bluuebunny/crossref_metadata_2025 huggingface dataset:
Fungal communities of submerged fine detritus from temperate peatland and stream habitats
Authors: Raudabaugh DB , Bach EM , Allen JM , Miller AN
Published: April 2021

Fungi are essential in aquatic ecosystems, transforming organic matter into energy sources that support higher trophic levels. However, researchers do not yet know the extent of fungal diversity and species distribution within these important ecosystems. Therefore, we examined the detrital fungal communities from contrasting aquatic habitats (temperate peatlands and streams) to provide an in-depth inventory and greater understanding of how these communities differ. Fine submerged detritus or substrate on or beneath the stream bed were collected from 6 sites. Fungal cultures were isolated from samples collected in May, July/August, and November from 2 sites in 2014 and 4 sites in 2016. Culture-independent analyses were conducted on 42 environmental samples collected in November 2016. Results indicated that peatland and stream fungal communities were taxonomically diverse, phylogenetically distinct, and harbored many unknown taxa from the kingdom Fungi. Specifically, stream habitats were more species-rich, in both number of species and phylogenetic diversity, compared to peatland habitats. In addition, fungal species and phylogenetic distribution within most major fungal classes were distinct between peatland and stream fungal communities. In light of global climate change, habitat loss, and water pollution, it has become increasingly important to examine these understudied and essential fungal communities within these ecosystems.
Warren Lewis: The Soldier Sailor
Authors: King Don W.
Published: April 2021

In the years immediately after his retirement from the Royal Army Service Corps on 21 December 1932, Captain Warren ‘Warnie’ Lewis expended most of his energy compiling the Lewis Papers, an extensive family archive that, by almost any measure, is an exceptional accomplishment. Shortly after finishing this massive yet pleasurable undertaking, Warnie turned to an even more delightful activity: sailing the waterways in and around Oxford and Cambridge on the Bosphorus, a small cabin cruiser he had specially built, therein realizing a life-long passion for ships and boats and reaching back to the childhood worlds of Animal Land and Boxen (shared with his younger brother), upon whose waters the first Bosphorus sailed. From 1936 until the outbreak of World War II, Warnie spent many days on his second Bosphorus, enjoying countless hours of relative freedom and personal satisfaction. This essay explores Warnie's days aboard his ‘ditchcrawler’, primarily through the lens of the eight essays he published in The Motor Boat and Yachting magazine in the late 1930s.
INCIDENCIA DEL SECTOR SOCIETARIO EN LA EMPLEABILIDAD DEL ECUADOR
Authors:   Escuela Superior Politécnica de Chimborazo, Villa Cesar , Merino Edgar ,   Instituto Superior Tecnológico Bolívar, Vargas Diana ,   Escuela Superior Politécnica de Chimborazo
Published: April 2021

In December 2017, the unemployment rate reached 4.6% nationwide. Considering a social problem, it is necessary to go to research to reduce this significant percentage, without increasing public spending. The corporate sector defined as natural persons, legal entities and other associative forms that develop a productive activity, in any part of the national territory, with a total of 64,259 companies, according to the 2017 ranking of the Superintendency of Companies, is analyzed as a development alternative. In this space we will analyze employability as the ability to obtain or keep a job and develop the necessary skills to improve the productivity of companies; the study is: observational, retrospective, cross-sectional and descriptive. It is concluded that the Corporate Sector is a strategic ally in reducing unemployment, it contributes 14.50% of the economically active population; and, in generating taxes for the state through its capital, sales of goods or services that they produce and the results they obtain in an economic period; The incidence of 1,172,439 with Adequate Employment allows observing the contribution of the Corporate Sector to the economy of Ecuador in terms of employability; it makes the difference with the Public Sector that requires State resources to guarantee the provision of services.
Bromsa bedragarna
Authors: Arvidsson Klara , Ibrahim Hadeel Ali , Rehn Isabelle
Published: April 2021

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Intravital Metabolic Autofluorescence Imaging Captures Macrophage Heterogeneity Across Normal and Cancerous Tissue
Authors: Heaster Tiffany M. , Heaton Alexa R. , Sondel Paul M. , Skala Melissa C.
Published: April 2021

