bluuebunny/crossref_metadata_2025 huggingface dataset:
Stakeholder Engagement in Decision Making and Pathways of Influence for Southern Ocean Ecosystem Services
Authors: Solomonsz Josh , Melbourne-Thomas Jess , Constable Andrew , Trebilco Rowan , van Putten Ingrid , Goldsworthy Lyn
Published: May 2021

Southern Ocean ecosystem management is characterized by a unique and complex international network of stakeholders and stakeholder relationships (a ‘transactional landscape’) relating to the globally significant services that these ecosystems support. This transactional landscape spans governments, industry (fishing and tourism), scientific research, conservation non-government organizations, civil society, and international decision-making forums. We used a network approach for stakeholder mapping to provide the first description of the transactional landscape for Southern Ocean ecosystem management – both in terms of the connections between stakeholders and ecosystem services, and directly between stakeholder groups. We considered 65 stakeholders and their relationships to 12 provisioning, regulating, supporting and cultural ecosystem services. An analysis of the connections within this network reveals differences in the degree of connectivity between stakeholders and ecosystem services. Notably, ecosystem science facilitates high connectivity between stakeholders and provisioning services, but there is little connectivity between stakeholders and supporting services. We then applied a formal ‘values-rules-knowledge’ framework to a set of case studies to analyze the decision-making process in relation to Southern Ocean ecosystem services, as well as the relative importance of different stakeholder groups which were considered in the network analysis. Our analyses suggest that emphases for decision making have been on knowledge and rules, but that wider consideration of values across the broader stakeholder landscape – together with science (knowledge) and governance (rules) – might better support decision making for Southern Ocean ecosystem conservation and management, and provide a stronger foundation for sustainable provision of ecosystem services into the future.
Distribution and Habitat Suitability of Ross Seals in a Warming Ocean
Authors: Wege Mia , Bornemann Horst , Blix Arnoldus Schytte , Nordøy Erling Sverre , Biddle Louise , Bester Marthán Nieuwoudt
Published: May 2021

Understanding the determinants of poorly studied species’ spatial ecology is fundamental to understanding climate change impacts on those species and how to effectively prioritise their conservation. Ross seals (Ommatophoca rossii) are the least studied of the Antarctic pinnipeds with a limited knowledge of their spatial ecology. We present the largest tracking study for this species to date, create the first habitat models, and discuss the potential impacts of climate change on their preferred habitat and the implications for conservation. We combined newly collected satellite tracking data (2016–2019: n = 11) with previously published data (2001: n = 8) from the Weddell, King Haakon VII and Lazarev seas, Antarctica, and used 16 remotely sensed environmental variables to model Ross seal habitat suitability by means of boosted regression trees for summer and winter, respectively. Five of the top environmental predictors were relevant in both summer and winter (sea-surface temperature, distance to the ice edge, ice concentration standard deviation, mixed-layer depth, and sea-surface height anomalies). Ross seals preferred to forage in waters ranging between −1 and 2°C, where the mixed-layer depth was shallower in summer and deeper in winter, where current speeds were slower, and away from the ice edge in the open ocean. Receding ice edge and shoaling of the mixed layer induced by climate change may reduce swimming distances and diving depths, thereby reducing foraging costs. However, predicted increased current speeds and sea-surface temperatures may reduce habitat suitability in these regions. We suggest that the response of Ross seals to climate change will be regionally specific, their future success will ultimately depend on how their prey responds to regional climate effects and their own behavioural plasticity.
Synergistic Effects of Thermal Stress and Estuarine Discharge on Transcriptomic Variation of Montastraea cavernosa Corals in Southeast Florida
Authors: Studivan Michael S. , Shatters Alycia , Dodge Danielle L. , Beal Jeff L. , Voss Joshua D.
Published: May 2021

Coral reefs at the northern extent of Florida’s coral reef tract are exposed to many localized anthropogenic influences including controlled freshwater discharges, runoff, upwelling, and seasonal environmental variability. To better understand coral responses to sublethal stressors in nearshore environments, we conducted complementary experiments to assess the impacts of estuarine runoff and temperature stress on local populations of the scleractinian coral species, Montastraea cavernosa, using Tag-Seq global gene expression profiling. In an in situ time series experiment, fate-tracked colonies were sampled during periods of relatively low and high estuarine discharge over 4 years to investigate temporal trends in transcriptional patterns and to identify if coral stress indicators were regulated through time. There was significant transcriptomic variation through time, but patterns did not appear to be attributed to distance from nearby estuarine tidal flux. In an ex situ factorial experiment, clonal replicates of coral genotypes were exposed to temperature (25°C and 30°C) and water (offshore and estuarine discharge, representing typical oceanic conditions and episodic discharge conditions, respectively) treatments to quantify the potential individual and synergistic effects of sublethal stress on coral and algal gene expression. Comparative analyses suggested that corals and their algal symbionts were more responsive to thermal stress than to estuarine discharge, although there was evidence of a synergistic relationship between the two stressors. Strong genotype effects also demonstrated that transcriptomic responses to thermal stress were largely based on coral genotype, indicating the potential for stress resilience among certain members of coral populations from southeast Florida.
Flow of Economic Benefits From Coral Reefs in a Multi-Use Caribbean Marine Protected Area Using Network Theory
Authors: Cavada-Blanco Francoise , Cróquer Aldo , Yerena Edgard , Rodríguez Jon P.
Published: May 2021

