we show that the size and diet of fish are two of the most common response and effect traits currently used in the literature, central to studies on both ecosystem disturbances and processes. Behavioral and life history traits are more commonly shown to respond to disturbances, while morphological traits tend to be used in capturing ecosystem processes. Pearson correlation coefficients quantifying the strength of the relationships between the most commonly studied process, herbivory, and key effect traits (size, gregariousness, and diel activity) are provided. We find that the most popular cluster of traits used in functional diversity metrics (e.g., functional richness, functional dispersion) is comprised of size, diet, space use/position in the water column, diel activity, gregariousness, and mobility, which encompass three of the broad trait categories. Our assessment of the literature highlights that more research is needed to support an evidence-based selection of traits to understand and predict ecosystem functioning. In synthesizing the literature, we identify research gaps and provide an avenue toward a more robust trait-selection process.
Influence of Non-metallic Inclusions on Corrosive Properties of Polar Steel
Authors: Li Ming , Wu Huajie , Sun Yanhui
Published: March 2021

Polar steel requires excellent toughness and corrosion resistance for breaking icy surfaces in low-temperature seawater environments. In this study, the effect of inclusions on the corrosion resistance of polar steel was examined. In the experiments conducted, the composition and morphology of the inclusions in steel were controlled using different deoxidation methods during steel refining. The morphology and composition of the corrosion-resistant active inclusions were analyzed using scanning electron microscopy and energy dispersive spectroscopy. The corrosion resistance of polar steel was determined by measuring the saturation current density of the anodic dissolution of steel in a corrosive medium via an electrochemical method. The corrosion resistance under simulated seawater was also investigated under laboratory conditions. It was found that as the ratio of Al/Mg approaches the stoichiometric composition of the spinel (2.3–2.5), the inclusions become less active; as the ratio increases further, the corrosion-resistant activity increases due to the formation of MgAl2O4⋅CaO complexes, leading to an increase in local stress around the inclusions. If steel is deoxidized with Zr–Ti, small Zr–Ti complex oxides form in the steel, providing nucleation particles for the precipitation of spheroidized and uniformly distributed MnS. Therefore, steel deoxidized with Zr–Ti has better seawater corrosion resistance than Al-deoxidized steel.
The In Situ Observation of Phase Transformations During Intercritical Annealing of a Medium Manganese Advanced High Strength Steel by High Energy X-Ray Diffraction
Authors: Hu Xiaohua , Mueller Josh J. , Sun Xin , De Moor Emmanuel , Speer John G. , Matlock David K. , Ren Yang
Published: March 2021

Microstructural changes during thermal processing of a medium manganese steel containing (in wt%) 0.19C and 4.39 Mn were evaluated in situ with a high energy X-ray diffraction system (HEXRD). Samples with an initial fully martensitic microstructure were heated to intercritical annealing (IA) temperatures of 600 or 650°C, held for 30 min, and cooled to room temperature. Diffraction data were analyzed to determine the variations in austenite and ferrite phase fractions and phase lattice constants throughout the ICA cycles. On heating, the 2 vol. pct of austenite present in the starting microstructure decomposed, and cementite precipitation then occurred. During isothermal holding, the austenite fraction increased, up to 20% for the sample annealed at 650°C. The measured austenite fractions were less than those calculated by Thermo-Calc for equilibrium conditions, indicating that the 30-min hold time was insufficient to achieve near-equilibrium conditions. Observed changes in lattice parameters during isothermal holding were interpreted to reflect composition changes due to redistribution of the C and Mn between austenite and ferrite. The results are discussed in relation to the potential for controlling austenite stability during ambient temperature deformation.
A Review on Structural Configurations of Magnetorheological Fluid Based Devices Reported in 2018–2020
Authors: Hua Dezheng , Liu Xinhua , Li Zengqiang , Fracz Pawel , Hnydiuk-Stefan Anna , Li Zhixiong
Published: March 2021