Macrophages are dynamic immune cells that govern both normal tissue function and disease progression. However, standard methods to measure heterogeneity in macrophage function within tissues require tissue excision and fixation, which limits our understanding of diverse macrophage function in vivo. Two-photon microscopy of the endogenous metabolic co-enzymes NAD(P)H and flavin adenine dinucleotide (FAD) (metabolic autofluorescence imaging) enables dynamic imaging of mouse models in vivo. Here, we demonstrate metabolic autofluorescence imaging to assess cell-level macrophage heterogeneity in response to normal and cancerous tissue microenvironments in vivo. NAD(P)H and FAD fluorescence intensities and lifetimes were measured for both tissue-resident macrophages in mouse ear dermis and tumor-associated macrophages in pancreatic flank tumors. Metabolic and spatial organization of macrophages were determined by performing metabolic autofluorescence imaging and single macrophage segmentation in mice engineered for macrophage-specific fluorescent protein expression. Tumor-associated macrophages exhibited decreased optical redox ratio [NAD(P)H divided by FAD intensity] compared to dermal macrophages, indicating that tumor-associated macrophages are more oxidized than dermal macrophages. The mean fluorescence lifetimes of NAD(P)H and FAD were longer in dermal macrophages than in tumor-associated macrophages, which reflects changes in NAD(P)H and FAD protein-binding activities. Dermal macrophages had greater heterogeneity in optical redox ratio, NAD(P)H mean lifetime, and FAD mean lifetime compared to tumor-associated macrophages. Similarly, standard markers of macrophage phenotype (CD206 and CD86) assessed by immunofluorescence revealed greater heterogeneity in dermal macrophages compared to tumor-associated macrophages. Ultimately, metabolic autofluorescence imaging provides a novel tool to assess tissue-specific macrophage behavior and cell-level heterogeneity in vivo in animal models.
Extraction, Purification, Bioactivities and Application of Matrix Proteins From Pearl Powder and Nacre Powder: A Review
Authors: Pei Jingying , Wang Yan , Zou Xianguo , Ruan Huajun , Tang Changming , Liao Jie , Si Guangjie , Sun Peilong
Published: April 2021

Natural pearls are formed when sand or parasites (irritants) accidentally enter into the oyster body and form pearls under the cover of the nacre layer. Pearl powder is a powdery substance by grinding pearls into small grains, however, the nacre powder is the inner layer of outer corner layer and middle prism layer. Pearl medicine in China has a history of more than 2,000 years, pearl has the effects of calming the mind, clearing the eyes, detoxifying the muscle and so on. In this paper, the researches on the extraction of pearl powder and nacre powder, the isolation and purification of matrix protein and the various biological activities (osteogenic activity, antioxidant, anti-inflammatory, anti-apoptotic, promoting the migration of fibroblasts, and so on) are reviewed in detail. To provide readers with a faster understanding, the method of extraction and purification and the application of nacre powder and pearl powder are clearly presented in the form of figures and tables. In line with the concept of waste or by-product, there are more reports of nacre extract than pearl extract, due to the expensive and limited in origin of pearls. Mainly on the direct use of nacre powder and pearl powder or on the use of extracts (mainly water soluble proteins) through experiments in vivo or in vitro, and shows whether it is effective through the results of various indexes. There is no further study on substances other than extracts, and the structural analysis of extracts needs further exploration.
F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis
Authors: Li Tiao , He Xue , Luo Lijuan , Zeng Huihui , Ren Siying , Chen Yan
Published: April 2021

Chronic obstructive pulmonary disease (COPD) is a chronic debilitating lung disease, characterized by progressive airway inflammation and lung structural cell death. Cigarette smoke is considered the most common risk factor of COPD pathogenesis. Understanding the molecular mechanisms of persistent inflammation and epithelial apoptosis induced by cigarette smoke would be extremely beneficial for improving the treatment and prevention of COPD. A histone methyl modifier, protein arginine N-methyltransferase 6 (PRMT6), is reported to alleviate cigarette smoke extract (CSE)-induced emphysema through inhibiting inflammation and cell apoptosis. However, few studies have focused on the modulation of PRMT6 in regulating inflammation and cell apoptosis. In this study, we showed that protein expression of PRMT6 was aberrantly decreased in the lung tissue of COPD patients and CSE-treated epithelial cells. FBXW17, a member of the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases, selectively bound to PRMT6 in nuclei to modulate its elimination in the proteasome system. Proteasome inhibitor or silencing of FBXW17 abrogated CSE-induced PRMT6 protein degradation. Furthermore, negative alteration of FBXW17/PRMT6 signaling lessened the proapoptotic and proinflammatory effects of CSE in lung epithelial cells. Our study, therefore, provides a potential therapeutic target against the airway inflammation and cell death in CS-induced COPD.
Cell Fate Decisions in the Wake of Histone H3 Deposition
Authors: Franklin Reuben , Murn Jernej , Cheloufi Sihem
Published: April 2021

An expanding repertoire of histone variants and specialized histone chaperone partners showcases the versatility of nucleosome assembly during different cellular processes. Recent research has suggested an integral role of nucleosome assembly pathways in both maintaining cell identity and influencing cell fate decisions during development and normal homeostasis. Mutations and altered expression profiles of histones and corresponding histone chaperone partners are associated with developmental defects and cancer. Here, we discuss the spatiotemporal deposition mechanisms of the Histone H3 variants and their influence on mammalian cell fate during development. We focus on H3 given its profound effect on nucleosome stability and its recently characterized deposition pathways. We propose that differences in deposition of H3 variants are largely dependent on the phase of the cell cycle and cellular potency but are also affected by cellular stress and changes in cell fate. We also discuss the utility of modern technologies in dissecting the spatiotemporal control of H3 variant deposition, and how this could shed light on the mechanisms of cell identity maintenance and lineage commitment. The current knowledge and future studies will help us better understand how organisms employ nucleosome dynamics in health, disease, and aging. Ultimately, these pathways can be manipulated to induce cell fate change in a therapeutic setting depending on the cellular context.
Lansoprazole Alone or in Combination With Gefitinib Shows Antitumor Activity Against Non-small Cell Lung Cancer A549 Cells in vitro and in vivo
Authors: Zhao Xiaoxia , Zhang Ning , Huang Yingying , Dou Xiaojing , Peng Xiaolin , Wang Wei , Zhang Zhe , Wang Ran , Qiu Yuling , Jin Meihua , Kong Dexin
Published: April 2021

