bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Non-coding RNA Aerrie Controls DNA Damage Repair via YBX1 to Maintain Endothelial Cell Function
Authors: Pham Tan Phát , Bink Diewertje I. , Stanicek Laura , van Bergen Anke , van Leeuwen Esmee , Tran Yvonne , Matic Ljubica , Hedin Ulf , Wittig Ilka , Dimmeler Stefanie , Boon Reinier A.
Published: January 2021

Aging is accompanied by many physiological changes. These changes can progressively lead to many types of cardiovascular diseases. During this process blood vessels lose their ability to maintain vascular homeostasis, ultimately resulting in hypertension, stroke, or myocardial infarction. Increase in DNA damage is one of the hallmarks of aging and can be repaired by the DNA signaling and repair system. In our study we show that long non-coding RNA Aerrie (linc01013) contributes to the DNA signaling and repair mechanism. Silencing of Aerrie in endothelial cells impairs angiogenesis, migration, and barrier function. Aerrie associates with YBX1 and together they act as important factors in DNA damage signaling and repair. This study identifies Aerrie as a novel factor in genomic stability and as a binding partner of YBX1 in responding to DNA damage.
Determinants of Phagosomal pH During Host-Pathogen Interactions
Authors: Westman Johannes , Grinstein Sergio
Published: January 2021

The ability of phagosomes to halt microbial growth is intimately linked to their ability to acidify their luminal pH. Establishment and maintenance of an acidic lumen requires precise co-ordination of H+pumping and counter-ion permeation to offset the countervailing H+leakage. Despite the best efforts of professional phagocytes, however, a number of specialized pathogens survive and even replicate inside phagosomes. In such instances, pathogens target the pH-regulatory machinery of the host cell in an effort to survive inside or escape from phagosomes. This review aims to describe how phagosomal pH is regulated during phagocytosis, why it varies in different types of professional phagocytes and the strategies developed by prototypical intracellular pathogens to manipulate phagosomal pH to survive, replicate, and eventually escape from the phagocyte.
Identifying Transcriptomic Signatures and Rules for SARS-CoV-2 Infection
Authors: Zhang Yu-Hang , Li Hao , Zeng Tao , Chen Lei , Li Zhandong , Huang Tao , Cai Yu-Dong
Published: January 2021

The world-wide Coronavirus Disease 2019 (COVID-19) pandemic was triggered by the widespread of a new strain of coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Multiple studies on the pathogenesis of SARS-CoV-2 have been conducted immediately after the spread of the disease. However, the molecular pathogenesis of the virus and related diseases has still not been fully revealed. In this study, we attempted to identify new transcriptomic signatures as candidate diagnostic models for clinical testing or as therapeutic targets for vaccine design. Using the recently reported transcriptomics data of upper airway tissue with acute respiratory illnesses, we integrated multiple machine learning methods to identify effective qualitative biomarkers and quantitative rules for the distinction of SARS-CoV-2 infection from other infectious diseases. The transcriptomics data was first analyzed by Boruta so that important features were selected, which were further evaluated by the minimum redundancy maximum relevance method. A feature list was produced. This list was fed into the incremental feature selection, incorporating some classification algorithms, to extract qualitative biomarker genes and construct quantitative rules. Also, an efficient classifier was built to identify patients infected with SARS-COV-2. The findings reported in this study may help in revealing the potential pathogenic mechanisms of COVID-19 and finding new targets for vaccine design.
Herpes Simplex Virus Cell Entry Mechanisms: An Update
Authors: Madavaraju Krishnaraju , Koganti Raghuram , Volety Ipsita , Yadavalli Tejabhiram , Shukla Deepak
Published: January 2021

Herpes simplex virus (HSV) can infect a broad host range and cause mild to life threating infections in humans. The surface glycoproteins of HSV are evolutionarily conserved and show an extraordinary ability to bind more than one receptor on the host cell surface. Following attachment, the virus fuses its lipid envelope with the host cell membrane and releases its nucleocapsid along with tegument proteins into the cytosol. With the help of tegument proteins and host cell factors, the nucleocapsid is then docked into the nuclear pore. The viral double stranded DNA is then released into the host cell’s nucleus. Released viral DNA either replicates rapidly (more commonly in non-neuronal cells) or stays latent inside the nucleus (in sensory neurons). The fusion of the viral envelope with host cell membrane is a key step. Blocking this step can prevent entry of HSV into the host cell and the subsequent interactions that ultimately lead to production of viral progeny and cell death or latency. In this review, we have discussed viral entry mechanisms including the pH-independent as well as pH-dependent endocytic entry, cell to cell spread of HSV and use of viral glycoproteins as an antiviral target.
Rheumatic Heart Valve Disease Pathophysiology and Underlying Mechanisms
Authors: Passos Livia S. A. , Nunes Maria Carmo P. , Aikawa Elena
Published: January 2021