Adaptation to changes in the delivery of ecosystem services while maintaining resilience of natural systems is one of the main challenges faced by multi-use marine protected areas (MPAs). To overcome this, it is crucial to improve our understanding of interdependencies among resource users and ecosystems. In this study we used networks to model the socio-ecological system of a multi-use MPA in the southern Caribbean. Using a mixed-method approach, we built a socio ecological network (SEN) from the flow of economic benefits that stakeholders obtain from coral reefs in Los Roques National Park. We specifically looked at how these benefits are distributed among stakeholder groups and how the structure and other network properties can inform management. For this, four networks (simple, weighted, directed and directed-weighted) were built from 125 nodes representing three services and six stakeholder groups, linked through 475 edges. The SEN structure indicated an open resource use pattern with reduced social capital, suggesting that community-based management could be challenging. Only 31% of the benefits from ecosystem services stay within the SEN. Regulation services, derived from the coral reef framework were the most important in terms of maintaining the flow of benefits through the SEN; however, most benefits depended on provisioning services. This approach, based on network theory allowed identification of inequalities in the access to benefits among groups, externalities in benefits derived from fisheries and trade-offs between provisioning and regulation services. Our results suggest that Los Roques might be falling into a socio-ecological trap. Improving access to benefits and increasing trust need be prioritized. Low-cost management intervention can help internalize financial benefits and reduce trade-offs affecting more vulnerable stakeholder groups. However, these would require changes in governance and institutions at the executive level.
Synthesis, Characterization and Electrochemical Evaluation of Layered Vanadium Phosphates as Cathode Material for Aqueous Rechargeable Zn-ion Batteries
Authors: De Luna Yannis , Bensalah Nasr
Published: May 2021

The potential application of rechargeable multivalent ion batteries in portable devices and renewable energy grid integration have gained substantial research interest in aqueous Zn-ion batteries (ZIBs). Compared to Li-based batteries, ZIBs offer lower costs, higher energy density, and safety that make them more attractive for energy storage in grid integration applications. Currently, more research is required to find a suitable cathode material for ZIBs with high capacity and structural stability during charge/discharge cycling. Vanadium phosphate (VOP) compounds as cathode material for ZIBs have been of particular interest, owing to vanadium’s diverse oxidation states. In this present work, two VOP compounds, [H0.6(VO)3(PO4)3(H2O)3].4H2O and VOPO4.2H2O, were synthesized from phosphoric acid and different sources of vanadium via a simple hydrothermal method. Various characterization techniques were carried out, revealing the layered structure of both products and high purity of [H0.6(VO)3(PO4)3(H2O)3].4H2O. Zn/VOP batteries were prepared using Zn metal as counter and reference electrode and 3 M ZnSO4.7H2O as electrolyte. Electrochemical tests were conducted to evaluate the cycling performance of VOPs as cathode material for aqueous Zn-ion batteries. Based on the results, both compounds have shown highly reversible Zn-ion intercalation and deintercalation. VOPO4.2H2O achieved a higher specific capacity of up to 85 mAh/g during discharging, as opposed to 65 mAh/g for the hydrated VOP complex. However, [H0.6(VO)3(PO4)3(H2O)3].4H2O is more stable with higher reproducibility than VOPO4.2H2O during cycling. Nevertheless, more research is still required to enhance the specific capacity and improve the cycling performance of VOP-based cathodes for their prospective use in aqueous ZIBs.
Optimization of the Indirect Extrusion Process of Copper-Clad Aluminum Rods by Methods of Statistical Experimental Designs and Numerical Analyses
Authors: Lechner Stefan , Rœmisch Ute , Nitschke René , Gensch Felix , Mueller Soeren
Published: May 2021

The success of composite extrusion is influenced by multiple process parameters. In order to investigate the significance of specific parameters during indirect extrusion of copper-clad aluminum (CCA) rods, statistical methods were applied and a central composite experimental design was implemented. The runs of the experimental design were modeled with the finite element method based software DEFORM 2D and evaluated with respect to product quality, described by four response variables. Using variance and regression analyses, as well significant linear and quadratic effects of the five investigated process parameters as interactions between them were identified. Based on a statistical model, an overall optimum setting for the process parameters was predicted utilizing the response surface methodology with a desirability approach. By applying the output of the statistical analysis to an extrusion trial, the extrusion of a high quality CCA rod was achieved. Moreover, the results of the statistical analysis could be verified by comparing predicted and experimentally determined values of the investigated quality characteristics.
Artificial Intelligence for Clinical Decision Support in Sepsis
Authors: Wu Miao , Du Xianjin , Gu Raymond , Wei Jie
Published: May 2021