Lansoprazole (Lpz) is an FDA-approved proton pump inhibitor (PPI) drug for the therapy of acid-related diseases. Aiming to explore the new application of old drugs, we recently investigated the antitumor effect of Lpz. We demonstrated that the PPI Lpz played a tumor suppressive role in non-small cell lung cancer (NSCLC) A549 cells. Mechanistically, Lpz induced apoptosis and G0/G1 cell cycle arrest by inhibiting the activation of signal transducer and activator of transcription (Stat) 3 and the phosphoinositide 3-kinase (PI3K)/Akt and Raf/ERK pathways. In addition, Lpz inhibited autophagy by blocking the fusion of autophagosomes with lysosomes. Furthermore, Lpz in combination with gefitinib (Gef) showed a synergistic antitumor effect on A549 cells, with enhanced G0/G1 cell cycle arrest and apoptosis. The combination inhibited Stat3 phosphorylation, PI3K/Akt and Raf/ERK signaling, affecting cell cycle-related proteins such as p-Rb, cyclin D1 and p27, as well as apoptotic proteins such as Bax, Bcl-2, caspase-3, and poly (ADP-ribose) polymerase (PARP). In vivo, coadministration with Lpz and Gef significantly attenuated the growth of A549 nude mouse xenograft models. These findings suggest that Lpz might be applied in combination with Gef for NSCLC therapy, but further evidence is required.
The Role of Mcl-1 in Embryonic Neural Precursor Cell Apoptosis
Authors: Flemmer Robert T. , Connolly Sarah P. , Geizer Brittany A. , Opferman Joseph T. , Vanderluit Jacqueline L.
Published: April 2021

Myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 protein, regulates neural precursor cell (NPC) survival in both the developing and adult mammalian nervous system. It is unclear when during the neurogenic period Mcl-1 becomes necessary for NPC survival and whether Bax is the sole pro-apoptotic target of Mcl-1. To address these questions, we used the nervous system-specific Nestin-Cre Mcl-1 conditional knockout mouse line (Mcl-1 CKO) to assess the anti-apoptotic role of Mcl-1 in developmental neurogenesis. Loss of Mcl-1 resulted in a wave of apoptosis beginning in the brainstem and cervical spinal cord at embryonic day 9.5 (E9.5) and in the forebrain at E10.5. Apoptosis was first observed ventrally in each region and spread dorsally over time. Within the spinal cord, apoptosis also spread in a rostral to caudal direction following the path of differentiation. Breeding the Mcl-1 CKO mouse with the Bax null mouse rescued the majority of NPC from apoptosis except in the dorsomedial brainstem and ventral thoracic spinal cord where only 50% were rescued. This demonstrates that Mcl-1 promotes NPC survival primarily by inhibiting the activation of Bax, but that Bax is not the sole pro-apoptotic target of Mcl-1 during embryonic neurogenesis. Interestingly, although co-deletion of Bax rescued the majority of NPC apoptosis, it resulted in embryonic lethality at E13, whereas conditional deletion of both Mcl-1 and Bax rescued embryonic lethality. In summary, this study demonstrates the widespread dependency on Mcl-1 during nervous system development.
Curating and Visualizing Dense Networks of Monsoon Precipitation Data: Integrating Computer Science Into Forward Looking Climate Services Development
Authors: McMahan Ben , Granillo Rey L. , Delgado Benni , Herrera Mauricio , Crimmins Michael A.
Published: April 2021

Monsoon precipitation demonstrates a wide range of spatial and temporal variability in the U.S. Southwest. A variety of precipitation monitoring networks, including official networks, municipal flood control districts, and citizen science observers, can help improve our characterization and understanding of the monsoon. The data management challenges of integrating these diverse data sources can be formidable. Computer science and data management techniques provide a pathway for the design of forward looking climate services, especially those developed in collaboration with experts in this field. In this paper we present such a collaboration, integrating natural, social and computer science expertise. We document how we identified data networks and their sources and the computer science and data management workflow we employed to integrate and curate these data. We also present the web based data visualization tool and API that we developed as part of this process (monsoon.environment.arizona.edu). We use case study examples from the Tucson, AZ region to demonstrate the visualizer. We also discuss how this type of collaboration could be extended to existing or potential stakeholder collaborations, as we facilitate access to a curated set of data that gives an increasingly granular perspective on monsoon precipitation variability. We also discuss what this collaborative approach integrating natural, social and computer science perspectives can add to the evolution of climate services.
Heart Transplantation in Mustard Patients Bridged With Continuous Flow Systemic Ventricular Assist Device - A Case Report and Review of Literature
Authors: Bou Chaaya Rody G. , Simon Joel W. , Turrentine Mark , Herrmann Jeremy L. , Kay William Aaron , Guglin Maya , Saleem Kashif , Rao Roopa A.
Published: April 2021