Rheumatic heart valve disease (RHVD) is a post-infectious sequel of acute rheumatic fever resulting from an abnormal immune response to a streptococcal pharyngitis that triggers valvular damage. RHVD is the leading cause of cardiovascular death in children and young adults, mainly in women from low and middle-income countries. It is known that long-term inflammation and high degree of fibrosis leads to valve dysfunction due to anatomic disruption of the valve apparatus. However, since public and private investments in RHVD studies are practically inexistent the number of publications is scarce. This disease shows different natural history and clinical presentations as compared to other degenerative heart valve diseases. Although more than five decades passed after the pioneering studies on the pathogenesis of RHVD, it is still unclear how self-tolerance mechanisms fail in this disease, and how humoral and cellular inflammatory responses are interconnected. Despite that pathological mechanisms have been already proposed for RHVD, none of them are able to explain the preferential involvement of the mitral valve. This review focuses on pathophysiology and underlying mechanisms of RHVD.
The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells
Authors: Xia Chao , Jiang Tianyuan , Wang Yonghui , Chen Xiaoting , Hu Yan , Gao Yanhong
Published: January 2021

The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is reduced. p53 not only regulates cellular senescence but also functions as a negative regulator in bone formation. However, the role of p53 in MSCs senescence and differentiation has not been extensively explored. In the present study, we investigated the molecular mechanism of p53 in MSCs senescence and osteogenic differentiation. We found that p53 was upregulated during cellular senescence and osteogenic differentiation of MSCs respectively induced by H2O2 and BMP9. Similarly, the expression of p53-induced miR-145a was increased significantly. Furthermore, Overexpression of miR-145a in MSCs promoted cellular senescence and inhibited osteogenic differentiation. Then, we identified that p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a. In summary, our results indicate that p53/miR-145a axis exert its functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel p53/miR-145a/Cbfb axis in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.
The Legacy Effects of Colonial and Apartheid Imprints on Urban Greening in South Africa: Spaces, Species, and Suitability
Authors: Shackleton Charlie M. , Gwedla N.
Published: January 2021

Colonialism is a significant legacy across most aspects of urban form, the nature and distribution of public green spaces, and tree species composition in many cities of the Global South. However, the legacy effects of colonialism on urban green infrastructure and the uses thereof have only recently come under scrutiny. Here we collate information from South Africa on urban greening and interpret it through a colonial and apartheid legacy lens in relation to the distribution and types of urban nature found and their resonance with contemporary needs as an African country. The analysis indicates marked inequalities in public green space distribution and quality between neighborhoods designated for different race groups during the colonial and apartheid periods, which continues to be reproduced by the post-colonial (and post-apartheid) state. Additionally, in the older, former colonial neighborhoods non-native tree species dominate in parks and streets, with most of the species having been introduced during the colonial period. Such colonial introductions have left a burdensome legacy of invasive species that costs billions of Rands annually to keep in check. Lastly, the forms of nature and activities provided in public urban green spaces remains reminiscent of the colonial norm, with little recognition of African worldviews, identity and needs. We conclude in emphasizing the necessity for urban authorities and planners to address these anachronistic legacies through adopting a more inclusive and co-design approach with respect to the extent, location and types of urban nature provided, as well as the types of cultural symbols and activities permitted and promoted.
A Multi-Locus Association Model Framework for Nested Association Mapping With Discriminating QTL Effects in Various Subpopulations
Authors: Bu Suhong , Wu Weiren , Zhang Yuan-Ming
Published: January 2021

Nested association mapping (NAM) has been an invaluable approach for plant genetics community and can dissect the genetic architecture of complex traits. As the most popular NAM analysis strategy, joint multifamily mapping can combine all information from diverse genetic backgrounds and increase population size. However, it is influenced by the genetic heterogeneity of quantitative trait locus (QTL) across various subpopulations. Multi-locus association mapping has been proven to be powerful in many cases of QTL mapping and genome-wide association studies. Therefore, we developed a multi-locus association model of multiple families in the NAM population, which could discriminate the effects of QTLs in all subpopulations. A series of simulations with a real maize NAM genomic data were implemented. The results demonstrated that the new method improves the statistical power in QTL detection and the accuracy in QTL effect estimation. The new approach, along with single-family linkage mapping, was used to identify QTLs for three flowering time traits in the maize NAM population. As a result, most QTLs detected in single family linkage mapping were identified by the new method. In addition, the new method also mapped some new QTLs with small effects, although their functions need to be identified in the future.
SNP-Density Crossover Maps of Polymorphic Transposable Elements and HLA Genes Within MHC Class I Haplotype Blocks and Junction
Authors: Kulski Jerzy K. , Suzuki Shingo , Shiina Takashi
Published: January 2021