Magnetorheological fluid (MRF) is a kind of smart materials with rheological behavior change by means of external magnetic field application, which has been widely adopted in many complex systems of different technical fields. In this work, the state-of-the-art MRF based devices are reviewed according to structural configurations reported from 2018 to 2020. Based on the rheological characteristic, the MRF has a variety of operational modes, such as flow mode, shear mode, squeeze mode and pinch mode, and has unique advantages in some special practical applications. With reference to these operational modes, improved engineering mechanical devices with MRF are summarized, including brakes, clutches, dampers, and mounts proposed over these 3 years. Furthermore, some new medical devices using the MRF are also investigated, such as surgical assistive devices and artificial limbs. In particular, some outstanding advances on the structural innovations and application superiority of these devices are introduced in detail. Finally, an overview of the significant issues that occur in the MRF based devices is reported, and the developing trends for the devices using the MRF are discussed.
In-situ Capacitance Sensing for the Settlement of Magnetorheological Fluid: Simulation and Experiments
Authors: Zhang Honghui , Zou Zhiyuan , An Na , Xiong Ningsong , Yang Xu
Published: March 2021

In light of the insurmountable sedimentation of magnetorheological (MR) fluid, it is of great significance to ensure the performability of an MR damper by introducing a sensing method for MR fluid settling, and a key indicator to identify the health status of the MR damper is critical. However, the settling monitoring system for MR fluid can nowadays only function in a laboratory with transparent and non-magnetic tubes, which is not qualified for the in-situ sensing in a steel-made cylinder. Under the analysis of an open plate capacitor (OPC) configuration, the relationship between the concentration of magnetorheological fluid and the capacitance is investigated by simulation and experiments, and based on OPC, an in-situ sensing method for the settlement monitoring of magnetorheological fluid is designed. Long-time settling monitoring is carried out with home-made MR fluids, and the test results show that the sensing method can effectively reflect the status of settled MR fluids, and has the potential to be utilized in the identification of MR fluid compression points, which provides the strategic signal for the probable active or operational re-dispersing of MR fluid.
Clinical Characteristics of Severe COVID-19 Patients Admitted to an Intensive Care Unit in Lombardy During the Italian Pandemic
Authors: Briguglio Matteo , Crespi Tiziano , Pino Fabio , Mazzocchi Marco , Porta Mauro , De Vecchi Elena , Banfi Giuseppe , Perazzo Paolo
Published: March 2021

Italy was one of the worst affected European countries during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. More than 50% of Italian cases occurred in the northern region of Lombardy, where the saturation of health services between March and April 2020 forced hospitals to allocate patients according to available resources. Eighteen severe coronavirus disease 2019 (COVID-19) patients were admitted to our hospital needing intensive support. Given the disease fatality, we investigated the patients' characteristics to identify mortality predictors. We counted seven deaths from multiple organ failure, two from septic shock, and two from collapsed lungs. The maximum case fatality was observed in patients who contracted SARS-CoV-2 in hospitals. The fatal outcome was associated with the following baseline characteristics: polymorbidity (OR 2.519, p = 0.048), low body mass index (OR 2.288, p = 0.031), low hemoglobin (OR 3.012, p = 0.046), and antithrombin III (OR 1.172, p = 0.048), along with a worsening of PaO2/FiO2 ratio in the first 72 h after admission (OR 1.067, p = 0.031). The occurrence of co-infections during hospitalization was associated with a longer need for intensive care (B = 4.511, p = 0.001). More information is needed to inform intensive care for patients with severe COVID-19, but our findings would certainly contribute to shed some light on this unpredictable and multifaceted disease.
Three-Dimensional CT for Quantification of Longitudinal Lung and Pneumonia Variations in COVID-19 Patients
Authors: Chen Qiuying , Chen Lv , Liu Shuyi , Chen Luyan , Li Minmin , Chen Zhuozhi , You Jingjing , Zhang Bin , Zhang Shuixing
Published: March 2021

Objectives: Visual chest CT is subjective with interobserver variability. We aimed to quantify the dynamic changes of lung and pneumonia on three-dimensional CT (3D-CT) images in coronavirus disease 2019 (COVID-19) patients during hospitalization.