Sepsis is one of the main causes of death in critically ill patients. Despite the continuous development of medical technology in recent years, its morbidity and mortality are still high. This is mainly related to the delay in starting treatment and non-adherence of clinical guidelines. Artificial intelligence (AI) is an evolving field in medicine, which has been used to develop a variety of innovative Clinical Decision Support Systems. It has shown great potential in predicting the clinical condition of patients and assisting in clinical decision-making. AI-derived algorithms can be applied to multiple stages of sepsis, such as early prediction, prognosis assessment, mortality prediction, and optimal management. This review describes the latest literature on AI for clinical decision support in sepsis, and outlines the application of AI in the prediction, diagnosis, subphenotyping, prognosis assessment, and clinical management of sepsis. In addition, we discussed the challenges of implementing and accepting this non-traditional methodology for clinical purposes.
Si-Based Hydrogen-Producing Nanoagent Protects Fetuses From Miscarriage Caused by Mother-to-Child Transmission
Authors: Usui Noriyoshi , Togawa Shogo , Sumi Takuya , Kobayashi Yuki , Koyama Yoshihisa , Nakamura Yukiko , Kondo Makoto , Shinoda Koh , Kobayashi Hikaru , Shimada Shoichi
Published: May 2021

Mother-to-child transmission of viruses and bacteria increases the risk of miscarriage and various diseases in children. Such transmissions can result in infections and diseases in infants or the induction of an inflammatory immune response through the placenta. Recently, we developed a silicon (Si)-based hydrogen-producing nanoagent (Si-based agent) that continuously and effectively produces hydrogen in the body. Since medical hydrogen has antioxidative, anti-inflammatory, antiallergic, and antiapoptotic effects, we investigated the effects of our Si-based agent on mother-to-child transmission, with a focus on the rate of miscarriage. In pregnant mice fed a diet containing the Si-based agent, lipopolysaccharide (LPS)-induced miscarriage due to mother-to-child transmission was reduced and inflammation and neutrophil infiltration in the placenta were suppressed. We also found that the Si-based agent suppressed IL-6 expression in the placenta and induced the expression of antioxidant and antiapoptotic genes, such as Hmox1 and Ptgs2. The observed anti-inflammatory effects of the Si-based agent suggest that it may be an effective preventative or therapeutic drug for miscarriage or threatened miscarriage during pregnancy by suppressing maternal inflammation caused by bacterial and viral infections.
A Diffusion Model to Quantify Membrane Repair Process in Listeria monocytogenes Exposed to High Pressure Processing Based on Fluorescence Microscopy Data
Authors: Nikparvar Bahareh , Subires Alicia , Capellas Marta , Hernandez-Herrero Manuela , Crauwels Peter , Riedel Christian U. , Bar Nadav
Published: May 2021

The effects of environmental stresses on microorganisms have been well-studied, and cellular responses to stresses such as heat, cold, acids, and salts have been extensively discussed. Although high pressure processing (HPP) is becoming more popular as a preservation method in the food industry, the characteristics of the cellular damage caused by high pressure are unclear, and the microbial response to this stress has not yet been well-explored. We exposed the pathogen Listeria monocytogenes to HPP (400 MPa, 8 min, 8°C) and found that the high pressure created plasma membrane pores. Using a common staining technique involving propidium iodide (PI) combined with high-frequency fluorescence microscopy, we monitored the rate of diffusion of PI molecules into hundreds of bacterial cells through these pores on days 0, 1, 2, 3, and 4 after pressurization. We also developed a mathematical dynamic model based on mass transfer and passive diffusion laws, calibrated using our microscopy experiments, to evaluate the response of bacteria to HPP. We found that the rate of diffusion of PI into the cells decreased over the 4 consecutive days after exposure to HPP, indicating repair of the pressure-created membrane pores. The model suggested a temporal change in the size of pores until closure. To the best of our knowledge, this is the first time that pressure-created membrane pores have been quantitatively described and shown to diminish with time. In addition, we found that the membrane repair rate in response to HPP was linear, and growth was temporarily arrested at the population level during the repair period. These results support the existence of a progressive repair process in some of the cells that take up PI, which can therefore be considered as being sub-lethally injured rather than dead. Hence, we showed that a subgroup of bacteria survived HPP and actively repaired their membrane pores.
Molecular Characterization of Multidrug-Resistant Yersinia enterocolitica From Foodborne Outbreaks in Sweden
Authors: Karlsson Philip A. , Tano Eva , Jernberg Cecilia , Hickman Rachel A. , Guy Lionel , Järhult Josef D. , Wang Helen
Published: May 2021

The foodborne pathogenYersinia enterocoliticacauses gastrointestinal infections worldwide. In the spring of 2019, the Swedish Public Health Agency and Statens Serum Institut in Denmark independently identified an outbreak caused byYersinia enterocolitica4/O:3 that after sequence comparison turned out to be a cross-border outbreak. A trace-back investigation suggested shipments of fresh prewashed spinach from Italy as a common source for the outbreak. Here, we determined the genome sequences of fiveY. enterocoliticaclinical isolates during the Swedish outbreak using a combination of Illumina HiSeq short-read and Nanopore Technologies’ MinION long-read whole-genome sequencing. WGS results showed that all clinical strains have a fully assembled chromosome of approximately 4.6 Mbp in size and a 72-kbp virulence plasmid; one of the strains was carrying an additional 5.7-kbp plasmid, pYE-tet. All strains showed a high pathogen probability score (87.5%) with associated genes for virulence, all of which are closely related to an earlier clinical strain Y11 from Germany. In addition, we identified a chromosomally encoded multidrug-resistance cassette carrying resistance genes against chloramphenicol (catA1), streptomycin (aadA1), sulfonamides (sul1), and a mercury resistance module. This chromosomally encoded Tn2670transposon has previously been reported associated with IncFII plasmids inEnterobacteriaceae: aShigella flexnericlinical isolate from Japan in 1950s, aKlebsiella pneumoniaeoutbreak from Australia in 1997, andSalmonella entericaserovar Typhimurium. Interestingly, we identified an additional 5.7-kbp plasmid withtetB (encoding an ABC transporter),Rep, and its own ORI and ORIt sites, sharing high homology with smalltetB-Repplasmids fromPasteurellaceae. This is the first time that Tn2670andPasteurellaceaeplasmids have been reported inY. enterocolitica. Taken together, our study showed that the SwedishY. enterocoliticaoutbreak strains acquired multi-antibiotic and metal-resistance genes through horizontal gene transfer, suggesting a potential reservoir of intraspecies dissemination of multidrug-resistance genes among foodborne pathogens. This study also highlights the concern of food-chain contamination of prewashed vegetables as a perpetual hazard against public health.
Heavy Metal Tolerance Genes Associated With Contaminated Sediments From an E-Waste Recycling River in Southern China
Authors: Long Shengqiao , Tong Hui , Zhang Xuxiang , Jia Shuyu , Chen Manjia , Liu Chengshuai
Published: May 2021