Thirty four-year-old male with history of D-transposition of the great arteries (D-TGA) who underwent Mustard operation at 14 months of age presented in cardiogenic shock secondary to severe systemic right ventricular failure. Catheterization revealed significantly increased pulmonary pressures. Due to the patient's inotrope dependence and prohibitive pulmonary hypertension, he underwent implantation of a Heart Ware HVAD® for systemic RV support. Within 4 months of continuous flow ventricular assist device (VAD) implantation complete normalization of pulmonary vascular resistance (PVR) was achieved. He ultimately underwent orthotopic heart transplantation with favorable outcomes. This is the second report of complete normalization of PVR following VAD implantation into a systemic RV in <4 months. We conducted a thorough literature review to identify Mustard patients that received systemic RV VAD as a bridge to a successful heart transplantation. In this article, we summarize the outcomes and focus on pulmonary hypertension reversibility following VAD implant.
A Mini Review on Non-augmentative Surgical Therapy of Peri-Implantitis—What Is Known and What Are the Future Challenges?
Authors: Bertl Kristina , Stavropoulos Andreas
Published: April 2021

Non-augmentative surgical therapy of peri-implantitis is indicated for cases with primarily horizontal bone loss or wide defects with limited potential for bone regeneration and/or re-osseointegration. This treatment approach includes a variety of different techniques (e.g., open flap debridement, resection of peri-implant mucosa, apically positioned flaps, bone re-contouring, implantoplasty, etc.) and various relevant aspects should be considered during treatment planning. The present mini review provides an overview on what is known for the following components of non-augmentative surgical treatment of peri-implantitis and on potential future research challenges: (1) decontamination of the implant surface, (2) need of implantoplasty, (3) prescription of antibiotics, and (4) extent of resective measures.
Analysis of Distributed Generation Accommodation in Flexible Distribution Networks
Authors: Xiao Jun , Wang Ying , Zu Guoqiang
Published: April 2021

This work proposes a method to analyze distributed generation (DG) accommodation in a flexible distribution network (FDN). Firstly, the DG-load matching degree is proposed to quantitatively describe the power balance degree of DG and load in a distribution network. Secondly, the accommodation ratio of DG is proposed and divided into a DG-load accommodation ratio and DG-network-load accommodation ratio, to distinguish whether the index takes the network operational constraints into account. We derive the DG-load accommodation ratio directly from the matching degree and propose the simulation model of sequential production to solve the DG-network-load accommodation ratio. Finally, the cases of FDN under the scenarios of different matching degrees are studied and compared with those of the traditional rigid distribution network. The results show that the improvement of the accommodation ratio by upgrading the rigid distribution network to an FDN is conditional, which is related to not only the matching degree of the whole network but also that of each local network. The DG-network-load accommodation ratio will tend to the DG-load accommodation ratio if proper planning or optimization measures are taken. We find that the capacity of branches adjacent to the DG bus mainly limit the DG accommodation in the FDN, and it is recommended to relocate the DGs and enlarge the capacity of those branches.
A Method to Deal With Inter-regional and Inter-provincial Transaction Settlement Deviation Quantity Based on Kernel Density–Entropy Weight
Authors: Wang Dongfa , Ding Weibin , Gao Feng , Xu Yang , Miao Qin
Published: April 2021

The mismatch between energy distribution and power load in China can be alleviated by inter-regional and inter-provincial power transactions. However, it also brings challenges to transaction settlement. In the new round of electric power reform, the transaction settlement deviation quantity needs to be more standardized. Based on the analysis of the related work, this article used the analytical framework of the analytic hierarchy process to calculate the transaction type weight, the inter-regional, and the inter-provincial weight, respectively, and accordingly, quantifies the amount of deviation quantity allocated by the corresponding trading subjects. According to the size and volatility of the trading quantity, we further propose a comprehensive weighting method based on kernel density and entropy weight to quantify the deviation quantity of inter-regional and inter-provincial trading subjects of different trading types. Specifically, this article first used the kernel function weighting method to calculate the weights of different transaction types that measure the transaction quantity, and then the improved entropy weight method was used to calculate the weights of different transaction types that reflect the volatility of the transaction quantity. Then, the comprehensive weights were constructed by considering the influence of the above two dimensions on the distribution of the deviation electricity simultaneously. The deviation electricity responsibility determination model was used to clarify the transaction subject's deviated electricity responsibility, and the deviated electric quantity calculation model was used for quantification. At last, the validity and practicability of the method were verified through the analysis of examples using the inter-regional and inter-provincial power transaction data from China.
Bark Water Storage Plays Key Role for Growth of Mediterranean Epiphytic Lichens
Authors: Porada Philipp , Giordani Paolo
Published: April 2021