Methods: A total of 110 laboratory-confirmed COVID-19 patients who underwent chest CT from January 3 to February 29, 2020 were retrospectively reviewed. Pneumonia lesions were classified as four stages: early, progressive, peak, and absorption stages on chest CT. A computer-aided diagnostic (CAD) system calculated the total lung volume (TLV), the percentage of low attenuation areas (LAA%), the volume of pneumonia, the volume of ground-glass opacities (GGO), the volume of consolidation plus the GGO/consolidation ratio. The CT score was visually assessed by radiologists. Comparisons of lung and pneumonia parameters among the four stages were performed by one-way ANOVA with post-hoc tests. The relationship between the CT score and the volume of pneumonia, and between LAA% and the volume of pneumonia in four stages was assessed by Spearman's rank correlation analysis.

Results: A total of 534 chest CT scans were performed with a median interval of 4 days. TLV, LAA%, and the GGO/consolidation ratio were significantly decreased, while the volume of pneumonia, GGO, and consolidation were significantly increased in the progressive and peak stages (for all, P < 0.05). The CT score was significantly correlated with the pneumonia volume in the four stages (r = 0.731, 0.761, 0.715, and 0.669, respectively, P < 0.001).

Conclusion: 3D-CT could be used as a useful quantification method in monitoring the dynamic changes of COVID-19 pneumonia.
Comparative Analysis of Gut Microbiota in Captive and Wild Oriental White Storks: Implications for Conservation Biology
Authors: Wu Hong , Wu Fang-Ting , Zhou Qi-Hai , Zhao Da-Peng
Published: March 2021

The oriental white stork (Ciconia boyciana) is considered an endangered species based on the International Union for Conservation of Nature (IUCN) Red List. This study presents the first evidence on comparative analysis of gut microbial diversity of C. boyciana from various breeding conditions. To determine the species composition and community structure of the gut microbiota, 24 fecal samples from Tianjin Zoo and Tianjin Qilihai Wetland were characterized by sequencing 16S rRNA gene amplicons using the Illumina MiSeq platform. Firmicutes was found to be the predominant phylum. Analysis of community structure revealed significant differences in the species diversity and richness between the populations of the two breeding conditions. The greatest α-diversity was found in wild C. boyciana, while artificial breeding storks from Tianjin Zoo had the least α-diversity. Principal coordinates analysis showed that the microbial communities were different between the two studied groups. In conclusion, this study reveals the species composition and structure of the gut microbiota of oriental white storks under two breeding conditions, and our findings could contribute to the integrative conservation of this endangered bird.
Genetic Causes of Non-pathogenic Pseudomonas syringae pv. actinidiae Isolates in Kiwifruit Orchards
Authors: Li Yue , Zhu Qiaomei , Zhi Taihui , Fan Rong , Xie Ting , Zhao Zhibo , Long Youhua , Li Zhong
Published: March 2021