Heavy metal pollution that results from electronic waste (e-waste) recycling activities has severe ecological environmental toxicity impacts on recycling areas. The distribution of heavy metals and the impact on the bacteria in these areas have received much attention. However, the diversity and composition of the microbial communities and the characteristics of heavy metal resistance genes (HMRGs) in the river sediments after long-term e-waste contamination still remain unclear. In this study, eight river sediment samples along a river in a recycling area were studied for the heavy metal concentration and the microbial community composition. The microbial community consisted of 13 phyla including Firmicutes (ranging from 10.45 to 36.63%), Proteobacteria (11.76 to 32.59%), Actinobacteria (14.81 to 27.45%), and unclassified bacteria. The abundance of Firmicutes increased along with the level of contaminants, while Actinobacteria decreased. A canonical correspondence analysis (CCA) showed that the concentration of mercury was significantly correlated with the microbial community and species distribution, which agreed with an analysis of the potential ecological risk index. Moreover, manually curated HMRGs were established, and the HMRG analysis results according to Illumina high-throughput sequencing showed that the abundance of HMRGs was positively related to the level of contamination, demonstrating a variety of resistance mechanisms to adapt, accommodate, and live under heavy metal-contaminated conditions. These findings increase the understanding of the changes in microbial communities in e-waste recycling areas and extend our knowledge of the HMRGs involved in the recovery of the ecological environment.
Multi-Omic Analyses Reveal Habitat Adaptation of Marine Cyanobacterium Synechocystis sp. PCC 7338
Authors: Jeong Yujin , Hong Seong-Joo , Cho Sang-Hyeok , Yoon Seonghoon , Lee Hookeun , Choi Hyung-Kyoon , Kim Dong-Myung , Lee Choul-Gyun , Cho Suhyung , Cho Byung-Kwan
Published: May 2021

Cyanobacteria are considered as promising microbial cell factories producing a wide array of bio-products. Among them, Synechocystis sp. PCC 7338 has the advantage of growing in seawater, rather than requiring arable land or freshwater. Nonetheless, how this marine cyanobacterium grows under the high salt stress condition remains unknown. Here, we determined its complete genome sequence with the embedded regulatory elements and analyzed the transcriptional changes in response to a high-salt environment. Complete genome sequencing revealed a 3.70 mega base pair genome and three plasmids with a total of 3,589 genes annotated. Differential RNA-seq and Term-seq data aligned to the complete genome provided genome-wide information on genetic regulatory elements, including promoters, ribosome-binding sites, 5′- and 3′-untranslated regions, and terminators. Comparison with freshwater Synechocystis species revealed Synechocystis sp. PCC 7338 genome encodes additional genes, whose functions are related to ion channels to facilitate the adaptation to high salt and high osmotic pressure. Furthermore, a ferric uptake regulator binding motif was found in regulatory regions of various genes including SigF and the genes involved in energy metabolism, suggesting the iron-regulatory network is connected to not only the iron acquisition, but also response to high salt stress and photosynthesis. In addition, the transcriptomics analysis demonstrated a cyclic electron transport through photosystem I was actively used by the strain to satisfy the demand for ATP under high-salt environment. Our comprehensive analyses provide pivotal information to elucidate the genomic functions and regulations in Synechocystis sp. PCC 7338.
A Survey of Bacterial Microcompartment Distribution in the Human Microbiome
Authors: Asija Kunica , Sutter Markus , Kerfeld Cheryl A.
Published: May 2021

Bacterial microcompartments (BMCs) are protein-based organelles that expand the metabolic potential of many bacteria by sequestering segments of enzymatic pathways in a selectively permeable protein shell. Sixty-eight different types/subtypes of BMCs have been bioinformatically identified based on the encapsulated enzymes and shell proteins encoded in genomic loci. BMCs are found across bacterial phyla. The organisms that contain them, rather than strictly correlating with specific lineages, tend to reflect the metabolic landscape of the environmental niches they occupy. From our recent comprehensive bioinformatic survey of BMCs found in genome sequence data, we find many in members of the human microbiome. Here we survey the distribution of BMCs in the different biotopes of the human body. Given their amenability to be horizontally transferred and bioengineered they hold promise as metabolic modules that could be used to probiotically alter microbiomes or treat dysbiosis.
On-Site Genomic Epidemiological Analysis of Antimicrobial-Resistant Bacteria in Cambodia With Portable Laboratory Equipment
Authors: Hirabayashi Aki , Yanagisawa Hideji , Takahashi Hiromizu , Yahara Koji , Boeing Philipp , Wolfenden Bethan , Nov Vandarith , Lorn Vichet , Veng Mom , Ann Vuth , Darapheak Chau , Shibayama Keigo , Suzuki Masato
Published: May 2021