The genomic region (~4 Mb) of the human major histocompatibility complex (MHC) on chromosome 6p21 is a prime model for the study and understanding of conserved polymorphic sequences (CPSs) and structural diversity of ancestral haplotypes (AHs)/conserved extended haplotypes (CEHs). The aim of this study was to use a set of 95 MHC genomic sequences downloaded from a publicly available BioProject database at NCBI to identify and characterise polymorphic human leukocyte antigen (HLA) class I genes and pseudogenes, MICA and MICB, and retroelement indels as haplotypic lineage markers, and single-nucleotide polymorphism (SNP) crossover loci in DNA sequence alignments of different haplotypes across the Olfactory Receptor (OR) gene region (~1.2 Mb) and the MHC class I region (~1.8 Mb) from the GPX5 to the MICB gene. Our comparative sequence analyses confirmed the identity of 12 haplotypic retroelement markers and revealed that they partitioned the HLA-A/B/C haplotypes into distinct evolutionary lineages. Crossovers between SNP-poor and SNP-rich regions defined the sequence range of haplotype blocks, and many of these crossover junctions occurred within particular transposable elements, lncRNA, OR12D2, MUC21, MUC22, PSORS1A3, HLA-C, HLA-B, and MICA. In a comparison of more than 250 paired sequence alignments, at least 38 SNP-density crossover sites were mapped across various regions from GPX5 to MICB. In a homology comparison of 16 different haplotypes, seven CEH/AH (7.1, 8.1, 18.2, 51.x, 57.1, 62.x, and 62.1) had no detectable SNP-density crossover junctions and were SNP poor across the entire ~2.8 Mb of sequence alignments. Of the analyses between different recombinant haplotypes, more than half of them had SNP crossovers within 10 kb of LTR16B/ERV3-16A3_I, MLT1, Charlie, and/or THE1 sequences and were in close vicinity to structurally polymorphic Alu and SVA insertion sites. These studies demonstrate that (1) SNP-density crossovers are associated with putative ancestral recombination sites that are widely spread across the MHC class I genomic region from at least the telomeric OR12D2 gene to the centromeric MICB gene and (2) the genomic sequences of MHC homozygous cell lines are useful for analysing haplotype blocks, ancestral haplotypic landscapes and markers, CPSs, and SNP-density crossover junctions.
Milestones in Personalized Medicine in Pemphigus and Pemphigoid
Authors: Bieber Katja , Kridin Khalaf , Emtenani Shirin , Boch Katharina , Schmidt Enno , Ludwig Ralf J.
Published: January 2021

Pemphigus and pemphigoid diseases are autoimmune bullous diseases characterized and caused by autoantibodies targeting adhesion molecules in the skin and/or mucous membranes. Personalized medicine is a new medical model that separates patients into different groups and aims to tailor medical decisions, practices, and interventions based on the individual patient`s predicted response or risk factors. An important milestone in personalized medicine in pemphigus and pemphigoid was achieved by verifying the autoimmune pathogenesis underlying these diseases, as well as by identifying and cloning several pemphigus/pemphigoid autoantigens. The latter has become the basis of the current, molecular-based diagnosis that allows the differentiation of about a dozen pemphigus and pemphigoid entities. The importance of autoantigen-identification in pemphigus/pemphigoid is further highlighted by the emergence of autoantigen-specific B cell depleting strategies. To achieve this goal, the chimeric antigen receptor (CAR) T cell technology, which is used for the treatment of certain hematological malignancies, was adopted, by generating chimeric autoantigen receptor (CAAR) T cells. In addition to these more basic science-driven milestones in personalized medicine in pemphigus and pemphigoid, careful clinical observation and epidemiology are again contributing to personalized medicine. The identification of clearly distinct clinical phenotypes in pemphigoid like the non-inflammatory and gliptin-associated bullous pemphigoid embodies a prominent instance of the latter. We here review these exciting developments in basic, translational, clinical, and epidemiological research in pemphigus and pemphigoid. Overall, we hereby aim to attract more researchers and clinicians to this highly interesting and dynamic field of research.
Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions
Authors: Mohammad Shireen , Thiemermann Christoph
Published: January 2021

Diet-induced metabolic endotoxemia is an important factor in the development of many chronic diseases in animals and man. The gut epithelium is an efficient barrier that prevents the absorption of liposaccharide (LPS). Structural changes to the intestinal epithelium in response to dietary alterations allow LPS to enter the bloodstream, resulting in an increase in the plasma levels of LPS (termed metabolic endotoxemia). LPS activates Toll-like receptor-4 (TLR4) leading to the production of numerous pro-inflammatory cytokines and, hence, low-grade systemic inflammation. Thus, metabolic endotoxemia can lead to several chronic inflammatory conditions. Obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) can also cause an increase in gut permeability and potential pharmacological and dietary interventions could be used to reduce the chronic low-grade inflammation associated with endotoxemia.
MHC II-PI3K/Akt/mTOR Signaling Pathway Regulates Intestinal Immune Response Induced by Soy Glycinin in Hybrid Grouper: Protective Effects of Sodium Butyrate
Authors: Yin Bin , Liu Hongyu , Tan Beiping , Dong Xiaohui , Chi Shuyan , Yang Qihui , Zhang Shuang
Published: January 2021

Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1β were upregulated in the GH group. IgG, IL-1β, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PI3KSer294/T-PI3K, P-AktSer473/T-Akt, and P-mTORSer2448/T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1β is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PI3K and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PI3K/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.
Predictability of Seawater DMS During the North Atlantic Aerosol and Marine Ecosystem Study (NAAMES)
Authors: Bell Thomas G. , Porter Jack G. , Wang Wei-Lei , Lawler Michael J. , Boss Emmanuel , Behrenfeld Michael J. , Saltzman Eric S.
Published: January 2021

This work presents an overview of a unique set of surface ocean dimethylsulfide (DMS) measurements from four shipboard field campaigns conducted during the North Atlantic Aerosol and Marine Ecosystem Study (NAAMES) project. Variations in surface seawater DMS are discussed in relation to biological and physical observations. Results are considered at a range of timescales (seasons to days) and spatial scales (regional to sub-mesoscale). Elevated DMS concentrations are generally associated with greater biological productivity, although chlorophyll a (Chl) only explains a small fraction of the DMS variability (15%). Physical factors that determine the location of oceanic temperature fronts and depth of vertical mixing have an important influence on seawater DMS concentrations during all seasons. The interplay of biomass and physics influences DMS concentrations at regional/seasonal scales and at smaller spatial and shorter temporal scales. Seawater DMS measurements are compared with the global seawater DMS climatology and predictions made using a recently published algorithm and by a neural network model. The climatology is successful at capturing the seasonal progression in average seawater DMS, but does not reproduce the shorter spatial/temporal scale variability. The input terms common to the algorithm and neural network approaches are biological (Chl) and physical (mixed layer depth, photosynthetically active radiation, seawater temperature). Both models predict the seasonal North Atlantic average seawater DMS trends better than the climatology. However, DMS concentrations tend to be under-predicted and the episodic occurrence of higher DMS concentrations is poorly predicted. The choice of climatological seawater DMS product makes a substantial impact on the estimated DMS flux into the North Atlantic atmosphere. These results suggest that additional input terms are needed to improve the predictive capability of current state-of-the-art approaches to estimating seawater DMS.
Thermal–Mechanical Processing and Strengthen in AlxCoCrFeNi High-Entropy Alloys
Authors: Li Jinshan , Yang Haoxue , Wang William Yi , Kou Hongchao , Wang Jun
Published: January 2021

In this study high-entropy alloys (HEAs) were devised based on a new alloy design concept, which breaks with traditional design methods for conventional alloys. As a novel alloy, HEAs have demonstrated excellent engineering properties and possible combinations of diverse properties for their unique tunable microstructures and properties. This review article explains the phase transition mechanism and mechanical properties of high-entropy alloys under the thermal-mechanical coupling effect, which is conducive to deepening the role of deformation combines annealing on the structure control and performance improvement of high-entropy alloys, giving HEAs a series of outstanding performance and engineering application prospect. To reach this goal we have explored the microstructural evolution, formation of secondary phases at high and/or intermediate temperatures and their effect on the mechanical properties of the well known AlxCoCrFeNi HEAs system, which not only has an important role in deepening the understanding of phase transition mechanism in AlxCoCrFeNi HEAs, but also has important engineering application value for promoting the application of high-entropy alloys.
Verifying Diagnosis of Refractory Celiac Disease With Urine Gluten Immunogenic Peptides as Biomarker
Authors: Moreno María de Lourdes , Sánchez-Muñoz Diego , Sanders David , Rodríguez-Herrera Alfonso , Sousa Carolina
Published: January 2021

Refractory celiac disease (RCD) involves T-lymphocyte activation despite supposed absence of gluten exposure. Assessing dietary adherence is the cornerstone of RCD diagnosis, but available diagnostic tools fail to monitor gluten-free diet (GFD). A recently acknowledged GFD biomarker is gluten immunogenic peptides (GIP) in urine. This study assessed urine GIP to verify whether RCD patients could be reclassified as “exposed to gluten.” Three out of four RCD patients had at least two positive-GIP urine samples in a follow-up of 3 months, demonstrating gluten exposure. Urine GIP may enable the accurate RCD verification and decrease overuse of immunosuppressants, increasing cost effectiveness.
Characterization of Biofilm Formation by Mycobacterium chimaera on Medical Device Materials
Authors: Siddam Archana D. , Zaslow Shari J. , Wang Yi , Phillips K. Scott , Silverman Matthew D. , Regan Patrick M. , Amarasinghe Jayaleka J.
Published: January 2021