Bacterial canker disease has become the largest threat to kiwifruit cultivation and production. A monomorphic subpopulation of Pseudomonas syringae pv. actinidiae biovar 3 (Psa3) is responsible for the pandemic worldwide. Diversity in pathogenicity has been found in the pandemic subpopulation and in other Psa3 subpopulations causing epidemics in China. However, the genetic bases have not yet been elucidated. In this study, 117 Psa3 isolates were identified by Psa- and Psa3-specific primers, and evaluated for pathogenicity. Three isolates G4, G40, and S2 are not pathogenic to kiwifruit and do not elicit hypersensitivity responses (HRs) in non-host Nicotiana benthamiana leaves. Two isolates, G25 and G35, exhibited attenuated HR-eliciting activity in non-host N. benthamiana, but they exhibited greatly and slightly reduced pathogenicity in host plants, respectively. The genomes of the five isolates were sequenced and compared with closely related isolates revealed by MLVA and whole-genome typing methods. The candidate genetic loci responsible for the changes in pathogenicity and HR elicitation, were further evaluated by allele replacement experiments. We found that the three non-pathogenic isolates were formed due to the independent, identical insertion events of ISPsy36 transposon in the hrpR gene, encoding a key regulator of type III secretion system (T3SS) and type III effectors (T3Es). In the symptomatic sample from which G4 was isolated, 27% HR negative isolates were detected. In isolate G25, transposon insertion of ISPsy32 at the non-coding sequence upstream of the hrpR gene was detected, similar to a previously reported low-virulent Psa3 strain M227. In isolate G35, we detected disruptions of T3Es hopBB1-1 and hopBB1-2, which induce HR in N. benthamiana leaves revealed by Agrobacterium tumefaciens infiltration. These phenotype-changed isolates were formed at low frequencies during the course of pathogen infection in host plants, supported by the binding assay of ISPsy32 and the non-coding DNA sequences upstream of the hrpR gene, the co-isolation of the virulent isolates belonging to the same MLVA clade, and the low levels of transcription of the transposon genes. Taken together, in terms of short-term field evolution, transposon insertions in the T3SS-related genes resulted in the formation of non-pathogenic and low-virulent Psa3 isolates.
ThermoScan: Semi-automatic Identification of Protein Stability Data From PubMed
Authors: Turina Paola , Fariselli Piero , Capriotti Emidio
Published: March 2021

During the last years, the increasing number of DNA sequencing and protein mutagenesis studies has generated a large amount of variation data published in the biomedical literature. The collection of such data has been essential for the development and assessment of tools predicting the impact of protein variants at functional and structural levels. Nevertheless, the collection of manually curated data from literature is a highly time consuming and costly process that requires domain experts. In particular, the development of methods for predicting the effect of amino acid variants on protein stability relies on the thermodynamic data extracted from literature. In the past, such data were deposited in the ProTherm database, which however is no longer maintained since 2013. For facilitating the collection of protein thermodynamic data from literature, we developed the semi-automatic tool ThermoScan. ThermoScan is a text mining approach for the identification of relevant thermodynamic data on protein stability from full-text articles. The method relies on a regular expression searching for groups of words, including the most common conceptual words appearing in experimental studies on protein stability, several thermodynamic variables, and their units of measure. ThermoScan analyzes full-text articles from the PubMed Central Open Access subset and calculates an empiric score that allows the identification of manuscripts reporting thermodynamic data on protein stability. The method was optimized on a set of publications included in the ProTherm database, and tested on a new curated set of articles, manually selected for presence of thermodynamic data. The results show that ThermoScan returns accurate predictions and outperforms recently developed text-mining algorithms based on the analysis of publication abstracts.

Availability: The ThermoScan server is freely accessible online at https://folding.biofold.org/thermoscan. The ThermoScan python code and the Google Chrome extension for submitting visualized PMC web pages to the ThermoScan server are available at https://github.com/biofold/ThermoScan.
Easy Synthesis of Complex Biomolecular Assemblies: Wheat Germ Cell-Free Protein Expression in Structural Biology
Authors: Fogeron Marie-Laure , Lecoq Lauriane , Cole Laura , Harbers Matthias , Böckmann Anja
Published: March 2021

Cell-free protein synthesis (CFPS) systems are gaining more importance as universal tools for basic research, applied sciences, and product development with new technologies emerging for their application. Huge progress was made in the field of synthetic biology using CFPS to develop new proteins for technical applications and therapy. Out of the available CFPS systems, wheat germ cell-free protein synthesis (WG-CFPS) merges the highest yields with the use of a eukaryotic ribosome, making it an excellent approach for the synthesis of complex eukaryotic proteins including, for example, protein complexes and membrane proteins. Separating the translation reaction from other cellular processes, CFPS offers a flexible means to adapt translation reactions to protein needs. There is a large demand for such potent, easy-to-use, rapid protein expression systems, which are optimally serving protein requirements to drive biochemical and structural biology research. We summarize here a general workflow for a wheat germ system providing examples from the literature, as well as applications used for our own studies in structural biology. With this review, we want to highlight the tremendous potential of the rapidly evolving and highly versatile CFPS systems, making them more widely used as common tools to recombinantly prepare particularly challenging recombinant eukaryotic proteins.
Modeling Microtubule Counterion Distributions and Conductivity Using the Poisson-Boltzmann Equation
Authors: Eakins Boden B. , Patel Sahil D. , Kalra Aarat P. , Rezania Vahid , Shankar Karthik , Tuszynski Jack A.
Published: March 2021