The rapid emergence of carbapenemase-producing gram-negative bacteria (CPGNB) is a global threat due to the high mortality of infection and limited treatment options. Although there have been many reports of CPGNB isolated from Southeast Asian countries, to date there has been no genetic analysis of CPGNB isolated from Cambodia. Sequence-based molecular epidemiological analysis enables a better understanding of the genotypic characteristics and epidemiological significance of antimicrobial-resistant (AMR) bacteria in each country, and allows countries to enact measures related to AMR issues. In this study, we performed on-site genomic epidemiological analysis of CPGNB isolated in Cambodia using a portable laboratory equipment called Bento Lab, which combines a PCR thermal cycler, microcentrifuge, gel electrophoresis apparatus, and LED transilluminator, along with the MinION nanopore sequencer. PCR targeting of major carbapenemase genes using Bento Lab revealed that twoEscherichia coliisolates and oneAcinetobacter baumanniiisolate harbored carbapenemase genes:blaNDM,blaOXA–48, andblaOXA–23, respectively. The results of phenotypic diagnostic tests for CPGNB, such as the carbapenem inactivation method and double-disk diffusion test using a specific inhibitor of metallo-β-lactamases, were consistent with their AMR genotypes. Whole-genome sequencing analysis using MinION revealed thatblaNDM–5gene was carried on a 93.9-kb plasmid with IncFIA/IncFIB/IncFII/IncQ1 replicons, andblaOXA–181gene was carried on a 51.5-kb plasmid with the IncX3 replicon inE. coliisolates.blaOXA–23was encoded in two locations on the chromosome ofA. baumannii. Plasmids carryingblaNDM–5orblaOXA–181inE. coliwere highly structurally identical to plasmids prevalent in Enterobacterales in China and other countries, suggesting that they disseminated from a common evolutionary origin. Our findings demonstrate the potential impact of portable laboratory equipment on AMR bacteria research in hospitals and research centers with limited research facilities, and provide the first glimpse into the genomic epidemiology of CPGNB in Cambodia.
Extended Archaeal Histone-Based Chromatin Structure Regulates Global Gene Expression in Thermococcus kodakarensis
Authors: Sanders Travis J. , Ullah Fahad , Gehring Alexandra M. , Burkhart Brett W. , Vickerman Robert L. , Fernando Sudili , Gardner Andrew F. , Ben-Hur Asa , Santangelo Thomas J.
Published: May 2021

Histone proteins compact and organize DNA resulting in a dynamic chromatin architecture impacting DNA accessibility and ultimately gene expression. Eukaryotic chromatin landscapes are structured through histone protein variants, epigenetic marks, the activities of chromatin-remodeling complexes, and post-translational modification of histone proteins. In most Archaea, histone-based chromatin structure is dominated by the helical polymerization of histone proteins wrapping DNA into a repetitive and closely gyred configuration. The formation of the archaeal-histone chromatin-superhelix is a regulatory force of adaptive gene expression and is likely critical for regulation of gene expression in all histone-encoding Archaea. Single amino acid substitutions in archaeal histones that block formation of tightly packed chromatin structures have profound effects on cellular fitness, but the underlying gene expression changes resultant from an altered chromatin landscape have not been resolved. Using the model organism Thermococcus kodakarensis, we genetically alter the chromatin landscape and quantify the resultant changes in gene expression, including unanticipated and significant impacts on provirus transcription. Global transcriptome changes resultant from varying chromatin landscapes reveal the regulatory importance of higher-order histone-based chromatin architectures in regulating archaeal gene expression.
Identification of the Core MicroRNAs and Potential Molecular Mechanismsin Sarcoidosis Using Bioinformatics Analysis
Authors: Cao Yuan , Zhang Hua , Zheng Lulu , Li Qiao
Published: May 2021

Sarcoidosis is a systemic heterogeneous inflammatory disease; however, the etiology and pathogenesis of sarcoidosis are still unknown. Herein, we investigated the core microRNAs and potential molecular mechanisms in sarcoidosis. The DE-miRNAs were diagnosed using the LIMMA software package. DIANA-mirPath was employed to perform pathway and GO enrichment analysis of the DE-miRNAs. PPI networks and miRNA-target gene regulatory networks were used to obtain insight into the actions of DE-miRNAs. Expression of the hub genes along with miRNAs was validated in clinical specimens. Overall, 266 DE-miRNAs were screened. Among these DE-miRNAs, hsa-miR-144, hsa-miR-126, as well as hsa-miR-106a were the upmost upregulated miRNAs; hsa-miR-151-3p, hsa-miR-320d, and hsa-miR-324-3p were the top downregulated miRNAs. NR3C1, ZBTB7A, NUFIP2, BZW1, ERGIC2, and VEGFA were mapped as the most targeted hub genes in the upregulation of miRNAs, and MCL1 and SAE1 were the most targeted hub genes in the downregulation of miRNA. VEGFA and NR3C1 were selected and potentially modulated by hsa-miR-20b, hsa-miR-126, and hsa-miR-106a. In sarcoidosis pathological tissue, hsa-miR-126 was highly expressed, and VEGFA and NR3C1 were overexpressed. In conclusion, our results revealed the dysregulation of hsa-miR-126 and a potential regulatory mechanism for pathogenesis in sarcoidosis.
Regulation of RNA Polymerase II Transcription Initiation and Elongation by Transcription Factor TFII-I
Authors: Linzer Niko , Trumbull Alexis , Nar Rukiye , Gibbons Matthew D. , Yu David T. , Strouboulis John , Bungert Jörg
Published: May 2021