Epiphytic lichens are a characteristic feature of many forests around the world, where they often cover large areas on stems and branches. Recently, it has been found that lichens may contribute substantially to carbon and nutrient uptake in forests. Moreover, they have a large influence on interception of rainfall at the global scale, which leads to a shift of the water balance toward evaporation and a cooling of near-surface air temperature. It is thus crucial to understand which environmental factors are relevant for their growth and survival, and which potential risks may result from climate change. Water supply is a key factor which controls active time and, consequently, the carbon balance of the epiphytes. However, it is largely unclear, to what extent different modes of water uptake, which include bark water, may affect active time and growth under varying environmental conditions. Quantitative estimates on the relevance of bark water storage and its interspecific variation are, however, missing. Here, we apply the process-based, dynamic non-vascular vegetation model LiBry to assess the relevance of bark water for epiphytic lichens. LiBry not only accounts for the main physiological processes of mosses and lichens, it also represents explicitly the diversity of the organisms, by simulating a large number of possible physiological strategies. We run the model for a site in Sardinia, where epiphytic lichens are abundant. Moreover, the Mediterranean region is of interest due to likely substantial effects of global warming on local epiphytes. For current climatic conditions, the LiBry model predicts net primary production (NPP) of 32 g C m−2a−1 per stem area and biomass of 48 g C m−2 for the study region. In a second run, where uptake of bark water is switched off in the model, estimated NPP is reduced by 21%. Moreover, the simulated number of surviving strategies, representing physiological diversity, decreases by 23%. This is accompanied by changes in the simulated community composition, where strategies which have a more compact thallus increase their share on the total cover. Hence, our model simulation suggests a substantial role of bark water for growth and morphology of epiphytic lichens in Sardinia.
IFN-I Mediates Lupus Nephritis From the Beginning to Renal Fibrosis
Authors: Ding Xuewei , Ren Yi , He Xiaojie
Published: April 2021

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) and a major risk factor for morbidity and mortality. The abundant cell-free nucleic (DNA/RNA) in SLE patients, especially dsDNA, is a key substance in the pathogenesis of SLE and LN. The deposition of DNA/RNA-immune complexes (DNA/RNA-ICs) in the glomerulus causes a series of inflammatory reactions that lead to resident renal cell disturbance and eventually renal fibrosis. Cell-free DNA/RNA is the most effective inducer of type I interferons (IFN-I). Resident renal cells (rather than infiltrating immune cells) are the main source of IFN-I in the kidney. IFN-I in turn damages resident renal cells. Not only are resident renal cells victims, but also participants in this immunity war. However, the mechanism for generation of IFN-I in resident renal cells and the pathological mechanism of IFN-I promoting renal fibrosis have not been fully elucidated. This paper reviews the latest epidemiology of LN and its development process, discusses the mechanism for generation of IFN-I in resident renal cells and the role of IFN-I in the pathogenesis of LN, and may open a new perspective for the treatment of LN.
Enhanced Magnetorheological Performance of Carbonyl Iron Suspension Added With Barium Ferrite Nanoparticle
Authors: Jang Hyo Seon , Lu Qi , Choi Hyoung Jin
Published: April 2021

Hard-magnetic barium ferrite (BF) nanoparticles with a hexagonal plate-like structure were used as an additive to a carbonyl iron (CI) microparticle-based magnetorheological (MR) fluid. The morphology of the pristine CI and CI/BF mixture particles was examined by scanning electron microscopy. The saturation magnetization and coercivity values of each particle were measured in the powder state by vibrating sample magnetometry. The MR characteristics of the CI/BF MR fluid measured using a rotation rheometer under a range of magnetic field strengths were compared with those of the CI-based MR fluid. The flow behavior of both MR fluids was fitted using a Herschel–Bulkley model, and their stress relaxation phenomenon was examined using the Schwarzl equation. The MR fluid with the BF additive showed higher dynamic and elastic yield stresses than the MR fluid without the BF additive as the magnetic field strength increased. Furthermore, the BF nanoparticles embedded in the space between the CI microparticles improved the dispersion stability and the MR performance of the MR fluid.
The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress
Authors: He Xiaoyun , Kuang Gaoyan , Zuo Yi , Li Shuangxi , Zhou Suxian , Ou Chunlin
Published: April 2021

Diabetic nephropathy (DN) is one of the main complications of diabetes and the main cause of diabetic end-stage renal disease, which is often fatal. DN is usually characterized by progressive renal interstitial fibrosis, which is closely related to the excessive accumulation of extracellular matrix and oxidative stress. Non-coding RNAs (ncRNAs) are RNA molecules expressed in eukaryotic cells that are not translated into proteins. They are widely involved in the regulation of biological processes, such as, chromatin remodeling, transcription, post-transcriptional modification, and signal transduction. Recent studies have shown that ncRNAs play an important role in the occurrence and development of DN and participate in the regulation of oxidative stress in DN. This review clarifies the functions and mechanisms of ncRNAs in DN-related oxidative stress, providing valuable insights into the prevention, early diagnosis, and molecular therapeutic targets of DN.
scFv-Anti-LDL(-)-Metal-Complex Multi-Wall Functionalized-Nanocapsules as a Promising Tool for the Prevention of Atherosclerosis Progression
Authors: Cavalcante Marcela Frota , Adorne Márcia Duarte , Turato Walter Miguel , Kemmerer Marina , Uchiyama Mayara Klimuk , Asbahr Ana Carolina Cavazzin , Alves Aline de Cristo Soares , Farsky Sandra Helena Poliselli , Drewes Carine , Spatti Marina Cecília , Kazuma Soraya Megumi , Boss Marcel , Guterres Silvia Stanisçuaski , Araki Koiti , Brüne Bernhard , Namgaladze Dmitry , Pohlmann Adriana Raffin , Abdalla Dulcineia Saes Parra
Published: April 2021