Non-tuberculous mycobacteria (NTM) are widespread in the environment and are a public health concern due to their resistance to antimicrobial agents. The colonization of surgical heater-cooler devices (HCDs) by the slow-growing NTM species Mycobacterium chimaera has recently been linked to multiple invasive infections in patients worldwide. The resistance of M. chimaera to antimicrobials may be aided by a protective biofilm matrix of extracellular polymeric substances (EPS). This study explored the hypothesis that M. chimaera can form biofilms on medically relevant materials. Several M. chimaera strains, including two HCD isolates, were used to inoculate a panel of medical device materials. M. chimaera colonization of the surfaces was monitored for 6 weeks. M. chimaera formed a robust biofilm at the air-liquid interface of borosilicate glass tubes, which increased in mass over time. M. chimaera was observed by 3D Laser Scanning Microscopy to have motility during colonization, and form biofilms on stainless steel, titanium, silicone and polystyrene surfaces during the first week of inoculation. Scanning electron microscopy (SEM) of M. chimaera biofilms after 4 weeks of inoculation showed that M. chimaera cells were enclosed entirely in extracellular material, while cryo-preserved SEM samples further revealed that an ultrastructural component of the EPS matrix was a tangled mesh of 3D fiber-like projections connecting cells. Considering that slow-growing M. chimaera typically has culture times on the order of weeks, the microscopically observed ability to rapidly colonize stainless steel and titanium surfaces in as little as 24 h after inoculation is uncharacteristic. The insights that this study provides into M. chimaera colonization and biofilm formation of medical device materials are a significant advance in our fundamental understanding of M. chimaera surface interactions and have important implications for research into novel antimicrobial materials, designs and other approaches to help reduce the risk of infection.
Unbiased Identification of Angiogenin as an Endogenous Antimicrobial Protein With Activity Against Virulent Mycobacterium tuberculosis
Authors: Noschka Reiner , Gerbl Fabian , Löffler Florian , Kubis Jan , Rodríguez Armando A. , Mayer Daniel , Grieshober Mark , Holch Armin , Raasholm Martina , Forssmann Wolf-Georg , Spellerberg Barbara , Wiese Sebastian , Weidinger Gilbert , Ständker Ludger , Stenger Steffen
Published: January 2021

Tuberculosis is a highly prevalent infectious disease with more than 1.5 million fatalities each year. Antibiotic treatment is available, but intolerable side effects and an increasing rate of drug-resistant strains of Mycobacterium tuberculosis (Mtb) may hamper successful outcomes. Antimicrobial peptides (AMPs) offer an alternative strategy for treatment of infectious diseases in which conventional antibiotic treatment fails. Human serum is a rich resource for endogenous AMPs. Therefore, we screened a library generated from hemofiltrate for activity against Mtb. Taking this unbiased approach, we identified Angiogenin as the single compound in an active fraction. The antimicrobial activity of endogenous Angiogenin against extracellular Mtb could be reproduced by synthetic Angiogenin. Using computational analysis, we identified the hypothetical active site and optimized the lytic activity by amino acid exchanges. The resulting peptide-Angie1-limited the growth of extra‐ and intracellular Mtb and the fast-growing pathogens Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Toward our long-term goal of evaluating Angie1 for therapeutic efficacy in vivo, we demonstrate that the peptide can be efficiently delivered into human macrophages via liposomes and is not toxic for zebrafish embryos. Taken together, we define Angiogenin as a novel endogenous AMP and derive the small, bioactive fragment Angie1, which is ready to be tested for therapeutic activity in animal models of tuberculosis and infections with fast-growing bacterial pathogens.
Comparison of the Multiple Platforms to Identify Various Aeromonas Species
Authors: Du Xiaoli , Wang Mengyu , Zhou Haijian , Li Zhenpeng , Xu Jialiang , Li Zhe , Kan Biao , Chen Daoli , Wang Xiaoli , Jin Yujuan , Ren Yan , Ma Yanping , Liu Jiuyin , Luan Yang , Cui Zhigang , Lu Xin
Published: January 2021