Transcription by RNA polymerase II (Pol II) is regulated by different processes, including alterations in chromatin structure, interactions between distal regulatory elements and promoters, formation of transcription domains enriched for Pol II and co-regulators, and mechanisms involved in the initiation, elongation, and termination steps of transcription. Transcription factor TFII-I, originally identified as an initiator (INR)-binding protein, contains multiple protein–protein interaction domains and plays diverse roles in the regulation of transcription. Genome-wide analysis revealed that TFII-I associates with expressed as well as repressed genes. Consistently, TFII-I interacts with co-regulators that either positively or negatively regulate the transcription. Furthermore, TFII-I has been shown to regulate transcription pausing by interacting with proteins that promote or inhibit the elongation step of transcription. Changes in TFII-I expression in humans are associated with neurological and immunological diseases as well as cancer. Furthermore, TFII-I is essential for the development of mice and represents a barrier for the induction of pluripotency. Here, we review the known functions of TFII-I related to the regulation of Pol II transcription at the stages of initiation and elongation.
Association Between Childhood Neighborhood Quality and the Risk of Cognitive Dysfunction in Chinese Middle-Aged and Elderly Population: The Moderation Effect of Body Mass Index
Authors: Xiong Peng , Liang Xiaohua , Chen Haiyan , Chen Li , Zuo Lei , Jing Chunxia , Hao Guang
Published: May 2021

Background: Identification of early modifiable factors is crucial to delay or prevent the development of cognitive impairment and reduce the social and economic burden.

Objective: This study aimed to examine the longitudinal associations of childhood neighborhood quality (CNQ) with the risk of later-life cognitive dysfunction and the role of body mass index (BMI) in this association.

Methods: A total of 8,289 community-dwelling middle-aged and elderly population from wave 2011, wave 2013, and wave 2015 of the China Health and Retirement Longitudinal Study (CHARLS) were included. Cognitive function and CNQ were measured by standardized questionnaires. Multilevel linear regression models were used to estimate the associations of CNQ and cognitive function. The interactions of BMI with CNQ in the progress of cognitive function were also estimated.

Results: The participants with higher CNQ had a significantly low risk of cognitive impairment than those with lower CNQ score (β = 0.067, 95% CI: 0.031, 0.103), and the results remained similar (β = 0.039, 95% CI: 0.004, 0.075) after controlling other confounding variables. Furthermore, there was an interaction between BMI with CNQ score (P < 0.001) for the risk of cognitive impairment. In BMI-stratified analysis, we found that the association of CNQ and cognitive function was not statistically significant in overweight or obese population (β = 0.019, 95% CI: −0.032, 0.070), but was statistically significant in people with lower BMI (β = 0.059, 95% CI: 0.010, 0.107).

Conclusions: Higher CNQ score is significantly associated with the lower risk of cognitive dysfunction in adulthood. BMI may moderate the associations of CNQ with the risk of cognitive function.
Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
Authors: Nishijima Haruo , Kimura Tamaki , Mori Fumiaki , Wakabayashi Koichi , Kinoshita Iku , Nakamura Takashi , Kon Tomoya , Suzuki Chieko , Tomiyama Masahiko
Published: May 2021

Background

It remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (L-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show young-onset Parkinson’s disease enhances LID.

Objectives

To evaluate the association of age at dopaminergic denervation (onset age) and initiation of L-dopa treatment (treatment age) with LID development in model rats.

Methods

We established rat models of young- and old-lesioned Parkinson’s disease (6-hydroxydopamine lesions at 10 and 88 weeks of age, respectively). Dopaminergic denervation was confirmed by the rotational behavior test using apomorphine. Rats in the young-lesioned group were allocated to either L-dopa treatment at a young or old age, or saline treatment. Rats in the old-lesioned group were allocated to either L-dopa treatment or saline group. We evaluated L-dopa-induced abnormal involuntary movements during the 14-day treatment period. We also examined preprodynorphin mRNA expression in the striatum (a neurochemical hallmark of LID) and the volume of the medial globus pallidus (a pathological hallmark of LID).

Results

LID-like behavior was enhanced in L-dopa-treated young-lesioned rats compared with L-dopa-treated old-lesioned rats. Preprodynorphin mRNA expression was higher in L-dopa-treated young-lesioned rats than in in L-dopa-treated old-lesioned rats. The volume of the medial globus pallidus was greater in L-dopa-treated young-lesioned rats than in L-dopa-treated old-lesioned rats. Treatment age did not affect LID-like behavior or the degree of medial globus pallidus hypertrophy in the young-lesioned model.