Atherosclerosis can be originated from the accumulation of modified cholesterol-rich lipoproteins in the arterial wall. The electronegative LDL, LDL(-), plays an important role in the pathogenesis of atherosclerosis once this cholesterol-rich lipoprotein can be internalized by macrophages, contributing to the formation of foam cells, and provoking an immune-inflammatory response. Herein, we engineered a nanoformulation containing highly pure surface-functionalized nanocapsules using a single-chain fragment variable (scFv) reactive to LDL(-) as a ligand and assessed whether it can affect the LDL(-) uptake by primary macrophages and the progression of atherosclerotic lesions inLdlr−/−mice. The engineered and optimized scFv-anti-LDL(-)-MCMN-Zn nanoformulation is internalized by human and murine macrophagesin vitroby different endocytosis mechanisms. Moreover, macrophages exhibited lower LDL(-) uptake and reduced mRNA and protein levels ofIL1Band MCP1 induced by LDL(-) when treated with this new nanoformulation. In a mouse model of atherosclerosis employingLdlr−/−mice, intravenous administration of scFv-anti-LDL(-)-MCMN-Zn nanoformulation inhibited atherosclerosis progression without affecting vascular permeability or inducing leukocytes-endothelium interactions. Together, these findings suggest that a scFv-anti-LDL(-)-MCMN-Zn nanoformulation holds promise to be used in future preventive and therapeutic strategies for atherosclerosis.
Resistance, Resilience, and Recovery of Dryland Soil Bacterial Communities Across Multiple Disturbances
Authors: Steven Blaire , Phillips Michala L. , Belnap Jayne , Gallegos-Graves La Verne , Kuske Cheryl R. , Reed Sasha C.
Published: April 2021

Dryland ecosystems are sensitive to perturbations and generally slow to recover post disturbance. The microorganisms residing in dryland soils are especially important as they contribute to soil structure and nutrient cycling. Disturbance can have particularly strong effects on dryland soil structure and function, yet the natural resistance and recovery of the microbial components of dryland soils has not been well documented. In this study, the recovery of surface soil bacterial communities from multiple physical and environmental disturbances is assessed. Samples were collected from three field sites in the vicinity of Moab, UT, United States, 6 to 7 years after physical and climate disturbance manipulations had been terminated, allowing for the assessment of community recovery. Additionally, samples were collected in a transect that included three habitat patches: the canopy zone soils under the dominant shrubs, the interspace soils that are colonized by biological soil crusts, and edge soils at the plot borders. Field site and habitat patch were significant factors structuring the bacterial communities, illustrating that sites and habitats harbored unique soil microbiomes. Across the different sites and disturbance treatments, there was evidence of significant bacterial community recovery, as bacterial biomass and diversity were not significantly different than control plots. There was, however, a small number of 16S rRNA gene amplicon sequence variants that distinguished particular treatments, suggesting that legacy effects of the disturbances still remained. Taken together, these data suggest that dryland bacterial communities may possess a previously unappreciated potential to recover within years of the original disturbance.
mcr-1 Identified in Fecal Escherichia coli and Avian Pathogenic E. coli (APEC) From Brazil
Authors: Barbieri Nicolle Lima , Pimenta Ramon Loureiro , de Melo Dayanne Araujo , Nolan Lisa K. , de Souza Miliane Moreira Soares , Logue Catherine M.
Published: April 2021

Colisitin-associated resistance in bacteria of food producing animals has gained significant attention with the mcr gene being linked with resistance. Recently, newer variants of mcr have emerged with more than nine variants currently recognized. Reports of mcr associated resistance in Escherichia coli of poultry appear to be relatively limited, but its prevalence requires assessment since poultry is one of the most important and cheapest sources of the world’s protein and the emergence of resistance could limit our ability to treat disease outbreaks. Here, 107 E. coli isolates from production poultry were screened for the presence of mcr 1–9. The isolates were collected between April 2015 and June 2016 from broiler chickens and free-range layer hens in Rio de Janeiro, Brazil. All isolates were recovered from the trachea and cloaca of healthy birds and an additional two isolates were recovered from sick birds diagnosed with colibacillosis. All isolates were screened for the presence of mcr-1 to 9 using PCR and Sanger sequencing for confirmation of positive genes. Additionally, pulse field gel electrophoresis (PFGE) analysis, avian fecal E. coli (APEC) virulence associated gene screening, plasmid replicon typing and antimicrobial resistance phenotype and resistance gene screening, were also carried out to further characterize these isolates. The mcr-1 gene was detected in 62 (57.9%) isolates (61 healthy and 1 APEC) and the mcr-5 gene was detected in 3 (2.8%) isolates; mcr-2, mcr-3, mcr-4, mcr-6, mcr-7, mcr-8, and mcr-9 were not detected in any isolate. In addition, mcr 1 and 5 positive isolates were phenotypically resistant to colistin using the agar dilution assay (> 8ug/ml). PFGE analysis found that most of the isolates screened had unique fingerprints suggesting that the emergence of colistin resistance was not the result of clonal dissemination. Plasmid replicon types IncI2, FIB, and B/O were found in 38, 36, and 34% of the mcr positive isolates and were the most prevalent replicon types detected; tetA and tetB (32 and 26%, respectively) were the most prevalent antimicrobial resistance genes detected and iutA, was the most prevalent APEC virulence associated gene, detected in 50% of the isolates. Approximately 32% of the isolates examined could be classified as APEC-like, based on the presence of 3 or more genes of APEC virulence associated path panel (iroN, ompT, hlyF, iss, iutA). This study has identified a high prevalence of mcr-1 in poultry isolates in Brazil, suggesting that animal husbandry practices could result in a potential source of resistance to the human food chain in countries where application of colistin in animal health is practiced. Emergence of the mcr gene and associated colisitin resistance in production poultry warrants continued monitoring from the animal health and human health perspective.
Virus Detection: A Review of the Current and Emerging Molecular and Immunological Methods
Authors: Cassedy A. , Parle-McDermott A. , O’Kennedy R.
Published: April 2021