We compared several identification methods for Aeromonas genus members, including traditional biochemical testing, multiplex-PCR amplification, mass spectrometry identification, whole-genome sequencing, multilocus phylogenetic analysis (MLPA), and rpoD, gyrA, and rpoD-gyrA gene sequencing. Isolates (n = 62) belonging to the Aeromonas genus, which were came from the bacterial bank in the laboratory, were used to assess the identification accuracy of the different methods. Whole-genome sequencing showed that the Aeromonas spp. isolates comprised A. caviae (n = 21), A. veronii (n = 18), A. dhakensis (n = 8), A. hydrophila (n = 7), A. jandaei (n = 5), A. enteropelogenes (n = 2), and A. media (n = 1). Using the whole-genome sequencing results as the standard, the consistency of the other methods was compared with them. The results were 46.77% (29/62) for biochemical identification, 83.87% (52/62) for mass spectrometric identification, 67.74% (42/62) for multiplex-PCR, 100% (62/62) for MLPA typing, 72.58% for gyrA, and 59.68% for rpoD and gyrA-rpoD. MLPA was the most consistent, followed by mass spectrometry. Therefore, in the public health laboratory, both MLPA and whole-genome sequencing methods can be used to identify various Aeromonas species. However, rapid and relatively accurate mass spectrometry is recommended for clinical lab.
High-Resolution Spectral Sleep Analysis Reveals a Novel Association Between Slow Oscillations and Memory Retention in Elderly Adults
Authors: Kawai Makoto , Schneider Logan D. , Linkovski Omer , Jordan Josh T. , Karna Rosy , Pirog Sophia , Cotto Isabelle , Buck Casey , Giardino William J. , O'Hara Ruth
Published: January 2021

Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults.

Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity).

Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size.

Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults.
HMGA1 Induction of miR-103/107 Forms a Negative Feedback Loop to Regulate Autophagy in MPTP Model of Parkinson’s Disease
Authors: Li Gehui , Luo Wanxian , Wang Baoyan , Qian Chen , Ye Yongyi , Li Yuantao , Zhang Shizhong
Published: January 2021

Autophagy dysfunction has been directly linked with the onset and progression of Parkinson’s disease (PD), but the underlying mechanisms are not well understood. High-mobility group A1 (HMGA1), well-known chromatin remodeling proteins, play pivotal roles in diverse biological processes and diseases. Their function in neural cell death in PD, however, have not yet been fully elucidated. Here, we report that HMGA1 is highly induced during dopaminergic cell death in vitro and mice models of PD in vivo. Functional studies using genetic knockdown of endogenous HMGA1 show that HMGA1 signaling inhibition accelerates neural cell death, at least partially through aggravating MPP+-induced autophagic flux reduction resulting from partial block in autophagic flux at the terminal stages, indicating a novel potential neuroprotective role for HMGA1 in dopaminergic neurons death. MicroRNA-103/107 (miR-103/107) family, which is highly expressed in neuron, coordinately ensures proper end-stage autophagy. We further illustrate that MPP+/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced HMGA1 elevation counterparts the effect of miR-103/107 downregulation by directly binding to their promoters, respectively, sustaining their expression in MPP+-damaged MN9D cells and modulates autophagy through CDK5R1/CDK5 signaling pathway. We also find that HMGA1 is a direct target of miR-103/107 family. Thus, our results suggest that HMGA1 forms a negative feedback loop with miR-103/107-CDK5R1/CDK5 signaling to regulate the MPP+/MPTP-induced autophagy impairment and neural cell death. Collectively, we identify a paradigm for compensatory neuroprotective HMGA1 signaling in dopaminergic neurons that could have important therapeutic implications for PD.
Modulating Microglial Cells for Promoting Brain Recovery and Repair
Authors: Hermann Dirk M. , Gunzer Matthias
Published: January 2021

Representing the brain’s innate immune cells that interact vividly with blood-derived immune cells and brain parenchymal cells, microglia set the stage for successful brain remodeling and repair in the aftermath of brain damage. With the development of pharmacological colony-stimulating factor-1 receptor inhibitors, which allow inhibiting or depleting microglial cells, and of transgenic mice, allowing the inducible depletion of microglial cells, experimental tools have become available for studying roles of microglia in neurodegenerative and neurorestorative processes. These models open fundamental insights into roles of microglia in controlling synaptic plasticity in the healthy and the injured brain. Acting as a switch from injury to repair, microglial cells might open opportunities for promoting neurological recovery in human patients upon brain injury.
Paclitaxel Coated Balloon vs. Bare Metal Stent for Endovascular Treatment of Symptomatic Vertebral Artery Origin Stenosis Patients: Protocol for a Randomized Controlled Trial
Authors: Wang Yabing , Ma Yan , Gao Peng , Chen Yanfei , Yang Bin , Feng Yao , Jiao Liqun
Published: January 2021

Background: Stenting treatment for refractory symptomatic patients with vertebral artery origin stenosis (VAOS) is safe; however, there is a high rate of in-stent restenosis. Although drug-eluting stents can reduce the incidence of restenosis to some extent, there is still a risk caused by stent fracture. Drug-coated balloon (DCB) has been proven to reduce the rate of restenosis in peripheral and coronary artery disease. DCB can prevent inflammation caused by extraneous material stimulation and allow the subsequent treatment that is characteristic of “leave nothing behind.” The purpose of this trial is to compare the efficacy and safety of DCB and bare metal stent (BMS) in the treatment of VAOS.