Microtubules are highly negatively charged proteins which have been shown to behave as bio-nanowires capable of conducting ionic currents. The electrical characteristics of microtubules are highly complicated and have been the subject of previous work; however, the impact of the ionic concentration of the buffer solution on microtubule electrical properties has often been overlooked. In this work we use the non-linear Poisson Boltzmann equation, modified to account for a variable permittivity and a Stern Layer, to calculate counterion concentration profiles as a function of the ionic concentration of the buffer. We find that for low-concentration buffers ([KCl] from 10 μM to 10 mM) the counterion concentration is largely independent of the buffer's ionic concentration, but for physiological-concentration buffers ([KCl] from 100 to 500 mM) the counterion concentration varies dramatically with changes in the buffer's ionic concentration. We then calculate the conductivity of microtubule-counterion complexes, which are found to be more conductive than the buffer when the buffer's ionic concentrations is less than ≈100 mM and less conductive otherwise. These results demonstrate the importance of accounting for the ionic concentration of the buffer when analyzing microtubule electrical properties both under laboratory and physiological conditions. We conclude by calculating the basic electrical parameters of microtubules over a range of ionic buffer concentrations applicable to nanodevice and medical applications.
Dual Role of Lysophosphatidic Acid Receptor 2 (LPA2) in Amyotrophic Lateral Sclerosis
Authors: Puigdomenech-Poch Maria , Martínez-Muriana Anna , Andrés-Benito Pol , Ferrer Isidre , Chun Jerold , López-Vales Rubèn
Published: March 2021

Lysophosphatidic acid (LPA) is a pleiotropic extracellular lipid mediator with many physiological functions that signal through six known G protein-coupled receptors (LPA1–6). In the central nervous system (CNS), LPA mediates a wide range of effects including neural progenitor cell physiology, neuronal cell death, axonal retraction, and inflammation. Since inflammation is a hallmark of most neurological conditions, we hypothesized that LPA could be involved in the physiopathology of amyotrophic lateral sclerosis (ALS). We found that LPA2 RNA was upregulated in post-mortem spinal cord samples of ALS patients and in the sciatic nerve and skeletal muscle of SOD1G93A mouse, the most widely used ALS mouse model. To assess the contribution of LPA2 to ALS, we generated a SOD1G93A mouse that was deficient in Lpar2. This animal revealed that LPA2 signaling accelerates disease onset and neurological decline but, unexpectedly, extended the lifespan. To gain insights into the early harmful actions of LPA2 in ALS, we studied the effects of this receptor in the spinal cord, peripheral nerve, and skeletal muscle of ALS mice. We found that LPA2 gene deletion increased microglial activation but did not contribute to motoneuron death, astrogliosis, degeneration, and demyelination of motor axons. However, we observed that Lpar2 deficiency protected against muscle atrophy. Moreover, we also found the deletion of Lpar2 reduced the invasion of macrophages into the skeletal muscle of SOD1G93A mice, linking LPA2 signaling with muscle inflammation and atrophy in ALS. Overall, these results suggest for the first time that LPA2 contributes to ALS, and its genetic deletion results in protective actions at the early stages of the disease but shortens survival thereafter.
Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy
Authors: Charif Majida , Bris Céline , Goudenège David , Desquiret-Dumas Valérie , Colin Estelle , Ziegler Alban , Procaccio Vincent , Reynier Pascal , Bonneau Dominique , Lenaers Guy , Amati-Bonneau Patrizia
Published: March 2021