Viruses are ubiquitous in the environment. While many impart no deleterious effects on their hosts, several are major pathogens. This risk of pathogenicity, alongside the fact that many viruses can rapidly mutate highlights the need for suitable, rapid diagnostic measures. This review provides a critical analysis of widely used methods and examines their advantages and limitations. Currently, nucleic-acid detection and immunoassay methods are among the most popular means for quickly identifying viral infection directly from source. Nucleic acid-based detection generally offers high sensitivity, but can be time-consuming, costly, and require trained staff. The use of isothermal-based amplification systems for detection could aid in the reduction of results turnaround and equipment-associated costs, making them appealing for point-of-use applications, or when high volume/fast turnaround testing is required. Alternatively, immunoassays offer robustness and reduced costs. Furthermore, some immunoassay formats, such as those using lateral-flow technology, can generate results very rapidly. However, immunoassays typically cannot achieve comparable sensitivity to nucleic acid-based detection methods. Alongside these methods, the application of next-generation sequencing can provide highly specific results. In addition, the ability to sequence large numbers of viral genomes would provide researchers with enhanced information and assist in tracing infections.
Sweet Melody or Jazz? Transcription Around DNA Double-Strand Breaks
Authors: Long Qilin , Liu Zhichao , Gullerova Monika
Published: April 2021

Genomic integrity is continuously threatened by thousands of endogenous and exogenous damaging factors. To preserve genome stability, cells developed comprehensive DNA damage response (DDR) pathways that mediate the recognition of damaged DNA lesions, the activation of signaling cascades, and the execution of DNA repair. Transcription has been understood to pose a threat to genome stability in the presence of DNA breaks. Interestingly, accumulating evidence in recent years shows that the transient transcriptional activation at DNA double-strand break (DSB) sites is required for efficient repair, while the rest of the genome exhibits temporary transcription silencing. This genomic shut down is a result of multiple signaling cascades involved in the maintenance of DNA/RNA homeostasis, chromatin stability, and genome fidelity. The regulation of transcription of protein-coding genes and non-coding RNAs has been extensively studied; however, the exact regulatory mechanisms of transcription at DSBs remain enigmatic. These complex processes involve many players such as transcription-associated protein complexes, including kinases, transcription factors, chromatin remodeling complexes, and helicases. The damage-derived transcripts themselves also play an essential role in DDR regulation. In this review, we summarize the current findings on the regulation of transcription at DSBs and discussed the roles of various accessory proteins in these processes and consequently in DDR.
Potential Fluid Biomarkers and a Prediction Model for Better Recognition Between Multiple System Atrophy-Cerebellar Type and Spinocerebellar Ataxia
Authors: Guo Shuo , Zhao Bi , An Yunfei , Zhang Yu , Meng Zirui , Zhou Yanbing , Zheng Mingxue , Yang Dan , Wang Minjin , Ying Binwu
Published: April 2021

Objective

This study screened potential fluid biomarkers and developed a prediction model based on the easily obtained information at initial inspection to identify ataxia patients more likely to have multiple system atrophy-cerebellar type (MSA-C).

Methods

We established a retrospective cohort with 125 ataxia patients from southwest China between April 2018 and June 2020. Demographic and laboratory variables obtained at the time of hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to construct a diagnosis score. The receiver operating characteristic (ROC) and decision curve analyses were performed to assess the accuracy and net benefit of the model. Also, independent validation using 25 additional ataxia patients was carried out to verify the model efficiency. Then the model was translated into a visual and operable web application using the R studio and Shiny package.

Results

From 47 indicators, five variables were selected and integrated into the prediction model, including the age of onset (AO), direct bilirubin (DBIL), aspartate aminotransferase (AST), eGFR, and synuclein-alpha. The prediction model exhibited an area under the curve (AUC) of 0.929 for the training cohort and an AUC of 0.917 for the testing cohort. The decision curve analysis (DCA) plot displayed a good net benefit for this model, and external validation confirmed its reliability. The model also was translated into a web application that is freely available to the public.