Conclusion

Both dopaminergic denervation and L-dopa initiation at a young age contributed to the development of LID; however, the former may be a more important factor.
Dual-Phase β-Amyloid PET Captures Neuronal Injury and Amyloidosis in Corticobasal Syndrome
Authors: Schmitt Julia , Palleis Carla , Sauerbeck Julia , Unterrainer Marcus , Harris Stefanie , Prix Catharina , Weidinger Endy , Katzdobler Sabrina , Wagemann Olivia , Danek Adrian , Beyer Leonie , Rauchmann Boris-Stephan , Rominger Axel , Simons Mikael , Bartenstein Peter , Perneczky Robert , Haass Christian , Levin Johannes , Höglinger Günter U. , Brendel Matthias ,   the German Imaging Initiative for Tauopathies (GII4T)
Published: May 2021

Objectives:In recent years several18F-labeled amyloid PET (Aβ-PET) tracers have been developed and have obtained clinical approval. There is evidence that Aβ-PET perfusion can provide surrogate information about neuronal injury in neurodegenerative diseases when compared to conventional blood flow and glucose metabolism assessment. However, this paradigm has not yet been tested in neurodegenerative disorders with cortical and subcortical affection. Therefore, we investigated the performance of early acquisition18F-flutemetamol Aβ-PET in comparison to18F-fluorodeoxyglucose (FDG)-PET in corticobasal syndrome (CBS).

Methods:Subjects with clinically possible or probable CBS were recruited within the prospective Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer’s Disease (ActiGliA) observational study and all CBS cases with an available FDG-PET prior to Aβ-PET were selected. Aβ-PET was acquired 0–10 min p.i. (early-phase) and 90–110 min p.i. (late-phase) whereas FDG-PET was recorded statically from 30 to 50 min p.i. Semiquantitative regional values and asymmetry indices (AI) were compared between early-phase Aβ-PET and FDG-PET. Visual assessments of hypoperfusion and hypometabolism were compared between both methods. Late-phase Aβ-PET was evaluated visually for assessment of Aβ-positivity.

Results:Among 20 evaluated patients with CBS, 5 were Aβ-positive. Early-phase Aβ-PET and FDG-PET SUVr correlated highly in cortical (meanR= 0.86, range 0.77–0.92) and subcortical brain regions (meanR= 0.84, range 0.79–0.90). Strong asymmetry was observed in FDG-PET for the motor cortex (mean |AI| = 2.9%), the parietal cortex (mean |AI| = 2.9%), and the thalamus (mean |AI| = 5.5%), correlating well with AI of early-phase Aβ-PET (meanR= 0.87, range 0.62–0.98). Visual assessments of hypoperfusion and hypometabolism were highly congruent.

Conclusion:Early-phase Aβ-PET facilitates assessment of neuronal injury in CBS for cortical and subcortical areas. Known asymmetries in CBS are captured by this method, enabling assessment of Aβ-status and neuronal injury with a single radiation exposure at a single visit.
Posterior Cortical Cognitive Deficits Are Associated With Structural Brain Alterations in Mild Cognitive Impairment in Parkinson’s Disease
Authors: Devignes Quentin , Viard Romain , Betrouni Nacim , Carey Guillaume , Kuchcinski Gregory , Defebvre Luc , Leentjens Albert F. G. , Lopes Renaud , Dujardin Kathy
Published: May 2021

Context: Cognitive impairments are common in patients with Parkinson’s disease (PD) and are heterogeneous in their presentation. The “dual syndrome hypothesis” suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia.

Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype.

Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n= 41) or as having a frontostriatal (n= 16), posterior cortical (n= 25), or a mixed (n= 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts.

Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype.

Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.
Impact of Preinjury Antithrombotic Therapy on 30–Day Mortality in Older Patients Hospitalized With Traumatic Brain Injury (TBI)
Authors: Rønning Pål , Helseth Eirik , Skaansar Ola , Tverdal Cathrine , Andelic Nada , Bhatnagar Rahul , Melberg Mathias , Skaga Nils Oddvar , Aarhus Mads , Halvorsen Sigrun , Helseth Ragnhild
Published: May 2021

Objective: Elderly patients are frequently in need of antithrombotic therapy for reducing thrombotic events. The association between antithrombotic drugs and survival after traumatic brain injury (TBI) is, nevertheless, unclear.

Methods: This retrospective study included patients ≥65 years admitted to a Norwegian Level 1 trauma center with TBI identified on cerebral computed tomography (cerebral-CT) during 2014–2019. Preinjury use of antiplatelets and anticoagulants was compared to the prescription rate in the general Norwegian population. The primary outcome was 30-day mortality. Uni- and multivariate logistic regression analyses estimated the association between the use of antithrombotic drugs and mortality.

Results: The study includes 832 consecutive TBI patients ≥65 years. The median age was 76 years, 58% were males, 51% had moderate or severe TBI, and 39% had multiple traumas. Preinjury use of antithrombotics was registered in 471/832 (55.6%) patients; antiplatelet therapy alone in 268, anticoagulant therapy alone in 172, and combined antiplatelet and anticoagulant therapy in 31. Antiplatelet use did not differ between the study cohort and the general Norwegian population ≥65 years (31 vs. 31%, p = 0.87). Anticoagulant therapy was used more commonly in the study cohort than in the general Norwegian population (24 vs. 19%, p = 0.04). Combined use of antiplatelet and anticoagulant therapy was significantly associated with 30-day mortality, while preinjury antiplatelet or anticoagulation treatment alone was not. No difference in 30-day mortality between patients using VKA, DOACs, or LMWH was encountered.