Method/Design: This trial is a 1:1 randomized, controlled, multicenter, non-inferiority trial that compares the DCB to BMS in terms of angiographically assessed target lesion binary restenosis (≥50%) at 12 months in endovascular treatment of symptomatic patients with VAOS.

Discussion: A total of 180 patients with symptomatic VAOS who match the trial eligibility criteria will be randomized 1:1 to treatment with DCB (n = 90) or BMS (n = 90). An angiographic core laboratory-adjudicated target lesion binary restenosis (≥50%) at 12 months of follow-up was selected as primary efficacy endpoint to assess the DCB treatment effect. A clinical events committee will assess the safety endpoints of all-cause death, target vessel related transient ischemic attack and ischemic or hemorrhagic stroke events. A data safety monitoring board will periodically review safety data for subject safety, the study conduct, and progress. In this trial, randomization is only allowed after successful pre-dilatation. We anticipate that this trial will provide rigorous data to clarify whether DCBs are beneficial in patients with symptomatic VAOS.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03910166.
Plaque Wall Distribution Pattern of the Atherosclerotic Middle Cerebral Artery Associates With the Circle of Willis Completeness
Authors: Li Jia , Zheng Lu , Yang Wen-Jie , Sze-To Cheuk-Yin , Leung Thomas Wai-Hong , Chen Xiang-Yan
Published: January 2021

Objective: Investigating the relevance of the incomplete circle of Willis (COW) to the plaque wall distribution in the atherosclerotic middle cerebral arteries (MCAs) through utilizing high-resolution magnetic resonance imaging (HR-MRI), and its potential clinical impact.

Methods: This hospital-based study enrolled consecutive adult patients with acute ischemic stroke or transient ischemic attack, who received a 3.0T Achieva MR system scanning. The COW completeness was evaluated on MR angiography imaging, including anterior (A) and posterior (P)-COW sections. The MCA plaque wall distribution was assessed on HR-MRI. The occurrence of perforator infarction was detected on diffusion-weighted imaging.

Results: Among 87 patients (mean age = 62.39 ± 11.64 years old) with atherosclerotic plaques in the MCA M1 segments, the incomplete COW types were more prevalent than the complete COW type (incomplete P-COW, 83.9%; incomplete A-COW, 36.8%; complete COW, 8.1%). The incomplete A-COW had more inferior but fewer ventral plaques of MCA atherosclerosis than the complete A-COW, while the incomplete P-COW had fewer inferior MCA plaques than the complete P-COW. Moreover, symptomatic MCA plaques causing perforator infarctions were more likely to locate on the superior wall.

Conclusion: Our findings suggested that the COW completeness could influence the vessel wall distribution of the MCA plaques, among which the superior plaques of symptomatic MCA atherosclerosis was associated with branch occlusive disease.
Developmental Differences in Probabilistic Reversal Learning: A Computational Modeling Approach
Authors: Weiss Eileen Oberwelland , Kruppa Jana A. , Fink Gereon R. , Herpertz-Dahlmann Beate , Konrad Kerstin , Schulte-Rüther Martin
Published: January 2021

Cognitive flexibility helps us to navigate through our ever-changing environment and has often been examined by reversal learning paradigms. Performance in reversal learning can be modeled using computational modeling which allows for the specification of biologically plausible models to infer psychological mechanisms. Although such models are increasingly used in cognitive neuroscience, developmental approaches are still scarce. Additionally, though most reversal learning paradigms have a comparable design regarding timing and feedback contingencies, the type of feedback differs substantially between studies. The present study used hierarchical Gaussian filter modeling to investigate cognitive flexibility in reversal learning in children and adolescents and the effect of various feedback types. The results demonstrate that children make more overall errors and regressive errors (when a previously learned response rule is chosen instead of the new correct response after the initial shift to the new correct target), but less perseverative errors (when a previously learned response set continues to be used despite a reversal) adolescents. Analyses of the extracted model parameters of the winning model revealed that children seem to use new and conflicting information less readily than adolescents to update their stimulus-reward associations. Furthermore, more subclinical rigidity in everyday life (parent-ratings) is related to less explorative choice behavior during the probabilistic reversal learning task. Taken together, this study provides first-time data on the development of the underlying processes of cognitive flexibility using computational modeling.
Correlation Between Cerebral Venous Oxygen Level and Cognitive Status in Patients With Alzheimer’s Disease Using Quantitative Susceptibility Mapping
Authors: Liu YangYingQiu , Dong JunYi , Song QingWei , Zhang Nan , Wang WeiWei , Gao BingBing , Tian ShiYun , Dong ChunBo , Liang ZhanHua , Xie LiZhi , Miao YanWei
Published: January 2021

Purpose

To quantitatively assess the blood oxygen levels of the cerebral vein using quantitative susceptibility mapping (QSM), and to analyze the correlation between magnetic susceptibility value (MSV) and clinical laboratory indicators/cognitive scores in patients with Alzheimer’s disease (AD).