Advances in next-generation sequencing (NGS) facilitate the diagnosis of genetic disorders. To evaluate its use for the molecular diagnosis of inherited optic neuropathy (ION), a blinding disease caused by the degeneration of retinal ganglion cells, we performed genetic analysis using targeted NGS of 22 already known and candidate genes in a cohort of 1,102 affected individuals. The panel design, library preparation, and sequencing reactions were performed using the Ion AmpliSeq technology. Pathogenic variants were detected in 16 genes in 245 patients (22%), including 186 (17%) and 59 (5%) dominant and recessive cases, respectively. Results confirmed that OPA1 variants are responsible for the majority of dominant IONs, whereas ACO2 and WFS1 variants are also frequently involved in both dominant and recessive forms of ION. All pathogenic variants were found in genes encoding proteins involved in the mitochondrial function, highlighting the importance of mitochondria in the survival of retinal ganglion cells.
Telemedicine and Virtual Reality at Time of COVID-19 Pandemic: An Overview for Future Perspectives in Neurorehabilitation
Authors: Matamala-Gomez Marta , Bottiroli Sara , Realdon Olivia , Riva Giuseppe , Galvagni Lucia , Platz Thomas , Sandrini Giorgio , De Icco Roberto , Tassorelli Cristina
Published: March 2021

In catastrophic situations such as pandemics, patients' healthcare including admissions to hospitals and emergency services are challenged by the risk of infection and by limitations of healthcare resources. In such a setting, the use of telemedicine interventions has become extremely important. New technologies have proved helpful in pandemics as a solution to improve the quality of life in vulnerable patients such as persons with neurological diseases. Moreover, telemedicine interventions provide at-home solutions allowing clinicians to telemonitor and assess patients remotely, thus minimizing risk of infection. After a review of different studies using telemedicine in neurological patients, we propose a telemedicine process flow for healthcare of subjects with chronic neurological disease to respond to the new challenges for delivering quality healthcare during the transformation of public and private healthcare organizations around the world forced by COVID-19 pandemic contingency. This telemedicine process flow represents a replacement for in-person treatment and thereby the provision equitable access to the care of vulnerable people. It is conceptualized as comprehensive service including (1) teleassistance with patient counseling and medical treatment, (2) telemonitoring of patients' health conditions and any changes over time, as well as (3) telerehabilitation, i.e., interventions to assess and promote body functions, activities, and consecutively participation. The hereby proposed telemedicine process flow could be adopted on a large scale to improve the public health response during healthcare crises like the COVID-19 pandemic but could equally promote equitable health care independent of people's mobility or location with respect to the specialized health care center.
Blast Exposure Causes Long-Term Degeneration of Neuronal Cytoskeletal Elements in the Cochlear Nucleus: A Potential Mechanism for Chronic Auditory Dysfunctions
Authors: Arun Peethambaran , Rossetti Franco , Wilder Donna M. , Wang Ying , Gist Irene D. , Long Joseph B.
Published: March 2021

Blast-induced auditory dysfunctions including tinnitus are the most prevalent disabilities in service members returning from recent combat operations. Most of the previous studies were focused on the effect of blast exposure on the peripheral auditory system and not much on the central auditory signal-processing regions in the brain. In the current study, we have exposed rats to single and tightly coupled repeated blasts and examined the degeneration of neuronal cytoskeletal elements using silver staining in the central auditory signal-processing regions in the brain at 24 h, 14 days, 1 month, 6 months, and 1 year. The brain regions evaluated include cochlear nucleus, lateral lemniscus, inferior colliculus, medial geniculate nucleus, and auditory cortex. The results obtained indicated that a significant increase in degeneration of neuronal cytoskeletal elements was observed only in the left and right cochlear nucleus. A significant increase in degeneration of neuronal cytoskeletal elements was observed in the cochlear nucleus at 24 h and persisted through 1 year, suggesting acute and chronic neuronal degeneration after blast exposure. No statistically significant differences were observed between single and repeated blasts. The localized degeneration of neuronal cytoskeletal elements in the cochlear nucleus suggests that the damage could be caused by transmission of blast shockwaves/noise through the ear canal and that use of suitable ear protection devices can protect against acute and chronic central auditory signal processing defects including tinnitus after blast exposure.
National and Subnational Incidence, Mortality, and Years of Life Lost Due to Breast Cancer in Iran: Trends and Age-Period-Cohort Analysis Since 1990
Authors: Ataeinia Bahar , Saeedi Moghaddam Sahar , Shabani Mahsima , Gohari Kimiya , Sheidaei Ali , Rezaei Nazila , Naderimagham Shohreh , Ghasemi Erfan , Rouhifard Khalilabad Mahtab , Roshani Shahin , Farzi Yosef , Farzadfar Farshad
Published: March 2021