Conclusions: In this cohort, neither antiplatelet nor anticoagulant therapy alone was associated with increased 30-day mortality. Anticoagulant use was more prevalent among TBI patients than the general population, suggesting that anticoagulation might contribute to the initiation of intracranial bleeding after blunt head trauma. Combined antiplatelet and anticoagulant therapy posed increased risk of 30-day mortality.
Occupational Injuries and Use of Benzodiazepines: A Systematic Review and Metanalysis
Authors: Garbarino Sergio , Lanteri Paola , Bragazzi Nicola Luigi , Gualerzi Giovanni , Riccò Matteo
Published: May 2021

Background: Benzodiazepines have been widely used in clinical practice for over four decades and continue to be one of the most consumed and highly prescribed class of drugs available in the treatment of anxiety, depression, and insomnia. The literature indicates that Benzodiazepine users at a significantly increased risk of Motor Vehicle accidents compared to non-users but the impact on injuries at workplace is not well-defined. We aimed to investigate whether use of benzodiazepine is associated with increased risk of occupational injuries (OI).

Methods: PubMed, Embase, and Scopus databases were searched. A meta-analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI) among case controls, cross-sectional studies, either questionnaire or laboratory exams based.

Results: A total of 13 studies met inclusion criteria, involving 324,168 OI from seven different countries, with an estimated occurrence of benzodiazepine positivity of 2.71% (95% CI 1.45–4.98). A total of 14 estimates were retrieved. Of them, 10 were based on laboratory analyses, three on institutional databases, while one study was based on questionnaires. Regarding the occupational groups, three estimates focused on commercial drivers (0.73%, 95% CI 0.12–4.30), that exhibited a reduced risk ratio for benzodiazepine positivity compared to other occupational groups (RR 0.109, 95% CI 0.063–0.187). Eventually, no increased risk for benzodiazepine positivity was identified, either from case control studies (OR 1.520, 95% CI 0.801–2.885, I2 76%), or cross sectional studies, when only laboratory based estimates were taken in account (OR 0.590, 95% CI 0.253–1.377, I2 63%).

Conclusions: Even though benzodiazepines have the potential to increase injury rates among casual and chronic users, available evidence are insufficient to sustain this hypothesis, particularly when focusing on laboratory-based studies (i.e., studies the characterized the benzodiazepine immediately before the event).
Dephosphorylation Passivates the Seeding Activity of Oligomeric Tau Derived From Alzheimer’s Brain
Authors: Wu Ruozhen , Li Longfei , Shi Ruirui , Zhou Yan , Jin Nana , Gu Jianlan , Tung Yunn Chyn , Liu Fei , Chu Dandan
Published: May 2021

Accumulation of intracellular neurofibrillary tangles (NFTs), which are constituted of abnormally phosphorylated tau, is one of the neuropathological hallmarks of Alzheimer’s disease (AD). The oligomeric aggregates of tau in AD brain (AD O-tau) are believed to trigger NFT spreading by seeding normal tau aggregation as toxic seeds, in a prion-like fashion. Here, we revealed the features of AD O-tau by Western blots using antibodies against various epitopes and determined the effect of dephosphorylation on the seeding activity of AD O-tau by capture and seeded aggregation assays. We found that N-terminal truncated and C-terminalhyperphosphorylated tau species were enriched in AD O-tau. Dephosphorylation of AD O-tau by alkaline phosphatasediminished its activity in capturing tau in vitro and ininducing insoluble aggregates in cultured cells. Our resultssuggested that dephosphorylation passivated the seeding activity ofAD O-tau. Inhibition of phosphorylation may be a potentstrategy to prevent the spreading of tau patho3logy.
Parkin Levels Decrease in Fibroblasts With Progranulin (PGRN) Pathogenic Variants and in a Cellular Model of PGRN Deficiency
Authors: Gaweda-Walerych Katarzyna , Walerych Dawid , Berdyński Mariusz , Buratti Emanuele , Zekanowski Cezary
Published: May 2021

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases with TDP-43 mislocalization and aggregation. Genetic forms of FTLD and ALS are caused by pathogenic variants in various genes, such asPGRN(progranulin). To date, depletion of parkin E3 ubiquitin protein ligase, a key mitophagy regulator, has been reported in sporadic ALS patients and ALS mice models with TDP-43 proteinopathy. In this work, we show parkin downregulation also in fibroblasts derived from FTLD patients with four different PGRN pathogenic variants. We corroborate this finding in control fibroblasts upon PGRN silencing, demonstrating additionally the decrease of parkin downstream targets, mitofusin 2 (MFN2) and voltage dependent anion channel 1 (VDAC1). Importantly, we show that TDP-43 overexpression rescues PRKN levels upon transient PGRN silencing, but not in FTLD fibroblasts with PGRN pathogenic variants, despite upregulating PGRN levels in both cases. Further observation of PRKN downregulation upon TDP-43 silencing, suggests that TDP-43 loss-of-function contributes to PRKN decrease. Our results provide further evidence that parkin downregulation might be a common and systemic phenomenon in neurodegenerative diseases with TDP- 43 loss-of-function.