Materials and Methods

Fifty-nine patients (21 males and 38 females) with clinically confirmed AD (AD group) and 22 control subjects (12 males, 10 females; CON group) were recruited. Clinical data and laboratory examination indexes were collected. All patients underwent Mini-mental State Examination, Montreal Cognitive Assessment, Clock Drawing Task, and Activity of Daily Living Scale test, as well as a routine MRI and enhanced gradient echo T2 star weighted angiography (ESWAN).

Results

Higher cerebral venous MSV was observed in AD group compared to CON group, significant differences were observed for bilateral thalamus veins and left dentate nucleus veins. The MSV of bilateral thalamus veins, bilateral internal cerebral veins, and bilateral dentate nucleus veins had significant negative correlation with Mini-mental State Examination score; the MSV of bilateral thalamus veins, bilateral dentate nucleus veins, right septal vein had a significant negative correlation with Montreal Cognitive Assessment scores; a significant negative correlation between the MSV of bilateral thalamus veins, left dentate nucleus vein, right septal vein and the Clock Drawing Task score; the MSV of bilateral thalamus veins, left dentate nucleus vein had a significant negative correlation with Activity of Daily Living Scale score. The MSV of left dentate nucleus vein was positively correlated with the course of the disease, the MSV of bilateral septal vein were positively correlated with the total cholesterol, and the MSV of left septal vein had a positive correlation with LDL.

Conclusion

Decreasing cerebral venous oxygen level in AD patients may affect cognitive status, and associated with the deterioration of the disease in AD patients.
To Reveal or Not to Reveal? Observation of Social Outcomes Facilitates Reward Processing
Authors: Shen Qiang , Zhu Lian , Meng Liang , Qiu Wenwei , Ma Qingguo , Ebstein Richard P. , Jin Jia
Published: January 2021

Motivation is a key topic that comprises considerable theoretical and practical implications, and its study is gaining increasing traction in recent years. Employing both behavioral and neural techniques, previous studies examined the extent to which intrinsic and extrinsic motivations collectively shape individual decision making. Investigations found that both processes play indispensable and interactive roles in choice behavior. However, despite its importance, little is known respecting the role of extrinsic social factors in contributing to individual variations in intrinsic motivation. Toward elucidating the role of extrinsic social factors in motivated decision making, the current study implements the stop watch task, combined with hyper-recording electrophysiological measurements. With the electrophysiological toolkit, our goal is to bring to light how extrinsic social signals impact intrinsic motivation and shape the reward processing over success and failure at the succeeding stage. Empirically, we show that, following social outcome presentation, there is an increased divergent feedback-related negativity (FRN), which reflects the failure/success discrepancy at the outcome stage of choice behavior. In summary, this study demonstrates the saliency of social information in intrinsic motivational processes that underpin success-failure outcomes.
Changes of Metabolites in Acute Ischemic Stroke and Its Subtypes
Authors: Wang Xin , Zhang Luyang , Sun Wenxian , Pei Lu-lu , Tian Mengke , Liang Jing , Liu Xinjing , Zhang Rui , Fang Hui , Wu Jun , Sun Shilei , Xu Yuming , Kang Jian-Sheng , Song Bo
Published: January 2021

Existing techniques have many limitations in the diagnosis and classification of ischemic stroke (IS). Considering this, we used metabolomics to screen for potential biomarkers of IS and its subtypes and to explore the underlying related pathophysiological mechanisms. Serum samples from 99 patients with acute ischemic stroke (AIS) [the AIS subtypes included 49 patients with large artery atherosclerosis (LAA) and 50 patients with small artery occlusion (SAO)] and 50 matched healthy controls (HCs) were analyzed by non-targeted metabolomics based on liquid chromatography–mass spectrometry. A multivariate statistical analysis was performed to identify potential biomarkers. There were 18 significantly different metabolites, such as oleic acid, linoleic acid, arachidonic acid, L-glutamine, L-arginine, and L-proline, between patients with AIS and HCs. These different metabolites are closely related to many metabolic pathways, such as fatty acid metabolism and amino acid metabolism. There were also differences in metabolic profiling between the LAA and SAO groups. There were eight different metabolites, including L-pipecolic acid, 1-Methylhistidine, PE, LysoPE, and LysoPC, which affected glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, histidine metabolism, and lysine degradation. Our study effectively identified the metabolic profiles of IS and its subtypes. The different metabolites between LAA and SAO may be potential biomarkers in the context of clinical diagnosis. These results highlight the potential of metabolomics to reveal new pathways for IS subtypes and provide a new avenue to explore the pathophysiological mechanisms underlying IS and its subtypes.