Breast cancer is the most common cancer among women, causing considerable burden and mortality. Demographic and lifestyle transitions in low and low-middle income countries have given rise to its increased incidence. The successful management of cancer relies on evidence-based policies taking into account national epidemiologic settings. We aimed to report the national and subnational trends of breast cancer incidence, mortality, years of life lost (YLL) and mortality to incidence ratio (MIR) since 1990. As part of the National and Subnational Burden of Diseases project, we estimated incidence, mortality and YLL of breast cancer by sex, age, province, and year using a two-stage spatio-temporal model, based on the primary dataset of national cancer and death registry. MIR was calculated as a quality of care indicator. Age-period-cohort analysis was used to distinguish the effects of these three collinear factors. A significant threefold increase in age-specific incidence at national and subnational levels along with a twofold extension of provincial disparity was observed. Although mortality has slightly decreased since 2000, a positive mortality annual percent change was detected in patients aged 25–34 years, leading to raised YLLs. A significant declining pattern of MIR and lower provincial MIR disparity was observed. We observed a secular increase of breast cancer incidence. Further evaluation of risk factors and developing national screening policies is recommended. A descending pattern of mortality, YLL and MIR at national and subnational levels reflects improved quality of care, even though mortality among younger age groups should be specifically addressed.
Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p
Authors: Luo Tingting , Zhou Xiaocheng , Jiang Erhui , Wang Lin , Ji Yaoting , Shang Zhengjun
Published: March 2021

Osteosarcoma (OS) is the most common primary bone cancer characterized by an aggressive phenotype with bone destruction. The prognosis of OS patients remains unoptimistic with the current treatment strategy. Recently, osteoclasts are believed to play a crucial role in cancer bone metastasis. Thus, osteoclast could be a target both in bone destruction and cancer progression in OS. However, mechanisms governing osteoclastogenesis in OS remain poorly understood. miRNA delivered by small extracellular vesicles (sEVs) could mediate cellular communications. In this study, we investigated the effects of sEVs on osteoclastogenesis and osteoclast function, also clarified the underlying mechanism. We herein found that sEVs promoted pre-osteoclast migration, osteoclastogenesis and resorption by exposing RAW264.7 cells to sEVs derived from OS cells. Bioinformatics analysis showed that phosphatase tension homologue (PTEN), and miR-19a-3p were involved in OS progression. Overexpression of miR-19a-3p or sEVs’ miR-19a-3p promoted osteoclast formation and function through PTEN/PI3K/AKT signaling pathway, while inhibition of miR-19a-3p showed the contrary results. The bone marrow macrophages (BMMs) were used to verify the results. OS mice, which were established by subcutaneous injection of OS cells, exhibited increased levels of sEVs’ miR-19a-3p in blood. Moreover, micro-computed tomography (CT) and histomorphometry analysis demonstrated that OS mice exhibited osteopenia with increased number of osteoclasts. In conclusion, miR-19a-3p delivery via OS cell-derived sEVs promotes osteoclast differentiation and bone destruction through PTEN/phosphatidylinositol 3 -kinase (PI3K)/protein kinase B (AKT) signaling pathway. These findings highlight sEVs packaging of miR-19a-3p as a potential target for prevention and treatment of bone destruction and cancer progression in OS patients. And this finding provides a novel potentially therapeutic target for the bone metastasis.
The Role of 2-Oxoglutarate Dependent Dioxygenases in Gliomas and Glioblastomas: A Review of Epigenetic Reprogramming and Hypoxic Response
Authors: Crake Rebekah L. I. , Burgess Eleanor R. , Royds Janice A. , Phillips Elisabeth , Vissers Margreet C. M. , Dachs Gabi U.
Published: March 2021