Conclusion

The prediction model that was developed based on laboratory and demographic variables obtained from ataxia patients at admission to the hospital might help improve the ability to differentiate MSA-C from spinocerebellar ataxia clinically.
Heschl’s Gyrus Duplication Pattern in Individuals at Risk of Developing Psychosis and Patients With Schizophrenia
Authors: Takahashi Tsutomu , Sasabayashi Daiki , Takayanagi Yoichiro , Higuchi Yuko , Mizukami Yuko , Nishiyama Shimako , Furuichi Atsushi , Kido Mikio , Pham Tien Viet , Kobayashi Haruko , Noguchi Kyo , Suzuki Michio
Published: April 2021

An increased prevalence of duplicated Heschl’s gyrus (HG), which may reflect an early neurodevelopmental pathology, has been reported in schizophrenia (Sz). However, it currently remains unclear whether individuals at risk of psychosis exhibit similar brain morphological characteristics. This magnetic resonance imaging study investigated the distribution of HG gyrification patterns [i.e., single HG, common stem duplication (CSD), and complete posterior duplication (CPD)] and their relationship with clinical characteristics in 57 individuals with an at-risk mental state (ARMS) [of whom 5 (8.8%) later developed Sz], 63 patients with Sz, and 61 healthy comparisons. The prevalence of duplicated HG patterns (i.e., CSD or CPD) bilaterally was significantly higher in the ARMS and Sz groups than in the controls, whereas no significant differences were observed in HG patterns between these groups. The left CSD pattern, particularly in the Sz group, was associated with a verbal fluency deficit. In the ARMS group, left CSD pattern was related to a more severe general psychopathology. The present results suggest that an altered gyrification pattern on the superior temporal plane reflects vulnerability factors associated with Sz, which may also contribute to the clinical features of high-risk individuals, even without the onset of psychosis.
Timing and Spectrum of Neurological Complications After Flow Diverter Implantation for Intracranial Aneurysms
Authors: Charbonnier Guillaume , Desilles Jean-Philippe , Escalard Simon , Maier Benjamin , Ciccio Gabriele , Smajda Stanislas , Fahed Robert , Delvoye François , Redjem Hocine , Blanc Raphaël , Piotin Michel , Mazighi Mikael
Published: April 2021

Background and Purpose: The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications.

Methods: This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD.

Results: Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186–1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month.

Conclusions: Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.
A Modified in vitro Clot Lysis Assay Predicts Outcomes in Non-traumatic Intracerebral Hemorrhage Stroke Patients—The IRONHEART Study
Authors: Orbán-Kálmándi Rita , Árokszállási Tamás , Fekete István , Fekete Klára , Héja Máté , Tóth Judit , Sarkady Ferenc , Csiba László , Bagoly Zsuzsa
Published: April 2021

Background: Non-traumatic intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes and results in a higher rate of mortality as compared to ischemic strokes. In the IRONHEART study, we aimed to find out whether a modified in vitro clot lysis assay method, that includes the effect of neutrophil extracellular traps (NETs) might predict ICH outcomes.

Patients and Methods: In this prospective, observational study, 89 consecutive non-traumatic ICH patients were enrolled. Exclusion criteria included aneurysm rupture, cancer, liver- or kidney failure or hemorrhagic diathesis. On admission, detailed clinical and laboratory investigations were performed. ICH volume was estimated based on CT performed on admission, day 14 and 90. A conventional in vitro clot lysis assay (CLA) and a modified CLA (mCLA) including cell-free-DNA and histones were performed from stored platelet-free plasma taken on admission. Clot formation and lysis in case of both assays were defined using the following variables calculated from the turbidimetric curves: maximum absorbance, time to maximum absorbance, clot lysis times (CLT) and area under the curve (CLA AUC). Long-term ICH outcomes were defined 90 days post-event by the modified Rankin Scale (mRS). All patients or relatives provided written informed consent.

Results: Patients with more severe stroke (NIHSS>10) presented significantly shorter clot lysis times of the mCLA in the presence of DNA and histone as compared to patients with milder stroke [10%CLT: NIHSS 0–10: median 31.5 (IQR: 21.0–40.0) min vs. NIHSS>10: 24 (18–31.0) min, p = 0.032]. Shorter clot lysis times of the mCLA showed significant association with non-survival by day 14 and with unfavorable long-term outcomes [mRS 0–1: 36.0 (22.5.0–51.0) min; mRS 2–5: 23.5 (18.0–36.0) min and mRS 6: 22.5 (18.0–30.5) min, p = 0.027]. Estimated ICH volume showed significant negative correlation with mCLA parameters, including 10%CLT (r = −0.3050, p = 0.009). ROC analysis proved good diagnostic performance of mCLA for predicting poor long-term outcomes [AUC: 0.73 (0.57–0.89)]. In a Kaplan-Meier survival analysis, those patients who presented with an mCLA 10%CLT result of >38.5 min on admission showed significantly better survival as compared to those with shorter clot lysis results (p=0.010).

Conclusion: Parameters of mCLA correlate with ICH bleeding volume and might be useful to predict ICH outcomes.