Gliomas are a heterogeneous group of cancers that predominantly arise from glial cells in the brain, but may also arise from neural stem cells, encompassing low-grade glioma and high-grade glioblastoma. Whereas better diagnosis and new treatments have improved patient survival for many cancers, glioblastomas remain challenging with a highly unfavorable prognosis. This review discusses a super-family of enzymes, the 2-oxoglutarate dependent dioxygenase enzymes (2-OGDD) that control numerous processes including epigenetic modifications and oxygen sensing, and considers their many roles in the pathology of gliomas. We specifically describe in more detail the DNA and histone demethylases, and the hypoxia-inducible factor hydroxylases in the context of glioma, and discuss the substrate and cofactor requirements of the 2-OGDD enzymes. Better understanding of how these enzymes contribute to gliomas could lead to the development of new treatment strategies.
Efficacy of Herbal Medicines Intervention for Colorectal Cancer Patients With Chemotherapy-Induced Gastrointestinal Toxicity — a Systematic Review and Meta-Analysis
Authors: Chen Yuanyuan , Cheng Chien-shan , Tan Hor-Yue , Tam Chi Wing , Wang Ning , Feng Yibin
Published: March 2021

Purpose: Chemotherapy-induced gastrointestinal (CIGI) toxicity affects the quality of life of patients with colorectal cancer (CRC) and the clinical application of treatment drugs. This review aims to evaluate the efficacy of traditional herbal medicines (HMs) in alleviating symptoms of CIGI toxicity (including nausea and vomiting, anorexia, diarrhea, constipation, oral mucositis, abdominal pain, and abdominal distension), and to explore further individual herb or herbal combinations in alleviating the CIGI toxicity.

Methods: Nine electronic databases were screened from 2010 to 2020. Twenty-two randomized controlled trials with a total of 1,995 patients evaluating the complementary efficacy of HMs with chemotherapy compared with chemotherapy-alone were included. Further, sensitivity analyses of orally administered multi-ingredient HM interventions were explored based on the composition of HM interventions.

Results: The meta-analysis showed that HM treatment combined with chemotherapy significantly alleviated the overall CIGI toxicity (RR = 0.78 [0.72, 0.84], p < 0.001, I2 = 44%), nausea and vomiting (RR = 0.74 [0.66, 0.82], p < 0.001, I2 = 35%), diarrhea (P = 0.02, RR = 0.64, 95% CI = 0.44–0.93, I2 = 50%), oral mucositis (RR = 0.65 [0.48, 0.88], P = 0.005, I2 = 24%), and abdominal distension (RR = 0.36 [0.18, 0.73], P = 0.004, I2 = 0%). However, no statistically significant effects of HMs were shown in studies with a double-blind design for CIGI toxicity. Based on the ingredients of the HMs, further sensitivity analyses identified five herbs [Glycyrrhiza uralensis Fisch., Atractylodes macrocephala Koidz., Astragalus membranaceus (Fisch.) Bge., Codonopsis pilosula (Franch.) Nannf., and the pericarp of Citrus reticulata Blanco.] that were associated with significant reductions in CIGI toxicity.

Conclusion: A statistically significant effect of HMs combined with chemotherapy on alleviating the overall CIGI toxicity, nausea and vomiting, diarrhea, oral mucositis, or abdominal distension is only shown in studies without a double-blind design. Further well-designed, double-blinded, large-scaled randomized controlled trials (RCTs) are warranted to comprehensively evaluate the treatment efficacy. Further clinical research that includes the five herbs with chemotherapy for patients, the safety of the combinations of these herbs, and the potential synergistic effects of these combinations of herbs should be conducted.